Serum Uric Acid and Kidney Disease Measures Independently Predict Cardiovascular and Total Mortality: The Uric Acid Right for Heart Health (URRAH) Project

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality. Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality. Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and <60 ml/min) was significantly higher in patients with hyperuricemia and albuminuria (3.8, 22.1 and 19.1, respectively) as compared to those with only one risk factor or none (0.4, 2.8 and 3.1, respectively). Serum uric acid and eGFR significantly interact in determining cardiovascular and all-cause mortality. For each SUA increase of 1 mg/dl the risk for mortality increased by 10% even after adjustment for potential confounding factors included eGFR and the presence of albuminuria. Conclusions: hyperuricemia is a risk factor for cardiovascular and all-cause mortality additively to eGFR strata and albuminuria, in patients at cardiovascular risk

Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project

Background: Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. Methods: Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. Results: Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides. Conclusions: The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR < 60 ml/min the occurrence of hyperuricemia is about 10 times higher than in those with eGFR > 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria

Serum uric acid / serum creatinine ratio as a predictor of cardiovascular events. Detection of prognostic cardiovascular cut-off values

Objective: In the frame of the Uric Acid Right for Heart Health (URRAH) study, a nationwide multicenter study involving adult participants recruited on a regional community basis from all the territory of Italy under the patronage of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, we searched for the cut-off values of the ratio between serum uric acid (SUA) and serum creatinine (sCr) able to predict cardiovascular (CV) events. Methods: Among 20 724 participants followed-up for 126 ± 64 months, after detecting cut-off by the receiver operating characteristic curves, we calculated by Cox models adjusted for confounders having CV events as dependent variable the hazard ratio (HR) of SUA/sCr > cut-off. We also verified if the role of cut-off varied with increasing SUA/sCr. Results: A plausible prognostic cut-off of SUA/sCr was found and was the same in the whole database, in men and in women (>5.35). The HR of SUA/sCr > cut-off was 1.159 (95% confidence interval [CI] 1.092-1.131, P < 0.03) in all, 1.161 (95% CI 1.021-1.335, P < 0.02) in men, and 1.444 (95% CI 1.012-1.113, P < 0.03) in women. In increasing quintiles of SUA/sCr the cut-offs were >3.08, >4.87, >5.35, >6.22 and >7.58, respectively. The HRs significantly increased from the 3rd to the 5th quintile (1.21, 95% CI 1.032-1.467, P = 0.018; 1.294, 95% CI 1.101-1.521, P = 0.002; and 1.642, 95% CI 1.405-1.919, P < 0.0001; respectively), that is, over 5.35, whereas the 2nd quintile was not significantly different from the 1st (reference). Conclusion: Having SUA/sCr >5.35 is an independent CV risk indicator both in men and women. The cut-off is dynamic and significantly increases with increasing SUA/sCr

Serum Uric Acid Predicts All-Cause and Cardiovascular Mortality Independently of Hypertriglyceridemia in Cardiometabolic Patients without Established CV Disease: A Sub-Analysis of the URic acid Right for heArt Health (URRAH) Study

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan-Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (≥4.7 mg/dL) and CVM (≥5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12-1.40], p < 0.001) and CVM (1.31 [1.11-1.74], p < 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12-1.43], p < 0.001) and hypertriglyceridemia (1.31 [1.02-1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23-1.73], p < 0.001) and hypertriglyceridemia (HR 1.31 [0.99-1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels

BP reactivity to public speaking in stage 1 hypertension: Influence of different task scenarios.

Aim. To investigate the blood pressure (BP) reaction to public speaking performed according to different emotionally distressing scenarios in stage 1 hypertension. Methods. We assessed 64 hypertensive and 30 normotensive subjects. They performed three speech tasks with neutral, anger and anxiety scenarios. BP was assessed with the Finometer beat-to-beat non-invasive recording system throughout the test procedure. Results. For all types of speech, the systolic BP response was greater in the hypertensive than the normotensive subjects (all p < 0.001). At repeated-measures analysis of covariate (R-M ANCOVA), a significant group-by-time interaction was found for all scenarios (p <= 0.001). For the diastolic BP response, the between-group difference was significant for the task with anxiety scenario (p < 0.05). At R-M ANCOVA, a group-by-time interaction of borderline statistical significance was found for the speech with anxiety content (p = 0.053) but not for the speeches with neutral or anger content. Within the hypertensive group, the diastolic BP increments during the speeches with anxiety and anger scenarios were greater than those during the speech with neutral scenario (both p < 0.001). Conclusions. These data indicate that reactivity to public speaking is increased in stage 1 hypertension. A speech with anxiety or anger scenario elicits a greater diastolic BP reaction than tasks with neutral content