People with normal body-mass index (BMI) tend to have unexpectedly higher cardiovascular event rates than overweight or obese patients. To understand this paradoxical finding Dr Michael Weber from SUNY Downstate Medical Centre, New York, USA, performed a prespecified analysis of the ACCOMPLISH trial. The trial enrolled 1,616 patients of normal weight, 4,157 overweight patients, and 5,709 obese patients. These patients were randomized to either a combination of benazepril and amlodipine or benazepril and hydrochlorothiazide.
The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), or stroke. Mean blood pressure at baseline was 146/80 mm Hg and during treatment 133/73 mm Hg and lower diastolic blood pressures were achieved with the amlodipine-based regimen.
In the hypertensive patients of normal weight or those who were overweight but not obese, the combination of the benazepril and amlodipine was significantly more effective at reducing cardiovascular events than the combination of benazepril and hydrochlorothiazide (HR 0.57, P=0.0037). The amlodipine-based regimen also was superior in overweight patients (HR 0.76, P=0.03) but not in obese patients (P=0.31).
Weber M, et al “Effect of body mass on cardiovascular outcomes during hypertension treatment: an ACCOMPLISH analysis” ASH 2012; Abstract LB-OR-03.
This data indicates that thiazide-based therapy is associated with reduced CV protection in non-obese patients. One reason may be that thiazides may stimulate adverse mechanisms such as increased sympathetic tone and activation of the renin angiotensin system, leading to poorer cardiovascular outcomes. The molecular and pathophysiological mechanisms responsible for the differences observed in lean and overweight patients, compared with obese subjects, are not known at present.