Showing papers by "Giuseppe Mancia published in 2021"

European Society of Hypertension position paper on renal denervation 2021.

Abstract: This ESH Position Paper 2021 with updated proposed recommendations was deemed necessary after the publication of a set of new pivotal sham-controlled randomized clinical trials (RCTs), which provided important information about the efficacy and safety of endovascular device-based renal denervation (RDN) for hypertension treatment. RDN is effective in reducing or interrupting the sympathetic signals to the kidneys and decreasing whole body sympathetic activity. Five independent, fully completed, sham-controlled RCTs provide conclusive evidence that RDN lowers ambulatory and office blood pressure (BP) to a significantly greater extent than sham treatment. BP-lowering efficacy is evident both in patients with and without concomitant antihypertensive medication. The average decrease of 10 mmHg in office BP is estimated to lower the incidence of cardiovascular events by 25-30%, based on meta-analyses of RCTs using pharmacological treatment. Neither peri-procedural, nor short-term or long-term adverse events or safety signals (available up to 3 years) have been observed. Implementing RDN as an innovative third option in the armamentarium of antihypertensive treatment requires a structured process that ensures the appropriate performance of the endovascular RDN procedure and adequate selection of hypertensive patients. The latter should also incorporate patients' perspective and preference that needs to be respected in a shared decision-making process.

Lifestyle, psychological, socioeconomic and environmental factors and their impact on hypertension during the coronavirus disease 2019 pandemic.

Abstract: SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic considerably affects health, wellbeing, social, economic and other aspects of daily life. The impact of COVID-19 on blood pressure (BP) control and hypertension remains insufficiently explored. We therefore provide a comprehensive review of the potential changes in lifestyle factors and behaviours as well as environmental changes likely to influence BP control and cardiovascular risk during the pandemic. This includes the impact on physical activity, dietary patterns, alcohol consumption and the resulting consequences, for example increases in body weight. Other risk factors for increases in BP and cardiovascular risk such as smoking, emotional/psychologic stress, changes in sleep patterns and diurnal rhythms may also exhibit significant changes in addition to novel factors such as air pollution and environmental noise. We also highlight potential preventive measures to improve BP control because hypertension is the leading preventable risk factor for worldwide health during and beyond the COVID-19 pandemic.

Coronavirus disease 2019 and cardiovascular complications: focused clinical review.

Abstract: The coronavirus disease 2019 (COVID-19) may cause not only an acute respiratory distress syndrome (ARDS) but also multiple organ damage and failure requiring intensive care and leading to death. Male sex, advanced age, chronic lung disease, chronic kidney disease and cardiovascular disease, such as hypertension, diabetes and obesity have been identified as risk factors for the COVID-19 severity. Presumably, as these three cardiovascular risk factors are associated with a high prevalence of multiorgan damage. In the present focused clinical review, we will discuss the cardiovascular complications of COVID-19 including acute cardiovascular syndrome (acute cardiac injury/COVID cardiomyopathy, thromboembolic complications and arrhythmias) and post-COVID-19 sequelae. Preliminary data shows that the cause of acute cardiovascular syndrome may be multifactorial and involve direct viral invasion of the heart and vascular system, as well as through the immune and inflammation-mediated systemic cytokine storm. COVID-19 survivors may also show persistently elevated blood pressure and sinus tachycardia at rest. Furthermore, poor diabetic control, persistent renal damage and cerebral sequelae, such as persistent cognitive and neuropsychiatric alterations are also frequently reported. A particular attention should be paid towards cardiovascular protection in COVID-19 patients who develop acute cardiovascular syndromes during hospitalization, and/or permanent/semipermanent sequelae after recovery from COVID-19. These conditions may require careful clinical assessment, treatment and close follow-up to avoid short-term and long-term complications.

Renin-angiotensin-system inhibitors and all-cause mortality in patients with COVID-19: a systematic review and meta-analysis of observational studies.

