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European Society of Cardiology (ESC): Annual Congress
Dalcetrapib Boosts HDL Without Bumping BP
PARIS – The investigational cholesteryl ester transfer protein inhibitor dalcetrapib increased HDL cholesterol without the toxic effects that have raised safety concerns over the use of CETP inhibitors as a cardiovascular therapy.
Dalcetrapib reduced CETP activity by 49% and increased HDL cholesterol by 31% without affecting LDL cholesterol among patients with or at risk of coronary heart disease in the randomized phase II dal-VESSEL trial.
Dalcetrapib did not cause endothelial dysfunction nor did it improve it. Unlike the CETP inhibitor torcetrapib, dalcetrapib did not raise blood pressure, providing further reassurance regarding the safety of the compound, Dr. Thomas Lüscher said at the annual congress of the European Society of Cardiology.
"I think we can say it’s safe and has no untoward effects like the others, and it does the job as far as the lipid profile is concerned," he told reporters. "It’s a bit less potent than torcetrapib, which increased HDL by about 60% to 70%, but [it] may be that’s even an advantage. We’ll see."
Dr. Lüscher said it was a bit disappointing that dalcetrapib (manufactured by Hoffmann-La Roche) did not improve vascular function, but noted that it wasn’t worsened either.
Whether the novel CETP inhibitor will have an effect on cardiovascular events will be determined by the phase III dal-OUTCOMES trial, with results expected sometime in 2013, said Dr. Lüscher, professor and chair of cardiology at University Hospital Zurich, Switzerland.
A total of 15,872 patients with stable heart disease following a recent acute coronary event have been enrolled, according to the drug maker’s Web site.
Invited discussant Dr. Keith A. A. Fox, with the University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, said the positive dal-VESSEL data represent a "clear advance," but urged caution because of the limited size of the trial.
"We need to know whether the modest changes in blood pressure are real or have an impact on outcomes," he said.
The recent DEFINE trial of Merck’s CETP inhibitor anacetrapib, however, illustrates the very real difficulties in achieving this goal. Anacetrapib raised HDL cholesterol 138% and reduced LDL cholesterol by 40% compared with placebo, but did not reduce cardiovascular events in 1,623 patients with or at high risk for coronary heart disease (N. Engl. J. Med. 2010;363:2406-15).
Torcetrapib, the first CTEP to be tested, increased HDL cholesterol by 61% and decreased LDL cholesterol by 20%, but was associated with a roughly 4.6 mm Hg increase in blood pressure (N. Engl. J. Med. 2007;356:1304-16). Development of the agent came to a screeching halt, however, when the ILLUMINATE trial subsequently reported that torcetrapib also increased the risk of cardiovascular events by 25% and all-cause mortality by 58% in patients at high cardiovascular risk (N. Engl. J. Med. 2007:357:2109-22).
Further research suggested that the negative effects were caused not by reducing CTEP activity, but by off-target effects on renal glands, diminished nitrous oxide levels and increased endothelin-1, Dr. Lüscher explained.
The dal-VESSEL study was conducted at 19 centers in Europe and randomized 476 patients with coronary heart disease or CHD risk equivalents and HDL cholesterol of less than 50 mg/dL to dalcetrapib 600 mg/day or placebo plus their standard medication for a total of 36 weeks. Endothelial function was measured at 12 weeks using brachial flow-mediated dilation (FMD), a validated marker of endothelial dysfunction. Their mean age was 62 years, and roughly 97% were on statins.
The mean change in HDL cholesterol from baseline at week 4 was 2.7% for placebo and 27.5% for dalcetrapib; at week 36 it was -0.14% vs. 30.7%, respectively (P less than .0001 for both), Dr. Lüscher said.
At 36 weeks lipoprotein A-1 levels were significantly increased with dalcetrapib, but lipoprotein B levels were not affected.
There was no significant change with dalcetrapib in the co-primary safety endpoints of 24-hour ambulatory BP at week 4 and FMD at week 12.
Death from coronary heart disease occurred in one patient given placebo and none given dalcetrapib. Non-fatal myocardial infarctions were reported in 3 and 2 patients, respectively.
