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Background: Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension. Methods: To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy. Results: We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes. Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients. Conclusions: Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

Background: Women have a worse prognosis after ST-segment elevation myocardial infarction (STEMI) than men. The prognostic role of thrombus burden (TB) in influencing the sex-related differences in clinical outcomes after STEMI has not been clearly investigated. Objectives: The aim of this study was to assess the sex-related differences in TB and its clinical implications in patients with STEMI. Methods: Individual patient data from the 3 major randomized clinical trials of manual thrombus aspiration were analyzed, encompassing a total of 19,047 patients with STEMI, of whom 13,885 (76.1%) were men and 4,371 (23.9%) were women. The primary outcome of interest was 1-year cardiovascular (CV) death. The secondary outcomes of interest were recurrent myocardial infarction, heart failure, all-cause mortality, stroke, stent thrombosis (ST), and target vessel revascularization at 1 year. Results: Patients with high TB (HTB) had worse 1-year outcomes compared with those presenting with low TB (adjusted HR for CV death: 1.52; 95% CI: 1.10-2.12; P = 0.01). In unadjusted analyses, female sex was associated with an increased risk for 1-year CV death regardless of TB. After adjustment, the risk for 1-year CV death was higher only in women with HTB (HR: 1.23; 95% CI: 1.18-1.28; P < 0.001), who also had an increased risk for all-cause death and ST than men. Conclusions: In patients with STEMI, angiographic evidence of HTB negatively affected prognosis. Among patients with HTB, women had an excess risk for ST, CV, and all-cause mortality than men. Further investigations are warranted to better understand the pathophysiological mechanisms leading to excess mortality in women with STEMI and HTB.

Background: Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated possible relationships between positron emission tomography/computed tomography–derived myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi). Methods: Seventy-eight patients with hypertensive without flow-limiting epicardial coronary artery disease underwent echocardiography, including MEEi computation, and cardiac positron emission tomography/computed tomography with assessment of MBF/mass ratio at rest and after stress and myocardial flow reserve. The lowest MEEi tertile (MEEi Results: Patients in the lowest MEEi tertile were older, had higher systolic blood pressure and body mass index. They also had higher prevalence of LV hypertrophy, whereas lower resting and stress MBF/mass ratio. MEEi was significantly correlated with both resting (r=0.51; P P P P =0.003) and resting (beta coefficient=0.35; P =0.008) MBF/mass ratio remained significant. Conclusions: In patients with hypertensive without flow-limiting epicardial coronary artery disease, low values of MEEi could detect an early LV dysfunction involving an impairment of both resting and hyperemic MBF/mass ratios. MEEi has the advantage of simpler detection, cheaper costs than positron emission tomography/computed tomography, and a lack of radiation exposure. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02211365.

Nowadays, there are robust clinical and pathophysiological evidence supporting the beneficial effects of physical activity on cardiovascular (CV) system. Thus, the physical activity is considered a key strategy for CV prevention. In fact, exercise training exerts favourable effects on all risk factors for CV diseases (i.e. essential hypertension, type 2 diabetes mellitus, hypercholesterolemia, obesity, metabolic syndrome, etc…). In addition, all training modalities such as the aerobic (continuous walking, jogging, cycling, etc.) or resistance exercise (weights), as well as the leisure-time physical activity (recreational walking, gardening, etc) prevent the development of the major CV risk factors, or delay the progression of target organ damage improving cardio-metabolic risk. Exercise training is also the core component of all cardiac rehabilitation programs that have demonstrated to improve the quality of life and to reduce morbidity in patients with CV diseases, mostly in patients with coronary artery diseases. Finally, it is still debated whether or not exercise training can influence the occurrence of atrial and ventricular arrhythmias. In this regard, there is some evidence that exercise training is protective predominantly for atrial arrhythmias, reducing the incidence of atrial fibrillation. In conclusion, the salutary effects evoked by physical acitvity are useful in primary and secondary CV prevention.

Background Women have a worse prognosis after ST-segment elevation myocardial infarction (STEMI) than men. The prognostic role of thrombus burden (TB) in influencing the sex-related differences in clinical outcomes after STEMI has not been clearly investigated. Objectives The aim of this study was to assess the sex-related differences in TB and its clinical implication in patients with STEMI. Methods We analyzed individual patient data from the 3 major randomized clinical trials of manual thrombus aspiration, encompassing a total of 19,047 patients with STEMI, of whom 13,885 (76.1%) were men and 4,371 (23.9%) were women. The primary outcome of interest was 1-year cardiovascular (CV) death. The secondary outcomes of interest were recurrent myocardial infarction, heart failure, all-cause mortality, stroke, stent thrombosis (ST), and target vessel revascularization at 1 year. Results Patients with high TB (HTB) had worse 1-year outcomes compared with those presenting with low TB (adjusted HR for CV death; 1.52; 95% CI: 1.10-2.12; P=0.01). In unadjusted analyses, female sex was associated with an increased risk for 1-year CV death regardless of TB. After adjustment, this risk for 1-year CV death was higher only in women with HTB (HR 1.23, 95% CI: 1.18-1.28; P Conclusion In patients with STEMI, angiographic evidence of HTB negatively affected prognosis. Among patients with HTB, women had an excess risk for stent thrombosis, CV and all-cause mortality than men. Further investigations are warranted to better understand the pathophysiological mechanisms leading to excess mortality in women with STEMI and HTB.

