AIMS:Hypertension and obesity frequently coexist and synergistically increase cardiovascular (CV) risk. Incretin-based therapies with glucagon-like peptide-1 receptor agonists (GLP-1-RAs), gastric inhibitory polypeptide (GIP)/GLP1-RAs, and glucagon/GIP/GLP-1RAs lead to substantial weight loss. However, their antihypertensive efficacy and safety profile have not been comprehensively quantified. Our study aimed to evaluate the effects of incretin-based therapies on office systolic blood pressure (BP) (SBP), diastolic BP (DBP), all-cause mortality, and key safety outcomes, i.e. hypoglycaemia and pancreatitis episodes, in adults with overweight or obesity. METHODS AND RESULTS:We searched PubMed, EMBASE, and ClinicalTrial.gov from inception to 30 April 2024 for randomized controlled trials (RCTs) comparing incretin-based therapy with placebo and ≥1 month of follow-up. The primary outcome was change in SBP; secondary outcomes were change in DBP, all-cause mortality, hypoglycaemia, and pancreatitis. Random effects meta-analyses generated mean differences (MDs) or risk ratios (RRs) along with 95% confidence intervals (CIs). Heterogeneity was explored with I2 statistics, subgroup analyses, and meta-regression. Eighty-five RCTs encompassing 90 977 participants (median follow-up time 8 months) met the eligibility criteria. GLP1-RAs reduced SBP by 3.4 mmHg (95% CI 2.8-4.0) and DBP by 0.9 mmHg (95% CI 0.5-1.2). A higher weight loss was significantly associated with a greater reduction in BP. The most significant BP reduction was associated with dual (SBP 5.1 mmHg; DBP 1.8 mmHg) and triple (SBP 6.6 mmHg; DBP 2.1 mmHg) receptor agonists. All-cause mortality was reduced by 18% (RR 0.82, 95% CI 0.76-0.90). Incretin-based therapy did not increase the risk of hypoglycaemia (RR 1.05, 95% CI 0.83-1.33) or pancreatitis (RR 0.84, 95% CI 0.61-1.15). CONCLUSION:Incretin-based therapy led to a modest but clinically meaningful BP reduction and lower all-cause mortality in adults with overweight or obesity, without excess in hypoglycaemia or pancreatitis episodes. There was a significant association between weight loss and the reduction in SBP and DBP. Dual and triple agonists exhibited the most pronounced antihypertensive effect. These findings support the use of incretin-based therapies as part of an integrated and multidisciplinary approach to managing obesity and hypertension, with multiple agonists showing particular promise. Our findings also underscore the need for long-term RCTs to clarify weight-independent mechanisms and the durability effect of BP reduction.

BACKGROUND:The role of beta-blockers in the management of uncomplicated arterial hypertension remains a subject of clinical debate. While beta-blockers are established cornerstones for heart failure and post-myocardial infarction care, their independent efficacy in reducing major adverse cardiovascular events (MACE) in patients without these compelling indications is less clear. This study aimed to evaluate the association between beta-blocker use and MACE in a real-world hypertensive population without prevalent cardiovascular diseases. METHODS:We analyzed 6,702 hypertensive patients from the Campania Salute Network (CSN) registry without prevalent coronary or cerebrovascular disease, valvular heart disease, or heart failure. The association between beta-blocker use and MACE was assessed using three statistical approaches: multivariable-adjusted Cox proportional hazards regression, propensity score matching (PSM), and overlap weighting (OW). An intention-to-treat (ITT) analysis was performed based on baseline prescription, and an exploratory per-protocol (PP) sensitivity analysis was conducted to evaluate the role of sustained treatment adherence. RESULTS:At baseline, 18.1% (n=1,247) of patients were receiving a beta-blocker. Over a median follow-up of 52 months, 308 MACE (4.5%) occurred. After multivariable adjustment and weighting, beta-blocker use was not associated with a lower risk of MACE in the ITT population (Adjusted hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.86-1.52; PSM HR 1.18, 95% CI 0.82-1.70; OW HR 1.10, 95% CI 0.82-1.46). In the exploratory PP sensitivity analysis, even among adherent patients, beta-blocker therapy was not associated with a lower risk of MACE. Conversely, adherence to renin-angiotensin system inhibitors and statins was associated with a lower risk of MACE. Beta-blocker users also exhibited a higher prevalence of metabolic risk factors, including elevated triglycerides, glycemia, and uric acid levels. CONCLUSIONS:In patients with uncomplicated hypertension, beta-blocker use was not associated with a lower risk of MACE, regardless of treatment adherence. These findings are consistent with clinical guidelines that prioritize non-beta-blocker regimens and recommend using beta-blockers in the presence of compelling indications.

