Cardiology

Patients with atrial fibrillation (A-fib) are often also diagnosed with sleep apnea, as noted and discussed by Ayache et al in this issue of the Journal. It is well recognized that A-fib is more prevalent in older patients and is associated with many comorbidities, including hypertension, diabetes mellitus, coronary artery disease, heavy alcohol use, obesity, and some valvular disorders, in addition to the association with sleep apnea. While causation (as distinct from association) is virtually impossible to prove from observational and epidemiologic studies alone, many of the above comorbidities are recognized before the onset of the A-fib. Sleep apnea shares many of these comorbidities, and thus it is no surprise that a significant proportion of patients with A-fib are diagnosed with it. But sleep apnea, with its associated intermittent hypoxia, seems to promote the onset or worsen the course of A-fib in some patients.

Is the relationship between A-fib and sleep apnea more than a coincidence stemming from the number of shared associated comorbidities? Significantly, the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) has been shown to decrease the recurrence of A-fib after pharmacologic or electrical conversion and after interventional pulmonary vein interruption.¹ This suggests that at least in some cases, sleep apnea plays an active role in initiating and possibly also maintaining A-fib. The immediate culprit mediators that come to mind are hypoxia and hypercapnea; both are at least partially ameliorated by the successful use of CPAP, and both are reasonable physiologic candidates for induction of A-fib. Hypoxia is supported by clinical observation, and hypercapnea by experimental modeling.²

It is easy for clinicians to conceptualize the organ effects of hypoxia and hypercapnea. We are accustomed to seeing clinical ramifications of these in the emergency department and intensive care unit, particularly those affecting the brain and heart, organs critically dependent on transmembrane ion flow. We may recall from biochemistry classes the effects of hypoxia on intracellular metabolism and the implications on energy stores, mitochondrial function, and ion translocation. Recent work on the cellular effects of hypoxia, including research that resulted in a Nobel prize, has drawn major attention to patterned cellular responses to intermittent and persistent hypoxia. This includes recognition of epigenetic changes resulting in localized cardiac remodeling and fibrosis,³ factors that clearly affect the expression of arrhythmias, including A-fib.

But the interrelationship between A-fib and sleep apnea may be even more convoluted and intriguing. It now seems that most things cardiac are associated with inflammation in some guise, and the A-fib connection with sleep apnea may not be an exception. Almost 20 years ago, it was recognized that A-fib is associated with an elevation in circulating C-reactive protein (CRP),⁴ a biomarker of “inflammation,” although not necessarily an active participant. Recent reviews of this connection have been published,⁵ and successful anti-inflammatory approaches to preventing A-fib using colchicine have been described.⁶ So how does this tie in with sleep apnea?

A number of papers have now demonstrated that sleep apnea is also associated with an elevation in CRP,⁷ perhaps due to increases in tumor necrosis factor (TNF)-alpha in response to the intermittent hypoxia of sleep apnea. TNF can drive the inflammatory response through increased expression of genes regulated by nuclear factor kappa-B.⁸ While it certainly warrants consideration that the elevated biomarkers of inflammation in patients with sleep apnea actually reflect the presence of the frequent comorbidities, including visceral obesity, treating sleep apnea with CPAP (comparable to what I noted above in patients with A-fib) has been shown to reduce circulating CRP levels.⁹

As our understanding of the biologic underpinnings of A-fib and sleep apnea continue to grow, the practical clinical implications of the relationship between them, as described by Ayache et al, may achieve greater clarity. The two conditions commonly coexist, and treating the sleep apnea results in better rhythm-directed outcomes in the A-fib.

Stay tuned, there is certainly more to learn about this.

Patients with atrial fibrillation (A-fib) are often also diagnosed with sleep apnea, as noted and discussed by Ayache et al in this issue of the Journal. It is well recognized that A-fib is more prevalent in older patients and is associated with many comorbidities, including hypertension, diabetes mellitus, coronary artery disease, heavy alcohol use, obesity, and some valvular disorders, in addition to the association with sleep apnea. While causation (as distinct from association) is virtually impossible to prove from observational and epidemiologic studies alone, many of the above comorbidities are recognized before the onset of the A-fib. Sleep apnea shares many of these comorbidities, and thus it is no surprise that a significant proportion of patients with A-fib are diagnosed with it. But sleep apnea, with its associated intermittent hypoxia, seems to promote the onset or worsen the course of A-fib in some patients.

Is the relationship between A-fib and sleep apnea more than a coincidence stemming from the number of shared associated comorbidities? Significantly, the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) has been shown to decrease the recurrence of A-fib after pharmacologic or electrical conversion and after interventional pulmonary vein interruption.¹ This suggests that at least in some cases, sleep apnea plays an active role in initiating and possibly also maintaining A-fib. The immediate culprit mediators that come to mind are hypoxia and hypercapnea; both are at least partially ameliorated by the successful use of CPAP, and both are reasonable physiologic candidates for induction of A-fib. Hypoxia is supported by clinical observation, and hypercapnea by experimental modeling.²

It is easy for clinicians to conceptualize the organ effects of hypoxia and hypercapnea. We are accustomed to seeing clinical ramifications of these in the emergency department and intensive care unit, particularly those affecting the brain and heart, organs critically dependent on transmembrane ion flow. We may recall from biochemistry classes the effects of hypoxia on intracellular metabolism and the implications on energy stores, mitochondrial function, and ion translocation. Recent work on the cellular effects of hypoxia, including research that resulted in a Nobel prize, has drawn major attention to patterned cellular responses to intermittent and persistent hypoxia. This includes recognition of epigenetic changes resulting in localized cardiac remodeling and fibrosis,³ factors that clearly affect the expression of arrhythmias, including A-fib.

But the interrelationship between A-fib and sleep apnea may be even more convoluted and intriguing. It now seems that most things cardiac are associated with inflammation in some guise, and the A-fib connection with sleep apnea may not be an exception. Almost 20 years ago, it was recognized that A-fib is associated with an elevation in circulating C-reactive protein (CRP),⁴ a biomarker of “inflammation,” although not necessarily an active participant. Recent reviews of this connection have been published,⁵ and successful anti-inflammatory approaches to preventing A-fib using colchicine have been described.⁶ So how does this tie in with sleep apnea?

A number of papers have now demonstrated that sleep apnea is also associated with an elevation in CRP,⁷ perhaps due to increases in tumor necrosis factor (TNF)-alpha in response to the intermittent hypoxia of sleep apnea. TNF can drive the inflammatory response through increased expression of genes regulated by nuclear factor kappa-B.⁸ While it certainly warrants consideration that the elevated biomarkers of inflammation in patients with sleep apnea actually reflect the presence of the frequent comorbidities, including visceral obesity, treating sleep apnea with CPAP (comparable to what I noted above in patients with A-fib) has been shown to reduce circulating CRP levels.⁹

As our understanding of the biologic underpinnings of A-fib and sleep apnea continue to grow, the practical clinical implications of the relationship between them, as described by Ayache et al, may achieve greater clarity. The two conditions commonly coexist, and treating the sleep apnea results in better rhythm-directed outcomes in the A-fib.

Stay tuned, there is certainly more to learn about this.

Patients with atrial fibrillation (A-fib) are often also diagnosed with sleep apnea, as noted and discussed by Ayache et al in this issue of the Journal. It is well recognized that A-fib is more prevalent in older patients and is associated with many comorbidities, including hypertension, diabetes mellitus, coronary artery disease, heavy alcohol use, obesity, and some valvular disorders, in addition to the association with sleep apnea. While causation (as distinct from association) is virtually impossible to prove from observational and epidemiologic studies alone, many of the above comorbidities are recognized before the onset of the A-fib. Sleep apnea shares many of these comorbidities, and thus it is no surprise that a significant proportion of patients with A-fib are diagnosed with it. But sleep apnea, with its associated intermittent hypoxia, seems to promote the onset or worsen the course of A-fib in some patients.

Is the relationship between A-fib and sleep apnea more than a coincidence stemming from the number of shared associated comorbidities? Significantly, the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) has been shown to decrease the recurrence of A-fib after pharmacologic or electrical conversion and after interventional pulmonary vein interruption.¹ This suggests that at least in some cases, sleep apnea plays an active role in initiating and possibly also maintaining A-fib. The immediate culprit mediators that come to mind are hypoxia and hypercapnea; both are at least partially ameliorated by the successful use of CPAP, and both are reasonable physiologic candidates for induction of A-fib. Hypoxia is supported by clinical observation, and hypercapnea by experimental modeling.²

It is easy for clinicians to conceptualize the organ effects of hypoxia and hypercapnea. We are accustomed to seeing clinical ramifications of these in the emergency department and intensive care unit, particularly those affecting the brain and heart, organs critically dependent on transmembrane ion flow. We may recall from biochemistry classes the effects of hypoxia on intracellular metabolism and the implications on energy stores, mitochondrial function, and ion translocation. Recent work on the cellular effects of hypoxia, including research that resulted in a Nobel prize, has drawn major attention to patterned cellular responses to intermittent and persistent hypoxia. This includes recognition of epigenetic changes resulting in localized cardiac remodeling and fibrosis,³ factors that clearly affect the expression of arrhythmias, including A-fib.

But the interrelationship between A-fib and sleep apnea may be even more convoluted and intriguing. It now seems that most things cardiac are associated with inflammation in some guise, and the A-fib connection with sleep apnea may not be an exception. Almost 20 years ago, it was recognized that A-fib is associated with an elevation in circulating C-reactive protein (CRP),⁴ a biomarker of “inflammation,” although not necessarily an active participant. Recent reviews of this connection have been published,⁵ and successful anti-inflammatory approaches to preventing A-fib using colchicine have been described.⁶ So how does this tie in with sleep apnea?

A number of papers have now demonstrated that sleep apnea is also associated with an elevation in CRP,⁷ perhaps due to increases in tumor necrosis factor (TNF)-alpha in response to the intermittent hypoxia of sleep apnea. TNF can drive the inflammatory response through increased expression of genes regulated by nuclear factor kappa-B.⁸ While it certainly warrants consideration that the elevated biomarkers of inflammation in patients with sleep apnea actually reflect the presence of the frequent comorbidities, including visceral obesity, treating sleep apnea with CPAP (comparable to what I noted above in patients with A-fib) has been shown to reduce circulating CRP levels.⁹

As our understanding of the biologic underpinnings of A-fib and sleep apnea continue to grow, the practical clinical implications of the relationship between them, as described by Ayache et al, may achieve greater clarity. The two conditions commonly coexist, and treating the sleep apnea results in better rhythm-directed outcomes in the A-fib.

Stay tuned, there is certainly more to learn about this.

Yes. The prevalence of sleep apnea is exceedingly high in patients with atrial fibrillation—50% to 80% compared with 30% to 60% in respective control groups.^1–3 Conversely, atrial fibrillation is more prevalent in those with sleep-disordered breathing than in those without (4.8% vs 0.9%).⁴

Sleep-disordered breathing comprises obstructive sleep apnea and central sleep apnea. Obstructive sleep apnea, characterized by repetitive upper-airway obstruction during sleep, is accompanied by intermittent hypoxia, rises in carbon dioxide, autonomic nervous system fluctuations, and intrathoracic pressure alterations.⁵ Central sleep apnea may be neurally mediated and, in the setting of cardiac disease, is characterized by alterations in chemosensitivity and chemoresponsiveness, leading to a state of high loop gain—ie, a hypersensitive ventilatory control system leading to ventilatory drive oscillations.⁶

Both obstructive and central sleep apnea have been associated with atrial fibrillation. Experimental data implicate obstructive sleep apnea as a trigger of atrial arrhythmogenesis,^7,8 and epidemiologic studies support an association between central sleep apnea, Cheyne-Stokes respiration, and incident atrial fibrillation.⁹

HOW SLEEP APNEA COULD LEAD TO ATRIAL FIBRILLATION

In experiments in animals, intermittent upper-airway obstruction led to forced inspiration, substantial negative intrathoracic pressure, subsequent left atrial distention, and increased susceptibility to atrial fibrillation.¹⁰ The autonomic nervous system may be a mediator of apnea-induced atrial fibrillation, as apnea-induced atrial fibrillation is suppressed with autonomic blockade.¹⁰

Emerging data also support the hypothesis that intermittent hypoxia⁷ and resolution of hypercapnia,⁸ as observed in obstructive sleep apnea, exert atrial electrophysiologic changes that increase vulnerability to atrial arrhythmogenesis.

In a case-crossover study,¹¹ the odds of paroxysmal atrial fibrillation occurring after a respiratory disturbance were 17.9 times higher than after normal breathing (95% confidence interval [CI] 2.2–144.2), though the absolute rate of overall arrhythmia events (including both atrial fibrillation and nonsustained ventricular tachycardia) associated with respiratory disturbances was low (1 excess arrhythmia event per 40,000 respiratory disturbances).

EFFECT OF SLEEP APNEA ON ATRIAL FIBRILLATION MANAGEMENT

Sleep apnea also seems to affect the efficacy of a rhythm-control strategy for atrial fibrillation. For example, patients with obstructive sleep apnea have a higher risk of recurrent atrial fibrillation after cardioversion (82% vs 42% in controls)¹² and up to a 25% greater risk of recurrence after catheter ablation compared with those without obstructive sleep apnea (risk ratio 1.25, 95% CI 1.08–1.45).¹³

Several observational studies showed a higher rate of atrial fibrillation after pulmonary vein isolation in obstructive sleep apnea patients who do not use continuous positive airway pressure (CPAP) than in those who do.^14–17 CPAP therapy appears to exert beneficial effects on cardiac structural remodeling;  cardiac magnetic resonance imaging shows that patients with sleep apnea who received less than 4 hours of CPAP per night had larger left atrial dimensions and increased left ventricular mass compared with those who received more than 4 hours of CPAP at night.¹⁷ However, a need remains for high-quality, large randomized controlled trials to eliminate potential unmeasured biases due to differences that may exist between CPAP users and non-users, such as general adherence to medical therapy and healthcare interventions.

An additional consideration is that the overall utility and value of obtaining a diagnosis of obstructive sleep apnea strictly as it pertains to atrial fibrillation management is affected by whether a rhythm- or rate-control strategy is pursued. In other words, if a patient is deemed to be in permanent atrial fibrillation and a rhythm-control strategy is therefore not pursued, the potential effect of untreated obstructive sleep apnea on atrial fibrillation recurrence could be less important. In this case, however, the other beneficial cardiovascular and systemic effects of diagnosing and treating underlying obstructive sleep apnea would remain.

 

 

POPULATION STUDIES

Epidemiologic and clinic-based studies have supported an association between sleep apnea (mostly central, but also obstructive) and atrial fibrillation.^4,18

Community-based studies such as the Sleep Heart Health Study⁴ and the Outcomes of Sleep Disorders in Older Men Study (MrOS Sleep),¹⁸ involving thousands of participants, have found the strongest cross-sectional associations of both obstructive and central sleep apnea with nocturnal atrial fibrillation. The findings included a 2 to 5 times higher odds of nocturnal atrial fibrillation, particularly in those with a moderate to severe degree of sleep-disordered breathing—even after adjusting for confounding influences (eg, obesity) and self-reported cardiac disease such as heart failure.

