Top

Published in:

01-06-2012 | Original Article

Cross-sectional and longitudinal associations between serum uric acid and metabolic syndrome

Authors: J. P. Gonçalves, A. Oliveira, M. Severo, A. C. Santos, C. Lopes

Published in: Endocrine | Issue 3/2012

Abstract

Research on the importance of serum uric acid (SUA) as a contributing metabolic factor to cardiovascular diseases has conducted to conflicting results, with most studies assuming a cross-sectional design. The aim of this study was to evaluate the association of SUA and metabolic syndrome (MetS) and its features. A representative sample of 2,485 individuals aged ≥18 years was randomly selected from the non-institutionalized resident population of Porto, Portugal. A total of 1,054 eligible subjects were included for the longitudinal analyses. Hyperuricemia was defined as SUA ≥70 mg/L in men and ≥60 mg/L in women. MetS was defined according the Joint Interim (2009) criteria. Associations were estimated using Poison regression and binomial models. In the cross-sectional analysis, subjects with hyperuricemia had a 2.10-fold increased risk of MetS as compared with normouricemic subjects (PR = 2.10, 95% CI: 1.68–2.63). Among MetS features, high triglycerides presented the strongest association with hyperuricemia (PR = 2.32, 95% CI: 1.84–2.91). The MetS crude incidence rate was 4.5/100 person-year (95% CI: 3.9–5.2) in normal uricemic and 13.0/100 person-year (95% CI: 8.5–20.0) in hyperuricemic participants. Using a multivariate longitudinal approach, hyperuricemia was positively associated with MetS incidence rate ratios (IRR = 1.73, 95% CI: 1.08–2.76). One standard deviation increase of SUA concentration was associated with a 1.22-fold increase in MetS risk (IRR = 1.22, 95% CI: 1.05–1.42). Elevated SUA presented the strongest association with high-triglycerides concentration (IRR = 1.44, 95%: 1.22–1.71) and waist circumference (IRR = 1.25, 95%: 1.05–1.49). The independent positive association between SUA and MetS suggested by this longitudinal study supports that SUA might be a risk factor for MetS.

D. Conen, V. Wietlisbach, P. Bovet, C. Shamlaye, W. Riesen, F. Paccaud, M. Burnier, Prevalence of hyperuricemia and relation of serum uric acid with cardiovascular risk factors in a developing country. BMC Public Health 4, 9 (2004). doi:10.1186/1471-2458-4-9 PubMedCrossRef

A.C. Gagliardi, M.H. Miname, R.D. Santos, Uric acid: a marker of increased cardiovascular risk. Atherosclerosis 202(1), 11–17 (2009). doi:10.1016/j.atherosclerosis.2008.05.022 PubMedCrossRef

T. Montalcini, G. Gorgone, C. Gazzaruso, G. Sesti, F. Perticone, A. Pujia, Relation between serum uric acid and carotid intima-media thickness in healthy postmenopausal women. Intern. Emerg. Med. 2(1), 19–23 (2007). doi:10.1007/s11739-007-0004-3 PubMedCrossRef

T. Nakagawa, P. Cirillo, W. Sato, M. Gersch, Y. Sautin, C. Roncal, W. Mu, L.G. Sanchez-Lozada, R.J. Johnson, The conundrum of hyperuricemia, metabolic syndrome, and renal disease. Intern. Emerg. Med. 3(4), 313–318 (2008). doi:10.1007/s11739-008-0141-3 PubMedCrossRef

J. Lee, D. Sparrow, P.S. Vokonas, L. Landsberg, S.T. Weiss, 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(3), 288–294 (1995)PubMed

W. Rathmann, B. Haastert, A. Icks, G. Giani, J.M. Roseman, Ten-year change in serum uric acid and its relation to changes in other metabolic risk factors in young black and white adults: the CARDIA study. Eur. J. Epidemiol. 22(7), 439–445 (2007). doi:10.1007/s10654-007-9132-3 PubMedCrossRef

D.I. Feig, D.H. Kang, R.J. Johnson, Uric acid and cardiovascular risk. N. Engl. J. Med. 359(17), 1811–1821 (2008). doi:10.1056/NEJMra0800885 PubMedCrossRef

R.J. Johnson, D.I. Feig, J. Herrera-Acosta, D.H. Kang, Resurrection of uric acid as a causal risk factor in essential hypertension. Hypertension 45(1), 18–20 (2005). doi:10.1161/01.HYP.0000150785.39055.e8 PubMed

M. Cigolini, G. Targher, M. Tonoli, F. Manara, M. Muggeo, G. De Sandre, Hyperuricaemia: relationships to body fat distribution and other components of the insulin resistance syndrome in 38-year-old healthy men and women. Int. J. Obes. Relat. Metab. Disord. 19(2), 92–96 (1995)PubMed

10.

