Triglyceride-Glucose Index, HOMA Index and metabolic syndrome in a sample of adult men.

BACKGROUND: Metabolic syndrome (MetS) and its components are directly associated with cardiovascular risk. Insulin resistance (IR) is the most common pathophysiological feature of MetS. A novel index, the triglyceride-glucose index (TyG), is considered a surrogate marker of IR. Hence, we estimated the ability of TyG to predict the risk to develop MetS over a follow-up period of 8 years. In addition, we compared the predictive role of TyG and that of the HOmeostatis Model Assessment (HOMA) of IR index (a widely used tool to evaluate IR). METHODS: The analysis included 440 adult men (The Olivetti Heart Study) without MetS at baseline. The optimal cut-off point of the association of continuous TyG or HOMA-IR with MetS was identified by ROC analysis. RESULTS: During the follow-up period, 21.6% of participants developed MetS. Baseline TyG and HOMA-IR were both significantly greater in those who developed MetS than in those who did not. These results were confirmed upon adjustment for the main confounders. After stratification by the optimal cut-off point, TyG >4.78 was a significant predictor of MetS, also after adjustment for main confounders. Likewise, HOMA-IR >2.14 was associated with the risk of MetS development in multivariate models. CONCLUSIONS: The results of this prospective study indicate a significant predictive role of TyG on the risk of MetS, independently of the main confounders. They suggest that TyG may serve as a low-cost and simple non-invasive marker for cardio-metabolic risk stratification, with respect to more complex and expensive assays of IR requiring the insulin measurement.

Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.

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.

Adherence to Mediterranean Diet, Dietary Salt Intake, and Susceptibility to Nephrolithiasis: A Case-Control Study.

Unhealthy dietary habits play a key role in the pathogenesis of nephrolithiasis (NL). The aims of this case-control study were to evaluate (i) the adherence to the Mediterranean Diet (MD) and the dietary salt intake in stone-forming patients (SF), (ii) the relationship occurring between MD adherence, salt intake and NL-related metabolic risk factors in SF, and (iii) the impact of combined high MD adherence and low salt intake on NL susceptibility. From 1 January 2018 to 31 December 2019, we recruited all SF consecutively referred to the Extracorporeal Shock Wave Lithotripsy (ESWL) center of Federico II University, and at least two control subjects without a personal history of NL, age-, sex-, and body mass index-matched to SF (NSF). All study participants were interviewed using the validated MEDI-LITE and MINISAL questionnaires. In an SF subgroup, the NL-related metabolic risk factors were also evaluated. SF showed a lower MD adherence and a higher salt intake compared with NSF. The NL susceptibility decreased by 36% [OR: 0.64 (0.59-0.70); p < 0.01] for each point of increase in MEDI-LITE score, while it increased by 13% [OR: 1.13 (1.03-1.25); p = 0.01] for each point of increase in MINISAL score. The SF prevalence was higher among subjects showing combined low MD adherence and high salt intake. In SF, the MEDI-LITE score directly correlated with 24 h-citraturia, whereas the MINISAL score directly correlated with urinary sodium and uric acid excretion. In conclusion, high MD adherence and low salt intake are associated with a reduced NL susceptibility, both separately and in combination.

Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).

PURPOSE: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk. METHODS: The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. RESULTS: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors. CONCLUSIONS: The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

BACKGROUND: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. METHODS AND RESULTS: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project.

Relationship between leptin and white blood cells: a potential role in infection susceptibility and severity-the Olivetti Heart Study.

A number of evidence showed an emerging role of leptin on immune system, involving inflammation, and innate and adaptive immunity. Few observational studies have evaluated the relationship between leptin and immunity, albeit with low statistical power and methodological differences. Therefore, the aim of this study was to evaluate the potential role of leptin on the immunity, expressed as white blood cells (WBC)-and its subpopulations, by comprehensive multivariate models in a sample of adult men. A cross-sectional evaluation of a general population comprised 939 subjects participating in the Olivetti Heart Study, with available leptin levels and WBC-and its subpopulations. WBC were significantly and positively associated with leptin, C-reactive protein and HOMA index (p < 0.05), but not with age and anthropometric indices (p > 0.05). The multivariate analysis confirmed the association between leptin and WBC, after accounting for main confounders (p < 0.05). Additional analysis on WBC subpopulations showed a positive and significant correlation between leptin and lymphocytes, monocytes and eosinophils (p < 0.05), but not with neutrophils and basophils (p > 0.05). After stratification by body weight, the positive and significant association between leptin and WBC-and its subpopulations-was found in excess body weight participants. The results of this study indicate a direct relationship between leptin levels and WBC-and its subpopulations-in excess body weight participants. These results support the hypothesis that leptin has modulatory functions on immunity and role in the pathophysiology of immune-related diseases, in particular in those associated with excess body weight.

