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Objective: To compare the vascular effects of pursuing more versus less glucose lowering in patients with younger or older age at diabetes diagnosis, and with shorter or longer diabetes duration., Research Design and Methods: We studied 11,138 participants from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, classified into subgroups defined by age at diabetes diagnosis (≤50, >50-60, and >60 years) and diabetes duration (≤5, >5-10, and >10 years)., Results: Intensive glucose lowering significantly lowered the risk of the primary composite outcome of major macrovascular and microvascular events (hazard ratio 0.90, 95% CI 0.82-0.98) with no evidence of heterogeneity in the proportional effects across subgroups defined by age at diagnosis or diabetes duration (P for heterogeneity = 0.86 and 0.47, respectively). Similar consistent treatment effects were also observed for all-cause death, cardiovascular death, and the components of major vascular events., Conclusions: Intensive glucose lowering may be recommended irrespective of age at diagnosis or diabetes duration., (© 2024 by the American Diabetes Association.)

The autonomic nervous system plays a crucial role in regulating physiological processes and maintaining homeostasis through its two branches: the sympathetic nervous system (SNS) and the parasympathetic nervous system. Dysregulation of the autonomic system, characterized by increased sympathetic activity and reduced parasympathetic tone, is a common feature in chronic kidney disease (CKD) and cardiovascular disease. This imbalance contributes to a pro-inflammatory state, exacerbating disease progression and increasing the risk for cardiovascular events. The sympathetic system promotes inflammation by releasing catecholamines, which activate adrenergic receptors on immune cells. The parasympathetic system exerts anti-inflammatory effects via the cholinergic anti-inflammatory pathway mediated by the vagus nerve. Targeting the autonomic system to restore the balance between the sympathetic and the parasympathetic components offers promising approaches to reduce inflammation and improve outcomes in CKD and cardiovascular disease. Beta-blockers, angiotensin-converting enzyme inhibitors (ACEi), and angiotensin II receptor blockers (ARBs) are pharmacological agents that modulate sympathetic activity and have shown anti-inflammatory effects. Lifestyle interventions, such as a healthy diet, physical exercise, mindfulness, and meditation, enhance parasympathetic activity and improve autonomic function. Vagus nerve stimulation has emerged as a promising therapy, demonstrating significant potential in reducing inflammation and improving clinical outcomes in various conditions, including CKD, myocardial infarction and stroke. Despite mixed results in heart failure trials, vagal nerve stimulation has consistently improved quality-of-life measures. Understanding the mechanisms underlying autonomic system regulation of inflammation can inform the development of novel therapeutic strategies to restore autonomic balance and improve patient outcomes in CKD and cardiovascular disease., (© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)

Aims: To compare adherence to perindopril/amlodipine/atorvastatin combination administrated as a polypill (one pill) vs separate tablets., Methods: Using the healthcare utilization database of Lombardy (Italy), 1 110 patients who received the perindopril/amlodipine/atorvastatin polypill during 2019-2021 were matched with 1 110 patients prescribed the same combination in separate tablets or as two antihypertensive drugs in a single tablet and the lipid-lowering drug tablet separately. Adherence to treatment was assessed over the year after the first perindopril/amlodipine/atorvastatin dispensation as the proportion of the follow-up days covered by prescription (PDC). Patients with a PDC > 75% and < 25% were defined as highly and poorly adherent, respectively. Adherence dynamics over time were evaluated through group-based trajectory modelling. Cardiovascular-related healthcare costs were also assessed. Log-binomial regression models were fitted to estimate the risk ratio (RR) of treatment adherence associated with the administration strategy., Results: Among the polypill and the separate-pill combination users, 60% and 18% of patients showed high adherence, respectively; the corresponding figures for the low adherence were 5% and 37%. Compared with the separate-pill combination, the polypill increased the propensity to be highly adherent to treatment by 3.29 times (95% confidence interval: 2.88-3.75) and reduced the low adherence risk (RR = 0.13, 0.10-0.18), irrespective of sex, age, comorbidities, and co-treatment burden also throughout the entire follow-up. The polypill was also associated with lower costs (€676 vs €1 068, p = 0.003)., Conclusions: In a real-life setting, the polypill improved treatment adherence and reduced healthcare costs compared to the corresponding separate-pill combination. These findings support current guidelines in favour of the polypill., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To systematically appraise and summarize the available evidence from published randomized controlled trials considering the effect of nebivolol on blood pressure in patients with hypertension., Methods: Literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until December 15, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis., Results: In total, 7,737 participants with hypertension, who were treated with nebivolol, were analyzed across 91 RCTs. Nebivolol was associated with significantly greater reduction in office systolic and diastolic BP compared to placebo (MD = - 6.01 mmHg; 95% CI = [- 7.46, - 4.55] and MD = - 5.01 mmHg; 95% CI = [- 5.91, - 4.11], respectively). Moreover, resulted a similar reduction in systolic BP (MD = - 0.22 mmHg; 95% CI = [- 0.91, 0.46]) and a significantly greater reduction in diastolic BP compared to the active comparator (MD = - 0.71 mmHg; 95% CI = [- 1.27, - 0.16]). When considering the effect of nebivolol on 24-hour ambulatory BP, notable reductions were observed compared to placebo. In contrast, compared to the active comparators, there was no significant difference in systolic BP reduction, but a significant reduction in diastolic BP favoring nebivolol. Based on moderator analyses, the impact of nebivolol on the pooled estimates remained independent of the dose of nebivolol, age, male sex, trial duration, body mass index (BMI), baseline diabetes, heart failure, and baseline systolic and diastolic BP., Conclusion: Nebivolol, compared to placebo, showed a significant BP reduction and was non-inferior to other active comparators in terms of BP reduction., Competing Interests: Declarations. Authors contribution: Athanasios Manolis: Conceptualization, Methodology, Investigation, Project administration, Writing—review & editing. Paschalis Karakasis: Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Visualization, Writing -original draft, Writing—review & editing. Dimitrios Patoulias: Conceptualization, Methodology, Investigation, Writing—original draft, Writing—review & editing. Michalis Doumas: Conceptualization, Methodology, Investigation, Project administration, Writing—review & editing. Manolis Kallistratos: Conceptualization, Methodology, Investigation, Writing—review & editing. Costas Thomopoulos: Conceptualization, Methodology, Investigation, Writing—review & editing. Maria Koutsaki: Investigation, Writing—review & editing. Guido Grassi: Conceptualization, Methodology, Investigation, Project administration, Writing—review & editing. Giuseppe Mancia: Conceptualization, Methodology, Investigation, Project administration, Writing—review & editing. All authors read and approved the final manuscript. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors for its design or conduction. Conflict of interest: The authors declare that they have no conflict of interest. Protocol: The study protocol was prepared a priori and registered in OSF ( https://osf.io/bm9cx/ ). Data availability: The data generated in this research will be shared on reasonable request to the corresponding author., (© 2024. The Author(s).)

