Accumulation of Deficits as a Key Risk Factor for Cardiovascular Morbidity and Mortality: A Pooled Analysis of 154 000 Individuals

BACKGROUND: Frailty is associated with higher mortality in individuals at high cardiovascular disease (CVD) risk. We hypothesize that frailty is a more important prognostic factor than CVD risk factors and aim to determine the prognostic value of a cumulative deficit frailty index in patients with or at high risk for CVD. METHODS AND RESULTS: We conducted an individual‐level pooled analysis of participants with or at risk for CVD, recruited in 14 multicenter clinical trials. The cumulative deficit index was calculated as the proportion of 26 deficits exhibited. Individuals were categorized as nonfrail, prefrail, or frail if they had indexes of ≤0.1, >0.1 to 0.21, or >0.21, respectively. CVD risk was assessed using the Framingham score. Outcomes included CVD event (new or recurrent myocardial infarction, stroke, or heart failure) and mortality. We studied 154 696 patients (mean age, 70.8 years; 63% men) with median follow‐up of 3.2 years. There were 17 535 CVD events and 15 067 deaths. The frail group (n=13 872) had higher risk of a CVD event (incidence rate ratio, 1.97; 95% CI, 1.85–2.08), all‐cause mortality (hazard ratio, 1.91; 95% CI, 1.79–2.03), and CVD mortality (hazard ratio, 1.91; 95% CI, 1.77–2.05) than the nonfrail group (n=101 343). Associations remained unchanged after adjusting for CVD risk factors. The index statistically outperformed the Framingham score in its ability to discriminate CVD events (C‐statistic, 0.60 [95% CI, 0.60–0.61] versus 0.58 [95% CI, 0.57–0.58], respectively; P<0.001). CONCLUSIONS: In individuals with or at high risk of developing CVD, the cumulative deficit index is associated with increased CVD events and mortality, independent of CVD risk factors, and adds incremental prognostic value.