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.

Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies.

(1) Background: Endothelial dysfunction is an early predictor of cardiovascular diseases. Although a large body of evidence shows an inverse association between potassium intake and cardiovascular risk, the studies on endothelial function provided contrasting results. Thus, we carried out a systematic review and a meta-analysis of the available intervention studies of the potassium supplementation on endothelial function. (2) Methods: A systematic search of the online databases available (up to December 2022) was conducted including the intervention trials that reported flow-mediated dilation (FMD) changes-a non-invasive method of assessing endothelial function-after two different potassium intake regimens. For each study, the mean difference (MD) and 95% confidence intervals were pooled using a random effect model. (3) Results: Five studies met the pre-defined inclusion criteria and provided eight cohorts with 332 participants. In the pooled analysis, potassium supplementation was associated with a significant increase in FMD (MD: 0.74%), with a higher effect for a urinary potassium excretion higher than 90 mmol/day. There was a moderate heterogeneity among studies (I2 = 59%), explained by the different amount of potassium supplementation. (4) Conclusions: The results of our meta-analysis indicate that dietary potassium supplement improves endothelial function. This effect is directly associated with the amount of potassium supplement. The findings support the campaigns in favour of an increase in dietary potassium intake to reduce cardiovascular risk.

Hyperuricemia increases the risk of cardiovascular mortality associated with very high HdL-cholesterol level.

BACKGROUND AND AIMS: Whether the association between very high HDL-cholesterol levels and cardiovascular mortality (CVM) is modulated by some facilitating factors is unclear. Aim of the study was to investigate whether the risk of CVM associated with very high HDL-cholesterol is increased in subjects with hyperuricemia. METHODS AND RESULTS: Multivariable Cox analyses were made in 18,072 participants from the multicentre URRAH study stratified by sex and HDL-cholesterol category. During a median follow-up of 11.4 years there were 1307 cases of CVM. In multivariable Cox models a J-shaped association was found in the whole population, with the highest risk being present in the high HDL-cholesterol group [>80 mg/dL, adjusted hazard ratio (HR), 1.28; 95%CI, 1.02-1.61; p = 0.031)]. However, a sex-specific analysis revealed that this association was present only in women (HR, 1.34; 95%CI, 1.02-1.77; p = 0.034) but not in men. The risk of CVM related to high HDL-cholesterol was much greater in the women with high uric acid (>0.30 mmol/L, HR 1.61; 95%CI, 1.08-2.39) than in those with low uric acid (HR, 1.17; 95%CI, 0.80-1.72, p for interaction = 0.016). In women older than 70 years with hyperuricemia the risk related to high HDL-cholesterol was 1.83 (95%CI, 1.19-2.80, p < 0.005). Inclusion of BMI in the models weakened the strength of the associations. CONCLUSION: Our data indicate that very high HDL-cholesterol levels in women are associated with CVM in a J-shaped fashion. The risk of CVM is increased by concomitant hyperuricemia suggesting that a proinflammatory/oxidative state can enhance the detrimental cardiovascular effects associated with high HDL-cholesterol.

Hypertension and mortality in SARS-COV-2 infection: A meta-analysis of observational studies after 2 years of pandemic.

BACKGROUND: The worldwide pandemic SARS-CoV-2 infection is associated with clinical course including a very broad spectrum of clinical manifestations, including death. Several studies and meta-analyses have evaluated the role of hypertension on prognosis, but with important limitations and conflicting results. Therefore, we decided to perform a new meta-analysis of the observational studies that explored the relationship between pre-existing hypertension and mortality risk in patients with SARS-CoV-2 infection, using more stringent inclusion criteria to overcome the limitations inherent previous meta-analyses. METHODS: A systematic search of the on-line databases available up to 31 March 2022 was conducted, including peer-reviewed original articles, involving the adult population, where the role of hypertension on mortality due to SARS-CoV-2 infection was determined by Cox-proportional hazard models. Pooled hazard ratio (HR) was calculated by a random effect model. Sensitivity, heterogeneity, publication bias, subgroup and meta-regression analyses were performed. RESULTS: Twenty-six studies (222,083 participants) met the pre-defined inclusion criteria. In the pooled analysis, pre-existing hypertension was significantly associated with mortality due to SARS-CoV-2 infection, both in unadjusted and adjusted models (HR: 1.55; 95% CI: 1.22 to 1.97). However, in separate analyses including results adjusted for crucial and strong predictors of mortality during SARS-CoV-2 infection (e.g. body weight), the association disappeared. CONCLUSIONS: The results of this meta-analysis indicate that pre-existing hypertension is not an independent predictor of mortality during SARS-CoV-2 infection. Further studies should nevertheless be carried out worldwide to evaluate this role, independent of, or in interaction with, other confounders that may affect the mortality risk.

