Elevated serum uric acid and risk of cardiovascular or all-cause mortality in people with suspected or definite coronary artery disease: A meta-analysis

doi:10.1016/j.atherosclerosis.2016.10.006

Atherosclerosis

Volume 254, November 2016, Pages 193-199

https://doi.org/10.1016/j.atherosclerosis.2016.10.006 Get rights and content

Highlights

•
The magnitude of Serum uric acid (SUA) level on cardiovascular and all-cause mortality risk varied across studies.
•
Subjects with highest SUA level was associated with an 80% increase in all-cause mortality.
•
Subjects with highest SUA level was associated with a 109% increase in cardiovascular mortality.
•
Each 1 mg/ml SUA rise increased 12% cardiovascular mortality and 20% all-cause mortality.

Abstract

Background and aims

Serum uric acid (SUA) has been recognized as an independent risk factor for mortality in the general population. We performed this meta-analysis to determine whether elevated SUA levels are associated with greater risk of cardiovascular or all-cause mortality in people with suspected or definite coronary artery disease (CAD).

Methods

The Pubmed and Embase databases were searched up to April 1, 2016 for the longitudinal studies that investigated the association between the elevated SUA and cardiovascular or all-cause mortality risk in people with suspected or definite CAD. Pooled adjusted risk ratio (RR) and corresponding 95% confidence interval (CI) were calculated for the highest vs. the lowest SUA category or each 1 mg/ml SUA rise.

Results

Nine studies enrolling 25,229 participants were included in the analyses. The highest vs. lowest SUA category was associated with greater risk of cardiovascular mortality (RR 2.09; 95% CI: 1.45–3.02) and all-cause mortality (RR 1.80; 95% CI: 1.39–2.34) after adjustment for potential confounders in a random effects model. Moreover, each 1 mg/ml SUA rise significantly increased by 12% cardiovascular mortality and by 20% all-cause mortality.

Conclusions

Elevated SUA levels are strongly and independently associated with greater risk of cardiovascular and all-cause mortality in people with suspected or definite CAD.

Introduction

Uric acid is the final product of purine metabolism in humans. Serum uric acid (SUA) is recognized as a marker of oxidative stress [1]. Increased UA levels may be an indicator of up-regulated activity of xanthine oxidase [2]. SUA is an easily assayed biomarker in routine clinical practice. Higher SUA was associated with incident coronary heart disease [3] or stroke [4] in the general population as well as an adverse prognosis in patients with acute myocardial infarction [5], [6] and heart failure [7], [8]. The presence of higher SUA levels may strengthen the conventional cardiovascular risk factors, such as hypertension [9], impaired fasting glucose/type 2 diabetes [10], overweight/obese [11], and metabolic syndrome [12]. These findings highlight adding SUA to traditional risk predictive model may improve outcome risk prediction.

Higher SUA has been considered as an independent predictor of cardiovascular mortality in the general population [13]. Despite higher SUA has been identified as a prognostic marker in the general population, the association of SUA levels and mortality risk in patients with coronary artery disease (CAD) has yielded controversial result [14], [15], [16]. Moreover, the magnitude of this association in CAD patients varied considerably. Currently, no previous systematic review or meta-analysis has been performed to assess the association between SUA levels and the subsequent risk of cardiovascular or all-cause mortality in patients with CAD.

Here, we conducted a meta-analysis of the available longitudinal studies to investigate the prognostic value of baseline SUA levels for cardiovascular or all-cause mortality in people with suspected or definite CAD.

Section snippets

Materials and methods

This meta-analysis was conducted in accordance with the guideline of the Meta-Analysis of Observational Studies in Epidemiology [17]. We searched the Pubmed and Embase databases up to April 1, 2016 using the following search key words: (uric acid OR hyperuricemia OR urate) AND (mortality OR death) AND (acute coronary syndrome OR coronary artery disease OR coronary heart disease) AND (follow-up OR longitudinal study) with limits “Title/Abstract, Human Subjects, English”. The reference lists of

