Relation of serum uric acid to cardiovascular disease

doi:10.1016/j.ijcard.2015.08.110

International Journal of Cardiology

Volume 213, 15 June 2016, Pages 4-7

https://doi.org/10.1016/j.ijcard.2015.08.110 Get rights and content

Abstract

This review summarizes recent published literature on the association between serum uric acid and cardiovascular disease, a relationship which is complex and not fully elucidated. Uric acid may be a marker for risk, a causative agent in cardiovascular disease, or both. Various biologic factors can influence serum uric acid levels, and serum uric acid level itself is closely related to conditions such as hypertension, dyslipidemia, obesity, and impaired glucose metabolism, that contribute to cardiovascular disease pathophysiology. Serum uric acid levels have been found to be associated with adverse outcomes, including mortality, in the general population. In addition, serum uric acid is associated with increased risk for incident coronary heart disease, heart failure, and atrial fibrillation. In the setting of established systolic heart failure, serum uric acid is positively associated with disease severity and mortality risk. Whether targeting treatment based on uric acid levels might affect clinical outcomes is still being studied.

Section snippets

Background

The association between serum uric acid (SUA) and cardiovascular (CV) disease has long been recognized. However, it has not been definitively established whether SUA is merely a marker for risk or a causative agent in CV disease, or whether treatment targeting SUA levels affects outcomes. SUA is closely related to conditions such as hypertension, dyslipidemia, obesity, impaired glucose metabolism, and metabolic syndrome, which contribute to CV disease pathophysiology [1], [2]. Although many

Pathophysiology

Variations in SUA levels exist in association with various demographic factors such as race and sex, as well as CV comorbidities and medications (Table 1). In general, higher SUA levels are found in men versus women, with older age, higher blood pressure, increasing cholesterol level and creatinine, and higher body mass index [3], [7], [8]. Higher SUA levels are also associated with reported diuretic use, and intake of alcohol, meat and seafood [3], [9], [10]. Smoking does not appear to

General population

There have been inconsistent results of large population analyses of relationships of SUA to CV and all-cause mortality risk. Analysis of the community-based Framingham cohort, including 117,276 person-years of follow-up, found that SUA level was ultimately not associated with risk for incident coronary heart disease (CHD), CV death, or all-cause death. On initial analysis, it appeared that there was an increased risk associated with higher SUA among women, but in fully adjusted multivariate Cox

Hypertension

SUA is positively associated with risk of incident hypertension [21]. Elevated SUA in the setting of hypertension may be related to renal involvement, leading to impaired uric acid excretion, and/or related to antihypertensive treatment. Hyperuricemia and hypertension may both result from the common pathway hyperinsulinemia due to insulin resistance, which increases urine sodium retention and decreases renal uric acid clearance. In the Systolic Hypertension in the Elderly (SHEP) study,

Coronary heart disease

SUA does not appear to be significantly associated with increased risk for incident CHD in the general population, but in groups at high risk for or with established CHD, the strength of the association found between SUA and mortality in various studies has been inconsistent. In the community-based Framingham population, SUA was associated with antihypertensive therapy, but after adjusting for multiple confounders, was not associated with development of CHD [1]. Among patients considered at

Heart failure

SUA is associated with increased risk for incident HF, and with increased mortality risk in patients with existing systolic HF. In the community-based population of the Cardiovascular Health Study, SUA was associated with an increased risk for new-onset HF, with a HR 1.12 (95% CI 1.03–1.22) per 1 mg/dl increase in the population as a whole, and HR 1.30 (95% CI 1.05–1.60) among persons with hyperuricemia versus normals. In subgroup analysis, this relationship between SUA and incident HF remained

Atrial fibrillation

Several studies have found an association between SUA and risk for atrial fibrillation, although it is not fully understood whether SUA plays a mechanistic role in the cause and maintenance of atrial fibrillation or whether it is simply a disease marker. In the multi-ethnic, community-based Atherosclerosis Risk in Communities (ARIC) population, increasing levels of SUA were associated with risk for incident atrial fibrillation, with a hazard ratio of 1.16 (95% CI 1.06–1.26) per quartile of

Treatment of hyperuricemia

Many of the clinical studies performed examining the effect of treating hyperuricemia on outcomes in CV disease have studied patients with HF. It is thought that in chronic HF, the failing myocardium is “energy starved” by virtue of inadequate adenosine triphosphate availability. XO regulates a terminal step in ATP and purine nucleoside degradation; thus XO inhibition could improve the energy balance in the failing myocardium. Intravenous infusion of allopurinol in patients with non-ischemic

Conclusion

In multiple studies, SUA appears positively associated with increased risk for CV disease and death, although it is still not definitively established whether SUA is an independent risk factor or is merely strongly correlated with known CV risk factors such as hypertension and dyslipidemia. At the current time, SUA can be considered to be a marker for CV risk, but data from published studies overall do not support specifically targeting CV treatment based on SUA levels. Mechanistic studies

Conflicts of interest

No conflicts of interest to report.

