Home Blood Pressure and Telemedicine: A Modern Approach for Managing Hypertension During and After COVID-19 Pandemic.

Hypertension is the most common cardiovascular risk factor for acute cardiovascular outcomes, including acute coronary disease, stroke, chronic kidney disease and congestive heart failure. Despite the fact that it represents the most prevalent risk factor in the general population, mostly in elderly individuals, its awareness is still relatively low, being about one third of patients living with undiagnosed hypertension and high risk of experiencing acute cardiovascular events. In addition, though recent improvement in pharmacological and non-pharmacological therapeutic options, hypertension is largely uncontrolled, with about 35-40% of treated hypertensive patients achieving the recommended therapeutic targets. Among different modern interventions proposed for improving blood pressure control in treated hypertensive patients, a systematic adoption of home BP monitoring has demonstrated to be one of the most effective. Indeed, it improves patients' awareness of the disease and adherence to prescribed medications and allows tailoring and personalizing BP lowering therapies. Home BP monitoring is particularly suitable for telemedicine and mobile-health solutions. Indeed, in specific conditions, when face-to-face interactions between patients and physicians are not allowed or even suspended, as in case of COVID-19 pandemic, telemedicine may ensure effective management of hypertension, as well as other cardiovascular and non-cardiovascular comorbidities. This review will summarize strengths and limitations of telemedicine in the clinical management of hypertension with a particular focus on the lessons learned during the COVID-19 pandemic.

Prevalence and clinical characteristics of isolated systolic hypertension in young: analysis of 24 h ambulatory blood pressure monitoring database.

Isolated systolic hypertension (ISHT) is common in elderly patients, whilst its prevalence and clinical impact in young adults are still debated. We aimed to estimate prevalence and clinical characteristics of ISHT and to evaluate out-of-office BP levels and their correlations with office BP in young adults. A single-center, cross-sectional study was conducted at our Hypertension Unit, by including treated and untreated individuals aged 18-50 years, who consecutively underwent home, clinic and 24 h ambulatory BP assessment. All BP measurements were performed and BP thresholds were set according to European guidelines: normotension (NT), clinic BP <140/<90 mmHg; ISHT, BP ≥140/<90 mmHg; isolated diastolic hypertension (IDHT), BP <140/≥90 mmHg; systolic-diastolic hypertension (SDHT), BP ≥140/≥90 mmHg. European SCORE, vascular and cardiac HMOD were also assessed. From an overall sample of 13,053 records, we selected 2127 young outpatients (44.2% female, age 40.5 ± 7.4 years, BMI 26.7 ± 5.0 kg/m2, clinic BP 141.1 ± 16.1/94.1 ± 11.8 mmHg, 24 h BP 129.0 ± 12.8/82.4 ± 9.8 mmHg), among whom 587 (27.6%) had NT, 391 (18.4%) IDHT, 144 (6.8%) ISHT, and 1005 (47.2%) SDHT. Patients with ISHT were predominantly male (61.1%), younger and with higher BMI compared to other groups. They also showed higher home and 24 h ambulatory SBP levels than those with NT or IDHT (P < 0.001), though similar to those with SDHT. ISHT patients showed significantly higher pulse pressure (PP) levels than other groups, at all BP measurements (P < 0.001 for all comparisons), and significantly higher proportion (65.3%) of patients with ISHT had PP >60 mmHg. European SCORE resulted significantly higher in patients with ISHT (1.6 ± 2.9%) and SDHT (1.5 ± 2.7%) compared to those with IDHT (0.9 ± 1.5%) or NT (0.8 ± 1.9%) (P = 0.017). Though relatively rare, ISHT should be not viewed as a benign condition, being associated with sustained SBP elevation, high European SCORE risk, and vascular HMOD.

ARB-Based Combination Therapy for the Clinical Management of Hypertension and Hypertension-Related Comorbidities: A Spotlight on Their Use in COVID-19 Patients.

