Patient-reported muscle symptoms and their characterization in a hypertensive population eligible for statin therapy: An exploratory study.

BACKGROUND AND AIMS: Statin-associated muscle symptoms (SAMS) are claimed to be frequent in clinical practice. We evaluated the prevalence and characteristics of patient-reported muscle symptoms (PRMS) attributed to drugs/nutraceuticals in hypertensive patients, focusing the attention on statin treatment. METHODS AND RESULTS: Observational study on 390 consecutive outpatients. All patients were asked the following question: "Have you ever taken a drug/nutraceutical that you think gave you muscle symptoms?". Patients who answered "yes" were evaluated with a modified version of the SAMS-clinical index (SAMS-CI). Mean age: 60.5 ± 13.5 years (males 53.8%.). Patients who have ever taken a statin: 250. Patients who have never taken a statin: 140. Prevalence of PRMS (48.5% of the entire study population) did not differ between groups (p = 0.217). Only age, followed by number of drugs taken, was significantly associated with PRMS at multivariate analysis. A high prevalence of low scores to all the questions of "modified" SAMS-CI was found in both groups. Localization and pattern of PRMS did not differ between groups (p = 0.170). Timing of PRMS onset after starting the drug (p = 0.036) and timing of improvement after withdrawal (p = 0.002) were associated with statin therapy. CONCLUSION: PRMS are highly prevalent among the hypertensive population and are believed to be drug-related, especially with aging and regardless of whether the drug taken is a statin or not. These findings are in line with the growing evidence that subjective muscle symptoms are often misattributed to statins, while they may more likely be related to the nocebo/drucebo effect or to other common undiagnosed conditions.

Role of NT-proBNP and lung ultrasound in diagnosing and classifying heart failure in a hospitalized oldest-old population: a cross-sectional study.

AIM: Diagnosing and classifying heart failure (HF) in the oldest-old patients has technical and interpretation issues, especially in the acute setting. We assessed the usefulness of both N-terminal pro-brain natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) for confirming HF diagnosis and predicting, among hospitalized HF patients, those with reduced ejection fraction (HFrEF). METHODS: We performed a cross-sectional study on 148 consecutive patients aged ≥ 80 years admitted to our Internal Medicine and Geriatrics ward with at least one symptom/sign compatible with HF and NT-proBNP ≥ 125 pg/mL. We measured serum NT-proBNP levels and performed LUS and transthoracic echocardiography (TTE) on admission before diuretic therapy. We divided our cohort into three subgroups according to the left ventricular ejection fraction (LVEF): reduced (LVEF ≤ 40%), mildly-reduced (LVEF = 41-49%) and preserved (LVEF ≥ 50%). RESULTS: The mean age was 88±5 years. Male prevalence was 42%. Patients with HFrEF were 19%. Clinical features and laboratory parameters did not differ between the three subgroups, except for higher NT-proBNP in HFrEF patients, which also had a higher number of total B-lines and intercostal spaces of pleural effusion at LUS. Overall, NT-proBNP showed an inverse correlation with LVEF (r = -0.22, p = 0.007) and a direct correlation with age, total pulmonary B-lines, and intercostal spaces of pleural effusion. According to the ROCs, NT-proBNP levels, pulmonary B-lines and pleural effusion extension were poorly predictive for HFrEF. The best-performing cut-offs were 9531 pg/mL for NT-proBNP (SP 0.70, SE 0.50), 13 for total B-lines (SP 0.69, SE 0.85) and one intercostal space for pleural effusion (SP 0.55, SE 0.89). Patients with admission NT-proBNP ≥ 9531 pg/mL had a 2-fold higher risk for HFrEF (OR 2.5, 95% CI 1.3-4.9), while we did not find any association for total B-lines ≥ 13 or pleural effusion ≥ 1 intercostal space with HFrEF. A significant association with HFrEF emerged for the combination of NT-proBNP ≥ 9531 pg/mL, total B-lines ≥ 13 and intercostal spaces of pleural effusion ≥ 1 (adjusted OR 4.3, 95% CI 1.5-12.9). CONCLUSIONS: Although NT-proBNP and LUS help diagnose HF, their accuracy in discriminating HFrEF from non-HFrEF was poor in our real-life clinical study on oldest-old hospitalized patients, making the use of TTE still necessary to distinguish HF phenotypes in this peculiar setting. These data require confirmation in more extensive and longer prospective studies.

