Abstract MP005: Plasma Phospholipid Concentration of Palmitoleic Acid is Associated with an Increased Risk of Heart Failure in Male Physicians

Background: Plasma fatty acids in the de novo lipogenesis including plamitoleic acid have been associated with a higher risk of blood pressure and type 2 diabetes (two major risk factors for heart failure -HF). However, limited data are available on the association between plasma levels of palmitoleic acid and HF risk. Objective: To test the hypothesis that plasma palmitoleic acid concentration is associated with an increased risk of HF. In a secondary aim, we examined whether stearoyl-CoA desaturase indices, cis -vaccenic acid, and oleic acid were associated with HF risk. Methods: We used a prospective nested case-control design for this project among participants of the Physicians' Health Study. For each of the 788 HF cases, we used the risk set method to randomly select a control among all eligible controls at the time of the index case occurrence. Each control was matched on age, year of birth, race, and time of blood collection of the index case. We used gas chromatography to measure plasma phospolipid fatty acids on frozen blood samples collected between 1997 and 2001 on study subjects free of HF. HF events were ascertained via annual follow-up questionnaires and validated in a subsample through review of medical records (positive predictive value 91% -- 50 confirmed out of 55 self-reported cases). Results: Mean age was 58.7 ± 8.0 years. In a conditional logistic regression controlling for matching factors, odds ratios (95% CI) for HF were 1.0 (reference), 1.00 (0.75–1.33), 1.22 (0.91–1.64), and 1.48 (1.10–1.99) across consecutive quartiles of palmitoleic acid (p trend 0.005). Additional adjustment for body mass index, smoking, alcohol intake, exercise, prevalent diabetes and coronary disease, marine omega-3 fatty acids, hypertension treatment, and plasma stearic acid did not alter the results [OR: 1.0, 1.00 (0.72–1.37), 1.23 (0.89–1.72), and 1.51 (1.06–2.15) from the lowest to the highest quartile, p trend 0.014]. When analyzed as a continuous variable, each standard deviation increase of plasma palmitoleic acid was associated with a 15% higher odds of HF [OR: 1.15 (1.01–1.31)] in a multivariable adjusted model. In a secondary analysis, plasma phospholipid oleic acid (18:1n−9) and cis-vaccenic acid (18:1n−7) were not associated with the odds of HF. Indices of stearoyl-CoA desaturase-1 (16:1n−7 to 16:0 ratio) and desaturase-2 (18:1n−9 to 18:0 ratio) were not significantly associated with the odds of HF. Conclusion: Our data showed that plasma concentration of palmitoleic acid is positively associated with the risk of HF in male physicians. This suggests that fatty acids in the de novo lipogenesis may play a role in the development of HF.