Background Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension. Methods To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy. Results We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes (Figure 1). Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients. Conclusions Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

Background Chronic left ventricular (LV) pressure overload determines both morphological and functional alterations in the heart and in the vascular system with occurrence of LV hypertrophy, coronary rarefaction and metabolic impairment, predisposing to heart failure. We aim at investigating early cardiac involvement in hypertensive disease by both Positron emission tomography (PET) and echo assessment and possible associations between alterations of PET-derived myocardial blood flow (MBF) and echocardiographic parameters of LV performance including mechano-energetic efficiency indexed for myocardial mass (MEEi), in a population of symptomatic hypertensive patients without flow-limiting epicardial coronary artery disease (CAD). Methods The study population included 78 symptomatic hypertensive patients without flow-limiting epicardial CAD. All patients underwent standard echocardiographic assessment, including evaluation of LV MEEi, and PET assessment with evaluation of MBF and MBF/mass ratio at rest and after stress and myocardial flow reserve (MFR). Results The study population included 67% males, 55% with dyslipidaemia, 42% with smoking habits and 21% obese. Prevalence of LV hypertrophy was of 43%. Among parameters of LV systolic performance, hyperaemic MBF/mass ratio resulted significantly correlated with LV MEEi (r=0.54, p In a multiple linear regression analysis, after adjusting for sex, systolic blood pressure, prevalence of LV hypertrophy and therapy with diuretics, the association between LV MEEi and hyperaemic MBF/mass ratio remained significant (beta coefficient =0.40, p=0.007). In a subsequent multivariate model, adjusting for the same confounders, by replacing hyperaemic MBF/mass ratio with resting MBF/mass ratio, LV MEEi and resting MBF/mass ratio continued to be significantly associated (beta coefficient =0.32, p=0.015). Conclusions In a population of hypertensive patients without flow-limiting epicardial CAD, an early myocardial impairment possibly related to coronary rarefaction and inadequate angiogenesis contributing to the altered myocardial metabolic demand and efficacy is detectable by both PET and echo-derived LV MEEi. Indeed, an independent association between LV MEEi and both MBF/mass ratio at rest and after stress exists, LV MEEi having the advantage over PET of being easily derived from standard echocardiography and not needing radiation exposure.

Arterial hypertension represents a systemic burden, and it is responsible of various morphological, functional and tissue modifications affecting the heart and the cardiovascular system. Advanced imaging techniques, such as speckle tracking and three-dimensional echocardiography, cardiac magnetic resonance, computed tomography and PET-computed tomography, are able to identify cardiovascular injury at different stages of arterial hypertension, from subclinical alterations and overt organ damage to possible complications related to pressure overload, thus giving a precious contribution for guiding timely and appropriate management and therapy, in order to improve diagnostic accuracy and prevent disease progression. The present review focuses on the peculiarity of different advanced imaging tools to provide information about different and multiple morphological and functional aspects involved in hypertensive cardiovascular injury. This evaluation emphasizes the usefulness of the emerging multiimaging approach for a comprehensive overview of arterial hypertension induced cardiovascular damage.

An empathetic approach may be particularly useful in patients with therapy-resistant hypertension (TRH), defined as the failure to achieve target blood pressure (BP) despite a maximal doses of 3 antihypertensive drugs including a diuretic. However, the effects of therapeutic concordance have not been determined in hypertensive patients.We designed a study to explore the impact of therapeutic concordance in patients with TRH, who were included in an intervention arm based on a protocol in which trained personnel periodically verified the pharmacological regimen of these patients.From a cohort of 5331 hypertensive patients followed-up for 77.64 ± 34.44 months, 886 subjects were found to have TRH; of these, 322 had apparent TRH (aTRH: uncontrolled office BP but optimal home BP) and 285 refused to participate in a second follow-up study, yielding a population of 279 patients with true TRH (tTRH). These tTRH patients were followed according to the therapeutic concordance protocol for 91.91 ± 54.7 months, revealing that 210 patients (75.27%) remained with uncontrolled BP (uncontrolled tTRH, Group I) while 69 patients (24.73%) reached an optimal BP control (average BP140/90 mmHg in at least 50% of follow-up visits, Group II). Strikingly, at the end of the second follow-up, the percentage of patients displaying a decline in kidney function was significantly smaller in Group II than in Group I (8.5% vs 23.4%, p 0.012).Taken together, our findings indicate for the first time that therapeutic concordance significantly improves the outcome of antihypertensive treatment in a population of patients with TRH.

