Introduction: De novo lipogenesis (DNL) is an endogenous pathway for converting excess carbohydrates and proteins into fatty acids (FAs). While elevated DNL is linked to several metabolic abnormalities, little is known about associations of longitudinal changes in DNL FAs with incident congestive heart failure (CHF), a growing condition in older adults.
Methods: We investigated relations of longitudinal changes in DNL FAs, measured at year 0, year 6, and year 13, with incident CHF using serial measures of plasma phospholipid myristic acid (14:0), palmitic acid (16:0), 7-hexadecenoic acid (16:1n-9), palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), and cis-vaccenic acid (18:1n-7). Time-varying covariates were measured using standardized methods in 2,005 older adults with two or more FA measures and free of CHF at baseline. Incident CHF was centrally adjudicated using medical records. Risk was assessed by multivariable-adjusted Cox proportional hazards.
Results: During 14,628 person-years, 553 CHF events occurred. After multivariate adjustment, serial changes in 16:0, 16:1n-9, and 18:1n-7 were positively associated with incident CHF, with HRs (95% CI) for each 30% change in levels of 2.84 (1.50, 5.37), 1.16 (1.00, 1.33), and 1.42 (1.15, 1.77), respectively (Table). Findings were similar in sensitivity analyses excluding individuals with prevalent coronary heart disease (not shown). In analyses evaluating absolute, rather than changes in, DNL FA levels, the associations of 16:0, 16:1n-9, and 18:1n-7 with incident CHF were no longer statistically significant although with consistent directions of association (not shown). Neither changes nor absolute levels of 14:0, 16:1n-7, 18:0, and 18:1n-9 were associated with CHF.
Conclusion: Serial changes in plasma phospholipid 16:0, 16:1n-9, and 18:1n-7 were associated with an elevated risk of CHF in older adults. These results indicate that potential mechanisms of risk, especially related to DNL, deserve further investigation.