Results

Briefly, a total of 1429 citations have been identified from Pubmed and Embase databases. After reviewing the abstracts or titles, 1347 articles were removed. We further assessed 82 full-text manuscripts for the eligibility. Of these, we removed 73 articles mainly due to the studied participants were in the general population or with other specific diseases (Fig. 1). Three articles [21], [22], [23] were further removed due to duplicate publications from the same study population. No additional

Discussion

To our best knowledge, this study is the first meta-analysis to investigate the association of SUA levels with mortality risk in people with suspected or definite CAD. The findings of the current meta-analysis suggested that, compared with peoples with the lowest baseline SUA levels, those with the highest SUA levels increased by 80% all-cause mortality and 109% cardiovascular mortality. In addition, each 1 mg/ml SUA rise significantly increased by 12% cardiovascular mortality and 20% all-cause

Conflict of interest

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

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No.81000068) and Project funding for the introduction of overseas students in Hebei Province (2015-243).

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The association between uric acid (UA) and long-term mortality in patients with coronary artery disease is poorly investigated. We assessed the association between UA and 10-year mortality after percutaneous coronary intervention (PCI) in 3,998 patients who underwent PCI. Patients were categorized in groups according to UA tertiles: tertile 1 (UA <5.80 mg/100 ml, n = 1,347), tertile 2 (UA 5.80 to 7.04 mg/100 ml, n = 1,340), and tertile 3 (UA >7.94 mg/100 ml, n = 1,311). The primary outcome was 10-year all-cause mortality. All-cause deaths occurred in 1,200 patients: 320 deaths (26.5%) in patients with UA in the first tertile, 325 deaths (26.9%) in patients with UA in the second tertile, and 555 deaths (46.0%) in patients with UA in the third tertile (adjusted hazard ratio 1.22, 95% confidence interval 1.17 to 1.27, p <0.001) for 1 mg/100 ml increment in UA level. Cardiac deaths occurred in 748 patients: 194 deaths (16.5%) in patients with UA in the first tertile, 202 deaths (17.0%) in patients with UA in the second tertile, and 352 deaths (29.7%) in patients with UA in the third tertile (adjusted hazard ratio 1.24 [1.17 to 1.32], p <0.001) for 1 mg/100 ml increment in the UA level. The 10-year rates of target lesion revascularization, target vessel revascularization, or nontarget vessel revascularization did not differ significantly according to the UA level. In conclusion, in patients with coronary artery disease treated with PCI, increased UA level was associated with higher 10-year mortality. Increased UA level was not associated with the progression of atherosclerosis in nontreated coronary vessels or progression of intimal hyperplasia in stented lesions requiring intervention.
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Albumin, the most abundant circulating protein in blood, is an essential protein which binds and transports various drugs and substances, maintains the oncotic pressure of blood and influences the physiological function of the circulatory system. Albumin also has anti-inflammatory, antioxidant, and antithrombotic properties. Evidence supports albumin's role as a strong predictor of cardiovascular (CV) risk in several patient groups. Its protective role extends to those with coronary artery disease, heart failure, hypertension, atrial fibrillation, peripheral artery disease or ischemic stroke, as well as those undergoing revascularization procedures or with aortic stenosis undergoing transcatheter aortic valve replacement, and patients with congenital heart disease and/or endocarditis. Hypoalbuminemia is a strong prognosticator of increased all-cause and CV mortality according to several cohort studies and meta-analyses in hospitalized and non-hospitalized patients with or without comorbidities. Normalization of albumin levels before discharge lowers mortality risk, compared with hypoalbuminemia before discharge. Modified forms of albumin, such as ischemia modified albumin, also has prognostic value in patients with coronary or peripheral artery disease. When albumin is combined with other risk factors, such as uric acid or C-reactive protein, the prognostic value is enhanced. Although albumin supplementation may be a plausible approach, its efficacy has not been established and in patients with hypoalbuminemia, priority is focused on diagnosing and managing the underlying condition. The CV effects of hypoalbuminemia and relevant issues are considered in this review. Large cohort studies and meta-analyses are tabulated and the physiologic effects of albumin and the deleterious effects of low albumin are pictorially illustrated.
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Citation Excerpt :
Apart from already commonly recognized consequences, such as nephrolithiasis and gout, hyperuricemia is presently in the scope of interest as a potential risk factor for cardiovascular diseases (Gromadziński et al., 2015). It has been evidenced that for every 1 mg/dL increase in serum UA, cardiovascular and all-cause mortality increased by 12% and 20%, respectively (Wang et al., 2016). However, despite the association in epidemiological studies between hyperuricemia and hypertension, coronary artery disease, atrial fibrillation, cardiac insufficiency, cerebrovascular disease and diseases contributing to vascular pathologies – metabolic syndrome, diabetes and chronic kidney disease, its treatment does not yield unequivocal results proved in large-scale clinical studies (Feig et al., 2008; Saito et al., 2020).
Hyperuricemia is an independent risk factor for renal and cardiovascular diseases and is closely associated with gout episodes. It is caused, inter alia, by nutritional habits and genetic factors, and also displays seasonal variability conditioned by meteorological factors. The impact of meteorological factors, including both cold and heat stress, on the human physiology is presented based on the Universal Thermal Climate Index (UTCI) – a biometeorological index derived from an analysis of human thermal balance. The aim of our study was to establish whether seasonal variations significantly affect routinely measured urine acid (UA) levels and could eventually support the clinical decision making process, as well as assessing whether UTCI values are correlated with UA levels in blood serum. This work presents a retrospective epidemiological study of data collected in Olsztyn (Poland). Study material comprised 54,536 results of ambulatory tests measuring UA levels, performed during the period 2016–2019. The analysis concerned correlations between UA and the ages of female and male subjects as well as existing biometeorological conditions as represented by UTCI values in an annual cycle. UA levels in females were found to be lower (4.94 ± 1.37 SD) as compared to those of males (6.13 ± 1.43 SD) and demonstrated a strong positive correlation with age. UA values differed significantly (p < 0.05) on days characterized by cold stress and heat stress, for the oldest age group. UA levels were found to differ depending on the season, but these relationships were not statistically significant, except for significantly higher UA levels in females in autumn (p < 0.001). However, there was an evident difference in population UA levels under cold stress conditions (lower) and heat stress conditions (higher) in the elderly. The UTCI is an adequate predictor of population variations in UA levels since it takes into account the variability of local meteorological conditions.
Treatment of type 2 diabetes
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Serum uric acid and outcome in hospitalized elderly patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes
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Therapy for type 2 diabetes
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View full text

