Miriam E. Tucker

WASHINGTON — The hypoandrogenic effects of oral contraceptives may not be completely reversible after discontinuation of their use, Claudia Panzer, M.D., reported at the annual meeting of the American Association of Clinical Endocrinologists.

Oral contraceptives (OCs) are known to decrease serum testosterone levels by decreasing ovarian production of testosterone and increasing production of sex hormone-binding globulin (SHBG) by the liver. Higher SHBG levels lower the amount of free testosterone that reaches the tissues. Such changes have been associated with decreases in sexual interest, arousal, vaginal lubrication, and frequency of sexual intercourse.

It has long been assumed that these changes are reversible after discontinuation of OC use, but findings from a review of 124 premenopausal women with female sexual dysfunction suggest otherwise, said Dr. Panzer, an endocrinologist at Boston University.

Among the subjects were 62 current OC users, 39 former users, and 23 who had never used OCs. None of the subjects had used OCs for reasons other than birth control. The “never users” were older than the current users (36 vs. 32 years), and had a longer duration of sexual dysfunction than both current and former OC users (9 years vs. 6 years in both OC groups).

Those who had never used OCs also scored higher on the Female Sexual Function Index, indicating better function (21 points, vs. 15 points for the current OC users and 10 points for the former users). Women on OCs had lower scores in the domain of sexual desire, compared with those who had never used them, and also complained more about sexual pain.

Of the 101 OC users, 39 said that the knowledge that the pill might cause sexual dysfunction would convince them to stop taking it. “I guess that is pretty good evidence that they were impacted enough to change things,” Dr. Panzer told this newspaper.

There were no differences between the groups in body mass index, Beck Depression Index scores (means were all in the normal range), or scores on the Sexual Distress Scale (means for all indicated moderate distress).

Baseline SHBG levels were four times higher in the current OC users (157 nmol/L) and the former users (161 nmol/L) than in the never users (41 nmol/L). Although SHBG levels did decrease after discontinuation of OC use, they remained elevated after 49–120 days (62 nmol/L) and again at more than 120 days (63 nmol/L), compared with the never users, for whom SHBG measured after 120 days was 35 nmol/L, she said.

The fact that the SHBG value after 120 days in the group that had discontinued OCs had fallen into the normal reference range despite being twice as high as for the never-users suggests that the currently used SHBG reference range may be too wide. A narrower range might better reflect hormonal changes seen in women who use OCs, Dr. Panzer commented.

Total testosterone levels at baseline did not differ between the three groups, but the never users had significantly higher free androgen indexes than did the current and former OC users (3.7 vs. 0.8 for both OC groups), calculated free testosterone levels (6.2 pg/mL vs. 2 pg/mL for both OC groups), and calculated bioavailable testosterone (146.5 pg/mL vs. 47.8 pg/mL for former users and 46.7 pg/mL for current users).

These data suggest that total testosterone is a poor test to evaluate androgen status in OC users and that assessments of free or bioavailable testosterone are superior, Dr. Panzer said.

Physicians who prescribe OCs should warn patients of possible sexual side effects associated with their use, she recommended.

WASHINGTON — The hypoandrogenic effects of oral contraceptives may not be completely reversible after discontinuation of their use, Claudia Panzer, M.D., reported at the annual meeting of the American Association of Clinical Endocrinologists.

Oral contraceptives (OCs) are known to decrease serum testosterone levels by decreasing ovarian production of testosterone and increasing production of sex hormone-binding globulin (SHBG) by the liver. Higher SHBG levels lower the amount of free testosterone that reaches the tissues. Such changes have been associated with decreases in sexual interest, arousal, vaginal lubrication, and frequency of sexual intercourse.

It has long been assumed that these changes are reversible after discontinuation of OC use, but findings from a review of 124 premenopausal women with female sexual dysfunction suggest otherwise, said Dr. Panzer, an endocrinologist at Boston University.

Among the subjects were 62 current OC users, 39 former users, and 23 who had never used OCs. None of the subjects had used OCs for reasons other than birth control. The “never users” were older than the current users (36 vs. 32 years), and had a longer duration of sexual dysfunction than both current and former OC users (9 years vs. 6 years in both OC groups).

Those who had never used OCs also scored higher on the Female Sexual Function Index, indicating better function (21 points, vs. 15 points for the current OC users and 10 points for the former users). Women on OCs had lower scores in the domain of sexual desire, compared with those who had never used them, and also complained more about sexual pain.

Of the 101 OC users, 39 said that the knowledge that the pill might cause sexual dysfunction would convince them to stop taking it. “I guess that is pretty good evidence that they were impacted enough to change things,” Dr. Panzer told this newspaper.

There were no differences between the groups in body mass index, Beck Depression Index scores (means were all in the normal range), or scores on the Sexual Distress Scale (means for all indicated moderate distress).

Baseline SHBG levels were four times higher in the current OC users (157 nmol/L) and the former users (161 nmol/L) than in the never users (41 nmol/L). Although SHBG levels did decrease after discontinuation of OC use, they remained elevated after 49–120 days (62 nmol/L) and again at more than 120 days (63 nmol/L), compared with the never users, for whom SHBG measured after 120 days was 35 nmol/L, she said.

The fact that the SHBG value after 120 days in the group that had discontinued OCs had fallen into the normal reference range despite being twice as high as for the never-users suggests that the currently used SHBG reference range may be too wide. A narrower range might better reflect hormonal changes seen in women who use OCs, Dr. Panzer commented.

Total testosterone levels at baseline did not differ between the three groups, but the never users had significantly higher free androgen indexes than did the current and former OC users (3.7 vs. 0.8 for both OC groups), calculated free testosterone levels (6.2 pg/mL vs. 2 pg/mL for both OC groups), and calculated bioavailable testosterone (146.5 pg/mL vs. 47.8 pg/mL for former users and 46.7 pg/mL for current users).

These data suggest that total testosterone is a poor test to evaluate androgen status in OC users and that assessments of free or bioavailable testosterone are superior, Dr. Panzer said.

Physicians who prescribe OCs should warn patients of possible sexual side effects associated with their use, she recommended.

WASHINGTON — The hypoandrogenic effects of oral contraceptives may not be completely reversible after discontinuation of their use, Claudia Panzer, M.D., reported at the annual meeting of the American Association of Clinical Endocrinologists.

Oral contraceptives (OCs) are known to decrease serum testosterone levels by decreasing ovarian production of testosterone and increasing production of sex hormone-binding globulin (SHBG) by the liver. Higher SHBG levels lower the amount of free testosterone that reaches the tissues. Such changes have been associated with decreases in sexual interest, arousal, vaginal lubrication, and frequency of sexual intercourse.

It has long been assumed that these changes are reversible after discontinuation of OC use, but findings from a review of 124 premenopausal women with female sexual dysfunction suggest otherwise, said Dr. Panzer, an endocrinologist at Boston University.

Among the subjects were 62 current OC users, 39 former users, and 23 who had never used OCs. None of the subjects had used OCs for reasons other than birth control. The “never users” were older than the current users (36 vs. 32 years), and had a longer duration of sexual dysfunction than both current and former OC users (9 years vs. 6 years in both OC groups).

Those who had never used OCs also scored higher on the Female Sexual Function Index, indicating better function (21 points, vs. 15 points for the current OC users and 10 points for the former users). Women on OCs had lower scores in the domain of sexual desire, compared with those who had never used them, and also complained more about sexual pain.

Of the 101 OC users, 39 said that the knowledge that the pill might cause sexual dysfunction would convince them to stop taking it. “I guess that is pretty good evidence that they were impacted enough to change things,” Dr. Panzer told this newspaper.

There were no differences between the groups in body mass index, Beck Depression Index scores (means were all in the normal range), or scores on the Sexual Distress Scale (means for all indicated moderate distress).

Baseline SHBG levels were four times higher in the current OC users (157 nmol/L) and the former users (161 nmol/L) than in the never users (41 nmol/L). Although SHBG levels did decrease after discontinuation of OC use, they remained elevated after 49–120 days (62 nmol/L) and again at more than 120 days (63 nmol/L), compared with the never users, for whom SHBG measured after 120 days was 35 nmol/L, she said.

The fact that the SHBG value after 120 days in the group that had discontinued OCs had fallen into the normal reference range despite being twice as high as for the never-users suggests that the currently used SHBG reference range may be too wide. A narrower range might better reflect hormonal changes seen in women who use OCs, Dr. Panzer commented.

Total testosterone levels at baseline did not differ between the three groups, but the never users had significantly higher free androgen indexes than did the current and former OC users (3.7 vs. 0.8 for both OC groups), calculated free testosterone levels (6.2 pg/mL vs. 2 pg/mL for both OC groups), and calculated bioavailable testosterone (146.5 pg/mL vs. 47.8 pg/mL for former users and 46.7 pg/mL for current users).

These data suggest that total testosterone is a poor test to evaluate androgen status in OC users and that assessments of free or bioavailable testosterone are superior, Dr. Panzer said.

Physicians who prescribe OCs should warn patients of possible sexual side effects associated with their use, she recommended.

WASHINGTON — Elderly adults with subclinical hypothyroidism and a thyroid stimulating hormone level at or above 7 mIU/L are at increased risk for heart failure, Nicolas Rodondi, M.D., reported at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

However, adults aged 70–79 with subclinical hypothyroidism with TSH values below 7 mIU/L are not at increased risk.

Subclinical hypothyroidism does not appear to be associated with other cardiovascular events in that age group, regardless of TSH level, said Dr. Rodondi of the University of California, San Francisco.

Previous studies have shown that subclinical hypothyroidism—in which T₄ is normal but TSH is elevated (4.5 mIU/L or above) —is associated with elevated total cholesterol, LDL cholesterol, and C-reactive protein. But data on cardiovascular outcomes are conflicting, he noted at the conference, also sponsored by the National Heart, Lung, and Blood Institute.

The current study included 2,740 men and women aged 70–79 participating in the Health, Aging, and Body Composition Study, funded by the National Institute on Aging. Subjects with abnormal T₄ levels or TSH levels at or below 0.1 mIU/L had been previously excluded.

The 339 individuals who had subclinical hypothyroidism at baseline were less likely than the 2,401 euthyroid subjects to be black (25.4% vs. 41.8%), but did not differ significantly by age or gender.

At baseline, total cholesterol was significantly higher among those with subclinical hypothyroidism (211.5 vs. 204.5 mg/dL). About 30% of both groups had prevalent cardiovascular disease (CVD) at baseline, while 8.3% of the subclinical hypothyroid and 6.2% of the euthyroid groups had preexisting heart failure.

Rates of heart failure were 17/1,000 person-years in the euthyroid group, compared with 22/1,000 person-years in the subclinical hypothyroid group.

Among subjects who had TSH levels of 10 mIU/L or greater, the mean rate of heart failure was 37/1,000 person-years, with a hazard ratio of 3.10 after adjustment for demographics, socioeconomic characteristics, thyroid hormone use, cardiovascular risk factors, and prevalent cardiovascular disease.

For those with TSH of 7–9.9 mIU/L, the rate was 37/1,000 person-years and the adjusted hazard ratio 2.88. The heart failure rate among subjects with TSH levels of 4.5–6.9 mIU/L was just 15/1,000 person-years, not significantly different from the euthyroid group, and none of the subclinical hypothyroid group had significantly elevated rates of CHD, stroke, peripheral artery disease, or mortality.

