A PPARγ Variant Influences Angiographic Outcome and Ten-Year Cardiovascular Risk in Male Symptomatic Coronary Artery Disease Patients

Abstract

Objective Activation of Peroxisome Proliferator-Activated Receptor-gamma (PPARγ) signaling influences metabolic profiles and the propensity towards inflammation. Small-molecule stimulation of PPARγ is investigated for secondary prevention of cardiovascular disease. The common PPARγ Pro12Ala variant has functional and prognostic consequences. A protective effect of the 12Ala allele carriership on diabetes and myocardial infarction (MI) in healthy populations has been suggested. The relevance of this pathway also needs exploration in patients with manifest vascular disease. We investigated the effects of carriership of the Pro12Ala variant on angiographical and cardiovascular event outcomes in male patients with symptomatic coronary artery disease (CAD).

Methods The REGression Growth Evaluation Statin Study (REGRESS) cohort was genotyped for the Pro12Ala variant (rs1801282). Ten-year follow-up was derived from nation-wide registries, and risks estimated using proportional hazards. Quantitative coronary angiography measurements were obtained and relations with genotype estimated using a generalized linear model.

Results Genotypes ascertained (n=679), comprised 540 (80%) Pro/Pro, 126 (19%) Pro/Ala and 13 (2 %) Ala/Ala subjects. The 12Ala allele was associated with less extensive focal (p=0.001) and diffuse (p=0.002) atherosclerosis and lower 10-year cardiovascular risk. Hazard Ratios were 0.10 (95% CI 0,01-0,70, p=0.02) for Ischemic Heart Disease (IHD)- and 0.24 (0.08-0.74, p=0.013) for Vascular death, per each added copy of 12Ala, respectively.

Conclusions: Carriers of the 12Ala allele of PPARγ have less widespread CAD, and are considerably protected against 10-year (cardio)vascular morbidity and mortality. These long-term findings in patients with manifest CAD support an important role of PPARγ in determining vascular risk.