In MrOS Sleep, in an older male cohort, both obstructive and central sleep apnea were associated with nocturnal atrial fibrillation, though central sleep apnea and Cheyne-Stokes respirations had a stronger magnitude of association.¹⁸

Further insights can be drawn specifically from patients with heart failure. Sin et al,¹⁹ in a 1999 study, found that in 450 patients with systolic heart failure (85% men), the prevalence of sleep-disordered breathing was 25% to 33% (depending on the apnea-hypopnea index cutoff used) for central sleep apnea, and similarly 27% to 38% for obstructive sleep apnea. The prevalence of atrial fibrillation in this group was 10% in women and 15% in men. Atrial fibrillation was reported as a significant risk factor for central sleep apnea, but not for obstructive sleep apnea (for which only male sex and increasing body mass index were significant risk factors). Directionality was not clearly reported in this retrospective study in terms of timing of sleep studies and other assessments: ie, the report did not clearly state which came first, the atrial fibrillation or the sleep apnea. Therefore, the possibility that central sleep apnea is a predictor of atrial fibrillation cannot be excluded.  

Yumino et al,²⁰ in a study published in 2009, evaluated 218 patients with heart failure (with a left ventricular ejection fraction of ≤ 45%) and reported a prevalence of moderate to severe sleep apnea of 21% for central sleep apnea and 26% for obstructive sleep apnea. In multivariate analysis, atrial fibrillation was independently associated with central sleep apnea but not obstructive sleep apnea.

In recent cohort studies, central sleep apnea was associated with 2 to 3 times higher odds of developing atrial fibrillation, while obstructive sleep apnea was not a predictor of incident atrial fibrillation.^9,21

Although most available studies associate sleep apnea with atrial fibrillation, findings of a case-control study²² did not support a difference in the prevalence of sleep apnea syndrome (defined as apnea index ≥ 5 and apnea-hypopnea index ≥ 15, and the presence of sleep symptoms) in patients with lone atrial fibrillation (no evident cardiovascular disease) compared with controls matched for age, sex, and cardiovascular morbidity.

But observational studies are limited by the potential for residual unmeasured confounding factors and lack of objective cardiac structural data, such as left ventricular ejection fraction and atrial enlargement. Moreover, there can be significant differences in sleep apnea definitions among studies, thus limiting the ability to reach a definitive conclusion about the relationship between sleep apnea and atrial fibrillation.

SCREENING AND DIAGNOSIS

The 2014 joint guidelines of the American Heart Association, American College of Cardiology, and Heart Rhythm Society for the management of atrial fibrillation state that a sleep study may be useful if sleep apnea is suspected.²³ The 2019 focused update of the 2014 guidelines²⁴ state that for overweight and obese patients with atrial fibrillation, weight loss combined with risk-factor modification is recommended (class I recommendation, level of evidence B-R, ie, data derived from 1 or more randomized trials or meta-analysis of such studies). Risk-factor modification in this case includes assessment and treatment of underlying sleep apnea, hypertension, hyperlipidemia, glucose intolerance, and alcohol and tobacco use.

Further study is needed to evaluate whether physicians should routinely use screening tools for sleep apnea in patients with atrial fibrillation. Standardized screening methods such as the Berlin questionnaire,²⁵ STOP-Bang,²⁶ and NoSAS²⁷ (Table 1) are limited by lack of validation in patients with atrial fibrillation, particularly as the symptom profile may be different from that in patients who do not have atrial fibrillation.

Laboratory polysomnography has long been considered the gold standard for sleep apnea diagnosis. In one study,¹³ obstructive sleep apnea was a greater predictor of atrial fibrillation when diagnosed by polysomnography (risk ratio 1.40, 95% CI 1.16–1.68) compared with identification by screening using the Berlin questionnaire (risk ratio 1.07, 95% CI 0.91–1.27). However, a laboratory sleep study is associated with increased patient burden and limited availability.

Home sleep apnea testing is being increasingly used in the diagnostic evaluation of obstructive sleep apnea and may be a less costly, more available alternative. However, since a home sleep apnea test is less sensitive than polysomnography in detecting obstructive sleep apnea, the American Academy of Sleep Medicine guidelines²⁸ state that if a single home sleep apnea test is negative or inconclusive, polysomnography should be done if there is clinical suspicion of sleep apnea. Moreover, current guidelines from this group recommend that patients with significant cardiorespiratory disease should be tested with polysomnography rather than home sleep apnea testing.²²

Further study is needed to determine the optimal screening method for sleep apnea in patients with atrial fibrillation and to clarify the role of home sleep apnea testing. While keeping in mind the limitations of a screening questionnaire in this population, as a general approach it is reasonable to use a screening questionnaire for sleep apnea. And if the screen is positive, further evaluation with a sleep study is merited, whether by laboratory polysomnography, a home sleep apnea test, or referral to a sleep specialist.

MULTIDISCIPLINARY CARE MAY BE IDEAL

Overall, given the high prevalence of sleep apnea in patients with atrial fibrillation, the deleterious effects of sleep apnea in general, the influence of sleep apnea on atrial fibrillation, and the cardiovascular and other beneficial effects of adequate treatment of sleep apnea, patients with atrial fibrillation should be assessed for sleep apnea.

While the optimal strategy in evaluating for sleep apnea in these patients needs to be further defined, a multidisciplinary approach to care involving a primary care provider, cardiologist, and sleep specialist may be ideal.

Yes. The prevalence of sleep apnea is exceedingly high in patients with atrial fibrillation—50% to 80% compared with 30% to 60% in respective control groups.^1–3 Conversely, atrial fibrillation is more prevalent in those with sleep-disordered breathing than in those without (4.8% vs 0.9%).⁴

Sleep-disordered breathing comprises obstructive sleep apnea and central sleep apnea. Obstructive sleep apnea, characterized by repetitive upper-airway obstruction during sleep, is accompanied by intermittent hypoxia, rises in carbon dioxide, autonomic nervous system fluctuations, and intrathoracic pressure alterations.⁵ Central sleep apnea may be neurally mediated and, in the setting of cardiac disease, is characterized by alterations in chemosensitivity and chemoresponsiveness, leading to a state of high loop gain—ie, a hypersensitive ventilatory control system leading to ventilatory drive oscillations.⁶

Both obstructive and central sleep apnea have been associated with atrial fibrillation. Experimental data implicate obstructive sleep apnea as a trigger of atrial arrhythmogenesis,^7,8 and epidemiologic studies support an association between central sleep apnea, Cheyne-Stokes respiration, and incident atrial fibrillation.⁹

HOW SLEEP APNEA COULD LEAD TO ATRIAL FIBRILLATION

In experiments in animals, intermittent upper-airway obstruction led to forced inspiration, substantial negative intrathoracic pressure, subsequent left atrial distention, and increased susceptibility to atrial fibrillation.¹⁰ The autonomic nervous system may be a mediator of apnea-induced atrial fibrillation, as apnea-induced atrial fibrillation is suppressed with autonomic blockade.¹⁰

Emerging data also support the hypothesis that intermittent hypoxia⁷ and resolution of hypercapnia,⁸ as observed in obstructive sleep apnea, exert atrial electrophysiologic changes that increase vulnerability to atrial arrhythmogenesis.

In a case-crossover study,¹¹ the odds of paroxysmal atrial fibrillation occurring after a respiratory disturbance were 17.9 times higher than after normal breathing (95% confidence interval [CI] 2.2–144.2), though the absolute rate of overall arrhythmia events (including both atrial fibrillation and nonsustained ventricular tachycardia) associated with respiratory disturbances was low (1 excess arrhythmia event per 40,000 respiratory disturbances).

EFFECT OF SLEEP APNEA ON ATRIAL FIBRILLATION MANAGEMENT

Sleep apnea also seems to affect the efficacy of a rhythm-control strategy for atrial fibrillation. For example, patients with obstructive sleep apnea have a higher risk of recurrent atrial fibrillation after cardioversion (82% vs 42% in controls)¹² and up to a 25% greater risk of recurrence after catheter ablation compared with those without obstructive sleep apnea (risk ratio 1.25, 95% CI 1.08–1.45).¹³

Several observational studies showed a higher rate of atrial fibrillation after pulmonary vein isolation in obstructive sleep apnea patients who do not use continuous positive airway pressure (CPAP) than in those who do.^14–17 CPAP therapy appears to exert beneficial effects on cardiac structural remodeling;  cardiac magnetic resonance imaging shows that patients with sleep apnea who received less than 4 hours of CPAP per night had larger left atrial dimensions and increased left ventricular mass compared with those who received more than 4 hours of CPAP at night.¹⁷ However, a need remains for high-quality, large randomized controlled trials to eliminate potential unmeasured biases due to differences that may exist between CPAP users and non-users, such as general adherence to medical therapy and healthcare interventions.

An additional consideration is that the overall utility and value of obtaining a diagnosis of obstructive sleep apnea strictly as it pertains to atrial fibrillation management is affected by whether a rhythm- or rate-control strategy is pursued. In other words, if a patient is deemed to be in permanent atrial fibrillation and a rhythm-control strategy is therefore not pursued, the potential effect of untreated obstructive sleep apnea on atrial fibrillation recurrence could be less important. In this case, however, the other beneficial cardiovascular and systemic effects of diagnosing and treating underlying obstructive sleep apnea would remain.

 

 

POPULATION STUDIES

Epidemiologic and clinic-based studies have supported an association between sleep apnea (mostly central, but also obstructive) and atrial fibrillation.^4,18

Community-based studies such as the Sleep Heart Health Study⁴ and the Outcomes of Sleep Disorders in Older Men Study (MrOS Sleep),¹⁸ involving thousands of participants, have found the strongest cross-sectional associations of both obstructive and central sleep apnea with nocturnal atrial fibrillation. The findings included a 2 to 5 times higher odds of nocturnal atrial fibrillation, particularly in those with a moderate to severe degree of sleep-disordered breathing—even after adjusting for confounding influences (eg, obesity) and self-reported cardiac disease such as heart failure.

In MrOS Sleep, in an older male cohort, both obstructive and central sleep apnea were associated with nocturnal atrial fibrillation, though central sleep apnea and Cheyne-Stokes respirations had a stronger magnitude of association.¹⁸

Further insights can be drawn specifically from patients with heart failure. Sin et al,¹⁹ in a 1999 study, found that in 450 patients with systolic heart failure (85% men), the prevalence of sleep-disordered breathing was 25% to 33% (depending on the apnea-hypopnea index cutoff used) for central sleep apnea, and similarly 27% to 38% for obstructive sleep apnea. The prevalence of atrial fibrillation in this group was 10% in women and 15% in men. Atrial fibrillation was reported as a significant risk factor for central sleep apnea, but not for obstructive sleep apnea (for which only male sex and increasing body mass index were significant risk factors). Directionality was not clearly reported in this retrospective study in terms of timing of sleep studies and other assessments: ie, the report did not clearly state which came first, the atrial fibrillation or the sleep apnea. Therefore, the possibility that central sleep apnea is a predictor of atrial fibrillation cannot be excluded.  

Yumino et al,²⁰ in a study published in 2009, evaluated 218 patients with heart failure (with a left ventricular ejection fraction of ≤ 45%) and reported a prevalence of moderate to severe sleep apnea of 21% for central sleep apnea and 26% for obstructive sleep apnea. In multivariate analysis, atrial fibrillation was independently associated with central sleep apnea but not obstructive sleep apnea.

In recent cohort studies, central sleep apnea was associated with 2 to 3 times higher odds of developing atrial fibrillation, while obstructive sleep apnea was not a predictor of incident atrial fibrillation.^9,21

Although most available studies associate sleep apnea with atrial fibrillation, findings of a case-control study²² did not support a difference in the prevalence of sleep apnea syndrome (defined as apnea index ≥ 5 and apnea-hypopnea index ≥ 15, and the presence of sleep symptoms) in patients with lone atrial fibrillation (no evident cardiovascular disease) compared with controls matched for age, sex, and cardiovascular morbidity.

But observational studies are limited by the potential for residual unmeasured confounding factors and lack of objective cardiac structural data, such as left ventricular ejection fraction and atrial enlargement. Moreover, there can be significant differences in sleep apnea definitions among studies, thus limiting the ability to reach a definitive conclusion about the relationship between sleep apnea and atrial fibrillation.

SCREENING AND DIAGNOSIS

The 2014 joint guidelines of the American Heart Association, American College of Cardiology, and Heart Rhythm Society for the management of atrial fibrillation state that a sleep study may be useful if sleep apnea is suspected.²³ The 2019 focused update of the 2014 guidelines²⁴ state that for overweight and obese patients with atrial fibrillation, weight loss combined with risk-factor modification is recommended (class I recommendation, level of evidence B-R, ie, data derived from 1 or more randomized trials or meta-analysis of such studies). Risk-factor modification in this case includes assessment and treatment of underlying sleep apnea, hypertension, hyperlipidemia, glucose intolerance, and alcohol and tobacco use.

Further study is needed to evaluate whether physicians should routinely use screening tools for sleep apnea in patients with atrial fibrillation. Standardized screening methods such as the Berlin questionnaire,²⁵ STOP-Bang,²⁶ and NoSAS²⁷ (Table 1) are limited by lack of validation in patients with atrial fibrillation, particularly as the symptom profile may be different from that in patients who do not have atrial fibrillation.

Laboratory polysomnography has long been considered the gold standard for sleep apnea diagnosis. In one study,¹³ obstructive sleep apnea was a greater predictor of atrial fibrillation when diagnosed by polysomnography (risk ratio 1.40, 95% CI 1.16–1.68) compared with identification by screening using the Berlin questionnaire (risk ratio 1.07, 95% CI 0.91–1.27). However, a laboratory sleep study is associated with increased patient burden and limited availability.

Home sleep apnea testing is being increasingly used in the diagnostic evaluation of obstructive sleep apnea and may be a less costly, more available alternative. However, since a home sleep apnea test is less sensitive than polysomnography in detecting obstructive sleep apnea, the American Academy of Sleep Medicine guidelines²⁸ state that if a single home sleep apnea test is negative or inconclusive, polysomnography should be done if there is clinical suspicion of sleep apnea. Moreover, current guidelines from this group recommend that patients with significant cardiorespiratory disease should be tested with polysomnography rather than home sleep apnea testing.²²

Further study is needed to determine the optimal screening method for sleep apnea in patients with atrial fibrillation and to clarify the role of home sleep apnea testing. While keeping in mind the limitations of a screening questionnaire in this population, as a general approach it is reasonable to use a screening questionnaire for sleep apnea. And if the screen is positive, further evaluation with a sleep study is merited, whether by laboratory polysomnography, a home sleep apnea test, or referral to a sleep specialist.

