Remnant cholesterol as a causal risk factor for ischemic heart disease.
By A. Varbo, M. Benn, A. Tybjærg-Hansen, A. Jørgensen, R. Frikke-Schmidt, Børge G. Nordestgaard. Journal of the American College of Cardiology, 2013
1,030 citations recorded by the source corpus.
OBJECTIVES The aim of this study was to test the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease independent of reduced high-density lipoprotein (HDL) cholesterol. BACKGROUND Elevated remnant cholesterol is associated with elevated levels of triglyceride-rich lipoproteins and with reduced HDL cholesterol, and all are associated with ischemic heart disease. METHODS A total of 73,513 subjects from Copenhagen were genotyped, of whom 11,984 had ischemic heart disease diagnosed between 1976 and 2010. Fifteen genetic variants were selected, affecting: 1) nonfasting remnant cholesterol alone; 2) nonfasting remnant cholesterol and HDL cholesterol combined; 3) HDL cholesterol alone; or 4) low-density lipoprotein (LDL) cholesterol alone as a positive control. The variants were used in a Mendelian randomization design. RESULTS The causal odds ratio for a 1 mmol/l (39 mg/dl) genetic increase of nonfasting remnant cholesterol was 2.8 (95% confidence interval [CI]: 1.9 to 4.2), with a corresponding observational hazard ratio of 1.4 (95% CI: 1.3 to 1.5). For the ratio of nonfasting remnant cholesterol to HDL cholesterol, corresponding values were 2.9 (95% CI: 1.9 to 4.6) causal and 1.2 (95% CI 1.2 to 1.3) observational for a 1-U increase. However, for HDL cholesterol, corresponding values were 0.7 (95% CI: 0.4 to 1.4) causal and 1.6 (95% CI: 1.4 to 1.7) observational for a 1 mmol/l (39 mg/dl) decrease. Finally, for LDL cholesterol, corresponding values were 1.5 (95% CI: 1.3 to 1.6) causal and 1.1 (95% CI: 1.1 to 1.2) observational for a 1 mmol/l (39 mg/dl) increase. CONCLUSIONS A nonfasting remnant cholesterol increase of 1 mmol/l (39 mg/dl) is associated with a 2.8-fold causal risk for ischemic heart disease, independent of reduced HDL cholesterol. This implies that elevated cholesterol content of triglyceride-rich lipoprotein particles causes ischemic heart disease. However, because pleiotropic effects of the genetic variants studied cannot be totally excluded, these findings need to be confirmed using additional genetic variants and/or randomized intervention trials.
Subfields: Endocrinology, Diabetes and Metabolism, Hematology, Surgery
View Paper: https://www.semanticscholar.org/paper/7d48e7fd9e19612bb5ea6281a8e1d4660813a4c7
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Citations in the corpus
- National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report. (2015, background): “When triglycerides are between 200 and 499 mg/dL, the targets of therapy are non–HDL-C and LDL-C.”
- National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2. (2015, background): “7 mg/dL (1 mmol/L) difference in VLDL-C (referred to as remnant cholesterol by the investigators) was associated with a CHD risk difference of 182%.(9) These findings are consistent with a causal role for VLDL-C (or some variable closely correlated with VLDL-C) in ASCVD event risk, and support the i”
- Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation (2013, background): “We have previously demonstrated that elevated remnant cholesterol is causally associated with increased risk of IHD and that this association is independent of low high-density lipoprotein cholesterol levels.(1,2) The causal association of nonfasting remnant cholesterol with low-grade inflammation o”
- Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology. (2016, neutral): “Genetics The most difficult problem to solve in understanding potential causality between elevated triglyceride-rich lipoproteins and ASCVD is to deal with pleiotropy, that is, most specifically that high triglycerides are associated with low HDL cholesterol on a population level.(23) In other words”
- 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. (2016, background): “Recent data from genetic studies utilizing a Mendelian randomization design have consistently linked both non-fasting TG levels as well as remnant cholesterol to increased risk of CVD events and all-cause mortality.(86,107) Remnant cholesterol is a calculated parameter in these studies and equals TC”