Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients.

BACKGROUND: Hypertension management in older patients represents a challenge, particularly when hospitalized. OBJECTIVE: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. METHODS: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. RESULTS: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. CONCLUSIONS: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.

The impact of COVID-19 pandemic on well-being of Italian physicians: a report from the Italian Society of Internal Medicine (SIMI) national survey.

Over the past few years, COVID-19 pandemic has imposed a high toll worldwide, with a high burden of morbidity and mortality. Healthcare practitioners (HCPs) have been in the frontline since the beginning of the outbreak, and the high level of stress have affected their physical and mental status, as well as their relationships. We aimed at exploring the self-reported changes in comprehensive well-being in a cohort of Italian physicians. An online-based survey was administered to the members of the Italian Society of Internal Medicine (SIMI) between March and June 2021. The survey was based on 32 multiple-choice questions exploring self-reported physical and mental well-being, as well as changes in workloads, work-related feelings and physicians' relationship with patients, colleagues and families. 228 physicians (mean age: 35.7 ± 9.8 years) participated in the survey; 120 (52.6%) were residents, 196 (86.0%) worked in COVID-19 units and 65 (28.5%) had COVID-19 during the pandemic. A significant proportion of respondents reported to have experience onset or worsening of physical and mental symptoms, with insomnia/sleep disorders (58.3%) and mood swings (47.8%) being the most common, respectively. The burden of physical and mental consequences was broadly higher among residents compared to specialists, with the former reporting more frequently an increase in the number of worked hours (p = 0.020) and being more frequently infected with COVID-19 (35.0% vs. 21.3, p = 0.032). Moreover, familiar and doctor-patient relationships were also considerably affected. Physicians have been suffering a wide spectrum of physical, mental and relational consequences during COVID-19 pandemic, with youngest doctors being more likely to present several physical and mental health symptoms. Further studies are needed to evaluate long-term consequences of COVID-19 pandemic on the well-being of HCPs, and potential preventive strategies.

Testosterone deficiency independently predicts mortality in women with HFrEF: insights from the T.O.S.CA. registry.

AIMS: Testosterone deficiency (TD) is associated with increased morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). However, data in women are scanty. The aim of this study was to investigate the prognostic impact of TD on women with HFrEF. METHODS: Among 480 patients prospectively enrolled in the T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, a prospective, multicentre, nationwide, observational study, 94 women were included in the current analysis. The TD was defined as serum testosterone levels lower than 25 ng/dl. Data regarding clinical status, echocardiography, exercise performance, cardiovascular hospitalization, and survival after an average follow-up of 36 months were analysed. RESULTS: Thirty patients (31.9%) displayed TD. TD was associated with lower tricuspid annular plane excursion (TAPSE) to pulmonary arterial systolic pressure PASP ratio (TAPSE/PASP) (P = 0.008), peak oxygen consumption (VO2 peak) (P = 0.03) and estimated glomerular filtration rate (P < 0.001). TD was an independent predictor of the combined endpoint of all-cause mortality/cardiovascular hospitalization (HR: 10.45; 95% CI: 3.54-17.01; P = 0.001), all-cause mortality (HR: 8.33; 95%: 5.36-15.11; P = 0.039), and cardiovascular hospitalization (HR: 2.41; 95% CI: 1.13-4.50; P = 0.02). CONCLUSIONS: One-third of women with HFrEF displays TD that impacts remarkably on their morbidity and mortality. TD is associated with a worse clinical profile including exercise capacity, right ventricular-pulmonary arterial coupling, and renal function. These findings lend support to an accurate profiling of women with HF, a problem often overlooked in clinical trials.

Monoclonal Antibodies and Antivirals against SARS-CoV-2 Reduce the Risk of Long COVID: A Retrospective Propensity Score-Matched Case-Control Study.