Among the 2,558 subjects without heart failure at baseline, the hazard ratio for developing heart failure during the 4-year follow-up among those with TSH at or above 7 mIU/L was 2.49, compared with those who were euthyroid.

Among the 182 who already had heart failure at baseline, the risk for recurrent heart failure was even greater, with a hazard ratio of 7.62.

WASHINGTON — Elderly adults with subclinical hypothyroidism and a thyroid stimulating hormone level at or above 7 mIU/L are at increased risk for heart failure, Nicolas Rodondi, M.D., reported at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

However, adults aged 70–79 with subclinical hypothyroidism with TSH values below 7 mIU/L are not at increased risk.

Subclinical hypothyroidism does not appear to be associated with other cardiovascular events in that age group, regardless of TSH level, said Dr. Rodondi of the University of California, San Francisco.

Previous studies have shown that subclinical hypothyroidism—in which T₄ is normal but TSH is elevated (4.5 mIU/L or above) —is associated with elevated total cholesterol, LDL cholesterol, and C-reactive protein. But data on cardiovascular outcomes are conflicting, he noted at the conference, also sponsored by the National Heart, Lung, and Blood Institute.

The current study included 2,740 men and women aged 70–79 participating in the Health, Aging, and Body Composition Study, funded by the National Institute on Aging. Subjects with abnormal T₄ levels or TSH levels at or below 0.1 mIU/L had been previously excluded.

The 339 individuals who had subclinical hypothyroidism at baseline were less likely than the 2,401 euthyroid subjects to be black (25.4% vs. 41.8%), but did not differ significantly by age or gender.

At baseline, total cholesterol was significantly higher among those with subclinical hypothyroidism (211.5 vs. 204.5 mg/dL). About 30% of both groups had prevalent cardiovascular disease (CVD) at baseline, while 8.3% of the subclinical hypothyroid and 6.2% of the euthyroid groups had preexisting heart failure.

Rates of heart failure were 17/1,000 person-years in the euthyroid group, compared with 22/1,000 person-years in the subclinical hypothyroid group.

Among subjects who had TSH levels of 10 mIU/L or greater, the mean rate of heart failure was 37/1,000 person-years, with a hazard ratio of 3.10 after adjustment for demographics, socioeconomic characteristics, thyroid hormone use, cardiovascular risk factors, and prevalent cardiovascular disease.

For those with TSH of 7–9.9 mIU/L, the rate was 37/1,000 person-years and the adjusted hazard ratio 2.88. The heart failure rate among subjects with TSH levels of 4.5–6.9 mIU/L was just 15/1,000 person-years, not significantly different from the euthyroid group, and none of the subclinical hypothyroid group had significantly elevated rates of CHD, stroke, peripheral artery disease, or mortality.

Among the 2,558 subjects without heart failure at baseline, the hazard ratio for developing heart failure during the 4-year follow-up among those with TSH at or above 7 mIU/L was 2.49, compared with those who were euthyroid.

Among the 182 who already had heart failure at baseline, the risk for recurrent heart failure was even greater, with a hazard ratio of 7.62.

WASHINGTON — Elderly adults with subclinical hypothyroidism and a thyroid stimulating hormone level at or above 7 mIU/L are at increased risk for heart failure, Nicolas Rodondi, M.D., reported at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

However, adults aged 70–79 with subclinical hypothyroidism with TSH values below 7 mIU/L are not at increased risk.

Subclinical hypothyroidism does not appear to be associated with other cardiovascular events in that age group, regardless of TSH level, said Dr. Rodondi of the University of California, San Francisco.

Previous studies have shown that subclinical hypothyroidism—in which T₄ is normal but TSH is elevated (4.5 mIU/L or above) —is associated with elevated total cholesterol, LDL cholesterol, and C-reactive protein. But data on cardiovascular outcomes are conflicting, he noted at the conference, also sponsored by the National Heart, Lung, and Blood Institute.

The current study included 2,740 men and women aged 70–79 participating in the Health, Aging, and Body Composition Study, funded by the National Institute on Aging. Subjects with abnormal T₄ levels or TSH levels at or below 0.1 mIU/L had been previously excluded.

The 339 individuals who had subclinical hypothyroidism at baseline were less likely than the 2,401 euthyroid subjects to be black (25.4% vs. 41.8%), but did not differ significantly by age or gender.

At baseline, total cholesterol was significantly higher among those with subclinical hypothyroidism (211.5 vs. 204.5 mg/dL). About 30% of both groups had prevalent cardiovascular disease (CVD) at baseline, while 8.3% of the subclinical hypothyroid and 6.2% of the euthyroid groups had preexisting heart failure.

Rates of heart failure were 17/1,000 person-years in the euthyroid group, compared with 22/1,000 person-years in the subclinical hypothyroid group.

Among subjects who had TSH levels of 10 mIU/L or greater, the mean rate of heart failure was 37/1,000 person-years, with a hazard ratio of 3.10 after adjustment for demographics, socioeconomic characteristics, thyroid hormone use, cardiovascular risk factors, and prevalent cardiovascular disease.

For those with TSH of 7–9.9 mIU/L, the rate was 37/1,000 person-years and the adjusted hazard ratio 2.88. The heart failure rate among subjects with TSH levels of 4.5–6.9 mIU/L was just 15/1,000 person-years, not significantly different from the euthyroid group, and none of the subclinical hypothyroid group had significantly elevated rates of CHD, stroke, peripheral artery disease, or mortality.

Among the 2,558 subjects without heart failure at baseline, the hazard ratio for developing heart failure during the 4-year follow-up among those with TSH at or above 7 mIU/L was 2.49, compared with those who were euthyroid.

Among the 182 who already had heart failure at baseline, the risk for recurrent heart failure was even greater, with a hazard ratio of 7.62.

WASHINGTON — Women gain more weight on thiazolidinedione therapy than do men, Amy Toscano-Zukor, D.O., and Xiangbing Wang, M.D., reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Weight gain is often noted in patients with type 2 diabetes after initiation of thiazolidinedione therapy. Proposed mechanisms include fluid retention and/or an increase in subcutaneous fat accompanied by a decrease in visceral fat, according to Dr. Toscano-Zukor and Dr. Wang of Saint Peter's University Hospital, New Brunswick, N.J., and Robert Wood Johnson Medical School, New Brunswick.

In the first study to compare weight gain by gender among patients on thiazolidinediones, the investigators randomly reviewed the charts of 31 men and 30 women in an outpatient endocrinology practice.

All patients were receiving either pioglitazone or rosiglitazone, as monotherapy or as part of a multidrug regimen for diabetes. The men and women did not differ significantly in mean age, initial body weight, body mass index, diabetes duration, hemoglobin A_1c, or number/type of diabetes medications.

The proportion of patients with significant weight gain, defined as a greater than 3% increase in weight from baseline, was 60% of female patients and 26% of males.

Among those who gained weight, women gained a higher percentage of body weight than did men (9.3% vs. 5.1%).

WASHINGTON — Women gain more weight on thiazolidinedione therapy than do men, Amy Toscano-Zukor, D.O., and Xiangbing Wang, M.D., reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Weight gain is often noted in patients with type 2 diabetes after initiation of thiazolidinedione therapy. Proposed mechanisms include fluid retention and/or an increase in subcutaneous fat accompanied by a decrease in visceral fat, according to Dr. Toscano-Zukor and Dr. Wang of Saint Peter's University Hospital, New Brunswick, N.J., and Robert Wood Johnson Medical School, New Brunswick.

In the first study to compare weight gain by gender among patients on thiazolidinediones, the investigators randomly reviewed the charts of 31 men and 30 women in an outpatient endocrinology practice.

All patients were receiving either pioglitazone or rosiglitazone, as monotherapy or as part of a multidrug regimen for diabetes. The men and women did not differ significantly in mean age, initial body weight, body mass index, diabetes duration, hemoglobin A_1c, or number/type of diabetes medications.

The proportion of patients with significant weight gain, defined as a greater than 3% increase in weight from baseline, was 60% of female patients and 26% of males.

Among those who gained weight, women gained a higher percentage of body weight than did men (9.3% vs. 5.1%).

WASHINGTON — Women gain more weight on thiazolidinedione therapy than do men, Amy Toscano-Zukor, D.O., and Xiangbing Wang, M.D., reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Weight gain is often noted in patients with type 2 diabetes after initiation of thiazolidinedione therapy. Proposed mechanisms include fluid retention and/or an increase in subcutaneous fat accompanied by a decrease in visceral fat, according to Dr. Toscano-Zukor and Dr. Wang of Saint Peter's University Hospital, New Brunswick, N.J., and Robert Wood Johnson Medical School, New Brunswick.

In the first study to compare weight gain by gender among patients on thiazolidinediones, the investigators randomly reviewed the charts of 31 men and 30 women in an outpatient endocrinology practice.

All patients were receiving either pioglitazone or rosiglitazone, as monotherapy or as part of a multidrug regimen for diabetes. The men and women did not differ significantly in mean age, initial body weight, body mass index, diabetes duration, hemoglobin A_1c, or number/type of diabetes medications.

The proportion of patients with significant weight gain, defined as a greater than 3% increase in weight from baseline, was 60% of female patients and 26% of males.

Among those who gained weight, women gained a higher percentage of body weight than did men (9.3% vs. 5.1%).

WASHINGTON — Muraglitazar, a novel agent targeting both glucose and lipid levels, is an effective monotherapy option for patients with type 2 diabetes, Robert Frederich, M.D., and his associates reported at the annual meeting of the American Association of Clinical Endocrinologists.

In the first phase III data to be released by comarketers Bristol-Myers Squibb Co. and Merck & Co., muraglitazar effectively lowered hemoglobin A_1c and triglycerides and raised HDL cholesterol levels in a 24-week, randomized, double-blind, placebo-controlled trial of drug-naive adults with type 2 diabetes who were inadequately controlled with diet and exercise alone, said Dr. Frederich, of Bristol-Myers Squibb in Princeton, N.J., and his associates.

The New Drug Application for muraglitazar is under review by the Food and Drug Administration. If approved, the drug would be the first of the new class called “glitazars,” agents that activate both α and γ peroxisome proliferator-activated receptors (PPARs).

The PPARs, members of the steroid hormone nuclear receptor family, are already established as therapeutic targets for treating diabetes and dyslipidemia: The thiazolidinedione class of glucose-lowering agents are PPAR-γ agonists, while fibrates improve lipid profiles via PPAR-α activation, Jorge Plutzky, M.D., explained at a satellite symposium sponsored by Bristol-Myers Squibb and Merck held during the AACE meeting.

“Such drugs hold out the potential for combining PPAR-α's lipid improvements, the PPAR-γ's insulin-sensitizing effects, and the possible anti-inflammatory/antiatherosclerotic effects of both receptors,” said Dr. Plutzky, director of The Vascular Disease Prevention Program at Brigham and Women's Hospital, Boston.

According to AACE past president Paul Jellinger, M.D., “combo pills are becoming more common and more accepted by many [physicians] largely because of reduced copayment.

Dual PPARs may be useful because the triglyceride/HDL part of diabetic dyslipidemia often gets overlooked in favor of straight LDL lowering with statins,” he told this newspaper after the meeting.

Most diabetics are already on lipid-lowering therapy, and statin therapy sometimes adequately addresses diabetic dyslipidemia, but often it does not. “On balance, I believe dual PPAR's will be a sensible and useful addition,” said Dr. Jellinger, of Hollywood, Fla.

