Jiayi Song1, Duan Wang1, Hongen Chen1, Xiuwei Huang1, Yuan Zhong1, Nan Jiang1, Chaogang Chen1, Min Xia2. 1. From the Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, China (J.S., H.C., X.H., Y.Z., N.J.); Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, China (J.S., H.C., X.H., Y.Z., N.J., M.X.); Department of Clinical Nutrition, Guangdong General Hospital, Guangzhou, China (D.W.); and Department of Clinical Nutrition, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China (C.C.). 2. From the Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, China (J.S., H.C., X.H., Y.Z., N.J.); Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, China (J.S., H.C., X.H., Y.Z., N.J., M.X.); Department of Clinical Nutrition, Guangdong General Hospital, Guangzhou, China (D.W.); and Department of Clinical Nutrition, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China (C.C.). xiamin@mail.sysu.edu.cn.
Abstract
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. 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 coronary artery disease who were recruited from December 2008 to December 2011 and followed up for a median of 4.6 years. We adjudicated myocardial infarction, hospitalization of heart failure, cardiovascular death, all-cause death, and composite end points of myocardial infarction/heart failure/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 end points 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 and NT-proBNP (N-terminal pro-B-type natriuretic peptide), 1 SD increase in the 7-KC level remained associated with a 36% higher rate of composite outcomes (hazard ratio, 1.36; 95% confidence interval, 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 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. 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 coronary artery disease who were recruited from December 2008 to December 2011 and followed up for a median of 4.6 years. We adjudicated myocardial infarction, hospitalization of heart failure, cardiovascular death, all-cause death, and composite end points of myocardial infarction/heart failure/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 end points 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 and NT-proBNP (N-terminal pro-B-type natriuretic peptide), 1 SD increase in the 7-KC level remained associated with a 36% higher rate of composite outcomes (hazard ratio, 1.36; 95% confidence interval, 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 coronary artery disease.
Authors: Katharina R Beck; Silvia G Inderbinen; Sharavan Kanagaratnam; Denise V Kratschmar; Anton M Jetten; Hideaki Yamaguchi; Alex Odermatt Journal: J Lipid Res Date: 2019-07-04 Impact factor: 5.922
Authors: Amelia Anderson; Angielyn Campo; Elena Fulton; Anne Corwin; W Gray Jerome; Matthew S O'Connor Journal: Redox Biol Date: 2019-11-14 Impact factor: 11.799