Abstract: AIMS: We sought to evaluate the association of angiotensin-converting-enzyme inhibitors (ACEI) or AT1 blockers (ARB) therapy with clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: Electronic databases were searched to identify published studies that reported clinical outcomes in patients with COVID-19 who were or were not taking an ACEI/ARB. We studied all-cause mortality and/or severe disease outcomes. Fully adjusted effect estimates from individual studies were pooled using a random-effects model. In total, 34 (31 cohort-based and three case-control) studies met our eligibility criteria. Due to the inherent differences between cohort and case-control studies, we did not combine results of these studies but used them to identify the consistency of their results. The 31 cohort studies provided outcome data for 87 951 patients with COVID-19, of whom 22 383/83 963 (26.7%) were on ACEI/ARB therapy. In pooled analysis, we found no association between the use of ACEI/ARB and all-cause mortality/severe disease [relative risk: 0.94, 95% confidence interval (CI): 0.86-1.03, I2 = 57%, P = 0.20] or occurrence of severe disease (relative risk: 0.93, 95% CI: 0.74-1.17, I2 = 56%, P = 0.55). Analysis of three population-based case-control studies identified no significant association between ACEI/ARB (pooled odds ratio: 1.00, 95% CI: 0.81-1.23, I2 = 0, P = 0.98) and all-cause mortality/severe disease. In 13 of the 31 cohort studies as well as in three case-control studies that reported outcomes separately for ACEI and ARB, there was no differential effect for mortality/severe disease outcomes. CONCLUSION: In patients with COVID-19, we found no association between ACEI/ARB treatment and mortality/severe disease. ACEI/ARB should not be discontinued, unless clinically indicated.

Hypertension and heart failure with preserved ejection fraction: position paper by the European Society of Hypertension.

Abstract: Hypertension constitutes a major risk factor for heart failure with preserved ejection fraction (HFpEF). HFpEF is a prevalent clinical syndrome with increased cardiovascular morbidity and mortality. Specific guideline-directed medical therapy (GDMT) for HFpEF is not established due to lack of positive outcome data from randomized controlled trials (RCTs) and limitations of available studies. Although available evidence is limited, control of blood pressure (BP) is widely regarded as central to the prevention and clinical care in HFpEF. Thus, in current guidelines including the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines, blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers provides the backbone of BP-lowering therapy in hypertensive patients. Although superiority of RAS blockers has not been clearly shown in dedicated RCTs designed for HFpEF, we propose that this core drug treatment strategy is also applicable for hypertensive patients with HFpEF with the addition of some modifications. The latter apply to the use of spironolactone apart from the treatment of resistant hypertension and the use of the angiotensin receptor neprilysin inhibitor. In addition, novel agents such as sodium-glucose co-transporter-2 inhibitors, currently already indicated for high-risk patients with diabetes to reduce heart failure hospitalizations, and finerenone represent promising therapies and results from ongoing RCTs are eagerly awaited. The development of an effective and practical classification of HFpEF phenotypes and GDMT through dedicated high-quality RCTs are major unmet needs in hypertension research and calls for action.

Hypertension and COVID-19: Ongoing Controversies

Abstract: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic responsible for millions of deaths around the world. Hypertension has been identified as one of the most common comorbidities and risk factors for severity and adverse outcome in these patients. Recent investigations have raised the question whether hypertension represents a predictor of outcome in COVID-19 patients independently of other common comorbidities such as diabetes, obesity, other cardiovascular diseases, chronic kidney, liver, and pulmonary diseases. However, the impact of chronic and newly diagnosed hypertension in COVID-19 patients has been insufficiently investigated. The same is true for the relationship between blood pressure levels and outcomes in COVID-19 patients. It seems that the long discussion about the impact of angiotensin-converting enzyme inhibitors (ACEI) and blockers of angiotensin I receptors (ARB) on severity and outcome in COVID-19 is approaching an end because the large number of original studies and meta-analyses discarded the initial findings about higher prevalence of ACEI/ARB use in patients with unfavorable outcomes. Nevertheless, there are many controversies in the relationship between hypertension and COVID-19. The aim of this review article is to provide a clinical overview of the currently available evidence regarding the predictive value of hypertension, the effect of blood pressure levels, the impact of previously known and newly diagnosed hypertension, and the effect of antihypertensive therapy on the severity and outcomes in COVID-19 patients.

Adding Home and/or Ambulatory Blood Pressure to Office Blood Pressure for Cardiovascular Risk Prediction.

