Heterozygote men with familial hypercholesterolaemia may have an abnormal triglyceride response post-prandially. Evidence for another predictor of vascular risk in familial hypercholesterolaemia

Abstract

Familial hypercholesterolaemia (FH) is associated with premature coronary heart disease (CHD). Post-prandial hypertriglyceridaemia has also been associated with cardiovascular disease. Thus, an abnormal post-prandial triglyceride (TG) clearance may contribute to the heterogeneity in the risk of CHD in heterozygous (h) FH. Therefore, we investigated the response of TG levels to a fatty meal in men with hFH. We studied 26 Greek men divided into two groups: the hFH group of 14 men, mean age 39 (SD = 11) years and the control group of 12 healthy men, mean age 43 (50:5) years. An increased TG response to the fatty meal was defined as a post-prandial TG concentration (at 4, 6 or 8 h) greater than the highest TG concentration in any hour in any control individual. All hFH patients had normal baseline fasting TG levels. However, seven hFH men showed an abnormal TG response after the fatty meal; these patients had higher baseline fasting TG levels than others [1.5 (0.2) vs. 1.0 (0.4) mmol/l, p = 0.005]. The hFH men constituted a heterogeneous group regarding their TG response to the fatty meal compared with healthy men because 50% with higher, but nevertheless 'normal' basal TG levels, had an abnormal post-prandial TG response. The reduced activity of low-density lipoprotein receptors in hFH together with other defects in TG handling may explain the abnormal rise of TG levels post-prandially.

Familial hypercholesterolemia and triglyceride metabolism

“…On the other hand, Watts et al [110] reported that the catabolism of CM remnants from plasma is not impaired in FH and that the hepatic uptake of these particles is not dependent on functional LDLR. If this is a case, the abnormal remnant accumulation should not have occurred in FH patients which is opposite to what was found by others [107,108] and our group [104].…”

“…Moreover, in hFH subjects the production rate of the VLDL is increased and this is even more pronounced in FH homozygotes [104]. The VLDL production rate has been reported 50% higher in heterozygotes and 109% in homozygotes when compared with healthy controls [104].…”

“…The postprandial lipemia in FH patients was evaluated only by few investigators, including us [101][102][103][104][105][106][107][108] (Table 1). It was found that patients with FH have delayed clearance of CMs.…”

Stress testing response in women heterozygous for familial hypercholesterolemia

“…The inclusion criteria for hFH women were clinical diagnosis of hFH [1], lack of CHD and the ability to walk on the treadmill at a moderate pace. They did not receive any medication, since they visited our Lipid Clinic for the first time.…”

Is it time to break the fast?—a paradigm shift in clinical lipidology

“…The absolute increase in TG seems similar between subjects with different levels of triglyceridemia and fasting TG are therefore the best predictor for non-fasting TG. It was also believed that TG variability increases in the non-fasting state, but the intraindividual variability of TG is not affected much throughout the day (22).…”