Abstract Background High blood pressure (BP) is a risk factor for cardiovascular disease and premature mortality. Observational studies have shown differential effects of high BP in frail and non-frail people. Consequently, the former may need different approaches to manage their BP compared to non-frail individuals. Purpose We aimed to determine the impact of frailty on MI, stroke and mortality outcomes, and to examine whether the effect of antihypertensive treatment on those outcomes varies by frailty status. Methods Single-stage individual-participant-data meta-analysis. Data were merged from four landmark double-blind placebo-controlled trials of antihypertensive drugs with blinded adjudicated non-fatal MI, non-fatal stroke and all-cause mortality endpoints. Baseline frailty was assessed using a robust tool, the frailty index (FI), and modelled as a continuous (per SD increase) and binary variable ≤0.21 for none/mild and 0.21 for moderate-severe frailty. Cox regression (adjusted for age, sex, education) yielding hazard ratios (HRs) for mortality and Fine and Grey models yielding subdistribution HRs (sHRs) for MI and stroke accounting for the competing risk of mortality, were used to model the associations of frailty on outcomes, and of antihypertensive treatment on outcomes by frailty status. Results Data were available for 24,122 participants (mean age 68.5 (SD 9.31) years, 44% female) with a median follow up of 4.3 years. The mean (SD) FI was 0.175 (0.086) and median (interquartile interval) 0.16 (0.11-0.23), and 29% of participants had moderate-severe frailty. Frailty (per SD increase) was associated with a higher risk of MI sHR 1.50 (95%CI 1.40, 1.61), stroke 1.21 (1.15, 1.28) and all-cause mortality HR 1.49 (95%CI 1.43, 1.55). The impact of anti-hypertensive treatment on non-fatal stroke for those with none/mild frailty was sHR 0.72 (95%CI 0.63, 0.82) compared to 1.00 (0.82, 1.23) for those with moderate-severe frailty (p for interaction = 0.008). Corresponding sHRs for MI were 0.74 (0.59, 0.93) and 0.87 (0.68, 1.12) (p=0.335) and HRs for all-cause mortality were 0.89 (0.79, 0.99) and 0.89 (0.79, 1.02) (p=0.920). Conclusion Individuals with higher frailty are at higher risk of MI, stroke and premature mortality. Antihypertensive treatment was shown to be effective regardless of frailty status on MI and all-cause mortality, but there was evidence of a differential effect on stroke outcomes. These data have implications for treatment guidelines for cardiovascular prevention alongside approaches to the management of people at high-risk of adverse outcomes.
Harris et al. (Sat,) studied this question.