Abstract: Home and 24-hour blood pressure (BPHome and BP24h) are believed to improve the prognostic value of office BP (BPOffice) alone, but the evidence has limitations such as that (1) these 3 BPs are characterized by multicollinearity and (2) the procedures adopted do not allow quantification of the prognostic advantage. One thousand eight hundred thirty-three individuals belonging to the PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni) were followed for 16 years. Prediction of cardiovascular and all-cause mortality was determined via the goodness of fit of individual data (Cox model), the area underlying the receiving operator curves and the net reclassification improvement of cardiovascular and all-cause mortality risk. Calculations were made for BPOffice alone and after addition of BPHome, BP24h, or both, limited to their residual portion which was found to be unexplained by, and thus independent on, BPOffice. With all methods addition of residual out-of-office systolic or diastolic BP to BPOffice significantly improved cardiovascular and all-cause mortality prediction. The improvement was more consistent when BPHome rather than BP24h was added to BPOffice and, compared with BPOffice plus BPHome, no better prediction was found when addition was extended to BP24h. With all additions, however, the improvement was quantitatively modest, which was the case also when data were separately analyzed in younger and older individuals or in dippers and nondippers. Thus, addition of out-of-office to BPOffice improves prediction of cardiovascular risk, even when data analysis avoids previous limitations. The improvement appears to be limited, however, which raises the question of the advantage to recommend their extended use in clinical practice.

Myocardial strain in hypertension: a meta-analysis of two-dimensional speckle tracking echocardiographic studies

Abstract: AIM Available evidence on systolic dysfunction in systemic hypertension, as assessed by left ventricular (LV) mechanics, is still based on single studies. Thus, we performed a systematic meta-analysis of two-dimensional speckle-tracking studies in order to provide an updated comprehensive information on this issue. METHODS The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English language articles published from the inception up to 31 December 2020. Studies were identified by using MeSH terms and crossing the following search items: 'myocardial strain', 'left ventricular mechanics', 'speckle tracking echocardiography', 'systolic dysfunction', 'hypertensive heart disease', 'systemic hypertension', 'essential hypertension'. RESULTS Data from 4276 individuals (2089 normotensive controls and 2187 mostly uncomplicated hypertensive patients) were included. Left ventricular (LV) mass index, relative wall thickness, left atrial volume index and E/e' ratio were significantly higher in hypertensive patients than in normotensive controls. LV ejection fraction did not differ in the two pooled groups (SMD -0.048 ± 0.054, 95% CI -0.20 to 0.10, P = 0.30), whereas LV global longitudinal strain (GLS) was significantly impaired in the hypertensive group (SMD: 1.07 ± 0. 15, 95% CI 0.77-1.36, P < 0.0001). Similar findings were obtained in a sub-analysis restricted to 15 studies in which mean age was similar in cases and controls (SMD 1.21 ± 0.23, 95% CI 0.76-1.67, P = 0.002). CONCLUSION The present meta-analysis suggests that GLS assessment unmasks systolic dysfunction undetected by conventional ejection fraction in the uncomplicated hypertension setting and that this parameter should be incorporated into routine work-up aimed to identify hypertension-mediated cardiac damage.

Sympathetic nerve traffic overactivity in chronic kidney disease: a systematic review and meta-analysis.

Abstract: BACKGROUND Studies based on microneurographic sympathetic nerve activity (MSNA) recordings have shown that the sympathetic system is overactivated in chronic kidney disease (CKD) patients but the relationship between MSNA and renal function and other risk factors has not been systematically reviewed in this population. DESIGN AND MEASUREMENTS This meta-analysis compares MSNA in cardiovascular complications-free CKD patients (n = 638) and healthy individuals (n = 372) and assesses the relationship of MSNA with the eGFR, age, BMI and hemodynamic variables. RESULTS In a global analysis, MSNA was higher in CKD patients than in healthy control individuals (P < 0.001). The difference in MSNA between patients and healthy individuals was more marked in end-stage kidney diseases patients than in stage 3A 3B CKD patients (P < 0.001). In an analysis combining patients and healthy individuals, MSNA rose gradually across progressively lower eGFR categories (P < 0.01). In separate meta-regression analyses in CKD patients and in healthy individuals, MSNA associated directly with age (CKD: r = 0.57, P = 0.022; healthy individuals: r = 0.71, P = 0.031) and with the BMI (r = 0.75, P = 0.001 and r = 0.93, P = 0.003). In both groups, MSNA correlated with heart rate (r = 0.77, P = 0.02 and r = 0.66, P = 0.01) but was unrelated to plasma norepinephrine. CONCLUSION Independently of comorbidities, MSNA is markedly increased in CKD patients as compared with healthy individuals and it is related to renal function, age, the BMI and heart rate. Sympathetic activation intensifies as CKD progresses toward kidney failure and such an intensification is paralleled by a progressive rise in heart rate but it is not reflected by plasma norepinephrine.