Neutrophil-to-lymphocyte ratio (NLR) predicts mortality in hospitalized geriatric patients independent of the admission diagnosis: a multicenter prospective cohort study.

BACKGROUND: The Neutrophil-to-lymphocyte ratio (NLR) is a marker of poor prognosis in hospitalized older patients with different diseases, but there is still no consensus on the optimal cut-off value to identify older patients at high-risk of in-hospital mortality. Therefore, in this study we aimed at both validating NLR as a predictor of death in older hospitalized patients and assess whether the presence of specific acute diseases can modify its predictive value. METHODS: This prospective cohort study included 5034 hospitalizations of older patients admitted to acute care units in the context of the ReportAge study. NLR measured at admission was considered as the exposure variable, while in-hospital mortality was the outcome of the study. ROC curves with Youden's method and restricted cubic splines were used to identify the optimal NLR cut-off of increased risk. Cox proportional hazard models, stratified analyses, and Kaplan-Meier survival curves were used to analyse the association between NLR and in-hospital mortality. RESULTS: Both continuous and categorical NLR value (cut-off ≥ 7.95) predicted mortality in bivariate and multivariate prognostic models with a good predictive accuracy. The magnitude of this association was even higher in patients without sepsis, congestive heart failure, and pneumonia, and those with higher eGFR, albumin, and hemoglobin (p < 0.001). A negative multiplicative interaction was found between NLR and eGFR < 45 (p = 0.001). CONCLUSIONS: NLR at admission is a readily available and cost-effective biomarker that could improve identification of geriatric patients at high risk of death during hospital stay independent of admitting diagnosis, kidney function and hemoglobin levels.

Blood circulating bacterial DNA in hospitalized old COVID-19 patients.

BACKGROUND: Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. RESULTS: BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65-99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. CONCLUSIONS: The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.

Molecular Therapies in Cardiovascular Diseases: Small Interfering RNA in Atherosclerosis, Heart Failure, and Hypertension.

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.

Effect of Cytomegalovirus Reactivation on Inflammatory Status and Mortality of Older COVID-19 Patients.

Herpesviridae reactivation such as cytomegalovirus (CMV) has been described in severe COVID-19 (COronaVIrusDisease-2019). This study aimed to understand if CMV reactivation in older COVID-19 patients is associated with increased inflammation and in-hospital mortality. In an observational single-center cohort study, 156 geriatric COVID-19 patients were screened for CMV reactivation by RT-PCR. Participants underwent a comprehensive clinical investigation that included medical history, functional evaluation, laboratory tests and cytokine assays (TNF-α, IFN-α, IL-6, IL-10) at hospital admission. In 19 (12.2%) of 156 COVID-19 patients, CMV reactivation was detected. Multivariate Cox regression models showed that in-hospital mortality significantly increased among CMV positive patients younger than 87 years (HR: 9.94, 95% CI: 1.66-59.50). Other factors associated with in-hospital mortality were C-reactive protein (HR: 1.17, 95% CI: 1.05-1.30), neutrophil count (HR: 1.20, 95% CI: 1.01-1.42) and clinical frailty scale (HR:1.54, 95% CI: 1.04-2.28). In patients older than 87 years, neutrophil count (HR: 1.13, 95% CI: 1.05-1.21) and age (HR: 1.15, 95% CI: 1.01-1.31) were independently associated with in-hospital mortality. CMV reactivation was also correlated with increased IFN-α and TNF-α serum levels, but not with IL-6 and IL-10 serum changes. In conclusion, CMV reactivation was an independent risk factor for in-hospital mortality in COVID-19 patients younger than 87 years old, but not in nonagenarians.

Structural Analysis of Social Behavior: Using Cluster Analysis to Examine Intrapsychic Personality Traits Associated With Depression in Women With Breast Cancer.