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Uric acid, the end-product of purine metabolism within the human body, has been the subject of studies exploring its potential association with cardiovascular and cerebrovascular diseases. However, the precise relationship between uric acid levels and heart failure remains elusive.
In this particular study, aggregated data from genome-wide association studies on uric acid and heart failure were utilized to perform a two-sample Mendelian randomization (MR) analysis utilizing R software. The aim was to uncover any causal link between these variables. The primary outcome was assessed using inverse variance weighted (IVW) methodology, while sensitivity analyses employed MR-Egger, weighted median (WME), and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) techniques. IVW results revealed a possible causal relationship between elevated uric acid levels and an increased risk of heart failure (OR: 1.09, 95 % CI: 1.01–1.17, P < 0.05). Encouragingly, the directions provided by MR-Egger and WME aligned with IVW findings, and no anomalies were detected in the remaining sensitivity analyses.
These outcomes indicate the stability of the results of the study, thereby suggesting that heightened uric acid levels may contribute to an augmented risk of heart failure.
Serum uric acid to creatinine ratio and metabolic syndrome in middle-aged and elderly population: Based on the 2015 CHARLS
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Serum uric acid to creatinine ratio (SUA/Cr) may be associated with metabolic syndrome (MS). Here, we investigated the correlation between SUA/Cr and MS in Chinese residents aged ≥ 45 years.
Data were obtained from the 2015 China Health and Retirement Longitudinal Study (CHARLS) database. MS was diagnosed using the Chinese Diabetes Society 2017 criteria. We grouped the population according to SUA/Cr quartiles and compared the index differences between groups. We used spearman correlation analysis and binary logistic regression. The possible dose-response association of SUA/Cr with MS were analyzed using restricted cubic spline model. Of 12,946 included participants, 3370 (26.0%) had MS, and 1900 (56.4%) were female. After adjusting for multiple confounders, binary logistic regression analysis showed that compared with Quartile 1, the odds ratio (95% confidence interval) of the MS risk was 1.29 (1.09–1.52), 1.47 (1.25–1.74), and 1.80 (1.53–2.12) in Quartiles 2, 3, and 4, respectively. The restricted cubic spline model indicated a significant nonlinear dose-response association (P_overall < 0.001, P_{non-linearity} = 0.029) between SUA/Cr and strength of MS prevalence association; MS risk began increasing when SUA/Cr > 6.22.
A significant positive correlation existed between SUA/Cr and MS risk in Chinese individuals aged ≥ 45 years, which may be a new predictive marker for MS risk.
Risk factors and characteristics of new-onset coronary heart disease in adults with physical disabilities: A retrospective cohort study
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There is limited information about coronary heart disease (CHD) in adults with physical disabilities. This study was performed to assess the incidence and predictors of the new development of CHD in adults with physical disabilities.
A retrospective cohort study was performed on 3902 physically disabled people in Shanghai, China. Baseline information was collected in January 2012, and participants were followed-up with for 7.5 years for CHD events. Risk factors for demographic characteristics, disease history, electrocardiography, and blood biochemical indicators were evaluated using a Cox proportional hazard model. Subgroup analyzes were performed according to gender and level of physical disability.
Out of the total 3902 adults with physical disabilities (average age 55.9 ± 8.5 years), 468 (12.0%) developed CHD, during a median follow-up period of 7 years. Independent predictors of CHD included the following: age (HR = 1.411, 95% CI = 1.255–1.587, p＜0.001), gender (HR = 0.773, 95% CI = 0.637–0.940, p = 0.010), abnormal electrocardiogram(HR = 1.396, 95% CI = 1.088–1.792, p = 0.009), hypertension (HR = 1.657, 95% CI = 1.369–2.006, p＜0.001), diabetes (HR = 1.649, 95% CI = 1.307–2.081, p＜0.001), serum uric acid (HR = 1.001, 95% CI = 1.000–1.002, p = 0.046), and total cholesterol (HR = 1.416, 95% CI = 1.054–1.902, p = 0.021). In addition to the risk factors of the total population with physical disability, triglyceride was also a significant risk factor for CHD in the subgroup with women and mild disability.
During a 7.5 years period, the CHD incidence rate among physically disabled people was 12.0%. We identified the role of CHD risk factors such as age, gender, hypertension, diabetes, serum uric acid, total cholesterol, and abnormal electrocardiogram.
Molecularly imprinted graphene based biosensor as effective tool for electrochemical sensing of uric acid
2023, Sensors International
Graphene oxide based molecularly imprinted polymer was designed by incorporating vinyltrimethoxysilane into the layers of graphene oxide, which was copolymerized with functional monomers such as Itaconic acid (IA) and methyl methacrylate (MMA) was developed via bulk imprinting technique. The prepared polymer was studied for selective sensing the uric acid (UA) in blood serum. The electrode was constructed by modifying bare glassy carbon electrodes with the prepared molecularly imprinted polymer (MIP) via drop cast method. Electrochemical measurements were made by Cyclic voltammetric (CV) and Differential Pulse Voltammetric (DPV) response of the sensor. The physical and chemical properties of the resultant material will be characterized by FTIR spectroscopy, XRD and FESEM. The constructed sensor showed a regression coefficient (R²) of 0.9302 with limit of detection (LOD) of about 0.565 μM. The developed sensor is reusable without any compromise in its selectivity. All the results confirm that the constructed biosensor requires no pre-treatment of samples and is suitable for real sample analysis.
The interaction between hyperuricemia and low-density lipoprotein cholesterol increases the risk of 1-year post-discharge all-cause mortality in ST-segment elevation myocardial infarction patients
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Hyperuricemia is a known risk factor for cardiovascular diseases, but little is known on whether the association between hyperuricemia and poor outcomes in ST-segment elevation myocardial infarction (STEMI) is modified by low-density lipoprotein cholesterol (LDL-c). This study aimed to investigate the effect of the interaction between hyperuricemia and LDL-c on the risk of 1-year post-discharge all-cause mortality in STEMI patients.
A total of 1396 STEMI patients were included. Cox proportional hazards models were used to determine the association between hyperuricemia and 1-year all-cause mortality in the overall population and subgroups stratified based on LDL-c levels (<3.0 mmol/L or ≥3.0 mmol/L). Multivariate analysis indicated that hyperuricemia was associated with 1-year mortality (HR: 2.66; 95% CI: 1.30–5.47; p = 0.008). However, the prognostic effect of hyperuricemia was only observed in patients with LDL-c level ≥3.0 mmol/L (HR: 12.90; 95% CI: 2.98–55.77; p < 0.001), but not in those with LDL-c level <3.0 mmol/L (HR: 0.91, 95% CI: 0.30–2.79, p = 0.875). The interaction between hyperuricemia and LDL-c levels had a significant effect on 1-year mortality.
Hyperuricemia was associated with increased 1-year post-discharge mortality in patients with LDL-c level≥ 3.0 mmol/L, but not in those with LDL-c level< 3.0 mmol/L.
Electrochemical sensing performance of nitrogen rich zero- and two-dimensional carbon nanomaterials modified electrodes towards purines catabolism
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Electrochemical sensing of uric acid (UA) by using nitrogen-rich carbon nanomaterials such as N-doped carbon dots (N-CDs), N-doped graphene quantum dots (N-GQDs) and graphitic carbon nitride (GCN) electrodeposited on screen printed carbon electrode (SPCE) was studied. These N-rich carbon materials were prepared by reported procedures and characterized by spectroscopic, XRD and SEM techniques. They were deposited on SPCE by potentiodynamic electrodeposition from -0.2 to +1.7 V. The topographical studies by SEM reveal that the dots like morphology of both N-CDs and N-GQDs was retained on SPC substrate whereas aggregated thin sheet like structure was noticed for the electrodeposited GCN. Then, the electrochemical sensing performance of these electrodes towards UA was studied. Among the different electrodes, SPCE deposited with GCN (SPCE/GCN) shows the highest oxidation current for UA due to its larger surface area and lower charge transfer resistance. Further, SPCE/GCN was exploited to determine UA in the presence of xanthine (XA), which was commonly present in blood serum. The amperometric method was deployed to determine UA from 0.2 to 1000 µM and achieved the limit of detection (LOD) of 24.4 nM (S/N=3) and sensitivity of 12.4 µA µM⁻¹ cm⁻². The practical application of SPCE/GCN was examined by quantifying UA in human blood serum sample and the obtained result was validated with the clinical method.