The trial was sponsored by Hoffmann-La Roche. Dr. Lüscher reports receiving research grants from Pfizer, Eli Lilly and Merck and consultancy or lecture fees from CSL, Merck, Pfizer and F. Hoffmann-La Roche.
PARIS – The investigational cholesteryl ester transfer protein inhibitor dalcetrapib increased HDL cholesterol without the toxic effects that have raised safety concerns over the use of CETP inhibitors as a cardiovascular therapy.
Dalcetrapib reduced CETP activity by 49% and increased HDL cholesterol by 31% without affecting LDL cholesterol among patients with or at risk of coronary heart disease in the randomized phase II dal-VESSEL trial.
Dalcetrapib did not cause endothelial dysfunction nor did it improve it. Unlike the CETP inhibitor torcetrapib, dalcetrapib did not raise blood pressure, providing further reassurance regarding the safety of the compound, Dr. Thomas Lüscher said at the annual congress of the European Society of Cardiology.
"I think we can say it’s safe and has no untoward effects like the others, and it does the job as far as the lipid profile is concerned," he told reporters. "It’s a bit less potent than torcetrapib, which increased HDL by about 60% to 70%, but [it] may be that’s even an advantage. We’ll see."
Dr. Lüscher said it was a bit disappointing that dalcetrapib (manufactured by Hoffmann-La Roche) did not improve vascular function, but noted that it wasn’t worsened either.
Whether the novel CETP inhibitor will have an effect on cardiovascular events will be determined by the phase III dal-OUTCOMES trial, with results expected sometime in 2013, said Dr. Lüscher, professor and chair of cardiology at University Hospital Zurich, Switzerland.
A total of 15,872 patients with stable heart disease following a recent acute coronary event have been enrolled, according to the drug maker’s Web site.
Invited discussant Dr. Keith A. A. Fox, with the University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, said the positive dal-VESSEL data represent a "clear advance," but urged caution because of the limited size of the trial.
"We need to know whether the modest changes in blood pressure are real or have an impact on outcomes," he said.
The recent DEFINE trial of Merck’s CETP inhibitor anacetrapib, however, illustrates the very real difficulties in achieving this goal. Anacetrapib raised HDL cholesterol 138% and reduced LDL cholesterol by 40% compared with placebo, but did not reduce cardiovascular events in 1,623 patients with or at high risk for coronary heart disease (N. Engl. J. Med. 2010;363:2406-15).
Torcetrapib, the first CTEP to be tested, increased HDL cholesterol by 61% and decreased LDL cholesterol by 20%, but was associated with a roughly 4.6 mm Hg increase in blood pressure (N. Engl. J. Med. 2007;356:1304-16). Development of the agent came to a screeching halt, however, when the ILLUMINATE trial subsequently reported that torcetrapib also increased the risk of cardiovascular events by 25% and all-cause mortality by 58% in patients at high cardiovascular risk (N. Engl. J. Med. 2007:357:2109-22).
Further research suggested that the negative effects were caused not by reducing CTEP activity, but by off-target effects on renal glands, diminished nitrous oxide levels and increased endothelin-1, Dr. Lüscher explained.
The dal-VESSEL study was conducted at 19 centers in Europe and randomized 476 patients with coronary heart disease or CHD risk equivalents and HDL cholesterol of less than 50 mg/dL to dalcetrapib 600 mg/day or placebo plus their standard medication for a total of 36 weeks. Endothelial function was measured at 12 weeks using brachial flow-mediated dilation (FMD), a validated marker of endothelial dysfunction. Their mean age was 62 years, and roughly 97% were on statins.
The mean change in HDL cholesterol from baseline at week 4 was 2.7% for placebo and 27.5% for dalcetrapib; at week 36 it was -0.14% vs. 30.7%, respectively (P less than .0001 for both), Dr. Lüscher said.
At 36 weeks lipoprotein A-1 levels were significantly increased with dalcetrapib, but lipoprotein B levels were not affected.
There was no significant change with dalcetrapib in the co-primary safety endpoints of 24-hour ambulatory BP at week 4 and FMD at week 12.
Death from coronary heart disease occurred in one patient given placebo and none given dalcetrapib. Non-fatal myocardial infarctions were reported in 3 and 2 patients, respectively.
