Remnant Cholesterol, Not LDL Cholesterol, Is Associated With Incident Cardiovascular Disease

• Published in: Journal of the American College of Cardiology Vol. 76; no. 23; pp. 2712 - 2724
• Main Authors: Castañer, Olga, Pintó, Xavier, Subirana, Isaac, Amor, Antonio J., Ros, Emilio, Hernáez, Álvaro, Martínez-González, Miguel Ángel, Corella, Dolores, Salas-Salvadó, Jordi, Estruch, Ramón, Lapetra, José, Gómez-Gracia, Enrique, Alonso-Gomez, Angel M., Fiol, Miquel, Serra-Majem, Lluís, Corbella, Emili, Benaiges, David, Sorli, Jose V., Ruiz-Canela, Miguel, Babió, Nancy, Sierra, Lucas Tojal, Ortega, Emilio, Fitó, Montserrat
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.12.2020
• Subjects: Aged; Body Mass Index; Cardiovascular; cardiovascular disease; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; Cholesterol - blood; Cohort Studies; Diet, Mediterranean; Female; Humans; Lipoproteins - blood; Male; Middle Aged; non−HDL-cholesterol; Proportional Hazards Models; remnant cholesterol; Risk Factors; triglycerides; Triglycerides - blood; CVD; HDL-C; Remnant-C; cardiovascular disease; LDL-C; MACE; non−HDL-cholesterol; remnant cholesterol; MedDiet; triglycerides; BMI; TRL; Mediterranean diet; body mass index; low-density lipoprotein cholesterol; major adverse cardiovascular event; high-density lipoprotein cholesterol; triglyceride-rich lipoproteins
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2020.10.008

Genetic, observational, and clinical intervention studies indicate that circulating levels of triglycerides and cholesterol transported in triglyceride-rich lipoproteins (remnant cholesterol) can predict cardiovascular events. This study evaluated the association of triglycerides and remnant cholesterol (remnant-C) with major cardiovascular events in a cohort of older individuals at high cardiovascular risk. This study determined the baseline lipid profile and searched for major adverse cardiovascular events (MACEs) in the high-risk primary prevention PREDIMED (Prevención con Dieta Mediterránea) trial population (mean age: 67 years; body mass index: 30 kg/m2; 43% men; 48% with diabetes) after a median follow-up of 4.8 years. Unadjusted and adjusted Cox proportional hazard models were used to assess the association between lipid concentrations (either as continuous or categorical variables) and incident MACEs (N = 6,901; n cases = 263). In multivariable-adjusted analyses, triglycerides (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.06, per 10 mg/dl [0.11 mmol/l]; p < 0.001), non−high-density lipoprotein cholesterol (HDL-C) (HR: 1.05; 95% CI: 1.01 to 1.10, per 10 mg/dl [0.26 mmol/l]; p = 0.026), and remnant-C (HR: 1.21; 95% CI: 1.10 to 1.33, per 10 mg/dl [0.26 mmol/l]; p < 0.001), but not low-density lipoprotein cholesterol (LDL-C) or HDL-C, were associated with MACEs. Atherogenic dyslipidemia (triglycerides >150 mg/dl [1.69 mmol/l] and HDL-C <40 mg/dl [1.03 mmol/l] in men or <50 mg/dl [1.29 mmol/l] in women) was also associated with MACEs (HR: 1.44; 95% CI: 1.04 to 2.00; p = 0.030). Remnant-C ≥30 mg/dl (0.78 mmol/l) differentiated subjects at a higher risk of MACEs compared with those at lower concentrations, regardless of whether LDL-C levels were on target at ≤100 mg/dl (2.59 mmol/l). In overweight or obese subjects at high cardiovascular risk, levels of triglycerides and remnant-C, but not LDL-C, were associated with cardiovascular outcomes independent of other risk factors. [Display omitted]