Altered fatty acid metabolism in patients with angiographically documented coronary artery disease

Abstract

Plasma lipids and fatty acids have been linked to coronary artery disease (CAD), and linoleic acid deficiency has been proposed as a risk factor for cardiovascular disease, but few studies have considered their multivariate effects or found the biochemical shifts associated with abnormal fatty acid metabolism or essential fatty acid (EFA) deficiency. We studied fatty acid patterns associated with CAD using high-resolution capillary column gas-liquid chromatography to analyze fasting plasma from 47 patients with angiographically documented CAD and 56 reference subjects. CAD patients exhibited a shift in fatty acid metabolism similar to that associated with EFA-deficient patients. Compared with reference subjects, CAD patients had (1) reduced percentages of polyunsaturated fatty acids ([PUFA] 45% v 50%, P < .001), (2) increased monounsaturated fatty acids (26% v 22%, P < .001), (3) higher ratios of Mead (20:3ω9) to arachidonic (20:4ω6) acid (0.016 v 0.013, P < .04), (4) increased levels of 16:1ω7 (2.10% v 1.55%, P < .001), and (5) higher concentrations of total fatty acids (356 v 284 mg/dL, P < .001), saturated fatty acids (101 v 75 mg/dL, P < .001), monounsaturated fatty acids (91 v 63 mg/dL, P < .001), PUFA (159 v 143 mg/dL, P < .01), 20:3ω9 (0.5 v 0.3 mg/dL, P < .01) and 16:1ω7 (7.7 v 4.5 mg/dL, P < .01). On indices of EFA status that depend on percentages or ratios of fatty acids or on the production of abnormal fatty acids, CAD patients were between severely EFA-deficient patients and healthy subjects, a state referred to as EFA insufficiency. Patients had metabolic shifts toward increased production of monounsaturated fatty acids and increased ratios of derivatives to precursors of ω6 fatty acids, shifts that occur when cells are EFA-deficient. Levels of EFAs were negatively correlated with levels of saturated and monounsaturated fatty acids. The percentage of 18:2ω6 was positively correlated with high-density lipoprotein (HDL) cholesterol and the ratio of HDL to total cholesterol ( r = .58, P < .001, and r = .61, P < .001, respectively) and negatively correlated with triglycerides and total cholesterol ( r = .61, P < .001, and r = −.24, P < .01, respectively). Opposite correlations with these parameters were observed with saturated and monounsaturated fatty acids. Saturated fatty acids, total cholesterol, and indicators of EFA deficiency increased and the HDL to total cholesterol ratio and PUFA decreased the probability of CAD as measured by multivariate linear regression. Reduced plasma percentages of EFAs are associated with CAD and with increased risk for CAD as measured by lipid levels. When plasma EFA percentages decline, monounsaturated fatty acids increase, and the increase is associated with reduced HDL to total cholesterol ratios ( r = −.64, P < .001). Relative EFA insufficiency is a condition with normal or increased whole-plasma concentrations of lipids and fatty acids, reduced concentrations of EFAs in plasma lipid fractions (reduced plasma % of EFAs), and increased plasma concentrations and percentages of markers of EFA deficiency such as 20:3ω9 and 16:1ω7. We hypothesize that this condition is caused by excessive levels of saturated fatty acids that saturate or disturb the transport of EFAs. We propose that the EFAs and their derivatives are major indicators of risk for CAD, and the diagnosis of relative EFA insufficiency and its optimal treatment with oils and antioxidants are significant factors in the management of CAD.