May 16, 2026Journal of the American College of Cardiology
Remnant Cholesterol as a Causal Risk Factor for Ischemic Heart Disease
Key result
Higher remnant cholesterol linked to ~2.8-fold higher ischemic heart disease risk independent of HDL.
- OR 2.8
- 95% CI 1.9 to 4.2
- n=73,513
Why the study?
Is elevated nonfasting remnant cholesterol a causal risk factor for ischemic heart disease independent of reduced HDL cholesterol?
Population
73,513 subjects from Copenhagen, including 11,984 with ischemic heart disease diagnosed between 1976 and 2010.
Design
Cohort, Mendelian randomization
Follow-up
between 1976 and 2010
Authors
Discussion
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Implication
Elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease, independent of reduced HDL cholesterol.
Key Points
- This study tests the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease, independent of HDL cholesterol levels.
- Analyzed 73,513 genotyped subjects from Copenhagen, with 11,984 diagnosed with ischemic heart disease.
- Selected fifteen genetic variants to impact remnant and HDL cholesterol and utilized a Mendelian randomization design.
- Causal odds ratio for 1 mmol/l increase in remnant cholesterol was 2.8 (95% CI: 1.9 to 4.2).
- For the nonfasting remnant to HDL cholesterol ratio, causal odds ratio was 2.9 (95% CI: 1.9 to 4.6).
- For HDL cholesterol, causal odds ratio showed a decrease for every 1 mmol/l (39 mg/dl) decrease at 0.7 (95% CI: 0.4 to 1.4).
Study Design
Type
Observational (n=73,513)
Randomization
Mendelian randomization
Structured PICO
Is elevated nonfasting remnant cholesterol a causal risk factor for ischemic heart disease independent of reduced HDL cholesterol?
P
Population
73,513 genotyped subjects from Copenhagen, including 11,984 with ischemic heart disease diagnosed between 1976 and 2010.
E
Exposure
15 genetic variants affecting nonfasting remnant cholesterol, HDL cholesterol, or LDL cholesterol (Mendelian randomization design)
O
Outcome
Ischemic heart diseasehard clinical
Main Result
Odds Ratio: 2.8 (95% CI 1.9–4.2)
Elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease, independent of reduced HDL cholesterol.
Limitations
- Pleiotropic effects of the genetic variants studied cannot be totally excluded
Cite This Study
Varbo et al. (2012) conducted an observational in Ischemic heart disease (n=73,513). Elevated nonfasting remnant cholesterol vs. Lower nonfasting remnant cholesterol was evaluated on Ischemic heart disease (OR 2.8, 95% CI 1.9 to 4.2). A 1 mmol/l genetic increase in nonfasting remnant cholesterol was associated with a 2.8-fold causal risk for ischemic heart disease (OR 2.8; 95% CI 1.9 to 4.2), independent of reduced HDL.