Abstract
To determine whether hyperalphalipoproteinemia modifies carotid intima-media thickness (cIMT) and/or influences the relationship of clinical and biochemical parameters with cIMT. This study was conducted on 169 asymptomatic individuals, classified as hyperalphalipoproteinemic (Hyper-A) (Hyper-A, n = 71, HDL-C ≥68 mg/dL) and controls (CTL) (CTL, n = 98, HDL-C >32 and <68 mg/dL). Enzymatic, nephelometric and ultracentrifugation methods were used for biochemical determinations. Hepatic lipase (HL), lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and phospholipids transfer protein (PLTP) activities were measured by radiometric exogenous methods. The prevalence of dyslipidemia, hypertension, smoking, sedentariness, postmenopausal women, coronary artery disease (CAD) and familial history of CAD were determined. High resolution β-mode carotid ultrassonography was performed. The Hyper-A group was older and had higher frequencies of hypercholesterolemia (40%), hypertension (31%), sedentariness (37%) and postmenopausal women (1%). In Hyper-A individuals, the mean cIMT after adjustment for age and gender was similar between the groups (0.85 ± 0.24 mm Hyper-A versus 0.69 ± 0.17 mm CTL). In multivariate models, age was a significant predictor of cIMT in Hyper-A (R 2 = 0.04, p ≤ 0.001), independently of other clinical or biochemical factors. In contrast to CTL, where age (R 2 = 0.63 p ≤ 0.001), male sex (R 2 = 0.03, p ≤ 0.001), blood pressure (R 2 = 0.006, p ≤ 0.001) and HDL-C (R 2 = 0.02, p < 0.022) accounted for the cIMT variations. Despite an increased prevalence of cardiovascular risk factors in Hyper-A and resistance of carotid thickness to modulation by metabolic and anthropometric factors (except age), the similarity in cIMT between Hyper-A and healthy individuals emphasizes the atheroprotective effects of HDL.
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Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M et al (1997) Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol 146(6):483–494
Bots ML (2006) Carotid intima-media thickness as a surrogate marker for cardiovascular disease in intervention studies. Curr Med Res Opin 22(11):2181–2190
Zureik M, Ducimetière P, Touboul PJ, Courbon D, Bonithon-Kopp C, Berr C, Magne C (2000) Common carotid intima-media thickness predicts occurrence of carotid atherosclerotic plaques: longitudinal results from the Aging Vascular Study (EVA) study. Arterioscler Thromb Vasc Biol 20(6):1622–1629
Hovingh GK, de Groot E, van der Steeg W, Boekhondt SM, Hutten BA et al (2005) Inheterited disorders of HDL metabolism and atherosclerosis. Curr Opin Lipidol 16(2):139–145
de Groot E, Hovingh GK, Wiegman A, Duriez P, Smit AJ, Fruchart JC, Kastelein JJ (2004) Measurement of arterial wall thickness as a surrogate marker for atherosclerosis. Circulation 109(23 (Suppl 1)):III33–III38 Review
Csiba L (2005) Carotid intima-media thickness measured by ultrasonography: effect of different pharmacotherapies on atherosclerosis progression. Orv Hetil 146(23):1239–1244
Fielding PE, Fielding CJ (1996) Intracellular transport of low-density lipoprotein derived free cholesterol begins at clathrin-coated pits and terminates at cell surface caveolae. Biochemistry 35(47):14932–14938
Kontush A, Chapman MJ (2006) Antiatherogenic small, dense HDL—guardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med 3(3):144–153 Review
Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP et al (1989) High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 79(1):8–15
Bruckert E, Hansel B (2007) HDL-C is a powerful lipid predictor of cardiovascular diseases. Int J Clin Pract. (61) 11: 1782–6
Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J et al (1990) Increased high-density-lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med 323(18):1234–1238
Sich D, Saidi Y, Giral P, Lagrost L, Egloff M, Auer C, Gautier V, Turpin G, Beucler I (1998) Hyperalphalipoproteinemia: characterization of a cardioprotective profile associating increased high-density lipoprotein2 levels and decreased hepatic lipase activity. Metabolism 47(8):965–973
Kontush A, de Faria EC, Chantepie S, Chapman MJ (2004) Antioxidative activity of HDL particle subspecies is impaired in hyperalphalipoproteinemia: relevance of enzymatic and physicochemical properties. Arterioscler Thromb Vasc Biol 24(3):526–533
Yamashita S, Maruyama T, Hirano K, Sakai N, Nakajima N, Matsuzawa Y (2000) Molecular mechanisms, lipoproteins abnormalities and athero genicity of hyperalphalipoproteinemia. Atherosclereosis 152:271–285
