Abstract P265: Plasma Phospholipid Trans Fatty Acids, Cardiovascular Diseases, and Total Mortality: The Cardiovascular Health Study

Abstract

Introduction: Whereas trans fatty acids (TFAs) have generally been evaluated as a group, emerging evidence suggests that trans18:2, but not trans18:1 or trans16:1, isomers are especially adverse for health. Few studies have investigated how biomarkers of different TFA isomers relate to CVD or total mortality. Objective: To examine prospective associations of circulating trans16:1n9 (16:1n9t), total trans18:1 (18:1t, the sum of 18:1n5-12), and n9cis/n6trans, n9trans/n6cis, and n9trans/n6trans 18:2 (18:2ct, 18:2tc, 18:2tt) with incident CVD events and total mortality. Methods: We prospectively evaluated 2,788 adults in the Cardiovascular Health Study, age 72±5y, free of prevalent CVD, and having plasma phospholipid TFA measures from blood stored in 1992. CVD events and mortality were centrally adjudicated through 2010, including total mortality, CVD death, CHD death, nonfatal MI (NFMI), and ischemic stroke. Risk associated with each TFA was assessed using Cox proportional hazards adjusting for sociodemographics, lifestyle, dietary habits, prevalent diseases, and the 5 TFA mutually. Results: During 31,863 person-years, 1,681 deaths occurred including 581 CVD and 373 CHD deaths; as well as 383 NFMI and 328 ischemic strokes. 18:2ct was associated with higher CVD mortality (quintile 5 vs. 1 HR 1.48, 95%CI 0.98-2.23, p trend 0.04), but not total mortality or nonfatal CVD events. 18:2tc was related to higher NFMI (HR 1.69, 95%CI 1.06-2.69, p trend<0.01), while 18:2tt was not significantly associated with mortality or CVD endpoints. Similarly, 16:1n9t was positively associated with NFMI (HR 2.96, 95%CI 1.80-4.88, p trend<0.01), and ischemic stroke (HR 2.00, 95%CI 1.19-3.36, p trend 0.02), but not mortality endpoints. 18:1t was associated with lower CVD (HR 0.52, 95%CI 0.34-0.79, p trend=0.01) and CHD (HR 0.49, 95%CI 0.29-0.84, p trend 0.02) mortality, but these findings for 18:1t were substantially (~50%+) weakened when analyses did not mutually adjust for all 5 TFA, which were intercorrelated (r -0.08 to 0.78). Conclusions: Specific 18:2 TFA isomers, 18:2ct and 18:2tc but not 18:2tt, as well as 16:1n9t are prospectively associated with higher incidence of CVD events. 18:1t is associated with lower CVD risk, perhaps owing at least partly to co-adjustment for multiple correlated TFAs. The general specificity of all findings for CVD events, rather than total mortality or non-CVD mortality, is consistent with adverse physiologic effects of TFA on CVD risk factors. These results highlight the need for further investigation of effects and determinants of specific TFA subclasses and isomers.