The Impact of Frailty on the Effectiveness and Safety of Intensive Glucose Control and Blood Pressure-Lowering Therapy for People With Type 2 Diabetes: Results From the ADVANCE Trial.

Abstract: OBJECTIVE: To develop a frailty index (FI) and explore the relationship of frailty to subsequent adverse outcomes on the effectiveness and safety of more intensive control of both blood glucose and blood pressure (BP), among participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. RESEARCH DESIGN AND METHODS: Cox proportional hazard models were used to estimate the effectiveness and safety of intensive glucose control and BP intervention according to frailty (defined as FI >0.21) status. The primary outcomes were macro- and microvascular events. The secondary outcomes were all-cause mortality, cardiovascular mortality, severe hypoglycemia, and discontinuation of BP treatment due to hypotension/dizziness. RESULTS: There were 11,140 participants (mean age, 65.8 years; 42.5% women, 25.7% frail). Frailty was an independent predictor of all primary outcomes and secondary outcomes. The effect of intensive glucose treatment on primary outcomes showed some evidence of attenuation in the frail: hazard ratios for combined major macro- and microvascular events 1.03 (95% CI 0.90-1.19) in the frail versus 0.84 (95% CI 0.74-0.94) in the nonfrail (P = 0.02). A similar trend was observed with BP intervention. Severe hypoglycemia rates (per 1,000 person-years) were higher in the frail: 8.39 (6.15-10.63) vs. 4.80 (3.84-5.76) in nonfrail (P < 0.001). There was no significant difference in discontinuation of BP treatment between frailty groups. CONCLUSIONS: It was possible to retrospectively estimate frailty in a trial population, and this FI identified those at higher risk of poor outcomes. Participants with frailty had some attenuation of benefit from intensive glucose-lowering and BP-lowering treatments.

White-Coat Hypertension: Pathophysiological and Clinical Aspects: Excellence Award for Hypertension Research 2020

Abstract: Few issues of modern cardiovascular medicine have been as controversial as the relationship between white-coat hypertension (WCH), that is, a common condition in which office blood pressure is elev...

Sodium--glucose co-transporter-2 inhibitors for patients with diabetic and nondiabetic chronic kidney disease: a new era has already begun.

Abstract: Chronic kidney disease (CKD) is a major issue of public health. Hypertension control and use of renin--angiotensin system (RAS) blockers are the cornerstones of treatment for CKD of any cause. However, even under optimal RAS blockade, many individuals will progress towards more advanced CKD. Within the past few years, evidence from cardiovascular outcome trials with sodium--glucose co-transporter-2 (SGLT-2) inhibitors clearly suggested that these agents substantially delay CKD progression in patients with diabetes mellitus on top of standard-of-care treatment. The Canagliflozin-and-Renal-Events-in-Diabetes-with-Established-Nephropathy-Clinical-Evaluation (CREDENCE) study, showed that canagliflozin substantially reduced the risk of doubling of SCr, end-stage kidney disease (ESKD), or death from renal or cardiovascular causes in 4401 patients with diabetic CKD compared with placebo (hazard ratio 0.70; 95% CI 0.59-0.82). Recently, the Study-to-Evaluate-the-Effect-of-Dapagliflozin-on-Renal-Outcomes-and-Cardiovascular-Mortality-in-Patients-With-Chronic-Kidney-Disease (DAPA-CKD), including 2510 patients with diabetic and 1803 with nondiabetic CKD, also showed an impressive reduction in the risk of ≥50% decline in eGFR, ESKD, or death from renal or cardiovascular causes (HR 0.61; 95% CI 0.51-0.72). The benefit was similar for patients with diabetic and nondiabetic CKD, including patients with glomerulonephritides. Following this conclusive evidence, relevant guidelines should accommodate their recommendations to implement treatment with SGLT-2 inhibitors for patients with diabetic and nondiabetic CKD.

Renal denervation in patients with versus without chronic kidney disease: results from the global SYMPLICITY Registry with follow-up data of 3 years.

