Generic placeholder image

Current Vascular Pharmacology

Author(s): Georgios Georgiopoulos, Costas Tsioufis*, Theodoros Kalos, Nikos Magkas, Dimitris Roussos, Christina Chrysohoou, Georgia Sarri, Kyriaki Syrmali, Panos Georgakopoulos and Dimitrios Tousoulis

DOI: 10.2174/1570161116666171226124959

DownloadDownload PDF Flyer Cite As
Serum Uric Acid is Independently Associated with Diastolic Dysfunction in Apparently Healthy Subjects with Essential Hypertension

Page: [99 - 106] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Objectives: Accumulating evidence suggests a direct role of Uric Acid (UA) on Left Ventricular (LV) diastolic function in chronic kidney disease and Heart Failure (HF) patients. Recently, UA has been linked to LV Hypertrophy (LVH) and Diastolic Dysfunction (DD) in women with preserved Ejection Fraction (pEF) but not in corresponding men. We sought to assess if UA could predict indices of DD in hypertensive subjects with pEF independently of gender.

Method: We consecutively recruited 382 apparently healthy hypertensive subjects (age: 61.7±10.7, women: 61.3%, median EF: 64%). In 318 patients in sinus rhythm, LV mass-indexed to body surface area-was calculated (LVMI). LVH was set as an LVMI >116g/m2 or 96 g/m2 in men and women, respectively. The ratio of early transmitral peak velocity (E) to the mitral annular early diastolic velocity (Em) was used as an approximation of mean left atrial pressure (E/Em).

Results: UA [median (interquartile range): 5.4(2) mg/dl] independently predicted E/Em (adjusted coefficient: 1.01, p =0.026) while an interaction term between gender and UA was no significant (p=0.684). An ordinal score of DD was calculated taking into account increased E/Em, left atrium dilatation and LVH. Women with increased UA had 254% increased odds (adjusted OR=2.54, p=0.005) to be classified in the upper range of the DD score.

Conclusion: In hypertensive subjects without HF, UA is independently associated with the presence of DD in both genders and correlates with its severity in women. Further prospective studies are warranted to evaluate the association of UA with adverse cardiovascular outcomes in high-risk populations such as HF with pEF.

Keywords: Uric acid, diastolic dysfunction, preserved ejection fraction, hypertension, heart failure, metabolic syndrome.

