Frailty Is Associated with an Increased Risk of Major Adverse Cardiac Events in Patients with Stable Claudication

Abstract

Background: Frailty, a syndrome characterized by decreased physiologic reserves and resistance to stressors, is associated with disability, poor surgical outcomes, and mortality. We evaluated the impact of frailty on cardiovascular disease (CVD) events in peripheral arterial disease (PAD) patients with intermittent claudication.

Methods: We conducted a retrospective review of patients with stable intermittent claudication enrolled in the OMEGA-PAD study between 2010 and 2015. The modified frailty index (mFI) is a retrospectively validated index of frailty derived from the Canadian Study of Health and Aging and was used in this study to categorize frailty as low, medium, or high. Our outcome was time to occurrence of a major adverse cardiac event (MACE), defined as a composite endpoint of myocardial infarction, coronary revascularization, stroke, or CVD-related death. Cox proportional hazards models were used to calculate relative hazards ratio.

Results: There were 129 subjects with a mean age of 67 years, 97% were men, 36% were diabetic, and 33% had known coronary heart disease. When the mFI criteria were applied, 38 subjects were "low" frailty, 72 were "medium" frailty, and 19 were "high" frailty. During the median follow-up period of 34 months (interquartile range: 25-43), 29 subjects experienced a MACE. When compared to the lowest mFI, patients with medium frailty were 2.8 times more likely to have an event (95% confidence interval [CI]: 0.95-8.46, P = 0.06), whereas patients with a high mFI were 4.8 times as likely (95% CI: 1.43-15.8, P = 0.01). In a model adjusted for age, smoking status, and presence of diabetes, those with a medium mFI were 4.3 times more likely to have an event (95% CI: 1.37-13.7, P = 0.01) and those with a high mFI were 9.2 times as likely (95% CI: 2.6-32.4, P = 0.001).

Conclusions: Higher mFI category is associated with a significantly increased risk of MACE in PAD patients with stable claudication. Frailty may serve as a useful adjunct for assessment of overall cardiac risk, particularly as treatment options are being contemplated.

Figure 1

Adjusted Kaplan-Meier estimates of time to major adverse cardiac events (MACE) by frailty categories of low (n=38), medium (n=72), and high (n=19) based on the modified frailty index (mFI). Trend test P=0.0004. The vertical dashed line indicates the cutoff for a standard error >10% for the high frailty score group only. All values of the low and medium frailty score groups had a standard error <10%.

Figure 2

The proportion of major adverse cardiac events (MACE) by frailty categories and Lee Criteria scores.