Abstract: BACKGROUND Activity of the sympathetic nervous system is increased in patients with hypertension and chronic kidney disease (CKD). Here we compare short- and long-term blood pressure (BP) lowering effects of renal denervation (RDN) between hypertensive patients with or without CKD in the Global SYMPLICITY Registry. METHODS Office and 24-hour ambulatory BP (ABP) were assessed at pre-specified time-points after RDN. The presence of CKD was defined according to estimated glomerular filtration rate (eGFR), and enrolled patients were stratified based on the presence (N = 475, eGFR < 60 ml/min/1.73m2) or absence (N = 1505, eGFR ≥ 60ml/min/1.73m2) of CKD. RESULTS Patients with CKD were older (p < 0.001) and were prescribed more antihypertensive medications (p < 0.001). eGFR-decline/year was not significantly different between groups after the first year. Office and 24-hour ABP were significantly reduced from baseline at all timepoints after RDN in both groups (all p < 0.001). After adjusting for baseline data, patients without CKD had a greater reduction in office systolic BP (-17.3 ± 28.3 vs. -11.7 ± 29.9 mmHg, p = 0.009), but not diastolic BP at 36 months compared to those with CKD. Similar BP and eGFR-results were found when the analysis was limited to patients with both baseline and 36-month BP data available. There was no difference in the safety profile of the RDN-procedure between groups. CONCLUSIONS After adjusting for baseline data, 24-hour systolic and diastolic ABP reduction was similar in patients with and without CKD after RDN, whereas office systolic but not diastolic BP was reduced less in patients with CKD. We conclude that RDN emerged as an effective antihypertensive treatment option in CKD patients.

Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control.

Abstract: Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk. We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study. The model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10−21 and p = 9.6 × 10−31, respectively) and a 4.4-fold (p = 6.8 × 10−33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. This novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy.

Obstructive sleep apnea and cardiac mechanics: how strain could help us?

Abstract: Obstructive sleep apnea (OSA) syndrome is the most common sleep-breathing disorder, which is associated with increase cardiovascular morbidity and mortality. OSA increases risk of resistant arterial hypertension, coronary artery disease, heart failure, pulmonary hypertension, and stroke. Studies showed the significant relationship between OSA and cardiac remodeling. The majority of investigations were focused on the left ventricle and its hypertrophy and function. Fewer studies investigated right ventricular structure and function revealing deteriorated diastolic and systolic function. Data regarding left and right ventricular mechanics in OSA patients are scarce and controversial. The results of the studies that were focused on the influence of continuous positive airway pressure and weight reduction on cardiac remodeling revealed favorable effect on left and right ventricular structure and function. Recently published analyses confirmed positive effect of treatment on cardiac mechanics. Deterioration of left and right ventricular mechanics occurs before functional and structural cardiac impairments in the cascade of cardiac remodeling and therefore the assessment of left and right ventricular strain may represent a cornerstone in detection of subtle cardiac changes that develop significantly before other, often irreversible, alterations. Considering the fact that left and right ventricular strains have important predictive value in wide range of cardiovascular diseases, one should consider the evaluation of left and right ventricular strains in the routine echocardiographic assessment at all stages of disease-from diagnosis, during follow-up and evaluation of therapeutic effects. The main aim of this review is to provide the current overview of cardiac mechanics in OSA patients before and after (during) therapy, as well as mechanisms that could be responsible for cardiac changes.

Reverse dipping and subclinical cardiac organ damage: a meta-analysis of echocardiographic studies.

Abstract: AIM Available evidence on the association between reverse dipping pattern and subclinical cardiac damage is scanty. We performed a systematic meta-analysis of echocardiographic studies in order to provide an updated and comprehensive information on this issue. METHODS The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from January from the inception up to 31 July 2020. Studies were identified by using MeSH terms and crossing the following search items: 'reverse dipping', 'nondipping', 'inverted dipping', 'ambulatory blood pressure', 'cardiac damage', 'hypertensive heart disease', 'left ventricular mass', 'left ventricular hypertrophy', and 'echocardiography'. RESULTS Data from 14 studies including 1429 patients with reverse dipping, 2584 dippers and 3508 nondippers were considered. Left ventricular (LV) mass index and relative wall thickness were greater in reverse dippers than in dippers (SMD: 0.40 ± 0.04 g/m2, P < 0.0001; 0.31 ± 0.07, P < 0.0001) and nondippers (SMD: 0.25 ± 0.04 g/m2, P < 0.0001; 0.21 ± 0.07, P = 0.004). The reverse dipping group had an increased risk of LV hypertrophy compared with dipping (OR = 1.85, CI 1.47-2.32, P < 0.0001) and nondipping group (OR = 1.45, CI 1.19-1.78, P < 0.0001). A significant progressive reduction in the E/A ratio, paralleled by an increase in left atrium diameter occurred from dippers, to nondippers and reverse dippers. CONCLUSION The present meta-analysis provides a novel piece of information about the unfavourable association between the reverse dipping pattern and subclinical cardiac alterations and suggests that the detection of this blood pressure phenotype may identify individuals at increased risk for subclinical organ damage.

