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Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are key drugs in the management of patients with cardiovascular diseases (CVD), particularly those with hypertension, diabetes, chronic kidney disease and heart failure (HF), given their demonstrated effectiveness in reducing the risk of both surrogate and hard endpoints. Despite their positive impact on the outcome, patients with RAASi and MRAs are particularly vulnerable to hyperkalaemia, with approximately 50 % of these individuals experiencing two or more recurrences annually. The common practice of reducing the dose or discontinuing the treatment with RAASi and MRAs in conditions of hyperkalaemia results in suboptimal management of these patients, with a potential impact on their mortality and morbidity risk. Recent guidelines from cardiovascular and renal international societies increasingly recognize the need for alternative strategies to manage the risk of hyperkalaemia, allowing the continuation of RAASi and MRA therapies. In this review, we summarise the new potential options available to manage hyperkalaemia in patients with CVD and the recommendations of the most recent guidelines on the topic., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hypertension remains a major problem worldwide, especially across the Asia-Pacific region, which reports high prevalence rates and slow improvements in treatment rate and blood pressure (BP) control rate. Asian patients with hypertension may also vary with regard to phenotype and the epidemiology of the complications of hypertension, especially when compared with Western patients. Given these differences, Western guidelines may not necessarily be applicable to countries in the Asia Pacific. This narrative review aims to provide a critical comparison between the recently published European Society of Hypertension (ESH) 2023 guidelines and existing local guidelines in select Asian countries, offer expert opinion on how to fill gaps in the ESH 2023 guidelines for hypertension in the Asian context, and examine the need for harmonisation of hypertension guidelines worldwide. This review focuses on the definition and diagnosis of hypertension, the treatment thresholds and targets, and recommendations on the use of pharmacotherapy., (Copyright © 2024. Published by Elsevier B.V.)

A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study., Aim: of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death., Methods: Subjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis. LV hypertrophy (LVH) was defined as LVMI > 95 g/m2 in women and 115 g/m2 in men., Results: A significant association between SUA and LVMI was observed in multiple regression analysis in men: beta 0,095, F 5.47, P< 0.001 and women: beta 0,069, F 4.36, P<0.001. During follow-up 319 CV deaths occurred. Kaplan-Meier curves showed a significantly poorer survival rate in subjects with higher SUA (> 5.6 mg/dl in men and 5.1 mg/dl in women) and LVH (log-rank chi-square 298.105; P<0.0001). At multivariate Cox regression analysis in women LVH alone and the combination of higher SUA and LVH but not hyperuricemia alone, were associated with a higher risk of CV death, while in men hyperuricemia without LVH, LVH without hyperuricemia and their combination were all associated with a higher incidence of CV death., Conclusions: Our findings demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Competing Interest This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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 <150 mg/dL, 150-500 mg/dL and >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<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<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<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<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., Competing Interests: Declaration of Competing Interest R. Pontremoli has served as a consultant for and has received lecturing fees from Novartis, MSD, AstraZeneca, Boehringer-Ingelheim, Lilly, Novonordisk and Alfasigma. G. Desideri has received research grant support from AstraZeneca and Menarini; has served as a consultant for Servier, Menarini, FIRMA, and Alfasigma; and received lecturing fees from Servier, Bayer, Guidotti, Bristol Myers Squibb, DOC, and Alfasigma M. Arca has received research grant support from Aegerion, Amgen, IONIS, Akcea Therapeutics, Pfizer, Regeneron, and Sanofi; has served as a consultant for Amgen, Aegerion, Akcea Therapeutics, Regeneron, Sanofi, and Alfasigma; and received lecturing fees from Amgen, Aegerion, Merck, Pfizer, Sanofi, and Alfasigma. P.L. Temporelli has received lecturing and consulting fees from Alfasigma; consulting fees from Bayer; lecturing fees from Menarini, MSD, and Servier. C. Borghi has received research grant support from Menarini Corporate and Novartis Pharma; has served as a consultant for Novartis Pharma, Alfasigma, Grunenthal, Menarini Corporate, and Laboratoires Servier; and received lecturing fees from Laboratoires Servier, Takeda, Astellas, Teijin, Novartis Pharma, Berlin Chemie, and Sanofi. The agreement signed by CliCon s.r.l. and Alfasigma does not create any entity, joint venture or any other similar relationship between the parties. CliCon s.r.l. is an independent company. Neither CliCon s.r.l. nor any of their representatives are employees of Alfasigma for any purpose. The remaining authors have no disclosures to report., (Copyright © 2023. Published by Elsevier B.V.)