Arterial hypertension (AH) is a major risk factor for the development of heart failure (HF) which represents one of the leading causes of mortality and morbidity worldwide. The chronic hemodynamic overload induced by AH is responsible for different types of functional and morphological adaptation of the cardiovascular system, defined as hypertensive mediated target organ damage (HMOD), whose identification is of fundamental importance for diagnostic and prognostic purposes. Among HMODs, left ventricular hypertrophy (LVH), coronary microvascular dysfunction (CMVD), and subclinical systolic dysfunction have been shown to play a role in the pathogenesis of HF and represent promising therapeutic targets. Furthermore, LVH represents a strong predictor of cardiovascular events in hypertensive patients, influencing per se the development of CMVD and systolic dysfunction. Clinical evidence suggests considering LVH as a diagnostic marker for HF with preserved ejection fraction (HFpEF). Several studies have also shown that microalbuminuria, a parameter of abnormal renal function, is implicated in the development of HFpEF and in predicting the prognosis of patients with HF. The present review highlights recent evidence on the main HMOD, focusing in particular on LVH, CMD, subclinical systolic dysfunction, and microalbuminuria leading to HFpEF.

Increased intima-media thickness (IMT) of common carotid artery (CA) is considered the hallmark of vascular hypertension-mediated target organ damage, even if vessel remodeling due to mechanical stress may also induce changes in diameter. We developed a method computing both diameter and IMT of CA, to assess correlates and prognostic impact of carotid cross-sectional area (CCSA) in a large registry of treated hypertensive patients. We selected 6300 hypertensive patients of the Campania Salute Network registry free of overt cardiovascular (CV) disease and with available CA ultrasound (54 ± 11 years; 57% male). CCSA was computed as:π×(CAdiameter+2×(meanIMT)2)2−π×(CAdiameter2)2. CCSA was considered high if >90th percentile of the sex-specific distribution (>48 mm2 in men and >41 mm2 in women). Patients with high CCSA were male, with older age, higher pulse pressure (PP), more prevalent obese and diabetic, with higher total and LDL cholesterol (p < 0.01 for all). During a median follow-up of 60 months (IQR 19–87), 206 incident composite major and minor CV events occurred. In Cox regression analysis high CCSA was associated with more than 100% increased risk of incident CV events ((HR 2.11, 95%CI 1.46–3.1, p < 0.0001), independently of the effect of older age, male sex, PP > 60 mmHg, presence of left ventricular hypertrophy (LVH), carotid plaque (CP), and less anti-RAS therapy (p < 0.05 for all). In treated hypertensive patients, increased CCSA is associated with worse metabolic and lipid profile and predict incident CV events, independently of high PP, presence of LVH and CP.

Purpose: Home blood pressure monitoring (HBPM) might be considered a valid alternative to ambulatory blood pressure monitoring (ABPM) for both the diagnosis and management of hypertension. Correct information on how to perform HBPM are crucial for its reliability. The aim of the present survey was to assess if hypertensive patients followed current recommendation on how to correctly perform HBPM measurements. Materials and methods: The survey included 30 different items on how to perform the HBPM. It was developed by the ‘Young Investigators’ group of the Italian Society of Arterial Hypertension (SIIA) and it was administered during the office visit between May 2019 and December 2021. Results: A total of 643 hypertensive patients participated in the study. Main results show that, despite the rate of informed patients was relatively high (71% of the whole population), unacceptable number of patients did not follow indications on how to perform a correct HBPM. Patients who were informed on how to measure home BP had a significantly higher rate of correct position during measurement (78 vs. 22%, p < 0.01), avoidance of talking and moving during measurement (68 vs. 32%, p < 0.0001), and correct number and time interval between two measurements (85 vs. 15%, p < 0.001). More accurate measurements of home BP were associated with less prevalence of carotid plaque. Conclusions: Correct performance for HBPM is low among patients treated in Italian hypertension centers. These findings shed light on the importance of correct HBPM measurements for the detection of accurate BP values for the proper management of hypertensive patients.

Cardiac rehabilitation (CR) following acute myocardial infarction (AMI) improves physical capacities and decreases hospitalizations and cardiovascular mortality. L-Arginine is the substrate used by nitric oxide (NO) synthase (NOS) to generate NO and it has been shown to exert its beneficial effects on endothelium driving vasodilatation, reducing inflammation, and ameliorating physical function. We hypothesized that L-Arginine could enhance physical capacities in patients who underwent CR after AMI. We designed a study aimed to assess the effects of L-arginine administration on the physical capacity of patients who underwent coronary revascularization after AMI. The trial was carried out amid the COVID-19 pandemic. Patients were assigned, with a 2:1 ratio, to add to their standard therapy 1 bottle containing 1.66 g of L-arginine or 1 bottle of identical aspect apart from not containing L-arginine, twice a day orally for 3 weeks. Patients performed a 6-minute walking test (6MWT) and were assessed their Borg modified 0-10 rating of perceived exertion (BRPE) before starting and at the end of the treatment. Seventy-five patients receiving L-Arginine, and thirty-five receiving placebo successfully completed the study. The 6MWT distance increased significantly in the L-Arginine group compared to both baseline and placebo (p

