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
