1.
Remnant Cholesterol, Not LDL Cholesterol, Is Associated With Incident Cardiovascular Disease.
Castañer, O, Pintó, X, Subirana, I, Amor, AJ, Ros, E, Hernáez, Á, Martínez-González, MÁ, Corella, D, Salas-Salvadó, J, Estruch, R, et al
Journal of the American College of Cardiology. 2020;(23):2712-2724
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.
2.
Amino acid change in the carbohydrate response element binding protein is associated with lower triglycerides and myocardial infarction incidence depending on level of adherence to the Mediterranean diet in the PREDIMED trial.
Ortega-Azorín, C, Sorlí, JV, Estruch, R, Asensio, EM, Coltell, O, González, JI, Martínez-González, MÁ, Ros, E, Salas-Salvadó, J, Fitó, M, et al
Circulation. Cardiovascular genetics. 2014;(1):49-58
-
-
Free full text
-
Abstract
BACKGROUND A variant (rs3812316, C771G, and Gln241His) in the MLXIPL (Max-like protein X interacting protein-like) gene encoding the carbohydrate response element binding protein has been associated with lower triglycerides. However, its association with cardiovascular diseases and gene-diet interactions modulating these traits are unknown. METHODS AND RESULTS We studied 7166 participants in the PREvención with DIeta MEDiterránea trial testing a Mediterranean diet (MedDiet) intervention versus a control diet for cardiovascular prevention, with a median follow-up of 4.8 years. Diet, lipids, MLXIPL polymorphisms, and cardiovascular events were assessed. Data were analyzed at baseline and longitudinally. We used multivariable-adjusted Cox regression to estimate hazard ratios for cardiovascular outcomes. The MLXIPL-rs3812316 was associated with lower baseline triglycerides (P=5.5×10(-5)) and lower hypertriglyceridemia (odds ratio, 0.73; 95% confidence interval [CI], 0.63-0.85; P=1.4×10(-6) in G-carriers versus CC). This association was modulated by baseline adherence to MedDiet. When adherence to MedDiet was high, the protection was stronger (odds ratio, 0.63; 95% CI, 0.51-0.77; P=8.6×10(-6)) than when adherence to MedDiet was low (odds ratio, 0.88; 95% CI, 0.70-1.09; P=0.219). Throughout the follow-up, both the MLXIPL-rs3812316 (P=3.8×10(-6)) and the MedDiet intervention (P=0.030) were significantly associated with decreased triglycerides. Likewise in G-carriers MedDiet intervention was associated with greater total cardiovascular risk reduction and specifically for myocardial infarction. In the MedDiet, but not in the control group, we observed lower myocardial infarction incidence in G-carriers versus CC (hazard ratios, 0.34; 95% CI, 0.12-0.93; P=0.036 and 0.90; 95% CI, 0.35-2.33; P=0.830, respectively). CONCLUSIONS Our novel results suggest that MedDiet enhances the triglyceride-lowering effect of the MLXIPL-rs3812316 variant and strengthens its protective effect on myocardial infarction incidence. CLINICAL TRIAL REGISTRATION URL: www.controlled-trials.com. Unique Identifier: ISRCTN35739639.