Abstract | OBJECTIVE: METHODS AND RESULTS: We examined serum Cp levels and their relationship with incident major adverse cardiovascular events ( MACE; death, myocardial infarction [MI], stroke) over 3-year follow-up in 4177 patients undergoing elective coronary angiography. We also carried out a genome-wide association study to identify the genetic determinants of serum Cp levels and evaluate their relationship to prevalent and incident cardiovascular risk. In our cohort (age 63±11 years, 66% male, 32% history of MI, 31% diabetes mellitus), mean Cp level was 24±6 mg/dL. Serum Cp level was associated with greater risk of MI at 3 years (hazard ratio [quartile 4 versus 1] 2.35, 95% confidence interval [CI] 1.79-3.09, P<0.001). After adjustment for traditional risk factors, high-sensitivity C-reactive protein, and creatinine clearance, Cp remained independently predictive of MACE (hazard ratio 1.55, 95% CI 1.10-2.17, P=0.012). A 2-stage genome-wide association study identified a locus on chromosome 3 over the CP gene that was significantly associated with Cp levels (lead single-nucleotide polymorphism rs13072552; P=1.90×10(-11)). However, this variant, which leads to modestly increased serum Cp levels (≈1.5-2 mg/dL per minor allele copy), was not associated with coronary artery disease or future risk of MACE. CONCLUSIONS: In stable cardiac patients, serum Cp provides independent risk prediction of long-term adverse cardiac events. Genetic variants at the CP locus that modestly affect serum Cp levels are not associated with prevalent or incident risk of coronary artery disease in this study population.
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Authors | W H Wilson Tang, Yuping Wu, Jaana Hartiala, Yiying Fan, Alexandre F R Stewart, Robert Roberts, Ruth McPherson, Paul L Fox, Hooman Allayee, Stanley L Hazen |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 32
Issue 2
Pg. 516-22
(Feb 2012)
ISSN: 1524-4636 [Electronic] United States |
PMID | 22075249
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Aged
- Biomarkers
(blood)
- Cardiovascular Diseases
(blood, epidemiology, genetics)
- Ceruloplasmin
(genetics, metabolism)
- Cohort Studies
- Female
- Follow-Up Studies
- Genetic Predisposition to Disease
(genetics)
- Genetic Variation
(genetics)
- Genome-Wide Association Study
- Humans
- Incidence
- Longitudinal Studies
- Male
- Middle Aged
- Myocardial Infarction
(blood, epidemiology, genetics)
- Predictive Value of Tests
- Prevalence
- Prospective Studies
- Retrospective Studies
- Risk Factors
- Stroke
(blood, epidemiology, genetics)
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