This review examines the principal preclinical and clinical findings assessing the effects of White Mulberry (Morus Alba Linn) plant extract supplementation currently available. Since it is one of the most cultivated species of mulberry tree, it has caught the eye of researchers for its rich phytochemical profile as well as multi-purpose usages. The leaves, fruits, and other parts of the White Mulberry plant take on the role of valuable sources of bioactive compounds, including flavonoids, phenolic acids, terpenoids, and alkaloids. These secondary metabolites have a wide range of health benefits, such as antioxidant, anti-inflammatory, and antidiabetic properties. Commonly used as dietary supplements, White Mulberry plant extracts have shown their great capacity in improving metabolic profile, decreasing the cardiovascular risk, and supporting overall health.

We aimed to investigate the link between LDL cholesterol (LDL-C) levels and hemorrhage risk over an extended period, both in subjects taking aspirin and in individuals not receiving any antiplatelet agent. We calculated the predicted adjusted relative hazard of bleeding by LDL-C concentration for the whole cohort and the aspirin-treated subgroup. The study included 39,784 individuals with a mean follow-up of 14.9 years, totaling over 500,000 patient-years. Across the cohort, 3380 bleeding events were reported, with a higher incidence in patients with LDL-C < 70 mg/dL compared to those with LDL-C ≥ 70 mg/dL (9.9 % vs 8.4 %). In aspirin-treated patients, multivariable analysis revealed that hemorrhagic events were significantly associated with aging, male sex, body mass index, hypertension, and LDL-C < 70 mg/dL. These patients had a significantly lower event-free survival probability if their LDL-C was < 70 mg/dL compared to ≥ 70 mg/dL. Low LDL-C values were a significant risk factor (HR >1) while higher LDL-C values were protective (HR <1). A stepwise increase of 10 mg/dL in LDL-C from < 30 to ≥ 200 mg/dL was associated with a decreasing trend for bleeding events in both the entire cohort and the aspirin-treated subgroup. This is the first report specifically addressing the relationship between LDL-C levels and bleeding risk in a population receiving low-intensity antithrombotic therapy. Our data demonstrate that in patients taking aspirin, LDL-C levels below 70 mg/dL significantly increase the risk of bleeding, with major implications for long-term cardiovascular risk management.

Statin therapy has been associated with increased risk of type 2 diabetes (T2D). We investigated the relationship between Low-Density Lipoprotein Cholesterol (LDL-C) plasma concentrations and incident T2D and evaluated the modifying effect of statin therapy in a large population-based cohort. Individuals free of T2D and cardiovascular disease at baseline were followed longitudinally for the development of new-onset T2D. Cox proportional hazards models were applied to evaluate the associations of LDL-C levels and statin therapy with T2D risk. From a population of 202,545 individuals, we selected 13,674 participants free of T2D and cardiovascular disease (of whom 52

The long-term risk of cardiovascular (CV) events in individuals who develop new-onset type 2 diabetes (T2D) after having received statin therapy in primary prevention is mostly unknown. We designed a population-based cohort study in individuals without T2D and atherosclerotic CV disease (ASCVD), divided in two groups according to the presence or not of statin therapy. We also balanced the study groups for demographic and clinical factors using propensity score matching. 119307 individuals without T2D and ASCVD were divided in statin users (N = 90906) or not (N = 28401) and followed-up for 70.1 ± 61.3 months. Yearly incidence of T2D rate was 0.3

