The substantial weight loss achieved with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin agonists has transformed the management of obesity and cardiometabolic risk. However, the accompanying reduction in lean mass has raised concerns regarding potential sarcopenia and impaired physical function, particularly in older adults. These concerns have become increasingly relevant as incretin-based therapies assume a central role in cardiovascular prevention. Importantly, reductions in lean mass measured by dual-energy X-ray absorptiometry and other body-composition techniques do not necessarily reflect deterioration in muscle quality, strength, or functional capacity. We propose that a substantial proportion of the observed decline in lean mass represents a physiological adaptation to the reduced mechanical loading associated with marked weight loss. Obesity imposes chronic biomechanical overload on weight-bearing musculature, promoting compensatory increases in muscle mass. Conversely, successful weight reduction lowers mechanical demands and may induce adaptive remodeling of antigravity muscles toward a new equilibrium appropriate for a lighter body. This interpretation is supported by established principles of unloading physiology derived from studies of immobilization, bed rest, and microgravity, as well as by emerging concepts linking body-weight sensing to musculoskeletal adaptation. We present a conceptual framework in which energy deficit, improvements in tissue composition, and mechanical unloading act as complementary contributors to lean mass reduction during GLP-1 RAs therapy. We also propose testable predictions that may help distinguish adaptive remodeling from pathological muscle loss (Fig. 1). From a cardiovascular prevention perspective, the key question may not be whether lean mass decreases during successful obesity treatment, but whether these changes impair physical function or diminish the substantial cardiometabolic benefits of weight reduction. Recognizing mechanical unloading as an underappreciated explanatory framework for interpreting lean mass loss during incretin-based therapy may improve risk-benefit assessment and redirect attention toward clinically meaningful outcomes, including muscle strength, physical performance, mobility, and cardiovascular health.
Achievement of blood pressure targets in hypertensive patients is a challenge for clinicians despite the different classes of drugs currently available. For this reason, taking advantage of the technological progress, new interventional strategies have been proposed. Each of these approaches acts on autonomic and vascular regulation, critical components of hypertension pathophysiology with the aim to recalibrate aberrant sympathetic activation and vascular dysfunction. Renal artery denervation is the only modality currently supported by guideline recommendations in selected patients. Baroreflex activation therapy, and carotid body modulation, thanks to good experimental results, are under evaluation as promising strategies. Concurrently, newer modalities, such as deep brain stimulation, cardiac neuromodulation, and arteriovenous shunts, are emerging with promising early data. The present narrative review provides an overview of interventional treatments for hypertension, describing their efficacy, mechanism of action, safety, and side effects. As clinical research progresses, there is the possibility that these techniques will emerge as promising treatment options for patients with resistant hypertension in the near future.
The 2025 European Society of Cardiology (ESC) Guidelines on cardiovascular disease in pregnancy introduce a life-course approach to cardiovascular prevention, extending risk assessment and management from preconception through the postpartum period. Beyond the management of established cardiovascular disease, the guidelines emphasize the importance of identifying modifiable risk factors and pregnancy-related complications as early markers of future cardiovascular risk. This narrative mini-review provides a prevention-oriented interpretation of the 2025 ESC Guidelines, focusing on their implications for hypertension prevention and long-term cardiovascular health in women. Pregnancy is increasingly recognized as a biological stress test capable of unmasking latent cardiometabolic and vascular vulnerability, while adverse pregnancy outcomes, including preeclampsia, gestational hypertension, gestational diabetes, fetal growth restriction, and preterm delivery, represent important predictors of future hypertension and cardiovascular disease. Particular emphasis is placed on preconception cardiovascular assessment, lifestyle optimization, obesity management, and the cardiovascular implications of assisted reproductive technologies. The Pregnancy Heart Team is discussed as a multidisciplinary model for integrating cardiovascular and obstetric care across the reproductive continuum. In addition, we propose a practical life-course prevention framework incorporating structured postpartum surveillance, blood pressure monitoring, cardiometabolic screening, and long-term follow-up after adverse pregnancy outcomes. By translating contemporary ESC recommendations into a clinically applicable prevention strategy, this review highlights pregnancy as a unique opportunity for early cardiovascular risk identification and implementation of sex-specific preventive interventions aimed at reducing the future burden of hypertension and cardiovascular disease in women.
