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Horm Metab Res 2013; 45(12): 905-910
DOI: 10.1055/s-0033-1351259
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Increased Cardiovascular Risk in South African Patients with Addison’s Disease

I. L. Ross
1   Division of Endocrinology Department of Medicine University of Cape Town, Cape Town, South Africa
,
R. Bergthorsdottir
2   Department of Endocrinology, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
,
N. S. Levitt
1   Division of Endocrinology Department of Medicine University of Cape Town, Cape Town, South Africa
,
D. A. Schatz
3   Department of Paediatrics, University of Florida, Florida, USA
,
G. Johannsson
2   Department of Endocrinology, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
,
A. D. Marais
4   Division of Chemical Pathology, Clinical Laboratory Sciences, National Health Laboratory, Service Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
› Author Affiliations
Further Information

Publication History

received 25 March 2013

accepted 25 June 2013

Publication Date:
05 August 2013 (online)

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Abstract

Patients with Addison’s disease (AD) are believed to be at risk for cardiovascular disease (CVD). South Africa, like the rest of the developing world is experiencing an increase in CVD and patients with AD may be at double the risk of their peers. We wished to explore AD patients’ CVD risk factors. A cross-sectional nationwide study in South Africa of patients with AD was conducted. A cohort of 147 patients with AD and 147 healthy control subjects were matched by age, gender, ethnicity, and BMI as far as was possible. Lipoproteins and highly-sensitive C-reactive-protein (hs-CRP) were the main outcome measures. AD patients had significantly higher triglycerides; (p=0.001), lower HDLC (p<0.001), higher hs-CRP (p<0.001), and more small dense LDL; (p=0.002) than controls. Nonesterified fatty acids were lower in patients (p<0.001). Approximately 65% [95% confidence interval (CI 55.6–72.4%)] had hypercholesterolaemia, 75% (CI 64.8–81.2%) had low HDLC, and 75% (CI 68.0–84.1%) had a higher LDLC. Thirteen percent of AD patients had diabetes mellitus, but none of the risk factors differed from the nondiabetics. Only HDLC correlated positively with daily hydrocortisone dose (r=0.32; p=0.005). In conclusion dyslipidaemia is common in South African AD patients; CVD risk assessment and intervention are probably warranted in the management of these patients.

