Plasma Oleic-to-Stearic Acid Ratio and Future Heart Failure Risk: From MESA

Abstract

Abstract Objectives Evidence for a role of delta-9-desaturase plasma (D9D) in heart failure (HF) is limited. We aimed to evaluate whether a biomarker for its activity, the oleic-to-stearic acid ratio, is associated with future heart failure risk in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort. Methods A total of 6562 participants aged 45 to 84 yr. old had their fatty acids measured at baseline. Cox regression was used to model the association between oleic-to-stearic acid ratio and risk for HF, including HF with reduced ejection fraction (EF) and HF with preserved EF, adjusting for potential covariates, including age, sex, race, study center, body mass index, diabetes mellitus, blood pressure, C-reactive protein, albuminuria, and lead fatty acid for non-oleic and non-stearic acid clusters. Mediation effects through hypertension, and diabetes were estimated using the causal mediation analysis. Results After a median of 7.1 years follow-up, 184 incident HF cases were documented, with 64 HF with reduced EF, and 72 HF with preserved EF and 48 with unknown EF status. Oleic-to-stearic acid ratio was lower in HF-free participants (0.57 ± 0.13) compared to participants with HF (0.60 ± 0.12) (P = 0.002) and was associated with a higher risk for HF incidence. Hazard ratio for HF was 4.81 (95%Confidence Interval: 1.46, 15.88) per unit increase in oleic-to-stearic ratio in the fully adjusted model. Secondary analysis showed no dependence on HF type. Mediation analysis showed hypertension and diabetes were not mediating. Conclusions This study indicates that increased delta-9-desaturase activity predicts future HF risk, in a manner not mediated by either hypertension or diabetes. Funding Sources This work was funded by grant from the National Heart, Lung, and Blood Institute.