The study patients were adults aged 18–70 years who had a mean baseline hemoglobin A_1c between 7% and 10%. None were on antihypertensive therapy in the 4–6 weeks before the study. Therapy with a stable dose of statins was allowed through the first 12 weeks of the trial.

A total of 111 patients were randomized to receive 2.5 mg of muraglitazar daily, 114 took 5.0 mg, and 109 received placebo. In a separate open-label trial, another 109 patients with baseline A_1c values of 10%–12% received 5.0 mg of muraglitazar daily, Dr. Frederich and his associates reported in a poster presentation.

At 24 weeks, the mean A_1c values dropped from 8.02% to 6.96% (−1.05) in the 2.5-mg muraglitazar group, from 7.89% to 6.68% (−1.23) in the blinded 5.0-mg patients, and from 10.68% to 8.06% (−2.62) in the open-label 5.0-mg group. In contrast, A_1c levels among the placebo patients fell by an insignificant 0.32 percentage points, from 7.99% to 7.67%.

In the randomized trial, 67% of the 2.5-mg group and 74% of the 5.0-mg group achieved the American Diabetes Association's A_1c target of less than 7.0%, compared with 32% of the placebo patients. The proportions who dropped below the AACE's 6.5% cutoff were 58%, 36%, and 18%, respectively. Fasting plasma glucose and insulin levels also were significantly reduced in both muraglitazar dosage groups in the double-blind trial, they said.

Triglyceride levels in the double-blind trial decreased significantly by 18% with 2.5 mg of muraglitazar and by 27% with 5.0 mg, compared with just 2% for placebo. In the open-label trial, triglycerides were reduced by 31%. Among the patients with baseline triglycerides of 150 mg/dL or above, reductions at 24 weeks were 24.8% with 2.5 mg of muraglitazar, 30.4% with 5.0 mg, 13.2% with placebo, and 31% in the open-label trial with 5.0 mg.

Mean HDL cholesterol levels rose by 10% and 16% with 2.5 mg and 5.0 mg of muraglitazar, respectively, in the blinded trial, both significant increases compared with the 2% rise with placebo. Levels of LDL cholesterol didn't change significantly with muraglitazar, but levels of apolipoprotein B, free fatty acid, and non-HDL cholesterol did, Dr. Frederich and his associates reported.

Adverse events occurred in 71% of patients with 2.5 mg of muraglitazar, 77% with 5.0 mg, 69% with placebo, and 70% in the open-label 5.0-mg group, with serious adverse events in 3%–4% of all groups with no significant differences between them. There were no cases of heart failure.

Edema-related events occurred in 8% with 2.5 mg, 11% with 5.0 mg, 8% with placebo, and 9% in the open-label group. All events in the muraglitazar patients were mild to moderate, while one placebo patient experienced serious edema. No patient treated with muraglitazar discontinued the study due to edema, but two placebo patients did.

There were no confirmed cases of glucose values at or below 50 mg/dL, and no patient dropped out of the study due to hypoglycemia. Mean change in body weight from baseline were gains of 1.1 kg in the 2.5-mg muraglitazar group and 2.1 kg with 5.0 mg, while the placebo group lost a mean of 0.8 kg. The open-label patients gained 2.9 kg.

Adverse events led to discontinuation of the study in 3%–4% of all muraglitazar groups and the placebo group, while rates of discontinuation due to lack of efficacy in the double-blind patients were 8% for 2.5 mg and 6% for 5.0 mg, compared with 23% for placebo.

WASHINGTON — Muraglitazar, a novel agent targeting both glucose and lipid levels, is an effective monotherapy option for patients with type 2 diabetes, Robert Frederich, M.D., and his associates reported at the annual meeting of the American Association of Clinical Endocrinologists.

In the first phase III data to be released by comarketers Bristol-Myers Squibb Co. and Merck & Co., muraglitazar effectively lowered hemoglobin A_1c and triglycerides and raised HDL cholesterol levels in a 24-week, randomized, double-blind, placebo-controlled trial of drug-naive adults with type 2 diabetes who were inadequately controlled with diet and exercise alone, said Dr. Frederich, of Bristol-Myers Squibb in Princeton, N.J., and his associates.

The New Drug Application for muraglitazar is under review by the Food and Drug Administration. If approved, the drug would be the first of the new class called “glitazars,” agents that activate both α and γ peroxisome proliferator-activated receptors (PPARs).

The PPARs, members of the steroid hormone nuclear receptor family, are already established as therapeutic targets for treating diabetes and dyslipidemia: The thiazolidinedione class of glucose-lowering agents are PPAR-γ agonists, while fibrates improve lipid profiles via PPAR-α activation, Jorge Plutzky, M.D., explained at a satellite symposium sponsored by Bristol-Myers Squibb and Merck held during the AACE meeting.

“Such drugs hold out the potential for combining PPAR-α's lipid improvements, the PPAR-γ's insulin-sensitizing effects, and the possible anti-inflammatory/antiatherosclerotic effects of both receptors,” said Dr. Plutzky, director of The Vascular Disease Prevention Program at Brigham and Women's Hospital, Boston.

According to AACE past president Paul Jellinger, M.D., “combo pills are becoming more common and more accepted by many [physicians] largely because of reduced copayment.

Dual PPARs may be useful because the triglyceride/HDL part of diabetic dyslipidemia often gets overlooked in favor of straight LDL lowering with statins,” he told this newspaper after the meeting.

Most diabetics are already on lipid-lowering therapy, and statin therapy sometimes adequately addresses diabetic dyslipidemia, but often it does not. “On balance, I believe dual PPAR's will be a sensible and useful addition,” said Dr. Jellinger, of Hollywood, Fla.

The study patients were adults aged 18–70 years who had a mean baseline hemoglobin A_1c between 7% and 10%. None were on antihypertensive therapy in the 4–6 weeks before the study. Therapy with a stable dose of statins was allowed through the first 12 weeks of the trial.

A total of 111 patients were randomized to receive 2.5 mg of muraglitazar daily, 114 took 5.0 mg, and 109 received placebo. In a separate open-label trial, another 109 patients with baseline A_1c values of 10%–12% received 5.0 mg of muraglitazar daily, Dr. Frederich and his associates reported in a poster presentation.

At 24 weeks, the mean A_1c values dropped from 8.02% to 6.96% (−1.05) in the 2.5-mg muraglitazar group, from 7.89% to 6.68% (−1.23) in the blinded 5.0-mg patients, and from 10.68% to 8.06% (−2.62) in the open-label 5.0-mg group. In contrast, A_1c levels among the placebo patients fell by an insignificant 0.32 percentage points, from 7.99% to 7.67%.

In the randomized trial, 67% of the 2.5-mg group and 74% of the 5.0-mg group achieved the American Diabetes Association's A_1c target of less than 7.0%, compared with 32% of the placebo patients. The proportions who dropped below the AACE's 6.5% cutoff were 58%, 36%, and 18%, respectively. Fasting plasma glucose and insulin levels also were significantly reduced in both muraglitazar dosage groups in the double-blind trial, they said.

Triglyceride levels in the double-blind trial decreased significantly by 18% with 2.5 mg of muraglitazar and by 27% with 5.0 mg, compared with just 2% for placebo. In the open-label trial, triglycerides were reduced by 31%. Among the patients with baseline triglycerides of 150 mg/dL or above, reductions at 24 weeks were 24.8% with 2.5 mg of muraglitazar, 30.4% with 5.0 mg, 13.2% with placebo, and 31% in the open-label trial with 5.0 mg.

Mean HDL cholesterol levels rose by 10% and 16% with 2.5 mg and 5.0 mg of muraglitazar, respectively, in the blinded trial, both significant increases compared with the 2% rise with placebo. Levels of LDL cholesterol didn't change significantly with muraglitazar, but levels of apolipoprotein B, free fatty acid, and non-HDL cholesterol did, Dr. Frederich and his associates reported.

Adverse events occurred in 71% of patients with 2.5 mg of muraglitazar, 77% with 5.0 mg, 69% with placebo, and 70% in the open-label 5.0-mg group, with serious adverse events in 3%–4% of all groups with no significant differences between them. There were no cases of heart failure.

Edema-related events occurred in 8% with 2.5 mg, 11% with 5.0 mg, 8% with placebo, and 9% in the open-label group. All events in the muraglitazar patients were mild to moderate, while one placebo patient experienced serious edema. No patient treated with muraglitazar discontinued the study due to edema, but two placebo patients did.

There were no confirmed cases of glucose values at or below 50 mg/dL, and no patient dropped out of the study due to hypoglycemia. Mean change in body weight from baseline were gains of 1.1 kg in the 2.5-mg muraglitazar group and 2.1 kg with 5.0 mg, while the placebo group lost a mean of 0.8 kg. The open-label patients gained 2.9 kg.

Adverse events led to discontinuation of the study in 3%–4% of all muraglitazar groups and the placebo group, while rates of discontinuation due to lack of efficacy in the double-blind patients were 8% for 2.5 mg and 6% for 5.0 mg, compared with 23% for placebo.

WASHINGTON — Muraglitazar, a novel agent targeting both glucose and lipid levels, is an effective monotherapy option for patients with type 2 diabetes, Robert Frederich, M.D., and his associates reported at the annual meeting of the American Association of Clinical Endocrinologists.

In the first phase III data to be released by comarketers Bristol-Myers Squibb Co. and Merck & Co., muraglitazar effectively lowered hemoglobin A_1c and triglycerides and raised HDL cholesterol levels in a 24-week, randomized, double-blind, placebo-controlled trial of drug-naive adults with type 2 diabetes who were inadequately controlled with diet and exercise alone, said Dr. Frederich, of Bristol-Myers Squibb in Princeton, N.J., and his associates.

The New Drug Application for muraglitazar is under review by the Food and Drug Administration. If approved, the drug would be the first of the new class called “glitazars,” agents that activate both α and γ peroxisome proliferator-activated receptors (PPARs).

The PPARs, members of the steroid hormone nuclear receptor family, are already established as therapeutic targets for treating diabetes and dyslipidemia: The thiazolidinedione class of glucose-lowering agents are PPAR-γ agonists, while fibrates improve lipid profiles via PPAR-α activation, Jorge Plutzky, M.D., explained at a satellite symposium sponsored by Bristol-Myers Squibb and Merck held during the AACE meeting.

“Such drugs hold out the potential for combining PPAR-α's lipid improvements, the PPAR-γ's insulin-sensitizing effects, and the possible anti-inflammatory/antiatherosclerotic effects of both receptors,” said Dr. Plutzky, director of The Vascular Disease Prevention Program at Brigham and Women's Hospital, Boston.

According to AACE past president Paul Jellinger, M.D., “combo pills are becoming more common and more accepted by many [physicians] largely because of reduced copayment.

Dual PPARs may be useful because the triglyceride/HDL part of diabetic dyslipidemia often gets overlooked in favor of straight LDL lowering with statins,” he told this newspaper after the meeting.

Most diabetics are already on lipid-lowering therapy, and statin therapy sometimes adequately addresses diabetic dyslipidemia, but often it does not. “On balance, I believe dual PPAR's will be a sensible and useful addition,” said Dr. Jellinger, of Hollywood, Fla.

The study patients were adults aged 18–70 years who had a mean baseline hemoglobin A_1c between 7% and 10%. None were on antihypertensive therapy in the 4–6 weeks before the study. Therapy with a stable dose of statins was allowed through the first 12 weeks of the trial.

