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The diverse associations of uric acid with low-grade inflammation, adiponectin and arterial stiffness in never-treated hypertensives

Journal of Human Hypertension volume 25, pages 554–559 (2011)Cite this article

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Abstract

The data regarding the role of serum uric acid (SUA) along with subclinical inflammation in the context of hypertensive vascular damage are rather scarce and controversial. Towards this end, we assess the links between SUA, high-sensitivity CRP (hs-CRP), adiponectin and carotid to femoral pulse wave velocity (c–f PWV) in 292 subjects with never-treated stage I–II essential hypertension. On the basis of the median SUA levels (0.31 mmol l−1), the study population was divided into subjects with low (n=149) and high (n=143) SUA values. By multiple regression analysis, it was revealed that SUA was independently associated with log hs-CRP (R2=0.098; P=0.02), log adiponectin (R2=0.102; P=0.03), waist circumference (R2=0.049; P=0.04), 24-h systolic blood pressure (SBP) (R2=0.179; P=0.001) and estimated glomerular filtration rate (R2=0.156; β (s.e.)=−0.169 (0.023); P=0.02). In addition, c–f PWV was independently associated with age (R2=0.116; P<0.0001), waist circumference (R2=0.088; P<0.0001), 24-h SBP (R2=0.167; P=0.001), log adiponectin (R2=0.07; P=0.006) and log hs-CRP (R2=0.06; P=0.034). In conclusion, SUA levels are independently associated with hs-CRP and adiponectin levels but not with c–f PWV in essential hypertensive patients. Increased SUA levels are accompanied by a state of pronounced inflammatory activation and hypoadiponectinemia that significantly impairs the arterial stiffness accelerating the vascular ageing process in this setting.

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References

  1. Cannon PJ, Stason WB, Demartini FE, Sommers SC, Laragh JH . Hyperuricemia in primary and renal hypertension. N Engl J Med 1966; 275: 457–464.

    Article  CAS  Google Scholar 

  2. Baker JF, Krishnan E, Chen L, Schumacher HR . Serum uric acid and cardiovascular disease: recent developments and where do they leave us? Am J Med 2005; 118: 816–826.

    Article  CAS  Google Scholar 

  3. Short RA, Johnson RJ, Tuttle KR . Uric acid, microalbuminuria and cardiovascular events in high-risk patients. Am J Nephrol 2005; 25: 36–44.

    Article  CAS  Google Scholar 

  4. Verdecchia P, Schillaci G, Reboldi G, Santeusanio F, Porcellati C, Brunetti P . Relation between serum uric acid and risk of cardiovascular disease in essential hypertension: the PIUMA study. Hypertension 2000; 36: 1072–1078.

    Article  CAS  Google Scholar 

  5. Sakata K, Hashimoto T, Ueshima H, Okayama A, NIPPON DATA 80 Research Group. Absence of an association between serum uric acid and mortality from cardiovascular disease: NIPPON DATA 80, 1980–1994. National integrated projects for prospective observation of noncommunicable diseases and its trend in the aged. Eur J Epidemiol 2001; 17: 461–468.

    Article  CAS  Google Scholar 

  6. Mazzali M, Kanellis J, Han L, Feng L, Xia YY, Chen Q et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol 2002; 282: 991–997.

    Article  Google Scholar 

  7. Rao GN, Corson MA, Berk BC . Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor a-chain expression. J Biol Chem 1991; 266: 8604–8608.

    CAS  PubMed  Google Scholar 

  8. Sanchez-Lozada LG, Tapia E, Santamaria J, Avila-Casado C, Soto V, Nepomuceno T et al. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 2005; 67: 237–247.

    Article  Google Scholar 

  9. Corry DB, Eslami P, Yamamoto K, Nyby MD, Makino H, Tuck ML . Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens 2008; 26: 269–275.

    Article  CAS  Google Scholar 

  10. Kanellis J, Watanabe S, Li JH, Kang DH, Li P, Nakagawa T et al. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension 2003; 41: 1287–1293.

    Article  CAS  Google Scholar 

  11. Tsioufis C, Dimitriadis K, Andrikou E, Thomopoulos C, Tsiachris D, Stefanadi E et al. ADMA, C-reactive protein, and albuminuria in untreated essential hypertension: a cross-sectional study. Am J Kidney Dis 2010; 55: 1050–1059.

    Article  CAS  Google Scholar 

  12. Tsioufis C, Dimitriadis K, Selima M, Thomopoulos C, Mihas C, Skiadas I et al. Low-grade inflammation and hypoadiponectinaemia have an additive detrimental effect on aortic stiffness in essential hypertensive patients. Eur Heart J 2007; 28: 1162–1169.

