The Road to Frailty Is Paved With Good Intentions.

Frailty is a relatively young area of investigation in cardiovascular research. The first wave of published research, circa 2001 to 2006, uncovered the epidemiological and pathophysiological links between frailty and cardiovascular disease (CVD). Compared to those without CVD, older adults with CVD were reported to have an odds ratio of 2.7 to 4.1 for prevalent frailty in cross-sectional studies and an odds ratio of 1.5 to 1.7 for incident frailty in the Women’s Health Initiative Observational Study (WHI-OS). The connection between frailty and CVD was reinforced by a seminal mechanistic study from Walston et al, in which the clinical phenotype of frailty was found to be independently associated with biomarkers of inflammation, coagulation, and glucose metabolism. The second wave, circa 2006 to 2016, has highlighted the prognostic value of frailty in older adults with various forms of CVD. Frailty was consistently found to be a potent risk factor (often trumping traditional risk factors in multivariable models) for mortality and major morbidity after cardiac surgery, transcatheter aortic valve replacement, myocardial infarction, percutaneous coronary intervention, and stable or decompensated heart failure. The third wave, present time, is evolving the use of frailty from a predictive marker to a therapeutic target and a longitudinal outcome measure—as exemplified by the 2 commendable studies published in this issue of Circulation: Cardiovascular Quality and Outcomes.