A total of 111 patients were randomized to receive 2.5 mg of muraglitazar daily, 114 took 5.0 mg, and 109 received placebo. In a separate open-label trial, another 109 patients with baseline A_1c values of 10%–12% received 5.0 mg of muraglitazar daily, Dr. Frederich and his associates reported in a poster presentation.

At 24 weeks, the mean A_1c values dropped from 8.02% to 6.96% (−1.05) in the 2.5-mg muraglitazar group, from 7.89% to 6.68% (−1.23) in the blinded 5.0-mg patients, and from 10.68% to 8.06% (−2.62) in the open-label 5.0-mg group. In contrast, A_1c levels among the placebo patients fell by an insignificant 0.32 percentage points, from 7.99% to 7.67%.

In the randomized trial, 67% of the 2.5-mg group and 74% of the 5.0-mg group achieved the American Diabetes Association's A_1c target of less than 7.0%, compared with 32% of the placebo patients. The proportions who dropped below the AACE's 6.5% cutoff were 58%, 36%, and 18%, respectively. Fasting plasma glucose and insulin levels also were significantly reduced in both muraglitazar dosage groups in the double-blind trial, they said.

Triglyceride levels in the double-blind trial decreased significantly by 18% with 2.5 mg of muraglitazar and by 27% with 5.0 mg, compared with just 2% for placebo. In the open-label trial, triglycerides were reduced by 31%. Among the patients with baseline triglycerides of 150 mg/dL or above, reductions at 24 weeks were 24.8% with 2.5 mg of muraglitazar, 30.4% with 5.0 mg, 13.2% with placebo, and 31% in the open-label trial with 5.0 mg.

Mean HDL cholesterol levels rose by 10% and 16% with 2.5 mg and 5.0 mg of muraglitazar, respectively, in the blinded trial, both significant increases compared with the 2% rise with placebo. Levels of LDL cholesterol didn't change significantly with muraglitazar, but levels of apolipoprotein B, free fatty acid, and non-HDL cholesterol did, Dr. Frederich and his associates reported.

Adverse events occurred in 71% of patients with 2.5 mg of muraglitazar, 77% with 5.0 mg, 69% with placebo, and 70% in the open-label 5.0-mg group, with serious adverse events in 3%–4% of all groups with no significant differences between them. There were no cases of heart failure.

Edema-related events occurred in 8% with 2.5 mg, 11% with 5.0 mg, 8% with placebo, and 9% in the open-label group. All events in the muraglitazar patients were mild to moderate, while one placebo patient experienced serious edema. No patient treated with muraglitazar discontinued the study due to edema, but two placebo patients did.

There were no confirmed cases of glucose values at or below 50 mg/dL, and no patient dropped out of the study due to hypoglycemia. Mean change in body weight from baseline were gains of 1.1 kg in the 2.5-mg muraglitazar group and 2.1 kg with 5.0 mg, while the placebo group lost a mean of 0.8 kg. The open-label patients gained 2.9 kg.

Adverse events led to discontinuation of the study in 3%–4% of all muraglitazar groups and the placebo group, while rates of discontinuation due to lack of efficacy in the double-blind patients were 8% for 2.5 mg and 6% for 5.0 mg, compared with 23% for placebo.

VANCOUVER, B.C. — Symptoms of depression predict increases in intima-media thickness, Jesse C. Stewart, Ph.D., reported at the annual meeting of the American Psychosomatic Society.

Intima-media thickness (IMT), a measure of the thickness of the intima and medial layers of the carotid artery wall, is a marker of subclinical atherosclerosis and has been shown to predict future coronary events, said Dr. Stewart, of the department of psychiatry, University of Pittsburgh.

Data from 357 healthy adult (mean age 60 years) participants in the Pittsburgh Healthy Heart Project suggest that the somatic-vegetative symptoms—such as loss of pleasure, crying, agitation, and changes in appetite—significantly predict 3-year changes in IMT, whereas cognitive-affective symptoms such as sadness, pessimism, and guilty feelings do not, Dr. Stewart said.

Ultrasound images were obtained of the right and left carotid arteries at baseline and again at 3 years. The average 3-year change in IMT—computed as the mean of the sum of the far wall measurements from the common carotid, internal carotid, and bulb regions—was 0.09 mm for the group as a whole.

After adjustment for age, sex, and race, higher scores on the Beck Depression Index-II (BDI-II) at baseline were significantly associated with greater increases in carotid IMT. Average changes were 0.11 mm for participants in the highest BDI-II quartile, compared with 0.06 mm among those in the lowest quartile, he reported.

In contrast, 3-year changes in IMT were not predicted by scores on the Cook-Medley Hostility Scale or the Beck Anxiety Inventory.

When specific items on the BDI-II were examined, the somatic-vegetative or physical symptoms of depression explained nearly all of the differences in IMT scores, whereas the cognitive-affective factors alone were not predictive of early heart disease.

Previous prospective studies have demonstrated that depression, hostility, and anxiety all increase the risk for cardiovasular disease (CVD), but few have simultaneously examined the influence of all three factors, Dr. Stewart said.

VANCOUVER, B.C. — Symptoms of depression predict increases in intima-media thickness, Jesse C. Stewart, Ph.D., reported at the annual meeting of the American Psychosomatic Society.

Intima-media thickness (IMT), a measure of the thickness of the intima and medial layers of the carotid artery wall, is a marker of subclinical atherosclerosis and has been shown to predict future coronary events, said Dr. Stewart, of the department of psychiatry, University of Pittsburgh.

Data from 357 healthy adult (mean age 60 years) participants in the Pittsburgh Healthy Heart Project suggest that the somatic-vegetative symptoms—such as loss of pleasure, crying, agitation, and changes in appetite—significantly predict 3-year changes in IMT, whereas cognitive-affective symptoms such as sadness, pessimism, and guilty feelings do not, Dr. Stewart said.

Ultrasound images were obtained of the right and left carotid arteries at baseline and again at 3 years. The average 3-year change in IMT—computed as the mean of the sum of the far wall measurements from the common carotid, internal carotid, and bulb regions—was 0.09 mm for the group as a whole.

After adjustment for age, sex, and race, higher scores on the Beck Depression Index-II (BDI-II) at baseline were significantly associated with greater increases in carotid IMT. Average changes were 0.11 mm for participants in the highest BDI-II quartile, compared with 0.06 mm among those in the lowest quartile, he reported.

In contrast, 3-year changes in IMT were not predicted by scores on the Cook-Medley Hostility Scale or the Beck Anxiety Inventory.

When specific items on the BDI-II were examined, the somatic-vegetative or physical symptoms of depression explained nearly all of the differences in IMT scores, whereas the cognitive-affective factors alone were not predictive of early heart disease.

Previous prospective studies have demonstrated that depression, hostility, and anxiety all increase the risk for cardiovasular disease (CVD), but few have simultaneously examined the influence of all three factors, Dr. Stewart said.

VANCOUVER, B.C. — Symptoms of depression predict increases in intima-media thickness, Jesse C. Stewart, Ph.D., reported at the annual meeting of the American Psychosomatic Society.

Intima-media thickness (IMT), a measure of the thickness of the intima and medial layers of the carotid artery wall, is a marker of subclinical atherosclerosis and has been shown to predict future coronary events, said Dr. Stewart, of the department of psychiatry, University of Pittsburgh.

Data from 357 healthy adult (mean age 60 years) participants in the Pittsburgh Healthy Heart Project suggest that the somatic-vegetative symptoms—such as loss of pleasure, crying, agitation, and changes in appetite—significantly predict 3-year changes in IMT, whereas cognitive-affective symptoms such as sadness, pessimism, and guilty feelings do not, Dr. Stewart said.

Ultrasound images were obtained of the right and left carotid arteries at baseline and again at 3 years. The average 3-year change in IMT—computed as the mean of the sum of the far wall measurements from the common carotid, internal carotid, and bulb regions—was 0.09 mm for the group as a whole.

After adjustment for age, sex, and race, higher scores on the Beck Depression Index-II (BDI-II) at baseline were significantly associated with greater increases in carotid IMT. Average changes were 0.11 mm for participants in the highest BDI-II quartile, compared with 0.06 mm among those in the lowest quartile, he reported.

In contrast, 3-year changes in IMT were not predicted by scores on the Cook-Medley Hostility Scale or the Beck Anxiety Inventory.

When specific items on the BDI-II were examined, the somatic-vegetative or physical symptoms of depression explained nearly all of the differences in IMT scores, whereas the cognitive-affective factors alone were not predictive of early heart disease.

Previous prospective studies have demonstrated that depression, hostility, and anxiety all increase the risk for cardiovasular disease (CVD), but few have simultaneously examined the influence of all three factors, Dr. Stewart said.

WASHINGTON — African American patients with dyslipidemia are less likely than non-Hispanic whites to achieve LDL cholesterol treatment goals, Luther T. Clark, M.D., and his associates reported in a poster at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

In a national survey of physician compliance with guidelines issued in the third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III), African American ethnicity remained a strong predictor of lower success in reaching LDL cholesterol goals, even after adjustment for cardiovascular disease risk factors, said Dr. Clark, chief of cardiovascular medicine at the State University of New York Downstate Medical Center, Brooklyn.

In the study, supported by AstraZeneca PLC, a total of 376 U.S. physicians who were high prescribers of lipid-modifying medications each enrolled 10 or 20 consecutive dyslipidemic patients. Data associated with a single office visit were entered into special software on a personal digital assistant and then uploaded to a central database via the Internet.

The 4,885 patients studied were aged 20–75 years and had been on a diet and/or a stable dose of drug therapy for at least 3 months. Most (80%) were non-Hispanic whites, 8% were African American or black, 4% were Hispanic, and 3% were Asian.

Physician specialties included family practice (40%), general internal medicine (40%), cardiology (15%), and endocrinology (2%).

Most physicians were male (90%), board certified (90%), and office based (99%).

Achievement of NCEP ATP III treatment goals for LDL cholesterol level was significantly lower overall among African Americans than in non-Hispanic whites (54% vs. 69%).

This was true in all risk categories—those with fewer than two cardiovascular risk factors (82% vs. 90%), those with two or more risk factors (59% vs. 77%), and those at highest risk by virtue of having either coronary heart disease (CHD) or a CHD risk equivalent (44% vs. 58%), Dr. Clark and his associates wrote.

The disparity in achievement of LDL goal remained, even after adjustment for age, gender, smoking status, family history of CHD, hypertension, HDL cholesterol category, type of therapy (diet vs. drug), hypertriglyceridemia, obesity, and physician specialty. After the full adjustment, African Americans were less than half as likely (odds ratio 0.48) to have reached their LDL cholesterol goals, they said.

“These findings are disappointing, but not surprising. [They] are consistent with those from other surveys that have shown that CHD risk factors are less well controlled in African Americans,” Dr. Clark told this newspaper in a follow-up interview.

Although the reasons are not clear, the fact that the difference persisted after adjustment for both physician specialty and receipt of statins suggests that patient behavior is at least a contributing factor. But physiologic variation may be at work as well.

“Surprisingly little data have been published directly comparing lipid responses to available treatments in African American and non-Hispanic white patients. Therefore, it is also possible that physiologic factors could have played a role in the lower frequency of goal achievement in African Americans,” Dr. Clark said.

Source:

WASHINGTON — African American patients with dyslipidemia are less likely than non-Hispanic whites to achieve LDL cholesterol treatment goals, Luther T. Clark, M.D., and his associates reported in a poster at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

In a national survey of physician compliance with guidelines issued in the third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III), African American ethnicity remained a strong predictor of lower success in reaching LDL cholesterol goals, even after adjustment for cardiovascular disease risk factors, said Dr. Clark, chief of cardiovascular medicine at the State University of New York Downstate Medical Center, Brooklyn.