MULTIDISCIPLINARY CARE MAY BE IDEAL

Overall, given the high prevalence of sleep apnea in patients with atrial fibrillation, the deleterious effects of sleep apnea in general, the influence of sleep apnea on atrial fibrillation, and the cardiovascular and other beneficial effects of adequate treatment of sleep apnea, patients with atrial fibrillation should be assessed for sleep apnea.

While the optimal strategy in evaluating for sleep apnea in these patients needs to be further defined, a multidisciplinary approach to care involving a primary care provider, cardiologist, and sleep specialist may be ideal.

Yes. The prevalence of sleep apnea is exceedingly high in patients with atrial fibrillation—50% to 80% compared with 30% to 60% in respective control groups.^1–3 Conversely, atrial fibrillation is more prevalent in those with sleep-disordered breathing than in those without (4.8% vs 0.9%).⁴

Sleep-disordered breathing comprises obstructive sleep apnea and central sleep apnea. Obstructive sleep apnea, characterized by repetitive upper-airway obstruction during sleep, is accompanied by intermittent hypoxia, rises in carbon dioxide, autonomic nervous system fluctuations, and intrathoracic pressure alterations.⁵ Central sleep apnea may be neurally mediated and, in the setting of cardiac disease, is characterized by alterations in chemosensitivity and chemoresponsiveness, leading to a state of high loop gain—ie, a hypersensitive ventilatory control system leading to ventilatory drive oscillations.⁶

Both obstructive and central sleep apnea have been associated with atrial fibrillation. Experimental data implicate obstructive sleep apnea as a trigger of atrial arrhythmogenesis,^7,8 and epidemiologic studies support an association between central sleep apnea, Cheyne-Stokes respiration, and incident atrial fibrillation.⁹

HOW SLEEP APNEA COULD LEAD TO ATRIAL FIBRILLATION

In experiments in animals, intermittent upper-airway obstruction led to forced inspiration, substantial negative intrathoracic pressure, subsequent left atrial distention, and increased susceptibility to atrial fibrillation.¹⁰ The autonomic nervous system may be a mediator of apnea-induced atrial fibrillation, as apnea-induced atrial fibrillation is suppressed with autonomic blockade.¹⁰

Emerging data also support the hypothesis that intermittent hypoxia⁷ and resolution of hypercapnia,⁸ as observed in obstructive sleep apnea, exert atrial electrophysiologic changes that increase vulnerability to atrial arrhythmogenesis.

In a case-crossover study,¹¹ the odds of paroxysmal atrial fibrillation occurring after a respiratory disturbance were 17.9 times higher than after normal breathing (95% confidence interval [CI] 2.2–144.2), though the absolute rate of overall arrhythmia events (including both atrial fibrillation and nonsustained ventricular tachycardia) associated with respiratory disturbances was low (1 excess arrhythmia event per 40,000 respiratory disturbances).

EFFECT OF SLEEP APNEA ON ATRIAL FIBRILLATION MANAGEMENT

Sleep apnea also seems to affect the efficacy of a rhythm-control strategy for atrial fibrillation. For example, patients with obstructive sleep apnea have a higher risk of recurrent atrial fibrillation after cardioversion (82% vs 42% in controls)¹² and up to a 25% greater risk of recurrence after catheter ablation compared with those without obstructive sleep apnea (risk ratio 1.25, 95% CI 1.08–1.45).¹³

Several observational studies showed a higher rate of atrial fibrillation after pulmonary vein isolation in obstructive sleep apnea patients who do not use continuous positive airway pressure (CPAP) than in those who do.^14–17 CPAP therapy appears to exert beneficial effects on cardiac structural remodeling;  cardiac magnetic resonance imaging shows that patients with sleep apnea who received less than 4 hours of CPAP per night had larger left atrial dimensions and increased left ventricular mass compared with those who received more than 4 hours of CPAP at night.¹⁷ However, a need remains for high-quality, large randomized controlled trials to eliminate potential unmeasured biases due to differences that may exist between CPAP users and non-users, such as general adherence to medical therapy and healthcare interventions.

An additional consideration is that the overall utility and value of obtaining a diagnosis of obstructive sleep apnea strictly as it pertains to atrial fibrillation management is affected by whether a rhythm- or rate-control strategy is pursued. In other words, if a patient is deemed to be in permanent atrial fibrillation and a rhythm-control strategy is therefore not pursued, the potential effect of untreated obstructive sleep apnea on atrial fibrillation recurrence could be less important. In this case, however, the other beneficial cardiovascular and systemic effects of diagnosing and treating underlying obstructive sleep apnea would remain.

 

 

POPULATION STUDIES

Epidemiologic and clinic-based studies have supported an association between sleep apnea (mostly central, but also obstructive) and atrial fibrillation.^4,18

Community-based studies such as the Sleep Heart Health Study⁴ and the Outcomes of Sleep Disorders in Older Men Study (MrOS Sleep),¹⁸ involving thousands of participants, have found the strongest cross-sectional associations of both obstructive and central sleep apnea with nocturnal atrial fibrillation. The findings included a 2 to 5 times higher odds of nocturnal atrial fibrillation, particularly in those with a moderate to severe degree of sleep-disordered breathing—even after adjusting for confounding influences (eg, obesity) and self-reported cardiac disease such as heart failure.

In MrOS Sleep, in an older male cohort, both obstructive and central sleep apnea were associated with nocturnal atrial fibrillation, though central sleep apnea and Cheyne-Stokes respirations had a stronger magnitude of association.¹⁸

Further insights can be drawn specifically from patients with heart failure. Sin et al,¹⁹ in a 1999 study, found that in 450 patients with systolic heart failure (85% men), the prevalence of sleep-disordered breathing was 25% to 33% (depending on the apnea-hypopnea index cutoff used) for central sleep apnea, and similarly 27% to 38% for obstructive sleep apnea. The prevalence of atrial fibrillation in this group was 10% in women and 15% in men. Atrial fibrillation was reported as a significant risk factor for central sleep apnea, but not for obstructive sleep apnea (for which only male sex and increasing body mass index were significant risk factors). Directionality was not clearly reported in this retrospective study in terms of timing of sleep studies and other assessments: ie, the report did not clearly state which came first, the atrial fibrillation or the sleep apnea. Therefore, the possibility that central sleep apnea is a predictor of atrial fibrillation cannot be excluded.  

Yumino et al,²⁰ in a study published in 2009, evaluated 218 patients with heart failure (with a left ventricular ejection fraction of ≤ 45%) and reported a prevalence of moderate to severe sleep apnea of 21% for central sleep apnea and 26% for obstructive sleep apnea. In multivariate analysis, atrial fibrillation was independently associated with central sleep apnea but not obstructive sleep apnea.

In recent cohort studies, central sleep apnea was associated with 2 to 3 times higher odds of developing atrial fibrillation, while obstructive sleep apnea was not a predictor of incident atrial fibrillation.^9,21

Although most available studies associate sleep apnea with atrial fibrillation, findings of a case-control study²² did not support a difference in the prevalence of sleep apnea syndrome (defined as apnea index ≥ 5 and apnea-hypopnea index ≥ 15, and the presence of sleep symptoms) in patients with lone atrial fibrillation (no evident cardiovascular disease) compared with controls matched for age, sex, and cardiovascular morbidity.

But observational studies are limited by the potential for residual unmeasured confounding factors and lack of objective cardiac structural data, such as left ventricular ejection fraction and atrial enlargement. Moreover, there can be significant differences in sleep apnea definitions among studies, thus limiting the ability to reach a definitive conclusion about the relationship between sleep apnea and atrial fibrillation.

SCREENING AND DIAGNOSIS

The 2014 joint guidelines of the American Heart Association, American College of Cardiology, and Heart Rhythm Society for the management of atrial fibrillation state that a sleep study may be useful if sleep apnea is suspected.²³ The 2019 focused update of the 2014 guidelines²⁴ state that for overweight and obese patients with atrial fibrillation, weight loss combined with risk-factor modification is recommended (class I recommendation, level of evidence B-R, ie, data derived from 1 or more randomized trials or meta-analysis of such studies). Risk-factor modification in this case includes assessment and treatment of underlying sleep apnea, hypertension, hyperlipidemia, glucose intolerance, and alcohol and tobacco use.

Further study is needed to evaluate whether physicians should routinely use screening tools for sleep apnea in patients with atrial fibrillation. Standardized screening methods such as the Berlin questionnaire,²⁵ STOP-Bang,²⁶ and NoSAS²⁷ (Table 1) are limited by lack of validation in patients with atrial fibrillation, particularly as the symptom profile may be different from that in patients who do not have atrial fibrillation.

Laboratory polysomnography has long been considered the gold standard for sleep apnea diagnosis. In one study,¹³ obstructive sleep apnea was a greater predictor of atrial fibrillation when diagnosed by polysomnography (risk ratio 1.40, 95% CI 1.16–1.68) compared with identification by screening using the Berlin questionnaire (risk ratio 1.07, 95% CI 0.91–1.27). However, a laboratory sleep study is associated with increased patient burden and limited availability.

Home sleep apnea testing is being increasingly used in the diagnostic evaluation of obstructive sleep apnea and may be a less costly, more available alternative. However, since a home sleep apnea test is less sensitive than polysomnography in detecting obstructive sleep apnea, the American Academy of Sleep Medicine guidelines²⁸ state that if a single home sleep apnea test is negative or inconclusive, polysomnography should be done if there is clinical suspicion of sleep apnea. Moreover, current guidelines from this group recommend that patients with significant cardiorespiratory disease should be tested with polysomnography rather than home sleep apnea testing.²²

Further study is needed to determine the optimal screening method for sleep apnea in patients with atrial fibrillation and to clarify the role of home sleep apnea testing. While keeping in mind the limitations of a screening questionnaire in this population, as a general approach it is reasonable to use a screening questionnaire for sleep apnea. And if the screen is positive, further evaluation with a sleep study is merited, whether by laboratory polysomnography, a home sleep apnea test, or referral to a sleep specialist.

MULTIDISCIPLINARY CARE MAY BE IDEAL

Overall, given the high prevalence of sleep apnea in patients with atrial fibrillation, the deleterious effects of sleep apnea in general, the influence of sleep apnea on atrial fibrillation, and the cardiovascular and other beneficial effects of adequate treatment of sleep apnea, patients with atrial fibrillation should be assessed for sleep apnea.

While the optimal strategy in evaluating for sleep apnea in these patients needs to be further defined, a multidisciplinary approach to care involving a primary care provider, cardiologist, and sleep specialist may be ideal.

Background: Prior studies have suggested that NOACs have a favorable risk-benefit profile when compared with warfarin, but it is unclear if this advantage also is present for those high-risk patients for whom NOAC dose reduction is recommended.

Study design: A meta-analysis.

Setting: Three phase 3 randomized, control trials.

Synopsis: From the three randomized, control trials, the authors identified 7,351 of the 46,426 patients as being eligible for dose-reduced NOACs. Of these patients, 3,702 were randomized to take a NOAC and 3,649 were randomized to take warfarin. For the primary outcomes of stroke or systemic embolism, there was no significant difference between patients randomized to receive dose-reduced NOAC versus warfarin. For outcomes of major bleeding, hemorrhagic stroke, intracranial hemorrhage, and fatal bleeding, dose-reduced NOACs had a significantly lower risk, compared with warfarin.

Bottom line: In patients eligible for dose-reduced NOACs, the use of dose-reduced NOACs may have a better safety profile without significant difference in the rate of ischemic stroke or systemic embolism.

Citation: Wang KL et al. Efficacy and safety of reduced-dose non–vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis of randomized controlled trials. Eur Heart J. 2018 Dec 22. doi: 10.1093/eurheartj/ehy802.

Dr. Biddick is a hospitalist at Beth Israel Deaconess Medical Center and instructor in medicine Harvard Medical School.

Background: Prior studies have suggested that NOACs have a favorable risk-benefit profile when compared with warfarin, but it is unclear if this advantage also is present for those high-risk patients for whom NOAC dose reduction is recommended.

Study design: A meta-analysis.

Setting: Three phase 3 randomized, control trials.

Synopsis: From the three randomized, control trials, the authors identified 7,351 of the 46,426 patients as being eligible for dose-reduced NOACs. Of these patients, 3,702 were randomized to take a NOAC and 3,649 were randomized to take warfarin. For the primary outcomes of stroke or systemic embolism, there was no significant difference between patients randomized to receive dose-reduced NOAC versus warfarin. For outcomes of major bleeding, hemorrhagic stroke, intracranial hemorrhage, and fatal bleeding, dose-reduced NOACs had a significantly lower risk, compared with warfarin.

Bottom line: In patients eligible for dose-reduced NOACs, the use of dose-reduced NOACs may have a better safety profile without significant difference in the rate of ischemic stroke or systemic embolism.

Citation: Wang KL et al. Efficacy and safety of reduced-dose non–vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis of randomized controlled trials. Eur Heart J. 2018 Dec 22. doi: 10.1093/eurheartj/ehy802.

Dr. Biddick is a hospitalist at Beth Israel Deaconess Medical Center and instructor in medicine Harvard Medical School.

Background: Prior studies have suggested that NOACs have a favorable risk-benefit profile when compared with warfarin, but it is unclear if this advantage also is present for those high-risk patients for whom NOAC dose reduction is recommended.

Study design: A meta-analysis.

Setting: Three phase 3 randomized, control trials.

Synopsis: From the three randomized, control trials, the authors identified 7,351 of the 46,426 patients as being eligible for dose-reduced NOACs. Of these patients, 3,702 were randomized to take a NOAC and 3,649 were randomized to take warfarin. For the primary outcomes of stroke or systemic embolism, there was no significant difference between patients randomized to receive dose-reduced NOAC versus warfarin. For outcomes of major bleeding, hemorrhagic stroke, intracranial hemorrhage, and fatal bleeding, dose-reduced NOACs had a significantly lower risk, compared with warfarin.

Bottom line: In patients eligible for dose-reduced NOACs, the use of dose-reduced NOACs may have a better safety profile without significant difference in the rate of ischemic stroke or systemic embolism.

Citation: Wang KL et al. Efficacy and safety of reduced-dose non–vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis of randomized controlled trials. Eur Heart J. 2018 Dec 22. doi: 10.1093/eurheartj/ehy802.

Dr. Biddick is a hospitalist at Beth Israel Deaconess Medical Center and instructor in medicine Harvard Medical School.

 

NEW ORLEANS – Single ventricle congenital heart disease (CHD) and worse social determinants of health are associated with more behavior problems and less total competency in children, and this relationship is mediated by disease-related chronic stress, self-perception, and family environment.

