Dr Sanjeev Bhavnani

"Over two years in this specific patient population, people with coronary artery disease, it's the obese individuals who receive the greatest benefit from aggressive blood-pressure control," lead investigator Dr Sanjeev Bhavnani (University of Connecticut Health Center, Manchester) told heartwire. "We were able to show that, in accordance with the literature, obese people, as with lean people, are at very high risk, but that risk might be attenuated in an obese population with aggressive blood-pressure lowering."

The results of the study, an analysis of the Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) trial, were presented here this past weekend at the American Society of Hypertension 2007 Scientific Sessions.

In CAMELOT, which was published in 2004 [2], investigators examined the effects of antihypertensive drugs in 1991 patients with CAD and normal blood pressure (average baseline BP was 129/78 mm Hg) over a 24-month period. Patients received amlodipine (10 mg), enalapril (20 mg), or placebo. The primary end point was the time to first occurrence of an adverse cardiovascular event, such as cardiovascular death, nonfatal MI, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke, or diagnosis of vascular disease.

As reported by heartwire at the time of publication, amlodipine reduced blood pressure by an average of 5/3 mm Hg and, compared with placebo, produced a 31% relative reduction (6.5% absolute reduction) in cardiovascular events. Enalapril treatment also reduced blood pressure, by an average of 5/2 mm Hg. However, the observed 15.3% relative reduction in cardiovascular events compared with placebo (2.9% absolute reduction) was not statistically significant.

"CAMELOT is a unique trial in that it looked at antihypertensive therapy among people at high risk, but who have fairly normal blood-pressure levels," said Bhavnani. "In this particular substudy, we wanted to look at outcomes stratified according to body-mass index—lean, overweight, and obese. A lot of recent data, as well as clinical practice experience, have shown that obese individuals with hypertension are at very high risk for cardiovascular events. This is a unique population of obese high-risk individuals who have normal blood pressure and yet are receiving antihypertensive therapy with amlodipine or enalapril."

Of the 1991 patients in CAMELOT, 264 were classified as lean (BMI <25 kg/m²), 824 were classified as overweight (BMI 25-29.9 kg/m²), and 903 were classified as obese (>30 kg/m²). The incidence of cardiovascular events, as noted, was highest in obese and lean patients, a paradoxical finding suggesting overweight might be cardioprotective, something that has been observed in other trials, Bhavnani noted.

Across all BMI tertiles, the mean systolic blood-pressure reduction was greater with amlodipine vs placebo and enalapril vs placebo, but there was no difference in systolic blood-pressure changes when amlodipine was compared with enalapril. Reductions in systolic blood pressure with amlodipine and enalapril were greater for lean patients than obese and overweight patients.

In a comparison of drug therapy vs placebo across BMI tertiles, amlodipine had the greatest benefit for the reduction of overall cardiovascular events in obese patients, a finding that was driven primarily by significant reductions in angina and coronary revascularization. There was only a trend toward benefit in reducing nonfatal MI and revascularization in obese patients treated with enalapril. The effect of enalapril vs placebo on overall cardiovascular events was nonsignificant across the different BMI groups. Differences in amlodipine vs enalapril for the reduction of cardiovascular events were nonsignificant, although amlodipine reduced the incidence of hospitalization for angina more than enalapril in obese patients.

Risk reduction and the need to get blood-pressure levels below conventional targets might be particularly important in an obese population, said Bhavnani. Explaining the results of the study, he noted that lean subjects had the greatest reduction in blood pressure but only a trend toward a reduction in cardiovascular events. At the moment, however, there is no one biological reason that explains the findings.

"There might be pleiotropic effects of antihypertensive therapy, whether with the calcium-channel blockers or the ACE inhibitors, that translates into cardiovascular benefit," he said. "It might be beyond the number alone, that bringing people to 120 or 125 mm Hg might not fully explain the cardiovascular risk reduction. It might be a unique property of the class of medication, whether through endothelial protection or vasomotor inhibition. It could also be that in this population with coronary artery disease, the physiology might be different."