Long COVID is a complex condition affecting quality of life, with limited therapeutic options. We investigated the occurrence of long COVID in subjects receiving early therapy with monoclonal antibodies (mAbs) or antivirals to reduce the risk of COVID-19 progression. In this retrospective study we enrolled 737 adult patients (aged 65.16 ± 13.46; 361F), who experienced COVID-19 between January 2021 and March 2022. Antiviral or mAbs were administered to symptomatic patients who did not require oxygen therapy or hospital admission for SARS-CoV-2 infection, and who were at high risk of progression to severe disease, as identified by age > 65 years or the presence of comorbidities. Long COVID, defined as newly or persistent long-term symptoms 4 weeks after the onset of the acute illness, was reported in 204 cases (28%). Age (OR 1.03; p < 0.001), gender (OR 1.88; p < 0.001) and at least three comorbidities (OR 3.49; p = 0.049) were directly associated with long COVID; conversely, vaccination (OR 0.59; p = 0.005) and mAbs/antivirals (OR 0.44; p = 0.002) were independently associated with a reduced risk of long COVID. At a propensity-score-matched analysis, the mAbs/antivirals group had a significantly lower occurrence of long COVID in comparison with untreated controls (11% vs. 34%; p = 0.001). In conclusion, mAbs and antivirals administered against the progression of COVID-19 were associated with a reduced risk of long COVID.

One-hour post-load hyperglycemia combined with HbA1c identifies individuals with augmented duodenal levels of sodium/glucose co-transporter 1.

AIMS: Individuals with HbA1c-defined prediabetes (HbA1c 5.7-6.4%) and 1-hour post-load plasma glucose (1hPG) ≥ 155 mg/dl have an increased risk to develop type 2 diabetes (T2DM). T2DM is associated with a higher intestinal expression of sodium/glucose co-transporter 1 (SGLT-1) and glucose transporter 2 (GLUT-2). It is currently unsettled whether HbA1c-defined dysglycemic conditions combined to 1hPG ≥ 155 mg/dl are associated with changes in SGLT-1 and GLUT-2 duodenal abundance. METHODS: SGLT-1 and GLUT-2 protein levels were assessed by western blot on duodenal mucosa biopsies of 57 individuals underwent an upper gastrointestinal endoscopy. RESULTS: Compared with the normal group (HbA1c < 5.7%), individuals with HbA1c-defined pre-diabetes and diabetes exhibit no significant change in duodenal SGLT-1 abundance. Conversely, duodenal GLUT-2 levels were progressively increased in subjects with prediabetes and diabetes. Stratifying participants according to HbA1c and 1hPG we found that amongst subjects with HbA1c-defined normal or prediabetes condition those having 1hPG ≥ 155 mg/dl displayed higher duodenal levels of SGLT-1 as compared to their counterparts with 1hPG < 155 mg/dl; in contrast to GLUT-2 levels, which were similar between normal and with prediabetes subjects, regardless of 1hPG value. CONCLUSION: A value of 1hPG ≥ 155 mg/dl may identify a subset of individuals within HbA1c-defined glycemic categories having a higher duodenal abundance of SGLT-1.

Multiple hormonal and metabolic deficiency syndrome predicts outcome in heart failure: the T.O.S.CA. Registry.

AIMS: Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. METHODS AND RESULTS: The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P < 0.001). Median follow-up was of 36 months. MHDS was independently associated with the occurrence of the primary endpoint [hazard ratio 95% (confidence interval), 1.93 (1.37-2.73), P < 0.001] and identified a group of patients with a higher mortality [2.2 (1.28-3.83), P = 0.01], with a graded relation between HDs and cumulative events (P < 0.01). CONCLUSION: MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT023358017.

Levels and Factors Associated with Resilience in Italian Healthcare Professionals during the COVID-19 Pandemic: A Web-Based Survey.

BACKGROUND: Resilience is defined as the capacity to cope successfully with change or adversity. The aims of our study were to investigate levels of resilience in Italian healthcare professionals (HCPs) during the Coronavirus disease 2019 (COVID-19) pandemic and to identify potential predictors of resilience. METHODS: We performed a web-based survey of HCPs (n = 1009) working in Italian hospitals during the COVID-19 pandemic. The survey contained a 14-item resilience scale (RS14) and questionnaires to evaluate depression and anxiety symptoms. Non-HCP individuals (n = 375) from the general population were used for comparison. RESULTS: HCPs showed significantly lower resilience compared to the control group (p = 0.001). No significant differences were observed after stratification for geographical area, work setting, role, or suspected/confirmed diagnosis of COVID-19. In a linear regression analysis, RS14 was inversely correlated with depression (R2 = 0.227, p < 0.001) and anxiety (R2 = 0.117, p < 0.001) and directly correlated with age (R2 = 0.012, p < 0.001) but not with body mass index (BMI, R2 = 0.002, p = 0.213). In male HCPs, higher depression score (odds ratio (OR) 1.147, p < 0.001) or BMI (OR 1.136, p = 0.011) significantly predicted having low resilience. In female HCPs, higher depression score (OR 1.111, p < 0.0001) and working in a COVID-19 free setting (OR 2.308, p = 0.002) significantly predicted having low resilience. HCPs satisfied with personal protective equipment had higher levels of resilience (p < 0.010). CONCLUSIONS: Our findings suggest that resilience was lower in Italian HCPs than in the general population after the first COVID-19 wave. Specific factors can be identified, and targeted interventions may have an important role to foster resilience of HCPs.

