Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP) are true hormones produced and released by cardiomyocytes, exerting several systemic effects. Together with C-type NP (CNP), mainly expressed by endothelial cells, they also exert several paracrine and autocrine activities on the heart itself, contributing to cardiovascular (CV) health. In addition to their natriuretic, vasorelaxant, metabolic and antiproliferative systemic properties, NPs prevent cardiac hypertrophy, fibrosis, arrhythmias and cardiomyopathies, counteracting the development and progression of heart failure (HF). Moreover, recent studies revealed that a protein structurally similar to NPs mainly produced by skeletal muscles and osteoblasts called musclin/osteocrin is able to interact with the NPs clearance receptor, attenuating cardiac dysfunction and myocardial fibrosis and promoting heart protection during pathological overload. This narrative review is focused on the direct activities of this molecule family on the heart, reporting both experimental and human studies that are clinically relevant for physicians.

Small interfering RNA (siRNA) represents a novel, fascinating therapeutic strategy that allows for selective reduction in the production of a specific protein through RNA interference. In the cardiovascular (CV) field, several siRNAs have been developed in the last decade. Inclisiran has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) circulating levels with a reassuring safety profile, also in older patients, by hampering proprotein convertase subtilisin/kexin type 9 (PCSK9) production. Olpasiran, directed against apolipoprotein(a) mRNA, prevents the assembly of lipoprotein(a) [Lp(a)] particles, a lipoprotein linked to an increased risk of ischemic CV disease and heart valve damage. Patisiran, binding transthyretin (TTR) mRNA, has demonstrated an ability to improve heart failure and polyneuropathy in patients with TTR amyloidosis, even in older patients with wild-type form. Zilebesiran, designed to reduce angiotensinogen secretion, significantly decreases systolic and diastolic blood pressure (BP). Thanks to their effectiveness, safety, and tolerability profile, and with a very low number of administrations in a year, thus overcoming adherence issues, these novel drugs are the leaders of a new era in molecular therapies for CV diseases.

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality.

(1) Background: Lifestyle changes, eventually coupled with a nutraceutical, are recommended strategies for managing high–normal blood pressure (BP) patients with low–moderate cardiovascular (CV) risk. In a real-life clinical setting, we evaluated the effects of generic written lifestyle advice, extrapolated from the 2018 ESC/ESH guidelines, and a beetroot-based nutraceutical on 24 h BP in a population with a high–normal office BP and low–moderate CV risk. (2) Methods: A longitudinal observational study was conducted in two ESH Hypertension Excellence Centres on 43 consecutive subjects with high–normal BP according to repeated office BP (OBP) measurements and a low–moderate CV risk based on SCORE2/SCORE2-OP. Additionally, 24 h ambulatory BP monitoring (ABPM) was carried out at baseline and three months after lifestyle changes, according to generic written advice from the 2018 ESC/ESH guidelines, coupled with a nutraceutical containing 500 mg of dry beetroot extract. (3) Results: The mean age was 50 ± 11 years, with male prevalence (54%). The prevalence of overweight/obesity was 58%. The mean OBP was 135 ± 3/85 ± 3 mmHg. At baseline, the mean 24 h BP, daytime BP, and night-time BP were 127 ± 7/80 ± 6 mmHg, 131 ± 8/83 ± 6 mmHg, and 118 ± 8/70 ± 5 mmHg, respectively, BP profiles compatible with hypertension status in some subjects. After a median follow-up of 98 (92–121) days, all BPs, except night-time diastolic BP, were significantly decreased: −3 ± 6/−2 ± 4 mmHg for 24 h BP, −3.9 ± 6.0/−3.0 ± 4.0 mmHg for daytime BP, and −3.3 ± 7.4/−1.3 ± 4.7 mmHg for night-time BP, respectively. No significant clinical changes in body weight were detected. BP decreased independently of baseline BP levels, sex, smoking status, and body mass index, while a more substantial BP decrease was observed in older patients. (4) Conclusions: Our exploratory study shows, for the first time, that written generic lifestyle advice taken from the ESC/ESH hypertension guidelines coupled with a beetroot-based nutraceutical may represent a valid initial non-pharmacological approach in subjects with a high–normal office BP and low–moderate CV risk, even without personalized diet interventions.

Since the first months of the coronavirus disease 2019 (COVID-19) pandemic, several specific physiologic traits, such as male sex and older age, or health conditions, such as overweight/obesity, arterial hypertension, metabolic syndrome, and type 2 diabetes mellitus, have been found to be highly prevalent and associated with increased risk of adverse outcomes in hospitalized patients. All these cardiovascular morbidities are widespread in the population and often coexist, thus identifying a common patient phenotype, characterized by a hyper-activation of the “classic” renin-angiotensin system (RAS) and mediated by the binding of angiotensin II (Ang II) to the type 1-receptor. At the same time, the RAS imbalance was proved to be crucial in the genesis of lung injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, where angiotensin-converting-enzyme-2 (ACE2) is not only the receptor for SARS-CoV-2, but its down-regulation through internalization and shedding, caused by the virus binding, leads to a further dysregulation of RAS by reducing angiotensin 1-7 (Ang 1-7) production. This focused narrative review will discuss the main available evidence on the role played by cardiovascular and metabolic conditions in severe COVID-19, providing a possible pathophysiological link based on the disequilibrium between the two opposite arms of RAS.

Our study aimed to identify clusters of hospitalized older COVID-19 patients according to their main comorbidities and routine laboratory parameters to evaluate their association with in-hospital mortality. We performed an observational study on 485 hospitalized older COVID-19 adults (aged 80+ years). Patients were aggregated in clusters by a K-medians cluster analysis. The primary outcome was in-hospital mortality. Medical history and laboratory parameters were collected on admission. Frailty, defined by the Clinical Frailty Scale (CFS), referred to the two weeks before hospitalization and was used as a covariate. The median age was 87 (83–91) years, with a female prevalence (59.2%). Three different clusters were identified: cluster 1 (337), cluster 2 (118), and cluster 3 (30). In-hospital mortality was 28.5%, increasing from cluster 1 to cluster 3: cluster 1 = 21.1%, cluster 2 = 40.7%, and cluster 3 = 63.3% (p < 0.001). The risk for in-hospital mortality was higher in clusters 2 [HR 1.96 (95% CI: 1.28–3.01)] and 3 [HR 2.87 (95% CI: 1.62–5.07)] compared to cluster 1, even after adjusting for age, sex, and frailty. Patients in cluster 3 were older and had a higher prevalence of atrial fibrillation, higher admission NT-proBNP and C-reactive protein levels, higher prevalence of concurrent bacterial infections, and lower estimated glomerular filtration rates. The addition of CFS significantly improved the predictive ability of the clusters for in-hospital mortality. Our cluster analysis on older COVID-19 patients provides a characterization of those subjects at higher risk for in-hospital mortality, highlighting the role played by cardio-renal impairment, higher inflammation markers, and frailty, often simultaneously present in the same patient.