VLDL cholesterol explains half of MI risk from apoB-containing lipoproteins
VLDL Cholesterol Accounts for One-Half of the Risk of Myocardial Infarction Associated With apoB-Containing Lipoproteins
Literature - Balling M, Afzal S, Varbo A, et al. - J Am Coll Cardiol 2020;76:2725–35, doi.org/10.1016/j.jacc.2020.09.610Introduction and methods
Although many observational and genetic studies showed that higher levels of triglyceride-rich remnants or very low-density lipoproteins (VLDLs) are associated with increased risk of ASCVD [1-6], the mechanism of the relationship is not fully understood. It has been hypothesized that triglyceride-rich remnants cross the arterial wall and hydrolysis of triglycerides may induce inflammation in the intima resulting in atherosclerosis and ASCVD. Randomized clinical trial evaluating triglyceride-lowering therapies have shown inconsistent findings [7-11].
This study examined which part of myocardial infarction (MI) risk from apoB-containing lipoproteins can be explained by VLDL cholesterol and triglycerides. Measurements of plasma apoB and cholesterol and triglyceride content of VLDL, IDL and LDL were used of 25,480 individuals in the Copenhagen General Population study.
The Copenhagen General Population Study is an ongoing study started in 2003 and is a cohort reflecting the general population. This analysis excluded individuals with MI before baseline and those receiving lipid-lowering therapy. Cholesterol and triglyceride content of VLDL, IDL and LDL were measured using NMR spectroscopy platform. Lipoprotein(a) was included in LDL. Median follow-up was 11 years (range 0 to 13 years).
Main results
- Multivariable-adjusted HRs increased with higher levels of VLDL cholesterol, VLDL triglycerides, IDL cholesterol and LDL cholesterol. Risk estimates for VLDL triglycerides reached a plateau from ~2 mmol/L (`177 mg/dL).
- Multivariable-adjusted HRs for MI were 2.07 (95%CI: 1.81 to 2.36) for VLDL, 5.38 (95%CI: 3.73 to 7.75) for IDL, 1.86 (95%CIL 1.62 to 2.14) for LDL and 1.49 (95%CI: 1.39 to 1.60) for non-HDL per 1 mmol/L higher cholesterol content.
- Risk estimates for 1 mmol/L higher triglycerides content were 1.19 (95%CI: 1.14 to 1.25) for VLDL triglycerides and 1.17 (95%CI: 1.12 to 1.22) for non-HDL triglycerides.
- For 1 g/L higher concentration of apoB, multivariable -adjusted HR for MI was 2.21 (95%CI: 1.90 to 2.58).
- In a Cox regression analysis adjusted for sex and age with a step-up model, HR was 1.77 (95%CI: 1.52 to 2.05) for 1 mmol/L higher VLDL cholesterol, 1.11 (95%CI: 1.07 to 1.23) for 10 mmHg higher SBP, 1.31 (95%CI: 1.18 to 1.46) for smokers (vs. non-smokers) and 1.32 (95%CI: 1.19 to 1.46) for 1 mmol/L higher IDL + LDL cholesterol. Forcing VLDL triglycerides in the model showed HR of 0.98 (95%CI: 0.89 to 2.46) for 1 mmol/L higher VLDL triglycerides.
- VLDL cholesterol explained 50% (95%CI: 22% to 78%, P=0.001) and IDL + LDL cholesterol 29% (95%CI: 13% to 45%, P<0.001) of risk in the association between apoB-containing lipoproteins and MI. VLDL triglycerides did not explain significant risk (8%, 95%CI: 0% to 24%, P=0.35). Remnant cholesterol explained 10% (95%CI: 0% to 26%, P=0.19).
Conclusion
Cholesterol in VLDL explained 50% of the risk in the association between apoB-containing lipoproteins and MI, whereases VLDL triglycerides did not contribute to this risk.
References
1. Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet 2014;384:
626–35.
2. Nordestgaard BG, Abildgaard S, Wittrup HH, Steffensen R, Jensen G, Tybjaerg-Hansen A. Heterozygous lipoprotein lipase deficiency: frequency in the general population, effect on plasma lipid levels, and risk of ischemic heart disease. Circulation 1997;96:1737–44.
3. Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation 1999;
99:2901–7.
4. Sarwar N, Sandhu MS, Ricketts SL, et al. Triglyceride- mediated pathways and coronary disease:
collaborative analysis of 101 studies. Lancet 2010;375:1634–9.
5. Do R, Willer CJ, Schmidt EM, et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet 2013; 45:1345–52.
6. Varbo A, Benn M, Tybjaerg-Hansen A, Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013;61:427–36.
7. Oliver MF, Heady JA, Morris J, Cooper J. A cooperative trial in the primary prevention of ischaemic heart disease using clofibrate. Report from the Committee of Principal Investigators. Br Heart J 1978;40:1069–118.
8. GISSI-Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999;354:447–55.
9. Meade T, Zuhrie R, Cook C, Cooper J. Bezafibrate in men with lower extremity arterial disease: randomised controlled trial. BMJ 2002;325:1139.
10. Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005;366:1849–61.
11. Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007;369:1090–8.
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