Association of Plasma 7-Ketocholesterol with Cardiovascular Outcomes and Total Mortality in Patients with Coronary Artery Disease
Rationale: 7-Ketocholesterol (7-KC), a form of cholesterol oxidation product, plays an essential role in the atherogenesis in animal models.
Objective: We sought to determine the association of circulating 7-KC with clinical cardiovascular outcomes and total mortality in patients with stable coronary artery disease (CAD).
Methods and Results: We measured the plasma 7-KC levels by high performance liquid chromatography in a prospective cohort study of 1016 patients (mean age 63.2 years, male 61.1%) with stable CAD who were recruited from December 2008 to December 2011, and followed up for a median of 4.6 years. We adjudicated myocardial infarction (MI), hospitalization of heart failure (HF), cardiovascular (CV) death, all-cause death, and composite endpoints of MI/HF/death by review of medical records and death certificates. We used multivariable Cox proportional hazards analysis to compare the incidence rate of cardiovascular events and all-cause death according to the quartile of the plasma 7-KC. During the median 4.6 years follow-up, totally 221 participants (21.8%) experienced a cardiovascular event or death. The adjusted risk of the composite endpoints was higher in the highest 7-KC quartile than in the lowest quartile (hazard ratio: 1.76; 95% confidence interval, 1.42-2.21; P < 0.001). After adjustment for demographic and clinical variables and other biomarkers including high-sensitivity C-reactive protein (hs-CRP) and N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), one standard deviation (SD) increase in the 7-KC level remained associated with a 36% higher rate of composite outcomes (hazard ratio: 1.36; 95% CI: 1.22-1.48, P = 0.007). Plasma 7-KC clearly improved various model performance measures, including C-statistics, integrated discrimination and category-free net reclassification.
Conclusions: High 7-KC levels are associated with increased risk of cardiovascular events, total death and composite outcomes in patients with stable CAD.
- cardiovascular disease risk factors
- cardiovascular events
- coronary artery disease
- risk prediction
- Received October 13, 2016.
- Revision received March 31, 2017.
- Accepted April 5, 2017.