Orforglipron, an oral non-peptide GLP-1 receptor agonist, improves multiple cardiometabolic risk factors. However, prior modeling used only the 2013 Pooled Cohort Equations (PCE), which ignore body mass index (BMI), estimated glomerular filtration rate (eGFR), and hemoglobin A1c (HbA1c). We re-evaluated its cardiovascular benefit using the 2023 AHA PREVENT equations, which account for more nuanced variables. To compare the projected cardiovascular risk reduction from orforglipron when modeled using the 2013 PCE versus the 2023 AHA PREVENT equations, and to quantify the additional exploratory cardiometabolic benefit captured by PREVENT’s equations. In this post-hoc analysis, we applied pooled effect estimates from our systematic review and meta-analysis of five orforglipron RCTs to representative hypothetical patient profiles. We calculated 10-year and 30-year Cardiovascular disease (CVD) risk using the 2013 PCE and the 2023 PREVENT equations (base and HbA1c-enhanced models) at baseline and after modeled treatment effects at each dose (12, 24, 36, and 45 mg). Absolute and relative risk reductions were compared across tools. A sensitivity analysis was performed using the 95
Orthostatic hypotension (OH) is defined as a decline in systolic blood pressure of at least 20 mmHg or a reduction in diastolic blood pressure of at least 10 mmHg, within the first 3 min of standing. To evaluate the prevalence of OH and to identify the characteristics of patients with OH in hypertensive patients hospitalized in medical inpatient departments. A multicenter, observational, prospective study (FADOI-HYP-OP) included 1000 hypertensive inpatients from 29 Departments throughout Italy. Demographic, clinical data, blood pressure and the presence of comorbidities were recorded at baseline. Factors associated with OH were assessed in multiple logistic regression analysis. The prevalence of OH was 25.1
Radiofrequency renal denervation (RF RDN) has achieved meaningful clinical benefit as an adjunct treatment for uncontrolled and resistant hypertension. This analysis evaluated the cost-effectiveness and budget impact of RF RDN in Italy. A previously published and validated Markov model was adapted to project strategy-specific costs, quality-adjusted life years (QALY), and clinical events over a lifetime horizon for RF RDN and standard of care (SOC) cohorts. The model consisted of seven primary health states, with state transitions informed by multivariate risk equations. Italian costs, utilities, and survival data informed key model inputs. Clinical data from the SPYRAL HTN-ON MED trial informed the base case treatment effect (− 4.9 mmHg reduction in office systolic blood pressure vs. sham), with alternative effect sizes explored in sensitivity analyses. Cost-effectiveness was evaluated against a threshold of €25,000 per QALY gained. The ten-year budget impact was evaluated. Over ten years, RF RDN was associated with meaningful reductions in relative risk for: myocardial infarction (0.88), stroke (0.80), and heart failure (0.72). Over lifetime, RF RDN added €3,418 in costs and 0.41 QALYs, resulting in an incremental cost-effectiveness ratio of €8282 per QALY gained. RF RDN was cost-effective across all scenarios explored. At ten years, RF RDN uptake among resistant hypertension patients was associated with per-patient cost savings of − €4302 (€8526 RF RDN vs. €12,829 SOC) from avoided clinical events. RF RDN was cost-effective over a lifetime horizon, with the associated increase in ten-year budget impact justified by corresponding reductions in clinical events.
