Serum Uric Acid Revealed a U-Shaped Relationship With All-Cause Mortality and Cardiovascular Mortality in High Atherosclerosis Risk Patients: The ASSURE Study

Background: Previous studies have demonstrated an association between hyperuricemia and cardiovascular disease (CVD). The Framingham study confirmed that patients with high atherosclerotic risks (HARs) had worse prognoses. However, after adjusting for confounding factors, the association between serum uric acid (SUA) and all-cause mortality and cardiovascular mortality remains unclear, especially for HAR patients.Objective: The aim of this study was to reveal the relationship of SUA with all-cause and cardiovascular mortality in HAR patients.Methods: This multicenter cohort study enrolled 3,047 participants, and the follow-up was 68.85 ± 11.37 months. Factors related to cardiovascular and all-cause mortality were tested by multivariate Cox regression analysis. Restricted cubic splines (RCSs) with knots were used to explore the shape of the dose–response relationship with SUA and the hazard ratio (HR) of all-cause and CVD mortality. SUA transformed by RCS was added to the Cox regression model as an independent variable, and all-cause and CVD mortality scores were calculated. Survival receiver operating characteristic curves were produced using a regression model predicting the score.Results: SUA demonstrated a “U-shaped” relationship with all-cause and cardiovascular mortality. SUA predicted all-cause and CVD mortality, with cutoff values of values of >370.5 μmol/L for males and >327.65 μmol/L for females and <180.5 μmol/L for males and <165.7 μmol/L for females, respectively. The survival ROC curve indicated that SUA is able to predict all-cause and CVD mortality, with areas under the curve of 0.702 and 0.711, respectively. The HRs of all-cause mortality (male and female) with hyperuricemia and hypouricemia were 2.08 and 2.01 and 2.04 and 1.98, respectively, and the HRs of CVD mortality (male and female) were 2.09 and 1.79, and 2.02 and 1.89, respectively.Conclusion: Abnormal SUA levels were significant and independent risk factors for all-cause and CVD mortality. Hyperuricemia and hypouricemia increased mortality in both males and females. Routine SUA evaluation and intensive management are needed for HAR patients.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03616769.

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Serum Uric Acid Showed U-shaped Relationship with All-Cause Mortality and Cardiovascular Mortality in High Atherosclerosis Risk Patients: ASSURE Study

10.21203/rs.3.rs-60123/v1 ◽

2020 ◽

Author(s):

Yan Cang ◽

Shaojie Xu ◽

Jinying Zhang ◽

Zijun Chen ◽

Keke Wang ◽

...

Keyword(s):

Uric Acid ◽

Serum Uric Acid ◽

Cardiovascular Mortality ◽

Cox Regression ◽

Rank Test ◽

Cardiac Events ◽

Cox Regression Analysis ◽

All Cause Mortality ◽

Risk Patients ◽

Restricted Cubic Splines

Abstract Background: Previous studys have demonstrated association between hyperuricemia and cardiovascular disease (CVD), and Framingham study has confirmed patients with high atherosclerotic risk (HAR) had worse prognosis. But after controlling other traditional atherosclerotic risks, the association between serum uric acid (SUA) and all-cause mortality, cardiovascular mortality remains controversial, especially in HAR patients.Objective: The aim of study was to reveal the relationship with SUA and all-cause mortality, cardiovascular mortality in HAR patients.Methods: The multi-center cohort study comprised 3,640 participants (1927male, 1713 female),whose mean age was 60.2±10.4 years andmean follow-uptimewere 68.85±11.37 months. Factors related to cardiovascular mortality and all-cause mortality, major adverse cardiac events in-hospital during follow-up were tested by multivariate Cox regression analysis and log-rank test. Restricted cubic splines with knots were used to explore theshape of dose-response relationship with SUA levels and Hazard risk (HR) of all-cause and CVD mortality.Results：The study showed SUA presented U-shaped relationship with all-cause and cardiovascular mortality. HR of all-cause mortality with hyperuricemia and hypouricemia was 2.11, 95% CI(1.61-3.07), and 2.05, 95% CI(1.35-2.90), respectively. HR of Cardiovascular mortality was 2.42, 95% CI (1.61-3.12), and 1.95, 95% CI(1.29-2.90), respectively. Conclusion：Abnormal SUA levels maybe significant and independent risk factors for all-cause and cardiovascular mortality. Routine SUA evaluation and intensive management are pressing needed, especially in HAR patients.