Metabolic and Cognitive Effects of Ranolazine in Type 2 Diabetes Mellitus: Data from an in vivo Model.

: Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive impairment. Ranolazine, an anti-ischemic drug used in the treatment of angina pectoris, has been shown to possess hypoglycemic properties in pre-clinical and clinical studies. The aim of this study was to evaluate the effects of ranolazine on glucose metabolism and cognitive function in a T2DM model of Wistar rats. Diabetes was induced by a high fat diet (HFD) and streptozotocin (STZ). The control group received a normal caloric diet (NCD) and sodium citrate buffer. Metformin, an effective hypoglycemic drug, was employed as a positive control. Animals were divided into the following groups: HFD/STZ + Ranolazine, HFD/STZ + Metformin, HFD/STZ + Vehicle, NCD + Vehicle, NCD + Ranolazine, and NCD + Metformin. Rats received ranolazine (20 mg/kg), metformin (300 mg/kg), or water, for 8 weeks. At the end of the treatments, all animals underwent to an intraperitoneal glucose tolerance test (IPGTT) and behavioral tests, including passive avoidance, novel object recognition, forced swimming, and elevate plus maze tests. Interleukin-6 plasma levels in the six treatment groups were assessed by Elisa assay. Body mass composition was estimated by nuclear magnetic resonance (NMR). Glucose responsiveness significantly improved in the HFD/STZ + Ranolazine (p < 0.0001) and HFD/STZ + Metformin (p = 0.003) groups. There was a moderate effect on blood glucose levels in the NCD + Ranolazine and NCD + Metformin groups. Lean body mass was significantly increased in the HFD/STZ + Ranolazine and HFD/STZ + Metformin animals, compared to HFD/STZ + Vehicle animals. Ranolazine improved learning and long-term memory in HFD/STZ + Ranolazine compared to HFD/STZ + Vehicle (p < 0.001) and ameliorated the pro-inflammatory profile of diabetic mice. These results support the hypothesis of a protective effect of ranolazine against cognitive decline caused by T2DM.

Different Patterns of Left Ventricular Hypertrophy in Metabolically Healthy and Insulin-Resistant Obese Subjects.

Obese subjects showed different cardiovascular risk depending by different insulin sensitivity status. We investigated the difference in left ventricular mass and geometry between metabolically healthy (MHO) and unhealthy (MUHO) obese subjects. From a cohort of 876 obese subjects (48.3 ± 14.1 years) without cardio-metabolic disease and stratified according to increasing values of Matsuda index after 75 g oral glucose tolerance test, we defined MHO (n = 292) those in the upper tertile and MUHO (n = 292) those in the lower tertile. All participants underwent echocardiographic measurements. Left ventricular mass was calculated by Devereux equation and normalized by height2,7 and left ventricular hypertrophy (LVH) was defined by values >44 g/m2.7 for females and >48 g/m2.7 for males. Left ventricular geometric pattern was defined as concentric or eccentric if relative wall thickness was higher or lower than 0.42, respectively. MHO developed more commonly a concentric remodeling (19.9 vs. 9.9%; p = 0.001) and had a reduced risk for LVH (OR 0.46; p < 0.0001) than MUHO, in which the eccentric type was more prevalent (40.4 vs. 5.1%; p < 0.0001). We demonstrated that obese subjects-matched for age, gender and BMI-have different left ventricular mass and geometry due to different insulin sensitivity status, suggesting that diverse metabolic phenotypes lead to alternative myocardial adaptation.

Glecaprevir/Pibrentasvir Induced Cholestatic Jaundice in a HCV Patient with Renal Failure. A Case Presentation.

