Abstract
The relationship between serum uric acid (SUA) and risk of coronary heart disease (CHD) mortality remains controversial, particularly in diabetic subjects. The aim of the present study is to evaluate whether SUA independently predicts CHD mortality in non-insulin-dependent elderly people from the general population and to investigate the interactions between SUA and other risk factors. Five hundred and eighty-one subjects aged ≥65 years with non-insulin-dependent diabetes mellitus were prospectively studied in the frame of the CArdiovascular STudy in the ELderly (CASTEL). Historical and clinical data, blood tests and 12-year fatal events were recorded. SUA as a continuous item was divided into tertiles and, for each tertile, adjusted relative risk (RR) with 95% confidence intervals (CI) was derived from multivariate Cox analysis. CHD mortality was predicted by SUA in a J-shaped manner. Mortality rate was 7.9% (RR 1.28, CI 1.05–1.72), 6.0% (reference tertile) and 12.1% (RR 1.76, CI 1.18–2.27) in the increasing tertiles of SUA, respectively, without any difference between genders. In diabetic elderly subjects, SUA independently predicts the risk of CHD mortality in a J-shaped manner.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Gertler MM, Garn SM, Levine SA (1951) Serum uric acid in relation to age and physique in health and coronary heart disease. Ann Intern Med 34:1421–1431
Fang J, Alderman MH (2000) Serum uric acid and cardiovascular mortality. The NHANES I epidemiological follow-up 1971–1992. JAMA 283:2404–2410
Alderman MH, Cohen H, Madhavan S, Kivlighn S (1999) Serum uric acid and cardiovascular events in successfully treated hypertensive patients. Hypertension 34:144–150
Franse LV, Pahor M, Di Bari M, Shorr RI, Wan JY, Somes GW, Applegate WB (2000) Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP). J Hypertens 18:1149–1154
— (1985) Mortality findings for stepped-care and referred-care participants in the hypertension detection and follow-up program, stratified by other risk factors. The Hypertension Detection and Follow-up Program Cooperative Research Group. Prev Med 14:312–335
Bengtsson C, Lapidus L, Stendahl C, Waldenstrom J (1988) Hyperuricaemia and risk of cardiovascular disease and overall death. A 12-year follow-up of participants in the population study of women in Gothenburg, Sweden. Acta Med Scand 224:549–555
Levine W, Dyer AR, Shekelle RB, Schoenberger JA, Stamler J (1989) Serum uric acid and 11.5-year mortality of middleaged women: findings of the Chicago Heart Association Detection Project in Industry. J Clin Epidemiol 42:257–267
Wannamethee SG, Shaper AG, Whincup PH (1997) Serum urate and risk of major coronary heart disease events. Heart 78:147–153
Liese AD, Hense HW, Löwel H, Döring A, Tietze M, Keil U (1999) Association of serum uric acid with all cause and cardiovascular disease mortality and incident myocardial infarction in the MONICA Augsburg cohort. Epidemiology 10:391–397
Brand FN, McGee DL, Kannel WB, Stokes J, Castelli WP (1985) Hyperuricemia a a risk factor of coronary heart disease: The Framingham Study. Am J Epidemiol 121:11–18
Moriarity JT, Folsom AR, Iribarren C, Nieto FJ, Rosamond WD (2000) Serum uric acid and risk of coronary heart disease: Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol 10:136–143
Lee J, Sparrow D, Vokonas PS, Landsberg L, Weiss ST (1995) Uric acid and coronary heart disease risk: evidence for a role of uric acid in the obesity-insulin resistance syndrome. The Normative Aging Study. Am J Epidemiol 142:288–294
Wang JG, Staessen JA, Fagard RH, Birkenhäger WH, Gong L, Liu L (2001) Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension. Hypertension 37:1069–1074
