Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low‐Density Lipoprotein Cholesterol

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Paul M Ridker¹  Robert J. Glynn¹  Samia Mora²  Akintunde O. Akinkuolie²  Patrick R. Lawler²  Svati H. Shah³  Damian Craig³  William E. Kraus³  Latha Padmanabhan⁴  Audrey Y. Chu⁴  Daniel I. Chasman⁴ 

[1] Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;Center for Lipid Metabolomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;Division of Cardiology and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC;Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;

关键词: atherosclerosis;    lipids and lipoproteins;    metabolomics;    nuclear magnetic resonance spectroscopy;    prevention;   

DOI  :  10.1161/JAHA.117.005549

来源: DOAJ

【 摘 要 】

BackgroundLevels of LDL (low‐density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid‐related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (<130 mg/dL) LDL cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations. Methods and ResultsWe performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of LDL and VLDL (very low‐density lipoprotein) particle subclasses in 11 984 JUPITER trial participants (NCT00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%CI] per SD increment) among placebo‐allocated participants was associated with total LDL particles (1.19 [1.02, 1.38]) and total VLDL particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non–high‐density lipoprotein cholesterol, and triglycerides, but not LDL‐c. Rosuvastatin reduced LDL measures but had variable effects on triglyceride and VLDL measures. On‐statin levels of the smallest VLDL particle subclass were associated with a 68% per‐SD (adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk—this risk was related to VLDL cholesterol and not triglyceride or larger VLDL particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key VLDL measures (Harrell C‐index 0.780 versus 0.712; P<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (CATHGEN), similar patterns of lipoprotein‐related risk were observed. ConclusionsAtherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when LDL cholesterol was low. VLDL lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

【 授权许可】

Unknown