Routine assessment of abdominal aorta (AA) is not currently advised by the available guidelines, although hypertension is a major risk factor for the development of AA aneurysm. In the present study, we assessed correlations and predictive factors of AA dimension in a cohort of hypertensive patients. 3083 Patients ≥ 18 years old with available AA ultrasound were included. AA dilatation was defined as an AA diameter ≥ 25 mm. Correlations of AA dimension and dilatation with demographics and metabolic profile were explored. Multivariable regression was also used to identify potential confounders influencing univariate correlations. To evaluate the prognostic impact of AA dilatation a propensity score model was implemented, and survival probability curves were constructed using the Kaplan-Meier method. Increased AA diameter was independently associated with older age, male sex, active smoking, higher diastolic and lower systolic blood pressure, higher LV mass index and aortic root dimension and less use of β-blockers at baseline (all p < 0.05). A significant effect of baseline use of β-blockers and calcium channel blockers therapy were found (all p < 0.01). During a mean follow-up of 4.76 ± 2.91 years, 32 MACE occurred. Kaplan-Meier analysis showed that having AA ≥ 25 mm is associated with significant risk of MACE compared to patients with AA < 25 mm. AA remodeling is strongly influenced by the cardiovascular (CV) risk profile and hypertension mediated target organ damage and AA dilatation contributes to increased CV risk in treated hypertensive patients.

This study aimed to determine whether daily low-dose aspirin reduces the risk of type 2 diabetes (T2D) associated with COVID-19. A longitudinal cohort of 200,000 adults followed from 2018 to 2022 was analyzed, comparing T2D incidence between aspirin users and non-users. Propensity score matching was used to balance the groups. The incidence of T2D was substantially lower in the aspirin group, with Cox regression showing a 52% risk reduction. Kaplan-Meier analysis confirmed a significant divergence in cumulative T2D risk after two years. This protective effect was observed both before and during the COVID-19 pandemic, with a stronger association during the pandemic period. These findings indicate that daily low-dose aspirin significantly reduces the risk of COVID-19-associated new-onset T2D, highlighting the role of inflammation in the pathogenesis of T2D triggered or unmasked by COVID-19.

Background: Acute hypertensive disorders, including hypertensive emergencies (HEs) and urgencies (HUs), are a frequent cause of emergency department (ED) visits. Early differentiation between HEs and HUs is essential, as their clinical management and prognostic implications differ substantially. Methods: We retrospectively analyzed patients admitted to an Italian second-level ED between January and June 2022 with systolic blood pressure (SBP) ≥ 180 mmHg and/or diastolic blood pressure(DBP) ≥ 110 mmHg. Patients were categorized based on the presence of acute hypertension-mediated organ damage (A-HMOD). To identify the main predictors of HEs, we applied both conventional logistic regression and machine learning approaches (Elastic Net and Random Forest). Results: Among 23,678 ED admissions, 261 patients (1.1%) had acute hypertensive disorders, of whom 115 (44%) were diagnosed with HEs and 146 (56%) with HUs. Compared with HU patients, HE patients were older and showed higher SBPand DBP at presentation, along with a greater prevalence of comorbidities such as diabetes, coronary artery disease, and chronic kidney disease (all p < 0.05). In multivariable logistic regression, troponin I levels independently predicted the occurrence of HEs (OR: 2.82; 95%CI: 1.65–4.82; p < 0.001), even after adjusting for confounders. Machine learning analyses confirmed troponin I as the most influential predictor, followed by age and SBP, with the Random Forest model achieving a high predictive performance (AUCROC: 0.93; 95%CI: 0.90–0.96). Elastic Net regression further highlighted troponin I as the most influential variable with the highest standardized coefficient (β = 4.13). As determined by the Youden index, the optimal diagnostic threshold for troponin I was 0.12 ng/mL (AUCROC: 0.66; 95%CI: 0.60–0.72). Conclusions: In patients presenting to the ED, withacute hypertensive disorders, elevated troponin I levels, older age, and higher SBP at admission may serve as early indicators of emergencies.

Prediabetes represents the final stage on the glycemic spectrum before the onset of type 2 diabetes mellitus (T2DM), and delaying its progression offers a unique opportunity to address the growing T2DM epidemic. In this longitudinal cohort study, we investigated the effect of daily low-dose aspirin on the development of T2DM in individuals with prediabetes residing in Naples, Italy, who were followed by their primary care physicians between 2018 and 2022. Outcomes in the aspirin-treated group were compared with those in a control group not receiving aspirin, using data from the same database. Propensity score matching was employed to ensure comparability of covariates at baseline. The primary outcome was the onset of T2DM, defined as a new diagnosis accompanied by antidiabetic prescriptions lasting more than 30 days. Gastrointestinal bleeding was assessed as the safety endpoint. Over the follow-up period, 488 new cases of T2DM were documented (15.6