Golik A, Weissgarten J, Cotariu D, Cohen N, Zaidenstein R, Ramot Y, Averbukh Z, Modai D (1993) Renal uric acid handling in non-insulin-dependent diabetic patients with elevated glomerular filtration rates. Clin Sci 85:713–716
Bo S, Cavallo-Perin P, Gentile L, Repetti E, Pagano G (2001) Hypouricemia and hyperuricemia in type 2 diabetes: two different phenotypes. Eur J Clin Invest 31:318–321
Facchini F, Chen YDI, Hollenbeck CB, Reaven GM (1991) Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration. JAMA 266:3008–3011
Casiglia E, Spolaore P, Mormino P, Maschio O, Colangeli G, Celegon L, Maggiolo G, Tittoto L, Pasinato A, Ambrosio GB (1991) The CASTEL project (CArdiovascular STudy in the ELderly): protocol, study design, and preliminary results of the initial survey. Cardiologia 36:569–576
Ledru F, Ducimetiere P, Battaglia S, Courbon D, Beverelli F, Guize L, Guermonprez JL, Diebold B (2001) New diagnostic criteria for diabetes and coronary artery disease: Insights from an angiographic study. J Am Coll Cardiol 37:1543–1550
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–35
Nicoll SR, Sainsburg R, Bailey RR, King A, Frampton C, Elliot JR (1991) Assessment of creatinine clearance in healthy subjects over 65 years of age. Nephron 59:621–625
Abbott RD, Brand FN, Kannel WB, Castelli WP (1988) Gout and coronary heart disease: the Framingham study. J Clin Epidemiol 41:237–242
Yoo TW, Sung KC, Shin HS, Kim BJ, Kim BS, Kang JH, Lee MH, Park JR, Kim H, Rhee EJ, Lee WY, Kim SW, Ryu SH, Keum DG (2005) Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome. Circ J 69:928–933
Wheeler JG, Juzwishin KDM, Eiriksdottir G, Gudnason V, Danesh J (2005) Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls: prospective study and meta-analysis. Plos Medicine 2:236–243
Suarna C, Dean RT, May J, Stocker R (1995) Human atherosclerotic plaque contains both axidiazed lipids and relatively large amounts of alpha-tocopherol and ascorbate. Arterioscler Thromb Vasc Biol 15:1616–1624
Maxwell SR, Thomason H, Sandler D, Leguen C, Baxter MA, Thorpe GH, Jones AF, Barnett AH (1997) Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabete mellitus. Eur J Clin Invest 27:484–490
Ceriello A, Bortolotti N, Pirisi M, Crescentini A, Tonutti L, Motz E, Russo A, Giacomello R, Stel G, Taboga C (1997) Total plasma antioxidant capacity predicts thrombosis-prone status in NIDDM patients. Diabetes Care 20:1589–1593
Ginsberg MH, Kozin F, O’Malley M, McCarty DJ (1977) Release of platelet constituents by monosodium urate crystals. J Clin Invest 60:999–1007
Alderman M, Kala JVA (2004) Uric acid: role in cardiovascular disease and effects of losartan. Curr Med Res Opin 20:369–379
Hsu SP, Pai MF, Peng SJ, Chiang CK, Ho TI, Hung KY (2004) Serum uric levels show a J-shaped trend association with all-cause mortality in haemodialysis patients. Nephrol Dial Transplant 19:457–462
Shichiri M, Iwamoto H, Marumo F (1990) Diabetic hypouricemia as an indicator of clinical nephropathy. Am J Nephrol 10:115–122
Tuttle KR, Short RA, Johnson JR (2001) Sex differences in uric acid and risk factors for coronary artery disease. Am J Cardiol 15:1411–1414
De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, Manger Cats V, Orth-Gomer K, Perk J, Pyorala K, Rodicio JL, Sans S, Sansoy V, Sechtem U, Silber S, Thomsen T, Wood D (2003) Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. European guidelines on cardiovascular disease prevention in clinical practice. Executive summary. Eur Heart J 24:1601–1610
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mazza, A., Zamboni, S., Rizzato, E. et al. Serum uric acid shows a J-shaped trend with coronary mortality in non-insulin-dependent diabetic elderly people. The CArdiovascular STudy in the ELderly (CASTEL). Acta Diabetol 44, 99–105 (2007). https://doi.org/10.1007/s00592-007-0249-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00592-007-0249-3