In the study, supported by AstraZeneca PLC, a total of 376 U.S. physicians who were high prescribers of lipid-modifying medications each enrolled 10 or 20 consecutive dyslipidemic patients. Data associated with a single office visit were entered into special software on a personal digital assistant and then uploaded to a central database via the Internet.

The 4,885 patients studied were aged 20–75 years and had been on a diet and/or a stable dose of drug therapy for at least 3 months. Most (80%) were non-Hispanic whites, 8% were African American or black, 4% were Hispanic, and 3% were Asian.

Physician specialties included family practice (40%), general internal medicine (40%), cardiology (15%), and endocrinology (2%).

Most physicians were male (90%), board certified (90%), and office based (99%).

Achievement of NCEP ATP III treatment goals for LDL cholesterol level was significantly lower overall among African Americans than in non-Hispanic whites (54% vs. 69%).

This was true in all risk categories—those with fewer than two cardiovascular risk factors (82% vs. 90%), those with two or more risk factors (59% vs. 77%), and those at highest risk by virtue of having either coronary heart disease (CHD) or a CHD risk equivalent (44% vs. 58%), Dr. Clark and his associates wrote.

The disparity in achievement of LDL goal remained, even after adjustment for age, gender, smoking status, family history of CHD, hypertension, HDL cholesterol category, type of therapy (diet vs. drug), hypertriglyceridemia, obesity, and physician specialty. After the full adjustment, African Americans were less than half as likely (odds ratio 0.48) to have reached their LDL cholesterol goals, they said.

“These findings are disappointing, but not surprising. [They] are consistent with those from other surveys that have shown that CHD risk factors are less well controlled in African Americans,” Dr. Clark told this newspaper in a follow-up interview.

Although the reasons are not clear, the fact that the difference persisted after adjustment for both physician specialty and receipt of statins suggests that patient behavior is at least a contributing factor. But physiologic variation may be at work as well.

“Surprisingly little data have been published directly comparing lipid responses to available treatments in African American and non-Hispanic white patients. Therefore, it is also possible that physiologic factors could have played a role in the lower frequency of goal achievement in African Americans,” Dr. Clark said.

Source:

WASHINGTON — African American patients with dyslipidemia are less likely than non-Hispanic whites to achieve LDL cholesterol treatment goals, Luther T. Clark, M.D., and his associates reported in a poster at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

In a national survey of physician compliance with guidelines issued in the third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III), African American ethnicity remained a strong predictor of lower success in reaching LDL cholesterol goals, even after adjustment for cardiovascular disease risk factors, said Dr. Clark, chief of cardiovascular medicine at the State University of New York Downstate Medical Center, Brooklyn.

In the study, supported by AstraZeneca PLC, a total of 376 U.S. physicians who were high prescribers of lipid-modifying medications each enrolled 10 or 20 consecutive dyslipidemic patients. Data associated with a single office visit were entered into special software on a personal digital assistant and then uploaded to a central database via the Internet.

The 4,885 patients studied were aged 20–75 years and had been on a diet and/or a stable dose of drug therapy for at least 3 months. Most (80%) were non-Hispanic whites, 8% were African American or black, 4% were Hispanic, and 3% were Asian.

Physician specialties included family practice (40%), general internal medicine (40%), cardiology (15%), and endocrinology (2%).

Most physicians were male (90%), board certified (90%), and office based (99%).

Achievement of NCEP ATP III treatment goals for LDL cholesterol level was significantly lower overall among African Americans than in non-Hispanic whites (54% vs. 69%).

This was true in all risk categories—those with fewer than two cardiovascular risk factors (82% vs. 90%), those with two or more risk factors (59% vs. 77%), and those at highest risk by virtue of having either coronary heart disease (CHD) or a CHD risk equivalent (44% vs. 58%), Dr. Clark and his associates wrote.

The disparity in achievement of LDL goal remained, even after adjustment for age, gender, smoking status, family history of CHD, hypertension, HDL cholesterol category, type of therapy (diet vs. drug), hypertriglyceridemia, obesity, and physician specialty. After the full adjustment, African Americans were less than half as likely (odds ratio 0.48) to have reached their LDL cholesterol goals, they said.

“These findings are disappointing, but not surprising. [They] are consistent with those from other surveys that have shown that CHD risk factors are less well controlled in African Americans,” Dr. Clark told this newspaper in a follow-up interview.

Although the reasons are not clear, the fact that the difference persisted after adjustment for both physician specialty and receipt of statins suggests that patient behavior is at least a contributing factor. But physiologic variation may be at work as well.

“Surprisingly little data have been published directly comparing lipid responses to available treatments in African American and non-Hispanic white patients. Therefore, it is also possible that physiologic factors could have played a role in the lower frequency of goal achievement in African Americans,” Dr. Clark said.

Source:

Always consider the possibility of bacterial contamination of blood products—particularly platelets—in patients who experience a febrile reaction to a transfusion, the Centers for Disease Control and Prevention advised.

Transfusion-associated bacterial sepsis is the second most frequently reported cause of transfusion-related mortality in the United States, accounting for 17% of 277 reported transfusion deaths during 1990–1998, the CDC said (MMWR 2005;54:168–70).

Platelets are particularly vulnerable to bacterial growth because they are stored at room temperature for up to 5 days, whereas other blood components are refrigerated or frozen. An estimated 1 in 1,000–3,000 platelet units are contaminated with bacteria, resulting in life-threatening sepsis in 1 of every 100,000 transfusion recipients and immediate death in 1 of every 500,000 recipients.

These risks are greater than those estimated for transfusion-associated viral infections such as hepatitis C virus or HIV—yet are still likely to be underestimates because bacterial infections attributed to contaminated platelets are underreported, the CDC said.

To reduce this risk, AABB (formerly the American Association of Blood Banks), adopted a new standard in March 2004 requiring member blood banks and transfusion services to implement measures to detect and limit bacterial contamination in all platelet components. Additional guidance for implementation of the standard—aimed at clinicians as well as institutions—was issued in February 2005. It is available at www.aabb.org

A survey conducted last summer by the Infectious Diseases Society of America (IDSA) suggested that awareness of the problem and of the new standard was not high.

The survey was distributed to all 870 infectious-disease consultant members of IDSA's Emerging Infections Network. Of the 399 who responded, only 36% reported being aware that bacterial contamination of platelets was one of the most common infection risks of transfusion therapy, and only 20% indicated having been familiar with the new AABB standard prior to participating in the survey.

Indeed, the CDC cited two case reports that illustrate the need for awareness and rapid diagnosis of transfusion-associated infections, since false negatives—leading to fatal bacterial sepsis—can occur even when pretransfusion testing complies with the new standard.

In one case, a 74-year-old man with leukemia died of sepsis 21 days after receiving a transfusion consisting of a pool of five platelet unit concentrates. Before transfusion, the pooled unit had been tested with a reagent strip to determine the pH level, a means for detecting the presence of bacteria. Despite the sample having been within the accepted range (pH greater than 6.4), the patient's blood cultures following transfusion grew Staphylococcus aureus.

Although the use of pH tests is an option under the AABB standard, they are less sensitive than are culture-based methods in whole-blood-derived samples, which are pooled from multiple donors. However, most blood collection centers only culture apheresis platelets, which are derived from single donors.

But culture had been performed in the second case, a 79-year-old man who received a transfusion of pheresis platelets for thrombocytopenia after coronary artery bypass surgery. Nonetheless, he developed shortness of breath, chills, a fever, and hypotension about an hour after the transfusion, experienced multiple thrombotic events, and died 27 hours later. Staphylococcus lugdunensis was later cultured from his blood and the leftover platelet bag.

Here, the volume of the platelet sample—4 mL in a standard aerobic blood culture bottle—was less than the manufacturer's recommended volume for platelet screening.

Always consider the possibility of bacterial contamination of blood products—particularly platelets—in patients who experience a febrile reaction to a transfusion, the Centers for Disease Control and Prevention advised.

Transfusion-associated bacterial sepsis is the second most frequently reported cause of transfusion-related mortality in the United States, accounting for 17% of 277 reported transfusion deaths during 1990–1998, the CDC said (MMWR 2005;54:168–70).

Platelets are particularly vulnerable to bacterial growth because they are stored at room temperature for up to 5 days, whereas other blood components are refrigerated or frozen. An estimated 1 in 1,000–3,000 platelet units are contaminated with bacteria, resulting in life-threatening sepsis in 1 of every 100,000 transfusion recipients and immediate death in 1 of every 500,000 recipients.

These risks are greater than those estimated for transfusion-associated viral infections such as hepatitis C virus or HIV—yet are still likely to be underestimates because bacterial infections attributed to contaminated platelets are underreported, the CDC said.

To reduce this risk, AABB (formerly the American Association of Blood Banks), adopted a new standard in March 2004 requiring member blood banks and transfusion services to implement measures to detect and limit bacterial contamination in all platelet components. Additional guidance for implementation of the standard—aimed at clinicians as well as institutions—was issued in February 2005. It is available at www.aabb.org

A survey conducted last summer by the Infectious Diseases Society of America (IDSA) suggested that awareness of the problem and of the new standard was not high.

The survey was distributed to all 870 infectious-disease consultant members of IDSA's Emerging Infections Network. Of the 399 who responded, only 36% reported being aware that bacterial contamination of platelets was one of the most common infection risks of transfusion therapy, and only 20% indicated having been familiar with the new AABB standard prior to participating in the survey.

Indeed, the CDC cited two case reports that illustrate the need for awareness and rapid diagnosis of transfusion-associated infections, since false negatives—leading to fatal bacterial sepsis—can occur even when pretransfusion testing complies with the new standard.

In one case, a 74-year-old man with leukemia died of sepsis 21 days after receiving a transfusion consisting of a pool of five platelet unit concentrates. Before transfusion, the pooled unit had been tested with a reagent strip to determine the pH level, a means for detecting the presence of bacteria. Despite the sample having been within the accepted range (pH greater than 6.4), the patient's blood cultures following transfusion grew Staphylococcus aureus.

Although the use of pH tests is an option under the AABB standard, they are less sensitive than are culture-based methods in whole-blood-derived samples, which are pooled from multiple donors. However, most blood collection centers only culture apheresis platelets, which are derived from single donors.

But culture had been performed in the second case, a 79-year-old man who received a transfusion of pheresis platelets for thrombocytopenia after coronary artery bypass surgery. Nonetheless, he developed shortness of breath, chills, a fever, and hypotension about an hour after the transfusion, experienced multiple thrombotic events, and died 27 hours later. Staphylococcus lugdunensis was later cultured from his blood and the leftover platelet bag.

Here, the volume of the platelet sample—4 mL in a standard aerobic blood culture bottle—was less than the manufacturer's recommended volume for platelet screening.

Always consider the possibility of bacterial contamination of blood products—particularly platelets—in patients who experience a febrile reaction to a transfusion, the Centers for Disease Control and Prevention advised.

Transfusion-associated bacterial sepsis is the second most frequently reported cause of transfusion-related mortality in the United States, accounting for 17% of 277 reported transfusion deaths during 1990–1998, the CDC said (MMWR 2005;54:168–70).