BACKGROUND: This study aimed to investigate personality traits associated with depression in breast cancer women (BCW). METHODS: Sample: 236 BCW recently diagnosed (early stages). Tests: SASB-Structural-Analysis of Social-Behavior; IPAT-CDQ-Depression. Statistical analysis: cluster K-Means analysis to explore SASB personality-traits considering the 8 SASB clusters (Cl); CDQ scores dichotomized by 50th percentile cutoff (high/low); Pearson's chi square test to compare CDQ levels and SASB traits. RESULTS: Cluster analysis results supported two distinguishable SASB personality traits (for all SASB Cl-Scales P < .001) classified as "Love and Autonomy" (62.2%) and "Control and Hate" (37.8%). Patients with Love/Autonomy traits are spontaneous, accept their deepest feelings and desire to be close to other people (Cl1, Cl2, Cl3, Cl4). They show a medium value of self-control and a low tendency to self-abusive and self-critical behaviors (Cl5, Cl6). They pay attention to themselves and to their needs at emotional and physical levels also if may be occasionally engaged in self-destructive behaviors (Cl7, Cl8). Women with Control/Hate traits are not spontaneous and do not always express emotions (C1, Cl2, Cl3, Cl4) and flexibility in their relationship with others (Cl5, Cl6). In stressful situations, they may ignore the option of choices for self-growth and neglect their needs and those of others (Cl7, Cl8). BCWs with Control/Hate traits scored higher in depression (P <.001) than those with the Love/Autonomy profile. CONCLUSIONS: Healthcare professionals should be aware of these personality traits and their association with depression to identify the psychologically most vulnerable BCW and improve the care they provide them. The psychotherapeutic intervention should be planned to face on the personality problems.

Role of Cardiac Natriuretic Peptides in Heart Structure and Function.

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.

May Measurement Month 2019: an analysis of blood pressure screening results from Italy.

Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness, and blood pressure (BP) control are still unsatisfactory. In 2017 and 2018, respectively >10 000 and >5000 individuals took part in the May Measurement Month (MMM) campaign in Italy, of whom 30.6% and 26.3% were found to have high BP, respectively. To raise public awareness on the importance of hypertension and to collect BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2019. BP measurement, the definition of hypertension, and statistical analysis followed the standard MMM protocol. Screening was conducted in multiple sites by health personnel. Among the 10 182 people screened (females: 52.3%, mean age 58 ± 16years) mean BP was 127/78 mmHg, and 3171 (31.1%) participants had arterial hypertension, of whom 62.1% were aware of being hypertensive. Diabetes, body mass index >25 kg/m2 were associated with higher BP and previous myocardial infarction with lower BP. For the third consecutive year we collected a nation-wide snapshot of BP control in a large sample of individuals. The high participation, with some yearly fluctuations likely due to the limitations of the sampling technique, confirms the power of this kind of health campaign in reaching a significant number of people to raise awareness on health topics.

Disequilibrium between the classic renin-angiotensin system and its opposing arm in SARS-CoV-2-related lung injury.

A dysregulation of the renin-angiotensin system (RAS) has been involved in the genesis of lung injury and acute respiratory distress syndrome 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)/Mas receptor (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 arm 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.

Sodium-glucose co-transporter-2 inhibitors: peculiar "hybrid" diuretics that protect from target organ damage and cardiovascular events.

AIMS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been proven to lead to relevant cardiovascular benefits, regardless of glycemic control function. SGLT2i have on the one hand led to reduction in cardiovascular events such as heart failure and on the other hand to renal protection. Blood pressure reduction and kidney function play a central role in these outcomes. This focused review describes the main mechanisms and clinical aspects of SGLT2i. DATA SYNTHESIS: These drugs act on the proximal renal tubule and behave as diuretics with a "hybrid" mechanism, as they can favour both natriuresis and enhanced diuresis due to an osmotic effect dependent on glycosuria, resulting in blood pressure decrease. The exclusive peculiarity of these "diuretics", which distinguishes them from loop and thiazide diuretics, lies also in the activation of the tubule-glomerular feedback. CONCLUSIONS: This mechanism, resulting in modulation of arterioles' tone and renin secretion, contributes to the favorable outcomes, suggesting a wider use of SGLT2i in internal medicine, nephrology and cardiology.

