Abstract 3492: The PPAR-gamma Signaling Pathway Has Strong Impact On 10yr Cardiovascular Risk In Symptomatic Coronary Artery Disease
INTRODUCTION Activation of the Peroxisome Proliferator-Activated Receptor-gamma (PPARG) signaling pathways influences cellular insulin sensitivity and impedes various inflammatory and atherothrombotic steps. Activity is genetically determined by Proline to Alanine substitution at codon 12. Prior findings in healthy populations (Physicians Health Study) imply a protective effect of the 12-Ala variant on MI. Since pharmacological induction of PPARG is suggested for secondary prevention, the relevance of this pathway needs exploration in patients with manifest vascular disease. We therefore investigated the long-term effects of Pro12Ala on cardiovascular outcome in patients with symptomatic coronary artery disease.
METHODS Long term mortality of the REGRESS cohort genotyped for Pro12Ala and comprising 884 male CAD patients was derived from nation-wide registries, and endpoints defined from recorded ICD codes. Risks according to genotype were estimated using proportional hazard analyses.
RESULTS Death related to ischemic heart diseases (IHD) and vascular diseases occurred in 58 (6.6%) and 71 (8.0%) patients respectively. Genotypes (n = 679, 77%) comprised 540 (80%) Pro/Pro, 126 (19%) Pro/Ala and 13 (1,9 %) Ala/Ala subjects. Hazard Ratios were 0.10 (95% CI 0,01– 0,70, p = 0.02) for IHD- and 0.24 (0.08 – 0.74, p = 0.013) for vascular death(figure⇓), per each added copy of Ala12.
DISCUSSION The Ala12 allele of PPARG, appears to strongly protect against 10-year (cardio)vascular mortality. These long-term findings in patients with manifest coronary artery disease emphasize the relevance and putative role of this pathway as a target to modify and predict vascular risk.