Metabolic syndrome severity and the effects of intensive blood pressure lowering: Results from the STEP randomized trial.

Several clinical trials have shown that intensive systolic blood pressure (SBP) lowering confers cardiovascular benefits. However, whether baseline metabolic syndrome (MetS) severity modifies these benefits and risks remains unclear. This post hoc analysis of the STEP trial included 8231 participants with complete MetS severity data. Baseline MetS severity was quantified using an age-, sex-, and ethnicity-specific MetS scoring model and analyzed as tertiles and continuously. The primary outcome was a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, and cardiovascular death. Cox models and restricted cubic spline analyses were used to assess treatment-effect heterogeneity. During a median follow-up of 3.32 years, intensive SBP lowering reduced the risk of the primary outcome compared with standard treatment. The absolute incidence of the primary outcome and major adverse cardiac events was highest in the highest MetS tertile. Across MetS tertiles, event rates were lower in the intensive-treatment group, with the largest reduction in the middle tertile for the primary outcome (Q2: HR, 0.66; 95% CI, 0.44-0.99). No significant treatment-by-MetS interaction was observed in tertile-based or spline analyses. For safety outcomes, no significant treatment-by-MetS tertile interaction was observed, although hypotension was numerically more frequent with intensive treatment among participants in the highest MetS tertile. These findings suggest that baseline MetS severity identifies patients with higher absolute cardiovascular risk but does not significantly modify the relative efficacy of intensive SBP lowering. Careful monitoring for treatment-related hypotension may be warranted, particularly among patients with higher metabolic burden.