BACKGROUND: Direct-acting Antivirals (DAA) are currently used in the treatment of chronic HCV infection. In patients with renal failure Glecaprevir/Pibrentasvir (genotype 1-6) is recommended for its safety and efficacy. CASE PRESENTATION: Although these pharmacological characteristics, an adverse drug reaction (ADR) has been reported during Glecaprevir/Pibrentasvir treatment, such as the development of cholestatic jaundice in an elderly patient with chronic HCV (genotype 2) infection. At examination, patient was jaundiced associated with intense pruritus. RESULTS: Ultrasound and laboratory biochemical tests excluded a liver failure (e.g. liver cancer, and liver lithiasis) or pancreatic cancer while Naranjo probability scale (score 6) suggested an association between cholestatic jaundice and Glecaprevir/Pibrentasvir administration. About 1 month after drug discontinuation, an improvement has been documented in both jaundice and pruritus, with a normalization in bilirubin levels (total bilirubin: 0.96 mg/dL), HCV-RNA was undetected also. It is worth mentioning that although we reported the development of cholestatic jaundice upon treatment with Glecaprevir/Pibrentasvir we recorded a clinical efficacy (HCV-RNA <15 IU/L) after 4 weeks from the beginning of the treatment, with a complete remission of clinical symptoms until 7 months after drug discontinuation. CONCLUSION: These data support the clinical efficacy of Glecaprevir/Pibrentasvir association in elderly patients, despite the sub-optimal period of treatment.

Uric Acid Impairs Insulin Signaling by Promoting Enpp1 Binding to Insulin Receptor in Human Umbilical Vein Endothelial Cells.

High levels of uric acid (UA) are associated with type-2 diabetes and cardiovascular disease. Recent pieces of evidence attributed to UA a causative role in the appearance of diabetes and vascular damage. However, the molecular mechanisms by which UA induces these alterations have not been completely elucidated so far. Among the mechanisms underlying insulin resistance, it was reported the role of a transmembrane glycoprotein, named either ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) or plasma cell antigen 1, which is able to inhibit the function of insulin receptor (IR) and it is overexpressed in insulin-resistant subjects. In keeping with this, we stimulated human umbilical vein endothelial cells (HUVECs) with insulin and UA to investigate the effects of UA on insulin signaling pathway, testing the hypothesis that UA can interfere with insulin signaling by the activation of ENPP1. Cultures of HUVECs were stimulated with insulin, UA and the urate transporter SLC22A12 (URAT1) inhibitor probenecid. Akt and endothelial nitric oxide synthase (eNOS) phosphorylation levels were investigated by immunoblotting. ENPP1 binding to IR and its tyrosine phosphorylation levels were tested by immunoprecipitation and immunoblotting. UA inhibited insulin-induced Akt/eNOS axis. Moreover, UA induced ENPP1 binding to IR that resulted in an impairment of insulin signaling cascade. Probenecid reverted UA effects, suggesting that UA intracellular uptake is required for its action. In endothelial cells, UA directly interferes with insulin signaling pathway at receptor level, through ENPP1 recruitment. This evidence suggests a new molecular model of UA-induced insulin resistance and vascular damage.

Duodenal Sodium/Glucose Cotransporter 1 Expression Under Fasting Conditions Is Associated With Postload Hyperglycemia.

Context: Type 2 diabetes (T2DM) is associated with a higher intestinal expression of the glucose transporters sodium/glucose cotransporter 1 (SGLT-1) and glucose transporter 2 (GLUT-2). It is currently unsettled whether prediabetes conditions characterized by postprandial hyperglycemia, such as impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) with 1-hour postload glucose ≥155 mg/dL (8.6 mmol/L) (NGT-1h-high) are associated with increased expression of these glucose carriers in the intestine. Objective: We evaluated whether duodenal abundance of SGLT-1 and GLUT-2 is augmented in subjects with IGT and NGT-1h-high, in comparison with subjects with NGT and 1-hour postload glucose ˂155 mg/dL (NGT-1h-low). Design: Cross-sectional. Patients: A total of 54 individuals underwent an upper gastrointestinal endoscopy. Main Outcome Measures: Duodenal SGLT-1 and GLUT-2 protein and messenger RNA levels were assessed by Western blot and reverse transcription polymerase chain reaction, respectively. Results: Of the 54 subjects examined, 18 had NGT-1h-low, 12 had NGT-1h-high, 12 had IGT, and 12 had T2DM. Duodenal SGLT-1 protein and messenger RNA levels were significantly higher in individuals with NGT-1h-high, IGT, or T2DM in comparison with NGT-1h-low subjects. GLUT-2 abundance was higher in individuals with T2DM in comparison with NGT-1h-low subjects; no substantial increase in GLUT-2 expression was observed in NGT-1h-high or IGT individuals. Univariate correlations showed that duodenal SGLT-1 abundance was positively correlated with 1-hour postload plasma glucose levels (r = 0.44; P = 0.003) but not with fasting or 2-hour postload glucose levels. Conclusions: Duodenal SGLT-1 expression is increased in individuals with 1-hour postload hyperglycemia or IGT, as well as in subjects with T2DM, and it positively correlates with early postload glucose excursion.