Essential hypertension is the most common cardiovascular (CV) risk factor, being primarily involved in the pathogenesis of CV disease and mortality worldwide. Given the high prevalence and growing incidence of this clinical condition in the general population in both high and low-income countries, antihypertensive drug therapies are frequently prescribed in different hypertension-related CV diseases and comorbidities. Among these conditions, evidence are available demonstrating the clinical benefits of lowering blood pressure (BP) levels, particularly in those hypertensive patients at high or very high CV risk profile. Preliminary studies, performed during the Sars-COVID-19 epidemic, raised some concerns on the potential implication of hypertension and antihypertensive medications in the susceptibility of having severe pneumonia, particularly with regard to the use of drugs inhibiting the renin-angiotensin system (RAS), including angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). These hypotheses were not confirmed by subsequent studies, which independently and systematically demonstrated no clinical harm of these drugs also in patients with Sars-COVID-19 infection. The aim of this narrative review is to critically discuss the available evidence supporting the use of antihypertensive therapies based RAS blocking agents in hypertensive patients with different CV risk profile and with additional clinical conditions or comorbidities, including Sars-COVID-19 infection, with a particular focus on single-pill combination therapies based on olmesartan medoxomil.

Antihypertensive drugs and the risks of cancer: More fakes than facts.

In the last century, the diffusion of medical news to the public has been profoundly changed by the progressive spread of more pervasive, but at the same time often unreliable, means of communication. The misinterpretation of scientific evidence or fallacious presentation through social media could play as a great drawback to the success in the management of many diseases. This may become particularly alarming when concerning chronic diseases widely affecting the population. Arterial hypertension is still today one of the major causes of mortality and morbidity in most countries, and its management generally requires chronic therapy lasting for decades. Therefore, a recent debate about the potential oncogenic effect of antihypertensive drugs has been made widely available to patients mostly through social media. Since this is a topic of great impact for millions of patients and of main relevance for the scientific community, it must not be contaminated by the spread of fake or twisted news. The objective of this article is to briefly discuss the almost complete lack of hard evidence about the potential oncogenic effect of the major classes of antihypertensive drugs as opposed to the exaggerated mediatic communication and impact of scattered and unconfirmed observations. We believe that it is of key importance to provide authoritative support for patients and clinicians from scientific societies and guidelines to balance an unopposed widespread penetration of twisted or even fake news.

Real-life appraisal on blood pressure targets achievement in adult outpatients at high cardiovascular risk.

BACKGROUND AND AIM: Although hypertension guidelines highlight the benefits of achieving the recommended blood pressure (BP) targets, hypertension control rate is still insufficient, mostly in high or very high cardiovascular (CV) risk patients. Thus, we aimed to estimate BP control in a cohort of patients at high CV risk in both primary and secondary prevention. METHODS AND RESULTS: A single-center, cross-sectional study was conducted by extracting data from a medical database of adult outpatients aged 40-75 years, who were referred to our Hypertension Unit, Rome (IT), for hypertension assessment. Office BP treatment targets were defined according to 2018 ESC/ESH guidelines as: a)<130/80 mmHg in individuals aged 40-65 years; b)<140/80 mmHg in subjects aged >65 years. Primary prevention patients with SCORE <5% were considered to be at low-intermediate risk, whilst individuals with SCORE ≥5% or patients with comorbidities were defined to be at very high risk. Among 6354 patients (47.2% female, age 58.4 ± 9.6 years), 4164 (65.5%) were in primary prevention with low-intermediate CV risk, 1831 (28.8%) in primary prevention with high-very high CV risk and 359 (5.6%) in secondary prevention. In treated hypertensive outpatients, uncontrolled hypertension rate was significantly higher in high risk primary prevention than in low risk primary prevention and secondary prevention patients (18.4% vs 24.4% vs. 12.5%, respectively; P < 0.001). In high risk primary prevention diabetic patients only 10% achieved the recommended BP targets. CONCLUSIONS: Our data confirmed unsatisfactory BP control among high-risk patients, both in primary and secondary prevention, and suggest the need for a more stringent BP control policies in these patients.

Blood Pressure Target Achievement Under Monotheraphy: A Real-Life Appraisal.