Alarcon SBK, Oliveira HCF, Harada LM, Nunes VS, Kaplan D et al (2004) Moderate hyperalphalipoproteinemia in a Brazilian population is related to lipoprotein lipase activity, alipoprotein A-I concentration, age and body mass index. Clin Sci 106:11–17
Kaplan DB, Schreiber R, Oliveira HC, Harada LM, Nakamura RT et al (2006) Cholesteryl ester transfer protein gene mutations in Brazilian hyperalphalipoproteinemia. Clin Gen 69(5):455–457
Matsuzawa Y, Yamashita S, Funahashi T, Yamamoto A, Tarui S (1988) Selective reduction of cholesterol in HDL2 fraction by probucol in familial hypercholesterolemia and hyper HDL2 cholesterolemia with abnormal cholesteryl ester transfer. Am J Cardiol 62:B66–72B
Hirano K, Yamashita S, Kuga Y, Sakai N, Nosaki S et al (1995) Atherosclerosis disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase. Aterioscler Thromb Vasc Biol 15(11):1849–1856
Agerholm-Larsen B, Nordestgaard BG, Steffensen R, Jensen G, Tybjaerg-Hansen A (2000) Elevated HDL cholesterol is a risk factor for ischemic heart disease in white women when caused by a common mutation in the cholesteryl ester transfer protein gene. Circulation 101(16):1907–1912
Sposito AC, Caramelli B, Fonseca FAH, Bertolami MC (2007) IV Diretriz Brasileira Sobre Dislipidemias e Prevenção da Aterosclerose. Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arquivos Brasileiros de Cardiologia 88(1): 2–19
Pedro AO, Pinto-Neto AM, Costa-Paiva LHS, Osis MJ, Hardy EE (2003) Idade de ocorrência da menopausa natural em mulheres brasileiras: resultados de um inquérito populacional domiciliar. Rev Saude Publica 37(6):735–742
Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN et al (2007) Physical activity and public health. Updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation 116(9):1081–1093
Friedewald WF, Levy RI, Frederickson DS (1972) Estimation of LDL-cholesterol concentration without use of preparitive ultracentrifuge. Clin Chem 18:499–502
Eyre J, Hammett F, Miller NE (1981) A micro-method for the rapid ultracentrifugal separation of human plasma high density lipoprotein subfractions, HDL2 and HDL3. Clin Chim Acta 114(2–3):225–231
Ehnholm C, Kuusi T (1986) Preparation, characterization and measurement of hepatic lipase. Methods Enzymol 129:716–738
Lagrost L (1998) Determination of the mass concentration and the activity of the plasma cholesteryl ester transfer protein (CETP). Methods Mol Biol 110:231–241
Damen J, Regts J, Scherphorp G (1982) Transfer of [14C] phosphatidylcholine between liposomes and human plasma high density lipoprotein. Partial purification of transfer stimulation plasma factor using a rapid transfer assay. Biochim Biophys Acta 712:444–452
Simons PC, Algra A, Bots ML, Grobbee DE, van der Graaf Y (1999) Common carotid intima-media thickness and arterial stiffness: indicators of cardiovascular risk in high-risk patients. The SMART Study (Second Manifestations of arterial disease). Circulation 100(9):951–957
Navab M, Anantharamaiah GM, Reddy ST, Van Lenten BJ, Ansell BJ, Fogelman AM (2006) Mechanisms of disease: proatherogenic HDL—an evolving field. Nat Clin Pract Endocrinol Metab 2(9):504–511 Review
Dodani S, Kaur R, Reddy S, Reed GL, Navab M, George V (2008) Can dysfunctional HDL explain high coronary artery disease risk in South Asians? Int J Cardiol 129(1):125–132
Baldassamare D, Amato M, Pustina L, Tremoli H, Sirtori C, Calabresi L, Franceschini G (2002) Increased carotid artery intima-media thickness in subjects with primary hypoalphalipoproteinemia. Arterioscl Thromb Vasc Biol 22(2):317–322
Howard G, Sharrett AR, Heiss G, Evans GW, Chambless LE, Riley WA, Burke GL (1993) Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC Investigators. Stroke 24(9):1297–1304
Kontush A, de Faria EC, Chantepie S, Chapman MJ (2005) A normotriglyceridemic, low HDL-cholesterol phenotype is characterised by elevated oxidative stress and HDL particles with attenuated antioxidative activity. Atherosclerosis 182(2):277–285
Acknowledgements
This work forms part of the master thesis of Fernanda Dutra Santiago and supported in part by grants from the Fundação de Amparo a Pesquisa de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We thank Miriam Danelon for the excellent technical work, and Helymar Machado for statistical support.
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Santiago, F.D., Nakamura, R.T., Kaplan, D. et al. Protective modulation of carotid atherosclerosis in hyperalphalipoproteinemic individuals. Int J Cardiovasc Imaging 26, 27–34 (2010). https://doi.org/10.1007/s10554-009-9498-2
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DOI: https://doi.org/10.1007/s10554-009-9498-2