Those are key findings from a large analysis of existing cross-sectional data presented at the annual meeting of the American Academy of Pediatrics. The study set out to assess what factors mediate the relationship between CHD severity, social determinants of health, and behavioral and emotional outcomes.

“We know that worse CHD severity is associated with worse parent-reported and self-reported behavioral and emotional functioning in children and adolescents survivors,” lead author Asad Qadir, MD, said in an interview. “We may be able to improve and optimize behavioral and emotional outcomes in children with congenital heart disease by taking measures that would decrease their and their caregivers’ disease-related chronic stress, improve family functioning, and improve the self-perception of the child. While social determinants of health are not modifiable, they are important for predicting which children may be at risk for behavior problems.”

Dr. Qadir, a cardiology fellow in the department of pediatrics at Northwestern University, Chicago, and colleagues performed a corollary analysis of the Pediatric Cardiac Quality of Life Inventory Testing study, an international, multicenter, cross-sectional study in which parents and patients with CHD completed questionnaires measuring behavioral and emotional functioning, self-perception, family environment, family coping, posttraumatic stress, and illness-related parenting stress (see Qual Life Res. 2008;17:613-26, Pediatrics. 2010;126[3]:498-508, and Cardiol Young. 2014;[2]:220-8). They assessed the relationships between CHD severity and social determinants of health (predictors), disease-related stress and psychosocial adaptation (mediators), and behavioral and emotional outcomes. They used structural equation modeling to determine the effects of predictors and mediators on outcomes, and created multivariable models for each patient- and parent-reported outcome.

The analysis included 981 patient-parent dyads. Of these, 210 patients had mild biventricular CHD, 620 had moderate biventricular CHD, and 151 had single ventricle CHD. The mean age of patients was 13 years and 55% were male. The researchers found that single ventricle CHD and worse social determinants of health were significant predictors of greater disease-related chronic stress for patients and caregivers and worse psychosocial adaptation in CHD survivors, including self-perception and family functioning constructs of cohesion and expressiveness (P less than .001 for all associations). In addition, single ventricle CHD and worse social determinants of health were associated with worse behavioral and emotional outcomes as reported by patients and parents, including internalizing behaviors, externalizing behaviors, and total competency (P less than .001 for all associations).

In multivariable models for all parent-reported outcomes, significant associations were observed between single ventricle CHD, social determinants of health, disease-related stress, child receiving mental health services, and cohesion/conflict in the family environment (P less than .001). In multivariable models for all patient-reported outcomes, significant associations were seen between single ventricle CHD, self-perception, and cohesion/conflict in the family environment (P less than 0.001).

Patient disease-related stress had the strongest association with externalizing problems, and worse social determinants of health significantly lowered patient-reported total competency.

“Many of the relationships found in the study make intuitive sense,” Dr. Qadir said. “For example, less favorable social determinants of health were associated with more parent disease-related chronic stress, which in turn was associated with parent-reported behavior problems in children. What was surprising was that worse behavioral outcomes were specifically associated with single ventricle disease only. Complex biventricular congenital heart disease patients (CHD that required a surgical- or catheter-based intervention) often have worse behavioral and emotional outcomes, similar to single ventricle patients. However, our model would argue that biventricular congenital heart disease complexity patients have more behavioral and emotional issues not because of their disease complexity, but due to their social determinants of health and the amount of disease-related chronic stress in the child and the parent and the amount of psychosocial adaptation found in the child and parent.”

Parent and patient disease-related chronic stress was not only an important mediator of the effect of CHD severity and social determinants of health on behavioral and emotional outcomes, he added, but it also had indirect effects that were mediated by family cohesion/conflict and patient self-perception.

“These data suggest that for those children with worse social determinants of health and single ventricle congenital heart disease, interventions that mitigate disease-related chronic stress, promote family functioning, and promote self-perception in the child may improve or optimize behavioral and emotional functioning during childhood and adolescence in CHD surgical survivors,” Dr. Qadir concluded.

He acknowledged certain limitations of the analysis, including the fact that it was a corollary cross-sectional analysis of an existing data set. “The results do not reflect possible changes over time,” he added. “There was also selection bias as non-English speakers were excluded, and the study population had a greater percentage of Caucasian and highly educated parents with higher income than the general population, which may affect the generalizability of our results.”

The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

 

NEW ORLEANS – Single ventricle congenital heart disease (CHD) and worse social determinants of health are associated with more behavior problems and less total competency in children, and this relationship is mediated by disease-related chronic stress, self-perception, and family environment.

Those are key findings from a large analysis of existing cross-sectional data presented at the annual meeting of the American Academy of Pediatrics. The study set out to assess what factors mediate the relationship between CHD severity, social determinants of health, and behavioral and emotional outcomes.

“We know that worse CHD severity is associated with worse parent-reported and self-reported behavioral and emotional functioning in children and adolescents survivors,” lead author Asad Qadir, MD, said in an interview. “We may be able to improve and optimize behavioral and emotional outcomes in children with congenital heart disease by taking measures that would decrease their and their caregivers’ disease-related chronic stress, improve family functioning, and improve the self-perception of the child. While social determinants of health are not modifiable, they are important for predicting which children may be at risk for behavior problems.”

Dr. Qadir, a cardiology fellow in the department of pediatrics at Northwestern University, Chicago, and colleagues performed a corollary analysis of the Pediatric Cardiac Quality of Life Inventory Testing study, an international, multicenter, cross-sectional study in which parents and patients with CHD completed questionnaires measuring behavioral and emotional functioning, self-perception, family environment, family coping, posttraumatic stress, and illness-related parenting stress (see Qual Life Res. 2008;17:613-26, Pediatrics. 2010;126[3]:498-508, and Cardiol Young. 2014;[2]:220-8). They assessed the relationships between CHD severity and social determinants of health (predictors), disease-related stress and psychosocial adaptation (mediators), and behavioral and emotional outcomes. They used structural equation modeling to determine the effects of predictors and mediators on outcomes, and created multivariable models for each patient- and parent-reported outcome.

The analysis included 981 patient-parent dyads. Of these, 210 patients had mild biventricular CHD, 620 had moderate biventricular CHD, and 151 had single ventricle CHD. The mean age of patients was 13 years and 55% were male. The researchers found that single ventricle CHD and worse social determinants of health were significant predictors of greater disease-related chronic stress for patients and caregivers and worse psychosocial adaptation in CHD survivors, including self-perception and family functioning constructs of cohesion and expressiveness (P less than .001 for all associations). In addition, single ventricle CHD and worse social determinants of health were associated with worse behavioral and emotional outcomes as reported by patients and parents, including internalizing behaviors, externalizing behaviors, and total competency (P less than .001 for all associations).

In multivariable models for all parent-reported outcomes, significant associations were observed between single ventricle CHD, social determinants of health, disease-related stress, child receiving mental health services, and cohesion/conflict in the family environment (P less than .001). In multivariable models for all patient-reported outcomes, significant associations were seen between single ventricle CHD, self-perception, and cohesion/conflict in the family environment (P less than 0.001).

Patient disease-related stress had the strongest association with externalizing problems, and worse social determinants of health significantly lowered patient-reported total competency.

“Many of the relationships found in the study make intuitive sense,” Dr. Qadir said. “For example, less favorable social determinants of health were associated with more parent disease-related chronic stress, which in turn was associated with parent-reported behavior problems in children. What was surprising was that worse behavioral outcomes were specifically associated with single ventricle disease only. Complex biventricular congenital heart disease patients (CHD that required a surgical- or catheter-based intervention) often have worse behavioral and emotional outcomes, similar to single ventricle patients. However, our model would argue that biventricular congenital heart disease complexity patients have more behavioral and emotional issues not because of their disease complexity, but due to their social determinants of health and the amount of disease-related chronic stress in the child and the parent and the amount of psychosocial adaptation found in the child and parent.”

Parent and patient disease-related chronic stress was not only an important mediator of the effect of CHD severity and social determinants of health on behavioral and emotional outcomes, he added, but it also had indirect effects that were mediated by family cohesion/conflict and patient self-perception.

“These data suggest that for those children with worse social determinants of health and single ventricle congenital heart disease, interventions that mitigate disease-related chronic stress, promote family functioning, and promote self-perception in the child may improve or optimize behavioral and emotional functioning during childhood and adolescence in CHD surgical survivors,” Dr. Qadir concluded.

He acknowledged certain limitations of the analysis, including the fact that it was a corollary cross-sectional analysis of an existing data set. “The results do not reflect possible changes over time,” he added. “There was also selection bias as non-English speakers were excluded, and the study population had a greater percentage of Caucasian and highly educated parents with higher income than the general population, which may affect the generalizability of our results.”

The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

 

NEW ORLEANS – Single ventricle congenital heart disease (CHD) and worse social determinants of health are associated with more behavior problems and less total competency in children, and this relationship is mediated by disease-related chronic stress, self-perception, and family environment.

Those are key findings from a large analysis of existing cross-sectional data presented at the annual meeting of the American Academy of Pediatrics. The study set out to assess what factors mediate the relationship between CHD severity, social determinants of health, and behavioral and emotional outcomes.

“We know that worse CHD severity is associated with worse parent-reported and self-reported behavioral and emotional functioning in children and adolescents survivors,” lead author Asad Qadir, MD, said in an interview. “We may be able to improve and optimize behavioral and emotional outcomes in children with congenital heart disease by taking measures that would decrease their and their caregivers’ disease-related chronic stress, improve family functioning, and improve the self-perception of the child. While social determinants of health are not modifiable, they are important for predicting which children may be at risk for behavior problems.”

Dr. Qadir, a cardiology fellow in the department of pediatrics at Northwestern University, Chicago, and colleagues performed a corollary analysis of the Pediatric Cardiac Quality of Life Inventory Testing study, an international, multicenter, cross-sectional study in which parents and patients with CHD completed questionnaires measuring behavioral and emotional functioning, self-perception, family environment, family coping, posttraumatic stress, and illness-related parenting stress (see Qual Life Res. 2008;17:613-26, Pediatrics. 2010;126[3]:498-508, and Cardiol Young. 2014;[2]:220-8). They assessed the relationships between CHD severity and social determinants of health (predictors), disease-related stress and psychosocial adaptation (mediators), and behavioral and emotional outcomes. They used structural equation modeling to determine the effects of predictors and mediators on outcomes, and created multivariable models for each patient- and parent-reported outcome.

The analysis included 981 patient-parent dyads. Of these, 210 patients had mild biventricular CHD, 620 had moderate biventricular CHD, and 151 had single ventricle CHD. The mean age of patients was 13 years and 55% were male. The researchers found that single ventricle CHD and worse social determinants of health were significant predictors of greater disease-related chronic stress for patients and caregivers and worse psychosocial adaptation in CHD survivors, including self-perception and family functioning constructs of cohesion and expressiveness (P less than .001 for all associations). In addition, single ventricle CHD and worse social determinants of health were associated with worse behavioral and emotional outcomes as reported by patients and parents, including internalizing behaviors, externalizing behaviors, and total competency (P less than .001 for all associations).

In multivariable models for all parent-reported outcomes, significant associations were observed between single ventricle CHD, social determinants of health, disease-related stress, child receiving mental health services, and cohesion/conflict in the family environment (P less than .001). In multivariable models for all patient-reported outcomes, significant associations were seen between single ventricle CHD, self-perception, and cohesion/conflict in the family environment (P less than 0.001).

Patient disease-related stress had the strongest association with externalizing problems, and worse social determinants of health significantly lowered patient-reported total competency.

“Many of the relationships found in the study make intuitive sense,” Dr. Qadir said. “For example, less favorable social determinants of health were associated with more parent disease-related chronic stress, which in turn was associated with parent-reported behavior problems in children. What was surprising was that worse behavioral outcomes were specifically associated with single ventricle disease only. Complex biventricular congenital heart disease patients (CHD that required a surgical- or catheter-based intervention) often have worse behavioral and emotional outcomes, similar to single ventricle patients. However, our model would argue that biventricular congenital heart disease complexity patients have more behavioral and emotional issues not because of their disease complexity, but due to their social determinants of health and the amount of disease-related chronic stress in the child and the parent and the amount of psychosocial adaptation found in the child and parent.”

Parent and patient disease-related chronic stress was not only an important mediator of the effect of CHD severity and social determinants of health on behavioral and emotional outcomes, he added, but it also had indirect effects that were mediated by family cohesion/conflict and patient self-perception.

“These data suggest that for those children with worse social determinants of health and single ventricle congenital heart disease, interventions that mitigate disease-related chronic stress, promote family functioning, and promote self-perception in the child may improve or optimize behavioral and emotional functioning during childhood and adolescence in CHD surgical survivors,” Dr. Qadir concluded.

He acknowledged certain limitations of the analysis, including the fact that it was a corollary cross-sectional analysis of an existing data set. “The results do not reflect possible changes over time,” he added. “There was also selection bias as non-English speakers were excluded, and the study population had a greater percentage of Caucasian and highly educated parents with higher income than the general population, which may affect the generalizability of our results.”

The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

 

PARIS – The Geriatric Nutritional Risk Index proved to be an independent predictor of 5-year overall survival as well as the composite of major adverse cardiovascular and limb events in a prospective cohort study of 1,219 patients with peripheral artery disease, Yae Matsuo, MD, reported at the annual congress of the European Society of Cardiology.

The Geriatric Nutritional Risk Index (GNRI) is a score calculated with a formula based upon a patient’s height, serum albumin, and the ratio between ideal and actual body weight (Am J Clin Nutr. 2005 Oct;82(4):777-83). The GNRI tool has been shown to be an accurate prognosticator for clinical outcomes in patients on hemodialysis and those with heart failure. However, it’s predictive accuracy hasn’t been evaluated in patients with PAD, according to Dr. Matsuo, a cardiologist at Kitakanto Cardiovascular Hospital in Shibukawa, Japan.

“The Geriatric Nutritional Risk Index is simple to calculate – so easy – and I think it’s a better predictor than BMI,” she said.

Fifty-six percent of the PAD patients had a GNRI score greater than 98, indicative of no increased risk of malnutrition and nutritional deficiencies. Their 5-year overall survival rate was 81%, compared with 62% in patients with a score of 92-98, 40% in those with a score of 82-91, and 23% with a score of less than 82. Other independent predictors of overall survival in multivariate analysis were age, estimated glomerular filtration rate, ankle brachial index, and C-reactive protein level.

A GNRI score above 98 was also predictive of significantly lower 5-year risk of both major adverse cardiovascular events and the composite of major adverse cardiovascular and limb events than in patients with a score of 98 or less.

The key remaining unanswered question is whether providing timely nutritional support to PAD patients with a low GNRI score will result in improved overall and limb survival and other outcomes.

Dr. Matsuo reported having no financial conflicts.

bjancin@mdedge.com

SOURCE: Matsuo Y. ESC CONGRESS 2019. Abstract P1956.

