PPAR gamma variant influences angiographic outcome and 10-year cardiovascular risk in male symptomatic coronary artery disease patients.
OBJECTIVE
Activation of peroxisome proliferator-activated receptor (PPAR)-gamma signaling influences metabolic profiles and the propensity toward inflammation. Small-molecule stimulation of PPARgamma is investigated for secondary prevention of cardiovascular disease. The common PPARgamma Pro12Ala variant has functional and prognostic consequences. A protective effect of the 12Ala-allele carriership on diabetes and myocardial infarction 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 angiographic 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 were 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 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 PPARgamma 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 PPARgamma in determining vascular risk.
Regieli
Jakub J
JJ
Juliuscenter for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Jukema
J Wouter
JW
Doevendans
Pieter A
PA
Zwinderman
Aeilko H
AH
van der Graaf
Yolanda
Y
Kastelein
John J
JJ
Grobbee
Diederick E
DE
D000409:Alanine; D019943:Amino Acid Substitution; D001794:Blood Pressure; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D011392:Proline; D016016:Proportional Hazards Models; D011859:Radiography
D047495:PPAR gamma; D011392:Proline; D000409:Alanine