Platelets are particularly vulnerable to bacterial growth because they are stored at room temperature for up to 5 days, whereas other blood components are refrigerated or frozen. An estimated 1 in 1,000–3,000 platelet units are contaminated with bacteria, resulting in life-threatening sepsis in 1 of every 100,000 transfusion recipients and immediate death in 1 of every 500,000 recipients.

These risks are greater than those estimated for transfusion-associated viral infections such as hepatitis C virus or HIV—yet are still likely to be underestimates because bacterial infections attributed to contaminated platelets are underreported, the CDC said.

To reduce this risk, AABB (formerly the American Association of Blood Banks), adopted a new standard in March 2004 requiring member blood banks and transfusion services to implement measures to detect and limit bacterial contamination in all platelet components. Additional guidance for implementation of the standard—aimed at clinicians as well as institutions—was issued in February 2005. It is available at www.aabb.org

A survey conducted last summer by the Infectious Diseases Society of America (IDSA) suggested that awareness of the problem and of the new standard was not high.

The survey was distributed to all 870 infectious-disease consultant members of IDSA's Emerging Infections Network. Of the 399 who responded, only 36% reported being aware that bacterial contamination of platelets was one of the most common infection risks of transfusion therapy, and only 20% indicated having been familiar with the new AABB standard prior to participating in the survey.

Indeed, the CDC cited two case reports that illustrate the need for awareness and rapid diagnosis of transfusion-associated infections, since false negatives—leading to fatal bacterial sepsis—can occur even when pretransfusion testing complies with the new standard.

In one case, a 74-year-old man with leukemia died of sepsis 21 days after receiving a transfusion consisting of a pool of five platelet unit concentrates. Before transfusion, the pooled unit had been tested with a reagent strip to determine the pH level, a means for detecting the presence of bacteria. Despite the sample having been within the accepted range (pH greater than 6.4), the patient's blood cultures following transfusion grew Staphylococcus aureus.

Although the use of pH tests is an option under the AABB standard, they are less sensitive than are culture-based methods in whole-blood-derived samples, which are pooled from multiple donors. However, most blood collection centers only culture apheresis platelets, which are derived from single donors.

But culture had been performed in the second case, a 79-year-old man who received a transfusion of pheresis platelets for thrombocytopenia after coronary artery bypass surgery. Nonetheless, he developed shortness of breath, chills, a fever, and hypotension about an hour after the transfusion, experienced multiple thrombotic events, and died 27 hours later. Staphylococcus lugdunensis was later cultured from his blood and the leftover platelet bag.

Here, the volume of the platelet sample—4 mL in a standard aerobic blood culture bottle—was less than the manufacturer's recommended volume for platelet screening.

WASHINGTON — Even without evidence of coronary calcium on CT, a large proportion of diabetic patients are still at risk for atherosclerosis, Liviu Klein, M.D., said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

“Diabetics are clearly at risk for atherosclerosis. Some people believe that CAC [coronary artery calcium] is a perfect tool for discrimination, but it's not. … My concern is that the absence of CAC will be used as a reason not to treat,” Dr. Klein, a fellow in cardiovascular epidemiology and prevention at Northwestern University, Chicago, said in an interview.

About 30% of diabetic adults aged 45 and older without clinically manifest coronary heart disease have no coronary artery calcium (CAC score of 0) on CT. No previous study compared other markers of atherosclerosis in that subgroup with those of nondiabetics without CAC. The first-ever study to do so is a part of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort of 6,814 African American, white, Chinese, and Hispanic adults aged 45–84 without symptoms or history of cardiovascular disease. A total of 350 (34%) of the diabetic participants and 2,825 (49%) of the nondiabetic participants had CAC scores of 0 on coronary CT. Diabetic subjects were older than nondiabetics (61 vs. 57 years) and were more likely to be African American (44% vs. 28%) or Hispanic (34% vs. 23%). Average body mass index (BMI), waist circumference, and triglyceride and LDL-cholesterol levels were also higher in the diabetics than in the nondiabetics, Dr. Klein reported.

On B-mode carotid ultrasound, diabetic patients had significantly higher common and internal carotid intimal medial thickness (IMT) than did nondiabetics, before and after adjustment for age, gender, ethnicity, and traditional risk factors for atherosclerosis, including blood pressure, cholesterol level, BMI, smoking, socioeconomic status, and statin and aspirin use.

After adjustment, common carotid IMTs were 0.84 mm for the diabetics and 0.81 mm for the nondiabetics; internal carotid IMTs were 0.98 mm and 0.86 mm, respectively. Levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin, interleukin-6, and C-reactive protein (CRP) were all significantly greater in the diabetic group, indicating a greater burden of atherosclerosis, Dr. Klein said.

Mean ankle-brachial index did not differ significantly between the two groups either before or after the same adjustments, nor were there differences in levels of the plaque instability markers matrix metalloproteinase (MMP)-3, MMP-9, or soluble CD40 ligand (CD40-L).

Whether diabetic patients without a history of myocardial infarction have the same risk of CHD events as nondiabetic patients with a history of MI remains controversial, despite two sets of evidence-based guidelines issued by the National Heart, Lung, and Blood Institute categorizing diabetes as a “risk equivalent” for coronary heart disease and advising that all individuals with diabetes receive intensive CHD risk factor management (JAMA 2001;285:2486–97; JAMA 2003;289:2560–72).

However, conflicting data have appeared both before and since the dissemination of those two documents (the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). One recent study, for example, found that diabetic patients without MI had a lower risk of CHD events and mortality from cardiovascular disease than did nondiabetic patients with MI, but stroke risk was similar between the two groups (Circulation 2004;109:855–60), while another suggested that 5-year survival among diabetics without CAC is similar to that of nondiabetic subjects without CAC (J. Am. Coll. Cardiol. 2004;43:1663–9).

But, according to Dr. Klein, there are multiple problems with these and similar studies.

First, they have not accounted for the fact that mean CAC differs among individuals of different races. In particular, African Americans and Hispanics have lower mean CAC values than do whites, despite having higher MI rates. “We don't really know what the calcium score means,” he said. Moreover, these new data from MESA show that even if someone with diabetes has a CAC of 0 now, that person is likely to have a significantly higher atherosclerotic burden, compared with a nondiabetic. “If you wait until a diabetic has CAC, you will have missed the chance to prevent diabetes complications. … It's not so much an issue of mortality as it is of morbidity,” Dr. Klein said at the meeting, also sponsored by NHLBI.

As it is, fewer than 25% of diabetics receive appropriate treatment for cholesterol, hypertension, and glucose. That number could drop significantly if physicians use a CAC score of 0 on CT as a threshold for intensive treatment, he noted.

WASHINGTON — Even without evidence of coronary calcium on CT, a large proportion of diabetic patients are still at risk for atherosclerosis, Liviu Klein, M.D., said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

“Diabetics are clearly at risk for atherosclerosis. Some people believe that CAC [coronary artery calcium] is a perfect tool for discrimination, but it's not. … My concern is that the absence of CAC will be used as a reason not to treat,” Dr. Klein, a fellow in cardiovascular epidemiology and prevention at Northwestern University, Chicago, said in an interview.

About 30% of diabetic adults aged 45 and older without clinically manifest coronary heart disease have no coronary artery calcium (CAC score of 0) on CT. No previous study compared other markers of atherosclerosis in that subgroup with those of nondiabetics without CAC. The first-ever study to do so is a part of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort of 6,814 African American, white, Chinese, and Hispanic adults aged 45–84 without symptoms or history of cardiovascular disease. A total of 350 (34%) of the diabetic participants and 2,825 (49%) of the nondiabetic participants had CAC scores of 0 on coronary CT. Diabetic subjects were older than nondiabetics (61 vs. 57 years) and were more likely to be African American (44% vs. 28%) or Hispanic (34% vs. 23%). Average body mass index (BMI), waist circumference, and triglyceride and LDL-cholesterol levels were also higher in the diabetics than in the nondiabetics, Dr. Klein reported.

On B-mode carotid ultrasound, diabetic patients had significantly higher common and internal carotid intimal medial thickness (IMT) than did nondiabetics, before and after adjustment for age, gender, ethnicity, and traditional risk factors for atherosclerosis, including blood pressure, cholesterol level, BMI, smoking, socioeconomic status, and statin and aspirin use.

After adjustment, common carotid IMTs were 0.84 mm for the diabetics and 0.81 mm for the nondiabetics; internal carotid IMTs were 0.98 mm and 0.86 mm, respectively. Levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin, interleukin-6, and C-reactive protein (CRP) were all significantly greater in the diabetic group, indicating a greater burden of atherosclerosis, Dr. Klein said.

Mean ankle-brachial index did not differ significantly between the two groups either before or after the same adjustments, nor were there differences in levels of the plaque instability markers matrix metalloproteinase (MMP)-3, MMP-9, or soluble CD40 ligand (CD40-L).

Whether diabetic patients without a history of myocardial infarction have the same risk of CHD events as nondiabetic patients with a history of MI remains controversial, despite two sets of evidence-based guidelines issued by the National Heart, Lung, and Blood Institute categorizing diabetes as a “risk equivalent” for coronary heart disease and advising that all individuals with diabetes receive intensive CHD risk factor management (JAMA 2001;285:2486–97; JAMA 2003;289:2560–72).

However, conflicting data have appeared both before and since the dissemination of those two documents (the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). One recent study, for example, found that diabetic patients without MI had a lower risk of CHD events and mortality from cardiovascular disease than did nondiabetic patients with MI, but stroke risk was similar between the two groups (Circulation 2004;109:855–60), while another suggested that 5-year survival among diabetics without CAC is similar to that of nondiabetic subjects without CAC (J. Am. Coll. Cardiol. 2004;43:1663–9).

But, according to Dr. Klein, there are multiple problems with these and similar studies.

First, they have not accounted for the fact that mean CAC differs among individuals of different races. In particular, African Americans and Hispanics have lower mean CAC values than do whites, despite having higher MI rates. “We don't really know what the calcium score means,” he said. Moreover, these new data from MESA show that even if someone with diabetes has a CAC of 0 now, that person is likely to have a significantly higher atherosclerotic burden, compared with a nondiabetic. “If you wait until a diabetic has CAC, you will have missed the chance to prevent diabetes complications. … It's not so much an issue of mortality as it is of morbidity,” Dr. Klein said at the meeting, also sponsored by NHLBI.

As it is, fewer than 25% of diabetics receive appropriate treatment for cholesterol, hypertension, and glucose. That number could drop significantly if physicians use a CAC score of 0 on CT as a threshold for intensive treatment, he noted.

WASHINGTON — Even without evidence of coronary calcium on CT, a large proportion of diabetic patients are still at risk for atherosclerosis, Liviu Klein, M.D., said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

“Diabetics are clearly at risk for atherosclerosis. Some people believe that CAC [coronary artery calcium] is a perfect tool for discrimination, but it's not. … My concern is that the absence of CAC will be used as a reason not to treat,” Dr. Klein, a fellow in cardiovascular epidemiology and prevention at Northwestern University, Chicago, said in an interview.

About 30% of diabetic adults aged 45 and older without clinically manifest coronary heart disease have no coronary artery calcium (CAC score of 0) on CT. No previous study compared other markers of atherosclerosis in that subgroup with those of nondiabetics without CAC. The first-ever study to do so is a part of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort of 6,814 African American, white, Chinese, and Hispanic adults aged 45–84 without symptoms or history of cardiovascular disease. A total of 350 (34%) of the diabetic participants and 2,825 (49%) of the nondiabetic participants had CAC scores of 0 on coronary CT. Diabetic subjects were older than nondiabetics (61 vs. 57 years) and were more likely to be African American (44% vs. 28%) or Hispanic (34% vs. 23%). Average body mass index (BMI), waist circumference, and triglyceride and LDL-cholesterol levels were also higher in the diabetics than in the nondiabetics, Dr. Klein reported.

