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

doi:10.1016/j.atherosclerosis.2011.11.042

Atherosclerosis

Volume 221, Issue 1, March 2012, Pages 183-188

https://doi.org/10.1016/j.atherosclerosis.2011.11.042 Get rights and content

Abstract

Objective

Although some studies have suggested that uric acid is a risk factor for mortality, this relationship is still uncertain in people with type 2 diabetes.

Methods

The study base was the population-based cohort of 1540 diabetic subjects (median age 68.9 years) of the Casale Monferrato Study. The role of serum uric acid on 15-years all-cause, cardiovascular and non-cardiovascular mortality was assessed by multivariate Cox proportional hazards modeling.

Results

Baseline levels of serum uric acid were negatively correlated with HbA1c, were higher in men and in the elderly and were independently associated with components of the metabolic syndrome. Out of 14,179 person-years, 1000 deaths (514 due to cardiovascular diseases) were observed. Compared to the lower quartile of uric acid, HRs (95% CI) in the upper quartile were 1.47 (1.22–1.76) for all-cause mortality; 1.40 (1.09–1.80) for cardiovascular mortality and 1.50 (1.15–1.96) for non-cardiovascular mortality. In multiple adjusted models, however, HRs were 1.30 (1.06–1.60) for all-cause mortality, 1.13 (0.85–1.50) for cardiovascular mortality and 1.50 (1.11–2.02) for non-cardiovascular mortality (men 1.87, 1.19–2.95; women 1.20, 0.80–1.80); the latter appeared to be due to neoplastic diseases (HR in all combined quartiles vs. lower quartile: both sexes 1.59, 1.05–2.40; men 1.54, 0.83–2.84, women 1.68, 0.95–2.92).

Conclusions

In diabetic people, uric acid is associated with components of the metabolic syndrome but it may not be accounted as an independent risk factor for cardiovascular mortality. The increased all-cause mortality risk with higher levels of uric acid might be due to increased neoplastic mortality and deserves future studies.

Section snippets

Materials and methods

The study-base included 1540 patients with known type 2 diabetes who were residents in the town of Casale Monferrato in 1991, North-West of Italy (93,477 inhabitants), were invited to a baseline examination in 1991–92 to assess the prevalence of diabetic nephropathy and cardiovascular risk factors and were then followed up to 31/12/2006 [14], [15], [16]. They were identified in the first prevalence survey of the Casale Monferrato Study, using multiple independent data sources (diabetes clinics,

Statistical analysis

Normally distributed variables are presented as means ± standard deviation (SD), whereas variables with skewed distribution were analyzed after logarithmic transformation (triglycerides, AER, creatinine) and results presented as geometric means and 95% CIs. Differences in clinical characteristics of patients were assessed by the ANOVA test for continuous variables and χ² test for categorical ones. Pearson's correlation coefficients for serum uric acid and continuous variables were also

Results

Measurements of serum uric acid were available for 1509 of 1540 diabetic people of the Casale Monferrato cohort, with mean value 321.79 ± 99.33 μmol/l. Sex differences in serum uric acid were evident, with higher values in men than in women (p < 0.001), even after adjustment for age, BMI, blood pressure and eGFR (330.11 μmol/l, 95% CI 322.98–337.85 vs. 314.65 μmol/l, 95% CI 308.11–321.19). Frequency of clinically relevant hyperuricemia (values higher than 416.36 μmol/l) was found in 13.2% of the

Discussion

Our study aimed to investigate the role of serum uric acid on all-cause and cardiovascular mortality in a large population-based cohort of people with type 2 diabetes, during a 15-years follow-up period. The cross-sectional analysis of our study confirms the association between serum uric acid and variables included in the cluster of the metabolic syndrome (obesity, hypertension, HDL-cholesterol and triglycerides). In the prospective analysis, however, uric acid was not significantly associated

Author contributions

PF, researched data and wrote the manuscript, MP, PF, FB, CR and GG researched data, PCP contributed to the discussion and reviewed/edited the manuscript, GB designed the study, researched data and wrote the manuscript.

Acknowledgments

We thank the patients, the nurses at the diabetes clinic, the diabetologists and general practitioners for long-standing collaboration in this study. The Casale Monferrato Study is supported by grants from the Piedmont Region (Ricerca Sanitaria Finalizzata 2008). The Authors have no conflict of interest with results of the study.