Recent studies based on hospital and outpatient clinic databases have reported a decline in cancer diagnoses during the COVID-19 pandemic, an observation that has been mainly attributed to halted screenings. We investigated the impact of COVID-19 on cancer incidence in the Campania Region (Italy) among adults followed by their primary care physicians over a 6-year period (2017–2022). Using a single-cohort design, we employed interrupted time series (ITS) analysis to compare cancer incidence rates during the 3 years preceding the pandemic (2017–2019) with those during the three pandemic years (2020–2022). We analyzed data from 212,656 individuals and found that the incidence of new cancer diagnoses rose from 14.3 to 23.1 per 1000 person-years when comparing the pre-pandemic to the COVID-19 period. ITS analysis revealed a stable trend in cancer diagnoses before the pandemic, followed by a marked increase of 8 new cases per month beginning in January 2020, with a peak observed in August 2021. Notably, diagnoses of brain and skin cancers increased by 300

Recent evidence suggests that inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a key enzyme in cholesterol biosynthesis, has beneficial effects on lipid metabolism and blood pressure (BP), but detrimental consequences on glycemia. Nutraceuticals (NUTs) containing both Monacolin K (MK) and Morus alba have been shown to be more effective in lowering lipids compared to NUT formulations containing only MK. However, the effects of these NUTs on glucose homeostasis have not been fully determined. To evaluate the association between LDL-C-lowering therapy and glycemia in patients receiving NUT combinations with or without Morus alba, we analyzed data from a prospective, randomized, active-treatment controlled trial (NCT02898805), which enrolled 359 patients to compare the effects of a NUT combination containing MK alone (Formulation 1, F1; n = 170) versus one containing MK and Morus alba (Formulation 1, F2; n = 189). Participants in the two treatment arms (F1 vs. F2) were comparable in terms of sex, age, metabolic parameters, and BP. After 3 months, both groups experienced significant reductions in LDL-C, fasting plasma glucose, HbA1c, and HOMA index. F2 treatment led to a significantly greater reduction in glycemic levels compared to F1 treatment (b = − 16, p < 0.001). Notably, a divergent trend emerged over time: an inverse relationship between LDL-C and glycemic levels was observed in the F1 group, while a significant direct association between LDL-C and glycemic levels was detected in the F2 group (b = 0.06, p = 0.002). Taken together, our findings indicate that the treatment with a NUT combination containing Morus alba simultaneously reduces plasma levels of LDL-C and glucose.

Aims We evaluated the incidence and relative risk of major post-acute cardiovascular consequences of SARS-CoV-2 infection in a large real-world population from a primary care database in a region at moderate cardiovascular risk followed up in the period 2020-22. Methods and results This is a retrospective cohort analysis using data from a cooperative of general practitioners in Italy. Individuals aged >18 affected by COVID-19 starting from January 2020 have been followed up for 3 years. Anonymized data from 228 266 patients in the period 2020-22 were considered for statistical analysis and included 31 764 subjects with a diagnosis of COVID-19. An equal group of subjects recorded in the same database in the period 2017-19 was used as propensity score-matched comparison as an unquestionable COVID-19-free population. Out of the 228 266 individuals included in the COMEGEN database during 2020-22, 31 764 (13.9%) were ascertained positive with SARS-CoV-2 infection by a molecular test reported to general practitioners. The proportion of individuals with a new diagnosis of major adverse cardiovascular and cerebrovascular events was higher in the 2020-22 COVID-19 group than in the 2017-19 COMEGEN propensity score-matched comparator, with an odds ratio of 1.73 (95% confidence interval: 1.53-1.94; P < 0.001). All major adverse cardiovascular and cerebrovascular events considered showed a significantly higher risk in COVID-19 individuals. Incidence calculated for each 6-month period after the diagnosis of COVID-19 in our population was the highest in the first year (1.39% and 1.45%, respectively), although it remained significantly higher than in the COVID-19-free patients throughout the 3 years. Conclusion The increase of cardiovascular risk associated with COVID-19 might be extended for years and not limited to the acute phase of the infection. This should promote the planning of longer follow-up for COVID-19 patients to prevent and promptly manage the potential occurrence of major adverse cardiovascular and cerebrovascular events. [GRAPHICS]