T. Nakagawa, K.R. Tuttle, R.A. Short, R.J. Johnson, Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol 1(2), 80–86 (2005). doi:10.1038/ncpneph0019 PubMedCrossRef

11.

K. Masuo, H. Kawaguchi, H. Mikami, T. Ogihara, M.L. Tuck, Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 42(4), 474–480 (2003)PubMedCrossRef

12.

A. Dehghan, M. van Hoek, E.J. Sijbrands, A. Hofman, J.C. Witteman, High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care 31(2), 361–362 (2008). doi:10.2337/dc07-1276 PubMedCrossRef

13.

T. Wang, Y. Bi, M. Xu, Y. Huang, Y. Xu, X. Li, W. Wang, G. Ning, Serum uric acid associates with the incidence of type 2 diabetes in a prospective cohort of middle-aged and elderly Chinese. Endocrine 40(1), 109–116 (2011). doi:10.1007/s12020-011-9449-2 PubMedCrossRef

14.

M. Alderman, K.J. Aiyer, Uric acid: role in cardiovascular disease and effects of losartan. Curr. Med. Res. Opin. 20(3), 369–379 (2004). doi:10.1185/030079904125002982 PubMedCrossRef

15.

M. Schachter, Uric acid and hypertension. Curr. Pharm. Des. 11(32), 4139–4143 (2005)PubMedCrossRef

16.

Y.Y. Sautin, T. Nakagawa, S. Zharikov, R.J. Johnson, Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol 293(2), C584–C596 (2007). doi:10.1152/ajpcell.00600.2006 PubMedCrossRef

17.

K.J. Cheung, I. Tzameli, P. Pissios, I. Rovira, O. Gavrilova, T. Ohtsubo, Z. Chen, T. Finkel, J.S. Flier, J.M. Friedman, Xanthine oxidoreductase is a regulator of adipogenesis and PPARgamma activity. Cell Metab. 5(2), 115–128 (2007). doi:10.1016/j.cmet.2007.01.005 PubMedCrossRef

18.

T. Nakagawa, H. Hu, S. Zharikov, K.R. Tuttle, R.A. Short, O. Glushakova, X. Ouyang, D.I. Feig, E.R. Block, J. Herrera-Acosta, J.M. Patel, R.J. Johnson, A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 290(3), F625–F631 (2006). doi:10.1152/ajprenal.00140.2005 PubMedCrossRef

19.

W.Y. Lin, C.S. Liu, T.C. Li, T. Lin, W. Chen, C.C. Chen, C.I. Li, C.C. Lin, In addition to insulin resistance and obesity, hyperuricemia is strongly associated with metabolic syndrome using different definitions in Chinese populations: a population-based study (Taichung Community Health Study). Ann. Rheum. Dis. 67(3), 432–433 (2008). doi:10.1136/ard.2007.073601 PubMedCrossRef

20.

N. Ishizaka, Y. Ishizaka, E. Toda, R. Nagai, M. Yamakado, Association between serum uric acid, metabolic syndrome, and carotid atherosclerosis in Japanese individuals. Arterioscler. Thromb. Vasc. Biol. 25(5), 1038–1044 (2005). doi:10.1161/01.ATV.0000161274.87407.26 PubMedCrossRef

21.

T. Wilsgaard, B.K. Jacobsen, Lifestyle factors and incident metabolic syndrome. The Tromso Study 1979–2001. Diabetes Res. Clin. Pract. 78(2), 217–224 (2007). doi:10.1016/j.diabres.2007.03.006 PubMedCrossRef

22.

