A dysregulation of the renin-angiotensin-system (RAS) has been involved in the genesis of lung injury and acute respiratory distress syndrome (ARDS) from different causes, including several viral infections. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection of pneumocytes, the hallmark of the pandemic coronavirus disease 2019 (COVID-19) involving both alveolar interstitium and capillaries, is linked to angiotensin-converting-enzyme 2 (ACE2) binding and its functional downregulation. ACE2 is a key enzyme for the balance between the two main arms of the RAS: the ACE/Angiotensin (Ang) II/Ang II type 1 receptor axis ("classic RAS"), and the ACE2/Ang 1-7/MasR axis ("anti-RAS"). The ACE2 downregulation, as a result of SARS-coronaviruses binding, enhances the "classic RAS", leading to lung damage and inflammation with leaky pulmonary blood vessels and fibrosis, when the attenuation mediated by the "anti-RAS" arm is reduced. ACE inhibitors (ACE-I) and Ang II type 1 receptor blockers (ARB), effective in cardiovascular diseases, were found to prevent and counteract acute lung injury in several experimental models, by restoring the balance between these two opposing arms. The evidence of RAS arms disequilibrium in COVID-19 and the hypothesis of a beneficial role of RAS modulation supported by preclinical and clinical studies are the focus of the present review. Preclinical and clinical studies on drugs balancing RAS arms might be the right way to counter COVID-19.

Prevalence of cardiovascular (CV) disease is increasing worldwide. One of the most important risk factors for CV disease is hypertension that is very often related to obesity and metabolic syndrome. The search for key mechanisms, linking high blood pressure (BP), glucose and lipid dysmetabolism together with higher CV risk and mortality, is attracting increasing attention. Cardiac natriuretic peptides (NPs), including ANP and BNP, may play a crucial role in maintaining CV homeostasis and cardiac health, given their impact not only on BP regulation, but also on glucose and lipid metabolism. The summa of all metabolic activities of cardiac NPs, together with their CV and sodium balance effects, may be very important in decreasing the overall CV risk. Therefore, in the next future, cardiac NPs system, with its two receptors and a neutralizing enzyme, might represent one of the main targets to treat these multiple related conditions and to reduce hypertension and metabolic-related CV risk.

Real-life data confirming the favourable renal outcome in patients with heart failure (HF) treated with Sacubitril/Valsartan, previously found in several trials (RCTs), are still scant. We evaluated the renal effects of Sacubitril/Valsartan in a real-life sample of HF patients. Observational analysis of 54 consecutive outpatients affected by HF with reduced ejection fraction (HFrEF) and clinical indication for Sacubitril/Valsartan. Patients were evaluated at baseline (T0) and after six (T6) and twelve (T12) months after initiating Sacubitril/Valsartan and compared with a group of 30 historical controls. Mean age: 65.5 ± 11.7 years. Older patients: 29 (53.7%). Mean baseline estimated glomerular filtration rate (eGFR): 59.4 ± 19.2 ml/ min/1.73 m 2. Patients with chronic kidney disease (CKD), defined by an eGFR < 60 ml/min/1.73 m 2 , were 29 (53.7%). Sacubitril/Valsartan was less titrated in both older patients and patients with CKD. There were no changes in diuretics during follow-up. Systolic blood pressure (BP) decreased during follow-up (p = 0.014), while left ventricular ejection fraction (LVEF) slighly increased (p < 0.001). Renal function improved after 12 months compared to historical controls (p for interaction < 0.001) and a greater benefit was found in subjects aged < 65 years (p for interaction = 0.002) and patients with CKD (p for interaction = 0.009). A statistically (p = 0.009), but not clinically significant increase in serum potassium was also found, regardless of age and CKD. This is the first study focused on the renal effects of Sacubitril/Valsartan in HFrEF patients followed for 12 months in a real-life clinical context. The improved eGFR, despite lower BP, represents an important confirmation outside the peculiar world of RCTs.