It has been reported that glucagon-like peptide-1 (GLP-1) agonists or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists exert beneficial effects on blood pressure and lipid profile. However, the impact of triple agonist retatrutide on these metabolic markers remains to be elucidated. This meta-analysis aims to investigate the effect of retatrutide on blood pressure and lipid levels through a meta-analysis of randomized controlled trials. The search process was performed in PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases using MeSH terms and keywords. For meta-analysis, a random-effects model and the generic inverse variance method were used. The meta-analysis showed that retatrutide significantly decreases systolic blood pressure (WMD: − 6.79 mmHg, 95
INTRODUCTION:Voluntary users of mobile health (mHealth) apps indicate an interest in lowering cardiovascular disease (CVD) risk. It is unclear by which extent blood pressure (BP) or cholesterol treatment targets are achieved in such individuals. AIM:This study aimed to evaluate the attainment of guideline-recommended BP and cholesterol targets across different CVD risk categories among mHealth app users. METHODS:We grouped users of the publicly available German mHealth app HerzFit, who donated their data for scientific evaluations, into individuals with "low-to-moderate risk", "high risk" and "very high risk" of future CVD events. Risk factor control was assessed according to presence of antihypertensive or cholesterol-lowering treatment and achievement of guideline-recommended BP and cholesterol treatment targets. RESULTS:Individual data sets from 1,230 HerzFit users without CVD who provided BP and cholesterol levels were used for the analysis. 471 users were categorized as low (-to-moderate) risk (38.3%), 595 as high risk (48.4%), and 164 as very high risk (13.3%). Antihypertensive treatment was reported in 36.9% of low-risk individuals, 58.2% of high-risk individuals (p<0.001 vs. low), and 59.1% of very high-risk individuals (p<0.001 vs. low). Cholesterol-lowering therapy was present in 29.3%, 41.7% (p<0.001 vs. low), and 40.9% (p=0.01 vs. low), respectively. Use of high-intensity statins (9%) and statin-ezetimibe combinations (5%) was low across all risk groups. BP control was achieved in 79.0% of low-risk individuals, 65.4% of high-risk individuals (P<0.001 vs. low) and 48.2% of very high-risk individuals (p<0.001 vs. low). Respective numbers for cholesterol control were 30.4%, 12.8% (p<0.001 vs. low) and 11.0% (p<0.001 vs. low). CONCLUSIONS:Despite being treated more frequently, individuals at high or very-high risk achieved poorer BP and cholesterol control compared to individuals at low-to-moderate risk. Thus, effective medications are particularly underutilized in individuals at high risk for future CVD events, despite an expressed interest in management of cardiovascular health.
The Atherogenic Index of Plasma (AIP), ratio between triglycerides and high-density lipoprotein cholesterol, has been associated with cardiovascular (CV) events, metabolic syndrome and hypertension (HT)-related vascular organ damage. However, the majority of the published studies suffer from important limitations, such as the cross-sectional or retrospective nature and the performance in selected Asian populations only. We performed a data analysis in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, examining longitudinally the relationships between AIP, diabetes mellitus (DM), HT and left ventricular hypertrophy (LVH) in a western European general population. At the study entry baseline data were collected in 2035 subjects, while longitudinal data were obtained in 1412 subjects examined for a median follow-up time lasting 10.7 years. 50.6
Unattended blood pressure (BP) measurement was introduced following the results of the SPRINT study. Conflicting results have been reported in relation to the concordance between unattended BP, attended BP and 24-hour ambulatory monitoring (ABPM). To evaluate the concordance between measurements of BP in unattended, attended and ABPM modes, and to analyse sex differences in the diagnostic accuracy in relation to the 24h ABPM. 307 patients were enrolled in 6 hypertension centers belonging to the Italian Society of Hypertension. Patients underwent BP measurement in unattended and attended modes before ABPM. BP was defined as controlled if the 24-hour average blood pressure was <130/80 mmHg on ABPM. Patients with 59.6 ±13.6 years, with a female prevalence of 48
Renal denervation (RDN) has re-entered the therapeutic landscape of hypertension following contemporary sham-controlled trials demonstrating reproducible reductions in blood pressure. However, variability in treatment response remains a defining feature, raising important questions regarding its clinical applicability. Emerging evidence indicates that this heterogeneity is primarily attributable to differences in patient phenotype rather than limitations of device technology. This narrative review synthesizes evidence from randomized trials, meta-analyses, and key observational studies to examine determinants of response to RDN across clinical and mechanistic domains. Particular emphasis is placed on hypertension phenotype, ambulatory blood pressure characteristics, baseline blood pressure levels, medication adherence, sympathetic nervous system activity, renal artery anatomy, and associated comorbid conditions. Available data consistently suggest that patients with sustained hypertension confirmed by ambulatory monitoring, higher baseline blood pressure, and features indicative of sympathetic overactivity derive greater benefit from denervation. In contrast, pseudoresistance, white-coat hypertension, advanced vascular stiffness, and unfavorable anatomical characteristics are associated with attenuated or inconsistent responses. Reinterpretation of contemporary trial data further indicates that the magnitude of blood pressure reduction, although moderate, is clinically meaningful when applied to appropriately selected populations. These findings support a shift toward mechanism-based, phenotype-guided patient selection as a means to reconcile prior inconsistencies, optimize clinical implementation, and inform future research. Within this framework, RDN may be more appropriately positioned as a targeted adjunctive therapy in personalized hypertension management.
