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Uric acid within the "normal" range predict 9-year cardiovascular mortality in older individuals. The InCHIANTI study.

ABSTRACT: BACKGROUND AND AIMS:Increased uric acid levels correlate with cardiovascular disease and cardiovascular/overall mortality. To identify a uric acid threshold above which cardiovascular mortality rises, we studied the relationship between uric acid concentration and overall/cardiovascular mortality. METHODS AND RESULTS:We analyzed data from the InCHIANTI study, a cohort study of Italian community-dwelling people with 9 years of follow-up. We selected a sample of 947 individuals over 64 years of age, free from cardio-cerebrovascular disease and with available uric acid measurement at baseline. The sample was divided according to plasma uric acid tertiles. The Hazard ratio (HR) for mortality was calculated by multivariate Cox proportional hazard model. Mean age of participants was 75.3 ± 7.3 years; the mean value of uric acid was 5.1 ± 1.4 mg/dl. Over 9-years of follow-up, 342 (36.1%) participants died, 143 deaths (15.1%) were due to cardiovascular disease. Subjects with higher uric acid concentrations presented a higher cardiovascular mortality [II (4.6-5.5 mg/dl) vs I (1.8-4.5 mg/dl) tertile HR: 1.98, 95%C.I. 1.22-3.23; III (?5.6 mg/dl) vs I tertile HR: 1.87, 95%C.I. 1.13-3.09]. We found a non-linear association between uric acid concentrations and cardiovascular mortality with the lowest mortality for values of about 4.1 mg/dl and a significant risk increment for values above 4.3 mg/dl. CONCLUSION:In community-dwelling older individuals free from cardio-cerebrovascular events, the lowest 9-year cardiovascular mortality was observed for uric acid values far below current target values. If confirmed, these data might represent the background for investigating the efficacy of uric acid levels reduction in similar populations.

SUBMITTER: Brombo G

PROVIDER: S-EPMC6744329 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Uric acid within the "normal" range predict 9-year cardiovascular mortality in older individuals. The InCHIANTI study.

Brombo Gloria G Bonetti Francesco F Volpato Stefano S Morieri Mario L ML Napoli Ettore E Bandinelli Stefania S Cherubini Antonio A Maggio Marcello M Guralnik Jack J Ferrucci Luigi L Zuliani Giovanni G

Nutrition, metabolism, and cardiovascular diseases : NMCD 20190628 10

<h4>Background and aims</h4>Increased uric acid levels correlate with cardiovascular disease and cardiovascular/overall mortality. To identify a uric acid threshold above which cardiovascular mortality rises, we studied the relationship between uric acid concentration and overall/cardiovascular mortality.<h4>Methods and results</h4>We analyzed data from the InCHIANTI study, a cohort study of Italian community-dwelling people with 9 years of follow-up. We selected a sample of 947 individuals over ...[more]

PMID: 31377184

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Project description:Evidence regarding thyroid-stimulating hormone (TSH) levels within the normal range and mortality in adults with diabetes is scarce. This study aimed to identify the association between TSH levels and cardiovascular disease (CVD) and all-cause mortality among euthyroid patients with diabetes. This prospective cohort study included 1830 adults with diabetes from the Third National Health and Nutrition Examination Survey III. Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Participants were categorized by tertiles of TSH levels (low-normal, 0.39-1.30 mIU/L; medium-normal, 1.30-2.09 mIU/L; high-normal, 2.09-4.60 mIU/L). Multivariable Cox proportional hazards models were used to explore the association between TSH levels within the normal range and overall and CVD mortality. Furthermore, restricted cubic spline analyses were used to determine the nonlinear relationship between TSH levels and mortality. During a median follow-up of 17.1 years, 1324 all-cause deaths occurred, including 525 deaths from CVD. After multivariate adjustment, a U-shaped relationship was observed between TSH levels in euthyroid status and all-cause or CVD mortality among patients with diabetes (both P < 0.05 for nonlinearity). Compared with participants with medium-normal TSH levels, those with high-normal TSH levels had a significantly higher risk of all-cause (hazard ratio, 1.31; 95% confidence interval, 1.07-1.61) and CVD (1.52; 1.08-2.12) mortality. Similarly, low-normal TSH levels also increased all-cause (1.39; 1.12-1.73) and CVD (1.69; 1.17-2.44) mortality risk. In stratum-specific analyses, we found that high-normal TSH levels were associated with higher mortality risk in younger (< 60 years) patients with diabetes but not in older (≥ 60 years) participants. Low- and high-normal serum TSH levels were associated with increased all-cause and CVD mortality in euthyroid adults with diabetes. Further studies are needed to confirm the present observation in a wider population.

