Postprandial hypertriglyceridaemia in patients with Tangier disease

Abstract

Background: Tangier disease (TD) is the phenotypic expression of rare familial syndromes with mutations in the ABCA1 transporter. TD results in extremely low high density lipoprotein (HDL) cholesterol and reduced low density lipoprotein cholesterol, with normal or mildly increased fasting triglyceride (TG) concentrations. Although there is a close relation between HDL cholesterol values and atherogenesis, the risk of coronary artery disease is variable in TD. Raised fasting or postprandial TG values frequently accompany low HDL cholesterol and can add to the risk of a vascular event. Aims: To investigate the postprandial TG response in TD. Patients and methods: Five patients (three homozygotes (HTD) and two heterozygotes (hTD)) from one family were studied. One was defined by DNA analysis as homozygous for a new mutation (C2033A) resulting in truncation of the ABCA1 protein. Their TG concentrations were measured before and four, six, and eight hours after a standardised fat load and compared with a control group. Results: Two patients with HTD had high fasting TG concentrations. The third patient with HTD, the two with hTD, and the control group had TG concentrations within the reference range. The patients with HTD had increased postprandial peak TG values when compared with those with hTD and controls. Conclusion: Patients with HTD, with or without fasting hypertriglyceridaemia, may have an increased TG response to a fatty meal. The small number of patients does not allow definitive conclusions to be made. However, postprandial hypertriglyceridaemia could be a reason why some patients with TD develop premature atherosclerosis.

The Influence of Natural Menopause on Postprandial Lipemia in Heterozygotes for Familial Hypercholesterolemia

“…As there are no official guidelines for abnormal postprandial TG values, a value of Ͼ219 mg/dl (2.5 mmol/L) was taken as an abnormal response to the fat load according to our previous studies. 18,19 Briefly, an abnormal TG response to a fatty meal was considered when any of the postprandial TG concentrations (at 2, 4, 6, or 8 hours) was higher than the highest TG concentration in any hour in any healthy subjects in our previous studies. 18,19 on a Roche Integra Biochemical analyzer with commercially available kits (Roche, Nutley, NJ).…”

“…18,19 Briefly, an abnormal TG response to a fatty meal was considered when any of the postprandial TG concentrations (at 2, 4, 6, or 8 hours) was higher than the highest TG concentration in any hour in any healthy subjects in our previous studies. 18,19 on a Roche Integra Biochemical analyzer with commercially available kits (Roche, Nutley, NJ). The serum LDL-C levels were calculated using the Friedewald formula 23 only in patients with TG levels Ͻ400 mg/dl (4.5 mmol/L).…”

“…14,15 The apparent increased risk associated with smaller LDL is a relatively novel finding in hFH patients, 16 although there are a few studies suggesting that TG levels increase postprandially in patients with FH. 16,17 In line with previous studies carried out in our laboratory, [18][19][20] the aim of this study was to evaluate the postprandial TG levels (after a standardized fatty meal) in premenopausal and postmenopausal women with hFH.…”

Familial hypercholesterolemia and triglyceride metabolism

“…Raised TG levels may also be associated with a higher risk of premature CHD in patients with hFH [124,125] (Table 1). The role of increased TG levels as a risk factor for CHD has also been described in a rare condition (Tangier Disease) [13].…”

“…Furthermore, the postprandial hypertriglyceridemia is considered as a risk factor for atherosclerosis, too [13][14][15][16][17][18][19]. Potentially atherogenic remnants of TG-rich lipoproteins, namely chylomicrons (CM), very low-density lipoproteins (VLDL), accumulate in the postprandial state [16,20,21].…”