Serum uric acid is an independent predictor of all‐cause mortality in patients at high risk of cardiovascular disease: A preventive cardiology information system (PreCIS) database cohort study

Objective

Uric acid is a product of the activity of xanthine oxidase, an enzyme linked to oxidative stress, endothelial dysfunction, and heart failure. It is unclear whether adding uric acid levels to the assessment of cardiovascular risk might contribute to the improved ability to stratify cardiovascular risk. The purpose of this study was to evaluate the prognostic value of serum uric acid levels in a large cohort of men and women at high risk of cardiovascular disease.

Methods

Serum uric acid levels were determined in all patients seen for primary/secondary cardiovascular disease prevention at the Cleveland Clinic Section of Preventive Cardiology and Rehabilitation between 1998 and 2004, and all data were entered into the Preventive Cardiology Information System (PreCIS) database. Vital status of the patients was determined through the Social Security Death Index. Death from all causes was summarized across quartiles of uric acid values.

Results

A total of 3,098 patients (age range 18–87 years) were identified in the database, among whom 43% had cardiovascular disease. There were 156 deaths (5%) during the 14,262 person‐years of followup. For each 1‐mg/dl increase in the serum uric acid level, there was a 39% increase in the risk of death (by Cox regression analysis). After adjusting for age, sex, smoking status, alcohol consumption, weight, body mass index, waist circumference, blood pressure, history of cardiovascular disease, estimated glomerular filtration rate, levels of cholesterol fractions, and plasma glucose levels, the serum uric acid level continued to predict the risk of death (hazard ratio = 1.26 [95% confidence interval 1.15–1.38], P < 0.001). This association was present regardless of diuretic use. Concordance index (C statistic) analyses showed that uric acid significantly improved the predictive accuracy of a model that included Framingham Heart Study score factors, metabolic syndrome components, and fibrinogen levels.

Conclusion

Serum uric acid levels are an independent predictor of death in patients at high risk of cardiovascular disease. Further studies are warranted to evaluate its prognostic implications and potential utility in the monitoring of therapy.

     

Serum uric acid concentration as a risk factor for cardiovascular mortality: a longterm cohort study of atomic bomb survivors

OBJECTIVE: To elucidate the association of serum uric acid concentration with cardiovascular mortality risk. METHODS: Serum uric acid level measured from 1966 through 1970 in 10,615 Japanese individuals from a cohort of atomic bomb survivors was analyzed for association with subsequent cardiovascular and all-cause mortality until 1999 using the Cox proportional hazard model. RESULTS: During an average followup of 24.9 years, 5225 deaths occurred, of which 1984 were ascribed to cardiovascular disease. In men, after adjustment for age, elevated serum uric acid level was associated with both cardiovascular and all-cause mortality. After additional adjustment for potential cardiovascular disease risk factors including body mass index, smoking status, alcohol consumption, systolic blood pressure, cholesterol level, and histories of hypertension, diabetes and cardiovascular disease, elevated serum uric acid level in men was associated with all-cause mortality but not with cardiovascular mortality. In women, even after these adjustments, elevated serum uric acid level was significantly associated with cardiovascular and all-cause mortality. CONCLUSION: Increased serum uric acid level is a significant and independent risk factor for cardiovascular mortality in women and for all-cause mortality in both men and women.     

Serum uric acid level and all-cause and cardiovascular mortality in Chinese elderly: A community-based cohort study in Shanghai

Background and aimsThe association between serum uric acid (SUA) and the all-cause and cardiovascular diseases (CVD) mortality remains controversial, but few studies based on the community population in Shanghai have been reported. We aimed to evaluate the association of SUA level with all-cause and CVD mortality in Chinese elderly based on a community-based cohort study in Shanghai of China.Methods and resultsA total of 12,071 eligible participants were included, with a cumulative follow-up period of 46,063.65 person-years and a median of 4.67 years. The time-dependent Cox regression model indicated that when SUA level was classified into quartile groups, no significant association was observed between SUA level and all-cause death in both men and women and between SUA level and CVD mortality in men. However, the HR (95%CI) between SUA groups and CVD death in women was 3.75 (1.49–9.43) for quartile 1, 3.66 (1.53–8.76) for quartile 2, and 2.98 (1.33–6.69) for quartile 4, respectively, when compared with the quartile 3 SUA level. A significant non-linear association was observed between SUA level and CVD death in elderly women. An increased risk of CVD death was observed among women with SUA level less than 4.30 mg/dL at the baseline, and a lower risk, among women with SUA level of 4.30–4.72 mg/dL at the baseline.ConclusionThe non-linear association between SUA level and CVD mortality in elderly women suggests a potential benefit of controlling SUA level at4.30–4.72 mg/dL in elderly Chinese women.     