Aims Aortic stenosis (AS) is a very common valve disease and is associated with high mortality once it becomes symptomatic. Arterial hypertension (HT) has a high prevalence among patients with AS leading to worst left ventricle remodelling and faster degeneration of the valve. HT also seems to interfere with the assessment of the severity of AS leading to an underestimation of the real degree of stenosis. Treatment of HT in AS has historically been associated with reluctance due to both the lack of clear guidelines and the fear of adverse effects, but the most recent evidence shows as several drugs that can be used. Methods The pathophysiology of the combination of AS and HT is the association of a first fixed mechanical obstruction of the aortic root and a second obstruction due to systemic vascular resistance. Consequently, a decrease in systemic vascular resistance through, for example, the administration of vasodilators could theoretically cause a drop in systemic pressure due to the fixed mechanical obstruction given by the stenosis which prevents an increase in cardiac output. This theory was the basis for avoiding vasodilators in patients with AS. Results There is a unanimous opinion on maintaining blood pressure values of 130–139 mmHg of systolic and 70–90 mmHg of diastolic, but there is not the same agreement on which drugs to adopt to achieve the aforementioned values. Renin-Angiotensin-Aldosterone system inhibitors are certainly the first-line treatment thanks to their cardioprotective, plaque stabilizing, and antiarrhythmic effect since they are also associated with increased survival rates and greater left ventricular mass reduction in patients after surgical or transcatheter aortic valve replacement for severe AS. If blood pressure is not yet controlled, the addition of a beta-blocker should be considered: metoprolol has the greatest literature, showing not only an improvement in haemodynamic and metabolic performance but also a reduction in mortality in patients who already presented with coronary artery disease. Mineralocorticoid receptor antagonist can be used, among them eplerenone has been studied and can be useful to relieve symptoms of patients with a flare-up of heart failure by reducing the preload, provided that a close fluid and echocardiographic monitoring is implemented. Conclusions The use of phosphodiesterase 5 inhibitors can improve the haemodynamic status of patients with aortic stenosis and reduce the level of left ventricular hypertrophy, as well as improve pulmonary circulation and exercise tolerability of patients with AS, however it should be considered that in other studies sildenafil was associated with a worse clinical outcome. Calcium channel blocker are one the most used medications in patients with HT, but their use was associated with a 7-fold relative risk of all-cause mortality independent of known confounders and was also associated with an adverse effect on treadmill exercise and higher risk of all-cause mortality in patients with AS.

Aortic stenosis (AS) is a very common valve disease and is associated with high mortality once it becomes symptomatic. Arterial hypertension (HT) has a high prevalence among patients with AS leading to worse left ventricle remodeling and faster degeneration of the valve. HT also interferes with the assessment of the severity of AS, leading to an underestimation of the real degree of stenosis. Treatment of HT in AS has not historically been pursued due to the fear of excess reduction in afterload without a possibility of increasing stroke volume due to the fixed aortic valve, but most recent evidence shows that several drugs are safe and effective in reducing BP in patients with HT and AS. RAAS inhibitors and beta-blockers provide benefit in selected populations based on their profile of pharmacokinetics and pharmacodynamics. Different drugs, on the other hand, have proved to be unsafe, such as calcium channel blockers, or simply not easy enough to handle to be recommended in clinical practice, such as PDE5i, MRA or sodium nitroprusside. The present review highlights all available studies on HT and AS to guide antihypertensive treatment.

The second half of the last century was characterized by intense research in the field of arterial hypertension and related therapies. These studies showed that the management of arterial hypertension requires a robust coordination with close integration of the "health care systems" and "health care professionals". In 1998, the health care organization named "Campania Salute Network" was set up at the University of Naples Federico II. The Campania Salute Network involves 23 outpatient hypertensive clinics distributed in different community hospitals of the Regione Campania's area, 60 randomly selected general practitioners uniformly distributed in the same area, and the Hypertension Clinic of the Federico II University in Naples (coordinating centre). Through this network, clinical data collected at each visit are shared (via text messages or emails) with peripheral units (general practitioners and community hospital outpatient hypertensive clinics). The coordinating centre works in co-operation with the peripheral units in the treatment and follow-up of all hypertensive patients (i.e. assessing hypertension mediated organ damage and associated diseases). Informations about patients are shared through on-line access to the remote web-based database. The integrated approach to the mamangement of hyperetension determined a better control of blood pressure, that was associated with a reduction of hypertension mediated organ damage and decreased incidence of fatal or non-fatal cardiovascular events. Furthermore, this innovative approach improved the adherence and the persistence to the initial pharmacologic treatment. Campania Salute Network is also a powerful tool for the clinical and translational research with more 15,000 hypertensive patients followed for more than 15 years. This database allowed, in prospetic, large scale studies, to identify the hemodimìnamic and metabolic determinants of hypertension mediated organ damage and major cardiovascular events. The experience of Campania Salute Netwiork indicates that the creation of large databases from real life experiences becomes an indispensable condition also for artificial intelligence which, in the near future, thanks to scientific knowledge, the availability of particularly advanced hardware and software, will also be able to transform the management of arterial hypertension.

