Two still unanswered questions about uric acid and cardiovascular prevention: Is a specific uric acid cut-off needed? Is hypouricemic treatment able to reduce cardiovascular risk?

Aims: The most frequent consequence of elevated uric acid (UA) levels is the development of gout and urate kidney disease. Besides these effects, several studies have investigated the association between hyperuricemia and cardiovascular (CV) disease. High serum UA has been identified as an important determinant of all-cause and CV mortality and CV events (acute and chronic coronary syndrome, stroke and peripheral artery disease). Despite the high number of publications on this topic, there are two questions that are still unanswered: do we need a specific CV cut-off of serum UA to better refine the CV risk? Is urate lowering treatment (ULT) able to reduce CV risk in asymptomatic patients? In this review, we will focus on these two points. Data synthesis: Although no doubt exists that the relationship between CV events starts at lower levels than the actually used cut-off, different papers found dissimilar cut-offs. Furthermore, heterogeneity is present depending on the specific CV events evaluated and none of the found cut-off have been tested in external populations (in order to confirm its discriminatory capacity). Furthermore, only few randomized clinical trials on the role of hypouricemic agents in reducing the CV risk have been published giving heterogeneous results. The last published one (ALL-HEART) has strong limitations, that we will deeply discuss. Conclusions: A definitive answer to the two questions is impossible with the actually published paper but, over identifying current gaps in knowledge we try to individuate how they can be overruled

Association of Hypertriglyceridemia with All-Cause Mortality and Atherosclerotic Cardiovascular Events in a Low-Risk Italian Population: The TG-REAL Retrospective Cohort Analysis

Background Evidence regarding the relationships among high plasma triglycerides (TG), all-cause mortality, and atherosclerotic cardiovascular disease (ASCVD) events in low-to-moderate risk individuals is limited. The aim of this study was to determine whether the presence of high TG levels influences the risk of all-cause mortality and ASCVD events in a population cohort followed in the real-world clinical setting. Methods and Results A retrospective longitudinal cohort analysis using administrative databases of 3 Italian Local Health Units was performed. All individuals with at least one TG measurement between January 1, 2010 and December 31, 2015 were followed through December 2016. Outcome measures included incident ASCVD events and all-cause mortality. Individuals with normal TG levels (<150 mg/dL) were compared with those with high (150-500 mg/dL) and very high TG (>500 mg/dL). 158 042 individuals (142 289 with normal, 15 558 with high, and 195 with very high TG) were considered. In the whole cohort, the overall incidence rates of ASCVD and all-cause mortality were 7.2 and 17.1 per 1000 person-years, respectively. After multivariate adjustment for potential confounders, individuals with high and very high TG showed a significantly increased risk of all-cause mortality (hazard ratio [HR]=1.49 [95% confidence interval (CI) 1.36-1.63], P<0.001, and HR=3.08 [95% CI 1.46-6.50], P<0.01, respectively) and incident ASCVD events (HR=1.61 [95% CI 1.43-1.82], P<0.001, and HR=2.30 [95% CI 1.02-5.18], P<0.05, respectively) as compared to those with normal TG. Conclusions Moderate-to-severe elevation of TG is associated with a significantly increased risk of all-cause mortality and ASCVD events in a large cohort of low-to-moderate cardiovascular risk individuals in a real-world clinical setting

Prognostic impact of in-hospital hyperglycemia in hospitalized patients with acute heart failure: Results of the IN-HF (Italian Network on Heart Failure) Outcome registry

