CHICAGO—The calcium channel blocker amlodipine decreases the risk of cardiovascular events (such as heart attack or heart-disease related deaths) in patients with coronary artery disease and normal blood pressure, as does the ACE inhibitor enalapril, but to a lesser extent, according to a study in the November 10 issue of JAMA.

Despite more than 30 years of clinical trials, uncertainty has existed regarding the optimal use of antihypertensive drugs in patients with coronary artery disease (CAD), according to background information in the article.

Steven E. Nissen, M.D., of the Cleveland Clinic Lerner School of Medicine, Cleveland, and colleagues examined the effects of antihypertensive drugs in 1,991 patients with CAD and normal blood pressure in the Comparison of Amlodipine vs. Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study, a double-blind, randomized, multicenter 24-month trial (enrollment April 1999-April 2002). Patients received either the calcium channel blocker amlodipine (10 mg); the angiotensin-converting enzyme (ACE) inhibitor enalapril (20 mg); or placebo. In addition, a subset of 274 patients underwent serial intravascular ultrasound (IVUS) examinations to determine if either or both medications reduced the progression of atherosclerosis.

The primary end point was the time to first occurrence of an adverse cardiovascular event such as cardiovascular death, nonfatal heart attack, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke, or diagnosis of vascular disease.

The researchers found that for patients with a baseline systolic blood pressure averaging only 129/78 mm Hg, amlodipine reduced blood pressure an average of 5/3 mm Hg and compared to placebo, produced a 31 percent relative reduction (6.5 percent absolute reduction; 23.1 percent event-rate for placebo, 16.6 percent event rate for amlodipine) in cardiovascular events. "The number needed to treat for amlodipine is 16, i.e., for every 16 patients who receive amlodipine, there will be on average 1 adverse cardiovascular event avoided during the 2-year period compared with patients who receive placebo," the authors write. "Enalapril treatment also reduced blood pressure by an average of 5/2 mm Hg. However, the observed 15.3 percent relative reduction compared to placebo (2.9 percent absolute reduction; 20.2 percent event rate in the enalapril group) in cardiovascular events was not statistically significant."

The IVUS substudy showed evidence of slowing of progression of coronary artery atherosclerosis with amlodipine.

CHICAGO—Elderly individuals with the metabolic syndrome, a grouping of several common conditions including abdominal obesity, low level of high-density lipoprotein (HDL, the "good cholesterol"), hypertension, and high triglyceride and blood sugar levels, are more likely to experience cognitive impairment than those without this syndrome, according to a study in the November 10 issue of JAMA. The researchers also found a link with high measurements of certain proteins in the blood and the metabolic syndrome and impairment.

According to background information in the article, several studies have reported an association between the metabolic syndrome and cardiovascular disease. Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there is little data on any link between the metabolic syndrome and cognition.

Kristine Yaffe, M.D., from the University of California, San Francisco, and colleagues investigated the association between the metabolic syndrome and high inflammation with change in cognition. Inflammation was defined as elevated levels of the proteins interleukin 6 and C-reactive protein in the blood. Participants, aged 70 to 79 years, were part of the Health, Aging and Body Composition (ABC) study, conducted from 1997 to 2002. Average age of the 2,632 participants at the study's onset was 74 years; 52 percent were women; 40 percent were black. Participants were reevaluated at three and five years.

The researchers found that compared with those without the metabolic syndrome (n = 1,616), persons with the metabolic syndrome (n = 1016) were 20 percent more likely to develop cognitive impairment (defined as at least a 5 point decline on the Modified Mini-Mental State Examination [3MS], a standard cognitive test). Those with both metabolic syndrome and high inflammation (n = 348) were 66 percent more likely to have cognitive impairment than those without the metabolic syndrome. The 668 participants who had the metabolic syndrome and low inflammation did not show an increased likelihood of impairment. Also, those with the metabolic syndrome and high inflammation had greater four-year decline in cognitive testing scores than those without the metabolic syndrome, while those with the metabolic syndrome and low inflammation did not.

CHICAGO—Preliminary research indicates that the dietary supplement DHEA could play a role in reducing abdominal fat in elderly men and women with age-related decreases in DHEA levels, according to a study in the November 10 issue of JAMA.

The accumulation of abdominal fat increases with advancing age, and there is extensive evidence that abdominal obesity increases the risk for development of insulin resistance, diabetes, and atherosclerosis, according to background information in the article. Hormonal/metabolic changes that occur with aging may contribute to the increase in abdominal fat that generally occurs during middle and old age. One such change is the decline in production of the adrenal hormone dehydroepiandrosterone (DHEA). The blood level of DHEA, most of which is present in the sulfated form (DHEAS), peaks at approximately 20 years of age and declines rapidly and markedly after age 25. DHEA administration has been shown to reduce accumulation of abdominal fat and protect against insulin resistance in laboratory animals, but it was not known whether DHEA decreases abdominal obesity in humans. DHEA is widely available as a dietary supplement without a prescription.

Dennis T. Villareal, M.D., and John O. Holloszy, M.D., of Washington University School of Medicine, St. Louis, conducted a study to test the hypothesis that DHEA replacement therapy results in a decrease in abdominal fat and an improvement in insulin action in elderly persons.

The randomized, double-blind, placebo-controlled trial included 56 elderly persons (28 women and 28 men, average age, 71 [range, 65-78]) with age-related decrease in DHEA level. The study was conducted at Washington University School of Medicine from June 2001 to February 2004. Participants were randomly assigned to receive 50 mg/d of DHEA or matching placebo for 6 months.

The researchers found that DHEA replacement therapy induced significant decreases in both visceral fat (within the abdomen) and subcutaneous abdominal fat (below the skin surface) in elderly men and women. "The decrease in visceral fat relative to initial values averaged 10.2 percent in the women and 7.4 percent in the men. The DHEA therapy also resulted in a significant decrease in abdominal subcutaneous fat, averaging approximately 6 percent in both the men and women," the researchers write. The DHEA replacement also resulted in a significant improvement in insulin action that correlated with the reduction in visceral fat.

"These findings provide evidence that DHEA replacement may partially reverse the aging-related accumulation of abdominal fat in elderly people with low serum levels of DHEAS. They also raise the possibility that long-term DHEA replacement therapy might reduce the accumulation of abdominal fat and protect against development of the metabolic/insulin resistance syndrome," they write.

HEART DISEASE PATIENTS WITH NORMAL BLOOD PRESSURE SUFFER A THIRD LESS HEART ATTACKS AND OTHER EVENTS WHEN TAKING BLOOD PRESSURE LOWERING MEDICATION