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.

Dietary Potassium Intake and Risk of Diabetes: A Systematic Review and Meta-Analysis of Prospective Studies.

(1) Background: Dietary potassium intake is positively associated with reduction of cardiovascular risk. Several data are available on the relationship between dietary potassium intake, diabetes risk and glucose metabolism, but with inconsistent results. Therefore, we performed a meta-analysis of the prospective studies that explored the effect of dietary potassium intake on the risk of diabetes to overcome these limitations. (2) Methods: A random-effects dose-response meta-analysis was carried out for prospective studies. A potential non-linear relation was investigated using restricted cubic splines. (3) Results: A total of seven prospective studies met the inclusion criteria. Dose-response analysis detected a non-linear relationship between dietary potassium intake and diabetes risk, with significant inverse association starting from 2900 mg/day by questionnaire and between 2000 and 5000 mg/day by urinary excretion. There was high heterogeneity among studies, but no evidence of publication bias was found. (4) Conclusions: The results of this meta-analysis indicate that habitual dietary potassium consumption is associated with risk of diabetes by a non-linear dose-response relationship. The beneficial threshold found supports the campaigns in favour of an increase in dietary potassium intake to reduce the risk of morbidity and mortality. Further studies should be carried out to explore this topic.

Trends of blood pressure, raised blood pressure, hypertension and its control among Italian adults: CUORE Project cross-sectional health examination surveys 1998/2008/2018.

OBJECTIVES: To assess in the Italian general adult population the trends of blood pressure (BP) and prevalence of raised BP (RBP), hypertension and its control in order to evaluate population health and care, and the achievement of an RBP 25% relative reduction as recommended by the WHO at population level. DESIGN: Results comparison of health examination surveys, cross-sectional observational studies based on health examination of randomly selected age and sex stratified samples including residents aged 35-74 years. Data of the 2018/2019 survey were compared with the previous ones collected in 1998/2002 and 2008/2012. SETTING: Health examination surveys conducted in Italy within the CUORE Project following standardised methodologies. PARTICIPANTS: 2985 men and 2955 women examined in 1998/2002, 2218 men and 2204 women examined in 2008/2012 and 1031 men and 1066 women examined in 2018/2019. PRIMARY AND SECONDARY OUTCOME MEASURES: Age-standardised mean of BP, prevalence of RBP (systolic BP and/or diastolic BP ≥140/90 mm Hg), hypertension (presenting or being treated for RBP) and its awareness and control, according to sex, age class and educational level. RESULTS: In 2018/2019, a significant reduction was observed in systolic BP and diastolic BP in men (1998/2002: 136/86 mm Hg; 2008/2012: 132/84 mm Hg; and 2018/2019: 132/78 mm Hg) and women (132/82 mm Hg, 126/78 mm Hg and 122/73 mm Hg), and in the prevalence of RBP (50%, 40% and 30% in men and 39%, 25% and 16% in women) and of hypertension (54%, 49% and 44% in men and 45%, 35% and 32% in women). Trends were consistent by age and education attainment. In 2018/2019, hypertensive men and women with controlled BP were only 27% and 41%, but a significant favourable trend was observed. CONCLUSIONS: Data from 2018/2019 underlined that RBP is still commonly observed in the Italian population aged 35-74 years, however, the WHO RBP target at that time may be considered met.

Evaluation of the Nutritional Status of Gaucher Disease Type I Patients under Enzyme Replacement Treatment.

(1) Background: Gaucher disease (GD) is a rare lysosomal storage disease. The few studies analyzing Resting Energy Expenditure (REE) in GD involved mainly untreated patients and supported a hypermetabolic condition possibly due to the associated inflammatory state. Definitive conclusions could not be drawn also because of the heterogeneity and the small size of the samples investigated. In order to expand current knowledge concerning, in particular the condition of patients under Enzyme Replacement Therapy (ERT), we evaluated the nutritional status of a relatively large sample of GD patients followed at Federico II University Hospital in Naples, Italy. (2) Methods: The study, having a cross-sectional design and involving 26 patients on ERT, included routine biochemical analyses, bioelectrical impedance analysis, indirect calorimetry, and administration of food frequency and physical activity questionnaires. The results in GD patients were compared with those from an appropriate control group. (3) Results: GD patients had normal biochemical parameters in 80% of cases, except for HDL-cholesterol, consumed a hyper-lipidic diet, and had a 60% prevalence of overweight/obesity. Body composition did not differ between patients and controls; however, measured REE was significantly lower than predicted and was reduced in comparison with the healthy controls. (4) Conclusions: This study provided novel elements to the present knowledge about REE and the nutritional status of GD patients under ERT. Its results warrant confirmation in even larger GD population samples and a more in-depth investigation of the long-term effects of treatment superimposed on the basic pathophysiological disease condition.

