Elevated habitual levels of palmitic acid (16:0), as well as increases over time in the levels of 16:0, 7-hexadecenoic acid (16:1n-9) and vaccenic acid (18:1n-7), were found to be associated with incident heart failure (HF) in older American adults, according to study results published in the Journal of the American Heart Association.

Palmitic acid, 7-hexadecenoic acid, and vaccenic acid are generated by de novo lipogenesis (DNL). Excessive conversion of dietary starch, sugar, alcohol, and protein into specific fatty acids (FAs) via DNL has been linked to several metabolic abnormalities. However, the relationship between increased DNL (and related FA biomarker levels) and new onset HF remains unclear.

This was a subanalysis of the Cardiovascular Health Study, a community-based prospective trial in which 4249 individuals age ≥65 years without HF at baseline (mean age, 75.6±5.3 years; 59.6% women; 84.9% white) were enrolled. Plasma phospholipid FA levels were measured at baseline, 6, and 13 years with gas chromatography. Central adjudication of incident HF was achieved using medical records. Associations between HF risk and habitual FA levels (with long-term exposure assessed via cumulative updating), as well as FA level changes over time, were prospectively evaluated.


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There were 1304 cases of incident HF during the follow-up period (maximum 22.1 years; 45,030 person-years). A positive association was established between incident HF and habitual 16:0 levels (interquintile hazard ratio [HR], 1.17; 95% CI, 1.00-1.36; Ptrend =.049), as well as changes in the level of 16:0 over time (HR, 1.26; 95% CI, 1.03-1.55; P =.03). In addition, changes over time in the levels of 16:1n-9 (HR, 1.36; 95% CI, 1.13-1.62; P =.001) and 18:1n-7 (HR, 1.43; 95% CI, 1.18-1.72; P <.001) were also associated with HF risk.

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No significant associations were detected between incident HF and habitual or changes in levels in other DNL FAs (ie, myristic acid, stearic acid, palmitoleic acid, and oleic acid).

Study strengths include excellent retention rates, a large sample size, the use of serial FA measurements that allowed objective FA concentration measurements, adequate power to detect associations, prospective standardized data collection, and minimization of confounding and misclassification.

Study limitations include non-generalizability to other races or younger populations, potential residual confounding, a lack of adjustment for multiple comparisons, and the possibility that circulating FAs were from dietary intake, not DNL.

“If these associations prove to be causal, DNL and its specific fatty acid products could be targeted to reduce [the] risk [for] heart failure, for example, by minimizing dietary refined starch, sugars, and alcohol or through novel molecular interventions,” noted the authors. They recommended that future research explore the biologic mechanisms linking HF with DNL FA levels.

Disclosures: Mozaffarian reports significant research funding from the National Institutes of Health and the Gates Foundation; significant personal fees from Acasti Pharma; significant relationships with scientific advisory boards of Elysium Health (with stock options) and DayTwo; modest personal fees from GOED, Nutrition Impact, Pollock Communications, Bunge, Indigo Agriculture, Amarin, Cleveland Clinic Foundation, America’s Test Kitchen, and Danone; modest relationship on scientific advisory board of Omaha Health; and modest chapter royalties from UpToDate. Reference

References

Lee Y, Lai HTM, Otto MCDO, et al. Serial biomarkers of de novo lipogenesis fatty acids and incident heart failure in older adults: the Cardiovascular Health Study. J Am Heart Assoc. 2020;9(4):1-12. doi:10.1161/jaha.119.014119