Elsevier

Atherosclerosis

Volume 269, February 2018, Pages 229-235
Atherosclerosis

Hyperuricemia as a prognostic factor after acute coronary syndrome

https://doi.org/10.1016/j.atherosclerosis.2018.01.017Get rights and content

Highlights

  • Hyperuricemia is independently associated with poor clinical outcomes after ACS.

  • If GRACE score includes hyperuricemia, risk classification for non-events improves.

  • It is known serum uric acid level is an inexpensive and commonly ordered measure.

  • Uric acid level might help stratify risk for poor outcomes after ACS.

Abstract

Background and aims

Many studies have reported the independent association between uric acid and cardiovascular disease, its role as a risk predictor for outcomes in people with acute coronary syndrome remains controversial. This study aims to assess the association between hyperuricemia and medium/long-term clinical outcomes in people with acute coronary syndrome and determine whether adding hyperuricemia to the GRACE score improves its predictive capability.

Methods

This cohort study included patients admitted for acute coronary syndrome between 2008 and 2013. Outcomes were cardiovascular and total mortality, and major cardiovascular events. We used a multivariate model to adjust for potential confounding covariates and presented event rates with Kaplan-Meier curves. After adding hyperuricemia to the GRACE score, we compared scores from the reclassification table and the net reclassification improvement.

Results

1119 participants were included and followed-up for a mean of 36 months. Multivariate models showed hyperuricemia was independently associated with higher cardiovascular mortality (HR:1.91; 95% CI:1.32–2.76; p < 0.01), higher all-cause mortality (HR:1.59; 95% CI:1.18–2.15; p < 0.01) and higher major cardiovascular event rates (HR:1.36; 95% CI:1.11–1.67; p < 0.01). The hyperuricemia addition to GRACE score led to reclassifying 26% of the participants, and net reclassification improvement was 34%. However, the area under the curve increase was 0.009 and not statistically significant (p > 0.05).

Conclusions

Hyperuricemia is associated with higher medium/long-term mortality and major cardiovascular event rates in patients following acute coronary syndrome. The addition of hyperuricemia to the GRACE score seems to improve risk classification but the discrimination of the new predictive model did not change. Hyperuricemic patients had higher all-cause mortality in medium and high-risk score categories.

Introduction

Different authors have suspected an association between elevated serum uric acid (SUA) levels and cardiovascular disease since the late nineteenth century [1,2]. A number of studies have shown that SUA concentration is significantly associated with cardiovascular conditions [[3], [4], [5], [6], [7]]. At the same time, elevated SUA levels are linked to various cardiovascular risk factors, including hypertension [8], dyslipidemia [9], diabetes [10], obesity [11], metabolic syndrome, kidney failure [12] and specific target organ damage, making it difficult to determine whether uric acid is a cause or a consequence of these conditions [13,14].

Many epidemiological studies have shown through multivariate analyses that hyperuricemia is an independent risk factor for the development of cardiovascular disease and/or vascular morbidity and mortality, particularly in patients with hypertension or congestive heart failure [15,16]. A recent systematic review showed that hyperuricemia may slightly increase the risk of CAD events, independently of traditional cardiovascular risk factors [17]. Nevertheless, not all population-based epidemiological studies support this hypothesis [18], and other authors have suggested that hyperuricemia is a risk marker rather than an independent risk factor [19,20]. Medical societies have not recognized elevated SUA as a cardiovascular risk factor [14].

The association between elevated SUA and poor clinical outcomes in people with stable CAD and heart failure is well documented [17,21], but less is known about SUA as a potential predictor of outcomes after acute myocardial infarction, particularly in high-risk patients [22,23]. Over the past few years, several studies have explored the value of on-admission SUA to predict outcomes in patients with acute coronary syndromes (ACS) [5,23]. A recent meta-analysis showed that hyperuricemia was associated with a 46% increased risk of adverse clinical events after any percutaneous coronary intervention (PCI) [24]. There is less evidence on how hyperuricemia impacts the long-term prognosis after ACS.

Acute myocardial infarction remains one of the most prevalent causes of death worldwide, with the highest mortality rates within the first month of an event [25]. Clinical decision-making requires an accurate assessment of cardiovascular risk, which has a significant influence on choosing between different management strategies that vary in terms of benefits, risks, and costs [26]. SUA may be a powerful tool to help stratify risk for cardiovascular disease [16], and risk stratification systems for patients with acute myocardial infarction, like the Global Registry of Acute Coronary Events (GRACE) [27], could benefit from including SUA, particularly as this marker is readily and reliably obtainable at a low cost [28].