INTRODUCTION: Despite hypertension guidelines suggest that the most effective treatment strategy to improve blood pressure (BP) target achievement is to implement the use of combination treatment, monotherapy is still widely used in the clinical practice of hypertension. AIM: To investigate BP control under monotherapy in the setting of real-life. METHODS: We extracted data from a medical database of adult outpatients who were referred to the Hypertension Unit, Sant'Andrea Hospital, Rome (IT), including anthropometric data, CV risk factors and comorbidities, presence or absence of antihypertensive therapy and concomitant medications. Among treated hypertensive patients, we identified only those under single antihypertensive agent (monotherapy). Office BP treatment targets were defined according to 2018 ESC/ESH guidelines as: (a) < 130/80 mmHg in individuals aged 18-65 years; (b) < 140/80 mmHg in those aged > 65 years. RESULTS: From an overall sample of 7797 records we selected 1578 (20.2%) hypertensive outpatients (47.3% female, age 59.5 ± 13.6 years, BMI 26.6 ± 4.4 kg/m2) treated with monotherapies, among whom 30.5% received ACE inhibitors, 37.7% ARBs, 15.8% beta-blockers, 10.6% CCBs, 3.0% diuretics, and 2.0% alpha-blockers. 36.6% of these patients reached the conventional clinic BP goal of < 140/90 mmHg, whilst the 2018 European guidelines BP treatment targets were fulfilled only in 14.0%. In particular, 10.2% patients aged 18-65 years and 20.4% of those aged > 65 years achieved the recommended BP goals. All these proportions results significantly lower than those achieved with dual (18.2%) or triple (22.2%) combination therapy, though higher than those obtained with life-style changes (10.8%). Proportions of patients on monotherapies with normal home and 24-h BP levels were 22.0% and 30.2%, respectively, though only 5.2% and 7.3% of these patients achieved sustained BP control, respectively. Ageing and dyslipidaemia showed significant and independent positive predictive value for the achievement of the recommended BP treatment targets, whereas European SCORE resulted a negative and independent predictor in outpatients treated with monotherapies. CONCLUSIONS: Our data showed a persistent use of monotherapy in the clinical practice, though with unsatisfactory BP control, especially in light of the BP treatment targets suggested by the last hypertension guidelines.

Epidemiological Impact and Clinical Consequences of Masked Hypertension: A Narrative Review.

Masked hypertension (MHT) is a clinical condition characterized by normal blood pressure (BP) levels during clinical consultation and above normal out-of-office BP values. MHT is associated to an increased risk of developing hypertension-mediated organ damage (HMOD) and major cardiovascular (CV) outcomes, such as myocardial infarction, stroke, and hospitalizations due to CV causes, as well as to metabolic abnormalities and diabetes, thus further promoting the development and progression of atherosclerotic disease. Previous studies showed contrasting data on prevalence and clinical impact of MHT, due to not uniform diagnostic criteria (including either home or 24-h ambulatory BP measurements, or both) and background antihypertensive treatment. Whatever the case, over the last few years the widespread diffusion of validated devices for home BP monitoring has promoted a better diagnostic assessment and proper identification of individuals with MHT in a setting of clinical practice, thus resulting in increased prevalence of this clinical condition with potential clinical and socio-economic consequences. Several other items, in fact, remain unclear and debated, particularly regarding the therapeutic approach to MHT. The aim of this narrative review is to illustrate the clinical definition of MHT, to analyze the diagnostic algorithm, and to discuss the potential pharmacological approaches to be adopted in this clinical condition, in the light of the recommendations of the recent European hypertension guidelines.

Awareness of major cardiovascular risk factors and its relationship with markers of vascular aging: Data from the Brisighella Heart Study.

BACKGROUND AND AIM: General population awareness about cardiovascular risk factors is usually low. The aim of the present study was to evaluate the vascular aging of subjects aware and not aware to be hypertensive, hypercholesterolemic, hypertriglyceridemic or diabetics in a general population sample. METHODS AND RESULTS: We interviewed 1652 subjects without atherosclerotic cardiovascular diseases (M: 46.6%, F: 53.4%) about their awareness of hypertension, hypercholesterolemia, hypertriglyceridemia or type 2 diabetes. Then we compared the augmentation index and pulse wave velocity of subjects aware and not aware of the investigated cardiovascular risk factors. 1049 participants declared not to be hypertensive, while 32 were not sure. Among them, respectively, 23.5% and 50% were hypertensive. Subjects not aware of their hypertension had significantly higher aortic blood pressure than aware ones (p < 0.001). 841 participants declared not to be hypercholesterolemic, while 60 were not sure. Among them, respectively, 18.1% and 40% were hypercholesterolemic. Subjects not aware of their hypercholesterolemia had significantly higher augmentation index than the aware ones (p < 0.05). 1226 participants declared not to be hypertriglyceridemic, while 200 were not sure. Among them, respectively, 19.2% and 44% were hypertriglyceridemic. Subjects not aware of their hypertriglyceridemia had significantly higher TG levels aware ones (p < 0.05), although this seemed to not related to increased arterial stiffness. 1472 participants declared not to be diabetic, while 20 were not sure. Among them, respectively, 2.0% and 25.0% were diabetics. Subjects not aware of their diabetes had significantly higher augmentation index than the aware ones (p < 0.05). CONCLUSIONS: In conclusion, the lack of awareness of hypertension and hypercholesterolemia is relatively frequent in the general population and is associated to significantly higher arterial stiffness.