Central and peripheral sympathetic activation in heart failure.

Abstract: The sympathetic nervous system overdrive occurring in heart failure has been reported since more than half a century. Refinements in the methodological approaches to assess human sympathetic neural function have allowed during recent years to better define various aspects related to the neuroadrenergic alteration. These include 1) the different participation of the individual regional sympathetic cardiovascular districts at the process, 2) the role of the central nervous system in determining the neuroadrenergic overdrive, 3) the involvement of baroreflex, cardiopulmonary reflex and chemoreflex mechanisms in the phoenomenon, which is also closely linked to inflammation and the immune reaction, 4) the relationships with the severity of the disease, its ischaemic or idiopathic nature and the preserved or reduced left ventricular ejection fraction and 5) the adverse functional and structural impact of the sympathetic activation on cardiovascular organs, such as the brain, the heart and the kidneys. Information have been also gained on the active role exerted by the sympathetic activation on the disease outcome and its potential relevance as target of the therapeutic interventions based on non-pharmacological, pharmacological and invasive approaches, including the renal denervation, the splanchnic sympathetic nerve ablation and the carotid baroreflex stimulation. The still undefined aspects of the neurogenic alterations and the unmet goals of the therapeutic approach having the sympathetic activation as a target of the intervention will be finally mentioned.

Blood pressure, glycemic status and advanced liver fibrosis assessed by transient elastography in the general United States population

Abstract: Objective Few studies investigated the role of different predictors of advanced liver fibrosis in unselected populations. Here, we estimate the prevalence of steatosis and fibrosis in the general United States population by means of transient elastography and evaluate the impact of blood pressure (BP) and diabetes on disease severity. Methods This is a cross-sectional study of United States adults participating in the 2017-2018 cycle of the National Health and Nutrition Examination Survey. Participants underwent a transient elastography examination, and liver steatosis and fibrosis were estimated through the controlled attenuation parameter (CAP) score and liver stiffness measurement (LSM), respectively. Results Four thousand, three hundred and seventy-one participants had reliable transient elastography and BP readings. Steatosis (CAP ≥ 248 dB/m), advanced fibrosis (LSM ≥ 9.6 kPa) and cirrhosis (LSM ≥ 13 kPa) were present in 56.9, 5.5 and 2.9% of participants, respectively. After controlling for potential confounders, risk of steatosis increased proportionally going from participants with optimal (reference) to those with normal [odds ratio (OR) 1.24, 95% confidence interval (CI) 0.83-1.86], high normal (OR 1.41, 95% CI 1.01-1.97) and elevated BP (OR 1.64, 95% CI 1.21-2.21), whereas no significant association was found between BP status and liver fibrosis. Conversely, presence of diabetes increased the risk of both steatosis (OR 2.15, 95% CI 1.49-3.11) and advanced fibrosis (OR 2.25, 95% CI 1.36-3.72). Conclusion Liver steatosis and fibrosis are highly prevalent in the multiethnic United States adult population, raising concerns for future incidence of cirrhosis and its complications. BP status was associated with a progressively higher risk of steatosis, whereas obesity and diabetes were consistently associated with both steatosis and fibrosis.