The trial was sponsored by Hoffmann-La Roche. Dr. Lüscher reports receiving research grants from Pfizer, Eli Lilly and Merck and consultancy or lecture fees from CSL, Merck, Pfizer and F. Hoffmann-La Roche.
PARIS – The investigational cholesteryl ester transfer protein inhibitor dalcetrapib increased HDL cholesterol without the toxic effects that have raised safety concerns over the use of CETP inhibitors as a cardiovascular therapy.
Dalcetrapib reduced CETP activity by 49% and increased HDL cholesterol by 31% without affecting LDL cholesterol among patients with or at risk of coronary heart disease in the randomized phase II dal-VESSEL trial.
Dalcetrapib did not cause endothelial dysfunction nor did it improve it. Unlike the CETP inhibitor torcetrapib, dalcetrapib did not raise blood pressure, providing further reassurance regarding the safety of the compound, Dr. Thomas Lüscher said at the annual congress of the European Society of Cardiology.
"I think we can say it’s safe and has no untoward effects like the others, and it does the job as far as the lipid profile is concerned," he told reporters. "It’s a bit less potent than torcetrapib, which increased HDL by about 60% to 70%, but [it] may be that’s even an advantage. We’ll see."
Dr. Lüscher said it was a bit disappointing that dalcetrapib (manufactured by Hoffmann-La Roche) did not improve vascular function, but noted that it wasn’t worsened either.
Whether the novel CETP inhibitor will have an effect on cardiovascular events will be determined by the phase III dal-OUTCOMES trial, with results expected sometime in 2013, said Dr. Lüscher, professor and chair of cardiology at University Hospital Zurich, Switzerland.
A total of 15,872 patients with stable heart disease following a recent acute coronary event have been enrolled, according to the drug maker’s Web site.
Invited discussant Dr. Keith A. A. Fox, with the University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, said the positive dal-VESSEL data represent a "clear advance," but urged caution because of the limited size of the trial.
"We need to know whether the modest changes in blood pressure are real or have an impact on outcomes," he said.
The recent DEFINE trial of Merck’s CETP inhibitor anacetrapib, however, illustrates the very real difficulties in achieving this goal. Anacetrapib raised HDL cholesterol 138% and reduced LDL cholesterol by 40% compared with placebo, but did not reduce cardiovascular events in 1,623 patients with or at high risk for coronary heart disease (N. Engl. J. Med. 2010;363:2406-15).
Torcetrapib, the first CTEP to be tested, increased HDL cholesterol by 61% and decreased LDL cholesterol by 20%, but was associated with a roughly 4.6 mm Hg increase in blood pressure (N. Engl. J. Med. 2007;356:1304-16). Development of the agent came to a screeching halt, however, when the ILLUMINATE trial subsequently reported that torcetrapib also increased the risk of cardiovascular events by 25% and all-cause mortality by 58% in patients at high cardiovascular risk (N. Engl. J. Med. 2007:357:2109-22).
Further research suggested that the negative effects were caused not by reducing CTEP activity, but by off-target effects on renal glands, diminished nitrous oxide levels and increased endothelin-1, Dr. Lüscher explained.
The dal-VESSEL study was conducted at 19 centers in Europe and randomized 476 patients with coronary heart disease or CHD risk equivalents and HDL cholesterol of less than 50 mg/dL to dalcetrapib 600 mg/day or placebo plus their standard medication for a total of 36 weeks. Endothelial function was measured at 12 weeks using brachial flow-mediated dilation (FMD), a validated marker of endothelial dysfunction. Their mean age was 62 years, and roughly 97% were on statins.
The mean change in HDL cholesterol from baseline at week 4 was 2.7% for placebo and 27.5% for dalcetrapib; at week 36 it was -0.14% vs. 30.7%, respectively (P less than .0001 for both), Dr. Lüscher said.
At 36 weeks lipoprotein A-1 levels were significantly increased with dalcetrapib, but lipoprotein B levels were not affected.
There was no significant change with dalcetrapib in the co-primary safety endpoints of 24-hour ambulatory BP at week 4 and FMD at week 12.
Death from coronary heart disease occurred in one patient given placebo and none given dalcetrapib. Non-fatal myocardial infarctions were reported in 3 and 2 patients, respectively.