 

PARIS – The Geriatric Nutritional Risk Index proved to be an independent predictor of 5-year overall survival as well as the composite of major adverse cardiovascular and limb events in a prospective cohort study of 1,219 patients with peripheral artery disease, Yae Matsuo, MD, reported at the annual congress of the European Society of Cardiology.

The Geriatric Nutritional Risk Index (GNRI) is a score calculated with a formula based upon a patient’s height, serum albumin, and the ratio between ideal and actual body weight (Am J Clin Nutr. 2005 Oct;82(4):777-83). The GNRI tool has been shown to be an accurate prognosticator for clinical outcomes in patients on hemodialysis and those with heart failure. However, it’s predictive accuracy hasn’t been evaluated in patients with PAD, according to Dr. Matsuo, a cardiologist at Kitakanto Cardiovascular Hospital in Shibukawa, Japan.

“The Geriatric Nutritional Risk Index is simple to calculate – so easy – and I think it’s a better predictor than BMI,” she said.

Fifty-six percent of the PAD patients had a GNRI score greater than 98, indicative of no increased risk of malnutrition and nutritional deficiencies. Their 5-year overall survival rate was 81%, compared with 62% in patients with a score of 92-98, 40% in those with a score of 82-91, and 23% with a score of less than 82. Other independent predictors of overall survival in multivariate analysis were age, estimated glomerular filtration rate, ankle brachial index, and C-reactive protein level.

A GNRI score above 98 was also predictive of significantly lower 5-year risk of both major adverse cardiovascular events and the composite of major adverse cardiovascular and limb events than in patients with a score of 98 or less.

The key remaining unanswered question is whether providing timely nutritional support to PAD patients with a low GNRI score will result in improved overall and limb survival and other outcomes.

Dr. Matsuo reported having no financial conflicts.

bjancin@mdedge.com

SOURCE: Matsuo Y. ESC CONGRESS 2019. Abstract P1956.

 

PARIS – The Geriatric Nutritional Risk Index proved to be an independent predictor of 5-year overall survival as well as the composite of major adverse cardiovascular and limb events in a prospective cohort study of 1,219 patients with peripheral artery disease, Yae Matsuo, MD, reported at the annual congress of the European Society of Cardiology.

The Geriatric Nutritional Risk Index (GNRI) is a score calculated with a formula based upon a patient’s height, serum albumin, and the ratio between ideal and actual body weight (Am J Clin Nutr. 2005 Oct;82(4):777-83). The GNRI tool has been shown to be an accurate prognosticator for clinical outcomes in patients on hemodialysis and those with heart failure. However, it’s predictive accuracy hasn’t been evaluated in patients with PAD, according to Dr. Matsuo, a cardiologist at Kitakanto Cardiovascular Hospital in Shibukawa, Japan.

“The Geriatric Nutritional Risk Index is simple to calculate – so easy – and I think it’s a better predictor than BMI,” she said.

Fifty-six percent of the PAD patients had a GNRI score greater than 98, indicative of no increased risk of malnutrition and nutritional deficiencies. Their 5-year overall survival rate was 81%, compared with 62% in patients with a score of 92-98, 40% in those with a score of 82-91, and 23% with a score of less than 82. Other independent predictors of overall survival in multivariate analysis were age, estimated glomerular filtration rate, ankle brachial index, and C-reactive protein level.

A GNRI score above 98 was also predictive of significantly lower 5-year risk of both major adverse cardiovascular events and the composite of major adverse cardiovascular and limb events than in patients with a score of 98 or less.

The key remaining unanswered question is whether providing timely nutritional support to PAD patients with a low GNRI score will result in improved overall and limb survival and other outcomes.

Dr. Matsuo reported having no financial conflicts.

bjancin@mdedge.com

SOURCE: Matsuo Y. ESC CONGRESS 2019. Abstract P1956.

NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.

Jen Smith/MDedge News

Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.

“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.

She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.

Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.

Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.

The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.

Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).

About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).

The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.

The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.

The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.

jensmith@mdedge.com

SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.

NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.

Jen Smith/MDedge News

Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.

“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.

She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.

Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.

Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.

The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.

Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).

About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).

The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.

The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.

The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.

jensmith@mdedge.com

SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.

NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.

Jen Smith/MDedge News

Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.

“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.

She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.

Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.

Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.

The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.

Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).

About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).

The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.

The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.

The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.

jensmith@mdedge.com

SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.

 

A significant portion of the increased cardiovascular disease risk seen in black adults may stem from hypertension, according to a prospective cohort study published by a team led by Donald Clark III, MD, of the University of Mississippi in Jackson.

The analysis showed that about one-third of cardiovascular disease can be traced to hypertension in black adults, and the influence was much stronger in individuals under 60, suggesting that early interventions to maintain normal blood pressure have the potential to reduce risk in this population.

Hypertension is already known to be the leading contributor to cardiovascular disease (CVD) in the United States, and non-Hispanic black adults experience it at a rate of 55%, higher than any other group.

The researchers used data from the Jackson Heart Study (JHS) and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between CVD and hypertension, and NHANES 2011-2014 to examine the rate of hypertension among non-Hispanic black adults in the United States.

At baseline, among 12,497 participants In the JHS and REGARDS studies, 33% had normal blood pressure, 41% had elevated BP, and 36% had hypertension. In the NHANES cohort, 35% had normal BP, 12% had elevated BP, and 53% had hypertension.

In the combined JHS and REGARDS cohorts, subjects with elevated BP and hypertension had greater odds of taking cholesterol-lowering medication compared to those with normal BP: 8.5% of normotensive patients and 9.9% of those with elevated BP were on medication, compared with 26.0% of hypertensive patient, emphasizing the importance of effective hypertension management, the investigators noted.

Similarly, 9.9% of patients with normal BP and 14.7% of those with elevated BP had diabetes, compared with 26.0% of hypertensive patients. Hypertensive patients were also less likely to have graduated from high school (81%) than were those with elevated BP (84.5%) and normal BP (89.9%), and they had a higher mean body mass index (31.4 kg/m2) than their counterparts with elevated (29.6) and normal (28.8) BP.

After a maximum of 14.3 years of follow-up, 9.9% of participants experienced a CVD event. The researchers calculated the population attributable risk (PAR) using the prevalence of hypertension from the NHANES dataset and the multivariable-adjusted association between elevated versus normal BP and hypertension versus normal BP in the JHS and REGARDS data.

“Hypertension was independently associated with incident [coronary heart disease], heart failure, and stroke,” the investigators wrote. The PARs associated with hypertension were 32.5% (95% CI, 20.5-43.6%) for CVD, 42.7% (95% CI, 24.0-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6-40.8%) for heart failure, and 38.9% (95% CI, 19.4-55.6%) for stroke.

Men and women had similar PAR values for CVD (33.9% vs. 31.1%). Participants younger than 60 had a higher value of PAR associated with hypertension than older participants (54.6% [95% CI, 37.2-68.7%] vs. 32.0% [95% CI, 11.9-48.1%]). Dr. Clark and his coinvestigators noted that the “most substantial finding” of the study was PAR of 69% for stroke associated with hypertension found in patients younger than 60 years. “These data suggest that interventions to maintain normal BP across the life course may reduce the incidence of CVD in this population,” they concluded.

The REGARDS study was funded by NIH and the American Heart Association. The JHS study was funded by Jackson State University, Tougaloo College, the Mississippi State Department of Health, and the University of Mississippi Medical Center. The authors have extensive financial ties to pharmaceutical companies.

SOURCE: JAMA Card. 2019. October 23, 2019. doi:10.1001/jamacardio.2019.3773.

 

A significant portion of the increased cardiovascular disease risk seen in black adults may stem from hypertension, according to a prospective cohort study published by a team led by Donald Clark III, MD, of the University of Mississippi in Jackson.

The analysis showed that about one-third of cardiovascular disease can be traced to hypertension in black adults, and the influence was much stronger in individuals under 60, suggesting that early interventions to maintain normal blood pressure have the potential to reduce risk in this population.

Hypertension is already known to be the leading contributor to cardiovascular disease (CVD) in the United States, and non-Hispanic black adults experience it at a rate of 55%, higher than any other group.

The researchers used data from the Jackson Heart Study (JHS) and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between CVD and hypertension, and NHANES 2011-2014 to examine the rate of hypertension among non-Hispanic black adults in the United States.

At baseline, among 12,497 participants In the JHS and REGARDS studies, 33% had normal blood pressure, 41% had elevated BP, and 36% had hypertension. In the NHANES cohort, 35% had normal BP, 12% had elevated BP, and 53% had hypertension.

In the combined JHS and REGARDS cohorts, subjects with elevated BP and hypertension had greater odds of taking cholesterol-lowering medication compared to those with normal BP: 8.5% of normotensive patients and 9.9% of those with elevated BP were on medication, compared with 26.0% of hypertensive patient, emphasizing the importance of effective hypertension management, the investigators noted.

Similarly, 9.9% of patients with normal BP and 14.7% of those with elevated BP had diabetes, compared with 26.0% of hypertensive patients. Hypertensive patients were also less likely to have graduated from high school (81%) than were those with elevated BP (84.5%) and normal BP (89.9%), and they had a higher mean body mass index (31.4 kg/m2) than their counterparts with elevated (29.6) and normal (28.8) BP.

After a maximum of 14.3 years of follow-up, 9.9% of participants experienced a CVD event. The researchers calculated the population attributable risk (PAR) using the prevalence of hypertension from the NHANES dataset and the multivariable-adjusted association between elevated versus normal BP and hypertension versus normal BP in the JHS and REGARDS data.

“Hypertension was independently associated with incident [coronary heart disease], heart failure, and stroke,” the investigators wrote. The PARs associated with hypertension were 32.5% (95% CI, 20.5-43.6%) for CVD, 42.7% (95% CI, 24.0-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6-40.8%) for heart failure, and 38.9% (95% CI, 19.4-55.6%) for stroke.

Men and women had similar PAR values for CVD (33.9% vs. 31.1%). Participants younger than 60 had a higher value of PAR associated with hypertension than older participants (54.6% [95% CI, 37.2-68.7%] vs. 32.0% [95% CI, 11.9-48.1%]). Dr. Clark and his coinvestigators noted that the “most substantial finding” of the study was PAR of 69% for stroke associated with hypertension found in patients younger than 60 years. “These data suggest that interventions to maintain normal BP across the life course may reduce the incidence of CVD in this population,” they concluded.

The REGARDS study was funded by NIH and the American Heart Association. The JHS study was funded by Jackson State University, Tougaloo College, the Mississippi State Department of Health, and the University of Mississippi Medical Center. The authors have extensive financial ties to pharmaceutical companies.

SOURCE: JAMA Card. 2019. October 23, 2019. doi:10.1001/jamacardio.2019.3773.

 

A significant portion of the increased cardiovascular disease risk seen in black adults may stem from hypertension, according to a prospective cohort study published by a team led by Donald Clark III, MD, of the University of Mississippi in Jackson.

The analysis showed that about one-third of cardiovascular disease can be traced to hypertension in black adults, and the influence was much stronger in individuals under 60, suggesting that early interventions to maintain normal blood pressure have the potential to reduce risk in this population.

Hypertension is already known to be the leading contributor to cardiovascular disease (CVD) in the United States, and non-Hispanic black adults experience it at a rate of 55%, higher than any other group.

The researchers used data from the Jackson Heart Study (JHS) and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between CVD and hypertension, and NHANES 2011-2014 to examine the rate of hypertension among non-Hispanic black adults in the United States.

At baseline, among 12,497 participants In the JHS and REGARDS studies, 33% had normal blood pressure, 41% had elevated BP, and 36% had hypertension. In the NHANES cohort, 35% had normal BP, 12% had elevated BP, and 53% had hypertension.

In the combined JHS and REGARDS cohorts, subjects with elevated BP and hypertension had greater odds of taking cholesterol-lowering medication compared to those with normal BP: 8.5% of normotensive patients and 9.9% of those with elevated BP were on medication, compared with 26.0% of hypertensive patient, emphasizing the importance of effective hypertension management, the investigators noted.

Similarly, 9.9% of patients with normal BP and 14.7% of those with elevated BP had diabetes, compared with 26.0% of hypertensive patients. Hypertensive patients were also less likely to have graduated from high school (81%) than were those with elevated BP (84.5%) and normal BP (89.9%), and they had a higher mean body mass index (31.4 kg/m2) than their counterparts with elevated (29.6) and normal (28.8) BP.

After a maximum of 14.3 years of follow-up, 9.9% of participants experienced a CVD event. The researchers calculated the population attributable risk (PAR) using the prevalence of hypertension from the NHANES dataset and the multivariable-adjusted association between elevated versus normal BP and hypertension versus normal BP in the JHS and REGARDS data.

“Hypertension was independently associated with incident [coronary heart disease], heart failure, and stroke,” the investigators wrote. The PARs associated with hypertension were 32.5% (95% CI, 20.5-43.6%) for CVD, 42.7% (95% CI, 24.0-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6-40.8%) for heart failure, and 38.9% (95% CI, 19.4-55.6%) for stroke.

Men and women had similar PAR values for CVD (33.9% vs. 31.1%). Participants younger than 60 had a higher value of PAR associated with hypertension than older participants (54.6% [95% CI, 37.2-68.7%] vs. 32.0% [95% CI, 11.9-48.1%]). Dr. Clark and his coinvestigators noted that the “most substantial finding” of the study was PAR of 69% for stroke associated with hypertension found in patients younger than 60 years. “These data suggest that interventions to maintain normal BP across the life course may reduce the incidence of CVD in this population,” they concluded.

The REGARDS study was funded by NIH and the American Heart Association. The JHS study was funded by Jackson State University, Tougaloo College, the Mississippi State Department of Health, and the University of Mississippi Medical Center. The authors have extensive financial ties to pharmaceutical companies.

SOURCE: JAMA Card. 2019. October 23, 2019. doi:10.1001/jamacardio.2019.3773.

PHILADELPHIA – For patients transitioning to home after a heart failure hospitalization, substituting in-person visits with virtual, video-based visits is feasible, safe, and may reduce appointment no-show rates, results of a randomized study suggest.

Connecting patients with clinicians over secure video cut no-show rates at 7 days post-discharge by about one-third, with no difference in risk of readmission, emergency department visits, or death, compared with the traditional in-person follow-up visit, investigator Eiran Z. Gorodeski, MD, MPH, reported here at the annual scientific meeting of the Heart Failure Society of America.

While the video meet-up doesn’t allow for a physical exam, it’s still possible to collect history of what happened since hospital discharge, assess breathing, and complete other aspects of the follow-up visit, according to Dr. Gorodeski, director of advanced heart failure section at the University Hospitals Cleveland Medical Center.

“The way we view use of virtual visits 7 days post-discharge is, in many ways, as a screening platform,” he said in a panel discussion. “If someone seems to be doing poorly, you can always invite them to come in, but most patients post discharge are not congested, and they’re doing quite well. Probably the more relevant issues are things like: Do they have their medications? Do they understand what their follow-up appointments are?”