S. Ryu, J. Song, B.Y. Choi, S.J. Lee, W.S. Kim, Y. Chang, D.I. Kim, B.S. Suh, K.C. Sung, Incidence and risk factors for metabolic syndrome in Korean male workers, ages 30 to 39. Ann. Epidemiol. 17(4), 245–252 (2007). doi:10.1016/j.annepidem.2006.10.001 PubMedCrossRef

23.

J. Tong, E.J. Boyko, K.M. Utzschneider, M.J. McNeely, T. Hayashi, D.B. Carr, T.M. Wallace, S. Zraika, F. Gerchman, D.L. Leonetti, W.Y. Fujimoto, S.E. Kahn, Intra-abdominal fat accumulation predicts the development of the metabolic syndrome in non-diabetic Japanese-Americans. Diabetologia 50(6), 1156–1160 (2007). doi:10.1007/s00125-007-0651-y PubMedCrossRef

24.

A.C. Santos, M. Severo, H. Barros, Incidence and risk factors for the metabolic syndrome in an urban South European population. Prev. Med. 50(3), 99–105 (2010). doi:10.1016/j.ypmed.2009.11.011 PubMedCrossRef

25.

E. Ramos, C. Lopes, H. Barros, Investigating the effect of nonparticipation using a population-based case-control study on myocardial infarction. Ann. Epidemiol. 14(6), 437–441 (2004). doi:10.1016/j.annepidem.2003.09.013 PubMedCrossRef

26.

Organization, W.H.: Guidelines for ATC classification. Collaborating centre for drug statistics methodology. Nordic Council on Medicines. WHO. (1990)

27.

M.C. Horchberg, J.S. Smolen et al., Rheumatology, 3rd edn. (Mosby, New York, 2003)

28.

C. Lopes, A. Aro, A. Azevedo, E. Ramos, H. Barros, Intake and adipose tissue composition of fatty acids and risk of myocardial infarction in a male Portuguese community sample. J. Am. Diet. Assoc. 107(2), 276–286 (2007). doi:10.1016/j.jada.2006.11.008 PubMedCrossRef

29.

Lopes, C.: Reproducibility and validity of a semi-quantitative food frequency questionnaire. In Diet and acute myocardial infarction: a population based case-control study. PhD thesis. University of Porto, Porto, 79–115 2000

30.

M. Camoes, M. Severo, A.C. Santos, H. Barros, C. Lopes, Testing an adaptation of the EPIC physical activity questionnaire in Portuguese adults: a validation study that assesses the seasonal bias of self-report. Ann. Hum. Biol. 37(2), 185–197 (2010). doi:10.3109/03014460903341836 PubMedCrossRef

31.

S.M. Grundy, J.I. Cleeman, S.R. Daniels, K.A. Donato, R.H. Eckel, B.A. Franklin, D.J. Gordon, R.M. Krauss, P.J. Savage, S.C. Smith Jr, J.A. Spertus, F. Costa, Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112(17), 2735–2752 (2005). doi:10.1161/CIRCULATIONAHA.105.169404 PubMedCrossRef

32.

K.G. Alberti, R.H. Eckel, S.M. Grundy, P.Z. Zimmet, J.I. Cleeman, K.A. Donato, J.C. Fruchart, W.P. James, C.M. Loria, S.C. Smith Jr, Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120(16), 1640–1645 (2009). doi:10.1161/CIRCULATIONAHA.109.192644 PubMedCrossRef

33.

L.Y. Chen, W.H. Zhu, Z.W. Chen, H.L. Dai, J.J. Ren, J.H. Chen, L.Q. Chen, L.Z. Fang, Relationship between hyperuricemia and metabolic syndrome. J Zhejiang Univ Sci B 8(8), 593–598 (2007). doi:10.1631/jzus.2007.B0593 PubMedCrossRef

34.

W. Rathmann, E. Funkhouser, A.R. Dyer, J.M. Roseman, Relations of hyperuricemia with the various components of the insulin resistance syndrome in young black and white adults: the CARDIA study. Coronary Artery Risk Development in Young Adults. Ann. Epidemiol. 8(4), 250–261 (1998)PubMedCrossRef

35.

H. Vuorinen-Markkola, H. Yki-Jarvinen, Hyperuricemia and insulin resistance. J. Clin. Endocrinol. Metab. 78(1), 25–29 (1994)PubMedCrossRef

36.