Hypertension-mediated organ damage (HMOD) is well established in the heart, kidneys, and vasculature; however, early markers of cerebral involvement remain poorly defined. This multicenter, cross-sectional Brazilian study investigated impaired intracranial compliance (ICC) across hypertension (HT) stages in adults without neurological disease or antihypertensive therapy, aiming to characterize early cerebral hemodynamic changes potentially related to hypertension-mediated brain organ damage. ICC was assessed noninvasively from intracranial pressure (ICP) waveforms using the P2/P1 ratio and time-to-peak (TTP). A total of 252 participants were included (52.4
Cognitive decline and dementia are frequent consequences of atherosclerosis and hypertension.Indeed, recent guidelines have identified cognitive decline as a major consequence of high blood pressure and one of the therapeutic targets in hypertension. Unfortunately, early assessment of cognitive decline in the clinical practice is often difficult due to the heterogeneity and the variable severity of the clinical presentations and manifestations.It would be of great help to rely on reproducible clinical markers that can herald the early onset of cognitive decline and can help in assessing the severity or guiding management on the basis of the response to treatment. In such a context, a link between natriuretic peptides (NPs), cognitive function and hypertension has been reported.The aim of this article is to analyse and update the available evidence in support of NPs as a potential biomarker of cognitive decline with regard to the context of hypertension and to identify potential future clinical diagnostic and therapeutic applications.
Aortic stenosis (AS) and hypertension (HTN) frequently co-exist in older adults, worsening disease progression and increasing mortality risk compared to either condition alone. To examine mortality trends and demographic-geographic disparities from comorbid AS and HTN in the U.S. from 1999–2020. Data were extracted from the CDC WONDER Multiple Cause of Death database. Crude and age-adjusted mortality rates (CMRs, AAMRs) per 100,000 were calculated. Joinpoint regression estimated annual (APC) and average annual percent change (AAPC). Trends were projected to 2030 using an autoregressive integrated moving average (ARIMA) model. Between 1999 and 2020, 100,507 deaths were attributed to comorbid AS and HTN. The overall AAMR significantly increased (AAPC: 5.01
Blood pressure variability (BPV) predicts cardiovascular risk beyond average BP, but evidence on the role of anxiety/depression on BPV in older adults is limited. To evaluate the association of anxiety and depressive symptoms with short-term BPV and white-coat effect (WCE) in older outpatients undergoing ambulatory blood pressure monitoring (ABPM). Cross-sectional multicenter study of outpatients aged ≥ 65 years undergoing 24-h ABPM across Italian geriatric centers. Anxiety and depressive symptoms were assessed with GAD-7, STAI-Y1/Y2 and GDS-15. Short-term BPV was quantified by daytime systolic average real variability (ARV). The office-daytime BP difference was calculated (ΔSBP and ΔDBP), and WCE was defined categorically as ΔSBP ≥ 20 mmHg and/or ΔDBP ≥ 10 mmHg. Multivariable models were adjusted for clinical and pharmacological confounders. Among 235 outpatients (median age 76.4 years, 60.0
Super Normal Vascular Aging (SUPERNOVA) describes individuals whose vascular system remains protected, despite exposure to cardiovascular risk factors. Understanding the determinants of arterial stiffness in this population may provide valuable insights into protection mechanisms. This study aims to investigate the key features of SUPERNOVA individuals and examine factors associated with carotid-femoral pulse wave velocity (cf-PWV) across different age subgroups. This cross-sectional study included individuals referred to a Hypertension Center for blood pressure (BP) evaluation. SUPERNOVA status was defined based on cf-PWV values lower than the age-expected averages derived from European population. Clinical, laboratory, and ambulatory BP measurements were recorded. From a total cohort of 829 participants, 37.2
Statin therapy up-titration is hindered in heart-transplant (HT) recipients due to concern for pharmacological interactions and side effects. Alternative lipid lowering therapies (LLT) are now available for patients who are poorly tolerant to statins or those with significant dyslipidaemia despite maximal dose statin treatment and dietary advice. Real-world studies with non-statin LLT are limited in HT population. To examine the lipid status of HT patients following the increased adoption of non-statin lipid lowering therapies. Single centre retrospective observational cohort study including adult HT patients under follow-up in a tertiary centre. From August 2024 to March 2025, 238 patients had lipid profile, prevalence of statin and non-statin LLT prescription assessed and compared to the same data measured in 2019/2020. Patients had a median age of 64 (IQR=53.3–72.0) years, 27
