Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: Results from a meta-analysis and exploratory meta-regression analysis

Frailty is common and associated with poorer outcomes in the elderly, but its role as potential cardiovascular disease (CVD) risk factor requires clarification. We thus aimed to meta-analytically evaluate the evidence of frailty and pre-frailty as risk factors for CVD. Two reviewers selected all studies comparing data about CVD prevalence or incidence rates between frail/pre-frail vs. robust. The association between frailty status and CVD in cross-sectional studies was explored by calculating and pooling crude and adjusted odds ratios (ORs) ±95% confidence intervals (CIs); the data from longitudinal studies were pooled using the adjusted hazard ratios (HRs). Eighteen cohorts with a total of 31,343 participants were meta-analyzed. Using estimates from 10 cross-sectional cohorts, both frailty and pre-frailty were associated with higher odds of CVD than robust participants. Longitudinal data were obtained from 6 prospective cohort studies. After a median follow-up of 4.4 years, we identified an increased risk for faster onset of any-type CVD in the frail (HR=1.70 [95%CI, 1.18-2.45]; I2=66%) and pre-frail (HR=1.23 [95%CI, 1.07-1.36]; I2=67%) vs. robust groups. Similar results were apparent for time to CVD mortality in the frail and pre-frail groups. In conclusion, frailty and pre-frailty constitute addressable and independent risk factors for CVD in older adults.