Blood Pressure Targets Achievement According to 2018 ESC/ESH Guidelines in Three European Excellence Centers for Hypertension.

INTRODUCTION: The most recent European guidelines on hypertension redefined office blood pressure (BP) treatment targets according to age strata and cardiovascular (CV) risk profile. AIM: To evaluate proportions of adult outpatients achieving office BP treatment targets recommended by current compared to previous hypertension guidelines. METHODS: We extracted data from medical databases of adult outpatients followed in three excellence centers in hypertension (Rome, Italy; L'Aquila, Italy; Valencia, Spain). Office BP treatment targets were defined according to either 2013 ESH/ESC guidelines (< 140/90 mmHg in non-diabetic individuals aged 18-80 years, < 150/90 mmHg in those aged ≥ 80 years, and < 140/85 mmHg in diabetic individuals), or 2018 ESC/ESH guidelines: (< 130/80 mmHg in individuals aged 18-65 years, < 140/80 mmHg in those aged 65-79 and ≥ 80 years). SCORE risk was assessed in all patients. RESULTS: From an overall sample of 14,229 adult subjects, 4049 (28.5%) resulted normotensive individuals, 3088 (21.7%) were untreated and 7092 (49.8%) treated hypertensive outpatients. Treated hypertensives showed significantly higher ESC score risk (8.3 ± 13.0% vs. 3.9 ± 8.4%; P < 0.001) and lower systolic/diastolic BP (140.6 ± 18.8/83.9 ± 11.5 vs. 148.3 ± 14.2/94.7 ± 10.1 mmHg; P < 0.001) than untreated hypertensives. Compared to previous guidelines, BP control significantly lowered in non-diabetic outpatients (n = 5847) of all age groups [18-65 years: (13.1% vs. 42.9%), 65-79 years (25.8% vs. 42.5%) and ≥ 80 years (29.1% vs. 66.0%); P < 0.001 for all comparisons]; similar reductions were observed in diabetic outpatients (n = 1245) [18-65 years (32.7% vs. 14.8%), 65-79 years (37.3% vs. 24.7%) and ≥ 80 years (47.1% vs. 27.9%); P < 0.001]. CONCLUSIONS: According to the recommended new office BP treatment targets, the proportions of treated uncontrolled hypertensive patients substantially increased. These findings should prompt a tighter application of therapeutic recommendations and, thus, highlight the need for improving hypertension management and control strategies.

Effects of dual inhibition of renin-angiotensin-aldosterone system on cardiovascular and renal outcomes: balancing the risks and the benefits.

Chronic kidney disease is a worldwide health problem often burdened by severe cardiovascular complications. Hypertension represents one of the most important risk factor in affecting cardiovascular profile of chronic kidney disease patients. Since renin-angiotensin-aldosterone system plays a major role in determining cardiovascular outcome, guidelines recommend the use of renin-angiotensin-aldosteron inhibitors in order to control hypertension.

Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies.