Risk reclassification ability of uric acid for cardiovascular outcomes in essential hypertension.

BACKGROUND: Hyperuricemia is associated with incident cardiovascular events in different settings of patients. We tested whether the inclusion of uric acid (UA) in Cox models including standard risk factors allows to better stratify cardiovascular risk in a cohort of 1522 naïve hypertensives with preserved renal function. METHODS: We used multiple Cox regression models to assess the independent effect of UA on cardiovascular outcomes, and Harrell'C index, Net Reclassification Index (NRI), and Integrated Discrimination Improvement (IDI) as indicators of the additional prognostic value of UA beyond and above that provided by standard risk factors and estimated glomerular filtration rate (e-GFR). Study outcomes were fatal and nonfatal cardiovascular events and fatal and nonfatal coronary outcomes/death due to other cardiovascular events. RESULTS: UA resulted strongly related to both outcomes in unadjusted Cox regression analyses (P<0.001). Inclusion of UA into multiple Cox regression models including Framingham risk factors and e-GFR did not affect the association between UA and outcomes (fatal and nonfatal cardiovascular events, HR=1.44, 95% CI=1.36-1.55, P<0.001; fatal and nonfatal coronary outcomes/death due to other cardiovascular events, HR=1.48, 95% CI=1.36-1.61, P<0.001). Inclusion of UA into basic Cox models provided an increase in all indexes of prognostic accuracy for both outcomes: Harrell'C index: +5%; NRI: +24.9%; IDI: +7.6%, all P<0.001; and Harrell'C index: +5%; NRI: +25%; IDI: +6.3%, all P<0.001, respectively. CONCLUSIONS: UA is an independent predictor of cardiovascular outcomes and increases prognostic accuracy of Cox models, including Framingham risk factors and e-GFR, in hypertensives with normal renal function, allowing a risk reclassification.

Additive Effect of Non-Alcoholic Fatty Liver Disease on Metabolic Syndrome-Related Endothelial Dysfunction in Hypertensive Patients.

Metabolic syndrome (MS) is characterized by an increased risk of incident diabetes and cardiovascular (CV) events, identifying insulin resistance (IR) and endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver disease (NAFLD) is bidirectionally linked with MS as a consequence of metabolic and inflammatory abnormalities. We addressed the question if the evolution in NAFLD might worsen endothelium-dependent vasodilating response in MS hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated hypertensive outpatients divided into three groups according to the presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and non-invasive fatty liver index, respectively. We determined IR by using the homeostasis model assessment (HOMA) index. Vascular function, as forearm blood flow (FBF), was determined through strain-gauge plethysmography after intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular profiles compared with MS-NAFLD- and MS+NAFLD-. HOMA resulted in being the strongest predictor of FBF both in the MS+NAFLD- and in the MS+NAFLD+ groups, accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent vasodilation compared with MS+NAFLD-, allowing for consideration of NAFLD as an early marker of endothelial dysfunction in hypertensives.

Renal function is impaired in normotensive chronic HCV patients: role of insulin resistance.

