Trans fatty acids, HDL-cholesterol, and cardiovascular disease risk - Effects of dietary changes on vascular reactivity

</font><FONT FACE="Garamond" SIZE=4>Intake of trans fatty acids increases the risk of coronary heart disease, even more so than saturated fatty acids. We wanted to investigate whether this higher risk was caused by the decrease in serum HDL-cholesterol by trans fatty acids. To do this, we studied the effect of diet-induced changes in HDL-cholesterol on vascular reactivity, a surrogate endpoint for coronary heart disease. Vascular reactivity was measured as flow-mediated vasodilation: the percentage increase in arterial diameter after a provoked increase in blood flow. The extent of flow-mediated vasodilation appears to be predictive of future coronary heart disease. The studies were performed in healthy men and women.Replacement of 9.2% of energy (en%) from saturated fatty acids by trans fatty acids lowered serum HDL-cholesterol after 4 weeks by 0.39 (95%CI 0.28, 0.50) mmol/L and impaired flow-mediated vasodilation from 6.2% to 4.4%, a decrease of 1.8%-points (0.4, 3.2). The activity of serum paraoxonase, an HDL-bound esterase which might protect against atherosclerosis, decreased by 6% (2%, 10%). We then verified whether a different HDL-lowering diet also impaired flow-mediated vasodilation. In this study, we replaced≈20en% monounsaturated fatty acids with carbohydrates: HDL-cholesterol decreased by 0.21 (0.17, 0.26) mmol/L and flow-mediated vasodilation increased from 4.1% to 4.8%, an increase of 0.7% (-0.6, 1.9). This result did not support our hypothesis that decreases in HDL-cholesterol increase risk of cardiovascular disease; however, the decrease might have been too small to cause an effect. We therefore investigated in an oral fat-loading test whether trans fatty acids could impair flow-mediated vasodilation while HDL-cholesterol was constant. This was not the case; flow-mediated vasodilation after an oral fat load of 1g/kg bodyweight was 3.1% versus 2.6% before, and trans fatty acids and saturated fatty acids had similar effects. Serum paraoxonase activity parallelled the change in flow-mediated vasodilation, and was slightly increased after an oral fat load with either trans or saturated fatty acids.We conclude that replacement of saturated fatty acids by trans fatty acids impairs vascular function within 4 weeks. This may explain why trans fatty acids relate more strongly to risk of cardiovascular disease than saturated fatty acids. Whether the effects on vascular function are caused by changes in HDL-cholesterol remains to be resolved.