Red blood cell fatty acid patterns and acute coronary syndrome
Gregory C Shearer1, James V Pottala, John A Spertus
1Sanford Research/USD, Cardiovascular Health Research Center, Sioux Falls, SD, USA.
Insights
Red blood cell fatty acid (RBC-FA) profiles significantly improve acute coronary syndrome (ACS) risk prediction compared to standard factors alone. Combining RBC-FA profiles with standard risk factors offers the best discrimination for ACS cases.
Area of Science:
- Cardiovascular Disease Research
- Lipidomics
- Biomarker Discovery
Background:
- Coronary heart disease (CHD) risk assessment traditionally relies on standard risk factors.
- Novel lipidomic approaches, specifically red blood cell fatty acid (RBC-FA) profiles, are being explored for enhanced risk stratification.
- The diagnostic and prognostic utility of RBC-FA profiles in acute coronary syndrome (ACS) requires further elucidation.
Purpose of the Study:
- To evaluate the discriminatory power of RBC-FA profiles for acute coronary syndrome (ACS) cases versus controls.
- To compare the performance of RBC-FA profiles against established standard risk factors (SRF) in ACS discrimination.
- To assess the added value of incorporating RBC-FA profiles into existing risk prediction models.
Main Methods:
- Red blood cell fatty acid (RBC-FA) profiles were analyzed in 668 ACS cases and 680 matched controls.
- Multivariable logistic regression models were constructed using FA profiles (FA) and standard risk factors (SRF) on a derivation set and validated.
- Model performance was assessed using receiver operating characteristic (ROC) curves (c-statistics), misclassification rates, and calibration.
Main Results:
- RBC-FA profiles demonstrated superior discrimination of ACS cases compared to SRF (c-statistic 0.85 vs. 0.77, p=0.003).
- The addition of RBC-FA profiles significantly improved the combined model's discrimination (c-statistic 0.88 vs. 0.77, p<0.0001).
- The combined model achieved the lowest misclassification rate (20%) and acceptable calibration.
Conclusions:
- RBC-FA profiles significantly enhance the discrimination of ACS cases.
- Combining RBC-FA profiles with standard risk factors provides a more robust risk prediction model.
- Further research is warranted to explore the clinical utility of FA patterns in cardiovascular risk prediction.
Background:
Assessment of coronary heart disease (CHD) risk is typically based on a weighted combination of standard risk factors. We sought to determine the extent to which a lipidomic approach based on red blood cell fatty acid (RBC-FA) profiles could discriminate acute coronary syndrome (ACS) cases from controls, and to compare RBC-FA discrimination with that based on standard risk factors.
Methodology/Principal Findings:
RBC-FA profiles were measured in 668 ACS cases and 680 age-, race- and gender-matched controls. Multivariable logistic regression models based on FA profiles (FA) and standard risk factors (SRF) were developed on a random 2/3(rds) derivation set and validated on the remaining 1/3(rd). The area under receiver operating characteristic (ROC) curves (c-statistics), misclassification rates, and model calibrations were used to evaluate the individual and combined models. The FA discriminated cases from controls better than the SRF (c = 0.85 vs. 0.77, p = 0.003) and the FA profile added significantly to the standard model (c = 0.88 vs. 0.77, p<0.0001). Hosmer-Lemeshow calibration was poor for the FA model alone (p = 0.01), but acceptable for both the SRF (p = 0.30) and combined models (p = 0.22). Misclassification rates were 23%, 29% and 20% for FA, the SRF, and the combined models, respectively.
Conclusions/Significance:
RBC-FA profiles contribute significantly to the discrimination of ACS cases, especially when combined with standard risk factors. The utility of FA patterns in risk prediction warrants further investigation.
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