Increased Carotid Artery Intima-Media Thickness in Subjects With Primary Hypoalphalipoproteinemia

Abstract

Abstract-The plasma concentration of high-density lipoprotein cholesterol (HDL-C) is inversely correlated with the incidence of atherosclerotic vascular events. In the present study, we evaluated pre-intrusive atherosclerosis in subjects with plasma HDL-C at the extremities of normal distribution. Fifty-five subjects with primary hypoalphalipoproteinemia (HypoALP) or hyperalphalipoproteinemia (HyperALP) were compared with fifty-five control subjects with average HDL-C levels, matched for sex, age, and plasma cholesterol. The average and maximal intima-media thicknesses (Avg-IMT and Max-IMT) of 48 carotid segments for each subject were approximately 40% greater in HypoALP than in control subjects (0.94Ϯ0.06 versus 0.69Ϯ0.04 mm, Pϭ0.004, and 1.86Ϯ0.16 versus 1.35Ϯ0.10 mm, Pϭ0.025, respectively). The IMT values in HyperALP subjects (Avg-IMT, 0.71Ϯ0.04 and Max-IMT, 1.38Ϯ0.14 mm) were the same as in controls. In a large cohort of hyperlipidemic subjects (nϭ559), significantly greater Avg-IMT and Max-IMT were found in subjects belonging to the first HDL-C quintile (Ͻ42 mg/dL) than in all the others. The measurement of carotid IMT in cases with HypoALP and HyperALP, and in a large series of hyperlipidemic patients, thus indicates that a low HDL-C is associated with significant pre-intrusive atherosclerosis, whereas a HDL-C level above average values does not lead to a further reduction of arterial wall thickening.

Antioxidative Activity of HDL Particle Subspecies Is Impaired in Hyperalphalipoproteinemia: Relevance of Enzymatic and Physicochemical Properties

“…These data are consistent with the observation of Baldassarre et al that HALP is not associated with accelerated development of atherosclerosis. 3 Nonetheless, given the multiple metabolic origins of HALP, the possibility that some forms of HALP may be associated with HDL particle phenotypes characterized by marked biological dysfunction, and concomitantly with accelerated atherosclerosis, cannot be excluded.…”

“…1 Marked elevation in HDL-C levels is typical of hyperalphalipoproteinemia (HALP), which is characterized by plasma levels of HDL-C above the 90th percentile for an age-and sex-matched general population. 2,3 Primary HALP can arise from genetic deficiency of plasma cholesteryl ester transfer protein (CETP) and/or hepatic lipase (HL), as well as from increased production of apolipoprotein A-I (apoA-I), a major HDL apolipoprotein; 2 equally, however, HALP may be of unknown etiology. HALP involves modification of the physicochemical properties, metabolism, and function of HDL; for example, large CE-rich HDL2 particles that accumulate in familial CETP deficiency possess diminished capacity for cholesterol efflux from macrophages.…”

Association of a fat-derived plasma protein omentin with carotid artery intima-media thickness in apparently healthy men

“…Maximal IMT (max-IMT) is defined as the highest IMT of several sites in bilateral carotid arteries. 13,14 Mean-IMT was measured at the site of max-IMT and at two other points, 1 cm upstream and 1 cm downstream from this site, and these determinations were averaged. 12,14 All measurements were performed by a single expert sonographer who was blinded to the patient's clinical details.…”

Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk

“…Carotid intima-media thickness (IMT) is one of the best established and most commonly used measures of preclinical atherosclerosis ( 13 ). It correlates with many cardiovascular risk factors, including low plasma HDL-C levels ( 14,15 ), and with the severity of CAD ( 16 ). Most importantly, in prospective studies, carotid IMT predicts clinical CAD ( 17 ).…”