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Prognostic Significance of Fragmented QRS in Patients with Hypertrophic Cardiomyopathy

Cardiology ◽

10.1159/000471845 ◽

2017 ◽

Vol 138 (1) ◽

pp. 26-33 ◽

Cited By ~ 3

Author(s):

Xili Lu ◽

Wei Wang ◽

Ling Zhu ◽

Yilu Wang ◽

Kai Sun ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Clinical Outcomes ◽

Cox Regression ◽

Prognostic Significance ◽

Cox Regression Analysis ◽

Fragmented Qrs ◽

All Cause Mortality ◽

The Relationship ◽

Cvd Mortality

Objectives: The relationship between a fragmented QRS (fQRS) and clinical outcomes in patients with hypertrophic cardiomyopathy (HCM) remains unclear. This study aimed to investigate the prognostic significance of fQRS in patients with HCM. Methods: Between 2000 and 2012, 326 unrelated patients with HCM (72% male with a mean age of 52 years) were included and were divided into 2 groups: those with fQRS and those without fQRS. Results: A total of 105/326(32.2%) patients with HCM presented with fQRS at enrollment. During a follow-up of 5.3 ± 2.4 years, 33 patients died, 30 of cardiovascular disease (CVD). Cox regression analysis revealed that fQRS predicted a higher risk of all-cause mortality (adjusted hazard ratio [HR] 2.24; 95% confidence interval [CI] 1.08-4.64; p = 0.030) and CVD mortality (adjusted HR 2.68; 95% CI 1.22-5.91; p = 0.014). Our study also showed that fQRS increased the risk of heart failure-related death (adjusted HR 3.75; 95% CI 1.24-11.30; p = 0.019). Conclusions: Our results indicate that fQRS is associated with adverse clinical outcomes in patients with HCM.

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Comparison of 24-hour and Office Pulse Wave Velocity for Prediction of Mortality in Hemodialysis Patients

American Journal of Nephrology ◽

10.1159/000499532 ◽

2019 ◽

Vol 49 (4) ◽

pp. 317-327 ◽

Cited By ~ 10

Author(s):

Julia Matschkal ◽

Christopher C. Mayer ◽

Pantelis A. Sarafidis ◽

Georg Lorenz ◽

Matthias C. Braunisch ◽

...

Keyword(s):

Regression Analysis ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Cardiovascular Mortality ◽

Pulse Wave ◽

Cox Regression ◽

Hemodialysis Patients ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

All Cause Mortality

Background: Mortality in hemodialysis patients still remains unacceptably high. Enhanced arterial stiffness is a known cardiovascular risk factor, and pulse wave velocity (PWV) has proven to be a valid parameter to quantify risk. Recent studies showed controversial results regarding the prognostic significance of PWV for mortality in hemodialysis patients, which may be due to methodological issues, such as assessment of PWV in the office setting (Office-PWV). Method: This study cohort contains patients from the “Risk stratification in end-stage renal disease – the ISAR study,” a multicenter prospective longitudinal observatory cohort study. We examined and compared the predictive value of ambulatory 24-hour PWV (24 h-PWV) and Office-PWV on mortality in a total of 344 hemodialysis patients. The endpoints of the study were all-cause and cardiovascular mortality. Survival analysis included Kaplan-Meier estimates and Cox regression analysis. Results: During a follow-up of 36 months, a total of 89 patients died, 35 patients due to cardiovascular cause. Kaplan-Meier estimates for tertiles of 24 h-PWV and Office-PWV were similarly associated with mortality. In univariate Cox regression analysis, 24 h-PWV and Office-PWV were equivalent predictors for all-cause and cardiovascular mortality. After adjustment for common risk factors, only 24 h-PWV remained solely predictive for all-cause mortality (hazard ratio 2.51 [95% CI 1.31–4.81]; p = 0.004). Conclusions: Comparing both measurements, 24 h-PWV is an independent predictor for all-cause-mortality in hemodialysis patients beyond Office-PWV.

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Hyperuricemia and Impaired Renal Function: A Prospective Cohort Study

Kidney Diseases ◽

10.1159/000511196 ◽

2020 ◽

pp. 1-9

Author(s):

Noppawit Aiumtrakul ◽

Puvanant Wiputhanuphongs ◽

Ouppatham Supasyndh ◽

Bancha Satirapoj

Keyword(s):

