Advertisement

Low plasma adiponectin exacerbates the risk of premature coronary artery disease in familial hypercholesterolemia

      Abstract

      Familial hypercholesterolemia (FH) is characterized by increased risk for premature coronary artery disease (CAD). This risk is exacerbated in the presence of abdominal obesity and insulin resistance. Low adiponectin is part of the clustering of metabolic abnormalities associated with abdominal obesity and insulin resistance. The present study, therefore, aims to examine the relationship between plasma adiponectin and age at CAD diagnosis in FH patients.
      Plasma adiponectin was measured by ELISA in 568 non-diabetic FH individuals of French-Canadian origin. CAD was defined according to strict clinical criteria. Prior to analyses, patients were grouped according to age and gender-specific tertiles of plasma adiponectin levels. Multivariate Cox proportional hazards regression was used to estimate the association between plasma adiponectin levels and age at diagnosis of CAD. Overall, FH patients in the lowest tertile of plasma adiponectin exhibited CAD at a significantly younger age (hazard ratio = 1.73, confidence interval 95%: [1.19–2.53]; p = 0.004).
      These results suggest that low plasma adiponectin is associated with an increased risk of premature CAD over and above the already exaggerated risk seen in FH patients.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Abifadel M.
        • Varret M.
        • Rabes J.P.
        • et al.
        Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.
        Nat Genet. 2003; 34: 154-156
        • Garcia C.K.
        • Wilund K.
        • Arca M.
        • et al.
        Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein.
        Science. 2001; 292: 1394-1398
        • Goldstein J.
        Familial hypercholesterolemia.
        in: Scriver C.B. Beaudet A.L. Sly W.S. Valle D. The metabolic basis of inherited disease. 8th ed. McGraw-Hill Book Co., New York2000: 2863-2913
        • Moorjani S.
        • Roy M.
        • Torres A.
        • et al.
        Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolaemia.
        Lancet. 1993; 341: 1303-1306
        • Lansberg P.J.
        • Tuzgol S.
        • van de Ree M.A.
        • Defesche J.C.
        • Kastelein J.J.
        Higher prevalence of familial hypercholesterolemia than expected in adult patients of four family practices in Netherlands.
        Ned Tijdschr Geneeskd. 2000; 144: 1437-1440
        • Moorjani S.
        • Roy M.
        • Gagne C.
        • et al.
        Homozygous familial hypercholesterolemia among French Canadians in Quebec Province.
        Arteriosclerosis. 1989; 9: 211-216
        • Vohl M.C.
        • Moorjani S.
        • Roy M.
        • et al.
        Geographic distribution of French-Canadian low-density lipoprotein receptor gene mutations in the Province of Quebec.
        Clin Genet. 1997; 52: 1-6
        • Reaven G.
        Metabolic syndrome: pathophysiology and implications for management of cardiovascular disease.
        Circulation. 2002; 106: 286-288
        • Gaudet D.
        • Vohl M.C.
        • Perron P.
        • et al.
        Relationships of abdominal obesity and hyperinsulinemia to angiographically assessed coronary artery disease in men with known mutations in the LDL receptor gene.
        Circulation. 1998; 97: 871-877
        • Jansen A.C.
        • van Aalst-Cohen E.S.
        • Tanck M.W.
        • et al.
        The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients.
        J Intern Med. 2004; 256: 482-490
        • Trujillo M.E.
        • Scherer P.E.
        Adiponectin—journey from an adipocyte secretory protein to biomarker of the metabolic syndrome.
        J Intern Med. 2005; 257: 167-175
        • Arita Y.
        • Kihara S.
        • Ouchi N.
        • et al.
        Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.
        Biochem Biophys Res Commun. 1999; 257: 79-83
        • Nakano Y.
        • Tobe T.
        • Choi-Miura N.H.
        • Mazda T.
        • Tomita M.
        Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma.
        J Biochem (Tokyo). 1996; 120: 803-812
        • Cnop M.
        • Havel P.J.
        • Utzschneider K.M.
        • et al.
        Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex.
        Diabetologia. 2003; 46: 459-469
        • Kondo H.
        • Shimomura I.
        • Matsukawa Y.
        • et al.
        Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome.
        Diabetes. 2002; 51: 2325-2328
        • Cote M.
        • Mauriege P.
        • Bergeron J.
        • et al.
        Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men.
        J Clin Endocrinol Metab. 2005; 90: 1434-1439
        • Scriver C.R.
        Human genetics: lessons from Quebec populations.
        Annu Rev Genomics Hum Genet. 2001; 2: 69-101
        • Gaudet D.
        • Tremblay G.
        • Perron P.
        • et al.
        Familial hypercholesterolemia in eastern Quebec: a public health problem? The experience of the hyperlipidemia clinic of Chicoutimi.
        Union Med Can. 1995; 124: 54-60
        • Gaudet D.
        • Gagne C.
        • Perron P.
        • Couture P.
        • Tonstad S.
        Ethical issues in molecular screening for heterozygous familial hypercholesterolemia: the complexity of dealing with genetic susceptibility to coronary artery disease.
        Community Genet. 1999; 2: 2-8
        • Ma Y.H.
        • Betard C.
        • Roy M.
        • Davignon J.
        • Kessling A.M.
        Identification of a second “French Canadian” LDL receptor gene deletion and development of a rapid method to detect both deletions.
        Clin Genet. 1989; 36: 219-228
        • Couture P.
        • Vohl M.C.
        • Gagne C.
        • et al.
        Identification of three mutations in the low-density lipoprotein receptor gene causing familial hypercholesterolemia among French Canadians.
        Hum Mutat. 1998; : S226-S231
        • Leitersdorf E.
        • Tobin E.J.
        • Davignon J.
        • Hobbs H.H.
        Common low-density lipoprotein receptor mutations in the French Canadian population.
        J Clin Invest. 1990; 85: 1014-1023
        • Vohl M.C.
        • Couture P.
        • Moorjani S.
        • et al.
        Rapid restriction fragment analysis for screening four point mutations of the low-density lipoprotein receptor gene in French Canadians.
        Hum Mutat. 1995; 6: 243-246
        • W.H.O.
        Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1. Diagnosis and classification of Diabetes mellitus.
        World Health Organization, Geneva1999
        • Alpert J.S.
        • Thygesen K.
        • Antman E.
        • Bassand J.P.
        Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction.
        J Am Coll Cardiol. 2000; 36: 959-969
        • Havel R.J.
        • Eder H.A.
        • Bragdon J.H.
        The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.
        J Clin Invest. 1955; 34: 1345-1353
      1. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 1997;20(7):1183–97.