Objectives: Although diabetes mellitus is frequently associated with heart failure (HF), the association between elevated admission glucose levels and adverse outcomes has not been well established in hospitalized patients with acute HF. Methods: We prospectively evaluated in-hospital mortality, post-discharge 1-year mortality and 1-year re-hospitalization rates in the Italian Network on Heart Failure (IN-HF) Outcome registry cohort of 1776 patients hospitalized with acute HF and stratified by their admission glucose levels (i.e., known diabetes, newly diagnosed hyperglycemia, no diabetes). Results: Compared with those without diabetes (n = 586), patients with either known diabetes (n = 749) (unadjusted-odds ratio [OR] 1.64, 95%CI 0.99\u20132.70) or newly diagnosed hyperglycemia (n = 441) (unadjusted-OR 2.34, 95%CI 1.39\u20133.94) had higher in-hospital mortality, but comparable post-discharge 1-year mortality rates. After adjustment for age, sex, systolic blood pressure, estimated glomerular filtration rate, left ventricular ejection fraction, HF etiology and HF worsening/de novo presentation, the results remained unchanged in patients with known diabetes (adjusted-OR 1.86, 95%CI 1.01\u20133.42), while achieved borderline significance in those with newly diagnosed hyperglycemia (adjusted-OR 1.81, 95%CI 0.95\u20133.45). One-year re-hospitalization rates were lower in patients with newly diagnosed hyperglycemia (adjusted-hazard ratio 0.74, 95%CI 0.56\u20130.96) than in other groups. Conclusions: Elevated admission blood glucose levels are associated with poorer in-hospital survival outcomes in patients with acute HF, especially in those with previously known diabetes. This finding further highlights the importance of tight glycemic control during hospital stay and address the need of dedicated intervention studies to identify customized clinical protocols to improve in-hospital survival of these high-risk patients

Three-dimension structure of ventricular myocardial fibers after myocardial infarction

<p>Abstract</p> <p>Background</p> <p>To explore the pathological changes of three-dimension structure of ventricular myocardial fibers after anterior myocardial infarction in dog heart.</p> <p>Methods</p> <p>Fourteen acute anterior myocardial infarction models were made from healthy dogs (mean weight 17.6 ± 2.5 kg). Six out of 14 dogs with old myocardial infarction were sacrificed, and their hearts were harvested after they survived the acute anterior myocardial infarction for 3 months. Each heart was dissected into ventricular myocardial band (VMB), morphological characters in infarction region were observed, and infarct size percents in descending segment and ascending segment were calculated.</p> <p>Results</p> <p>Six dog hearts were successfully dissected into VMB. Uncorresponding damages in myocardial fibers of descending segment and ascending segment were found in apical circle in anterior wall infarction. Infarct size percent in the ascending segment was significantly larger than that in the descending segment (23.36 ± 3.15 (SD) vs 30.69 ± 2.40%, P = 0.0033); the long axis of infarction area was perpendicular to the orientation of myocardial fibers in ascending segment; however, the long axis of the infarction area was parallel with the orientation of myocardial fibers in descending segment.</p> <p>Conclusions</p> <p>We found that damages were different in both morphology and size in ascending segment and descending segment in heart with myocardial infarction. This may provide an important insight for us to understand the mechanism of heart failure following coronary artery diseases.</p

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 car&#x2;diovascular 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 14189 subjects aged 18 to 95years 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 (150mg/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 an&#x2;tihypertensive and lipid-lowering drugs. During 139375 person-years of follow-up, 1601 participants experienced cardiovas&#x2;cular events. Receiver operating characteristic curve showed that 89mg/dL (95% CI, 75.8–103.3, sensitivity 76.6, specificity 34.1, P&lt;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 (89mg/dL) than conventional (150mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohor

Hypertriglyceridemia is associated with decline of estimated glomerular filtration rate and risk of end-stage kidney disease in a real-word Italian cohort: Evidence from the TG-RENAL Study

