Sex differences in arterial hypertension.

There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension.

Chronic obstructive pulmonary disease and ischemic heart disease comorbidity: overview of mechanisms and clinical management.

In the last few years, many studies focused their attention on the relationship between chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD), showing that these diseases are mutually influenced. Many different biological processes such as hypoxia, systemic inflammation, endothelial dysfunction, heightened platelet reactivity, arterial stiffness and right ventricle modification interact in the development of the COPD-IHD comorbidity, which therefore deserves special attention in early diagnosis and treatment. Patients with COPD-IHD comorbidity have a worst outcome, when compared to patients with only COPD or only IHD. These patients showed a significant increase on risk of adverse events and of hospital readmissions for recurrent myocardial infarction, heart failure, coronary revascularization, and acute exacerbation of COPD. Taken together, these complications determine a significant increase in mortality. In most cases death occurs for cardiovascular cause, soon after an acute exacerbation of COPD or a cardiovascular adverse event. Recent data regarding incidence, mechanisms and prognosis of this comorbidity, along with the development of new drugs and interventional approaches may improve the management and long-term outcome of COPD-IHD patients. The aim of this review is to describe the current knowledge on COPD-IHD comorbidity. Particularly, we focused our attention on underlying pathological mechanisms and on all treatment and strategies that may improve and optimize the clinical management of COPD-IHD patients.

Relationship between Troponin Elevation, Cardiovascular History and Adverse Events in Patients with acute exacerbation of COPD.

Evidence suggests that troponin (Tn) elevation during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may predict an increase in mortality risk. We performed an observational study of 935 patients admitted to hospital for AECOPD from January 2010 to December 2012. Principal clinical and laboratory data were recorded, especially ischemic heart disease (IHD) history, Tn T values and cardiovascular drug prescription. The occurrence of all-cause death, cardiac death (CD), nonfatal myocardial infarction (MI), heart failure and cerebrovascular accident (CVA) was assessed on December 2013. Overall, 694 patients respected inclusion and exclusion criteria. We identified 210 (30%) patients without Tn elevation (negative Tn T group) and 484 (70%) patients with Tn elevation (positive Tn T group). With the exception of CVA, all adverse events were significantly higher in positive Tn T group as compared to negative Tn T group. At multivariable analysis, positive Tn T failed to predict all-cause death. Contrarily, positive Tn T emerged as independent predictors of CD (HR 1.61, 95%CI 1.2-2.2, p = 0.04), nonfatal MI (HR 3.12, 95%CI 1.4-8.1, p = 0.03) and composite endpoint including CD and nonfatal MI (HR 1.73, 95%CI 1.2-2.7, p = 0.03). Of note, positive Tn T stratified prognosis in patients without IHD history, but not in those with IHD history. In conclusion, after hospital admission for AECOPD, we observed a significant increase in the risk of cardiac adverse events in patients with Tn T elevation, especially in those without IHD history.

Heart failure and chronic obstructive pulmonary disease: the challenges facing physicians and health services.

Pulmonary disease is common in patients with heart failure, through shared risk factors and pathophysiological mechanisms. Adverse pulmonary vascular remodelling and chronic systemic inflammation characterize both diseases. Concurrent chronic obstructive pulmonary disease presents diagnostic and therapeutic challenges, and is associated with increased morbidity and mortality. The cornerstones of therapy are beta-blockers and beta-agonists, whose pharmacological properties are diametrically opposed. Each disease is implicated in exacerbations of the other condition, greatly increasing hospitalizations and associated health care costs. Such multimorbidity is a key challenge for health-care systems oriented towards the treatment of individual diseases. Early identification and treatment of cardiopulmonary disease may alleviate this burden. However, diagnostic and therapeutic strategies require further validation in patients with both conditions.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023.

Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs.

Oral anticoagulation in patients with left ventricular thrombus: a systematic review and meta-analysis.