Insulin resistance (IR) and the related hyperinsulinamia play a key role in the genesis and progression of the continuum of cardiovascular (CV) disease. Thus, it is reasonable to pursue in primary and secondary CV prevention, the pharmacological strategies that are capable to interfere with the development of IR. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of IR. In particular, angiotensin II (Ang II) through the generation of reactive oxygen species, induces a low grade of inflammation, which impairs the insulin signal transduction. The angiotensin converting enzyme (ACE) inhibitors are effective not only as blood pressure-lowering agents, but also as modulators of metabolic abnormalities. Indeed, experimental evidence indicates that in animal models of IR, ACE inhibitors are capable to ameliorate the insulin sensitivity. The Ang II receptor blockers (ARBs) modulate the peroxisome proliferator-activated receptor (PPAR)-γ activity. PPAR–γ is a transcription factor that controls the gene expression of several key enzymes of glucose metabolism. A further mechanism that accounts for the favorable metabolic properties of ARBs is the capability to modulate the hypothalamic–pituitary-adrenal (HPA) axis. The available clinical evidence is consistent with the concept that both ACE inhibitors and ARBs are able to interfere with the development of IR and its consequences like type 2 diabetes. In addition, pharmacological inhibition of the RAAS has favourable effects on dyslipidaemias, metabolic syndrome and obesity. Therefore, the pharmacological antagonism of the RAAS, nowadays, represents the first choice in the prevention of cardio-metabolic diseases.

Background Exaggerated variability of blood pressure (BP) poses additional stress on cardiovascular system independent of BP average value, increasing risk of target organ damage (HMOD) and cardiovascular events. We assessed the impact of visit-to-visit variability (VVV) of BP on development of cardiovascular events and HMOD. Methods Standard deviation (SD) and coefficient of variability of mean SBP and DBP were calculated in 3555 patients from the Campania Salute Network registry, with available echocardiogram and more than six visits during follow-up. Values from the first visit were excluded. The impact of VVV of BP on cardiovascular events, and mediation of HMOD were assessed at final visit. Results Mean number of visits was 11 ± 6 with mean interval between visits of 9.1 ± 3.7 months. Mean visit-to-visit SD during follow-up was 13 ± 5 for systolic and 8 ± 3 mmHg for DBP; coefficients of variability were 9.7 ± 3.5 and of 9.6 ± 3.2, respectively. In multivariable analysis, left ventricular mass at follow-up was correlated with systolic VVV of BP independently of significant effect of age, BMI, mean SBP during follow-up and initial left ventricular mass. Follow-up GFR was inversely associated with systolic and diastolic VVV, independently of significant effect of age, mean glucose and SBP during follow-up, and initial GFR. In Cox regression, high VVV of BP was also associated with increased risk of cardiovascular events (hazard ratio 1.49, 95% confidence interval 1.08-2.06, P = 0.015), independently of significant effect of HMOD. Conclusion VVV is associated with prevalent HMOD and development of cardiovascular events, independently of mean BP value during follow-up and HMOD.

Context: Cardiovascular disease (CVD) costs the economy €210 billion per year in Europe. There is an association between low-density lipoprotein cholesterol (LDL-C) and CVD risk. Objective: To evaluate the cost and effectiveness of LopiGLIK® (LOPI) in lowering LDL-C and CVD risk. Design: Single blind multicenter randomized controlled trial; patients were divided into two groups, subjected to centralized randomization. Setting: Four Italian regions. Participants: Thirty-one physicians enrolled 573 adult patients with mild hypercholesterolemia between January 2016 and January 2018. Intervention: Patients were treated for 16 weeks either with LOPI (intervention) or Armolipid Plus® (AP; control). Outcome measures: Primary outcome: percentage of patients who achieved LDL-C

Background: In general, women have lower risk for cardiovascular disease. We tested whether this sex-specific protection persists also in the presence of hypertensive left ventricular hypertrophy (LVH). Methods: 12,329 women and men with hypertension and free from prevalent cardiovascular disease enrolled in the prospective Campania Salute Network registry were followed over a median of 4.1years. Subjects were grouped according to the absence or the presence of LVH identified by echocardiography using validated sex-specific cut-off values of LV mass index (>47g/m2.7 in women and >50g/m2.7 in men). Main outcome was major cardiovascular events (MACE; combined acute coronary syndromes, stroke, hospitalization for heart failure and incident atrial fibrillation). Results: The cardiovascular risk profile accompanying LVH did not differ between sexes, but presence of obesity and diabetes carried higher probability for LVH in women, and LVH was more prevalent in women than men (43.4 vs. 32.1%, p