Key words

lipids - lipoproteins - primary hypoadrenalism - atherosclerosis risk
 

  • References

  • 1 Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003; 361: 1881-1893
    CrossrefPubMedGoogle Scholar
  • 2 Erichsen MM, Lovas K, Fougner KJ, Svartberg J, Hauge ER, Bollerslev J, Berg JP, Mella B, Husebye ES. Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. Eur J Endocrinol 2009; 160: 233-237
    CrossrefPubMedGoogle Scholar
  • 3 Bergthorsdottir R, Leonsson-Zachrisson M, Oden A, Johannsson G. Premature mortality in patients with Addison’s disease: a population-based study. J Clin Endocrinol Metab 2006; 91: 4849-4853
    CrossrefPubMedGoogle Scholar
  • 4 Sholter DE, Armstrong PW. Adverse effects of corticosteroids on the cardiovascular system. Can J Cardiol 2000; 16: 505-511
    PubMedGoogle Scholar
  • 5 Reaven EP, Kolterman OG, Reaven GM. Ultrastructural and physiological evidence for corticosteroid-induced alterations in hepatic production of very low density lipoprotein particles. J Lipid Res 1974; 15: 74-83
    PubMedGoogle Scholar
  • 6 Hazra A, Pyszczynski NA, DuBois DC, Almon RR, Jusko WJ. Modeling of corticosteroid effects on hepatic low-density lipoprotein receptors and plasma lipid dynamics in rats. Pharm Res 2008; 25: 769-780
    CrossrefPubMedGoogle Scholar
  • 7 Faggiano A, Pivonello R, Spiezia S, De Martino MC, Filippella M, Di Somma C, Lombardi G, Colao A. Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing’s disease during active disease and 1 year after disease remission. J Clin Endocrinol Metab 2003; 88: 2527-2533
    CrossrefPubMedGoogle Scholar
  • 8 Danilowicz K, Bruno OD, Manavela M, Gomez RM, Barkan A. Correction of cortisol overreplacement ameliorates morbidities in patients with hypopituitarism: a pilot study. Pituitary 2008; 11: 279-285
    CrossrefPubMedGoogle Scholar
  • 9 Ettinger Jr WH, Hazzard WR. Prednisone increases very low density lipoprotein and high density lipoprotein in healthy men. Metabolism 1988; 37: 1055-1058
    CrossrefPubMedGoogle Scholar
  • 10 Bagdade JD, Yee E, Albers J, Pykalisto OJ. Glucocorticoids and triglyceride transport: effects on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rat. Metabolism 1976; 25: 533-542
    CrossrefPubMedGoogle Scholar
  • 11 Nanjee MN, Miller NE. Plasma lipoproteins and adrenocortical hormones in men – positive association of low density lipoprotein cholesterol with plasma cortisol concentration. Clin Chim Acta 1989; 180: 113-120
    CrossrefPubMedGoogle Scholar
  • 12 Giordano R, Marzotti S, Balbo M, Romagnoli S, Marinazzo E, Berardelli R, Migliaretti G, Benso A, Falorni A, Ghigo E, Arvat E. Metabolic and cardiovascular profile in patients with Addison’s disease under conventional glucocorticoid replacement. J Endocrinol Invest 2009; 32: 917-923
    PubMedGoogle Scholar
  • 13 Gurnell EM, Hunt PJ, Curran SE, Conway CL, Pullenayegum EM, Huppert FA, Compston JE, Herbert J, Chatterjee VK. Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial. J Clin Endocrinol Metab 2008; 93: 400-409
    CrossrefPubMedGoogle Scholar
  • 14 Norman R, Bradshaw D, Schneider M, Jewkes R, Mathews S, Abrahams N, Matzopoulos R, Vos T. Estimating the burden of disease attributable to interpersonal violence in South Africa in 2000. S Afr Med J 2007; 97: 653-656
    PubMedGoogle Scholar
  • 15 Steyn K, Levitt NS, Hoffman M, Marais AD, Fourie JM, Lambert EV, Gaziano TA, Kepe L, Lombard CJ. The global cardiovascular diseases risk pattern in a peri-urban working-class community in South Africa. The Mamre study. Ethn Dis 2004; 14: 233-242
    PubMedGoogle Scholar
  • 16 Steyn K, Steyn M, Swanepoel AS, Jordaan PC, Jooste PL, Fourie JM, Rossouw JE. Twelve-year results of the Coronary Risk Factor Study (CORIS). Int J Epidemiol 1997; 26: 964-971
    CrossrefPubMedGoogle Scholar
  • 17 Oelofse A, Jooste PL, Steyn K, Badenhorst CJ, Lombard C, Bourne L, Fourie J. The lipid and lipoprotein profile of the urban black South Africa population of the Cape Peninsula – the BRISK study. S Afr Med J 1996; 86: 162-166
    PubMedGoogle Scholar
  • 18 Steyn K, Rossouw JE, Joubert G. The coexistence of major coronary heart disease risk factors in the coloured population of the Cape Peninsula (CRISIC study). S Afr Med J 1990; 78: 61-63
    PubMedGoogle Scholar
  • 19 Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease in developing countries. Circulation 1998; 97: 596-601
    CrossrefPubMedGoogle Scholar
  • 20 Ross I, Boulle A, Soule S, Levitt N, Pirie F, Karlsson A, Mienie J, Yang P, Wang H, She JX, Winter W, Schatz D. Autoimmunity predominates in a large South African cohort with Addison’s disease of mainly European descent despite long-standing disease and is associated with HLA DQB*0201. Clin Endocrinol (Oxf) 2010; 73: 291-298
    CrossrefPubMedGoogle Scholar