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Hypouricemia is a risk factor for diabetes in Chinese adults
2022, Obesity Medicine
It is unknown whether low serum uric acid (hypouricemia) is associated with diabetes diagnosis. This study aimed to investigate this association in Chinese adults.
This cross-sectional study included 22,546 Chinese adults. The reference interval for serum uric acid was determined in a sub-group of healthy individuals. The association between hypouricemia and diabetes was analyzed using binary logistic regression.
The serum uric acid reference intervals were 3.78–8.31 mg/dL for males and 2.76–6.24 mg/dL for females. Hypouricemia was defined as serum uric acid concentration <3.78 mg/dL for males and <2.76 mg/dL for females. Hypouricemia was associated with an increased likelihood of diabetes diagnosis in both unadjusted (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.78–2.79) and risk factor adjusted (OR, 2.67; 95% CI, 2.08–3.43) analyses. In a sub-group analysis, hypouricemia was significantly independently associated with an increased likelihood of diabetes diagnosis in males but not females.
This study suggests that hypouricemia is independently associated with an increased risk of diabetes diagnosis. The findings should be validated in prospective cohort studies.
Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project
2022, Nutrition, Metabolism and Cardiovascular Diseases
Citation Excerpt :
In our population, we found an inverse relation between SUA and fasting glucose, with lower glucose levels in subjects with hyperuricemia. This finding is in line with previous reports in literature [19–22]. In our population of diabetic patients, SUA levels above 4.7 mg/dl were associated with a 40% greater risk of total mortality as compared to SUA levels <4.7 mg/dl.
The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes.
The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up.
A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04–1.47) and CV mortality (HR:1.31, 95%CI:1.03–1.66), than those with SUA <5.6 mg/dl. Increased all-cause mortality risk was shown in participants with SUA ≥4.7 mg/dl vs SUA below 4.7 mg/dl, but not statistically significant after adjustment for all confounders.
SUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.
Association between serum uric acid levels and cardiovascular events in hospitalized patients with type 2 diabetes
2021, Primary Care Diabetes
This study aimed to determine the association between serum uric acid (UA) levels and cardiovascular events in hospitalized patients with type 2 diabetes mellitus (T2DM).
A retrospective cohort study was conducted in 2227 hospitalized patients with T2DM. Cox proportional hazards regression was used to assess the association between serum UA and cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, heart failure, unstable angina, and arrhythmias requiring hospitalization.
Among 1314 men, 143 (10.9%) experienced cardiovascular events. Serum UA level was not associated with the risk of cardiovascular events (hazard ratio [HR] per 100 μmol/L increase in serum UA: 1.12, 95% confidence interval [CI]: 0.90–1.40). Among 913 women, 96 (10.5%) experienced cardiovascular events. For every 100 μmol/L increase in serum UA level, the risk of experiencing a cardiovascular event increased by 27% (HR: 1.27, 95% CI: 1.02–1.57).
In hospitalized patients with T2DM, baseline serum UA levels were positively associated with cardiovascular events in women, but not in men. Serum UA levels may be a significant independent risk factor for cardiovascular events in women with T2DM.
Serum uric acid as a risk factor of all-cause mortality and cardiovascular events among type 2 diabetes population: Meta-analysis of correlational evidence
2019, Journal of Diabetes and its Complications
To explore the association between serum uric acid (SUA) level and the risk of cardiovascular complications and all-cause mortality rates among individuals with type 2 diabetes.
Web of Science and PubMed database were searched for studies reported associations between SUA level and cardiovascular complications and all-cause mortality among individuals with type 2 diabetes. Hazard ratios (HRs) were independently extracted by two investigators and synthesized through meta-analysis across selected studies.
6 (n = 11,750 patients), 4 (n = 3044 patients) and 2 studies (n = 7792 patients) were identified reporting associations between SUA level and all-cause mortality, coronary heart disease (CHD) and stroke respectively. HR for all-cause mortality, CHD, and stroke per 59 μmol/l increase was 1.06 (95% CI: 1.03, 1.09), 1.09 (95% CI: 0.94, 1.26) and 1.19 (95% CI: 1.08, 1.31), respectively.
Overall, the SUA level was associated with a higher risk of all-cause mortality and stroke. We found no significant association between SUA level and CHD among type 2 diabetes population.
Determination of the optimal cut-off value of serum uric acid concentration in patients with acute coronary syndrome
2018, Atherosclerosis
Serum uric acid levels are associated with cardiovascular risk score: A post hoc analysis of the EURIKA study
2018, International Journal of Cardiology
Reports are conflicting on whether serum uric acid (sUA) levels are independently associated with increased cardiovascular (CV) death risk.
This post hoc analysis assessed the relationship between sUA levels and CV death risk score in 7531 patients from the cross-sectional, multinational EURIKA study (NCT00882336). Patients had at least one CV risk factor but no clinical CV disease. Ten-year risk of CV death was estimated using SCORE-HDL and SCORE algorithms, categorized as low (< 1%), intermediate (1% to < 5%), high (≥ 5% to < 10%) or very high (≥ 10%).
Mean serum sUA levels increased significantly with increasing CV death risk category in the overall population and in subgroups stratified by diuretics use or renal function (all P < 0.0001). Multivariate ordinal logistic regression analyses, adjusted for factors significantly associated with CV death risk in univariate analyses (study country, body mass index, number of CV risk factors and comorbidities, use of lipid lowering therapies, antihypertensives and antidiabetics), showed a significant association between sUA levels and SCORE-HDL category in the overall population (OR: 1.39 [95% CI: 1.34–1.44]) and all subgroups (using diuretics: 1.32 [1.24–1.40]; not using diuretics: 1.46 [1.39–1.53]; estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m²: 1.30 [1.22–1.38]; eGFR ≥ 60 ml/min/1.73 m²: 1.44 [1.38–1.51]; all P < 0.0001). Similar results were obtained when using SCORE.
Higher sUA levels are associated with progressively higher 10-year CV death risk score in patients with at least one CV risk factor but no CV disease.

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View full text

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

Abstract

Objective

Methods

Results

Conclusions

Section snippets

Materials and methods

Statistical analysis

Results

Discussion

Author contributions

Acknowledgments

Am J Kidney Dis

Int J Cardiol

Nutr Metab Cardiovasc Dis

Am J Hypertens

Ann Epidemiol

Ann Oncol

J Clin Epidemiol

Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project

Circulation

Novel and conventional biomarkers for prediction of incident cardiovascular events in the community

JAMA

Uric acid and cardiovascular risk

N Engl J Med

Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease

Hypertension

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 cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971–1992. National Health and Nutrition Examination Survey

JAMA

Serum uric acid and risk of cardiovascular mortality: a prospective long-term study of 83,683 Austrian men

Clin Chem