During the virtual visit, patients are asked to hold their medication bottles up to the camera so the clinician can see what they are taking.

“Frequently, we are able to catch mistakes,” Dr. Gorodeski said. “Of note, most patients don’t bring their pill bottles to the clinic, so in some ways doing the virtual visit for that aspect was more valuable.”

Patients who opt for a virtual visit can do so from any smart phone, laptop, or desktop computer. Once logged in, they enter a virtual waiting room as the clinician receives a text notification to log in and begin the visit.

“It’s very efficient with time, and my questions were answered quickly,” said a patient in a short video Dr. Gorodeski played to illustrate the technology.

“I still feel the same connectivity with the patient,” a clinician in the video said.

There is currently no way to bill insurance companies for this type of visit, Dr. Gorodeski said when asked what initial barriers other institutions might have implementing a similar approach.

In the randomized, single-center clinical trial Dr. Gorodeski presented here at the HFSA meeting, called VIV-HF (Virtual Visits in Heart Failure Care Transitions), a total of 108 patients were randomized to the virtual visit (52 patients) or an in-person visit (56 patients).

The majority of patients (over 60%) had heart failure with reduced ejection fraction, according to the reported study results.

No-show rates were 50% for the in-person visit, and 34.6% for the virtual visit, for a relative risk reduction of 31%. However, this difference did not reach statistical significance, likely because the study was underpowered, according to Dr. Gorodeski.

“This strategy may reduce postdischarge appointment no-show rates, and this needs to be studied further in larger and appropriately powered clinical trials,” he said in presenting the results.

The 7-day postdischarge outpatient clinic visit is recommended in guidelines and viewed as a way to increase care engagement while reducing risk of poor outcomes, according to VIV-HF investigators.

Support for the study came from the Hunnell Fund. Dr. Gorodeski reported being a consultant and advisor to Abbott.

cardnews@mdedge

SOURCE: Gorodeski EZ, et al. HFSA 2019. Late-Breaking Clinical Trials session.

PHILADELPHIA – For patients transitioning to home after a heart failure hospitalization, substituting in-person visits with virtual, video-based visits is feasible, safe, and may reduce appointment no-show rates, results of a randomized study suggest.

Connecting patients with clinicians over secure video cut no-show rates at 7 days post-discharge by about one-third, with no difference in risk of readmission, emergency department visits, or death, compared with the traditional in-person follow-up visit, investigator Eiran Z. Gorodeski, MD, MPH, reported here at the annual scientific meeting of the Heart Failure Society of America.

While the video meet-up doesn’t allow for a physical exam, it’s still possible to collect history of what happened since hospital discharge, assess breathing, and complete other aspects of the follow-up visit, according to Dr. Gorodeski, director of advanced heart failure section at the University Hospitals Cleveland Medical Center.

“The way we view use of virtual visits 7 days post-discharge is, in many ways, as a screening platform,” he said in a panel discussion. “If someone seems to be doing poorly, you can always invite them to come in, but most patients post discharge are not congested, and they’re doing quite well. Probably the more relevant issues are things like: Do they have their medications? Do they understand what their follow-up appointments are?”

During the virtual visit, patients are asked to hold their medication bottles up to the camera so the clinician can see what they are taking.

“Frequently, we are able to catch mistakes,” Dr. Gorodeski said. “Of note, most patients don’t bring their pill bottles to the clinic, so in some ways doing the virtual visit for that aspect was more valuable.”

Patients who opt for a virtual visit can do so from any smart phone, laptop, or desktop computer. Once logged in, they enter a virtual waiting room as the clinician receives a text notification to log in and begin the visit.

“It’s very efficient with time, and my questions were answered quickly,” said a patient in a short video Dr. Gorodeski played to illustrate the technology.

“I still feel the same connectivity with the patient,” a clinician in the video said.

There is currently no way to bill insurance companies for this type of visit, Dr. Gorodeski said when asked what initial barriers other institutions might have implementing a similar approach.

In the randomized, single-center clinical trial Dr. Gorodeski presented here at the HFSA meeting, called VIV-HF (Virtual Visits in Heart Failure Care Transitions), a total of 108 patients were randomized to the virtual visit (52 patients) or an in-person visit (56 patients).

The majority of patients (over 60%) had heart failure with reduced ejection fraction, according to the reported study results.

No-show rates were 50% for the in-person visit, and 34.6% for the virtual visit, for a relative risk reduction of 31%. However, this difference did not reach statistical significance, likely because the study was underpowered, according to Dr. Gorodeski.

“This strategy may reduce postdischarge appointment no-show rates, and this needs to be studied further in larger and appropriately powered clinical trials,” he said in presenting the results.

The 7-day postdischarge outpatient clinic visit is recommended in guidelines and viewed as a way to increase care engagement while reducing risk of poor outcomes, according to VIV-HF investigators.

Support for the study came from the Hunnell Fund. Dr. Gorodeski reported being a consultant and advisor to Abbott.

cardnews@mdedge

SOURCE: Gorodeski EZ, et al. HFSA 2019. Late-Breaking Clinical Trials session.

PHILADELPHIA – For patients transitioning to home after a heart failure hospitalization, substituting in-person visits with virtual, video-based visits is feasible, safe, and may reduce appointment no-show rates, results of a randomized study suggest.

Connecting patients with clinicians over secure video cut no-show rates at 7 days post-discharge by about one-third, with no difference in risk of readmission, emergency department visits, or death, compared with the traditional in-person follow-up visit, investigator Eiran Z. Gorodeski, MD, MPH, reported here at the annual scientific meeting of the Heart Failure Society of America.

While the video meet-up doesn’t allow for a physical exam, it’s still possible to collect history of what happened since hospital discharge, assess breathing, and complete other aspects of the follow-up visit, according to Dr. Gorodeski, director of advanced heart failure section at the University Hospitals Cleveland Medical Center.

“The way we view use of virtual visits 7 days post-discharge is, in many ways, as a screening platform,” he said in a panel discussion. “If someone seems to be doing poorly, you can always invite them to come in, but most patients post discharge are not congested, and they’re doing quite well. Probably the more relevant issues are things like: Do they have their medications? Do they understand what their follow-up appointments are?”

During the virtual visit, patients are asked to hold their medication bottles up to the camera so the clinician can see what they are taking.

“Frequently, we are able to catch mistakes,” Dr. Gorodeski said. “Of note, most patients don’t bring their pill bottles to the clinic, so in some ways doing the virtual visit for that aspect was more valuable.”

Patients who opt for a virtual visit can do so from any smart phone, laptop, or desktop computer. Once logged in, they enter a virtual waiting room as the clinician receives a text notification to log in and begin the visit.

“It’s very efficient with time, and my questions were answered quickly,” said a patient in a short video Dr. Gorodeski played to illustrate the technology.

“I still feel the same connectivity with the patient,” a clinician in the video said.

There is currently no way to bill insurance companies for this type of visit, Dr. Gorodeski said when asked what initial barriers other institutions might have implementing a similar approach.

In the randomized, single-center clinical trial Dr. Gorodeski presented here at the HFSA meeting, called VIV-HF (Virtual Visits in Heart Failure Care Transitions), a total of 108 patients were randomized to the virtual visit (52 patients) or an in-person visit (56 patients).

The majority of patients (over 60%) had heart failure with reduced ejection fraction, according to the reported study results.

No-show rates were 50% for the in-person visit, and 34.6% for the virtual visit, for a relative risk reduction of 31%. However, this difference did not reach statistical significance, likely because the study was underpowered, according to Dr. Gorodeski.

“This strategy may reduce postdischarge appointment no-show rates, and this needs to be studied further in larger and appropriately powered clinical trials,” he said in presenting the results.

The 7-day postdischarge outpatient clinic visit is recommended in guidelines and viewed as a way to increase care engagement while reducing risk of poor outcomes, according to VIV-HF investigators.

Support for the study came from the Hunnell Fund. Dr. Gorodeski reported being a consultant and advisor to Abbott.

cardnews@mdedge

SOURCE: Gorodeski EZ, et al. HFSA 2019. Late-Breaking Clinical Trials session.

 

PARIS – Fewer than half of commercial drivers who received implantable cardioverter-defibrillators (ICDs) recalled being told they should never drive professionally again, according to a recent Danish survey. Further, about a third of patients overall reported that they began driving soon after they received an ICD, during the period when guidelines recommend refraining from driving.

“These devices, they save lives – so what’s not to like?” lead investigator Jenny Bjerre, MD, asked at the annual congress of the European Society of Cardiology. “Well, if you are a patient qualifying for an ICD, you also automatically qualify for some driving restrictions.” These are put in place because of the concern for an arrhythmia causing a loss of consciousness behind the wheel, she said.

A European consensus statement calls for a 3-month driving moratorium when an ICD is implanted for secondary prevention or after an appropriate ICD shock, and a 4-week restriction when an ICD is placed for primary prevention. All these restrictions apply to personal driver’s licenses; anyone with an ICD is permanently restricted from commercial driving according to the consensus statement, said Dr. Bjerre, of the University Hospital, Copenhagen.

“As you can imagine, these restrictions are not that popular with the patients,” she said. She related the story of a patient, a taxi driver who had returned to a full range of physically taxing activities after his ICD implantation, but whose livelihood had been taken away from him.

Dr. Bjerre said she sought to understand the perspective of this patient, who said, “Sometimes I wish I hadn’t been resuscitated!” She saw that the loss of freedom and a meaningful occupation had profoundly affected the daily life of this patient, and she became curious about adherence to driving restrictions in patients with ICDs.

Using the nationwide Danish medical record database, Dr. Bjerre and her colleagues looked at a nationwide cohort of ICD patients to see they remembered hearing about restrictions on personal and commercial driving activities after ICD implantation. They also investigated adherence to restrictions, and sought to identify what factors were associated with nonadherence.

The questionnaire developed by Dr. Bjerre and her colleagues was made available to the ICD cohort both electronically and in a paper version. Questionnaires received were linked with a variety of nationwide registries through each participant’s unique national identification number, she explained. They obtained information about comorbidities, pharmacotherapies, and socioeconomic status. Not only did this linkage give more precise and complete data than would a questionnaire alone, but it also allowed the investigators to see how responders differed from nonresponders – important in questionnaire research, said Dr. Bjerre.

The investigators were able to locate and distribute questionnaires to a total of 3,913 living adults who had received first-time ICDs during the 3-year study period. In the end, even after excluding 31 responses for missing data, 2,741 responses were used for analysis – a response rate of over 70%.

The median age of respondents was 67, and 83% were male. About half – 46% – of respondents had an ICD implanted for primary prevention. Compared with those who did respond, said Dr. Bjerre, the nonresponders “were younger, sicker, more likely to be female, had lower socioeconomic status, and were less likely to be on guideline-directed therapy.”

Over 90% of respondents held a private driver’s license at the time of their ICD implantation, and just 7% were actively using a commercial license prior to implantation. Participants had a variety of commercial driving occupations, including driving trucks, buses, and taxis.

“Only 43% of primary prevention patients and 64% of secondary prevention patients stated that they had been informed about any driving restrictions,” said Dr. Bjerre. The figure was slightly better for patients after an ICD shock was delivered – 72% of these patients recalled hearing about driving restrictions.

“Among professional drivers – who are never supposed to drive again – only 45% said they had been informed about any professional driving restrictions,” she added.

What did patients report about their actual driving behaviors? Of patients receiving an ICD for primary prevention, 34% resumed driving within one week of ICD implantation. For those receiving an ICD for secondary prevention and those who had received an appropriate ICD shock, 43% and 30%, respectively, began driving before the recommended 3 months had elapsed.

The driving behavior of those with commercial licenses didn’t differ from the cohort as a whole: 35% of this group had resumed commercial driving.

In all the study’s subgroups, nonadherence to driving restrictions was more likely if the participant didn’t recall having been informed of the restrictions, with an odds ratio (OR) of 3.34 for nonadherence. However, noted Dr. Bjerre, at least 20% of patients in all subgroups who said they’d been told not to drive still resumed driving in contravention of restrictions. “So it seems that information can’t explain everything,” she said.

Additional predictors of nonadherence included male sex, with an OR of 1.53, being the only driver in the household (OR 1.29), and being at least 60 years old (OR, 1.20). Those receiving an ICD for secondary prevention had an OR of 2.20 for nonadherence, as well.

The study had a large cohort of real-life ICD patients and the response rate was high, said Dr. Bjerre. However, there was a risk of recall bias; additionally, nonresponders differed from responders, limiting full generalizability of the data. Finally, she observed that participants may have given the answers they thought were socially desirable.

“I want to get back to our friend the taxi driver,” who was adherent to restrictions, but who kept wanting to know what the actual chances were that he’d harm someone if he resumed driving. Realizing she couldn’t give him a very precise answer, Dr. Bjerre concluded, “I do think we owe it to our patients to provide more evidence on the absolute risk of traffic accidents in these patients.”

Dr. Bjerre reported that she had no conflicts of interest.

koakes@mdedge.com

 

PARIS – Fewer than half of commercial drivers who received implantable cardioverter-defibrillators (ICDs) recalled being told they should never drive professionally again, according to a recent Danish survey. Further, about a third of patients overall reported that they began driving soon after they received an ICD, during the period when guidelines recommend refraining from driving.

“These devices, they save lives – so what’s not to like?” lead investigator Jenny Bjerre, MD, asked at the annual congress of the European Society of Cardiology. “Well, if you are a patient qualifying for an ICD, you also automatically qualify for some driving restrictions.” These are put in place because of the concern for an arrhythmia causing a loss of consciousness behind the wheel, she said.

A European consensus statement calls for a 3-month driving moratorium when an ICD is implanted for secondary prevention or after an appropriate ICD shock, and a 4-week restriction when an ICD is placed for primary prevention. All these restrictions apply to personal driver’s licenses; anyone with an ICD is permanently restricted from commercial driving according to the consensus statement, said Dr. Bjerre, of the University Hospital, Copenhagen.

“As you can imagine, these restrictions are not that popular with the patients,” she said. She related the story of a patient, a taxi driver who had returned to a full range of physically taxing activities after his ICD implantation, but whose livelihood had been taken away from him.

Dr. Bjerre said she sought to understand the perspective of this patient, who said, “Sometimes I wish I hadn’t been resuscitated!” She saw that the loss of freedom and a meaningful occupation had profoundly affected the daily life of this patient, and she became curious about adherence to driving restrictions in patients with ICDs.

Using the nationwide Danish medical record database, Dr. Bjerre and her colleagues looked at a nationwide cohort of ICD patients to see they remembered hearing about restrictions on personal and commercial driving activities after ICD implantation. They also investigated adherence to restrictions, and sought to identify what factors were associated with nonadherence.