Sympathetic Neural Mechanisms Underlying Attended and Unattended Blood Pressure Measurement

Abstract: Whether blood pressure (BP) values differ when BP is measured with or without the presence of a doctor (attended and unattended BP measurements) is controversial, and no information exists on whether and to what extent neurogenic mechanisms participate at the possible BP differences between these measurements. In this study, we assessed continuous beat-to-beat finger systolic BP and diastolic BP, heart rate, muscle, and skin sympathetic nerve traffic (microneurography) before and during BP measurement by an automatic device in the presence or absence of a doctor. This was done in 18 untreated mild-to-moderate essential hypertensive patients (age, 40.2±2.8 years, mean±SEM). During attended BP measurement, there was an increase in systolic BP, diastolic BP, heart rate, and skin sympathetic nerve traffic and a muscle sympathetic nerve traffic decrease, the peak changes being +5.3%,+8.4%,+9.4%,+30.9%, and -15.2%, respectively (P<0.05 for all). In contrast, during unattended BP measurement, systolic BP, diastolic BP, heart rate, and skin sympathetic nerve traffic were modestly, albeit in most instances significantly, reduced, whereas muscle sympathetic nerve traffic remained almost unchanged. During unattended BP measurement, peak systolic BP was 14.1 mm Hg lower, peak heart rate was 10.6 bpm lower, and peak skin sympathetic nerve traffic was 8.5 bursts/min lower than the peak values detected during attended BP measurement. Thus the cardiovascular and neural sympathetic responses to the alerting reaction elicited by BP measurement in the presence of a doctor are almost absent during unattended BP measurement, during which, if anything, a modest cardiovascular sympathoinhibition occurs. This has important implications for comparison of studies using these different BP measurement approaches as well as for decision concerning threshold and target BP values for treatment.

New antidiabetic therapy and HFpEF: light at the end of tunnel?

Abstract: New antidiabetic therapy that includes sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors showed significant benefit on cardiovascular outcomes in patients with and without type 2 diabetes mellitus, and this was particularly confirmed for SGLT2 inhibitors in subjects with heart failure (HF) with reduced ejection fraction (HFrEF). Their role on patients with HF with preserved ejection fraction (HFpEF) is still not elucidated, but encouraging results coming from the clinical studies indicate their beneficial role. The role of GLP-1R agonists and particularly DPP-4 inhibitors is less clear and debatable. Findings from the meta-analyses are sending positive message about the use of GLP-1R agonists in HFrEF therapy and revealed the improvement of left ventricular (LV) diastolic function in HFpEF. Nevertheless, the relevant medical societies still consider their effect as neutral or insufficiently investigated in HF patients. The impact of DPP-4 inhibitors in HF is the most controversial due to conflicting data that range from negative impact and increased risk of hospitalization due to HF, throughout neutral effect, to beneficial influence on LV diastolic dysfunction. However, this is a very heterogeneous group of medications and some professional societies made clear discrepancy between saxagliptin that might increase risk of HF hospitalization and those DPP-4 inhibitors that have no effect on hospitalization. The aim of this review is to summarize current clinical evidence about the effect of new antidiabetic medications on LV diastolic function and their potential benefits in HFpEF patients.

Monotherapy vs combination treatments of different complexity: a meta-analysis of blood pressure lowering randomized outcome trials.

Abstract: Background Use of drug combinations is recommended by hypertension guidelines for most patients because of the greater blood pressure (BP)-lowering effect compared with monotherapy. However, no evidence is available on outcome benefits of treatment strategies based on drug combinations vs. simpler treatment regimens, using data from randomized clinical trials (RCTs). We evaluated drug combination therapies of different complexity. Methods Electronic databases were searched for BP-lowering RCTs that compared combination treatment or monotherapy vs. placebo, no-treatment or less-complex treatment. Combination treatment was considered as follows: background treatment continued during follow-up on top of the trial drug(s) of interest and drug(s) were added to the initial drug(s) of interest in the majority of the patients. Monotherapy was considered whenever pre-randomization treatment was withdrawn or absent and a single drug was administered at randomization. Complexity of treatment indicates the higher averaged number of daily medications used in the eligible RCTs. Results We selected 93 trials (290 304 patients; follow-up, 3.9 years). The on-treatment mean number of drugs was 2.10 and 0.99 in the more and less actively treated patients, respectively. Compared with placebo, no-treatment or less-complex treatment, combination treatments of any complexity (mean number of drugs, 1.40 vs. 0.41, 2.32 vs. 0.48, 2.56 vs. 1.62 and 3.14 vs. 2.19) were associated with reduction of all or most fatal and nonfatal outcomes. There was also an increased rate of side effects leading to treatment discontinuation, although in absolute numbers the benefit usually prevailed. Conclusion These data provide randomized-based trial evidence that antihypertensive combination treatment up to three or more drugs is protective. The net benefit, however, may be attenuated when side effects are considered.

Autonomic Cardiovascular Alterations in Chronic Kidney Disease: Effects of Dialysis, Kidney Transplantation, and Renal Denervation.

