Clinical cardiologyOct 14, 2015

Remaining 'Bad' Cholesterol and Death Risk After Heart Attack: More Evidence for the High Cholesterol Paradox from the TRIUMPH Study

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 18, 2026

Abstract

After 2 years, 9% of 2465 acute myocardial infarction survivors died, with mortality decreasing as remnant lipoprotein cholesterol levels increased.

Mortality was 12.4% in the lowest tertile of remnant lipoprotein cholesterol (0-15 mg/dL), 8.5% in the middle tertile (16-23 mg/dL), and 6.8% in the highest tertile (24-120 mg/dL).
A 1-standard deviation increase in remnant lipoprotein cholesterol (11 mg/dL) was linked to a 24% lower risk of death (hazard ratio: 0.76).
A similar association was observed for intermediate-density lipoprotein cholesterol, where a 1-standard deviation increase (8 mg/dL) correlated with a lower risk of mortality (hazard ratio: 0.80).
Very-low-density lipoprotein cholesterol also showed a consistent pattern, with a 1-standard deviation increase (4 mg/dL) predicting a 26% reduction in mortality risk (hazard ratio: 0.74).
The findings suggest that higher levels of remnant lipoprotein cholesterol may be paradoxically associated with better survival outcomes after an acute myocardial infarction.

Simplified

BACKGROUND: Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that, like other apolipoprotein B-containing lipoproteins, are atherogenic. Prior observational studies suggest paradoxically better outcomes in hypercholesterolemic patients who sustain an acute myocardial infarction (AMI), one of several known recurrent risk paradoxes. To date, the association of directly measured remnant lipoprotein cholesterol (RLP-C) with survival after an AMI has not been examined.

HYPOTHESIS: Higher RLP-C levels may be paradoxically associated with lower mortality.

METHODS: We examined 2465 AMI survivors in a prospective, 24-center US study of AMI outcomes. Lipoprotein cholesterol subfractions were directly measured by ultracentrifugation. RLP-C was defined as intermediate-density lipoprotein cholesterol (IDL-C) + very-low-density lipoprotein cholesterol subfraction 3 (VLDL3 -C). Given a linear relationship between RLP-C and mortality, we examined RLP-C by tertiles and continuously. Cox regression hazard ratios (HRs) were adjusted for the Global Registry of Acute Coronary Events (GRACE) score and 23 other covariates.

RESULTS: Participants were age 58 ± 12 years (mean ± SD), and 68% were men. After 2 years of follow-up, 226 (9%) participants died. The mortality proportion was 12.4% in the lowest tertile of RLP-C (0-15 mg/dL), 8.5% in the middle tertile (16-23 mg/dL), and 6.8% in the highest tertile (24-120 mg/dL; P < 0.001). A 1-SD increase in RLP-C (11 mg/dL) predicted a 24% lower adjusted risk of 2-year mortality (HR: 0.76, 95% confidence interval [CI]: 0.64-0.91). Similar results were found for a 1-SD increase in IDL-C (HR per 8 mg/dL: 0.80, 95% CI: 0.67-0.96), VLDL3 -C (HR per 4 mg/dL: 0.74, 95% CI: 0.61-0.89), and very-low-density lipoprotein cholesterol (VLDL-C; HR per 8 mg/dL: 0.69, 95% CI: 0.55-0.85).

CONCLUSIONS: Higher RLP-C levels were associated with lower mortality 2 years after AMI despite rigorous adjustment for known confounders. Unknown protective factors or a lead-time bias likely explains the paradox.

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Funding

Competing interests

Conflicts of interest: None for KF, AAK, MJB, PHJ, TMM, EPH, FT. SSM and SRJ: listed as co-inventors on a pending patent filed by Johns Hopkins University for a method of low-density lipoprotein cholesterol estimation.

PubMed

Remaining 'Bad' Cholesterol and Death Risk After Heart Attack: More Evidence for the High Cholesterol Paradox from the TRIUMPH Study

Abstract

Full Text

Funding

Competing interests

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