Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21–1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146–2.97]; P <0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL [95% CI, 4.3–5.1 mg/dL]) and CVM status (5.6 mg/dL [95% CI, 4.99–6.21 mg/dL]) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively ( P <0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.

Introduction Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim We assessed the prognostic role of SUA in patients with and without MS. Methods We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Results A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p < 0.0001) and provided a significant net reclassification improvement of 7.1% over the diagnosis of MS for CVM (p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15–2.79]; p < 0.0001) after the adjustment for MS, its single components and renal function. Three specific combinations of the MS components were associated with higher CVM when increasing SUA levels were reported, and systemic hypertension was the only individual component ever-present (all p < 0.0001). Conclusion Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification. Graphic abstract

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Aims  Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results  Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P &lt; 0.0001) over a multivariable model. However, the risk of CVM related to high UA (≥5.5 mg/dL, top tertile) was much lower in the subjects with HR &lt;median [71.3 b.p.m., adjusted hazard ratio 1.38, 95% confidence interval (CI) 1.20–1.59] than in those with HR ≥median [2.09 (95% CI 1.75–2.51)]. In the participants stratified by HR tertile, the risk related to hyperuricaemia was 2.38 (95% CI 1.82–3.10) in people with HR ≥76 b.p.m. and was 1.24 (95% CI 0.92–1.67) in those with HR &lt;66 b.p.m. Similar results were obtained in the hypertensive patients, in the participants ≥65 years, and in the subjects not taking beta-blockers. Conclusion  This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.

500 infertile patients (250 with and 250 without left side varicocele) and 33 fertile men were evaluated as far as seminal parameters and the hormonal status were concerned. Sperm motility was constantly lower in infertile patients also when infertile group was compared to fertile one with the same sperm density. Serum testosterone levels were lower in infertile groups when compared to fertile men, and this c o n f m s the existence of an androgenic deficit as a common finding in infertility associated or not to varicocele. FSH and LH increased (p < 0.001) when sperm density dropped to less than 5 x lo6 spermatozoa/ml. A negative correlation was found between both gonadotropins and sperm count (p < 0.001), also after exclusion of azoo-and oligozoospermic (less than 5 x lo6 spermatozoa/ml) patients (p < 0.01). Gonadotropins were moreover tightly correlated between each other (p < 0.001). Our data suggest that both gonadotropins are tightly tuned with sperm output and thus with the spermatogenic potential. Hormonale und Spermaparameter bei unfruchtbaren MannernZusammenfassung: Insgesamt wurden 500 Manner (250 mit und 250 ohne linksseitige Varikocele) hinsichtlich der Spermaparameter und der Hormonanalysen mit 33 fruchtbaren Miinnern verglichen. Dabei ergab sich, dai3 die Spermatozoenmotilitat in der infertilen Gruppe sigdikant niedriger lag. Der Testosteronwert war in der infertilen Gruppe ebenfalls niedriger; daraus wird die SchluBfolgerung eines androgenen Defuites gezogen. Die Werte fir FSH und LH zeigten einen Anstieg, sobald die Spermatozoendichte unter 5 x lo6 Spermatozoen abfiel (p < 0.001). Zwischen den Gonadotropinen und der Spermatozoendichte ergab sich eine negative Korrelation (p < 0,001), und zwar auch nach Aus-schlul3 der Azoo-und Oligozoospermie-Gruppe (unter 5 x lo6 Sp,/ml) (p < 0,Ol). Daruber hinaus waren die Gonadotropine untereinander starker korreliert (p < 0,OOOl). Die Ergebnisse legen nahe, d& FSH und LH starker ubereinstimmen mit dem Spermatozoen-ausstoB und dementsprechend mit dem spermatogenetischen Potential.Sperm density is predictive of a prevalent male factor in an infertile couple when it is