Angiotensin converting enzyme inhibitors (ACEi) have consistently demonstrated improved survival and reduced risk of major cardiovascular events, across the spectrum of cardiovascular disease, including hypertension, coronary artery disease, myocardial infarction, and heart failure. The cardioprotective effects of ACEi result from inhibiting the conversion of angiotensin I to angiotensin II, and inhibition of bradykinin degradation. They are generally well tolerated but may cause the onset of a dry cough in some patients. This review presents current evidence on the incidence and mechanisms of cough associated with ACEi use, and then considers how to manage ACEi-related cough in clinical practice. The incidence of ACEi-induced cough in the published literature varies widely due to heterogeneity in the source data and lack of adequate controls. Incidence also varies among individual ACEi with agents such as perindopril, which has a high tissue ACE affinity, associated with a lower rate of cough. Evidence from real-world studies shows that the incidence of ACEi-associated cough is lower than rates reported in clinical trials. Patients who experience any dry cough are often switched to angiotensin- receptor blockers or other classes of antihypertensive drugs, regardless of cough severity. To avoid inappropriate discontinuation of ACEi in clinical practice, an alternative approach in patients with persistent cough is to perform a challenge/re-challenge to determine if re-introduction of ACEi is associated with recurrence of symptoms. Incidence of cough should not be considered a class effect for ACEi, and the patient may benefit by a switch from one ACEi to another. Every effort should be made to enable patients to continue ACEi therapy to reduce adverse cardiovascular outcomes and improve survival., (Copyright © 2023. Published by Elsevier B.V.)

Background/aims: H. pylori treatment remains a challenge for clinicians, and a definite quote of patients require two or more treatments. We evaluated the efficacy of rifabutin-based therapy and Pylera® regimen as rescue therapies., Methods: Between January 2016 and December 2019, dyspeptic patients with at least one therapeutic failure observed in clinical practice received either a 12-day rifabutin-based triple therapy (esomeprazole 40 mg and amoxicillin 1 g, both twice daily, and rifabutin 150 mg once daily) or 10-day quadruple therapy with Pylera® (three in one capsule containing 140 mg bismuth subcitrate potassium, 125 mg metronidazole and 125 mg tetracycline). The eradication rates according to previous number of eradication failure therapies were calculated. The role antibiotic resistance pattern in H. pylori isolates was also investigated., Results: Data of 423 patients were available. A total of 270 patients were treated with rifabutin-based therapy, and the overall eradication rate was 61.9%. Pylera® therapy was administered to 153 patients and the cure rate was 88.3%. According to the number of previous therapeutic failures, the eradication rate for the rifabutin-based therapy was 68.3% as second-line and further decreased to 63.1% in fourth-line therapy. Following Pylera® regimen, the cure rate was 94.8% in second-line, and remained 89.6% in fourth-line therapy. Efficacy of rifabutin-based and Pylera® therapies significantly decreased when clarithromycin and levofloxacin resistance, respectively, were present., Conclusions: Our data documented a decreasing trend for rifabutin-based therapy efficacy according to previous therapy failures, whilst this did not occur for Pylera®., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