Results of previous clinical trials evaluating the effect of pycnogenol supplementation on blood pressure (BP) are controversial. Therefore, we aimed to assess the impact of pycnogenol on BP through a systematic review of literature and meta-analysis of available randomized, double-blind, placebo-controlled clinical studies (randomized clinical trials [RCTs]). Literature search included SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases up to January 10, 2019 to identify RCTs investigating the impact of pycnogenol on BP. Two investigators independently extracted data on study characteristics, methods, and outcomes. This systematic review and meta-analysis is registered in International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42018112172. Overall, the impact of pycnogenol on BP was reported in 7 trials involving 626 participants. Meta-analysis did not suggest any significant improvement in systolic BP (weighted mean difference [WMD]: -0.028 mm Hg; 95% confidence interval [CI]: -0.182 to 0.127; P = .726; I2 = 46%), diastolic BP (WMD: -0.144 mm Hg; 95% CI: -0.299 to 0.010; P = .067; I2 = 0%), mean arterial pressure (WMD: -0.091 mm Hg; 95% CI: -0.246 to 0.063; P = .246; I2 = 0%), and pulse pressure (WMD: -0.003 mm Hg; 95% CI: -0.151 to 0.158; P = .966; I2 = 0%) following pycnogenol treatment. Results persisted in the leave-one-out sensitivity analysis. Therefore, the present meta-analysis does not suggest any significant effect of pycnogenol on BP.

Conventional and new electrocardiographic criteria for hypertension-mediated cardiac organ damage: A narrative review.

Hypertension-mediated organ damage (HMOD) is frequently observed in hypertensive patients at different cardiovascular (CV) risk profile. This may have both diagnostic and therapeutic implications for the choice of the most appropriate therapies. Among different markers of HMOD, the most frequent functional and structural adaptations can be observed at cardiac level, including left ventricular hypertrophy (LVH), diastolic dysfunction, aortic root dilatation, and left atrial enlargement. In particular, LVH was shown to be a strong and independent risk factor for major CV events, namely myocardial infarction, stroke, congestive heart failure, CV death. Thus, early identification of LVH is a key element for preventing CV events in hypertension. Although echocardiographic assessment of LVH represents the gold standard technique, this is not cost-effective and cannot be adopted in routine clinical practice of hypertension. On the other hand, electrocardiographic (ECG) assessment of HMOD relative to the heart is a simple, reproducible, widely available and cost-effective method to assess the presence of LVH, and could be preferred in large scale screening tests. Several new indicators have been proposed and tested in observational studies and clinical trials of hypertension, in order to improve the relatively low sensitivity of the conventional ECG criteria for LVH, despite high specificity. This article reviews the differences in the use of the main conventional and the new 12 lead ECG criteria of LVH for early assessment of asymptomatic, subclinical cardiac HMOD in a setting of clinical practice of hypertension.

Immigration Emergency in Italy: The Impact of Socioeconomic Status on Blood Pressure Levels and Control.

INTRODUCTION: Nowadays there are more than 5 millions of immigrants (8.3% of general adult population) in Italy. AIM: To evaluate the potential impact of immigration and the possession of a permanent residence on blood pressure (BP) levels and control in a low income population of immigrants from different countries. METHODS: We evaluated clinical characteristics and social status of adult individuals with known diagnosis of hypertension afferent to the Poliambulatorio della Caritas Diocesana in Rome, Italy, between 2010-2016. Subjects were stratified according to their macro-areas of origin (Europe, Asia, Africa, South-America), housing (with or without house), and immigration status (presence or absence of residence permit). BP levels were measured in three consecutive visits according to recommendations from current European Guidelines. RESULTS: From an overall population sample of 9827 adult individuals, we initially identified 994 patients with a diagnosis of hypertension (10.1%), among whom 536 (5.4%) had valid BP data. Among these, 50.6% came from Europe, 21.6% from Africa, 24.1% from Asia, and 3.7% from South-America. They were predominantly male (54.7%), middle aged (42.8 ± 12.1 years at arrival and 51.6 ± 10.6 years at first visit) and untreated (72.8%) individuals with baseline systolic/diastolic BP levels of 156.9 ± 22.2/97.3 ± 12.4 mmHg). BP levels remained higher in homeless than in housed people at both visit 2 (150.0 ± 21.8/92.6 ± 12.9 mmHg vs. 142.9 ± 19.3/89.9 ± 11.6 mmHg; P < 0.001) and visit 3 (147.9 ± 22.2/91.7 ± 12.5 mmHg vs. 141.8 ± 19.4/89.2 ± 12.0 mmHg; P = 0.013). We also observed reductions of both systolic and diastolic BP levels compared to baseline values in immigrants stratified according to residence permit, although without relevant differences among groups. CONCLUSIONS: Beyond conventional risk factors, socio-economic issues, including lack of residence permit or habitation, may affect BP levels and control in frail populations of immigrants, which have been marginally considered before.

