Parental Intermittent Claudication as Risk Factor for Claudication in Adults

Abstract

Conclusion: Intermittent claudication (IC) in parents increases the risk of IC in adult offspring, independent of established risk factors. Summary: A consensus statement from the National Institutes of Health indicates family history is important to patient care because it contributes information to the risk of developing common diseases, including diabetes mellitus, stroke, heart disease, and cancer (Berg AO et al, Ann Intern Med 2009;151:872-7). For example, parental stroke is associated with a threefold increase in the risk of stroke in offspring (Seshaderi S et al, Circulation 2010;121:1304-12). There is, however, little known about familial aggregation of peripheral arterial disease. The Framingham Heart Study provides an opportunity to use prospectively collected data from a large community sample to study IC across two generations. This study tested the hypothesis that parental IC increases risk of IC in adult offspring. The authors evaluated the offspring of participants in the Framingham Heart Study who were aged ≥30 years, free of cardiovascular disease, and had both parents enrolled in the Framingham Heart Study (n = 2970 unique participants, 53% women). The 12-year risk of incidence IC in offspring participants was associated with parental IC and analyzed using pooled proportional hazard regression analysis and adjusting for age, sex, diabetes, smoking, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and antihypertensive and lipid treatment. There were 909 individuals examined in the group with parental IC history and 5,397 in the group with no parental IC history. There were 101 incident IC events during follow-up; 29 in the group with parental IC history and 72 in the group without parental IC history. The age-adjusted and sex-adjusted 12-year cumulative incidence IC rate/1,000 person-years was 5.08 (95% confidence interval [CI], 2.74-7.33) and 2.34 (95% CI, 1.46-3.19) in participants with and without a parental IC history. A parental history of IC increased the risk of incidence IC in offspring (multivariable adjusted hazard ratio, 1.81; 95% CI, 1.14-2.88). Adjustment for the occurrence of cardiovascular disease did not change the hazard ratio. Comment: The hazard ratio for development of IC in children of patients with IC was independent of established cardiac risk factors, which suggests a genetic component or genetic predisposition to IC. The importance of this potential genetic component in influencing the development of IC cannot truly be determined from these data. There are assuredly environmental and life style factors likely shared within families that could also contribute to the susceptibility to IC. Limitations to this study include that IC was diagnosed by symptoms alone and that the risk factors used for adjustment in the multivariable model were from a single occasion measurement and may not reflect accumulation of lifetime risk factor exposures.