Abstract 15680: Increased Risk of Ischemic Coronary and Cerebrovascular Events in Patients With Chronic Granulomatous Disease
Chronic inhibition of NADPH oxidase (NOX) activity confers cardiovascular protection in preclinical models of hypertension, atherosclerosis and stroke, highlighting it as a potential therapeutic target. Here we investigated the risk of cardiovascular events in patients with chronic granulomatous disease (CGD); a rare genetically-determined immunodeficiency disorder caused by a defective NOX complex. A population-level cohort study was performed using linked data, classified according to WHO ICD codes, and capturing all hospitalisations in the Australian state of Victoria from 1993-2010. Logistic regression was used to estimate the risk of ischemic coronary (myocardial infarction/angina) and cerebrovascular (ischemic stroke/transient ischemic attacks) events in CGD versus non-CGD individuals. We identified 77 people with CGD (43.0±26.7 y, mean±SD) and randomly selected 415,800 in-patient non-CGD controls (37.8±25.7 y). A total of 17 (22.1%) CGD patients and 36,598 (8.8%) controls suffered a cardiovascular event during the study period. After adjusting for age and sex, the odds ratio (OR) of a coronary event in CGD versus non-CGD patients was 2.37 [95% confidence interval (CI), 1.20-4.68; P=0.013] while that for a cerebrovascular event was 2.95 (95% CI, 1.13-7.71; P=0.028). Further adjustment for the presence of hypertension markedly attenuated the association of CGD with both coronary (OR, 1.68; 95% CI, 0.80-3.54; P=0.174) and cerebrovascular (OR, 2.19; 95% CI, 0.82-5.88; P=0.118) events. Adjusting for other comorbidities including diabetes, smoking and sleep apnea did not alter the associations. Thus, CGD in humans is associated with increased risk of coronary and cerebrovascular events. These observations, which are at odds with a large body of literature from experimental animal studies, cast doubt over the validity of targeting NOX as a future therapy for cardiovascular disease.
- © 2013 by American Heart Association, Inc.