Circulating long and very long-chain saturated fatty acids and heart failure: Results from a large US cohort study

BACKGROUND Elevated saturated fatty acids (SFAs) have generally been associated with higher cardiovascular risk, whereas emerging evidence suggests that long- and very-long-chain SFAs (LVLSFAs) may be inversely associated with cardiometabolic outcomes. OBJECTIVE This study aimed to investigate the associations of circulating LVLSFAs with incident heart failure (HF) in a prospective US cohort. METHODS We conducted a prospective analysis of 6408 participants from the Multi-Ethnic Study of Atherosclerosis cohort (2002-2015). Plasma phospholipid fatty acids (FAs) were measured and expressed as % of total FAs. Cox proportional hazards models, adjusted for established risk factors, estimated hazard ratios (HRs) and 95% CIs for associations between LVLSFAs (as both continuous and quartile) and HF. RESULTS Over a median follow-up of 14 years, 320 cases of HF were identified. Significant inverse associations were observed between incident HF and a 1% increase in the concentration of SFAs (expressed as a percentage of total FAs) for C18:0 (0.91; 0.84-0.98), C20:0 (0.19; 0.06-0.57), and C22:0 (0.62; 0.44-0.87). Quartile analyses revealed that participants in the Q3 of C18:0 had a 30% lower risk of HF compared to the Q1 (0.70, 0.50-0.98). For C20:0 and C22:0, the strongest inverse associations were observed in the Q4 vs Q1, with HRs of 0.61 (0.43-0.84) and 0.62 (0.44-0.87), respectively. These associations were consistent across subgroups by sex, age, race, body mass index, smoking status, and hypertension, with a stronger inverse association for C18:0 among participants with diabetes (P interaction = .007). CONCLUSION These results highlight VLCSFAs as promising biomarkers for HF risk stratification and warrant further investigation into the underlying biological mechanisms.