BACKGROUND. Recent studies conducted in individuals who survived COVID-19 suggest that SARS-CoV-2 infection is associated with an increased risk of dyslipidemia. However, it remains unclear whether this augmented risk is confirmed in the general population and how this phenomenon is affecting the overall burden of cardiometabolic diseases. METHODS. To address these aspects, we conducted a 6-year longitudinal study to examine the broader effects of COVID-19 on dyslipidemia incidence in a real-world population (228,266 individuals) residing in Naples in southern Italy. The pre-COVID-19 and COVID-19 groups were balanced for demographic and clinical factors using propensity score matching. RESULTS. Our analysis spans a period of 3 years during the COVID-19 pandemic (2020-2022), comparing dyslipidemia incidence with pre-pandemic data (2017-2019), with a follow-up of at least 1,095 days corresponding to 21,349,215 person- years. During the COVID-19 period, we detected an increased risk of developing any dyslipidemia when compared with the pre-COVID-19 triennium (OR = 1.29; 95% CI, 1.19-1.39). Importantly, these estimates were adjusted for comorbidities by a multivariate analysis. CONCLUSIONS. Taken together, our data reveal a notable rise in dyslipidemia incidence during the COVID-19 pandemic, suggesting the utility of establishing specialized clinical monitoring protocols for patients who survive COVID-19 to mitigate the risk of developing dyslipidemia.

The low-density lipoprotein cholesterol (LDL-C) lowering decreases the risk to develop major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). Therefore, the “fast track” use of PCSK9 inhibitors (PCSK9i) has been introduced in ACS patients not achieving LDL-C target (70 mg/dl) despite an ongoing lipid lowering therapy with statin at maximum tolerated dosage plus ezetimibe or stain-naïve (LDL-C > 130 mg/dl). PCSK9i “fast track” use has shown to achieve the regression of “non-culprit” atherosclerotic plaques leading to a further MACE decrease. Interestingly, it has been also hypothesized a role of PCSK9i beyond the LDL-C lowering in ACS. PCSK9i have been demonstrated to decrease the inflammation of atherosclerotic plaques and myocardium, inhibit platelet aggregation, and improve the cardiomyocyte survival against the reperfusion injury. All these findings may positively impact on the prognosis and suggest the PCSK9i use in the acute phase of ACS independently on the baseline LDL-C values.

No data are available on the diagnostic algorithms recommended by guidelines for the assessment of diastolic dysfunction (DD) in patients with arterial hypertension. To fill this gap, we evaluated diastolic function in hypertensive patients with and without LVH matched with healthy subjects by applying 2016 American Society of Echocardiography-European Association of Cardiovascular Imaging Guidelines for the evaluation of LV diastolic function. 717 healthy and hypertensives with normal LV ejection fraction and with and without LV hypertrophy (LVH), matched 1:1:1 from two prospective registries, represented the study population. By applying algorithm A, indeterminate pattern was found in 0.4

Objective: We evaluated the incidence and relative risk of major cardiovascular events in a large real-world population from a primary care database in a region at moderate cardiovascular risk in the period 2020-2022 (e.g. during COVID-19 pandemic). Design and method: This is a retrospective cohort analysis using the whole database of a cooperative of general practitioners in the city of Naples, Italy (COMEGEN). All individuals aged >18 were followed up to three years. These data were compared with those derived from the same database in the years 2017-2019, considered as a pre-COVID 19 period. Results: Anonymized data from of 228,266 patients in the period 2020-2022 were considered for statistical analysis (these included 31,764 subjects with a molecular diagnosis of COVID 19). In the 2020-2022 population demographic features and the prevalence of major cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia and smoking) did not differ from those reported in the 2017-2019 cohort (Table 1). On the contrary, the incidence of individuals with a new diagnosis of major adverse cardiovascular and cerebrovascular events was significantly higher in the 2020-2022 compared to the 2017-2019 triennium (Table 1). Conclusions: We report a substantial increase of cardiovascular events during the COVID-19 triennium which is independent of risk factors. Whether this is caused to direct cardiovascular consequences of SARS-CoV-2 (diagnosed or undiagnosed) infection or to other factors such as the reduced access to healthcare facilities cannot be clarified by our present study.