Background Whether increasing body mass index (BMI) is independently associated with parallel increased prevalence of hypertensive vascular and cardiac target organ damage (TOD) needs further clarification. Methods We analyzed 8815 hypertensive patients without prevalent cardiovascular disease, participating in the Campania Salute Network, grouped into BMI classes (normal 20–24.9kg/m 2 , overweight 25–29.9kg/m 2 and obese ≥30kg/m 2 ). Vascular and cardiac TOD was defined as ultrasound plaque (intima-media thickness>1.5mm) in >1 of the common or internal carotid arteries and echocardiographic left ventricular (LV) hypertrophy (LVH) (LV mass/height 2.7 >47g/m 2.7 in women and >50g/m 2.7 in men), respectively. Results A majority of patients were either overweight (49%) or obese (27%). In spite of more use of combination therapy, the obese group had higher blood pressure (BP) and prevalence of TOD. In multivariate logistic analyses, obesity was associated with a 6.9 times higher prevalence of LVH (95% confidence interval [CI] 5.84–8.17, p =0.0001), independent of significant associations with female sex, age, diabetes mellitus, office systolic BP, antihypertensive and antiplatelet treatment. In contrast, only a 17% increased prevalence of carotid plaques (OR=1.17; 95% CI 1.02–1.33, p =0.02) was found in obese patients independent of significant effect of male sex, older age and higher clinic systolic BP, an association that disappeared once effect of metabolic risk factors and related therapy was also considered. Conclusions In hypertensive patients participating in the Campania Salute Project, concomitant obesity was associated with a modestly increased prevalence of carotid plaques and a pronounced increase in prevalent LVH.

Background: Cardio-vascular target organ damage predicts the onset of type 2 diabetes mellitus (DM) in hypertensive patients. Whether an increased incidence of DM is also in relation to the severity of coronary atherosclerosis is unknown. Objective: We evaluated the onset of DM in relation to the extent and severity of coronary atherosclerosis, using the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (SS), in patients with stable angina or acute coronary syndromes, referred for coronary angiography (CA). Methods: Non-diabetic patients that underwent CA for the first time were included, and the SS was computed. Predictors of DM onset in low, medium, and high SSs were investigated. Results: Five hundred and seventy patients were included, and the mean SS was 6.3 ± 7.6. During a median follow-up of 79 months (interquartile range (IQR): 67−94), 74 patients (13%) developed DM. The risk of DM onset was significantly higher in the patients with a medium or high SS (hazard ratio (HR)—95% confidence interval (CI): 16 (4−61), p < 0.0001; and 30 (9−105), p < 0.0001, vs low SS, respectively), even after adjustment for obesity, history of hypertension, impaired fasting glucose, and cardiovascular therapy. Conclusions: The severity and extent of the coronary atherosclerosis, evaluated by the SS, is a strong and independent predictor of the development of DM in patients, referred to CA.

Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study “Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives”. This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study.

The ESC-2018 guidelines suggest the use of Unattended automated office blood pressure (UAOBP) to avoid or at least reduce the white coat effect, even if do not support its use as preferred method. To assess the pressure difference between UAOBP and Attended office blood pressure (AOBP) and to evaluate their correlations with target organ damage in hypertensive patients. UAOBP and AOBP were taken in a cohort of 48 outpatients. The pressure difference between the 2 methods and their correlation with anthropometric and cardiac parameters were analyzed. Unattended systolic and diastolic BP were lower than Attended systolic and diastolic BP (135 ± 17 mmHg vs 139 ± 21 mmHg and 79 ± 10 mmHg vs 82 ± 10 mmg). ΔDBP was significantly directly correlated with female sex (r = 0.347, p = 0.016) and it was lower in men compared to women (0.11 ± 8.9 mmHg vs 6.07 ± 7.42 mmHg, p = 0.016). Correlation coefficients for LVMi and RWT for attended and unattended BP were not statistically different (for LVMi r = 0.286 vs r = 0.381, p = 0.61, for RWT r = 0.413 vs r = 0.363, p = 0.78). The relationship between attended and unattended BP was described by the following equation: y = − 4.68 + 1.06*x; where Y is the attended systolic BP and X is the unattended systolic BP; in accordance with this equation, an unattended systolic BP of 140 mmHg corresponds to an attended systolic BP of 143.7 mmHg. UAOBP provides significantly lower values than AOBP. The difference in BP values between the two methods is much lower than the one obtained in most clinical studies.

Background and aims The clustering of high levels of LDL cholesterol (LDL-C) and other risk factors represents a predisposing condition for atherosclerotic disease development. Cardiovascular prevention is based on effective control of these conditions. In adult subjects with mild hypercholesterolemia we compared in the real life the effects of a new combination of nutraceuticals on lipid and glucose metabolism and blood pressure with those of an established nutraceutical combination. Method and results This multicenter, controlled, randomized, single-blind trial was designed to compare the effect of Armolipid Plus® versus that of LopiGLIK® on lipid and glucose levels and blood pressure (BP) in subjects with mild hypercholesterolemia not on statin therapy. Primary outcome was the proportion of subjects achieving therapeutic targets of LDL-C ( Data from an overall sample of 359 adult individuals (age 55.2 ± 11.1 years, women 57.7%, LDL-C 157.3 ± 22.6 mg/dl, HDL-C 50.7 ± 13.0 mg/dl) are reported. 72% of subjects treated with LopiGLIK® and 43% treated with Armolipid Plus® achieved the primary endpoint (p Conclusions The present analysis shows that LopiGLIK® may represent a more effective tool for clinical management of CV risk factors in subjects with mild hypercholesterolemia.