Serum uric acid as a cardiovascular risk factor for heart disease

Cardiovascular risk factors are those environmental, behavioral, genetic, and/or personal factors whose presence indicates a heightened risk of subsequent vascular disease events. Smoking, hypertension, and hyperlipidemia, initially identified by astute clinicians, were all subsequently confirmed and defined as risk factors through formal prospective epidemiologic study, long before evidence of causality was available. Ultimately, clinical trials demonstrated a reversible contribution of both high blood pressure and elevated lipids to stroke and heart disease. As a result, these risk factors are now the cornerstones for both assessment of relative cardiovascular risk and targets for preventive intervention. The criterion for risk factor status is a strong, consistent, timely, and statistically significant association to disease events that is independent of and unconfounded by other known risk factors. The purpose of this review is to assess available data to determine whether or not serum uric acid meets the standard for designation as a risk factor.     

升高的血清Nexilin是缺血性脑卒中的独立危险因素

目的探讨缺血性脑卒中患者检测血清Nexilin水平的临床价值。方法连续收集急性缺血性脑卒中患者185例〔男120例,女65例,平均年龄(64.6±9.3)岁〕,对照组215例〔男120例,女95例,平均年龄(64.7±9.0)岁〕。采用ELISA方法检测血清Nexilin含量。结果与对照组比较,急性缺血性脑卒中患者血清Nexilin含量明显升高〔0.81(0.51~1.33)ng/ml vs.0.15(0.11~0.26)ng/ml,P0.001〕,以Nexilin≥0.80 ng/ml(对照组95百分位数)作为升高标准,缺血性脑卒中患者高血清Nexilin比率明显高于对照组(50.81%vs.5.58%,P0.001)。多因素回归分析显示升高的血清Nexilin水平是缺血性脑卒中的独立危险因素。结论急性缺血性脑卒中患者血清Nexilin水平明显升高,升高的血清Nexilin是缺血性脑卒中的独立危险因素。     

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

BACKGROUND: Despite abundant epidemiologic evidence, the role of elevated serum uric acid level as a cardiovascular risk factor is controversial. We assessed the predictive value of serum uric acid levels for cardiovascular and overall mortality. METHODS: A population-based prospective cohort study was performed of 1423 middle-aged Finnish men initially without cardiovascular disease, cancer, or diabetes. The main outcome measure was death from cardiovascular disease and any cause. RESULTS: The mean follow-up was 11.9 years. There were 157 deaths during follow-up, of which 55 were cardiovascular. In age-adjusted analyses, serum uric acid levels in the upper third were associated with a greater than 2.5-fold higher risk of death from cardiovascular disease than levels in the lower third. Taking into account cardiovascular risk factors and variables commonly associated with gout increased the relative risk to 3.73. Further adjustment for factors related to the metabolic syndrome strengthened the risk to 4.77. Excluding the 53 men using diuretics did not alter the results. In age-adjusted analyses, men with serum uric acid levels in the upper third were 1.7-fold more likely to die of any cause than men with levels in the lower third. Adjustment for further risk factors strengthened the association somewhat. CONCLUSIONS: Serum uric acid levels are a strong predictor of cardiovascular disease mortality in healthy middle-aged men, independent of variables commonly associated with gout or the metabolic syndrome. Serum uric acid measurement is an easily available and inexpensive risk marker, but whether its relationship to cardiovascular events is circumstantial or causal remains to be answered.     

Serum uric acid as a risk factor for cardiovascular and renal disease: an old controversy revived

Hyperuricemia is commonly associated with traditional risk factors such as abnormalities in glucose metabolism, dyslipidemia, and hypertension. Recent studies have revived the controversy over the role of serum uric acid as an independent prognostic factor for cardiovascular mortality. The authors review clinical and experimental evidence concerning the role of serum uric acid in the development of cardiovascular and renal damage. Results of trials suggesting that serum uric acid variations over time may have a prognostic impact are also discussed.     