        • Laurell C.B.
        Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies.
        Anal Biochem. 1966; 15: 45-52
      2. Standardization of anthropometric measurements.
        in: Lohman T.R.A. Martorel R. The Airlie (VA) consensus conference, Human Kinetics, Champaign, IL1988: 39-80
        • Gaudet D.
        • Arsenault S.
        • Belanger C.
        • et al.
        Procedure to protect confidentiality of familial data in community genetics and genomic research.
        Clin Genet. 1999; 55: 259-264
        • Hotta K.
        • Funahashi T.
        • Arita Y.
        • et al.
        Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.
        Arterioscler Thromb Vasc Biol. 2000; 20: 1595-1599
        • Pischon T.
        • Girman C.J.
        • Hotamisligil G.S.
        • et al.
        Plasma adiponectin levels and risk of myocardial infarction in men.
        JAMA. 2004; 291: 1730-1737
        • Ouchi N.
        • Kihara S.
        • Arita Y.
        • et al.
        Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages.
        Circulation. 2001; 103: 1057-1063
        • Kubota N.
        • Terauchi Y.
        • Yamauchi T.
        • et al.
        Disruption of adiponectin causes insulin resistance and neointimal formation.
        J Biol Chem. 2002; 277: 25863-25866
        • Rothenbacher D.
        • Brenner H.
        • Marz W.
        • Koenig W.
        Adiponectin, risk of coronary heart disease and correlations with cardiovascular risk markers.
        Eur Heart J. 2005; 26: 1640-1646
        • Gaudet D.
        • Bouhali T.
        • Couture P.
        • et al.
        HDL-cholesterol and other covariables associated with CAD-free survival among familial hypercholesterolemic heterozygotes or homozygotes over 70 years of age.
        Atherosclerosis Suppl. 2003; 4 (Abstract): 333-334
        • Isobe T.
        • Saitoh S.
        • Takagi S.
        • et al.
        Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study.
        Eur J Endocrinol. 2005; 153: 91-98
        • Jansen A.C.
        • van Wissen S.
        • Defesche J.C.
        • Kastelein J.J.
        Phenotypic variability in familial hypercholesterolaemia: an update.
        Curr Opin Lipidol. 2002; 13: 165-171
        • Adamczak M.
        • Rzepka E.
        • Chudek J.
        • Wiecek A.
        Ageing and plasma adiponectin concentration in apparently healthy males and females.
        Clin Endocrinol (Oxford). 2005; 62: 114-118
        • CnopF M.H.P.
        • Utzschneider K.M.
        • Carr D.B.
        • et al.
        Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex.
        Diabetologia. 2003; 46: 459-469
        • Nishizawa H.
        • Shimomura I.
        • Kishida K.
        • et al.
        Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein..
        Diabetes. 2002; 51: 2734-2741
        • Combs T.P.
        • Berg A.H.
        • Rajala M.W.
        • et al.
        Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin.
        Diabetes. 2003; 52: 268-276
        • Pajvani U.B.
        • Du X.
        • Combs T.P.
        • et al.
        Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications for metabolic regulation and bioactivity.
        J Biol Chem. 2003; 278: 9073-9085