On B-mode carotid ultrasound, diabetic patients had significantly higher common and internal carotid intimal medial thickness (IMT) than did nondiabetics, before and after adjustment for age, gender, ethnicity, and traditional risk factors for atherosclerosis, including blood pressure, cholesterol level, BMI, smoking, socioeconomic status, and statin and aspirin use.

After adjustment, common carotid IMTs were 0.84 mm for the diabetics and 0.81 mm for the nondiabetics; internal carotid IMTs were 0.98 mm and 0.86 mm, respectively. Levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin, interleukin-6, and C-reactive protein (CRP) were all significantly greater in the diabetic group, indicating a greater burden of atherosclerosis, Dr. Klein said.

Mean ankle-brachial index did not differ significantly between the two groups either before or after the same adjustments, nor were there differences in levels of the plaque instability markers matrix metalloproteinase (MMP)-3, MMP-9, or soluble CD40 ligand (CD40-L).

Whether diabetic patients without a history of myocardial infarction have the same risk of CHD events as nondiabetic patients with a history of MI remains controversial, despite two sets of evidence-based guidelines issued by the National Heart, Lung, and Blood Institute categorizing diabetes as a “risk equivalent” for coronary heart disease and advising that all individuals with diabetes receive intensive CHD risk factor management (JAMA 2001;285:2486–97; JAMA 2003;289:2560–72).

However, conflicting data have appeared both before and since the dissemination of those two documents (the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). One recent study, for example, found that diabetic patients without MI had a lower risk of CHD events and mortality from cardiovascular disease than did nondiabetic patients with MI, but stroke risk was similar between the two groups (Circulation 2004;109:855–60), while another suggested that 5-year survival among diabetics without CAC is similar to that of nondiabetic subjects without CAC (J. Am. Coll. Cardiol. 2004;43:1663–9).

But, according to Dr. Klein, there are multiple problems with these and similar studies.

First, they have not accounted for the fact that mean CAC differs among individuals of different races. In particular, African Americans and Hispanics have lower mean CAC values than do whites, despite having higher MI rates. “We don't really know what the calcium score means,” he said. Moreover, these new data from MESA show that even if someone with diabetes has a CAC of 0 now, that person is likely to have a significantly higher atherosclerotic burden, compared with a nondiabetic. “If you wait until a diabetic has CAC, you will have missed the chance to prevent diabetes complications. … It's not so much an issue of mortality as it is of morbidity,” Dr. Klein said at the meeting, also sponsored by NHLBI.

As it is, fewer than 25% of diabetics receive appropriate treatment for cholesterol, hypertension, and glucose. That number could drop significantly if physicians use a CAC score of 0 on CT as a threshold for intensive treatment, he noted.

Testing for hepatitis A infection should be reserved for patients who have symptoms consistent with the diagnosis or who have had recent exposure to a person known to be infected with hepatitis A, the Centers for Disease Control and Prevention said.

Specifically, IgM anti-hepatitis A virus (HAV) testing should not be done routinely to screen people who have liver function test abnormalities or who are suspected of having hepatitis C, the CDC said (MMWR 2005;54:453–6).

After receiving multiple reports of positive IgM anti-HAV test results in individuals who did not have clinical illness consistent with HAV infection, the CDC investigated the clinical and epidemiologic characteristics of these cases for the first time. The CDC's findings suggest that these people are unlikely to have the illness unless they have been exposed recently to someone with acute HAV infection. The findings also indicate that their contacts are unlikely to require immunoprophylaxis. Therefore, testing these individuals only serves to lower the predictive value of the IgM anti-HAV test.

In Connecticut, the state health department investigated 127 positive IgM anti-HAV test results; 108 of the individuals had clinical illness consistent with hepatitis A infection. Of the other 19 persons (aged 28–88 years), 3 had elevated alanine aminotransferase (ALT) concentrations and 3 had a previous report of a positive IgM anti-HAV test but did not have illness that met the case definition at that time either.

Among 10 such people in Alaska (aged 9–77 years), 7 had abnormal ALT concentrations, suggesting the presence of liver injury or disease. However, six did not have an illness with acute onset, while the seventh had an acute illness traced to acetaminophen toxicity. The other three were asymptomatic. One person previously had a positive IgM anti-HAV test.

In a third investigation involving six U.S. counties with demographic compositions representative of the U.S. population, 140 persons were reported to have a positive IgM anti-HAV test result. Of those, 62% (87) did not have an illness consistent with the case definition, while 38% (53) did.

The 87 persons who did not have illness meeting the case definition were significantly older and more likely to be female (this was also the case in Connecticut). Of 31 for whom serum samples were available for repeat testing at the CDC, only 2 tested positive for IgM anti-HAV. Of 25 specimens tested for HAV nucleic acid, only 1 (4%), from a 77-year-old man, had detectable HAV RNA. In contrast, 34 of 51 specimens from persons with both clinical and laboratory evidence of HAV infection had detectable HAV RNA.

A repeat test of the 77-year-old man's specimen was negative for IgM anti-HAV, suggesting that his RNA test was a false positive, the CDC said.

A positive IgM anti-HAV test in a person without typical symptoms of hepatitis A infection might indicate asymptomatic acute HAV infection, previous HAV infection with prolonged presence of IgM anti-HAV, or a false-positive result. The findings from these reports suggest that in older adults, the most likely explanations are a false-positive result or a HAV infection that occurred months to years previously, rather than more recent infection requiring consideration of postexposure immunoprophylaxis for contacts.

Published guidelines for the work-up of abnormal liver enzyme tests do not include IgM anti-HAV testing, yet physicians may be tempted to order a multitest “hepatitis panel” offered by some laboratories at a cheaper price than the individual tests, James Hadler, M.D., state epidemiologist in the Connecticut Department of Public Health in Hartford, told this newspaper.

“It is this kind of reflex bargain basement testing that may result in getting back false-positive results,” Dr. Hadler said.

HAV infection causes an acute illness with discrete onset of fatigue, abdominal pain, loss of appetite, intermittent nausea and/or vomiting, and jaundice or elevated serum alanine aminotransferase levels.

Testing for hepatitis A infection should be reserved for patients who have symptoms consistent with the diagnosis or who have had recent exposure to a person known to be infected with hepatitis A, the Centers for Disease Control and Prevention said.

Specifically, IgM anti-hepatitis A virus (HAV) testing should not be done routinely to screen people who have liver function test abnormalities or who are suspected of having hepatitis C, the CDC said (MMWR 2005;54:453–6).

After receiving multiple reports of positive IgM anti-HAV test results in individuals who did not have clinical illness consistent with HAV infection, the CDC investigated the clinical and epidemiologic characteristics of these cases for the first time. The CDC's findings suggest that these people are unlikely to have the illness unless they have been exposed recently to someone with acute HAV infection. The findings also indicate that their contacts are unlikely to require immunoprophylaxis. Therefore, testing these individuals only serves to lower the predictive value of the IgM anti-HAV test.

In Connecticut, the state health department investigated 127 positive IgM anti-HAV test results; 108 of the individuals had clinical illness consistent with hepatitis A infection. Of the other 19 persons (aged 28–88 years), 3 had elevated alanine aminotransferase (ALT) concentrations and 3 had a previous report of a positive IgM anti-HAV test but did not have illness that met the case definition at that time either.

Among 10 such people in Alaska (aged 9–77 years), 7 had abnormal ALT concentrations, suggesting the presence of liver injury or disease. However, six did not have an illness with acute onset, while the seventh had an acute illness traced to acetaminophen toxicity. The other three were asymptomatic. One person previously had a positive IgM anti-HAV test.

In a third investigation involving six U.S. counties with demographic compositions representative of the U.S. population, 140 persons were reported to have a positive IgM anti-HAV test result. Of those, 62% (87) did not have an illness consistent with the case definition, while 38% (53) did.

The 87 persons who did not have illness meeting the case definition were significantly older and more likely to be female (this was also the case in Connecticut). Of 31 for whom serum samples were available for repeat testing at the CDC, only 2 tested positive for IgM anti-HAV. Of 25 specimens tested for HAV nucleic acid, only 1 (4%), from a 77-year-old man, had detectable HAV RNA. In contrast, 34 of 51 specimens from persons with both clinical and laboratory evidence of HAV infection had detectable HAV RNA.

A repeat test of the 77-year-old man's specimen was negative for IgM anti-HAV, suggesting that his RNA test was a false positive, the CDC said.

A positive IgM anti-HAV test in a person without typical symptoms of hepatitis A infection might indicate asymptomatic acute HAV infection, previous HAV infection with prolonged presence of IgM anti-HAV, or a false-positive result. The findings from these reports suggest that in older adults, the most likely explanations are a false-positive result or a HAV infection that occurred months to years previously, rather than more recent infection requiring consideration of postexposure immunoprophylaxis for contacts.

Published guidelines for the work-up of abnormal liver enzyme tests do not include IgM anti-HAV testing, yet physicians may be tempted to order a multitest “hepatitis panel” offered by some laboratories at a cheaper price than the individual tests, James Hadler, M.D., state epidemiologist in the Connecticut Department of Public Health in Hartford, told this newspaper.

“It is this kind of reflex bargain basement testing that may result in getting back false-positive results,” Dr. Hadler said.

HAV infection causes an acute illness with discrete onset of fatigue, abdominal pain, loss of appetite, intermittent nausea and/or vomiting, and jaundice or elevated serum alanine aminotransferase levels.

Testing for hepatitis A infection should be reserved for patients who have symptoms consistent with the diagnosis or who have had recent exposure to a person known to be infected with hepatitis A, the Centers for Disease Control and Prevention said.

Specifically, IgM anti-hepatitis A virus (HAV) testing should not be done routinely to screen people who have liver function test abnormalities or who are suspected of having hepatitis C, the CDC said (MMWR 2005;54:453–6).

After receiving multiple reports of positive IgM anti-HAV test results in individuals who did not have clinical illness consistent with HAV infection, the CDC investigated the clinical and epidemiologic characteristics of these cases for the first time. The CDC's findings suggest that these people are unlikely to have the illness unless they have been exposed recently to someone with acute HAV infection. The findings also indicate that their contacts are unlikely to require immunoprophylaxis. Therefore, testing these individuals only serves to lower the predictive value of the IgM anti-HAV test.

In Connecticut, the state health department investigated 127 positive IgM anti-HAV test results; 108 of the individuals had clinical illness consistent with hepatitis A infection. Of the other 19 persons (aged 28–88 years), 3 had elevated alanine aminotransferase (ALT) concentrations and 3 had a previous report of a positive IgM anti-HAV test but did not have illness that met the case definition at that time either.

Among 10 such people in Alaska (aged 9–77 years), 7 had abnormal ALT concentrations, suggesting the presence of liver injury or disease. However, six did not have an illness with acute onset, while the seventh had an acute illness traced to acetaminophen toxicity. The other three were asymptomatic. One person previously had a positive IgM anti-HAV test.

In a third investigation involving six U.S. counties with demographic compositions representative of the U.S. population, 140 persons were reported to have a positive IgM anti-HAV test result. Of those, 62% (87) did not have an illness consistent with the case definition, while 38% (53) did.

