Renal Insufficiency and the Risk of Lower Extremity Peripheral Arterial Disease: Results from the Heart and Estrogen/Progestin Replacement Study (HERS)

Abstract

ABSTRACT. Renal insufficiency is a risk factor for coronary heart disease and stroke, but whether it predicts lower extremity peripheral arterial disease (PAD) is unknown. The authors evaluated was the association of baseline renal insufficiency with future PAD events in the Heart and Estrogen/Progestin Replacement Study (HERS) and follow-up study (HERS II). A total of 2763 postmenopausal women with known coronary heart disease were enrolled in HERS and randomly assigned to receive hormone therapy with conjugated estrogens and medroxyprogesterone acetate or placebo and followed for up to 8 yr for clinical end points. The outcome was time from randomization to first occurrence of either a lower extremity amputation, revascularization (surgical or percutaneous), or lumbar sympathectomy during follow-up. Incident lower extremity PAD event rates among women with creatinine clearances ≥60, 30 to 59, and <30 ml/min/1.73 m² were, respectively, 0.55%, 0.92%, and 2.73% per year. After multivariable proportional-hazard adjustment for potential confounders and other known risk factors for PAD, women with a creatinine clearance 30 to 59 ml/min/1.73 m² (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.04 to 2.54, P = 0.032) and <30 ml/min/1.73 m² (HR, 3.24; 95% CI, 1.20 to 8.78, P = 0.021) had a significantly increased risk of PAD compared with participants with a creatinine clearance ≥60 ml/min/1.73 m². Renal insufficiency was independently associated with future PAD events among postmenopausal women with coronary heart disease. Future studies should determine whether this association is present in other populations and investigate its potential mechanisms.