The trial was sponsored by Hoffmann-La Roche. Dr. Lüscher reports receiving research grants from Pfizer, Eli Lilly and Merck and consultancy or lecture fees from CSL, Merck, Pfizer and F. Hoffmann-La Roche.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: Dalcetrapib increased HDL cholesterol levels by 31%, compared with placebo.
Data Source: Phase IIb randomized trial in 476 patients with or at risk of coronary heart disease.
Disclosures: The trial was sponsored by F. Hoffmann-La Roche. Dr. Lüscher reports receiving research grants from Pfizer, Eli Lilly and Merck and consultancy or lecture fees from CSL, Merck, Pfizer and F. Hoffmann-La Roche.
Triglycerides Predict Heart Risk When Glucose Tolerance Is Normal
PARIS – Postprandial triglyceride levels helped assess cardiovascular risk in patients with normal glucose tolerance but provided no extra prognostic information in those with impaired glucose tolerance or diabetes in a prospective study of 514 consecutive patients with stable coronary artery disease.
In the Homburg Cream and Sugar Study participants who were undergoing coronary angiography ate a standardized dinner at 6 p.m., fasted overnight, and at 8 a.m. drank 250 ml of cream containing 75 g of fat. Three hours later those who were not receiving treatment for diabetes also drank 250 ml of water containing 75 g of glucose.
Investigators then measured fasting and postprandial triglyceride concentrations, followed by insulin concentrations and glucose tolerance. Follow-up 12 and 18 months later identified cardiovascular events.
Diabetes was present in 46% of patients, and only 25% had completely normal glucose tolerance. Patient characteristics were typical of those with coronary artery disease, Dr. Ulrich Laufs and his associates reported at the annual congress of the European Society of Cardiology.
For the cohort as a whole, postprandial triglyceride levels did not correlate with the primary outcome, a composite of cardiovascular deaths or hospitalizations for cardiovascular events. A weak correlation between fasting triglycerides and the primary outcome became non-significant in multivariate analysis.
Fasting triglyceride levels, and to an even greater extent postprandial triglyceride levels, were independent markers for the primary cardiovascular outcomes, said Dr. Laufs of Saarland University Hospital, Homburg, Germany. In patients with diabetes and impaired fasting glucose, however, absolute fasting and postprandial triglyceride levels were high but did not independently predict risk of cardiovascular death or hospitalization.
The highest tertile of triglyceride concentrations – levels above 150 mg/dL – in patients with normal glucose tolerance predicted a tripling in risk for the cardiovascular endpoints, compared with the middle and lowest tertiles. The highest tertile of postprandial triglyceride levels predicted a four-fold increased risk in patients with normal glucose tolerance. The study controlled for the effects of other risk factors, including other lipids, age, and sex.
These findings were "a little bit surprising," he said.
The study was designed to help address ongoing debate about whether triglyceride levels add to other measures of cardiovascular risk. "There is evidence from primary prevention studies and from mechanistic basic science studies that maybe the triglyceride-rich lipoproteins that are increased after a meal may be especially atherogenic," Dr. Laufs said.
Triglycerides are regulated not only by the time and type of meal but other factors as well. Importantly, glucose metabolism influences triglyceride kinetics, the study showed. Compared to patients with diabetes, those without diabetes had lower concentrations of fasting and absolute triglycerides and increased postprandial triglycerides. The relative increase, however, was similar between these two groups, he said.
"For the majority of patients, the primary consequence of this analysis is that we have to look very carefully at glucose metabolism," he said. "We may have to focus more on patients with normal glucose tolerance. If those patients have high fasting triglycerides, they have increased risk. It may be interesting in the future to look at whether these patients may benefit from intervention."
The study was limited by looking at only the first 5 hours after a meal, statin therapy in 95% of patients, the absence of genetic testing, and a predominantly Caucasian cohort, he said.
Dr. Laufs has been a speaker for nearly all pharmaceutical companies dealing with lipids.
This study addresses a very complicated and confusing question. There are as may answers to the question of the relationship between triglycerides and cardiovascular risk as there are studies looking at it.