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Relation of serum uric acid to cardiovascular disease

Abstract

Section snippets

Background

Pathophysiology

General population

Hypertension

Coronary heart disease

Heart failure

Atrial fibrillation

Treatment of hyperuricemia

Conclusion

Conflicts of interest

Ann. Epidemiol.

Lancet

Lancet

Am. J. Cardiol.

Kidney Int.

Am. J. Cardiol.

Am. J. Cardiol.

Am. J. Cardiol.

Int. J. Cardiol.

Am. J. Cardiol.

Am. Heart J.

Am. Heart J.

Am. Heart. J.

Am. J. Cardiol.

Am. J. Cardiol.

Heart Rhythm

J. Am. Coll. Cardiol.

J. Am. Coll. Cardiol.

J. Am. Coll. Cardiol.

J. Am. Coll. Cardiol.

Hyperuricemia as a risk factor of coronary heart disease: the Framingham Study

Am. J. Epidemiol.

Serum uric acid and cardiovascular mortality the NHANES I Epidemiologic Follow-up Study, 1971–1992. National Health and Nutrition Examination Survey

JAMA

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

Arch. Intern. Med.

Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study

Ann. Intern. Med.

Effect of aging on serum uric acid levels: longitudinal changes in a large Japanese population group

J. Gerontol. A Biol. Sci. Med. Sci.

Serum urate and the risk of major coronary heart disease events

Heart

Serum urate and its relationship with alcoholic beverage intake in men and women: findings from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort

Ann. Rheum. Dis.

Purine-rich foods, dairy and protein intake, and the risk of gout in men

N. Engl. J. Med.

Uric acid and the cardiovascular profile of African and Caucasian men

J. Hum. Hypertens