Serum uric acid: a forgotten prognostic marker in acute coronary syndromes?

Abstract

Background:

Serum uric acid (UA) has been shown to be an independent predictor of outcome in the general population and in patients with heart failure. There are, however, limited data regarding the prognostic value of UA in the context of acute coronary syndromes (ACS) particularly in medium-term follow up and the available results are contradictory.

Materials and methods:

Study of consecutive patients admitted with an ACS (with and without ST-segment elevation) at a single-centre coronary care unit. Primary endpoint was all-cause mortality at 1-year follow up. We evaluated if serum UA is an independent predictor of outcome and if it has any added value on top of GRACE risk score for risk prediction.

Results:

We included 683 patients, mean age 64±13 years, 69% males. In-hospital and 1-year mortality were 4.5 and 7.6% respectively. The best cut-off of UA to predict 1-year mortality was 6.25 mg/dl (sensitivity 59%, specificity 72%) and 30.2% of the patients had an increased UA according to this cut off. Independent predictors of UA were male gender (β= 0.078), body mass index (β=0.163), diuretics before admission (β=0.142), and admission serum creatinine (β=0.403). One-year mortality was significantly higher in patients with increased UA (15.5 vs. 4.2%, p<0.001; log rank, p<0.001). After adjustment, both increased UA as a categorical variable (HR 2.25, 95% CI 1.23–4.13, p=0.008) and as a continuous variable (HR 1.26, 95% CI 1.13–1.41, p<0.001) are independent predictors of mortality. The AUC increases only slightly after inclusion of UA in the model with GRACE risk score (from 0.78 to 0.79, p=0.350). Both models had a good fit; however, model fit worsened after inclusion of UA. Overall, the inclusion of UA in the original was associated with an improvement in both the net reclassification improvement (continuous NRI=44%), and the integrated discrimination improvement (IDI=0.052) suggesting effective reclassification.

Conclusions:

Serum UA is an independent predictor of all-cause mortality in medium-term after the whole spectrum of ACS and has an added value for risk stratification.

Keywords

Acute coronary syndromes prognosis serum uric acid

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References

Leyva

Anker

Swan

. Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure. Eur Heart J 1997; 18: 858–865.

Fessel

. High uric acid as an indicator of cardiovascular disease: independence from obesity. Am J Med 1980; 68: 401–404.

Fang

Alderman

. Serum uric acid and cardiovascular mortality: the NHANES I epidemiologic follow-up study, 1971–1992: National Health and Nutrition Examination Survey. JAMA 2000; 283: 2404–2410.

Weir

Muir

Walters

. Serum urate as an independent predictor of poor outcome and future vascular events after acute stroke. Stroke 2003; 34: 1951–1956.

Levya

Anker

Godsland

. Uric acid in chronic heart failure: a marker of chronic inflammation. Eur Heart J 1998; 19: 1814–1822.

Cockcroft

Gault

. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41.

Granger

Goldberg

Dabbous

. Predictors of hospital mortality in the Global Registry of Acute Coronary Events. Arch Intern Med 2003; 163: 2345–2353.

Pencina

D’Agostino

Steyerberg

. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Statis Med 2011; 30: 11–21.

Nieto

Iribarren

Gross

. Uric acid and serum antioxidant capacity: a reaction to atherosclerosis? Atherosclerosis 2000; 148: 131–139.

10.

Hayden

Tyagi

. 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.

11.

Hare

Johnson

. Uric acid predicts clinical outcomes in heart failure: insights regarding the role of xanthine oxidase and uric acid in disease pathophysiology. Circulation 2003; 107: 1951–1953.

12.

Anker

Doehner

Rauchhaus

. Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging. Circulation 2003; 107: 1991–1997.

13.

Basar

Sen

Ozcan

. Elevated serum uric acid predicts angiographic impaired reperfusion and 1-year mortality in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention. J Invest Med 2011; 59: 931–937.

14.

Feig

Kang

Johnson

. Uric acid and cardiovascular risk. N Engl J Med 2008; 359: 1811–1821.

15.

Johnson

Kang

Feig

. Is there a pathogenic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 2003; 41: 1183–1890.

16.

Culleton

Lansom

Kannel

. Serum uric acid and risk for cardiovascular disease and death: The Framingham Heart Study. Ann Intern Med 1999; 131: 7–13.

17.

Homayounfar

Ansari

Kashani

. Evaluation of independent prognostic importance of hyperuricemia in hospital death after acute myocardial infarction. Saudi Med J 2007; 28: 759–761.

18.

Lazzeri

Valente

Chiostri

. Uric acid in the acute phase of ST elevation myocardial infarction submitted to primary PCI: its prognostic role and relation with inflammatory markers. Int J Cardiol 2010; 21: 206–209.

19.

Lazzeri

Valente

Chiostri . Uric acid in the early risk stratification of ST-elevation myocardial infarction. Intern Emerg Med 2012; 7: 33–39.

20.

Kojima

Sakamoto

Ishihara

. Prognostic usefulness of serum uric acid after acute myocardial infarction (the Japanese Acute Coronary Syndrome Study). Am J Cardiol 2005; 96: 489–495.

21.

Bae

Lee

. Serum uric acid as an independent and incremental prognostic marker in addition to N-terminal Pro-B-type natriuretic peptide in patients with acute myocardial infarction. Circ J 2011; 75: 1440–1447.

22.

Car

Trkulja

. Higher serum uric acid on admission is associated with higher short-term mortality and poorer long-term survival after myocardial infarction: retrospective prognostic study. Croat Med J 2009; 50: 559–566.

23.

Akpek

Kaya

Uyarel

. The association of serum uric acid levels on coronary flow in patients with STEMI undergoing primary PCI. Atherosclerosis 2011; 219: 334–341.

24.

Kato

Hisatome

Tomikura

. Status of endothelial dependent vasodilation in patients with hiperuricemia. Am J Cardiol 2005; 96: 1576–1578.

25.

Ndrepepa

Braun

Haase

. Prognostic value of uric acid in patients with acute coronary syndromes. Am J Cardiol 2012; 109: 1260–1265.

26.

Kaya

Uyarel

Akpek

. Prognostic value of uric acid in patients with ST-elevated myocardial infarction undergoing primary coronary intervention. Am J Cardiol 2012; 109: 486–491.

27.

Gotsman

Keren

Lotan

. Changes in uric acid levels and allopurinol use in chronic heart failure: association with improved survival. J Card Fail 2012; 18: 694–701.

28.

Wei

Fahey

Struthers

. Association between allopurinol and mortality in heart failure patients: a long-term follow-up study. Int J Clin Pract 2009; 63: 1327–1333.

29.

Doehner

Schoene

Rauchhaus

. Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies. Circulation 2002; 105: 2619–2624.

30.

Rentoukas

Tsarouhas

Tsitsimpikou

. The prognostic impact of allopurinol in patients with acute myocardial infarction undergoing primary percutaneous coronary interventions. Int J Cardiol 2010; 145: 257–258.