May Measurement Month 2018: an analysis of blood pressure screening results from Italy.

Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness and blood pressure (BP) control are still unsatisfactory. In 2017, 30.6% of a >10 000 individual sample who took part in the May Measurement Month (MMM) campaign in Italy was found to have high BP. To raise awareness on the hypertension issue and to report BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2018. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Screenings were conducted in multiple sites by health care personnel. Among the 5554 people screened (females: 48.3%, mean age 58 ± 17 years) mean BP was 127/77 mmHg, and after imputations, 1462 (26.3%) participants were found to have high BP levels. Body mass index >25 was associated with higher systolic BP and diastolic BP (DBP), while diabetes was associated with high DBP only. Our data provide a nation-wide snapshot of BP control in a sample of individuals participating in a national health care campaign, and confirm the power of this kind of healthcare-related activities in reaching a significant number of people to raise awareness on health topics. The apparent positive trend in BP control compared to available data from other similar campaigns carried out during the past years needs to be confirmed with more methodologically robust studies.

PCSK9 is Expressed in Human Visceral Adipose Tissue and Regulated by Insulin and Cardiac Natriuretic Peptides.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to and degrades the low-density lipoprotein receptor (LDLR), contributing to hypercholesterolemia. Adipose tissue plays a role in lipoprotein metabolism, but there are almost no data about PCSK9 and LDLR regulation in human adipocytes. We studied PCSK9 and LDLR regulation by insulin, atrial natriuretic peptide (ANP, a potent lipolytic agonist that antagonizes insulin), and LDL in visceral adipose tissue (VAT) and in human cultured adipocytes. PCSK9 was expressed in VAT and its expression was positively correlated with body mass index (BMI). Both intracellular mature and secreted PCSK9 were abundant in cultured human adipocytes. Insulin induced PCSK9, LDLR, and sterol-regulatory element-binding protein-1c (SREBP-1c) and -2 expression (SREBP-2). ANP reduced insulin-induced PCSK9, especially in the context of a medium simulating hyperglycemia. Human LDL induced both mature and secreted PCSK9 and reduced LDLR. ANP indirectly blocked the LDLR degradation, reducing the positive effect of LDL on PCSK9. In conclusion, PCSK9 is expressed in human adipocytes. When the expression of PCSK9 is induced, LDLR is reduced through the PCSK9-mediated degradation. On the contrary, when the induction of PCSK9 by insulin and LDL is partially blocked by ANP, the LDLR degradation is reduced. This suggests that NPs could be able to control LDLR levels, preventing PCSK9 overexpression.

Combination Therapy of Inhaled Indacaterol/Glycopyrronium for Chronic Obstructive Pulmonary Disease in the Very Elderly: Is It Safe? An Electrocardiographic Evaluation.

Cardiovascular (CV) comorbidities in patients with chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality, especially in old and very old subjects. The question if long-acting beta-agonist and long-acting muscarinic antagonist could be associated with the increased prevalence of CV-related adverse effects has puzzled, particularly in the past, specialists involved in the management of respiratory diseases. The safety of these compounds has scarcely been tested in patients aged ≥ 65 years with CV comorbidities, since randomized controlled trials rarely include this subpopulation. However, the fixed combination indacaterol/glycopyrronium has shown a favorable CV safety profile in both healthy volunteers and COPD patients. Thus, we aimed to assess the CV safety pro-- file of the fixed combination indacaterol/glycopyrronium 110/50 µg in a series of COPD patients aged ≥ 80 years with several comorbidities. Our results indicate that this combination is safe in the comorbid elderly, since no significant electrocardiographic abnormalities were recorded after the administration of the inhaled therapy. Only rare and nonclinically significant changes in heart rate and corrected QT interval duration were evident, mainly in females and in patients with concomitant impaired kidney function.