Despite extensive research, the role of SUA as a potential risk predictor for outcomes in people with ACS remains controversial. Therefore, the present study aims to assess the prognostic value of hyperuricemia in ACS patients for medium/long-term clinical outcomes after hospital discharge and to evaluate the reclassification of the GRACE risk score.

Section snippets

Patients and methods

This is a prospective cohort study in a tertiary university hospital with a 24 h a day, seven days per week primary percutaneous coronary intervention service. We initiated a continuous registry of all non-scheduled admissions in the Cardiology Unit in December 2008 [29], and we included all consecutive patients admitted for an ACS between December 2008 and December 2013. ACS diagnosis was defined as [1] typical clinical symptoms of chest pain [2]; electrocardiographic changes indicative of

Results

The study population included 1323 patients, 204 of whom were excluded due to lack of SUA determination during hospital stay. Thus, the study cohort consisted of 1119 participants (74% men, n = 830) with a mean age of 68 (SD 13) years. Baseline characteristics are presented in Table 1. The prevalence of hyperuricemia was 34.4%; participants with high SUA levels were slightly older; had higher prevalence of hypertension, previous heart failure and kidney failure; and were more likely to be

Discussion

The prevalence of hyperuricemia was 34.4% in our ACS participants, and a SUA level above the normal range was independently associated with both total and cardiovascular mortality as well as major cardiovascular events in medium/long-term follow-up. The association of hyperuricemia with mortality remained significant in patients without kidney failure, but not in participants without diabetes. Moreover, the addition of hyperuricemia information to the GRACE risk score seemed to improve

Conflict of interest

The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

Financial support

This study was supported by grants from Instituto de Salud Carlos III RD12/0042/0068 and from CIBER Cardiovascular: CIBER CV CB16/11/00420 FEDER and CB16/11/00226. These organizations had no involvement in the design of the study; the collection, analysis, and interpretation of the data; or the decision to approve publication of the finished manuscript.

Author contributions

AC, VBM and AL contributed to the design and implementation of the research, AC, VBM and AL contributed to acquisition of data, AC and AL performed the statistical analysis and drafted the manuscript. All authors discussed the results and contributed to the final manuscript.

Acknowledgements

We would like to thank all members of the cardiology department for their participation in this registry.

References (50)

  • F. Panero et al.

    Uric acid is not an independent predictor of cardiovascular mortality in type 2 diabetes: a population-based study

    Atherosclerosis

    (2012 Mar)
  • J.A. Barrabes et al.

    Prognosis and management of acute coronary syndrome in Spain in 2012: the DIOCLES Study

    Rev. Esp. Cardiol.

    (2015 Feb)
  • F.A. Mohamed

    On Bright's disease, and its essential symptoms

    Lancet

    (1879)
  • A. Haig

    On uric acid and arterial tension

    BMJ

    (1889)
  • M. Kanbay et al.

    The role of uric acid in the pathogenesis of human cardiovascular disease

    Heart

    (2013)
  • F. Braga et al.

    Hyperuricemia as risk factor for coronary heart disease incidence and mortality in the general population: a systematic review and meta-analysis

    Clin. Chem. Lab. Med.

    (2016 Jan)
  • L. Yan et al.

    Uric acid as a predictor of in-hospital mortality in acute myocardial infarction: a meta-analysis

    Cell Biochem. Biophys.

    (2014 Dec)
  • L.K. Niskanen et al.

    Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study

    Arch. Intern. Med.

    (2004 Jul 26)
  • J.P. Forman et al.

    Plasma uric acid level and risk for incident hypertension among men

    J. Am. Soc. Nephrol.

    (2007 Jan)
  • T.C. Peng et al.

    Relationship between hyperuricemia and lipid profiles in US adults

    BioMed Res. Int.

    (2015)
  • N. Katsiki et al.

    Uric acid and diabetes: is there a link?

    Curr. Pharmaceut. Des.

    (2013)
  • K. Masuo et al.

    Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation

    Hypertension

    (2003 Oct)
  • Z. Soltani et al.

    Potential role of uric acid in metabolic syndrome, hypertension, kidney injury, and cardiovascular diseases: is it time for reappraisal?

    Curr. Hypertens. Rep.

    (2013 Jun)
  • S. Shetty et al.

    Serum uric acid as a prognostic biomarker and its correlation with Killip class in acute myocardial infarction

    Int. J. Biomed. Res.

    (2013)
  • D.I. Feig et al.

    Uric acid and cardiovascular risk

    N. Engl. J. Med.

    (2008 Oct 23)
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