During the last century, there has been an increasing prevalence of hyperuricaemia noted in many populations. While uric acid is usually discussed in the context of gout, hyperuricaemia is also associated with hypertension, chronic kidney disease, hypertriglyceridaemia, obesity, atherosclerotic heart disease, metabolic syndrome, and type 2 diabetes. Here we review the connection between hyperuricaemia and cardiovascular, kidney and metabolic diseases. Contrary to the popular view that uric acid is an inert metabolite of purine metabolism, recent studies suggest serum uric acid may have a variety of pro-inflammatory, pro-oxidative and vasoconstrictive actions that may contribute to cardiometabolic diseases. Hyperuricaemia is a predictive factor for the development of hypertension, metabolic syndrome, type 2 diabetes, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, myocardial infarction, stroke, heart failure and chronic kidney disease. Treatment with uric acid-lowering therapies has also been found to improve outcomes in patients with hypertension and kidney disease, in some but not all studies. In conclusion, uric acid is emerging as a potentially treatable risk factor for cardiometabolic diseases, and more clinical trials investigating the potential benefit of lowering serum uric acid are recommended in individuals with hyperuricaemia with and without deposition and concomitant hypertension, metabolic syndrome or chronic kidney disease., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Competing Interests Dear Prof.Agnelli, as far as my commentary entitled: “Hyperuricemia and mortality in Heart Failure: it is time to change the route?” that I have submitted to you, I declare that I do not have any conflict of interest.

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is associated to increased risk of cardiovascular disease. Our aim was to evaluate association of indexes of fatty liver with arterial stiffness (AS)., Methods: We analyzed data of adult volunteers visited during the last Brisighella survey. We evaluated the Pulse Wave Velocity (PWV) and the following non-invasive indexes of liver steatosis: Fatty Liver Index (FLI), Lipid Accumulation Product (LAP), Hepatic Steatosis Index (HSI). We compared patients according to the risk of Non-Alcoholic Steatohepatitis (NASH): low-risk (BMI < 28 and no diabetes), intermediate-risk (BMI ≥ 28 or diabetes), high-risk (BMI ≥ 28 and diabetes). Multiple Linear Regression analysis was assessed for predictors of AS., Results: We studied 1731 volunteers. In subjects with low metabolic risk, HSI (RR = 0.138, 95%CI 0.105-0.170, p < 0.001), FLI (RR = 0.024, 95%CI 0.016-0.032, p < 0.001), LAP (RR = 0.014, 95%CI 0.008-0.020, p < 0.001) and Serum Uric Acid (RR = 0.150, 95%CI 0.024-0.275, p = 0.019) were significant predictors of AS. HSI and FLI emerged as predictors of PWV in intermediate risk group (RR = 0.116, 95%CI 0.071-0.160, p < 0.001; RR = 0.010, 95%CI 0.001-0.020, p = 0.041). In volunteers with high risk, FLI and Uric Acid were related to PWV (RR = 0.049, 95%CI 0.011-0.087, p = 0.013; RR = 0.632, 95% CI 0.222-1.041, p = 0.003)., Conclusion: Fatty liver indirect indexes were associated to AS in subjects with different metabolic risk profiles., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: High lipoprotein(a) [Lp(a)] levels have been re-evaluated as an independent risk factor for atherosclerotic vascular diseases., Methods: We assessed whether serum Lp(a) levels can significantly influence long-term survival in subjects with an equal general cardiovascular (CV) risk profile. We prospectively evaluated a sample of 1215 adult subjects from the Brisighella Heart Study cohort (M: 608; F: 607; aged 40-69) who had no cardiovascular disease at enrolment. According to the CUORE project risk-charts (Italian-specific risk-charts), individuals were stratified into a low-(n=865), an intermediate-(n=275) and a high-(n=75) cardiovascular risk groups. Kaplan-Meier 25-year survival analysis was carried out examining apart each class of risk and the log-rank statistic was used to estimate, when statistically possible, the survival time of the subjects stratified into quartiles of Lp(a)., Results: Subjects at high and intermediate CV risk aged 56-69years (regardless of gender) and women aged 40-55years with a low CV risk profile who had lower Lp(a) levels showed a significant benefit on CV mortality (P<0.05 always) and, indicatively, on the estimated survival time (even P<0.05). The ROC curves constructing for each CV risk group using Lp(a) as test-variable and