Prognostic Role of NECPAL CCOMS-ICO Tool on One-Year Mortality in a Hospitalized Older Population.

Background: It is essential to establish both the appropriateness of palliative care (PC) and the prognosis in daily clinical practice to guide decision making in the management of older people with multiple advanced chronic diseases. Objectives: We assessed patients who were appropriate for PC using the NECPAL tool in a hospitalized older population and then we investigated its predictive validity on one-year mortality compared with the multidimensional prognostic index (MPI), a validated geriatric prognostic tool. Design: Prospective cohort study. Setting/Subjects: We enrolled 103 older adults hospitalized for acute medical and surgical conditions in a geriatric hospital in Italy. Measurements: The variables of interest were obtained at baseline through interviews of the ward medical staff and by consulting the computerized medical records. Long-term mortality (one-year) was assessed through the analysis of data acquired from hospital or territorial databases or through telephone contact with caregivers. Results: Mean age was 86.8 ± 7.2 years, with a female prevalence of 54.4%. Prevalence of NECPAL+ patients was 65.1%. MPI low risk: 30.1%; moderate risk: 41.7%; severe risk: 28.2%. Patients deceased during follow-up were 54.4%. NECPAL+ patients were more likely to die, even after adjusting for age, sex, and MPI score (hazard ratio [HR] 2.7, p = 0.020). All the NECPAL categories were associated with one-year mortality. MPI showed a better predictive power than NECPAL (area under the curve [AUC] 0.85 vs. 0.75, p = 0.030). After the exclusion of "Comorbidity: ≥2 concurrent diseases" item from NECPAL, its AUC increased to 0.78 with no statistically significant differences from MPI (p = 0.122). Conclusions: NECPAL is useful to identify the appropriateness of PC in hospitalized older adults, also allowing to predict long-term mortality with a performance similar to that of a validated geriatric prognostic tool.

Implementation of the Care Bundle for the Management of Chronic Obstructive Pulmonary Disease with/without Heart Failure.

Chronic obstructive pulmonary disease (COPD) is often part of a more complex cardiopulmonary disease, especially in older patients. The differential diagnosis of the acute exacerbation of COPD and/or heart failure (HF) in emergency settings is challenging due to their frequent coexistence and symptom overlap. Both conditions have a detrimental impact on each other's prognosis, leading to increased mortality rates. The timely diagnosis and treatment of COPD and coexisting factors like left ventricular overload or HF in inpatient and outpatient care can improve prognosis, quality of life, and long-term outcomes, helping to avoid exacerbations and hospitalization, which increase future exacerbation risk. This work aims to address existing gaps, providing management recommendations for COPD with/without HF, particularly when both conditions coexist. During virtual meetings, a panel of experts (the authors) discussed and reached a consensus on the differential and paired diagnosis of COPD and HF, providing suggestions for risk stratification, accurate diagnosis, and appropriate therapy for inpatients and outpatients. They emphasize that when COPD and HF are concomitant, both conditions should receive adequate treatment and that recommended HF treatments are not contraindicated in COPD and have favorable effects. Accurate diagnosis and therapy is crucial for effective treatment, reducing hospital readmissions and associated costs. The management considerations discussed in this study can potentially be extended to address other cardiopulmonary challenges frequently encountered by COPD patients.

Adipocentric origin of the common cardiometabolic complications of obesity in the young up to the very old: pathophysiology and new therapeutic opportunities.

Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, affecting people of all ages. In the last 40 years, the incidence of overweight and obesity almost tripled worldwide. The accumulation of "visceral" adipose tissue increases with aging, leading to several cardio-metabolic consequences: from increased blood pressure to overt arterial hypertension, from insulin-resistance to overt type 2 diabetes mellitus (T2DM), dyslipidemia, chronic kidney disease (CKD), and obstructive sleep apnea. The increasing use of innovative drugs, namely glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2-i), is changing the management of obesity and its related cardiovascular complications significantly. These drugs, first considered only for T2DM treatment, are now used in overweight patients with visceral adiposity or obese patients, as obesity is no longer just a risk factor but a critical condition at the basis of common metabolic, cardiovascular, and renal diseases. An adipocentric vision and approach should become the cornerstone of visceral overweight and obesity integrated management and treatment, reducing and avoiding the onset of obesity-related multiple risk factors and their clinical complications. According to recent progress in basic and clinical research on adiposity, this narrative review aims to contribute to a novel clinical approach focusing on pathophysiological and therapeutic insights.