Introduction: The prevalence of systemic arterial hypertension in young adults is increasing worldwide in association with modifiable risk factors. Aim: To assess the prevalence of high blood pressure (BP) in young adults participating to a screening campaign during the World Hypertension Day (17/05/2014), and to determine the possible association with lifestyle factors. Methods: 493 individuals aged 18–35 years were selected in 13 Italian cities. All participants underwent BP measurement together with the administration of a questionnaire exploring: medical and drug history; traditional cardiovascular risk factors and diseases; dietary pattern; salt intake; sleep habits; mood disorders. Results: High BP (≥140/90 mmHg) was found in 54 individuals, with a prevalence of 11 % and awareness of 28 %. Those with high BP values were more frequently men, reported a higher BMI and a greater use of corticosteroids and non-steroidal anti-inflammatory drugs, and had a lower anxiety score. Concerning dietary habits, they were more likely to eat cheese/cold cuts ≥3 times/week, to have their meals out ≥1/day and to eat in fast foods ≥1/week. In the multiple logistic regression analysis, male sex [OR 3.19, 95 % CI (1.33–7.63)], BMI [OR 1.14 95 % CI (1.04–1.25)], eating in fast foods [OR 3.10 95 % CI (1.21–7.95)], and anxiety [OR 0.85 95 % CI (0.75–0.97)], were independently associated with high BP. Conclusions: High BP values were found in 11 % young adults. Male sex, adiposity and alimentary habits were the main determinants of high BP values, indicating that young men are a suitable target for healthy lifestyle interventions.

BACKGROUND Left atrial (LA) dilatation is associated with unfavorable outcome in hypertension. However, there are few data on clinical, demographic, and echocardiographic findings correlated with LA dilatation development. METHODS From the Campania-Salute Network registry, we identified 5,375 hypertensive patients (52±11 years, 38% women) in normal sinus rhythm, with normal LA diameter (parasternal short-axis

Background: Current hypertension management guidelines do not recommend drug treatment in subjects with blood pressure (BP) in the high-normal range due to the risk of side effects of the currently available antihypertensive agents that overcomes the possible benefit. Nutraceuticals are free from relevant side effects and could be a valuable strategy for the treatment of these patients. Aim: The objective of this study was to compare the efficacy of two nutraceutical compositions given by the combination of policosanol, red yeast rice extract, berberine, folic acid and coenzyme Q10 with or without Orthosiphon stamineus in lowering the BP and lipid profile. Methods: Thirty patients with grade 1 essential hypertension and low cardiovascular risk were analysed. At the end of a run-in period, patients were divided into two study arms and assigned to receive the nutraceutical combination with and without Orthosiphon stamineus. All participants underwent 24-hour ambulatory BP monitoring at the end of the run-in period and of the 4-week treatment with each of the two different nutraceutical combinations. Results: In patients treated with Orthosiphon stamineus a significant reduction of mean 24-hour systolic and diastolic BP levels compared with baseline values was registered and the smoothness index calculated for systolic and diastolic BP showed a more reliable and homogeneous effect on BP over 24 hours. In contrast, nutraceutical treatment without Orthosiphon stamineus was not associated with a significant reduction of BP. Conclusions: Our results show that the addition of Orthosiphon stamineus to the combination of nutraceuticals confers an antihypertensive effect that allows a surprisingly effective 24-hour BP control in hypertensive patients.

Reduced myocardial mechano-energetic efficiency (MEE), estimated as stroke volume/heart rate ratio per g of left ventricular (LV) mass (LVM), and expressed in μl s(-1) g(-1) (MEEi), is a strong predictor of cardiovascular (CV) events, independently of LV hypertrophy and other confounders, including type II diabetes (DM). Decreased MEEi is more frequent in patients with diabetes. In the present analysis we evaluated the interrelation among MEEi, DM and metabolic syndrome (MetS) in the setting of arterial hypertension. Hypertensive patients from the Campania Salute Network, free of prevalent CV disease and with ejection fraction >50% (n=12 503), were analysed. Coexistence of MetS and DM was ordinally categorized into 4 groups: 8235 patients with neither MetS nor DM (MetS-/DM-); 502 without MetS and with DM (MetS-/DM+); 3045 with MetS and without DM (MetS+/DM-); and 721 with MetS and DM (MetS+/DM+). After controlling for sex, systolic blood pressure, body mass index, relative wall thickness (RWT), antihypertensive medications and type of antidiabetic therapy, MEEi was 333 μl s(-1) g(-1) in MetS-/DM-, 328 in MetS-/DM+, 326 in MetS+/DM- and 319 in MetS+/DM+ (P for trend

The recommendation to start antihypertensive therapy with diuretics (D) might produce delay in blood pressure (BP) control and, possibly, increase cost/benefit ratio.We evaluate the effects of D in relation to the administration of other anti-hypertensive medications, in clinical practice.General practitioners recruited 2,409 hypertensive patients with indication to antihypertensive therapy, who were randomized to start treatment with chlorthalidone (12.5-25 ???mg daily, group D) or any other single medications (excluding thiazides, group A). The patients have been followed for at least 2 years.Among the 2,409 patients recruited (42.5 \% women), 1,205 were randomized in group D and 1,204 in group A, of which 1,051 (or 87 \%) and 1026 (or 85 \%) respectively, completed the study. The number of patients in optimal BP control was similar in the two groups (65.0 vs 64.0 \%; p = NS). During follow-up, the group D had prescribed a slightly greater number of medications compared to the group A who added D as second line (2.3 vs 2.1; p