Elevated serum uric acid and risk of cardiovascular or all-cause mortality in people with suspected or definite coronary artery disease: A meta-analysis

Highlights

Abstract

Background and aims

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Discussion

Conflict of interest

Acknowledgements

Uric acid and oxidative stress: relative impact on cardiovascular risk?

Nutr. Metab. Cardiovasc Dis.

Xanthine oxidase and uric acid in cardiovascular disease: clinical impact and therapeutic options

Semin. Nephrol.

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.

Hyperuricemia and risk of stroke: a systematic review and meta-analysis

Arthritis Rheum.

On-admission serum uric acid predicts outcomes after acute myocardial infarction: systematic review and meta-analysis of prognostic studies

Croat. Med. J.

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

Cell Biochem. Biophys.

Uric acid as a predictor of all-cause mortality in heart failure: a meta-analysis

Congest. Heart Fail

Uric acid and risk of heart failure: a systematic review and meta-analysis

Eur. J. Heart Fail

Hyperuricemia and risk of incident hypertension: a systematic review and meta-analysis of observational studies

PLoS One

Serum uric acid levels and incidence of impaired fasting glucose and type 2 diabetes mellitus: a meta-analysis of cohort studies

Diabetes Res. Clin. Pract.

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

Hypertension

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

Endocrine

Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: a meta-analysis of prospective studies

Atherosclerosis

Uric Acid is not an independent predictor of cardiovascular death in patients with angiographically proven coronary artery disease

Chang. Gung Med. J.

The association of serum uric acid levels with outcomes following percutaneous coronary intervention

J. Interv. Cardiol.

Uric acid is predictive of cardiovascular mortality and sudden cardiac death in subjects referred for coronary angiography

Nutr. Metab. Cardiovasc Dis.