Serum uric acid is not an independent risk factor for coronary heart disease

Many large epidemiologic studies have confirmed a positive association between raised serum uric acid and risk of coronary heart disease or cardiovascular disease, both in the general population and among hypertensive patients. There is much controversy concerning the role of uric acid as an independent risk factor in the development of coronary heart disease because serum uric acid is related to many of the established etiologic risk factors for cardiovascular disease that could confound the observed association. This review finds little support for an independent causal role for serum uric acid in the development of coronary heart disease.     

Serum uric acid and risk of ischemic stroke: the ARIC Study

AIMS: Since serum uric acid (UA) is strongly associated with cardiovascular risk factors, it has been debated whether serum UA is a stroke risk factor or whether UA may be simply "marking" subjects with other, causal risk factors. We therefore investigated the relation between UA and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS AND RESULTS: Of 15,792 ARIC participants, 13,413 who were free of recognized stroke or coronary heart disease (CHD) at baseline and had a baseline UA measurement were included in the analysis. We followed the participants for ischemic stroke incidence (N=381) over 12.6 years. Although serum UA was independently and positively related to ischemic stroke incidence when we adjusted for age, sex, race, and education, the positive relation was weakened when additionally adjusted for possible confounding variables. The positive multivariate-adjusted association between serum UA and ischemic stroke was observed among subjects not using diuretics (adjusted relative hazard in the highest quartile versus the lowest: relative hazard (RH)=1.49; 95% confidence interval (CI): 1.00-2.23) (P for trend: 0.02), but not among diuretic users (P for interaction: 0.08). CONCLUSION: Our findings suggest that UA is an independent predictor of ischemic stroke among subjects not using diuretics, but that elevated UA itself may not cause ischemic stroke.     

Serum uric acid as an independent predictor of early death after acute stroke.

BACKGROUND: The prognostic significance of uric acid (UA) levels in acute stroke is unclear, so the objective of this study was to determine the association between levels of serum UA (SUA) and mortality in acute stroke. METHODS AND RESULTS: Consecutive patients (n=435) presenting with ischemic stroke and intracerebral hemorrhage were included in the study. The length of stay in hospital and the occurrence of death were recorded. On univariate analysis, the occurrence of death was associated with older age, smoking, presence of congestive heart failure or atrial fibrillation, absence of hyperlipidemia, and intracerebral hemorrhage as the index event. Furthermore, glucose, urea, creatinine and SUA at admission were significantly higher in patients who died, whereas total and high-density-lipoprotein cholesterol were significantly lower. On multiple logistic regression analysis, the independent relationship between higher SUA levels and death was confirmed (odds ratio (OR), 1.37; 95%confidence interval (CI), 1.13-1.67; p=0.001). The only other variables independently associated with the occurrence of death were urea concentration and presence of atrial fibrillation. If urate was >7.8 mg/dl (0.47 mmol/L), then there would be a high probability of early death (87%). CONCLUSIONS: Elevated levels of SUA are independently associated with an increased risk of early death in acute stroke.     

Serum uric acid is an independent predictor of all-cause mortality in patients at high risk of cardiovascular disease: a preventive cardiology information system (PreCIS) database cohort study

OBJECTIVE: Uric acid is a product of the activity of xanthine oxidase, an enzyme linked to oxidative stress, endothelial dysfunction, and heart failure. It is unclear whether adding uric acid levels to the assessment of cardiovascular risk might contribute to the improved ability to stratify cardiovascular risk. The purpose of this study was to evaluate the prognostic value of serum uric acid levels in a large cohort of men and women at high risk of cardiovascular disease. METHODS: Serum uric acid levels were determined in all patients seen for primary/secondary cardiovascular disease prevention at the Cleveland Clinic Section of Preventive Cardiology and Rehabilitation between 1998 and 2004, and all data were entered into the Preventive Cardiology Information System (PreCIS) database. Vital status of the patients was determined through the Social Security Death Index. Death from all causes was summarized across quartiles of uric acid values. RESULTS: A total of 3,098 patients (age range 18-87 years) were identified in the database, among whom 43% had cardiovascular disease. There were 156 deaths (5%) during the 14,262 person-years of followup. For each 1-mg/dl increase in the serum uric acid level, there was a 39% increase in the risk of death (by Cox regression analysis). After adjusting for age, sex, smoking status, alcohol consumption, weight, body mass index, waist circumference, blood pressure, history of cardiovascular disease, estimated glomerular filtration rate, levels of cholesterol fractions, and plasma glucose levels, the serum uric acid level continued to predict the risk of death (hazard ratio = 1.26 [95% confidence interval 1.15-1.38], P < 0.001). This association was present regardless of diuretic use. Concordance index (C statistic) analyses showed that uric acid significantly improved the predictive accuracy of a model that included Framingham Heart Study score factors, metabolic syndrome components, and fibrinogen levels. CONCLUSION: Serum uric acid levels are an independent predictor of death in patients at high risk of cardiovascular disease. Further studies are warranted to evaluate its prognostic implications and potential utility in the monitoring of therapy.     