The questionnaire developed by Dr. Bjerre and her colleagues was made available to the ICD cohort both electronically and in a paper version. Questionnaires received were linked with a variety of nationwide registries through each participant’s unique national identification number, she explained. They obtained information about comorbidities, pharmacotherapies, and socioeconomic status. Not only did this linkage give more precise and complete data than would a questionnaire alone, but it also allowed the investigators to see how responders differed from nonresponders – important in questionnaire research, said Dr. Bjerre.

The investigators were able to locate and distribute questionnaires to a total of 3,913 living adults who had received first-time ICDs during the 3-year study period. In the end, even after excluding 31 responses for missing data, 2,741 responses were used for analysis – a response rate of over 70%.

The median age of respondents was 67, and 83% were male. About half – 46% – of respondents had an ICD implanted for primary prevention. Compared with those who did respond, said Dr. Bjerre, the nonresponders “were younger, sicker, more likely to be female, had lower socioeconomic status, and were less likely to be on guideline-directed therapy.”

Over 90% of respondents held a private driver’s license at the time of their ICD implantation, and just 7% were actively using a commercial license prior to implantation. Participants had a variety of commercial driving occupations, including driving trucks, buses, and taxis.

“Only 43% of primary prevention patients and 64% of secondary prevention patients stated that they had been informed about any driving restrictions,” said Dr. Bjerre. The figure was slightly better for patients after an ICD shock was delivered – 72% of these patients recalled hearing about driving restrictions.

“Among professional drivers – who are never supposed to drive again – only 45% said they had been informed about any professional driving restrictions,” she added.

What did patients report about their actual driving behaviors? Of patients receiving an ICD for primary prevention, 34% resumed driving within one week of ICD implantation. For those receiving an ICD for secondary prevention and those who had received an appropriate ICD shock, 43% and 30%, respectively, began driving before the recommended 3 months had elapsed.

The driving behavior of those with commercial licenses didn’t differ from the cohort as a whole: 35% of this group had resumed commercial driving.

In all the study’s subgroups, nonadherence to driving restrictions was more likely if the participant didn’t recall having been informed of the restrictions, with an odds ratio (OR) of 3.34 for nonadherence. However, noted Dr. Bjerre, at least 20% of patients in all subgroups who said they’d been told not to drive still resumed driving in contravention of restrictions. “So it seems that information can’t explain everything,” she said.

Additional predictors of nonadherence included male sex, with an OR of 1.53, being the only driver in the household (OR 1.29), and being at least 60 years old (OR, 1.20). Those receiving an ICD for secondary prevention had an OR of 2.20 for nonadherence, as well.

The study had a large cohort of real-life ICD patients and the response rate was high, said Dr. Bjerre. However, there was a risk of recall bias; additionally, nonresponders differed from responders, limiting full generalizability of the data. Finally, she observed that participants may have given the answers they thought were socially desirable.

“I want to get back to our friend the taxi driver,” who was adherent to restrictions, but who kept wanting to know what the actual chances were that he’d harm someone if he resumed driving. Realizing she couldn’t give him a very precise answer, Dr. Bjerre concluded, “I do think we owe it to our patients to provide more evidence on the absolute risk of traffic accidents in these patients.”

Dr. Bjerre reported that she had no conflicts of interest.

koakes@mdedge.com

 

PARIS – Fewer than half of commercial drivers who received implantable cardioverter-defibrillators (ICDs) recalled being told they should never drive professionally again, according to a recent Danish survey. Further, about a third of patients overall reported that they began driving soon after they received an ICD, during the period when guidelines recommend refraining from driving.

“These devices, they save lives – so what’s not to like?” lead investigator Jenny Bjerre, MD, asked at the annual congress of the European Society of Cardiology. “Well, if you are a patient qualifying for an ICD, you also automatically qualify for some driving restrictions.” These are put in place because of the concern for an arrhythmia causing a loss of consciousness behind the wheel, she said.

A European consensus statement calls for a 3-month driving moratorium when an ICD is implanted for secondary prevention or after an appropriate ICD shock, and a 4-week restriction when an ICD is placed for primary prevention. All these restrictions apply to personal driver’s licenses; anyone with an ICD is permanently restricted from commercial driving according to the consensus statement, said Dr. Bjerre, of the University Hospital, Copenhagen.

“As you can imagine, these restrictions are not that popular with the patients,” she said. She related the story of a patient, a taxi driver who had returned to a full range of physically taxing activities after his ICD implantation, but whose livelihood had been taken away from him.

Dr. Bjerre said she sought to understand the perspective of this patient, who said, “Sometimes I wish I hadn’t been resuscitated!” She saw that the loss of freedom and a meaningful occupation had profoundly affected the daily life of this patient, and she became curious about adherence to driving restrictions in patients with ICDs.

Using the nationwide Danish medical record database, Dr. Bjerre and her colleagues looked at a nationwide cohort of ICD patients to see they remembered hearing about restrictions on personal and commercial driving activities after ICD implantation. They also investigated adherence to restrictions, and sought to identify what factors were associated with nonadherence.

The questionnaire developed by Dr. Bjerre and her colleagues was made available to the ICD cohort both electronically and in a paper version. Questionnaires received were linked with a variety of nationwide registries through each participant’s unique national identification number, she explained. They obtained information about comorbidities, pharmacotherapies, and socioeconomic status. Not only did this linkage give more precise and complete data than would a questionnaire alone, but it also allowed the investigators to see how responders differed from nonresponders – important in questionnaire research, said Dr. Bjerre.

The investigators were able to locate and distribute questionnaires to a total of 3,913 living adults who had received first-time ICDs during the 3-year study period. In the end, even after excluding 31 responses for missing data, 2,741 responses were used for analysis – a response rate of over 70%.

The median age of respondents was 67, and 83% were male. About half – 46% – of respondents had an ICD implanted for primary prevention. Compared with those who did respond, said Dr. Bjerre, the nonresponders “were younger, sicker, more likely to be female, had lower socioeconomic status, and were less likely to be on guideline-directed therapy.”

Over 90% of respondents held a private driver’s license at the time of their ICD implantation, and just 7% were actively using a commercial license prior to implantation. Participants had a variety of commercial driving occupations, including driving trucks, buses, and taxis.

“Only 43% of primary prevention patients and 64% of secondary prevention patients stated that they had been informed about any driving restrictions,” said Dr. Bjerre. The figure was slightly better for patients after an ICD shock was delivered – 72% of these patients recalled hearing about driving restrictions.

“Among professional drivers – who are never supposed to drive again – only 45% said they had been informed about any professional driving restrictions,” she added.

What did patients report about their actual driving behaviors? Of patients receiving an ICD for primary prevention, 34% resumed driving within one week of ICD implantation. For those receiving an ICD for secondary prevention and those who had received an appropriate ICD shock, 43% and 30%, respectively, began driving before the recommended 3 months had elapsed.

The driving behavior of those with commercial licenses didn’t differ from the cohort as a whole: 35% of this group had resumed commercial driving.

In all the study’s subgroups, nonadherence to driving restrictions was more likely if the participant didn’t recall having been informed of the restrictions, with an odds ratio (OR) of 3.34 for nonadherence. However, noted Dr. Bjerre, at least 20% of patients in all subgroups who said they’d been told not to drive still resumed driving in contravention of restrictions. “So it seems that information can’t explain everything,” she said.

Additional predictors of nonadherence included male sex, with an OR of 1.53, being the only driver in the household (OR 1.29), and being at least 60 years old (OR, 1.20). Those receiving an ICD for secondary prevention had an OR of 2.20 for nonadherence, as well.

The study had a large cohort of real-life ICD patients and the response rate was high, said Dr. Bjerre. However, there was a risk of recall bias; additionally, nonresponders differed from responders, limiting full generalizability of the data. Finally, she observed that participants may have given the answers they thought were socially desirable.

“I want to get back to our friend the taxi driver,” who was adherent to restrictions, but who kept wanting to know what the actual chances were that he’d harm someone if he resumed driving. Realizing she couldn’t give him a very precise answer, Dr. Bjerre concluded, “I do think we owe it to our patients to provide more evidence on the absolute risk of traffic accidents in these patients.”

Dr. Bjerre reported that she had no conflicts of interest.

koakes@mdedge.com

PARIS – Though cardiovascular disease still accounts for 40% of deaths around the world, cancer is eclipsing cardiovascular disease as a cause of mortality in high income nations, according to new data from a global prospective study.

“Cancer deaths are becoming more frequent not because the rates of death from cancer are going up, but because we have decreased the deaths from cardiovascular disease,” said the study’s senior author, Salim Yusuf, MD, at the annual congress of the European Society of Cardiology.

A striking pattern emerged when cause of death was stratified by country income level, said fellow investigator Darryl P. Leong, MBBS, in presenting data regarding shifting global mortality patterns. Fully 55% of deaths in high-income nations were caused by cancer, compared with 30% in middle-income countries and 15% in low-income countries. In high-income countries, by contrast, cardiovascular disease (CVD) was the cause of death 23% of the time, while that figure was 42% and 43% for middle- and low-income countries, respectively.

Looking at the data slightly differently, the ratio of cardiovascular deaths to cancer deaths for high-income countries is 0.4; for middle-income countries, the ratio is 1.3, and “One is threefold more likely to die from cardiovascular disease as from cancer” in low-income countries, said Dr. Leong. Although the United States is not included in the PURE study, “recent data shows that some states in the U.S. also have higher cancer mortality than cardiovascular disease. This is a success story,” said Dr. Yusuf, since the shift is largely attributable to decreased mortality from CVD.

Dr. Leong and Dr. Yusuf each presented results from the PURE (Prospective Urban Rural Epidemiology) study, which has enrolled a total of 202,000 individuals from 27 countries on every inhabited continent but Australia. Follow-up data are available for 167,000 individuals in 21 countries. Canada, Russia, China, India, Brazil, and Chile are among the most populous national that are included. Their findings were published simultaneously in the Lancet with the congress presentations (2019 Sep 3; doi: 10.1016/S0140-6736(19)32008-2 and doi: 10.1016/S0140-6736(19)32007-0).

The INTERHEART risk score, an integrated cardiovascular risk score that uses non-laboratory values such as age, smoking status, family history, and comorbidities, was calculated for all participants. “We observed that the highest predicted cardiovascular risk is in high-income countries, and the lowest, in low-income countries,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Over the study period, 11,307 deaths occurred. Over 9,000 incident cardiovascular events were observed, as were over 5,000 new cancers.

“We have some interesting observations from these data,” said Dr. Leong. “Firstly, there is a gradient in the cardiovascular disease rates, moving from lowest in high-income countries – despite the fact that their INTERHEART risk score was highest – through to highest incident cardiovascular disease in low-income countries, despite their INTERHEART risk score being lowest.” This difference, said Dr. Leong, was driven by higher myocardial infarction rates in low-income countries and higher stroke rates in middle-income countries, when compared to high-income countries.

Once a participant was subject to one of the incident diseases, though, the patterns shifted. For CVD, cancer, chronic obstructive pulmonary disease, pneumonia, and injury, the likelihood of death within 1 year was highest in low-income countries – markedly higher, in the case of CVD. For all conditions, the one-year case-fatality rate after the occurrence of an incident disease was lowest in high-income countries.

“So we are seeing a new transition,” said Dr. Yusuf, the executive director of the Population Health Research Institute and Distinguished University Professor of Medicine, McMaster University, both in Hamilton, Ont. “The old transition was infectious diseases giving way to noncommunicable diseases. Now we are seeing a transition within noncommunicable diseases: In rich countries, cardiovascular disease is going down, perhaps due to better prevention, but I think even more importantly, due to better treatments.

“I want to hasten to add that the difference in risk between high-, middle-, and low-income countries in cardiovascular disease is not due to risk factors,” he went on. “Risk factors, if anything, are lower in the poor countries, compared to the higher-income countries.”

The shift away from cardiovascular disease mortality toward cancer mortality is also occurring in some countries that are in the upper tier of middle-income nations, including Chile, Argentina, Turkey, and Poland, said Dr. Yusuf, who presented data regarding the relative contributions of risk factors to cardiovascular disease and mortality.

Risk factors for cardiovascular disease in the PURE study were expressed by a measure called the population attributable fraction (PAF) that captures both the hazard ratio for a particular risk factor and the prevalence of the risk factor, explained Dr. Yusuf. “Hypertension, by far, was the biggest risk factor of cardiovascular disease globally,” he added, noting that the PAF for hypertension was over 20%. Hypertension far outstripped the next most significant risk factor, high non-HDL cholesterol, which had a PAF of less than 10%.

“This was a big surprise to us: Household pollution was a big factor,” said Dr. Yusuf, who later added that particulate matter from cooking, particularly with solid fuels such as wood or charcoal, was likely the source of much household air pollution, “a big problem in middle- and low-income countries.”

Tobacco usage is decreasing, as is its contribution to cardiovascular deaths, but other commonly cited culprits for cardiovascular disease were not significant contributors to cardiovascular disease in the PURE population.

“Abdominal obesity, and not BMI” contributes to cardiovascular risk. “BMI is not a good indicator of risk,” said Dr. Yusuf in a video interview. These results were presented separately at the congress.

“Grip strength is important; in fact, it is more important than low physical activity. People have focused on physical activity – how much you do. But strength seems to be more important…We haven’t focused on the importance of strength in the past.”

“Salt doesn’t figure in at all; salt has been exaggerated as a risk factor,” said Dr. Yusuf. “Diet needs to be rethought,” and conventional thinking challenged, he added, noting that consumption of full-fat dairy, nuts, and a moderate amount of meat all were protective among the PURE cohort.

Looking next at factors contributing to mortality in the global PURE population, low educational level had the highest attributable fraction of mortality of any single risk factor, at about 12%. “This has been ignored,” said Dr. Yusuf. “In most epidemiological studies, it’s been used as a covariate, or a stratifier,” rather than addressing low education itself as a risk factor, he said.

Tobacco use, low grip strength, and poor diet all had attributable fractions of just over 10%, said Dr. Yusuf, again noting that it wasn’t fat or meat consumption that made for the riskiest diet.

Overall, metabolic risk factors accounted for the largest fraction of risk of cardiovascular disease in the PURE population, with behavioral risk factors such as alcohol and tobacco use coming next. This held true across all income categories. However, in higher income nations where environmental factors and household air pollution are lower contributors to cardiovascular disease, metabolic and behavioral risk factors contributed more to cardiovascular disease risk.

Global differences in cardiovascular disease rates, stressed Dr. Yusuf, are not primarily attributable to metabolic risk factors. “The [World Health Organization] has focused on risk factors and has not focused on improved health care. Health care matters, and it matters in a big way.”

Adults aged 35-70 were recruited from 4 high-, 12 middle- and 5 low-income countries for PURE, and followed for a median 9.5 years. Cardiovascular disease and other health events salient to the study were documented both through direct contact and administrative record review, said Dr. Leong, and data about cardiovascular events and vital status were known for well over 90% of study participants.

