Five-year follow-up of waist circumference, insulin and ALT levels in familial combined hyperlipidaemia.

INTRODUCTION: Familial combined hyperlipidemia (FCHL), an entity with many features of the metabolic syndrome, is characterized by changes in cholesterol and triglyceride phenotype over time. This study was conducted to investigate the relation of alanineaminotransferase (ALT) levels, used as a surrogate for the amount of hepatic fat, with the switch in triglyceride phenotype and the increased susceptibility to develop hypertriglyceridemia in FCHL. METHODS: Body mass index, waist circumference, plasma triglycerides, insulin and ALT levels were measured in 145 FCHL family members and 54 spouses at baseline and after a five-year follow-up. RESULTS: A switch from normotriglyceridemia to hypertriglyceridemia or vice versa, as observed in 22 of 145 FCHL family members, was associated with changes in plasma ALT levels (p=0.001), but not with insulin levels or waist circumference. In five-year follow-up, an intra-individual relation was observed between waist circumference and both plasma triglycerides, insulin and ALT levels. For each waist circumference FCHLpatients, but not their normolipidemic relatives, exhibited higher triglyceride and insulin levels than spouses (p<0.001). Remarkably, both FCHL patients and the normolipidemic relatives showed higher ALT levels for each waist circumference as compared to spouses(p<0.001 for FCHL patients, p=0.035 for normolipidemic relatives). CONCLUSION: The present study shows that the longitudinal relation abdominal obesity-ALT is more specific for all FCHL family members, i.e. patients and their normolipidemic relatives, than the relation abdominal obesity-triglycerides. Additionally,the association of ALT with the switch in triglyceride phenotype suggests a central role of the liver in the pathogenesis of FCHL.

Reduced structural and functional skin capillaries in familial combined hyperlipidemia affected men, associated with increased remnant-like lipoprotein cholesterol levels.

We determined whether abnormalities in the number of basal (BC) and post-occlusive (POC) capillaries are present in familial combined hyperlipidemia (FCHL), and investigated the possible relationship of BC and POC with lipids, remnant-like lipoprotein particles (RLP-C), blood pressure, and insulin resistance. Fifty age-matched subjects, 23 (12 men) hyperlipidemic, normotensive FCHL subjects and 27 (14 men) healthy controls participated in this study. Capillary density was measured just above the finger nailfold, before and after 4 min of arterial occlusion. The number of BC and POC were significantly lower in FCHL men compared with healthy men, 113.7+/-15.1 versus 132.0+/-18.0 (P=0.02) and 123+/-19.1 versus 142.3+/-18.3 (P=0.03), respectively. No differences were found between FCHL women and control women. In univariate analyses in FCHL men, BC was inversely correlated with total cholesterol (r=-0.63; P=0.05). POC tended to be inversely correlated with total cholesterol (r=-0.62; P=0.056). No univariate correlations (P>0.3) were observed between BC or POC and blood pressure or insulin resistance. Multivariate analyses revealed that logRLP-C was the only significant independent contributor to BC and POC. This is the first description of a reduction in skin capillaries in FCHL men, which was associated with increased atherogenic lipoprotein levels. Loss of capillary surface may be important in the pathophysiology or can result from adaptation to the hyperlipidemia in FCHL.