Renal Function ◽

Uric Acid ◽

Regression Analysis ◽

Cohort Study ◽

Serum Uric Acid ◽

Prospective Cohort ◽

Impaired Renal Function ◽

Cox Regression ◽

Community Based ◽

Cox Regression Analysis

Background: Related studies have demonstrated a relationship of elevated serum uric levels with a decline in kidney function. However, limited evidence exists in a Southeast Asian community-based population. Objective: The study aimed to examine the relationship between serum uric acid levels and impaired renal function. Methods: A prospective cohort study was conducted in the Thai army health checkup population between July 1, 2006 and December 31, 2012. Inclusion criteria included age older than 20 years and baseline estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73 m2. Cox regression analysis was used to evaluate the association between incidence of impaired renal function and baseline serum uric acid quartiles. Impaired renal function was defined as eGFR <60 mL/min/1.73 m2 over 3 months. Results: A total of 9,534 participants (7,474 men and 2,060 women) were enrolled. Cox regression analysis revealed a significant association of serum uric acid level with impaired renal function in the whole population as the unadjusted hazard ratio (HR) (95% CI) of impaired renal function in second, third, and fourth quartiles were 2.1 (1.39, 3.17), 2.39 (1.6, 3.59), and 3.94 (2.71, 5.74), respectively, when compared with serum uric acid in the first quartile, respectively. After adjusting in 2 models, the HR still significantly persisted with similar magnitudes in all quartiles. Higher incidences of impaired renal function were observed among males than among females in all quartiles. Kaplan-Meier curve showed better renal survival rate in the lower quartile groups. Linear regression analysis showed that eGFR negatively correlated with serum uric acid (r = −0.213, p < 0.001). Conclusion: Our study suggests that an independent association exists of serum uric acid levels with the incidence of impaired renal function and renal progression in the Southeast Asian community-based population.

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Association between uric acid lowering and renal function progression: a longitudinal study

PeerJ ◽

10.7717/peerj.11073 ◽

2021 ◽

Vol 9 ◽

pp. e11073

Author(s):

Liyi Liu ◽

Lili You ◽

Kan Sun ◽

Feng Li ◽

Yiqin Qi ◽

...

Keyword(s):

Renal Function ◽

Uric Acid ◽

Serum Uric Acid ◽

Regression Models ◽

Cox Regression ◽

Population Based ◽

Hazard Ratio ◽

Cox Regression Analysis ◽

Renal Function Decline ◽

Reduced Risk

Background This study aimed to explore the association between uric acid lowering and renal function. Materials and Methods We conducted a population-based cohort study with 1,534 subjects for 4 years from 2012 to 2016. The population was divided into four groups according to the interquartile range of changes in serum uric acid with quartile 1 representing lower quarter. Renal function decline was defined as eGFR decreased more than 10% from baseline in 2016. Renal function improvement was defined as eGFR increased more than 10% from baseline in 2016. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results In the adjusted Cox regression models, compared to quartile 4, quartile 1 (HR = 0.64, 95% CI [0.49–0.85]), quartile 2 (HR = 0.65, 95% CI [0.50–0.84]) and quartile 3 (HR = 0.75, 95% CI [0.58–0.96]) have reduced risk of renal function decline. An increasing hazard ratio of renal function improvement was shown in quartile 1 (HR = 2.27, 95% CI [1.45–3.57]) and quartile 2 (HR = 1.78, 95% CI [1.17–2.69]) compared with quartile 4. Conclusions Uric acid lowering is associated with changes in renal function. The management of serum uric acid should receive attention in clinical practice and is supposed to be part of the treatment of chronic kidney disease.

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Association between uric acid level and incidence of macroalbuminuria in people with type 2 diabetes mellitus: A 4.5-year cohort study

10.21203/rs.2.18350/v1 ◽

2019 ◽

Author(s):