C. Russo, O. Olivieri, D. Girelli, P. Guarini, R. Corrocher, Relationships between serum uric acid and lipids in healthy subjects. Prev. Med. 25(5), 611–616 (1996). doi:10.1006/pmed.1996.0096 PubMedCrossRef

37.

Y. Moriwaki, T. Yamamoto, S. Takahashi, Z. Tsutsumi, K. Higashino, Apolipoprotein E phenotypes in patients with gout: relation with hypertriglyceridaemia. Ann. Rheum. Dis. 54(5), 351–354 (1995)PubMedCrossRef

38.

F. Cardona, F.J. Tinahones, E. Collantes, A. Escudero, E. Garcia-Fuentes, F.J. Soriguer, The elevated prevalence of apolipoprotein E2 in patients with gout is associated with reduced renal excretion of urates. Rheumatology (Oxford) 42(3), 468–472 (2003)

39.

J.M. Boer, C. Ehnholm, H.J. Menzel, L.M. Havekes, M. Rosseneu, D.S. O’Reilly, L. Tiret, Interactions between lifestyle-related factors and the ApoE polymorphism on plasma lipids and apolipoproteins. The EARS Study. European Atherosclerosis Research Study. Arterioscler. Thromb. Vasc. Biol. 17(9), 1675–1681 (1997)PubMedCrossRef

40.

A. Bedir, M. Topbas, F. Tanyeri, M. Alvur, N. Arik, Leptin might be a regulator of serum uric acid concentrations in humans. Jpn. Heart J. 44(4), 527–536 (2003)PubMedCrossRef

41.

O. Bosello, M. Zamboni, Visceral obesity and metabolic syndrome. Obes. Rev. 1(1), 47–56 (2000)PubMedCrossRef

42.

J.P. Forman, H. Choi, G.C. Curhan, Plasma uric acid level and risk for incident hypertension among men. J. Am. Soc. Nephrol. 18(1), 287–292 (2007). doi:10.1681/ASN.2006080865 PubMedCrossRef

43.

P.B. Mellen, A.J. Bleyer, T.P. Erlinger, G.W. Evans, F.J. Nieto, L.E. Wagenknecht, M.R. Wofford, D.M. Herrington, Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study. Hypertension 48(6), 1037–1042 (2006). doi:10.1161/01.HYP.0000249768.26560.66 PubMedCrossRef

44.

A. Shankar, R. Klein, B.E. Klein, F.J. Nieto, The association between serum uric acid level and long-term incidence of hypertension: population-based cohort study. J. Hum. Hypertens. 20(12), 937–945 (2006). doi:10.1038/sj.jhh.1002095 PubMedCrossRef

45.

J. Lee, Odds ratio or relative risk for cross-sectional data? Int. J. Epidemiol. 23(1), 201–203 (1994)PubMedCrossRef

46.

O. Axelson, M. Fredriksson, K. Ekberg, Use of the prevalence ratio v the prevalence odds ratio in view of confounding in cross sectional studies. Occup. Environ. Med. 52(7), 494 (1995)PubMedCrossRef

47.

P. Neil, Effect measures in prevalence studies. Environ. Health Perspect. 112(10), 1047–1050 (2004)CrossRef

48.

M.L. Thompson, J.E. Myers, D. Kriebel, Prevalence odds ratio or prevalence ratio in the analysis of cross sectional data: what is to be done? Occup. Environ. Med. 55(4), 272–277 (1998)PubMedCrossRef

Title: Cross-sectional and longitudinal associations between serum uric acid and metabolic syndrome
Authors: J. P. Gonçalves
A. Oliveira
M. Severo
A. C. Santos
C. Lopes
Publication date: 01-06-2012
Publisher: Springer US
Published in: Endocrine / Issue 3/2012
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-012-9629-8

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Cross-sectional and longitudinal associations between serum uric acid and metabolic syndrome

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2012

Salivary cortisol and the diagnosis of Cushing’s syndrome: a coming of age

Mini-review: new therapeutic options in hypoparathyroidism

Triiodothyronine stimulates glucose transport in bone cells

The impact of birth weight and maternal history on acne, hirsutism, and menstrual disorder symptoms in Turkish adolescent girls

A new insight of mechanisms, diagnosis and treatment of diabetic cardiomyopathy

High prevalence of radiological vertebral fractures in HIV-infected males

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page