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Randomized Controlled Trial
. 2020 Dec 8;76(23):2712-2724.
doi: 10.1016/j.jacc.2020.10.008.

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

Olga Castañer  1 , Xavier Pintó  2 , Isaac Subirana  3 , Antonio J Amor  4 , Emilio Ros  5 , Álvaro Hernáez  6 , Miguel Ángel Martínez-González  7 , Dolores Corella  8 , Jordi Salas-Salvadó  9 , Ramón Estruch  10 , José Lapetra  11 , Enrique Gómez-Gracia  12 , Angel M Alonso-Gomez  13 , Miquel Fiol  14 , Lluís Serra-Majem  15 , Emili Corbella  2 , David Benaiges  16 , Jose V Sorli  8 , Miguel Ruiz-Canela  7 , Nancy Babió  9 , Lucas Tojal Sierra  13 , Emilio Ortega  17 , Montserrat Fitó  18
Affiliations
Free article
Randomized Controlled Trial

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

Olga Castañer et al. J Am Coll Cardiol. .
Free article

Abstract

Background: 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.

Objectives: 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.

Methods: 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).

Results: 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).

Conclusions: 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.

Keywords: cardiovascular disease; non−HDL-cholesterol; remnant cholesterol; triglycerides.

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Conflict of interest statement

Author Disclosures This work was supported by grants of the Instituto de Salud Carlos III- FEDER (CB06/03/0017, CB06/03/0028, CD17/00122, JR17/00022, PI15/00047, and PI18/00020), Fundació La Marató de TV3 (201512.31), and Agència de Gestió d’Ajuts Universitaris i de Recerca (2017 BP 00021, 2017 SGR 222). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of the Instituto de Salud Carlos III, Madrid, Spain, and financed by the European Regional Development Fund. Dr. Salas-Salvadó was supported by ICREA under the ICREA Academia program. Dr. Pinto has received Advisory Board and lecture fees from Ferrer, Mylan, Sanofi, Amgen, and Rubió; has received advisory fees from Danone, Akcea, and Daiichi-Sankyo; and has received writing fees from Menarini and Esteve. Dr. Ros has received personal fees, grants, and nonfinancial support from the California Walnut Commission and Ferrer International; has received personal fees and nonfinancial support from Amarin, Danone, and Merck, Sharp & Dohme; has received personal fees and grants from Sanofi; and has received grants from Amgen and Pfizer. Dr. Salas-Salvadó has been a board member of and received personal fees from Instituto Danone Spain; has been a board member of and received grants from the International Nut and Dried Fruit Foundation; has received personal fees from Aguas Font Vella Lanjarón, and Danone S.A; and has received grants from Eroski Distributors. Dr. Estruch has been a board member of the Research Foundation on Wine and Nutrition, the Beer and Health Foundation, and the European Foundation for Alcohol Research; has received personal fees from KAO Corporation; has received lecture fees from Instituto Cerventes, Fundacion Dieta Mediterranea, Cerveceros de España, Lilly Laboratories, AstraZeneca, and Sanofi; and has received grants from Novartis, Amgen, Bicentury, and Grand Fountaine. Dr. Ortega has received lecture or Advisory Board fees from AMGEN, Lilly, Boehringer Ingelheim, Novo-Nordisk, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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