In a previous study, an unadjusted analysis found that triglyceride levels in the fasting state were highly predictive of cardiovascular events, but that relationship was completely lost after adjustment for multiple variables, in particular other lipids. This led us to believe that triglycerides may be a marker of cardiovascular risk but that they are not causally related, and when other risk factors are included, they do not contribute to risk.
However, in the Women’s Health Study and another study, non-fasting triglycerides did predict cardiovascular risk after adjustment for multiple variables.
The current study certainly confirmed that fasting triglycerides did not predict cardiovascular risk in the whole cohort, and it also found that postprandial triglycerides did not predict risk after adjusting for other risk factors.
However, they found that both the fasting and postprandial triglyceride levels predicted cardiovascular outcomes in those who had normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This is something that has not been reported before.
There are some limitations and weaknesses in this study. The relatively small sample size for what is essentially an epidemiologic study and the relatively short follow-up – and, as a consequence, the small number of cardiovascular events – really does limit the conclusions. It doesn’t invalidate them, but it does mean that we cannot just assume that this is a proven case.
Also, the combined endpoint was rather soft. The hospitalization endpoint allows for a subjective element. Furthermore, there is no indication of the mechanism responsible for the findings.
Despite those limitations, this is a very, very interesting finding, if real. This was the first study designed to assess whether glucose metabolism status impacts the ability of triglyceride levels to predict cardiovascular risk. From this small study and with its limitations, the answer is, "Yes." I do not understand why there was no prediction in those with glucose intolerance or diabetes.
I think the results are provocative and, if real, have important clinical implications in terms of identifying those who need to treat triglyceride levels as distinct from other variables. I do believe this study requires confirmation.
Dr. Philip Barter of the Heart Research Institute, Sydney, Australia, has been a consultant, advisor, or lecturer for AstraZeneca, CSL, Merck, Novartis, Pfizer, Roche, and Sanofi Aventis. He made these comments during the meeting as the official discussant of the paper.
This study addresses a very complicated and confusing question. There are as may answers to the question of the relationship between triglycerides and cardiovascular risk as there are studies looking at it.
In a previous study, an unadjusted analysis found that triglyceride levels in the fasting state were highly predictive of cardiovascular events, but that relationship was completely lost after adjustment for multiple variables, in particular other lipids. This led us to believe that triglycerides may be a marker of cardiovascular risk but that they are not causally related, and when other risk factors are included, they do not contribute to risk.
However, in the Women’s Health Study and another study, non-fasting triglycerides did predict cardiovascular risk after adjustment for multiple variables.
The current study certainly confirmed that fasting triglycerides did not predict cardiovascular risk in the whole cohort, and it also found that postprandial triglycerides did not predict risk after adjusting for other risk factors.
However, they found that both the fasting and postprandial triglyceride levels predicted cardiovascular outcomes in those who had normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This is something that has not been reported before.
There are some limitations and weaknesses in this study. The relatively small sample size for what is essentially an epidemiologic study and the relatively short follow-up – and, as a consequence, the small number of cardiovascular events – really does limit the conclusions. It doesn’t invalidate them, but it does mean that we cannot just assume that this is a proven case.
Also, the combined endpoint was rather soft. The hospitalization endpoint allows for a subjective element. Furthermore, there is no indication of the mechanism responsible for the findings.
Despite those limitations, this is a very, very interesting finding, if real. This was the first study designed to assess whether glucose metabolism status impacts the ability of triglyceride levels to predict cardiovascular risk. From this small study and with its limitations, the answer is, "Yes." I do not understand why there was no prediction in those with glucose intolerance or diabetes.
I think the results are provocative and, if real, have important clinical implications in terms of identifying those who need to treat triglyceride levels as distinct from other variables. I do believe this study requires confirmation.
Dr. Philip Barter of the Heart Research Institute, Sydney, Australia, has been a consultant, advisor, or lecturer for AstraZeneca, CSL, Merck, Novartis, Pfizer, Roche, and Sanofi Aventis. He made these comments during the meeting as the official discussant of the paper.
This study addresses a very complicated and confusing question. There are as may answers to the question of the relationship between triglycerides and cardiovascular risk as there are studies looking at it.
In a previous study, an unadjusted analysis found that triglyceride levels in the fasting state were highly predictive of cardiovascular events, but that relationship was completely lost after adjustment for multiple variables, in particular other lipids. This led us to believe that triglycerides may be a marker of cardiovascular risk but that they are not causally related, and when other risk factors are included, they do not contribute to risk.
