Benefits and risks of more intensive blood pressure lowering in hypertensive patients of the HOT study with different risk profiles: does a J-shaped curve exist in smokers?

BACKGROUND: The Hypertension Optimal Treatment (HOT) Study investigated 18 790 hypertensives randomized to three diastolic blood pressure (DBP) targets (< or = 90, < or = 85, < or = 80 mmHg) for 3.8 years and found marked, significant reductions in cardiovascular events and mortality the lower the target DBP in the subset of diabetics. We investigated whether the benefits of intensive DBP lowering could be extended to other subgroups, and whether there are hypertensives in whom the risk of aggressive DBP lowering may outnumber the benefits. METHODS AND RESULTS: The 18 790 patients were stratified as: medium/high-very high global cardiovascular risk; men/women; older/younger; current smokers/non-smokers; higher/lower serum cholesterol; higher/lower serum creatinine; with/without diabetes; with/without ischaemic heart disease (IHD). Comparisons were made between the less aggressive target group (DBP < 90 mmHg) and the two more aggressive target groups together (< or = 85 and < or = 80 mmHg). A Cox proportional hazards model was used to calculate treatment-subgroup interactions and relative risks (RR) with 95% confidence intervals. Benefits were greatest in diabetics (RR 0.53 for cardiovascular events, and 0.67 for cardiovascular death), whereas in smokers more intensive DBP lowering was associated with increased risk of all types of cardiovascular event (RR 1.71-2.67; P = 0.01-0.001), except myocardial infarction. After excluding smokers, intensive DBP lowering was associated with significant reductions in cardiovascular events in diabetics (-49%), high-very high risk patients (-23%), IHD patients (-32%), patients with lower creatinine (-18%), women (-33%) and older patients (-23%). CONCLUSIONS: Although subanalyses have only a descriptive value, it appears reasonable to recommend intensive antihypertensive treatment to hypertensives with diabetes, IHD and high global cardiovascular risk. In smokers, treatment intensification should be associated with the greatest efforts to induce smoking cessation