2019
DOI: 10.1001/jama.2018.20045
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Association of Triglyceride-Lowering LPL Variants and LDL-C–Lowering LDLR Variants With Risk of Coronary Heart Disease

Abstract: IMPORTANCE Triglycerides and cholesterol are both carried in plasma by apolipoprotein B (ApoB)-containing lipoprotein particles. It is unknown whether lowering plasma triglyceride levels reduces the risk of cardiovascular events to the same extent as lowering low-density lipoprotein cholesterol (LDL-C) levels. OBJECTIVE To compare the association of triglyceride-lowering variants in the lipoprotein lipase (LPL) gene and LDL-C-lowering variants in the LDL receptor gene (LDLR) with the risk of cardiovascular dis… Show more

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Cited by 540 publications
(407 citation statements)
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“…MR study also suggested that LDL-C had a causal effect on CHD [36], which was consistent with our results. Similar results were found in TG [38]. Since TC included LDL-C, we assumed that the causal effects between TC and CHD might likely due to the effect of LDL-C. Epidemiological studies had repeatedly indicated that HDL-C was inversely correlated with CHD risk.…”
Section: Discussionsupporting
confidence: 76%
“…MR study also suggested that LDL-C had a causal effect on CHD [36], which was consistent with our results. Similar results were found in TG [38]. Since TC included LDL-C, we assumed that the causal effects between TC and CHD might likely due to the effect of LDL-C. Epidemiological studies had repeatedly indicated that HDL-C was inversely correlated with CHD risk.…”
Section: Discussionsupporting
confidence: 76%
“…Furthermore, in analyses using generalized linear models to estimate relative risks (RRs) using logbinomial regression and a log link function, the RR associated with lifetime exposure to 38.67-mg/dL lower LDL-C and 10-mm Hg lower SBP was very similar to the OR estimated using both logistic regression or a logit-binomial regression (RR, 0.24; 95% CI, 0.19-0.29; P < .001). Because the associations of LDL-C with cardiovascular disease may be mediated by changes in the concentration of circulating LDL particles as measured by apolipoprotein B (apo B), rather than by the concentration of cholesterol carried by those particles as measured by plasma LDL-C, all analyses were repeated using directly measured changes in apo B rather than changes in LDL-C. 24 In these analyses, combined exposure to 30-mg/dL lower apo B and 10-mm Hg lower SBP was associated with an OR of 0.20 for major coronary events (95% CI, 0.18-0.21; P < .001) (eTable 6 in the Supplement).…”
Section: Sensitivity Analysesmentioning
confidence: 99%
“…In addition to the well established role of LDL-C [35], the contribution of triglycerides (TG) to a raised CV risk has become clear both after long-term prospective studies [36] and a recent mendelian randomization analysis [37]. TG-rich lipoproteins may penetrate the arterial wall and are retained within the sub-endothelial space; after oxidative modification they may lead to the development of atherosclerotic plaques.…”
Section: Lipid Mediated-inflammationmentioning
confidence: 99%