death as state-variable identified serum Lp(a) as an independent long-term CV mortality prognosticator for subjects at high CV risk (AUC=0.63, 95%CI [0.50-0.76], P=0.049) and women with an intermediate CV risk profile (AUC=0.7, 95%CI [0.52-0.79], P=0.034)., Conclusions: In the light of our finding and at the best of the previous knowledge, dosing Lp(a) is confirmed as important in subjects at high or medium risk (even if in primary prevention for CV diseases), especially in women., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: Serum uric acid (SUA) has been associated to incident hypertension and increased risk of cardiovascular diseases., Materials and Methods: Among the 2191 subjects enrolled during the last population survey of the Brisighella Heart Study, we identified 146 new cases of arterial hypertension and 394 treated but uncontrolled hypertensive patients with different levels of SUA. Their hemodynamic characteristics have been compared with those of age- and sex-matched normotensive (N. 324) and controlled hypertensive (N. 470) subjects. Then, by logistic regression analysis, we evaluated which factors were associated with a worse BP control under pharmacological treatment., Results: SUA levels were significantly higher in untreated hypertensive and uncontrolled hypertensive patients when compared to normotensives and controlled hypertensive patients. Pulse wave velocity (PWV) was significantly higher (p<0.001) in undiagnosed and uncontrolled hypertensive patients, while controlled hypertensive patients had PWV values comparable to normotensive controls. A similar trend has been observed for the augmentation index (AI). A worse BP control was associated with SUA levels (OR 1277, 95% CI 1134-1600 per mg/dL), AI (OR 1066, 95%CI 1041-1092 per unit), and PWV (OR 1201, 95% CI 1089-1423, per m/s), but not with age, body mass index, nor estimated glomerular filtration rate., Conclusion: Based on our data, SUA seems to be associated with an inadequate BP control in subjects treated with antihypertensive drugs, and subjects with both uncontrolled BP and relatively high SUA levels have also an increased arterial stiffness that (per se) could be a cause of worse BP control under treatment., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: Recent studies show that serum uric acid (SUA) is a predictor of atrial fibrillation, while its association with other kinds of arrhythmias is not yet established. We aimed to evaluate the incidence of the most common electrocardiographic alterations in a relatively large sample of general population and their association with SUA., Materials and Methods: We selected a Brisighella Heart Study cohort sample of 1557 subjects, consecutively visited in the 2004 and 2008 surveys, in a setting of primary prevention for cardiovascular disease and without a known diagnosis of arrhythmia or left ventricular hypertrophy, excluding subjects affected by gout or taking any antihyperuricemic agent or drugs able to interfere with the QT interval. A step-wise Cox regression analysis was used to determine the independent prognostic significance of age, gender, physical activity, smoking, body mass index (BMI), fasting plasma glucose, mean arterial pressure (MAP), heart rate, LDL-cholesterol, HDL-cholesterol, triglycerides, SUA and eGFR on ECG alterations during a 4-year follow-up., Results: No one of the considered variables was associated with the incident diagnosis of sinus tachycardia and sinus bradycardia. SUA predicted incident tachyarrhythmias, Q waves and ECG signs of left ventricular hypertrophy; age, female sex and active smoking predicted incident tachyarrhythmias; male sex, active smoking and LDL-cholesterol predicted incident ECG signs of previous myocardial infarction; BMI and MAP predicted incident ECG-diagnosed left ventricular hypertrophy., Conclusion: In a cohort of general population, SUA seems to be a significant middle-term predictor of electrocardiographically diagnosed myocardial infarction, left ventricular hypertrophy and tachyarrhythmias., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)