Tumor-induced Osteomalacia: A Systematic Review and Individual Patient's Data Analysis.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign, and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is characterized by renal phosphate leak, causing hypophosphatemia and osteomalacia. This review was performed to assess the clinical characteristics of TIO patients described worldwide so far. EVIDENCE ACQUISITION: On June 26, 2021, a systematic search was performed in Medline, Google Scholar, Google book, and Cochrane Library using the terms: "tumor induced osteomalacia," "oncogenic osteomalacia," "hypophosphatemia." There were no language restrictions. This review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria. EVIDENCE RESULTS: Overall, 1725 TIO cases were collected. TIO was more frequent in adult men, who showed a higher incidence of fractures compared with TIO women. The TIO-causing neoplasms were identified in 1493 patients. The somatostatin receptor-based imaging modalities have the highest sensitivity for the identification of TIO-causing neoplasms. TIO-causing neoplasms were equally located in bone and soft tissues; the latter showed a higher prevalence of fractures and deformities. The surgery is the preferred TIO definitive treatment (successful in > 90% of patients). Promising nonsurgical therapies are treatments with burosumab in TIO patients with elevated fibroblast growth factor-23 levels, and with radiolabeled somatostatin analogs in patients with TIO-causing neoplasm identified by somatostatin receptor-based imaging techniques. CONCLUSION: TIO occurs preferentially in adult men. The TIO clinical expressiveness is more severe in men as well as in patients with TIO-causing neoplasms located in soft tissues. Treatments with burosumab and with radiolabeled somatostatin analogs are the most promising nonsurgical therapies.

Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project.

BACKGROUND AND AIM: The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes. METHODS AND RESULTS: The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up. A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04-1.47) and CV mortality (HR:1.31, 95%CI:1.03-1.66), than those with SUA <5.6 mg/dl. Increased all-cause mortality risk was shown in participants with SUA ≥4.7 mg/dl vs SUA below 4.7 mg/dl, but not statistically significant after adjustment for all confounders. CONCLUSIONS: SUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.

Trends of overweight, obesity and anthropometric measurements among the adult population in Italy: The CUORE Project health examination surveys 1998, 2008, and 2018.

BACKGROUND/OBJECTIVES: Obesity is associated with an increased risk of noncommunicable diseases, such as diabetes, coronary heart disease, stroke, cancers, and conditions, including obstructive sleep apnea and osteoarthritis. Obesity is largely preventable, and halting its rise is one of the World Health Organization Global Action Plan for the Prevention of Noncommunicable Diseases targets. This study aimed to assess trends of anthropometric measurements in Italy using the data collected within the CUORE Project health examination surveys (HESs) 1998, 2008, and 2018. SUBJECTS/METHODS: Within the HESs 1998-2002, 2008-2012, and 2018-2019, anthropometric measurements were collected in random samples of the resident population aged 35-74 years, stratified by age and sex, from 10 Italian Regions in Northern, Central, and Southern Italy (2984 men and 2944 women, 2224 men and 2188 women, 1035 men and 1065 women, respectively). Weight, height, and waist and hip circumferences were measured using standardized methodologies. A standardized questionnaire was used to collect data on education. Indicators were age standardized. RESULTS: For both men and women, mean body mass index in 2018 was comparable with those in 1998 and 2008 (in 1998, 2008, and 2018-men: 26.7, 27.5, and 27.0 kg/m2; women: 26.2, 26.6, and 26.3 kg/m2). In 1998, 2008, 2018 prevalence of overweight resulted 49%, 47%, 46% in men and 33%, 32%, 28% in women respectively; prevalence of obesity resulted 17%, 24% 20% in men and 19%, 23%, 23% in women respectively. All indicators of excess weight worsen with increasing age and are more severe in persons with a lower educational level. CONCLUSIONS: Although the overall trend of excess weight over the past two decades appeared to be substantially stable in the Italian adult population, the continuous strengthening of undertaken initiatives should continue since there remains a high proportion of overweight or obesity and a gap between educational levels.

Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study.

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.