Project description:AIMS:There is uncertainty about which estimated glomerular filtration rate eGFR equation to use in older people with respect to the prediction of prognosis. Our aim was: (i) to compare the discriminative capacity of eGFR estimated by different equations with respect to all-cause mortality; and (ii) to identify the eGFR threshold at which the risk of mortality starts to increase for each equation. METHODS:We used data from 828 community-dwelling older adults aged >65 years enrolled in the InCHIANTI study. The outcome measure was all-cause mortality at 9 years. GFR was estimated by five different equations: Chronic Kidney Disease Epidemiological Collaboration (creatinine equation [CKD-EPIcre ], and creatinine and cystatin C equation [CKD-EPIcre-cys ]), Berlin Initiative Study (BIScre and BIScre-cys ) and full age spectrum. Sensitivity, specificity, areas under receiver operating curve (AUC) and C-statistics were used to compare their predictive capacity. RESULTS:The best mix of sensitivity, specificity, AUC and C-statistic value in predicting mortality was observed with BIS equations. BIScre (AUC 0.65, 95% CI 0.61-0.69) outperformed both CKD-EPIcre (AUC 0.60, 95% CI 0.56-0.64; P = 0.005) and full age spectrum (AUC 0.63, 95% CI 0.59-0.67; P = 0.002) in terms of predictivity. Similarly, BIScre-cys (AUC 0.67, 95% CI 0.63-0.71) outperformed CKD-EPIcre-cys (AUC 0.63, 95% CI 0.59-0.67; P = 0.01). AUC obtained with equations also including cystatin C were not significantly different compared with their creatinine-based counterparts. The risk of long-term mortality began to increase at under 65.6 mL/min/1.73 m2 for CKD-EPIcre-cys , 60.5 for CKD-EPIcre , 60 for BIScre-cys , 56.3 for BIScre and 55.2 for full age spectrum. CONCLUSIONS:The BIS equation discriminates the risk of all-cause mortality better than other equations in older community-dwelling individuals. The eGFR threshold under which mortality starts to increase could change as a function of the equation used. Geriatr Gerontol Int 2018; 18: 607-614.

Project description:Background Associations between serum uric acid (SUA) and changes in cognitive function are understudied in non-normotensive populations, and many previous studies only considered the baseline SUA at a single time point. We aimed to examine the effects of baseline SUA and 4-year changes in SUA on cognitive changes in the non-normotensive population. Materials and methods In the China Health and Retirement Longitudinal Study (CHARLS), cognitive function was measured based on executive function and episodic memory in four visits (years: 2011, 2013, 2015, and 2018). We identified two study cohorts from CHARLS. The first cohort included 3,905 non-normotensive participants. Group-based single-trajectory and multi-trajectory models were applied to identify 7-year cognitive trajectories. Adjusted ordinal logistics models were performed to assess the association between baseline SUA and 7-year cognitive trajectories, and subgroup analyses were conducted according to the presence of hyperuricemia or SUA levels. The second cohort included 2,077 eligible participants. Multiple linear regression was used to explore the effect of a 4-year change in SUA on cognitive change during the subsequent 3-year follow-up. Results Four distinct single-trajectories of global cognitive performance and four multi-trajectories of executive function and episodic memory were identified. Higher baseline SUA levels were significantly associated with more favorable cognitive single-trajectories (ORQ4 vs. Q1: 0.755; 95% CI: 0.643, 0.900) and multi-trajectories (ORQ4 vs. Q1: 0.784; 95% CI: 0.659, 0.933). Subgroup analyses revealed that the protective effect of SUA was significant in the non-hyperuricemia groups or the low-level SUA groups. Additionally, changes in SUA could influence future cognitive changes. Compared with non-hyperuricemia participants with elevated SUA, non-hyperuricemia participants with decreased SUA and patients with persistent hyperuricemia had a higher risk for cognitive decline. Furthermore, only the Q3 group of changes in SUA could enhance global cognitive function compared with the Q1 group (β: 0.449; 95% CI: 0.073, 0.826). Conclusion Our study indicates that the maintenance of normal SUA levels and a moderate increase of SUA were advantageous in improving cognitive function or trajectories in a non-normotensive population. Conversely, SUA may impair cognitive function in patients with persistent hyperuricemia.

Project description:Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

Project description:BackgroundElevated serum uric acid (SUA) has a positive correlation with insulin secretion and insulin resistance indexes. However, whether weight- and gender-specific differences regarding the relationship between SUA within the normal range and β-cell function and insulin resistance exist is unknown in type 2 diabetes mellitus (T2DM) patients.MethodsA total of 380 patients with type 2 diabetes were divided into two groups as overweight/obesity (n = 268) and normal weight (n = 112). Each group were again divided into low (LSUA) and high normal SUA (HSUA). The HbA1c, C-peptide, SUA, creatinine, and lipids profiles were measured. HOMA2IR and HOMA%2B were estimated using fasting glucose and C-peptide by homeostasis model assessment (HOMA). Pearson's correlations and multiple linear regression analyses were conducted to assess the associations between SUA levels and islet function indexes.ResultsIn overweight/obesity subgroup, the levels of body mass index, fasting C-peptide (FCP), P2hCP, fasting CPI (FCPI), postprandial CPI (PPCPI), ΔC-peptide, HOMA2%B, and HOMA2IR were higher in HSUA group than in LSUA group. In contrast, the HbA1c, FBS, and P2hBS were lower in HSUA than in LSUA. In normal weight subgroup, there were no differences between the HSUA than LSUA group in terms of clinical characteristics. Pearson's correlations indicated that there were no significant correlations between SUA and insulin secretory capacity in normal weight group, but in overweight/obesity group, SUA had positive significant correlations with P2hCP, FCPI, PPCPI, ΔC-peptide, and HOMA2%B. In the female group, there were no significant correlations between SUA and insulin secretory capacity. However, in the male group, SUA had positive significant correlations with insulin secretory capacity include P2hCP, FCPI, PPCPI, ΔC-peptide, and HOMA2%B. Multiple linear regression showed that SUA was significantly associated with HOMA2%B, but not with HOMA2IR in overweight/obesity and male group.ConclusionsOur study shows that SUA levels within normal range were associated with β-cell function in T2DM patients with overweight/obesity or male. This finding supports that the association between SUA within normal range and insulin secretion ability differs by weight and sex.

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Uric acid within the "normal" range predict 9-year cardiovascular mortality in older individuals. The InCHIANTI study.

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Uric acid within the "normal" range predict 9-year cardiovascular mortality in older individuals. The InCHIANTI study.

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