AIMS: Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analysed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety. METHODS: We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs vs. VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effects model meta-analysis, and their robustness was investigated using sensitivity and influential analyses. RESULTS: We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3587 patients (2489 VKA vs. 1098 DOAC therapy). The pooled estimates for stroke or systemic embolism [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.57, 1.15] and thrombus resolution (OR: 1.12; 95% CI: 0.86, 1.46) were comparable, and there was low heterogeneity overall across the included studies. The use of DOACs was associated with lower odds of all-cause death (OR: 0.65; 95% CI: 0.46, 0.92) and a composite bleeding endpoint (OR: 0.67; 95% CI: 0.47, 0.97). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots. CONCLUSION: In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution, compared with VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT.

Plasma sRAGE and N-(carboxymethyl) lysine in patients with CHF and/or COPD.

BACKGROUND: Knowledge of the role of the receptor for advanced glycation end products (RAGE), particularly its soluble form (sRAGE), and of its advanced glycation end product (AGE) ligand, N-(carboxymethyl)lysine adducts (CML), is limited in chronic heart failure (CHF) and in chronic obstructive pulmonary disease (COPD). We evaluated whether the AGE/RAGE system is activated in stable CHF and COPD, and whether plasma sRAGE and CML levels are affected by clinical and functional parameters. MATERIALS AND METHODS: We measured plasma levels of sRAGE and CML using a sandwich enzyme-linked immunosorbent assay (ELISA) in 143 subjects, aged ≥ 65 years, divided into five groups: 58 with CHF, 23 with COPD, 27 with CHF+COPD and 35 controls (17 healthy smokers and 18 healthy nonsmokers). Individuals with diabetes were excluded from the study. RESULTS: Plasma levels of sRAGE and CML were higher in CHF patients than in controls [sRAGE: 0.48 (0.37-0.83) vs. 0.42 (0.29-0.52) ng/mL, P = 0.01; CML: 1.95 (1.58-2.38) vs. 1.68 (1.43-2.00) ng/mL, P = 0.01]. By contrast, sRAGE and CML were not different between both COPD and CHF+COPD patients and controls (P > 0.05). N-terminal pro-brain natriuretic peptide (Nt-pro BNP) correlated with sRAGE, but not with CML, in the patient groups: CHF (r = 0.43, P < 0.001), COPD (r = 0.77, P < 0.0001) and CHF/COPD (r = 0.43, P = 0.003). CONCLUSIONS: Plasma levels of sRAGE and CML are increased in CHF, but not in COPD patients. The robust association between NT-pro BNP, a diagnostic and prognostic marker in CHF, and sRAGE concentrations might suggest a possible BNP pathway of amplification of inflammation via the AGE/RAGE system.

Occurrence and impact of chronic obstructive pulmonary disease in elderly patients with stable heart failure.

BACKGROUND AND OBJECTIVE: The coexistence of chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) increases with age. The occurrence, prognosis and therapeutic implications of concurrent COPD in elderly patients with CHF were investigated. METHODS: One hundred and eighteen consecutive patients, ≥ 65 years old with ≥ 10 pack/years of smoking and with a verified diagnosis of CHF in stable condition, were enrolled. They were followed for a mean of 1029 (range 758-1064) days. All patients had spirometry and the diagnosis and classification of COPD were made according to Global Initiative for Chronic Obstructive Lung Disease guidelines. RESULTS: The mean occurrence of COPD was 30% (90% confidence interval: 24-37%). At baseline in patients with CHF and COPD, there was a shorter 6-min walk distance, lower arterial oxygen tension, glomerular filtration rate and higher N-terminal pro-B-type natriuretic peptide (all P < 0.05). The prescription of CHF therapies, including ß-blockers, was similar in the two groups. After follow up, the presence of COPD in patients with CHF did not appear to influence survival. CONCLUSIONS: COPD is relatively frequent in elderly patients with CHF. COPD did not alter survival.

[Gaps in evidence in recent cardiovascular guidelines: uncertainties in chronic coronary syndrome]. / "Gaps in evidence" nelle recenti linee guida cardiovascolari: incertezze nella sindrome coronarica cronica.