Prevalence, Clustering, and Current Management of Cardiovascular Risk Factors Upon First Referral to Hypertension Specialists: the APPROACH Study.

INTRODUCTION: Several observational studies have been conducted to assess the prevalence of cardiovascular risk factors in hypertensive patients; however, none has yet investigated prevalence, clustering, and current management of cardiovascular risk factors upon first referral to hypertension specialists, which is the aim of the present study. METHODS: Consecutive adult outpatients with essential/secondary hypertension were included at the time of their first referral to hypertension specialists at 13 Italian centers in the period April 2022-2023 if they had at least one additional major cardiovascular risk factor among LDL-hypercholesterolemia, type 2 diabetes, and cigarette smoking. Prevalence, degree of control, and current management strategies of cardiovascular risk factors were assessed. RESULTS: A total of 255 individuals were included, 40.2% women and 98.4% Caucasian. Mean age was 60.3±13.3 years and mean blood pressure [BP] was 140.3±17.9/84.8±12.3 mmHg). Most participants were smokers (55.3%), had a sedentary lifestyle (75.7%), suffered from overweight/obesity (51%) or high LDL-cholesterol (41.6%), had never adopted strategies to lose weight (55.7%), and were not on a low-salt diet (57.4%). Only a minority of patients reported receiving specialist counseling, and 27.9% had never received recommendations to correct unhealthy lifestyle habits. Nearly 90% of individuals with an estimated high/very high cardiovascular risk profile did not achieve recommended LDL-cholesterol targets. CONCLUSIONS: In patients with hypertension, both pharmacological and lifestyle therapeutic advice are yet to improve before referral to hypertension specialists. This should be considered in the primary care setting in order to optimize cardiovascular risk management strategies.

Validation of the Novel Web-Based Application HUMTELEMED for a Comprehensive Assessment of Cardiovascular Risk Based on the 2021 European Society of Cardiology Guidelines.

Background and aims: SCORE2/SCORE2-OP cardiovascular risk (CVR) charts and online calculators do not apply to patients with comorbidities, target organ damage, or atherosclerotic cardiovascular disease, for whom the assessment relies on the conventional consultation of the 2021 ESC guidelines (qualitative approach). To simplify the CVR evaluation, we developed an integrated multi-language and free-to-use web application. This study assessed the agreement between the conventional method versus our web app. Methods: A cross-sectional study was carried out on 1306 consecutive patients aged 40+ years referred to our center for the diagnosis and management of hypertension and dyslipidemia. Two double-blind operators performed the CVR assessment and classified each patient into low-moderate-, high-, and very-high-risk categories by using the conventional method (SCORE2/SCORE2-OP charts and consultation of the 2021 ESC guidelines) and the web app. The Kappa statistics were used to compare the two methods. Results: The mean age was 60.3 ± 11.9 years, with male prevalence (51.4%). Patients in primary prevention were 77.0%. According to the SCORE2/SCORE2-OP charts and 2021 ESC guideline consultation, the CVR was low-moderate in 18.6% (n° 243), high in 36.8% (n° 480), and very high in 44.6% (n° 583). According to the web app, individual CVR was low-moderate in 19.5% (n° 255), high in 35.4% (n° 462), and very high in 45.1% (n° 589). The two methods strongly agreed (Kappa = 0.960, p < 0.001), with a 97.5% concordance. Conclusions: our application has excellent reliability in a broad "real life" population and may help non-expert users and busy clinicians to assess individual CVR appropriately, representing a free-to-use, simple, time-sparing and widely available alternative to the conventional CVR evaluation using SCORE2/SCORE2-OP and 2021 ESC guideline charts.