Graphical Abstract

[1]
Bergamini C, Cicoira M, Rossi A, Vassanelli C. Oxidative stress and hyperuricaemia: Pathophysiology, clinical relevance, and therapeutic implications in chronic heart failure. Eur J Heart Fail 2009; 11: 444-52.
[2]
Kanellis J, Kang DH. Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. Semin Nephrol 2005; 25: 39-42.
[3]
Gromadzinski L, Januszko-Giergielewicz B, Pruszczyk P. Hyperuricemia is an independent predictive factor for left ventricular diastolic dysfunction in patients with chronic kidney disease. Adv Clin Exp Med 2015; 24: 47-54.
[4]
Johnson RJ, Kang DH, Feig D, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 2003; 41: 1183-90.
[5]
Borghi C, Rosei EA, Bardin T, et al. Serum uric acid and the risk of cardiovascular and renal disease. J Hypertens 2015; 33: 1729-41.
[6]
Huang H, Huang B, Li Y, et al. Uric acid and risk of heart failure: A systematic review and meta-analysis. Eur J Heart Fail 2014; 16: 15-24.
[7]
Yoo TW, Sung KC, Shin HS, et al. Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome. Circ J 2005; 69: 928-33.
[8]
Zoppini G, Targher G, Bonora E. The role of serum uric acid in cardiovascular disease in type 2 diabetic and non-diabetic subjects: a narrative review. J Endocrinol Invest 2011; 34: 881-6.
[9]
Cicoira M, Zanolla L, Rossi A, et al. Elevated serum uric acid levels are associated with diastolic dysfunction in patients with dilated cardiomyopathy. Am Heart J 2002; 143: 1107-11.
[10]
Nogi S, Fujita S, Okamoto Y, et al. Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction. Am J Physiol Heart Circ Physiol 2015; 309: 986-94.
[11]
Mandinov L, Eberli FR, Seiler C, Hess OM. Diastolic heart failure. Cardiovasc Res 2000; 45: 813-25.
[12]
Georgiopoulos G, Tsioufis C, Tsiachris D, et al. Metabolic syndrome, independent of its components, affects adversely cardiovascular morbidity in essential hypertensives. Atherosclerosis 2016; 244: 66-72.
[13]
Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34: 2159-219.
[14]
Mancia G, De Backer G, Dominiczak A, et al. ESH-ESC practice guidelines for the management of arterial hypertension: ESH-ESC task force on the management of arterial hypertension. J Hypertens 2007; 25: 1751-62.
[15]
Paulus WJ, Tschöpe C, Sanderson JE, et al. How to diagnose diastolic heart failure: A consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the heart failure and echocardiography associations of the European society of cardiology. Eur Heart J 2007; 28: 2539-50.
[16]
Das M, Borah NC, Ghose M, Choudhury N. Reference ranges for serum uric acid among healthy assamese people. Biochem Res Int 2014; 2014: 171053.
[17]
Collett D. Modelling Survival Data in Medical Research. 3rd ed. Chapman & Hall: London 1994; pp. 84-90.
[18]
Tavil Y, Kaya MG, Sen N, et al. Assessment of left ventricular systolic and diastolic function by tissue doppler analysis in patients with hypertension with or without hyperuricemia. Blood Press Monit 2008; 13: 79-84.
[19]
Chao TF, Hung CL, Chen SJ, et al. The association between hyperuricemia, left atrial size and new-onset atrial fibrillation. Int J Cardiol 2013; 168: 4027-32.
[20]
Yoshimura A, Adachi H, Hirai Y, et al. Serum uric acid is associated with the left ventricular mass index in males of a general population. Int Heart J 2014; 55: 65-70.
[21]
Tang ZH, Fang Z, Zeng F, Li Z, Zhou L. Association and interaction analysis of metabolic syndrome and serum uric acid on diastolic heart failure. J Endocrinol Invest 2013; 36: 579-83.
[22]
Shimizu T, Yoshihisa A, Kanno Y, et al. Relationship of hyperuricemia with mortality in heart failure patients with preserved ejection fraction. Am J Physiol Heart Circ Physiol 2015; 309: 1123-9.
[23]
Gotsman I, Keren A, Lotan C, Zwas DR. Changes in uric acid levels and allopurinol use in chronic heart failure: Association with improved survival. J Card Fail 2012; 18: 694-701.
[24]
Lin JC, Lin CL, Chen MC, et al. Gout, not hyperuricemia alone, impairs left ventricular diastolic function. Arthritis Res Ther 2015; 17: 323.
[25]
Münzel T, Gori T, Keaney JF Jr, Maack C, Daiber A. Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications. Eur Heart J 2015; 36: 2555-64.
[26]
Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: Comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 2013; 62: 263-71.
[27]
Hayden MR, Tyagi SC. Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle. Nutr Metab 2004; 1: 10.
[28]
Sautin YY, Johnson RJ. Uric acid: The oxidant-antioxidant paradox. Nucleos Nucleot Nucl Acids 2008; 27: 608-19.
[29]
Ruggiero C, Cherubini A, Ble A, et al. Uric acid and inflammatory markers. Eur Heart J 2006; 27: 1174-81.
[30]
Franssen C, Paulus WJ. The future diagnosis of heart failure with normal ejection fraction: Less imaging, more biomarkers? Eur J Heart Fail 2011; 13: 1043-5.
[31]
Sciarretta S, Paneni F, Palano F, et al. Role of the renin-angiotensin-aldosterone system and inflammatory processes in the development and progression of diastolic dysfunction. Clin Sci 2009; 116: 467-77.
[32]
Zoccali C, Maio R, Mallamaci F, Sesti G, Perticone F. Uric acid and endothelial dysfunction in essential hypertension. J Am Soc Nephrol 2006; 17: 1466-71.
[33]
Lam CS, Brutsaert DL. Endothelial dysfunction: A pathophysiologic factor in heart failure with preserved ejection fraction. J Am Coll Cardiol 2012; 60: 1787-9.
[34]
Doehner W, Schoene N, Rauchhaus M, et al. Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patient with chronic heart failure: Results from 2 placebo-controlled studies. Circulation 2002; 105: 2619-24.
[35]
Perlstein TS, Gumieniak O, Hopkins PN, et al. Uric acid and the state of the intrarenal renin-angiotensin system in humans. Kidney Int 2004; 66: 1465-70.
[36]
Lacolley P, Regnault V, Nicoletti A, Li Z, Michel JB. The vascular smooth muscle cell in arterial pathology: A cell that can take on multiple roles. Cardiovasc Res 2012; 95: 194-204.
[37]
Chow B, Rabkin SW. The relationship between arterial stiffness and heart failure with preserved ejection fraction: A systemic meta-analysis. Heart Fail Rev 2015; 20: 291-303.
[38]
Von Bibra H, St John Sutton M. Diastolic dysfunction in diabetes and the metabolic syndrome: promising potential for diagnosis and prognosis. Diabetologia 2010; 53: 1033-45.
[39]
Georgiopoulos GA, Lambrinoudaki I, Athanasouli F, et al. Free androgen index as a predictor of blood pressure progression and accelerated vascular aging in menopause. Atherosclerosis 2016; 247: 177-83.
[40]
Hare JM, Mangal B, Brown J, et al. Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study. J Am Coll Cardiol 2008; 51: 2301-9.
[41]
Sattarzade Badkoobeh R, Nozari Y, Larti F, Safari S, Ahmadi F, Emami M. Allopurinol effects on diastolic dysfunction in ESRD patients with hyperuricemia. Tehran Univ Med J 2011; 68: 618-23.
[42]
Kao MP, Ang DS, Gandy SJ, et al. Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease. J Am Soc Nephrol 2011; 22: 1382-9.