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Updated: Jun 29, 2025
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Lipoprotein Insulin Resistance Score and Mortality Risk Stratification in Heart Failure
Sarah Turecamo1, Carolina G Downie1, Anna Wolska2
1Heart Disease Phenomics Laboratory, Epidemiology and Community Health Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Insights
In heart failure patients, a higher lipoprotein insulin resistance (LP-IR) score is linked to reduced mortality. This inverse relationship may be influenced by smaller high-density lipoprotein (HDL) particle size.
Area of Science:
- Cardiology
- Metabolic Syndrome
- Lipidomics
Background:
- Total serum cholesterol is paradoxically linked to lower mortality in heart failure patients.
- Investigating lipoprotein subfractions may clarify this inverse cholesterol-mortality association.
Purpose of the Study:
- To examine the relationship between the lipoprotein insulin resistance (LP-IR) score, derived from lipoprotein subfractions, and all-cause mortality in a heart failure cohort.
- To identify specific lipoprotein parameters contributing to the observed association.
Main Methods:
- Prospective community-based cohort study of heart failure patients (2003-2012) with vital status assessed through 2021.
- Lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy.
- LP-IR score calculated using a composite algorithm; associations with mortality analyzed using Cox proportional hazards regression.
Main Results:
- A one-standard deviation increase in LP-IR score was associated with a 7% reduction in mortality (HR 0.93; 95% CI, 0.97-0.99).
- Smaller mean high-density lipoprotein (HDL) particle size was significantly associated with lower mortality (HR per 1-SD decrement = 0.83; 95% CI, 0.78-0.89).
Conclusions:
- The LP-IR score demonstrates an inverse association with mortality in heart failure patients.
- This protective effect may be primarily driven by smaller HDL particle size.
Background:
Higher total serum cholesterol is associated with lower mortality in heart failure. Evaluating associations between lipoprotein subfractions and mortality among people with heart failure may provide insights into this observation.
Methods:
We prospectively enrolled a community cohort of people with heart failure from 2003 to 2012 and assessed vital status through 2021. Plasma collected at enrollment was used to measure lipoprotein subfractions via nuclear magnetic resonance spectroscopy. A composite score of 6 lipoprotein subfractions was generated using the lipoprotein insulin resistance index (LP-IR) algorithm. Using covariate-adjusted proportional hazards regression models, we evaluated associations between LP-IR score and all-cause mortality.
Results:
Among 1382 patients with heart failure (median follow-up 13.9 years), a one-standard-deviation (SD) increment in LP-IR score was associated with lower mortality (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.97-0.99). Among LP-IR parameters, mean high-density lipoprotein (HDL) particle size was significantly associated with lower mortality (HR per 1-SD decrement in mean HDL particle size = 0.83; 95% CI, 0.78-0.89), suggesting that the inverse association between LP-IR score and mortality may be driven by smaller mean HDL particle size.
Conclusions:
LP-IR score was inversely associated with mortality among patients with heart failure and may be driven by smaller HDL particle size.
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