Abstract
OBJECTIVES: Physical frailty has been found to increase the risk of multiple adverse outcomes including cardiovascular disease (CVD) in diabetic patients, but whether this could be modified by traditional risk factor control remains unknown. We aimed to explore the joint and interaction effects of frailty and traditional risk factor control on the risk of CVD. DESIGN: A population-based cohort study. SETTING AND PARTICIPANTS: We included 15,753 participants with type 2 diabetes at baseline from UK Biobank. MEASUREMENTS: Physical frailty was assessed by Fried criteria's frailty phenotype. The degree of risk factor control was determined by the numbers of the following factors controlled within the target range, including glycated hemoglobin, blood pressure, low-density lipoprotein cholesterol, smoking, and kidney condition. Incident CVD included coronary heart disease, stroke, or heart failure. Cox proportional hazard models were used to assess the individual and joint effects of frailty and risk factor control on the risk of CVD. RESULTS: After a median follow-up of 13.5 years, 1129 incident CVD events were observed. Compared with non-frailty, both prefrailty and frailty were significantly associated with increased risk of CVD (HR 1.22, 95% CI [1.13, 1.31] for pre-frailty and 1.70 [1.53, 1.90] for frailty). For the joint effects, participants with frailty and a low degree of risk factor control (control of 0-1 risk factors) had the highest risk of CVD (2.92 [2.04, 4.17]) compared to those with non-frailty and optimal risk factor control (control of 4-5 risk factors). Moreover, a significant additive interaction between frailty and risk factor control was observed, with around 3.8% of CVD risk attributed to the interactive effects. CONCLUSIONS: Both prefrailty and frailty were associated with a higher risk of CVD in participants with type 2 diabetes. Moreover, physical frailty could interact with the degree of risk factor control in an additive manner to increase the CVD risk.