INTRODUCTION:The Naples Prognostic Score (NPS) has demonstrated prognostic value in oncology and certain chronic diseases. Its utility in cardio-renal-metabolic multimorbidity (CRMM) remains unexplored. AIM:This study aims to evaluate the association between NPS and all-cause mortality in individuals with CRMM. METHODS:We analyzed data from the National Health and Nutrition Examination Survey (1999-2018) comprising 3,602 adults with CRMM. The NPS was derived from serum albumin, total cholesterol (TC), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR). Weighted Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to evaluate associations between NPS and all-cause mortality. RESULTS:Over a median follow-up of 79 months, 1,621 (41.4%) deaths occurred. After comprehensive adjustment for potential confounders, each 1-point increase in NPS was associated with a 24.6% higher risk of all-cause mortality (HR 1.246, 95% CI 1.150-1.350, P < 0.0001). The HRs for all-cause mortality was 1.133 (95 % CI: 0.846-1.518, P = 0.401) in the medium NPS group and 1.721 (95 % CI: 1.248-2.375, P = 0.0009) in the high NPS group, as compared with the low NPS group. RCS analysis indicated a nonlinear relationship between NPS and all-cause mortality among participants with CRMM (Pnonlinear=0.014). Weighted quantile sum regression analysis identified NLR as the primary contributor to mortality risk (weight: 0.612 at 2 years, 0.580 at 5 years), followed by TC. CONCLUSION:This study identified a positive, nonlinear association between NPS and all-cause mortality in CRMM individuals. The NPS integrates inflammatory, metabolic, and nutritional biomarkers into a practical prognostic tool that may enhance risk stratification and guide personalized management in multimorbidity.
INTRODUCTION:Effective cardiovascular (CV) prevention requires accurate risk estimation and patient engagement, which depends on perceived risk. The Perception of Risk of Heart Disease Scale (PRHDS) is a validated tool, yet clinical thresholds for its brief Italian version are lacking. AIM:To provide further validation of the Brief Italian version of the PRHDS (PRHDS-BI) in a new cohort, examining convergent and divergent validity, and to establish clinical thresholds and a discrepancy index comparing perceived risk with objective estimates. METHODS:285 adults (40-69 years) were involved in this multicentre cross-sectional study (NCT06190743). Participants were without a history of CV disease and completed the PRHDS-BI and the Patient Health Questionnaire-4 (PHQ-4). CV real risk was estimated using the Systematic Coronary Risk Evaluation 2 (SCORE2). Confirmatory Factor Analysis (CFA), correlation analyses, and cut-off definitions were used to validate the scale and analyze risk discrepancies. RESULTS:The PRHDS-BI showed good internal consistency and strong convergent validity. Clinical thresholds were defined by percentiles: scores 6-12 (low/moderate), 13-17 (high), and 18-24 (very high). A significant mismatch emerged: 63.5% of participants at low/moderate actual risk overestimated their risk, while 80% at very high actual risk underestimated it. This perception-reality gap was statistically confirmed. CONCLUSIONS:The PRHDS-BI is a valid tool for assessing CV risk perception. Establishing thresholds allows for tailored risk communication and patient-centered interventions, particularly by nursing professionals in primary prevention settings.
Interventions targeting sympathetic activity, such as renal denervation, have produced only modest blood pressure (BP) reductions. Historically, thoracolumbar sympathectomy (1935–1960) improved BP control and long-term outcomes. Thoracoscopic sympathectomy now applies this principle in a minimally invasive manner, for example in hyperhidrosis and facial blushing. To evaluate the efficacy and safety of thoracoscopic sympathectomy in patients with resistant hypertension. In this small, blinded study of patients with resistant hypertension (24-h systolic BP ≥ 150 mmHg on ≥ 3 antihypertensive agents) five patients were randomized to thoracoscopic sympathectomy (n = 3) or sham (n = 2). All procedures were well tolerated, with no persistent adverse events. At three-year follow-up, the sympathectomy group showed 24-h systolic BP reductions of 26, 62, and 56 mmHg; sham patients had reductions of 49 and 2 mmHg. Biochemical markers of sympathetic activity and heart rate variability showed no significant group differences. Thoracoscopic sympathectomy appears safe, but the study does not allow meaningful conclusions about its effect on BP due to the small sample size and treatment adjustments.