However, in the Women’s Health Study and another study, non-fasting triglycerides did predict cardiovascular risk after adjustment for multiple variables.
The current study certainly confirmed that fasting triglycerides did not predict cardiovascular risk in the whole cohort, and it also found that postprandial triglycerides did not predict risk after adjusting for other risk factors.
However, they found that both the fasting and postprandial triglyceride levels predicted cardiovascular outcomes in those who had normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This is something that has not been reported before.
There are some limitations and weaknesses in this study. The relatively small sample size for what is essentially an epidemiologic study and the relatively short follow-up – and, as a consequence, the small number of cardiovascular events – really does limit the conclusions. It doesn’t invalidate them, but it does mean that we cannot just assume that this is a proven case.
Also, the combined endpoint was rather soft. The hospitalization endpoint allows for a subjective element. Furthermore, there is no indication of the mechanism responsible for the findings.
Despite those limitations, this is a very, very interesting finding, if real. This was the first study designed to assess whether glucose metabolism status impacts the ability of triglyceride levels to predict cardiovascular risk. From this small study and with its limitations, the answer is, "Yes." I do not understand why there was no prediction in those with glucose intolerance or diabetes.
I think the results are provocative and, if real, have important clinical implications in terms of identifying those who need to treat triglyceride levels as distinct from other variables. I do believe this study requires confirmation.
Dr. Philip Barter of the Heart Research Institute, Sydney, Australia, has been a consultant, advisor, or lecturer for AstraZeneca, CSL, Merck, Novartis, Pfizer, Roche, and Sanofi Aventis. He made these comments during the meeting as the official discussant of the paper.
PARIS – Postprandial triglyceride levels helped assess cardiovascular risk in patients with normal glucose tolerance but provided no extra prognostic information in those with impaired glucose tolerance or diabetes in a prospective study of 514 consecutive patients with stable coronary artery disease.
In the Homburg Cream and Sugar Study participants who were undergoing coronary angiography ate a standardized dinner at 6 p.m., fasted overnight, and at 8 a.m. drank 250 ml of cream containing 75 g of fat. Three hours later those who were not receiving treatment for diabetes also drank 250 ml of water containing 75 g of glucose.
Investigators then measured fasting and postprandial triglyceride concentrations, followed by insulin concentrations and glucose tolerance. Follow-up 12 and 18 months later identified cardiovascular events.
Diabetes was present in 46% of patients, and only 25% had completely normal glucose tolerance. Patient characteristics were typical of those with coronary artery disease, Dr. Ulrich Laufs and his associates reported at the annual congress of the European Society of Cardiology.
For the cohort as a whole, postprandial triglyceride levels did not correlate with the primary outcome, a composite of cardiovascular deaths or hospitalizations for cardiovascular events. A weak correlation between fasting triglycerides and the primary outcome became non-significant in multivariate analysis.
Fasting triglyceride levels, and to an even greater extent postprandial triglyceride levels, were independent markers for the primary cardiovascular outcomes, said Dr. Laufs of Saarland University Hospital, Homburg, Germany. In patients with diabetes and impaired fasting glucose, however, absolute fasting and postprandial triglyceride levels were high but did not independently predict risk of cardiovascular death or hospitalization.
The highest tertile of triglyceride concentrations – levels above 150 mg/dL – in patients with normal glucose tolerance predicted a tripling in risk for the cardiovascular endpoints, compared with the middle and lowest tertiles. The highest tertile of postprandial triglyceride levels predicted a four-fold increased risk in patients with normal glucose tolerance. The study controlled for the effects of other risk factors, including other lipids, age, and sex.
These findings were "a little bit surprising," he said.
The study was designed to help address ongoing debate about whether triglyceride levels add to other measures of cardiovascular risk. "There is evidence from primary prevention studies and from mechanistic basic science studies that maybe the triglyceride-rich lipoproteins that are increased after a meal may be especially atherogenic," Dr. Laufs said.