代谢综合征在缺血性卒中患者心脑血管事件发生中的作用

Objective To explore the association between metabolic syndrome (MS) and risk of cardiovascular disease events (CVD) in patients with ischemic stroke. Method A total of 1087 patients with ischemic stroke were enrolled from 5 community-based medical centres and underwent baseline evaluation on risk factors of stroke during the period of Jar. 2003 to Dec. 2006. After baseline survey, all patients were followed up until Dec 31, 2008 and new CVD events were recorded. MS was defined using CDS criteria. Proportional hazard models were used to assess the HRus and 95% CI of CVD events associated with MS and other components. Results The prevalence of MS was 40. 4% at baseline. During an average follow-up of 3.5 years, 178 patients developed new CVD events. After adjusted for age, gender, smoking,drinking, marriage status, education level, hospitalization, recurrence of stroke, stroke duration,depression, cognition impairment and ADL, MS remains the independent predictor for the risk of CVD events. Compared with patients with non-MS, the risk of CVD events increased by 44% (HR:1.44, 95%CI:1.06-1.95 ). The risk of CVD also increased with the number of MS components. Compared with patients with 1 or less than 1 components of MS, the risk of CVD events increased by 30% (HR:1. 30,95%CI:0.83-2.04) in those with 2 components and by 69% ( HR: 1.69,95% CI: 1.11-2.56) in those with 3or more components of MS. Hypertension and hyperglycemia and impaired fasting glucose also served as independent risk factors for CVD event ( all P ＜ 0. 001 ) . Conclusions MS was independently associated with increased risk of CVD events in patients with ischemic stroke. There was a dose-response relationship between the numbers of MS components and the risk of CVD event.     

代谢综合征在缺血性卒中患者心脑血管事件发生中的作用

Objective To explore the association between metabolic syndrome (MS) and risk of cardiovascular disease events (CVD) in patients with ischemic stroke. Method A total of 1087 patients with ischemic stroke were enrolled from 5 community-based medical centres and underwent baseline evaluation on risk factors of stroke during the period of Jar. 2003 to Dec. 2006. After baseline survey, all patients were followed up until Dec 31, 2008 and new CVD events were recorded. MS was defined using CDS criteria. Proportional hazard models were used to assess the HRus and 95% CI of CVD events associated with MS and other components. Results The prevalence of MS was 40. 4% at baseline. During an average follow-up of 3.5 years, 178 patients developed new CVD events. After adjusted for age, gender, smoking,drinking, marriage status, education level, hospitalization, recurrence of stroke, stroke duration,depression, cognition impairment and ADL, MS remains the independent predictor for the risk of CVD events. Compared with patients with non-MS, the risk of CVD events increased by 44% (HR:1.44, 95%CI:1.06-1.95 ). The risk of CVD also increased with the number of MS components. Compared with patients with 1 or less than 1 components of MS, the risk of CVD events increased by 30% (HR:1. 30,95%CI:0.83-2.04) in those with 2 components and by 69% ( HR: 1.69,95% CI: 1.11-2.56) in those with 3or more components of MS. Hypertension and hyperglycemia and impaired fasting glucose also served as independent risk factors for CVD event ( all P ＜ 0. 001 ) . Conclusions MS was independently associated with increased risk of CVD events in patients with ischemic stroke. There was a dose-response relationship between the numbers of MS components and the risk of CVD event.