• Anette Varbo, Jacob J Freiberg, and Børge G Nordestgaard.
• Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
• Clin. Chem. 2015 Mar 1; 61 (3): 533-43.

BackgroundIncreased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD, myocardial infarction (MI), and all-cause mortality.MethodsWe compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years of complete follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died.ResultsCompared with participants with nonfasting remnant cholesterol <0.5 mmol/L (19.3 mg/dL), hazard ratios for IHD ranged from 1.3 (95% CI 1.1-1.5) for remnant cholesterol of 0.5-0.99 mmol/L (19.3-38.2 mg/dL) to 2.4 (1.9-2.9) for remnant cholesterol of ≥1.5 mmol/L (58 mg/dL) (P for trend <0.001). Compared with participants with LDL cholesterol <3.0 mmol/L (115.8 mg/dL), hazard ratios for IHD ranged from 1.3 (1.1-1.5) for LDL cholesterol of 3-3.99 mmol/L (115.8-154 mg/dL) to 2.3 (1.9-2.8) for LDL cholesterol of ≥5 mmol/L (193 mg/dL) (P < 0.001). Corresponding hazard ratios for MI ranged from 1.8 (1.4-2.3) to 3.4 (2.5-4.8) for remnant cholesterol (P < 0.001), and from 1.7 (1.4-2.2) to 4.7 (3.5-6.3) for LDL cholesterol (P < 0.001). Nonfasting remnant cholesterol concentrations were associated stepwise with all-cause mortality ranging from hazard ratio 1.0 (0.9-1.1) to 1.6 (1.4-1.9) (P < 0.001), whereas LDL cholesterol concentrations were associated with decreased all-cause mortality risk in a U-shaped pattern, with hazard ratios from 0.8 (0.7-0.8) to 0.9 (0.8-1.0) (P = 0.002). After mutual adjustment, LDL cholesterol best predicted MI, and remnant cholesterol best predicted all-cause mortality.ConclusionsBoth lipoproteins were associated equally with risk of IHD and MI; however, only nonfasting remnant cholesterol concentrations were associated stepwise with increased all-cause mortality risk.© 2015 American Association for Clinical Chemistry.

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