Background: This analysis investigated the role of hypertriglyceridemia on renal function decline and development of end-stage kidney disease (ESKD) in a real-world clinical setting. Methods: A retrospective analysis using administrative databases of 3 Italian Local Health Units was performed searching patients with at least one plasma triglyceride (TG) measurement between 2013 and June 2020, followed-up until June 2021. Outcome measures included reduction in estimated glomerular filtration rate (eGFR) ≥30% from baseline and ESKD onset. Subjects with normal (normal-TG), high (HTG) and very high TG levels (vHTG) (respectively &lt;150 mg/dL, 150-500 mg/dL and &gt;500 mg/dL) were comparatively evaluated. Results: Overall 45,000 subjects (39,935 normal-TGs, 5,029 HTG and 36 vHTG) with baseline eGFR of 96.0 ± 66.4 mL/min were considered. The incidence of eGFR reduction was 27.1 and 31.1 and 35.1 per 1000 person-years, in normal-TG, HTG and vHTG subjects, respectively (P&lt;0.01). The incidence of ESKD was 0.7 and 0.9 per 1000 person-years, in normal-TG and HTG/vHTG subjects, respectively (P&lt;0.01). Univariate and multivariate analyses revealed that HTG subjects had a risk of eGFR reduction or ESKD occurrence (composite endpoint) increased by 48% compared to normal-TG subjects (adjusted OR:1.485, 95%CI 1.300-1.696; P&lt;0.001). Moreover, each 50 mg/dL increase in TG levels resulted in significantly greater risk of eGFR reduction (OR:1.062, 95%CI 1.039-1.086 P&lt;0.001) and ESKD (OR:1.174, 95%CI 1.070-1.289, P = 0.001). Conclusions: This real-word analysis in a large cohort of individuals with low-to-moderate cardiovascular risk suggests that moderate-to-severe elevation of plasma TG levels is associated with a significantly increased risk of long-term kidney function deterioration

Clinical characteristics and course of patients entering cardiac rehabilitation withchronic kidney disease: data from the Italian Survey on Cardiac Rehabilitation(ISYDE)

Purpose: Data from the Italian SurveY on carDiac rEhabilitation (ISYDE-2008) provide insight into the characteristics and clinical course of patients with chronic kidney disease (CKD) admitted to Cardiac Rehabilitation (CR) programs. Methods: Data from 165 CR units were collected online from January 28th to February 10th, 2008. Results: The study cohort consisted of 2281 patients (66.911.8 yrs); 200 (71.312.2 yrs, 66% male) CKD patients and 2081 (66.311.6 yrs, 74% male) non-CKD patients. Compared to non-CKD, CKD patients were older and their admission diagnosis of acute myocardial infarction, myocardial revascularization or heart failure was more frequent. They also showed more cardiac and non cardiac comorbidities, mostly diabetes, chronic obstructive lung disease and cognitive impairment. During the course of CR, CKD patients had reduced access to exercise functional evaluation, more complications (particularly atrial fibrillation, worsening of chronic kidney disease and anaemia) requiring more intense medical treatment, and longer length of in-hospital stay. CKD patients were less likely discharged at home (88% versus 91%, p¼0.05), were more likely transferred to the intensive care units (8% versus 4%, p¼0.005), and had higher death rate during CR programs (2.0% versus 0.5%, p¼0.02). After adjusting for age, ejection fraction, comorbidities (acute myocardial infarction, percutaneous coronary intervention, cardiac surgery, carotid artery critical lesions, peripheral artery disease, respiratory insufficiency, heart failure, diabetes, stroke and cognitive impairment), and complications during CR program (atrial fibrillation and severe ventricular arrhythmias), multivariate logistic analysis showed that heart failure (OR 1.6, 95% CI, 1.1 to 2.4, p¼0.04), respiratory insufficiency (OR 2.4, 95% CI, 1.4 to 4.0, p¼0.0007), and cognitive impairment (OR 4.5, 95% CI, 2.5 to 8.1, p < 0.0001) were significant predictors of death during the CR program in CKD patients. Conclusions: This subanalysis of the ISYDE-2008 survey provided a detailed snapshot of the clinical characteristics, complexity and more severe clinical course of patients admitted to CR presenting with CK