Renal dysfunction is an independent predictor for cardiovascular morbidity and mortality. We investigated whether chronic hepatitis C virus (HCV) infection and the related insulin resistance/hyperinsulinemia influence renal function in comparison with a group of healthy subjects and with another group with metabolic syndrome. We enrolled 130 newly diagnosed HCV outpatients matched for age and gender with 130 patients with metabolic syndrome and 130 healthy subjects. Renal function was evaluated by calculation of glomerular filtration rate (e-GFR, mL/min/1.73 m(2)) using the CKD-EPI equation. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, and HOMA to evaluate insulin sensitivity. HCV patients with respect to both healthy subjects and metabolic syndrome patients have a decreased e-GFR: 86.6 ± 16.1 vs 120.2 ± 23.1 mL/min/1.73 m(2) (P < 0.0001) and 94.9 ± 22.6 mL/min/1.73 m(2) (P = 0.003), respectively. Regarding biochemical variables, HCV patients, in comparison with healthy subjects, have a higher triglyceride level, creatinine, fasting insulin and HOMA (3.4 ± 1.4 vs 2.6 ± 1.3; P < 0.0001). At linear regression analysis, the correlation between e-GFR and HOMA is similar in the metabolic syndrome (r = -0.555, P < 0.0001) and HCV (r = -0.527, P < 0.0001) groups. At multiple regression analysis, HOMA is the major determinant of e-GFR in both groups, accounting for, respectively, 30.8 and 27.8 % of its variation in the metabolic syndrome and HCV. In conclusion, we demonstrate that HCV patients have a significant reduction of e-GFR and that insulin resistance is the major predictor of renal dysfunction.

Uric acid is an independent predictor of cardiovascular events in post-menopausal women.

BACKGROUND: Uric acid (UA) is a risk factor for cardiovascular (CV) disease. In post-menopause UA levels are increased and strongly associated with subclinical organ damage. We investigated the prognostic significance of UA levels in predicting CV morbidity and mortality in post-menopausal women. METHODS: We considered 645 post-menopausal outpatients not taking hormone replacement therapy or any drugs interfering with UA levels. We evaluated major adverse cardiovascular events (MACE) as primary endpoint, with coronary, stroke or total events as secondary endpoint. Survival curves for tertiles of UA were obtained by using the Kaplan-Meier and Mantel methods. Effect of prognostic factors on survival was evaluated by multivariable Cox regression model, considering P<0.05 as statistically significant. RESULTS: During a mean (SD) follow-up at 72.5 (23.5) months, there were 90 new CV events (2.31%): 62 coronary and 28 cerebrovascular events. The rate of nonfatal CV events (3.15% versus 2.03% and 1.52%, P=0.009) as well as that of MACE (3.23% versus 2.11% and 1.59%, P=0.011) were significantly higher in the third tertile than in the other two groups. Interestingly, cerebrovascular (1.15% versus 0.62% and 0.30%, P=0.027) but not coronary events were significantly different among the three groups. In the Cox regression model, UA was independently and strongly associated with the incident risk of MACE (HR=1.248, P=0.001), cerebrovascular (HR=1.657, P<0.0001) and total events (HR=1.391, P<0.0001). CONCLUSIONS: In post-menopause, independently of other CV risk factors and menopause duration, UA levels are associated with increased risk of death and MACE, in particular cerebrovascular but not coronary events.

CHADS2 and CHA2DS2-VASc scores are independently associated with incident atrial fibrillation: the Catanzaro Atrial Fibrillation Project.

No data exist concerning a possible association between CHADS2 or CHA2DS2-VASc scores and atrial fibrillation (AF). In this prospective observational study, we tested the hypothesis whether thromboembolic risk scores predict AF. We investigated 3549 subjects, 1829 men and 1720 women, aged 60.7 ± 10.6 years, without baseline AF. Patients with thyroid disorders were excluded. CHADS2 and CHA2DS2-VASc scores were evaluated as categorical variables. To test the effect of some clinical confounders on incident AF, we constructed different models including clinical and laboratory parameters. During follow-up (53.3 ± 18.1 months), 546 subjects developed AF (4.5 events/100 patient-years). Progressors to AF are older, have a higher body mass index (BMI), blood pressure, LDL-cholesterol, and glucose. Hypertension, metabolic syndrome, diabetes and carotid wall thickening were more common among AF cases than among control subjects. In the final Cox-regression model, variables that remained significantly associated with incident AF were BMI (HR = 1.022, 95% CI = 1.008-1.037), LDL-cholesterol (HR = 1.032, 95% CI = 1.008-1.056), CHA2DS2-VASc score (HR = 1.914, 95% CI = 1.439-2.546), and CHADS2 score (HR = 2.077, 95% CI = 1.712-2.521). In conclusion, CHADS2 and CHA2DS2-VASc scores are independent predictors of AF.