    Article  CAS  Google Scholar 

  13. Feig DI, Kang D-H, Johnson RJ . Uric acidand cardiovascular risk. N Engl J Med 2008; 359: 1811–1821.

    Article  CAS  Google Scholar 

  14. Tsioufis C, Chatzis D, Vezali E, Dimitriadis K, Antoniadis D, Zervoudaki A et al. The controversial role of serum uric acid in essential hypertension: relationships with indices of target organ damage. J Hum Hypertens 2005; 19: 211–217.

    Article  CAS  Google Scholar 

  15. Tsioufis C, Stefanadis C, Antoniadis D, Kallikazaros I, Zambaras P, Pitsavos C et al. Absence of any significant effects of circadian blood pressure variations on carotid artery elastic properties in essential hypertensive subjects. J Hum Hypertens 2000; 14: 813–818.

    Article  CAS  Google Scholar 

  16. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H et al. Recommendations for quantitation of the left ventricular dimensions by two-dimensional echocardiography. American society of echocardiography committee on standards, subcommittee on quantitation of the two-dimensional echocardiograms. J Am Soc Echocardiogr 1989; 2: 358–367.

    Article  CAS  Google Scholar 

  17. Tsioufis C, Chatzis D, Dimitriadis K, Stougiannos P, Kakkavas A, Vlasseros I et al. Left ventricular diastolic dysfunction is accompanied by increased aortic stiffness in the early stages of essential hypertension: a TDI approach. J Hypertens 2005; 23: 1745–1750.

    Article  CAS  Google Scholar 

  18. Netea MG, Kullberg BJ, Block WL, Netea RT, van der Meer JW . The role of hyperuricemia in the increased cytokine production after lipopolysaccharide challenge in neutropenic mice. Blood 1997; 89: 577–582.

    CAS  PubMed  Google Scholar 

  19. Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 2003; 41: 1183–1190.

    Article  CAS  Google Scholar 

  20. Shetty GK, Economides PA, Horton ES, Mantzoros CS, Veves A . Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 2004; 27: 2450–2457.

    Article  CAS  Google Scholar 

  21. Teijeira-Fernandez E, Eiras S, Grigorian-Shamagian L, Fernandez A, Adrio B, Gonzalez-Juanatey JR . Epicardial adipose tissue expression of adiponectin is lower in patients with hypertension. J Hum Hypertens 2008; 22: 856–863.

    Article  CAS  Google Scholar 

  22. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res 2002; 10: 1104–1110.

    Article  CAS  Google Scholar 

  23. González-Sánchez JL, Zabena CA, Martínez-Larrad MT, Fernández-Pérez C, Pérez-Barba M, Laakso M et al. An SNP in the adiponectin gene is associated with decreased serum adiponectin levels and risk for impaired glucose tolerance. Obes Res 2005; 13: 807–812.

    Article  Google Scholar 

  24. Yamamoto Y, Hirose H, Saito I, Tomita M, Taniyama M, Matsubara K et al. Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin Sci 2002; 103: 137–142.

    Article  CAS  Google Scholar 

  25. Fessel WJ . High uric acid as an indicator of cardiovascular disease. Am J Med 1980; 68: 401–404.

    Article  CAS  Google Scholar 

  26. Freedman DS, Williamson DF, Gunter EW, Byers T . Relation of serum uric acid to mortality and ischemic heart disease. Am J Epidemiol 1995; 141: 637–644.

    Article  CAS  Google Scholar 

  27. Moriarity JT, Folsom AR, Iribarren C, Nieto FJ, Rosamond WD . Serum uric acid and risk of coronary heart disease: Atherosclerosis Risk in Communities (ARIC) Study. Ann Epidemiol 2000; 10: 136–143.

    Article  CAS  Google Scholar 

  28. Tomiyama H, Kushiro T, Okazaki R, Yoshida H, Doba N, Yamashina A . Influences of age and gender on results of noninvasive brachial-ankle pulse wave velocity measurement a survey of 12517 subjects. Atherosclerosis 2003; 166: 303–309.

    Article  CAS  Google Scholar 

  29. Cuspidi C, Valerio C, Sala C, Meani S, Esposito A, Zanchetti A et al. Lack of association between serum uric acid and organ damage in a never-treated essential hypertensive population at low prevalence of hyperuricemia. Am J Hypertens 2007; 20: 678–685.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. First Cardiology Clinic, Hippokration Hospital, University of Athens, Athens, Greece

    C Tsioufis, S Kyvelou, K Dimitriadis, D Syrseloudis, S Sideris, I Skiadas, V Katsi, E Stefanadi, S Lalos, C Mihas, M Poulakis & C Stefanadis

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  1. C Tsioufis
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  2. S Kyvelou
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  3. K Dimitriadis
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Correspondence to C Tsioufis.

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Tsioufis, C., Kyvelou, S., Dimitriadis, K. et al. The diverse associations of uric acid with low-grade inflammation, adiponectin and arterial stiffness in never-treated hypertensives. J Hum Hypertens 25, 554–559 (2011). https://doi.org/10.1038/jhh.2010.98

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