The 87 persons who did not have illness meeting the case definition were significantly older and more likely to be female (this was also the case in Connecticut). Of 31 for whom serum samples were available for repeat testing at the CDC, only 2 tested positive for IgM anti-HAV. Of 25 specimens tested for HAV nucleic acid, only 1 (4%), from a 77-year-old man, had detectable HAV RNA. In contrast, 34 of 51 specimens from persons with both clinical and laboratory evidence of HAV infection had detectable HAV RNA.

A repeat test of the 77-year-old man's specimen was negative for IgM anti-HAV, suggesting that his RNA test was a false positive, the CDC said.

A positive IgM anti-HAV test in a person without typical symptoms of hepatitis A infection might indicate asymptomatic acute HAV infection, previous HAV infection with prolonged presence of IgM anti-HAV, or a false-positive result. The findings from these reports suggest that in older adults, the most likely explanations are a false-positive result or a HAV infection that occurred months to years previously, rather than more recent infection requiring consideration of postexposure immunoprophylaxis for contacts.

Published guidelines for the work-up of abnormal liver enzyme tests do not include IgM anti-HAV testing, yet physicians may be tempted to order a multitest “hepatitis panel” offered by some laboratories at a cheaper price than the individual tests, James Hadler, M.D., state epidemiologist in the Connecticut Department of Public Health in Hartford, told this newspaper.

“It is this kind of reflex bargain basement testing that may result in getting back false-positive results,” Dr. Hadler said.

HAV infection causes an acute illness with discrete onset of fatigue, abdominal pain, loss of appetite, intermittent nausea and/or vomiting, and jaundice or elevated serum alanine aminotransferase levels.

The incidence of several major food-borne infections declined markedly between 1996 and 2004, preliminary data from the Centers for Disease Control and Prevention suggest.

For the first time in 2004, the national incidence of Shiga-toxin-producing Escherichia coli (STEC) O157 infections fell below the Healthy People 2010 goal of 1 case per 100,000 population. In addition, rates of Campylobacter are approaching the target of less than 12.3 cases per 100,000, while the 2004 rate of Listeria, 2.7 per 1 million population, is nearly down to the goal of 2.5 cases per million, to be reached by the end of 2005.

But although most of the news from the CDC's 10-site Food-Borne Diseases Active Surveillance Network (FoodNet) was good, there were increases in the incidence of both Vibrio and of two Salmonella serotypes from baseline in 1996–1998 to 2004, according to the CDC (MMWR 2005;54:352–6).

In 2004, a total of 15,806 laboratory-confirmed cases of infections were identified in the FoodNet surveillance area, which included 44.1 million individuals, or 15.2% of the U.S. population. The three most frequent were Salmonella (6,464 cases), Campylobacter (5,665), and Shigella (2,231), followed by Cryptosporidium (613), STEC O157 (401), Yersinia (173), Vibrio (124), Listeria (120), and Cyclospora (15).

FoodNet cases were part of 239 nationally reported food-borne disease outbreaks, of which 58% were associated with restaurants. Of the 152 outbreaks in which an etiology was reported, the most common pathogens were norovirus (57%) and Salmonella (18%).

In 2003, FoodNet collected data on 52 cases of hemolytic-uremic syndrome in children less than 15 years of age (rate 0.6 per 100,000). Of those, 36 (69%) were among those younger than 5 years, the CDC said.

In comparing the preliminary 2004 numbers with those from 1996 to 1998, the CDC adjusted for the difference in FoodNet's population, which was just 14.2 million during the earlier time period. The estimated incidence of infections with Campylobacter decreased by 31%, Cryptosporidium by 40%, STEC O157 by 42%, Listeria by 40%, Yersinia by 45%, and overall Salmonella infections by 8%.

The estimated incidence of Shigella infections in 2004 wasn't significantly different from the baseline period, while overall Vibrio infections increased by 47%, to 2.8 per 100,000 population in 2004, the CDC reported.

Although the incidence of Salmonella decreased overall, only one of the five most common serotypes, S. typhimurium, actually dropped significantly (by 41%). Two of the others—S. enteritidis and S. heidelberg—didn't change, while both S. newport and S. javiana rose by 41% and 167%, respectively. The substantial increase in S. javiana was due in part to a multistate outbreak in 2004 that was associated with Roma tomatoes, they noted.

The substantial decline in STEC O157, first seen in 2003, coincides with several important food safety initiatives and educational efforts, and is consistent with reports from the U.S. Department of Agriculture of declines in contamination of ground beef following industry responses to governmental food safety initiatives.

The drop in Campylobacter, on the other hand, likely reflects efforts to reduce contamination of poultry and to educate consumers about safe food handling, the CDC said.

Rises in some Salmonella strains reflect a lack of understanding about the epidemiology of the organism and the methods by which it contaminates produce. Multidrug resistance is also a problem with Salmonella, particularly the newport strain. The reasons for the increase in Vibrio, typically associated with seafood, are not clear. The Food and Drug Administration is currently conducting an assessment.

The incidence of several major food-borne infections declined markedly between 1996 and 2004, preliminary data from the Centers for Disease Control and Prevention suggest.

For the first time in 2004, the national incidence of Shiga-toxin-producing Escherichia coli (STEC) O157 infections fell below the Healthy People 2010 goal of 1 case per 100,000 population. In addition, rates of Campylobacter are approaching the target of less than 12.3 cases per 100,000, while the 2004 rate of Listeria, 2.7 per 1 million population, is nearly down to the goal of 2.5 cases per million, to be reached by the end of 2005.

But although most of the news from the CDC's 10-site Food-Borne Diseases Active Surveillance Network (FoodNet) was good, there were increases in the incidence of both Vibrio and of two Salmonella serotypes from baseline in 1996–1998 to 2004, according to the CDC (MMWR 2005;54:352–6).

In 2004, a total of 15,806 laboratory-confirmed cases of infections were identified in the FoodNet surveillance area, which included 44.1 million individuals, or 15.2% of the U.S. population. The three most frequent were Salmonella (6,464 cases), Campylobacter (5,665), and Shigella (2,231), followed by Cryptosporidium (613), STEC O157 (401), Yersinia (173), Vibrio (124), Listeria (120), and Cyclospora (15).

FoodNet cases were part of 239 nationally reported food-borne disease outbreaks, of which 58% were associated with restaurants. Of the 152 outbreaks in which an etiology was reported, the most common pathogens were norovirus (57%) and Salmonella (18%).

In 2003, FoodNet collected data on 52 cases of hemolytic-uremic syndrome in children less than 15 years of age (rate 0.6 per 100,000). Of those, 36 (69%) were among those younger than 5 years, the CDC said.

In comparing the preliminary 2004 numbers with those from 1996 to 1998, the CDC adjusted for the difference in FoodNet's population, which was just 14.2 million during the earlier time period. The estimated incidence of infections with Campylobacter decreased by 31%, Cryptosporidium by 40%, STEC O157 by 42%, Listeria by 40%, Yersinia by 45%, and overall Salmonella infections by 8%.

The estimated incidence of Shigella infections in 2004 wasn't significantly different from the baseline period, while overall Vibrio infections increased by 47%, to 2.8 per 100,000 population in 2004, the CDC reported.

Although the incidence of Salmonella decreased overall, only one of the five most common serotypes, S. typhimurium, actually dropped significantly (by 41%). Two of the others—S. enteritidis and S. heidelberg—didn't change, while both S. newport and S. javiana rose by 41% and 167%, respectively. The substantial increase in S. javiana was due in part to a multistate outbreak in 2004 that was associated with Roma tomatoes, they noted.

The substantial decline in STEC O157, first seen in 2003, coincides with several important food safety initiatives and educational efforts, and is consistent with reports from the U.S. Department of Agriculture of declines in contamination of ground beef following industry responses to governmental food safety initiatives.

The drop in Campylobacter, on the other hand, likely reflects efforts to reduce contamination of poultry and to educate consumers about safe food handling, the CDC said.

Rises in some Salmonella strains reflect a lack of understanding about the epidemiology of the organism and the methods by which it contaminates produce. Multidrug resistance is also a problem with Salmonella, particularly the newport strain. The reasons for the increase in Vibrio, typically associated with seafood, are not clear. The Food and Drug Administration is currently conducting an assessment.

The incidence of several major food-borne infections declined markedly between 1996 and 2004, preliminary data from the Centers for Disease Control and Prevention suggest.

For the first time in 2004, the national incidence of Shiga-toxin-producing Escherichia coli (STEC) O157 infections fell below the Healthy People 2010 goal of 1 case per 100,000 population. In addition, rates of Campylobacter are approaching the target of less than 12.3 cases per 100,000, while the 2004 rate of Listeria, 2.7 per 1 million population, is nearly down to the goal of 2.5 cases per million, to be reached by the end of 2005.

But although most of the news from the CDC's 10-site Food-Borne Diseases Active Surveillance Network (FoodNet) was good, there were increases in the incidence of both Vibrio and of two Salmonella serotypes from baseline in 1996–1998 to 2004, according to the CDC (MMWR 2005;54:352–6).

In 2004, a total of 15,806 laboratory-confirmed cases of infections were identified in the FoodNet surveillance area, which included 44.1 million individuals, or 15.2% of the U.S. population. The three most frequent were Salmonella (6,464 cases), Campylobacter (5,665), and Shigella (2,231), followed by Cryptosporidium (613), STEC O157 (401), Yersinia (173), Vibrio (124), Listeria (120), and Cyclospora (15).

FoodNet cases were part of 239 nationally reported food-borne disease outbreaks, of which 58% were associated with restaurants. Of the 152 outbreaks in which an etiology was reported, the most common pathogens were norovirus (57%) and Salmonella (18%).

In 2003, FoodNet collected data on 52 cases of hemolytic-uremic syndrome in children less than 15 years of age (rate 0.6 per 100,000). Of those, 36 (69%) were among those younger than 5 years, the CDC said.

In comparing the preliminary 2004 numbers with those from 1996 to 1998, the CDC adjusted for the difference in FoodNet's population, which was just 14.2 million during the earlier time period. The estimated incidence of infections with Campylobacter decreased by 31%, Cryptosporidium by 40%, STEC O157 by 42%, Listeria by 40%, Yersinia by 45%, and overall Salmonella infections by 8%.

The estimated incidence of Shigella infections in 2004 wasn't significantly different from the baseline period, while overall Vibrio infections increased by 47%, to 2.8 per 100,000 population in 2004, the CDC reported.

Although the incidence of Salmonella decreased overall, only one of the five most common serotypes, S. typhimurium, actually dropped significantly (by 41%). Two of the others—S. enteritidis and S. heidelberg—didn't change, while both S. newport and S. javiana rose by 41% and 167%, respectively. The substantial increase in S. javiana was due in part to a multistate outbreak in 2004 that was associated with Roma tomatoes, they noted.

The substantial decline in STEC O157, first seen in 2003, coincides with several important food safety initiatives and educational efforts, and is consistent with reports from the U.S. Department of Agriculture of declines in contamination of ground beef following industry responses to governmental food safety initiatives.

The drop in Campylobacter, on the other hand, likely reflects efforts to reduce contamination of poultry and to educate consumers about safe food handling, the CDC said.

Rises in some Salmonella strains reflect a lack of understanding about the epidemiology of the organism and the methods by which it contaminates produce. Multidrug resistance is also a problem with Salmonella, particularly the newport strain. The reasons for the increase in Vibrio, typically associated with seafood, are not clear. The Food and Drug Administration is currently conducting an assessment.