  • 21 Soule S. Addison’s disease in Africa – a teaching hospital experience. Clin Endocrinol (Oxf) 1999; 50: 115-120
    CrossrefPubMedGoogle Scholar
  • 22 Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97: 1837-1847
    CrossrefPubMedGoogle Scholar
  • 23 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
    CrossrefPubMedGoogle Scholar
  • 24 Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) . Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-2497
    CrossrefPubMedGoogle Scholar
  • 25 Gidez LI, Miller GJ, Burstein M, Slagle S, Eder HA. Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure. J Lipid Res 1982; 23: 1206-1223
    PubMedGoogle Scholar
  • 26 Blom DJ, Byrnes P, Jones S, Marais AD. Non-denaturing polyacrylamide gradient gel electrophoresis for the diagnosis of dysbetalipoproteinemia. J Lipid Res 2003; 44: 212-217
    CrossrefPubMedGoogle Scholar
  • 27 Klug ERF, Marais AD, Taskinen M-R, Dalby AJ, Schamroth C, Rapeport N, Jankelow D, Blom DJ, Catsicas R, Webb DA. South African dyslipidaemia guideline consensus statement. S Afr Med J 2012; 102: 178-187
    PubMedGoogle Scholar
  • 28 van der Westhuyzen DR, de Beer FC, Webb NR. HDL cholesterol transport during inflammation. Curr Opin Lipidol 2007; 18: 147-151
    CrossrefPubMedGoogle Scholar
  • 29 Beentjes JA, van Tol A, Sluiter WJ, Dullaart RP. Decreased plasma cholesterol esterification and cholesteryl ester transfer in hypopituitary patients on glucocorticoid replacement therapy. Scand J Clin Lab Invest 2000; 60: 189-198
    CrossrefPubMedGoogle Scholar
  • 30 Garcia-Gomez C, Nolla JM, Valverde J, Narvaez J, Corbella E, Pinto X. High HDL-cholesterol in women with rheumatoid arthritis on low-dose glucocorticoid therapy. Eur J Clin Invest 2008; 38: 686-692
    CrossrefPubMedGoogle Scholar
  • 31 Staels B, van Tol A, Chan L, Verhoeven G, Auwerx J. Variable effects of different corticosteroids on plasma lipids, apolipoproteins, and hepatic apolipoprotein mRNA levels in rats. Arterioscler Thromb 1991; 11: 760-769
    CrossrefPubMedGoogle Scholar
  • 32 Lin RC. Effects of hormones on apolipoprotein secretion in cultured rat hepatocytes. Metabolism 1988; 37: 745-751
    CrossrefPubMedGoogle Scholar
  • 33 Brotman DJ, Girod JP, Garcia MJ, Patel JV, Gupta M, Posch A, Saunders S, Lip GY, Worley S, Reddy S. Effects of short-term glucocorticoids on cardiovascular biomarkers. J Clin Endocrinol Metab 2005; 90: 3202-3208
    CrossrefPubMedGoogle Scholar
  • 34 Atger V, Leclerc T, Cambillau M, Guillemain R, Marti C, Moatti N, Girard A. Elevated high density lipoprotein concentrations in heart transplant recipients are related to impaired plasma cholesteryl ester transfer and hepatic lipase activity. Atherosclerosis 1993; 103: 29-41
    CrossrefPubMedGoogle Scholar
  • 35 Berg AL, Nilsson-Ehle P. Direct effects of corticotropin on plasma lipoprotein metabolism in man – studies in vivo and in vitro. Metabolism 1994; 43: 90-97
    CrossrefPubMedGoogle Scholar
  • 36 Bjornheden T, Babyi A, Bondjers G, Wiklund O. Accumulation of lipoprotein fractions and subfractions in the arterial wall, determined in an in vitro perfusion system. Atherosclerosis 1996; 123: 43-56
    CrossrefPubMedGoogle Scholar
  • 37 Monteiro CM, Pinheiro LF, Izar MC, Barros SW, Vasco MB, Fischer SM, Povoa RM, Brandao SA, Santos AO, Oliveira L, Carvalho AC, Fonseca FA. Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event. Braz J Med Biol Res 2010; 43: 297-302
    CrossrefPubMedGoogle Scholar
  • 38 Rice SPL, Agarwal N, Bolusani H, Newcombe R, Scanlon MF, Ludgate M, Rees DA. Effects of Dehydroepiandrosterone Replacement on Vascular Function in Primary and Secondary Adrenal Insufficiency: A Randomized Crossover Trial. J Clin Endocrinol Metabol 2009; 94: 1966-1972
    CrossrefPubMedGoogle Scholar
  • 39 Carlsson M, Wessman Y, Almgren P, Groop L. High levels of nonesterified fatty acids are associated with increased familial risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 2000; 20: 1588-1594
    CrossrefPubMedGoogle Scholar
  • 40 Straznicky NE, Eikelis N, Lambert EA, Esler MD. Mediators of sympathetic activation in metabolic syndrome obesity. Curr Hypertens Rep 2008; 10: 440-447
    CrossrefPubMedGoogle Scholar
  • 41 Early J. Comprehensive management of cardiometabolic risk factors. Clin Cornerstone 2007; 8: 69-80
    CrossrefPubMedGoogle Scholar
  • 42 Hafstrom I, Rohani M, Deneberg S, Wornert M, Jogestrand T, Frostegard J. Effects of low-dose prednisolone on endothelial function, atherosclerosis, and traditional risk factors for atherosclerosis in patients with rheumatoid arthritis – a randomized study. J Rheumatol 2007; 34: 1810-1816
    PubMedGoogle Scholar
  • 43 The metabolic and molecular basis of inherited disease. New York: McGraw-Hill; 2001
    Google Scholar