Abstract: To review the results of studies of the effects of dialysis and kidney transplantation on the autonomic nervous system alterations that occur in chronic kidney disease. Vagal control of the heart mediated by arterial baroreceptors is altered early in the course of the renal disease. Sympathetic activation occurs, with increases in resting heart rate, venous plasma norepinephrine levels, muscle sympathetic nerve traffic, and other indirect indices of adrenergic drive. The magnitude of the changes reflects the clinical severity of the kidney disease. Both the sympathetic and parasympathetic alterations have a reflex origin, depending on the impairment in baroreflex and cardiopulmonary reflex control of the cardiovascular system. These alterations are partially reversed during acute hemodialysis, but the responses are variable depending on the specific type of dialytic treatment that is employed. Renal transplantation improves reflex cardiovascular control, resulting in sympathoinhibition following renal transplantation if the native kidneys are removed. Sympathoinhibitory effects have been also reported in renal failure patients after bilateral renal denervation. Assessment of autonomic nervous system responses to dialysis and renal transplantation provides information of clinical interest, given the evidence that autonomic alterations are involved in the development and progression of cardiovascular complications, as well as in the prognosis of chronic kidney disease.

Stratification of the risk of developing severe or lethal Covid-19 using a new score from a large Italian population: a population-based cohort study.

Abstract: Objectives To develop a population-based risk stratification model (COVID-19 Vulnerability Score) for predicting severe/fatal clinical manifestations of SARS-CoV-2 infection, using the multiple source information provided by the healthcare utilisation databases of the Italian National Health Service. Design Retrospective observational cohort study. Setting Population-based study using the healthcare utilisation database from five Italian regions. Participants Beneficiaries of the National Health Service, aged 18-79 years, who had the residentship in the five participating regions. Residents in a nursing home were not included. The model was built from the 7 655 502 residents of Lombardy region. Main outcome measure The score included gender, age and 29 conditions/diseases selected from a list of 61 conditions which independently predicted the primary outcome, that is, severe (intensive care unit admission) or fatal manifestation of COVID-19 experienced during the first epidemic wave (until June 2020). The score performance was validated by applying the model to several validation sets, that is, Lombardy population (second epidemic wave), and the other four Italian regions (entire 2020) for a total of about 15.4 million individuals and 7031 outcomes. Predictive performance was assessed by discrimination (areas under the receiver operating characteristic curve) and calibration (plot of observed vs predicted outcomes). Results We observed a clear positive trend towards increasing outcome incidence as the score increased. The areas under the receiver operating characteristic curve of the COVID-19 Vulnerability Score ranged from 0.85 to 0.88, which compared favourably with the areas of generic scores such as the Charlson Comorbidity Score (0.60). A remarkable performance of the score on the calibration of observed and predicted outcome probability was also observed. Conclusions A score based on data used for public health management accurately predicted the occurrence of severe/fatal manifestations of COVID-19. Use of this score may help health decision-makers to more accurately identify high-risk citizens who need early preventive or treatment interventions.

Comprehensive assessment of hypertensive heart disease: cardiac magnetic resonance in focus.

Abstract: Arterial hypertension represents the most frequent cardiovascular risk factor that is associated with cardiac remodeling. Hypertensive heart disease was defined by the presence of left ventricular hypertrophy (LVH) and diastolic dysfunction, and it has been diagnosed by echocardiography in everyday clinical practice. Interstitial myocardial fibrosis is the underlying cause of hypertension-induced cardiac remodeling, and it could not be visualized with different echocardiographic methods. Cardiac magnetic resonance (CMR) and its methods such as late gadolinium enhancement, and T1 mapping provides qualitative and quantitative assessment of interstitial myocardial fibrosis in hypertensive patients. Furthermore, CMR can provide differentiation of LVH between hypertensive patients and cardiomyopathies (hypertrophic or Fabry disease). Timely diagnosis of cardiac impairment and early treatment is essential because regression of LVH could be achieved with adequate treatment. Diffuse cardiac fibrosis in hypertensive patients might be an underlying mechanism that explains the increased cardiovascular morbidity and mortality in this population. Future longitudinal investigations are necessary to determine causal relationship between diffuse fibrosis and cardiovascular outcome in these patients. The aim of this review is to summarize the current knowledge regarding CMR techniques and their potential usage in patients with hypertensive heart disease.