Introduction: We evaluated the prevalence and control of dyslipidemia in a wide sample of patients referred to our ESH ''Hypertension Excellence Centre'' for high blood pressure (BP). Furthermore, we evaluated the role of adiposity on the serum lipid profile. Methods: Observational study on 1219 consecutive outpatients with valid ambulatory BP monitoring (ABPM) referred for high BP. Patients with body mass index (BMI) C 25 kg/m 2 were defined as overweight/obese (OW/OB). Dyslipidemia and the control rates of low-density lipoprotein cholesterol (LDLc) were defined according to the 2016 ESC/EAS Guidelines. Results: Mean age: 56.5 ± 13.7 years. Male prevalence: 55.6%. OW/OB patients were 70.2%. The prevalence of dyslipidemia was 91.1%. Lipidlowering drugs were taken by 23.1% of patients. Patients with controlled LDLc comprised 28.5%, while BP was controlled in 41.6% of patients. Only 12.4% of patients had both 24-h BP and LDLc controlled at the same time. The higher the cardiovascular (CV) risk was, the lower was the rate of LDLc control (p \ 0.001). Patients in secondary prevention had worse LDLc control than patients in primary prevention (OR 3.5 for uncontrolled LDLc, p \ 0.001). OW/OB showed a more atherogenic lipid profile, characterized by lower highdensity lipoprotein cholesterol (HDLc) (p \ 0.001), higher non-HDLc (p = 0.006), higher triglycerides (p \ 0.001), higher non-HDLc/HDLc (p \ 0.001) and higher (non-HDLc ? non-LDLc) (p \ 0.001). Conclusion: Dyslipidemia is still too often neglected in hypertensives, especially in patients at higher CV risk. OW/OB hypertensives have a ''double-trouble'' atherogenic lipid pattern likely driven by adiposity. We encourage a comprehensive evaluation of the lipid profile in all hypertensives, especially if they are OW/OB, to correctly assess their CV risk and improve their management. Funding: Article processing charges funded by Servier SpA.

Tobacco use is one of the major public health concerns and it is the most preventable cause of morbidity and mortality worldwide. Smoking cessation reduces subsequent cardiovascular events and mortality. Smoking is a real chronic disorder characterized by the development of an addiction status mainly due to nicotine. This condition makes the smokers generally unable to quit smoking without help. Different strategies are available to treat smoking dependence that include both non-pharmacological (behavioral counselling) and pharmacological therapies. Currently, it is well accepted that smoking cessation drugs are effective and safe in real-world settings. Nicotine replacement therapy (NRT), varenicline, bupropion and cytisine are the main pharmacological strategies available for smoking cessation. Their efficacy and safety have been proved even in patients with chronic cardiovascular disease. Each of these drugs has peculiar characteristics and the clinician should customize the smoking cessation strategy based on currently available scientific evidence and patient's preference, paying particular attention to those patients having specific cardiovascular and psychiatric comorbidities. The present document aims to summarize the current viable pharmacological strategies for smoking cessation, also discussing the controversial issue regarding the use of alternative tobacco products, in order to provide useful practical indications to all physicians, mainly to those involved in cardiovascular prevention.

A worsening renal function is prevalent among patients with cardiovascular disease, especially heart failure (HF). Sacubitril/valsartan appears to prevent worsening of renal function and progression of chronic kidney disease (CKD) as compared with renin-angiotensin system (RAS) inhibitors alone in HF patients. It is unclear whether these advantages are present in HF patients only, or can be extended to other categories of patients, in which this drug was studied. We performed a systematic review and meta-analysis to assess the consistency of effect size regarding renal outcome across randomized controlled trials (RCTs) that compared sacubitril/valsartan with RAS inhibitors in patients with or without HF. We searched Medline (PubMed), Scopus, and Thomson Reuters Web of Science databases until June 2020. We took into account RCTs that compared sacubitril/valsartan with a RAS inhibitor and reported data regarding renal function. We used random-effects models to obtain summary odds ratio (OR) with 95% confidence interval (CI). We extracted hazard ratios for renal outcomes, glomerular filtration rate slopes or rates of renal adverse events. Sensitivity analyses were performed by moderator analysis and random-effects meta-regression. The search revealed 10 RCTs (published between 2012 and 2019) on 16 456 subjects. Sacubitril/valsartan resulted in a lower risk of renal dysfunction as compared with RAS inhibitors alone [k ¼ 10; pooled OR ¼ 0.70 (95% CI 0.57-0.85); P < 0.001], with a moderate inconsistency between studies [Q(9) ¼ 15.18; P ¼ 0.086; I 2 ¼ 40.73%]. A stronger association was found in studies including older patients (k ¼ 10; β ¼ À0.047730; P ¼ 0.020) or HF patients with preserved ejection fraction [pooled OR ¼ 0.53 (0.41-0.68) vs. 0.76 (0.57-1.01) for studies on HF patients with reduced ejection fraction; P for comparison ¼ 0.065]. The effect size did not change with different comparators (angiotensin-converting enzyme inhibitors vs. angiotensin II type 1 receptor blockers, P ¼ 0.279). No significant association was found when the analysis was restricted to studies on non-HF patients [k ¼ 3; pooled OR ¼ 0.86 (0.61-1.22); P ¼ 0.403] and studies with high risk of bias [k ¼ 3; pooled OR ¼ 0.34 (0.08-1.44); P ¼ 0.143]. Our findings support the role of sacubitril/valsartan on preservation of renal function, especially in older patients and HF patients with preserved ejection fraction. However, evidence is currently limited to HF patients, while the renal outcome of sacubitril/valsartan therapy outside the HF setting needs to be further investigated.

No abstract

No abstract