Associations of serum nonesterified fatty acids with coronary heart disease mortality and nonfatal myocardial infarction: the CHS (cardiovascular health study) cohort

Authors: HUANG, NEIL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BUZKOVA, PETRA - University Of Washington; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DJOUSSE, LUC - Brigham & Women'S Hospital; HIRSCH, CALVIN - University Of California, Davis; KIZER, JORGE - University Of California; LONGSTRETH, W - University Of Washington; MUKAMAL, KENNETH - Beth Israel Deaconess Medical Center; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of the American Heart Association
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/3/2021
Publication Date: 3/16/2021
Citation: Huang, N.K., Buzkova, P., Matthan, N., Djousse, L., Hirsch, C.H., Kizer, J.R., Longstreth, W.T., Mukamal, K., Lichtenstein, A.H. 2021. Associations of serum nonesterified fatty acids with coronary heart disease mortality and nonfatal myocardial infarction: the CHS (cardiovascular health study) cohort. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.120.019135.
DOI: https://doi.org/10.1161/JAHA.120.019135

Interpretive Summary: Significant associations have been reported between serum total non-esterified fatty acid (NEFA) concentrations and coronary heart disease mortality and incident non-fatal myocardial infarction in some prospective cohort studies. Little is known about whether serum NEFA individual or sub-classes relate to coronary heart disease mortality and non-fatal myocardial infarction. Participants from the Cardiovascular Health Study participants were used to address this gap. Individual NEFAs and the 5 sub-classes were assessed relative to coronary heart disease composite (coronary heart disease mortality and non-fatal MI), coronary heart disease mortality and incident non-fatal MI. These data indicate in Cardiovascular Health Study participants, no significant associations between NEFA and coronary heart disease composite were observed. Two diet-derived NEFAs, dihomo-y-linolenic and elaidic acids, were positively associated with coronary heart disease mortality and non-fatal myocardial infarction, respectively, suggesting potential biomarkers for risks of coronary heart disease mortality and non-fatal myocardial infarction.

Technical Abstract: BACKGROUND: Significant associations have been reported between serum total nonesterified fatty acid (NEFA) concentrations and coronary heart disease (CHD) mortality and incident nonfatal myocardial infarction (MI) in some prospective cohort studies. Little is known about whether individual or subclasses (saturated, polyunsaturated [n-6 and n-3], and trans fatty acids) of serum NEFAs relate to CHD mortality and nonfatal MI. METHODS AND RESULTS: CHS (Cardiovascular Health Study) participants (N=1681) who had no history of MI, angina, or re-vascularization or were free of MI at baseline (1996-1997) were included. NEFAs were quantified using gas chromatography. Cox regression analysis was used to evaluate associations of 5 subclasses and individual NEFAs with CHD composite (CHD mortality and nonfatal MI), CHD mortality, and incident nonfatal MI. During a median follow-up of 11.7 years, 266 cases of CHD death and 271 cases of nonfatal MI occurred. In the fully adjusted model, no significant associations were identified between individual NEFA and CHD composite. Exploratory analyses indicated that lauric acid (12:0) was negatively associated (hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; P=0.0328) and dihomo-y-linolenic acid (20:3n-6) was positively associated with CHD mortality (HR, 1.34; 95% CI, 1.02-1.76; P=0.0351). Elaidic acid (18:1n-7t) was positively associated with incident nonfatal MI (HR, 1.46; 95% CI, 1.01-2.12; P=0.0445). No significant associations were observed for NEFA subclass and any outcomes. CONCLUSIONS: In CHS participants, 2 NEFAs, dihomo-y-linolenic and elaidic acids, were positively associated with CHD mortality and nonfatal MI, respectively, suggesting potential susceptibility biomarkers for risks of CHD mortality and nonfatal MI.