Triglycerides are regulated not only by the time and type of meal but other factors as well. Importantly, glucose metabolism influences triglyceride kinetics, the study showed. Compared to patients with diabetes, those without diabetes had lower concentrations of fasting and absolute triglycerides and increased postprandial triglycerides. The relative increase, however, was similar between these two groups, he said.
"For the majority of patients, the primary consequence of this analysis is that we have to look very carefully at glucose metabolism," he said. "We may have to focus more on patients with normal glucose tolerance. If those patients have high fasting triglycerides, they have increased risk. It may be interesting in the future to look at whether these patients may benefit from intervention."
The study was limited by looking at only the first 5 hours after a meal, statin therapy in 95% of patients, the absence of genetic testing, and a predominantly Caucasian cohort, he said.
Dr. Laufs has been a speaker for nearly all pharmaceutical companies dealing with lipids.
PARIS – Postprandial triglyceride levels helped assess cardiovascular risk in patients with normal glucose tolerance but provided no extra prognostic information in those with impaired glucose tolerance or diabetes in a prospective study of 514 consecutive patients with stable coronary artery disease.
In the Homburg Cream and Sugar Study participants who were undergoing coronary angiography ate a standardized dinner at 6 p.m., fasted overnight, and at 8 a.m. drank 250 ml of cream containing 75 g of fat. Three hours later those who were not receiving treatment for diabetes also drank 250 ml of water containing 75 g of glucose.
Investigators then measured fasting and postprandial triglyceride concentrations, followed by insulin concentrations and glucose tolerance. Follow-up 12 and 18 months later identified cardiovascular events.
Diabetes was present in 46% of patients, and only 25% had completely normal glucose tolerance. Patient characteristics were typical of those with coronary artery disease, Dr. Ulrich Laufs and his associates reported at the annual congress of the European Society of Cardiology.
For the cohort as a whole, postprandial triglyceride levels did not correlate with the primary outcome, a composite of cardiovascular deaths or hospitalizations for cardiovascular events. A weak correlation between fasting triglycerides and the primary outcome became non-significant in multivariate analysis.
Fasting triglyceride levels, and to an even greater extent postprandial triglyceride levels, were independent markers for the primary cardiovascular outcomes, said Dr. Laufs of Saarland University Hospital, Homburg, Germany. In patients with diabetes and impaired fasting glucose, however, absolute fasting and postprandial triglyceride levels were high but did not independently predict risk of cardiovascular death or hospitalization.
The highest tertile of triglyceride concentrations – levels above 150 mg/dL – in patients with normal glucose tolerance predicted a tripling in risk for the cardiovascular endpoints, compared with the middle and lowest tertiles. The highest tertile of postprandial triglyceride levels predicted a four-fold increased risk in patients with normal glucose tolerance. The study controlled for the effects of other risk factors, including other lipids, age, and sex.
These findings were "a little bit surprising," he said.
The study was designed to help address ongoing debate about whether triglyceride levels add to other measures of cardiovascular risk. "There is evidence from primary prevention studies and from mechanistic basic science studies that maybe the triglyceride-rich lipoproteins that are increased after a meal may be especially atherogenic," Dr. Laufs said.
Triglycerides are regulated not only by the time and type of meal but other factors as well. Importantly, glucose metabolism influences triglyceride kinetics, the study showed. Compared to patients with diabetes, those without diabetes had lower concentrations of fasting and absolute triglycerides and increased postprandial triglycerides. The relative increase, however, was similar between these two groups, he said.
"For the majority of patients, the primary consequence of this analysis is that we have to look very carefully at glucose metabolism," he said. "We may have to focus more on patients with normal glucose tolerance. If those patients have high fasting triglycerides, they have increased risk. It may be interesting in the future to look at whether these patients may benefit from intervention."
The study was limited by looking at only the first 5 hours after a meal, statin therapy in 95% of patients, the absence of genetic testing, and a predominantly Caucasian cohort, he said.
Dr. Laufs has been a speaker for nearly all pharmaceutical companies dealing with lipids.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: Higher triglyceride levels independently predicted higher cardiovascular risk in patients with stable coronary artery disease who had normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes.
Data Source: Prospective cohort study of 514 patients with stable coronary artery disease who were undergoing coronary angiography.
Disclosures: Dr. Laufs has been a speaker for nearly all pharmaceutical companies dealing with lipids.