The clinical guidelines, while representing an objective reference to perform correct therapeutic choices, contain grey zones, where the recommendations are not supported by solid evidence. In the fifth National Congress Grey Zones held in Bergamo in June 2022, an attempt was made to highlight some of the main grey zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies regarding ischemic cardiomyopathy. The manuscript represents the organization of the meeting, with an initial review of the current guidelines on this topic, followed by an expert presentation of pros (White) and cons (Black) related to the identified "gaps of evidence". For every issue is then reported the "response" derived from the votes of the experts and the public, the discussion and, finally, the highlights, which are intended as practical take home messages to be used in the everyday clinical practice. The first gap in evidence discussed regards the validity of the indication to search for ischemia in light of the data from the ISCHEMIA trial. The second examines the possibility of modifying the algorithm proposed by the European guidelines on anti-ischemic therapy in chronic coronary syndromes. The last gap in evidence evaluates the comparability of long-term antithrombotic strategies in chronic coronary syndromes.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus ß-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis.

Link between chronic obstructive pulmonary disease and coronary artery disease: implication for clinical practice.

Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are global epidemics that incur significant morbidity and mortality. These diseases are frequently found in combination, and they can also be found independent of the common causal factors, primarily smoking. Both conditions are systemic disorders with overlapping mechanisms and pathophysiologic processes. CAD has a strong effect on the severity and prognosis of COPD and vice versa, including acute exacerbations. Even the most recent practical clinical recommendations driven by Clinical Practice Guidelines still focus on one disease at a time, and do not provide advice for the management of patients with associated chronic conditions. COPD should be approached in a more comprehensive manner, including the treatment of cardiac comorbidities, particularly CAD. To focus treatment on these comorbidities might modify the natural course of the disease in patients with COPD who may not find relief from treatment of COPD alone.

Facing the challenge of polypharmacy when prescribing for older people with cardiovascular disease. A review by the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

Population ageing has resulted in an increasing number of older people living with chronic diseases (multimorbidity) requiring five or more medications daily (polypharmacy). Ageing produces important changes in the cardiovascular system and represents the most potent single cardiovascular risk factor. Cardiovascular diseases (CVDs) constitute the greatest burden for older people, their caregivers, and healthcare systems. Cardiovascular pharmacotherapy in older people is complex because age-related changes in body composition, organ function, homeostatic mechanisms, and comorbidities modify the pharmacokinetic and pharmacodynamic properties of many commonly used cardiovascular and non-cardiovascular drugs. Additionally, polypharmacy increases the risk of adverse drug reactions and drug interactions, which in turn can lead to increased morbi-mortality and healthcare costs. Unfortunately, evidence of drug efficacy and safety in older people with multimorbidity and polypharmacy is limited because these individuals are frequently underrepresented/excluded from clinical trials. Moreover, clinical guidelines are largely written with a single-disease focus and only occasionally address the issue of coordination of care, when and how to discontinue treatments, if required, or how to prioritize recommendations for patients with multimorbidity and polypharmacy. This review analyses the main challenges confronting healthcare professionals when prescribing in older people with CVD, multimorbidity, and polypharmacy. Our goal is to provide information that can contribute to improving drug prescribing, efficacy, and safety, as well as drug adherence and clinical outcomes.

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed.

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.

Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling.

The aim of this study was to investigate the effect of chronic heart rate (HR) reduction with the hyperpolarization-activated current inhibitor ivabradine on the global phenotype of left ventricular (LV) remodeling in a ligated rat model. Seven days after coronary artery ligation, Wistar rats received ivabradine (10 mg · kg(-1) · day(-1) administered in drinking water) [myocardial infarction + ivabradine (MI+IVA), n = 22] or vehicle only (drinking water) (MI, n = 20) for 90 days. A sham group (n = 20) was included for model validation. MI+IVA rats had 12% lower HR (P < 0.01), improved LV volumes, 15% higher LV ejection fraction (LVEF, P < 0.01) than MI rats, and 33% reductions in both plasma atrial natriuretic peptide (ANP, P = 0.052) and cardiac hydroxyproline. Using patch-clamp, action potential duration was reduced and transient outward current density increased (P < 0.05). Cardiac energy metabolism was also improved (+33% creatine phosphate, P < 0.001; +15% ATP; and +9% energy charge, P < 0.05). Significant correlations were found between HR and parameters of cardiac metabolism, ANP, and LVEF (all P < 0.05). The HR-reducing properties of ivabradine prevent changes in the global phenotype of LV remodeling in the rat, optimize energy consumption, and avoid electrophysiological and structural remodeling.