Diabetic foot (DF) is a chronic and highly disabling complication of diabetes. The prevalence of peripheral arterial disease (PAD) is high in diabetic patients and, associated or not with peripheral neuropathy (PN), can be found in 50% of cases of DF. It is worth pointing out that the number of major amputations in diabetic patients is still very high. Many PAD diabetic patients are not revascularised due to lack of technical expertise or, even worse, negative beliefs because of poor experience. This despite the progress obtained in the techniques of distal revascularisation that nowadays allow to reopen distal arteries of the leg and foot. Italy has one of the lowest prevalence rates of major amputations in Europe, and has a long tradition in the field of limb salvage by means of an aggressive approach in debridement, antibiotic therapy and distal revascularisation. Therefore, we believe it is appropriate to produce a consensus document concerning the treatment of PAD and limb salvage in diabetic patients, based on the Italian experience in this field, to share with the scientific community.

Fixed combinations of antihypertensive drugs have the potentiality to improve blood pressure (BP) control. However, when pharmacokinetic parameters of the two drugs are different, both method and time of administration of the two drugs may modify the antihypertensive response. In an open-label, single-blind, randomized study we compared antihypertensive effect of four administration schemes of a combination therapy of olmesartan and amlodipine in the same group of hypertensive patients, using ambulatory blood pressure monitoring (ABPM). The olmesartan + amlodipine combination has demonstrated to provide a good control of BP, with systolic and diastolic BP constantly below 130 and 85 mmHg over the 24 h. The simultaneous or separate administration of the 2 drugs fully overlapped, suggesting that the fixed combination and the separate administration induce a similar and sustained BP control.

OBJECTIVES The study investigated the effects of physical activity on preinfarction angina, a clinical equivalent of ischemic preconditioning (PC), in adult and elderly patients with acute myocardial infarction (AMI). BACKGROUND Preinfarction angina seems to confer protection against in-hospital mortality in adult but not in elderly patients. However, it has been experimentally demonstrated that exercise training restores the protective effect of PC in the aging heart. METHODS We retrospectively verified whether physical activity preserved the protective effect of preinfarction angina against in-hospital mortality in 557 elderly patients with AMI. Physical activity was quantified according to the Physical Activity Scale for the Elderly (PASE). RESULTS In-hospital mortality was 22.2% in elderly patients with preinfarction angina and 27.2% in those without (p = 0.20). When the PASE score was stratified in quartiles (0 to 40, 41 to 56, 57 to 90, >90), a high score was strongly associated with reduced in-hospital mortality (30.8%, 32.2%, 17.2% and 15.3%, respectively, p < 0.001 for trend). Interestingly, a high level of physical activity reduced in-hospital mortality in elderly patients with preinfarction angina (35.7%, 35.4%, 12.3% and 4.23%, respectively, p < 0.001 for trend) but not in those without (23.0%, 27.2%, 26.0% and 35.0%, respectively, p = 0.35 for trend). Accordingly, the protective role of preinfarction angina on in-hospital mortality was present only in elderly patients showing a high level of physical activity (adjusted odds ratio, 0.09; 95% confidence interval, 0.01 to 0.57; p < 0.05). CONCLUSIONS Physical activity and not preinfarction angina protects against in-hospital mortality in elderly patients with myocardial infarction. Nevertheless, the protective effect of preinfarction angina is preserved in elderly patients with a high level of physical activity.

INTRODUCTION: Nutraceuticals (NUT) are forms of compounds with biological activity commonly used to improve health in dosage largely exceeding those obtainable in food. AIM: We compared, in a double blind randomized cross-over trial, the effects of two NUT combinations on the control of glico-lipidic metabolism in patients with hypercholesterolemia not on statins. METHODS: At study start patients were given dietary counseling and received placebo for 2 weeks. After this run-in period, patients were randomized: (1) Combination A [Policosanol, Red yeast rice (Monakolin K 3 mg), Berberine 500 mg, Astaxantine, Folic Acid and Coenzyme Q10] for 4 weeks followed by 4 weeks of Combination B [Red yeast rice (Monakolin K 3.3 mg), Berberine 531.25 mg and leaf extract of Morus alba]; (2) Combination B for 4 weeks followed by 4 weeks of Combination A. RESULTS: Combination B reduced LDL cholesterol below 130 mg/dl in 56.5 % of the patients, and Cambination A only in 21.7 % of them (p ≤ 0.027). Both treatments reduced plasma levels of triglycerides, total and LDL cholesterol and increased HDL cholesterol (all p < 0.03). Total and LDL cholesterol reduction was more pronounced in patients taking Combination B (p < 0.005). Combination B reduced also glycated hemoglobin, fasting glucose and insulin plasma levels as well as HOMA index (p < 0.005). CONCLUSIONS: An increased content of Berberin and Monacolin K and the addition of Morus alba extract improves the effect on plasma cholesterol and on glucose metabolism of the NUT Combination. These effects may allow the speculation of a more marked improvement in cardiovascular prognosis.