Achievement of low density lipoprotein (LDL) cholesterol targets in primary and secondary prevention: Analysis of a large real practice database in Italy.

BACKGROUND AND AIMS: Target and intensity of low-density lipoprotein cholesterol (LDL-C) lowering therapy should be tailored according to the individual global cardiovascular (CV) risk. We aimed at retrospectively evaluating real-life LDL-C goal attainment and predictive factors for predefined LDL-C therapeutic goals both in primary and secondary prevention. METHODS: We collected data from a large cohort of outpatients aged 40-65 years, followed by general practitioners, cardiologists and diabetologists in Italy. All data were centrally analysed for global CV risk assessment and rates of control of major CV risk factors, including LDL-C. Study population was stratified according to the presence or absence of previous CV events, including coronary artery disease (CAD), peripheral artery disease (PAD) or stroke/TIA. CV risk profile characterization was based on the European SCORE. Predefined therapeutic goals were set according to the European guidelines on dyslipidaemia: LDL-C levels <70 mg/dl for very high CV risk patients in primary prevention and for those in secondary prevention; <100 mg/dl LDL-C levels for high CV risk patients in primary prevention. Logistic regression analysis with clinical covariates was used to identify predictive factors for achieving these goals; lipid lowering therapy entered in the analysis as continuous (model 1) or categorical variable (model 2). RESULTS: We included 4,142 outpatients (43,7% female, age 58.0 ±â€¯5.2 years, BMI 28.5 ±â€¯5.0 kg/m2) among whom 2,964 (71.6%) in primary and 1,178 (28.4%) in secondary prevention. In primary prevention, none of the patients at very high CV risk had LDL-C <70 mg/dl and 8.9% of patients at high CV risk showed LDL-C <100 mg/dl. Only 5.8% of patients in secondary prevention had LDL-C levels <70 mg/dl, specifically 6.5% of patients with CAD, 2.6% of patients with PAD and 4.7% of patients with CVD (p < 0.001). Beyond diabetes and lipid lowering therapy, high risk SCORE estimation resulted a strong and independent predictor for the lack of achieving all predefined therapeutic targets, including LDL-C <100 mg/dl [OR: 0.806 (0.751-0.865)); p < 0.001], and LDL-C <70 mg/dl [OR: 0.712 (0-576-0.880); p = 0.002], in primary prevention. CONCLUSIONS: Despite high or very high SCORE risk and use of lipid lowering therapies, we observed poor achievement of LDL-C targets in this large cohort of outpatients followed in a setting of real practice in Italy.

Molecular and clinical implications of natriuretic peptides in aortic valve stenosis.

Aortic valve stenosis (AS) is the most common heart valve disease in North America and Europe leading to an increased risk of heart failure and death. A multidisciplinary evaluation of symptoms, individual risk profile, echocardiographic parameters, biomarkers assessment is required for an appropriate clinical and therapeutic management of AS. The natriuretic peptides (NPs) represent an important biomarker for diagnostic, prognostic and therapeutic purposes in several cardiovascular diseases. The present review article provides an overview of the current knowledge on the role of NPs in the pathogenesis, diagnosis, risk stratification and potential therapeutic implications in AS. C-type natriuretic peptide (CNP) level is reduced in AS, favoring the formation of calcified aggregates and an increased expression of bone-related transcripts and proteins (Runx2, osteonectin, osteocalcin, alkaline phospahatase). Consistent results were obtained through the inhibition of the type A and B natriuretic peptide receptors (NPRA, NPRB) and of the proprotein convertase furin expression. Increased plasma B-type natriuretic peptide (BNP) level contributes to monitor the progression of AS and to identify patients who would most benefit from an early therapeutic intervention, such as surgical or transcatheter aortic valve replacement. Moreover, a risk stratification of AS patients that takes into account the NPs level has a major impact toward the occurrence of heart failure, syncope and sudden cardiac death. Finally, the development of novel therapeutic strategies, such as the neprilysin inhibition, may represent a suitable pharmacological approach for the treatment of AS. Due to the above mentioned multiple roles, NPs represent key players in AS development, management and treatment.