Genetic determinants of treatment benefit of the angiotensin-converting enzyme-inhibitor perindopril in patients with stable coronary artery disease.

AIMS: The efficacy of angiotensin-converting enzyme (ACE)-inhibitors in stable coronary artery disease (CAD) may be increased by targeting the therapy to those patients most likely to benefit. However, these patients cannot be identified by clinical characteristics. We developed a genetic profile to predict the treatment benefit of ACE-inhibitors exist and to optimize therapy with ACE-inhibitors. METHODS AND RESULTS: In 8907 stable CAD patients participating in the randomized placebo-controlled EUROPA-trial, we analysed 12 candidate genes within the pharmacodynamic pathway of ACE-inhibitors, using 52 haplotype-tagging-single nucleotide polymorphisms (SNPs). The primary outcome was the reduction in cardiovascular mortality, non-fatal myocardial infarction, and resuscitated cardiac arrest during 4.2 years of follow-up. Multivariate Cox regression was performed with multiple testing corrections using permutation analysis. Three polymorphisms, located in the angiotensin-II type I receptor and bradykinin type I receptor genes, were significantly associated with the treatment benefit of perindopril after multivariate adjustment for confounders and correction for multiple testing. A pharmacogenetic score, combining these three SNPs, demonstrated a stepwise reduction of risk in the placebo group and a stepwise decrease in treatment benefit of perindopril with an increasing scores (interaction P < 0.0001). A pronounced treatment benefit was observed in a subgroup of 73.5% of the patients [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.56-0.79], whereas no benefit was apparent in the remaining 26.5% (HR 1.26; 95% CI 0.97-1.67) with a trend towards a harmful effect. In 1051 patients with cerebrovascular disease from the PROGRESS-trial, treated with perindopril or placebo, an interaction effect of similar direction and magnitude, although not statistically significant, was observed. CONCLUSION: The current study is the first to identify genetic determinants of treatment benefit of ACE-inhibitor therapy. We developed a genetic profile which predicts the treatment benefit of ACE-inhibitors and which could be used to optimize therapy.

[Preventive cardiology: comparisons of European and Italian projects with the Cardiac Units from Emilia Romagna region. A workshop of IACPR/GICR - Emilia Romagna]. / La Cardiologia Preventiva: prospettive nazionali ed europee a confronto con le Cardiologie dell'Emilia Romagna. Workshop IACPR/GICR - Emilia Romagna.

A workshop endorsed by the Italian Association of Cardiovascular Prevention and Rehabilitation--Emilia Romagna Section--held in Piacenza in May 2011, gave the opportunity to discuss the emerging role of Preventive Cardiology in the modern era. From the new documents recently published by the European and Italian Scientific Associations, the barriers in their implementation, and the contribution of the health care providers, physicians, nurses, both in primary and secondary prevention were discussed. The local initiatives of cardiac prevention in different areas were presented and compared. A new project of secondary prevention in the follow-up and management of patients with dilated cardiomyopathy and heart failure promoted by the Emilia Romagna Region Health Authority was presented.

Update on management of hypokalaemia and goals for the lower potassium level in patients with cardiovascular disease: a review in collaboration with the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

Hypokalaemia is common in patients with cardiovascular disease. In this review, we emphasize the importance of tight potassium regulation in patients with cardiovascular disease based on findings from observational studies. To enhance the understanding, we also describe the mechanisms of potassium homeostasis maintenance, the most common causes of hypokalaemia and present strategies for monitoring and management of low potassium levels. We propose elevation of potassium in asymptomatic patients with lower normal concentrations and concurrent cardiovascular disease. These proposals are intended to assist clinicians until more evidence is available.