Yun-Ju Lai ◽

Yu-Yen Chen ◽

Li-Jung Chen ◽

Po-Wen Ku ◽

Kuo-Chuan Hung ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Uric Acid ◽

Serum Uric Acid ◽

Cox Regression ◽

Characteristic Curve ◽

Cox Regression Analysis ◽

Increased Risk

Abstract Background: Using animal models and molecular biology researches, hyperuricemia has been shown to instruct renal arteriolopathy, arterial hypertension, and microvascular injury involving the renin-angiotensin system and resulting in renal function impairment. Nevertheless, the association between uric acid levels and the development of macroalbuminuria has been under-investigated in people with type 2 diabetes mellitus. Methods: Patients with type 2 diabetes and regular outpatient visits were recruited from a community hospital in Taiwan since January 2014. Demographics, lifestyle features, and medical history were gathered by well-trained interviewers. All participants underwent comprehensive physical examinations, including a biochemical assay of venous blood specimens and urine samples after an 8-hour overnight fast. Participants were followed until June 2018. The primary outcome was the macroalbuminuria incidence. Univariable and multivariable Cox regression analysis were employed to explore the relation between uric acid and incident macroalbuminuria. Uric acid cutoffs for incident macroalbuminuria were determined with the receiver operator characteristic curve. Results: We included 247 qualified subjects (mean age: 64.78 years old [standard deviation=11.29 years]; 138 [55.87%] men). During a 4.5-year follow-up duration, 20 subjects with incident macroalbuminuria were recognized. Serum uric acid was significantly associated with an increased risk of incident macroalbuminuria (adjusted hazard ratio=2.39; 95% confidence interval: 1.53-3.75; p<0.001) with potential confounders adjustment. The uric acid cutoff point was 6.9 mg/dL (area under the curve 0.708, sensitivity 60.0%, specificity 84.58%) for incident macroalbuminuria. Conclusions: Serum uric acid was associated with incident macroalbuminuria among people with type 2 diabetes.

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The Significance of Follow-Up Serum Uric Acid Levels in Predicting All-Cause Mortality and Cardiovascular Mortality in Peritoneal Dialysis Patients

10.21203/rs.3.rs-146953/v1 ◽

2021 ◽

Author(s):

Pingping Ren ◽

Qilong Zhang ◽

Yixuan Pan ◽

Yi Liu ◽

Chenglin Li ◽

...

Keyword(s):

Uric Acid ◽

Peritoneal Dialysis ◽

Serum Uric Acid ◽

Cardiovascular Mortality ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Kaplan Meier ◽

Significant Difference ◽

All Cause Mortality

Abstract Background: Studies on the correlation between serum uric acid (SUA) and all-cause mortality in peritoneal dialysis (PD) patients were mainly based on the results of baseline SUA. We aimed to analyze the change of SUA level post PD, and the correlation between follow-up SUA and prognosis in PD patients. Methods: All patients who received PD catheterization and maintaining PD in our center from March 2, 2001 to March 8, 2017 were screened. Kaplan-Meier and Cox proportional-hazards regression models were used to analyze the effect of SUA levels on the risks of death. We graded SUA levels at baseline, 6 months, 12 months, 18 months and 24 months post PD by mean of SUA plus or minus a standard deviation as cut-off values, and compared all-cause and cardiovascular mortality among patients with different SUA grades. Results: A total of 1402 patients were included, 763 males (54.42%) and 639 females (45.58%). Their average age at PD start was 49.50±14.20 years. The SUA levels were 7.97±1.79mg/dl at baseline, 7.12±1.48mg/dl at 6 months, 7.05±1.33mg/dl at 12 months, 7.01±1.30mg/dl at 18 months, and 6.93±1.26mg/dl at 24 months. During median follow-up time of 31 (18, 49) months, 173 (12.34%) all-cause deaths occurred, including 68 (4.85%) cardiovascular deaths. There were no significant differences on all-cause mortality among groups with graded SUA levels at baseline, 12 months, 18 months and 24 months during follow-up or on cardiovascular mortality among groups with graded SUA levels at baseline, 6 months, 12 months, 18 months and 24 months during follow-up. At 6 months post PD，Kaplan Meier analysis showed there was significant difference on all-cause mortality among graded SUA levels (c2=11.315, P=0.010), and the all-cause mortality was lowest in grade of 5.65mg/dl≤SUA<7.13mg/dl. Conclusion: SUA level decreased during follow up post PD. At 6 months post PD, a grade of 5.65mg/dl≤SUA<7.13mg/dl was appropriate for better patients’ survival.

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Joint association of ankle-brachial index and serum uric acid on the outcomes of six-year all-cause mortality and cardiovascular mortality in Chinese patients

International Journal of Cardiology ◽

10.1016/j.ijcard.2012.04.034 ◽

2012 ◽

Vol 158 (1) ◽

pp. 144-145 ◽

Cited By ~ 7

Author(s):

Yong Wang ◽

Yawei Xu ◽

Dayi Hu ◽

Xiaoyan Guo ◽

Dongdong Zhao ◽

...

Keyword(s):

Uric Acid ◽

Serum Uric Acid ◽

Cardiovascular Mortality ◽

Ankle Brachial Index ◽

Chinese Patients ◽

All Cause Mortality

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Effect of uric acid levels on mortality in Japanese peritoneal dialysis patients

Peritoneal Dialysis International ◽

10.1177/0896860820929476 ◽

2020 ◽

pp. 089686082092947

Author(s):

Naoki Sugano ◽

Yukio Maruyama ◽

Iwao Ohno ◽

Atsushi Wada ◽

Takashi Shigematsu ◽

...