Slightly less than half of participants were male, and over 108,000 participants were from middle income countries.

The PURE study was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Ontaario Ministry of Health and Long-Term Care, Astra Zeneca, Boehringer Ingelheim, Sanofi-Aentis, Servier Laboratories, and Glaxo Smith Kline. The study also received additional support in individual participating countries. Dr. Yusuf and Dr. Leon reported that they had no relevant conflicts of interest.

koakes@mdedge.com

PARIS – Though cardiovascular disease still accounts for 40% of deaths around the world, cancer is eclipsing cardiovascular disease as a cause of mortality in high income nations, according to new data from a global prospective study.

“Cancer deaths are becoming more frequent not because the rates of death from cancer are going up, but because we have decreased the deaths from cardiovascular disease,” said the study’s senior author, Salim Yusuf, MD, at the annual congress of the European Society of Cardiology.

A striking pattern emerged when cause of death was stratified by country income level, said fellow investigator Darryl P. Leong, MBBS, in presenting data regarding shifting global mortality patterns. Fully 55% of deaths in high-income nations were caused by cancer, compared with 30% in middle-income countries and 15% in low-income countries. In high-income countries, by contrast, cardiovascular disease (CVD) was the cause of death 23% of the time, while that figure was 42% and 43% for middle- and low-income countries, respectively.

Looking at the data slightly differently, the ratio of cardiovascular deaths to cancer deaths for high-income countries is 0.4; for middle-income countries, the ratio is 1.3, and “One is threefold more likely to die from cardiovascular disease as from cancer” in low-income countries, said Dr. Leong. Although the United States is not included in the PURE study, “recent data shows that some states in the U.S. also have higher cancer mortality than cardiovascular disease. This is a success story,” said Dr. Yusuf, since the shift is largely attributable to decreased mortality from CVD.

Dr. Leong and Dr. Yusuf each presented results from the PURE (Prospective Urban Rural Epidemiology) study, which has enrolled a total of 202,000 individuals from 27 countries on every inhabited continent but Australia. Follow-up data are available for 167,000 individuals in 21 countries. Canada, Russia, China, India, Brazil, and Chile are among the most populous national that are included. Their findings were published simultaneously in the Lancet with the congress presentations (2019 Sep 3; doi: 10.1016/S0140-6736(19)32008-2 and doi: 10.1016/S0140-6736(19)32007-0).

The INTERHEART risk score, an integrated cardiovascular risk score that uses non-laboratory values such as age, smoking status, family history, and comorbidities, was calculated for all participants. “We observed that the highest predicted cardiovascular risk is in high-income countries, and the lowest, in low-income countries,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Over the study period, 11,307 deaths occurred. Over 9,000 incident cardiovascular events were observed, as were over 5,000 new cancers.

“We have some interesting observations from these data,” said Dr. Leong. “Firstly, there is a gradient in the cardiovascular disease rates, moving from lowest in high-income countries – despite the fact that their INTERHEART risk score was highest – through to highest incident cardiovascular disease in low-income countries, despite their INTERHEART risk score being lowest.” This difference, said Dr. Leong, was driven by higher myocardial infarction rates in low-income countries and higher stroke rates in middle-income countries, when compared to high-income countries.

Once a participant was subject to one of the incident diseases, though, the patterns shifted. For CVD, cancer, chronic obstructive pulmonary disease, pneumonia, and injury, the likelihood of death within 1 year was highest in low-income countries – markedly higher, in the case of CVD. For all conditions, the one-year case-fatality rate after the occurrence of an incident disease was lowest in high-income countries.

“So we are seeing a new transition,” said Dr. Yusuf, the executive director of the Population Health Research Institute and Distinguished University Professor of Medicine, McMaster University, both in Hamilton, Ont. “The old transition was infectious diseases giving way to noncommunicable diseases. Now we are seeing a transition within noncommunicable diseases: In rich countries, cardiovascular disease is going down, perhaps due to better prevention, but I think even more importantly, due to better treatments.

“I want to hasten to add that the difference in risk between high-, middle-, and low-income countries in cardiovascular disease is not due to risk factors,” he went on. “Risk factors, if anything, are lower in the poor countries, compared to the higher-income countries.”

The shift away from cardiovascular disease mortality toward cancer mortality is also occurring in some countries that are in the upper tier of middle-income nations, including Chile, Argentina, Turkey, and Poland, said Dr. Yusuf, who presented data regarding the relative contributions of risk factors to cardiovascular disease and mortality.

Risk factors for cardiovascular disease in the PURE study were expressed by a measure called the population attributable fraction (PAF) that captures both the hazard ratio for a particular risk factor and the prevalence of the risk factor, explained Dr. Yusuf. “Hypertension, by far, was the biggest risk factor of cardiovascular disease globally,” he added, noting that the PAF for hypertension was over 20%. Hypertension far outstripped the next most significant risk factor, high non-HDL cholesterol, which had a PAF of less than 10%.

“This was a big surprise to us: Household pollution was a big factor,” said Dr. Yusuf, who later added that particulate matter from cooking, particularly with solid fuels such as wood or charcoal, was likely the source of much household air pollution, “a big problem in middle- and low-income countries.”

Tobacco usage is decreasing, as is its contribution to cardiovascular deaths, but other commonly cited culprits for cardiovascular disease were not significant contributors to cardiovascular disease in the PURE population.

“Abdominal obesity, and not BMI” contributes to cardiovascular risk. “BMI is not a good indicator of risk,” said Dr. Yusuf in a video interview. These results were presented separately at the congress.

“Grip strength is important; in fact, it is more important than low physical activity. People have focused on physical activity – how much you do. But strength seems to be more important…We haven’t focused on the importance of strength in the past.”

“Salt doesn’t figure in at all; salt has been exaggerated as a risk factor,” said Dr. Yusuf. “Diet needs to be rethought,” and conventional thinking challenged, he added, noting that consumption of full-fat dairy, nuts, and a moderate amount of meat all were protective among the PURE cohort.

Looking next at factors contributing to mortality in the global PURE population, low educational level had the highest attributable fraction of mortality of any single risk factor, at about 12%. “This has been ignored,” said Dr. Yusuf. “In most epidemiological studies, it’s been used as a covariate, or a stratifier,” rather than addressing low education itself as a risk factor, he said.

Tobacco use, low grip strength, and poor diet all had attributable fractions of just over 10%, said Dr. Yusuf, again noting that it wasn’t fat or meat consumption that made for the riskiest diet.

Overall, metabolic risk factors accounted for the largest fraction of risk of cardiovascular disease in the PURE population, with behavioral risk factors such as alcohol and tobacco use coming next. This held true across all income categories. However, in higher income nations where environmental factors and household air pollution are lower contributors to cardiovascular disease, metabolic and behavioral risk factors contributed more to cardiovascular disease risk.

Global differences in cardiovascular disease rates, stressed Dr. Yusuf, are not primarily attributable to metabolic risk factors. “The [World Health Organization] has focused on risk factors and has not focused on improved health care. Health care matters, and it matters in a big way.”

Adults aged 35-70 were recruited from 4 high-, 12 middle- and 5 low-income countries for PURE, and followed for a median 9.5 years. Cardiovascular disease and other health events salient to the study were documented both through direct contact and administrative record review, said Dr. Leong, and data about cardiovascular events and vital status were known for well over 90% of study participants.

Slightly less than half of participants were male, and over 108,000 participants were from middle income countries.

The PURE study was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Ontaario Ministry of Health and Long-Term Care, Astra Zeneca, Boehringer Ingelheim, Sanofi-Aentis, Servier Laboratories, and Glaxo Smith Kline. The study also received additional support in individual participating countries. Dr. Yusuf and Dr. Leon reported that they had no relevant conflicts of interest.

koakes@mdedge.com

PARIS – Though cardiovascular disease still accounts for 40% of deaths around the world, cancer is eclipsing cardiovascular disease as a cause of mortality in high income nations, according to new data from a global prospective study.

“Cancer deaths are becoming more frequent not because the rates of death from cancer are going up, but because we have decreased the deaths from cardiovascular disease,” said the study’s senior author, Salim Yusuf, MD, at the annual congress of the European Society of Cardiology.

A striking pattern emerged when cause of death was stratified by country income level, said fellow investigator Darryl P. Leong, MBBS, in presenting data regarding shifting global mortality patterns. Fully 55% of deaths in high-income nations were caused by cancer, compared with 30% in middle-income countries and 15% in low-income countries. In high-income countries, by contrast, cardiovascular disease (CVD) was the cause of death 23% of the time, while that figure was 42% and 43% for middle- and low-income countries, respectively.

Looking at the data slightly differently, the ratio of cardiovascular deaths to cancer deaths for high-income countries is 0.4; for middle-income countries, the ratio is 1.3, and “One is threefold more likely to die from cardiovascular disease as from cancer” in low-income countries, said Dr. Leong. Although the United States is not included in the PURE study, “recent data shows that some states in the U.S. also have higher cancer mortality than cardiovascular disease. This is a success story,” said Dr. Yusuf, since the shift is largely attributable to decreased mortality from CVD.

Dr. Leong and Dr. Yusuf each presented results from the PURE (Prospective Urban Rural Epidemiology) study, which has enrolled a total of 202,000 individuals from 27 countries on every inhabited continent but Australia. Follow-up data are available for 167,000 individuals in 21 countries. Canada, Russia, China, India, Brazil, and Chile are among the most populous national that are included. Their findings were published simultaneously in the Lancet with the congress presentations (2019 Sep 3; doi: 10.1016/S0140-6736(19)32008-2 and doi: 10.1016/S0140-6736(19)32007-0).

The INTERHEART risk score, an integrated cardiovascular risk score that uses non-laboratory values such as age, smoking status, family history, and comorbidities, was calculated for all participants. “We observed that the highest predicted cardiovascular risk is in high-income countries, and the lowest, in low-income countries,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Over the study period, 11,307 deaths occurred. Over 9,000 incident cardiovascular events were observed, as were over 5,000 new cancers.

“We have some interesting observations from these data,” said Dr. Leong. “Firstly, there is a gradient in the cardiovascular disease rates, moving from lowest in high-income countries – despite the fact that their INTERHEART risk score was highest – through to highest incident cardiovascular disease in low-income countries, despite their INTERHEART risk score being lowest.” This difference, said Dr. Leong, was driven by higher myocardial infarction rates in low-income countries and higher stroke rates in middle-income countries, when compared to high-income countries.

Once a participant was subject to one of the incident diseases, though, the patterns shifted. For CVD, cancer, chronic obstructive pulmonary disease, pneumonia, and injury, the likelihood of death within 1 year was highest in low-income countries – markedly higher, in the case of CVD. For all conditions, the one-year case-fatality rate after the occurrence of an incident disease was lowest in high-income countries.

“So we are seeing a new transition,” said Dr. Yusuf, the executive director of the Population Health Research Institute and Distinguished University Professor of Medicine, McMaster University, both in Hamilton, Ont. “The old transition was infectious diseases giving way to noncommunicable diseases. Now we are seeing a transition within noncommunicable diseases: In rich countries, cardiovascular disease is going down, perhaps due to better prevention, but I think even more importantly, due to better treatments.

“I want to hasten to add that the difference in risk between high-, middle-, and low-income countries in cardiovascular disease is not due to risk factors,” he went on. “Risk factors, if anything, are lower in the poor countries, compared to the higher-income countries.”

The shift away from cardiovascular disease mortality toward cancer mortality is also occurring in some countries that are in the upper tier of middle-income nations, including Chile, Argentina, Turkey, and Poland, said Dr. Yusuf, who presented data regarding the relative contributions of risk factors to cardiovascular disease and mortality.

Risk factors for cardiovascular disease in the PURE study were expressed by a measure called the population attributable fraction (PAF) that captures both the hazard ratio for a particular risk factor and the prevalence of the risk factor, explained Dr. Yusuf. “Hypertension, by far, was the biggest risk factor of cardiovascular disease globally,” he added, noting that the PAF for hypertension was over 20%. Hypertension far outstripped the next most significant risk factor, high non-HDL cholesterol, which had a PAF of less than 10%.

“This was a big surprise to us: Household pollution was a big factor,” said Dr. Yusuf, who later added that particulate matter from cooking, particularly with solid fuels such as wood or charcoal, was likely the source of much household air pollution, “a big problem in middle- and low-income countries.”

Tobacco usage is decreasing, as is its contribution to cardiovascular deaths, but other commonly cited culprits for cardiovascular disease were not significant contributors to cardiovascular disease in the PURE population.

“Abdominal obesity, and not BMI” contributes to cardiovascular risk. “BMI is not a good indicator of risk,” said Dr. Yusuf in a video interview. These results were presented separately at the congress.

“Grip strength is important; in fact, it is more important than low physical activity. People have focused on physical activity – how much you do. But strength seems to be more important…We haven’t focused on the importance of strength in the past.”

“Salt doesn’t figure in at all; salt has been exaggerated as a risk factor,” said Dr. Yusuf. “Diet needs to be rethought,” and conventional thinking challenged, he added, noting that consumption of full-fat dairy, nuts, and a moderate amount of meat all were protective among the PURE cohort.

Looking next at factors contributing to mortality in the global PURE population, low educational level had the highest attributable fraction of mortality of any single risk factor, at about 12%. “This has been ignored,” said Dr. Yusuf. “In most epidemiological studies, it’s been used as a covariate, or a stratifier,” rather than addressing low education itself as a risk factor, he said.

Tobacco use, low grip strength, and poor diet all had attributable fractions of just over 10%, said Dr. Yusuf, again noting that it wasn’t fat or meat consumption that made for the riskiest diet.

Overall, metabolic risk factors accounted for the largest fraction of risk of cardiovascular disease in the PURE population, with behavioral risk factors such as alcohol and tobacco use coming next. This held true across all income categories. However, in higher income nations where environmental factors and household air pollution are lower contributors to cardiovascular disease, metabolic and behavioral risk factors contributed more to cardiovascular disease risk.

Global differences in cardiovascular disease rates, stressed Dr. Yusuf, are not primarily attributable to metabolic risk factors. “The [World Health Organization] has focused on risk factors and has not focused on improved health care. Health care matters, and it matters in a big way.”

Adults aged 35-70 were recruited from 4 high-, 12 middle- and 5 low-income countries for PURE, and followed for a median 9.5 years. Cardiovascular disease and other health events salient to the study were documented both through direct contact and administrative record review, said Dr. Leong, and data about cardiovascular events and vital status were known for well over 90% of study participants.

Slightly less than half of participants were male, and over 108,000 participants were from middle income countries.

The PURE study was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Ontaario Ministry of Health and Long-Term Care, Astra Zeneca, Boehringer Ingelheim, Sanofi-Aentis, Servier Laboratories, and Glaxo Smith Kline. The study also received additional support in individual participating countries. Dr. Yusuf and Dr. Leon reported that they had no relevant conflicts of interest.

koakes@mdedge.com