Keyword(s):

Infectious Disease ◽

Uric Acid ◽

Regression Analysis ◽

Peritoneal Dialysis ◽

Cox Regression ◽

Reference Group ◽

Continuous Variable ◽

Cox Regression Analysis ◽

Covariate Data ◽

All Cause Mortality

Background: Unlike the situation in the general population, most studies of patients receiving hemodialysis have reported lower uric acid (UA) as associated with higher mortality. However, the relationship between UA level and mortality remains unclear among patients receiving peritoneal dialysis (PD). Methods: We collected baseline data for 4742 prevalent PD patients (age, 63 ± 14 years; male, 61.5%; diabetes, 29.1%; median dialysis duration, 28 months) from a nationwide dialysis registry in Japan at the end of 2012. One-year all-cause and cardiovascular (CV) mortality and mortality caused by infectious disease were assessed using Cox regression analysis and competing-risks regression analysis, respectively. We used multiple imputation to deal with missing covariate data. Results: Within 1 year, 379 patients (8.0%) died, including 129 patients (2.7%) from CV causes and 95 patients (2.0%) from infectious disease. In multivariate analysis, serum UA, treated as a continuous variable, was not associated with any outcome. Conversely, both lower (<297 µmol/L) and higher (≥476 µmol/L) UA levels were independently associated with higher all-cause mortality compared to the reference group (416 to <446 µmol/L) in analyses where serum UA was treated as a categorical variable. Body mass index (BMI) affected the association between serum UA and all-cause mortality (interaction p = 0.049). Conclusions: A U-shaped relationship appears to exist between UA levels and all-cause mortality among Japanese PD patients. Additionally, lower BMI significantly enhanced the effect of UA levels on mortality.

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Baseline Serum Magnesium Level and Its Variability in Maintenance Hemodialysis Patients: Associations with Mortality

Kidney & Blood Pressure Research ◽

10.1159/000498957 ◽

2019 ◽

Vol 44 (2) ◽

pp. 222-232 ◽

Cited By ~ 5

Author(s):

Lingping Wu ◽

Kedan Cai ◽

Qun Luo ◽

Lailiang Wang ◽

Yue Hong

Keyword(s):

Cardiovascular Mortality ◽

Cox Regression ◽

Serum Magnesium ◽

Magnesium Level ◽

Maintenance Hemodialysis ◽

Serum Magnesium Level ◽

Baseline Serum ◽

Cox Regression Analysis ◽

All Cause Mortality ◽

Group Serum

Background/Aims: The study aimed at investigating the impact of serum magnesium (Mg) baseline level and its variability on mortality in maintenance hemodialysis (MHD) patients. Methods: Eligible patients receiving regular MHD at Ningbo No. 2 Hospital between January 2009 and August 2016 were enrolled and follow-ups were conducted afterwards until death or transplantation. General information, laboratory results, and outcomes of subjects were collected. The relationship between baseline serum Mg level, its coefficient of variation (CV), and all-cause mortality and cardiovascular disease mortality were assessed, respectively. Subjects were divided into groups in 2 manners: by serum Mg level (lower Mg group: serum Mg <1.00 mmol/L, higher Mg group: serum Mg ≥1.00 mmol/L) and by serum Mg CV (high variation group: CV ≥0.149 mmol/L, middle variation group: 0.114 mmol/L ≤ CV < 0.149 mmol/L, and low variation group: CV <0.114 mmol/L). Results: 169 MHD patients were recruited in the study, with mean serum Mg 1.00 ± 0.18 mmol/L, average age 60.20 ± 15.64 years, and median dialysis duration 37.00 (18.30, 77.97) months. During the follow-up, 69 (40.83%) patients died, 24 (34.78%) of which died due to cardiovascular disease. Comparing the two groups, patients in the lower Mg group had a higher all-cause mortality (50.00 vs. 29.33%, p = 0.007). The multivariate Cox regression analysis suggested that lower Mg level was an independent factor for all-cause mortality as well as cardiovascular mortality (HR = 13.268, 95% CI 6.234–28.237, p < 0.001; HR = 12.702, 95% CI 3.737–43.174, p < 0.001, respectively). However, there were no significant statistical differences of all-cause and cardiovascular mortality among these three groups concerning Mg variation. And in the univariate and multivariate Cox regression analysis, serum magnesium CV was not the independent factor for all-cause mortality and cardiovascular mortality. Conclusions: The lower baseline serum magnesium level was associated with all-cause and cardiovascular mortality in MHD patients. However, the variability of magnesium level was not independently associated with the risk of death and further studies need to be conducted.

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