Objective: The COVID-19 pandemic had a major impact on medical care. This study evaluated the influence of the pandemic on blood pressure (BP) control and hypertension phenotypes as assessed by office and 24-hour ambulatory BP monitoring (ABPM)., Design and Methods: Data were collected from 33 centers including Excellence Centers of the European Society of Hypertension. Two groups of patients with treated hypertension were compared. Pandemic group: including participants who had ABPM twice - at visit 2 during the COVID-19 pandemic and visit 1 performed 9-15 months prior to visit 2. Pre-pandemic group: had ABPM at two visits, performed before the pandemic within 9-15 months interval. We determined the following hypertension phenotypes: masked hypertension, white coat hypertension, sustained controlled hypertension (SCH) and sustained uncontrolled hypertension (SUCH). We analyzed the prevalence of phenotypes and their changes between visits., Results: Data of 1419 patients, 616 (43 %) in the pandemic group and 803 (57 %) in the pre-pandemic group, were analyzed. At baseline (visit 1), the prevalence of hypertension phenotypes did not differ between groups. In the pandemic group, the change in hypertension phenotypes between two visits was not significant (p = 0.08). In contrast, in the pre-pandemic group, the prevalence of SCH increased during follow-up (28.8 % vs 38.4 %, p < 0.01) while the prevalence of SUCH decreased (34.2 % vs 27.8 %, p < 0.01). In multivariable adjusted analysis, the only factor influencing negative changes of hypertension phenotypes was the COVID-19 pandemic period., Conclusion: These results indicate a negative impact of the COVID-19 pandemic on BP control assessed by hypertension phenotypes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hypertension is responsible for more than two million deaths due to cardiovascular disease annually in Latin America (LATAM), of which one million occurs before 70 years of age. Hypertension is the main risk factor for cardiovascular morbidity and mortality, affecting between 20 and 40% of LATAM adults. Since the publication of the 2017 LASH hypertension guidelines, reports from different LATAM countries have confirmed the burden of hypertension on cardiovascular disease events and mortality in the region. Many studies in the region have reported and emphasized the dramatically insufficient blood pressure control. The extremely low rates of awareness, treatment, and control of hypertension, particularly in patients with metabolic disorders, is a recognized severe problem in LATAM. Earlier implementation of antihypertensive interventions and management of all cardiovascular risk factors is the recognized best strategy to improve the natural history of cardiovascular disease in LATAM. The 2024 LASH guidelines have been developed by a large group of experts from internal medicine, cardiology, nephrology, endocrinology, general medicine, geriatrics, pharmacology, and epidemiology of different countries of LATAM and Europe. A careful search for novel studies on hypertension and related diseases in LATAM, together with the new evidence that emerged since the 2017 LASH guidelines, support all statements and recommendations. This update aims to provide clear, concise, accessible, and useful recommendations for health professionals to improve awareness, treatment, and control of hypertension and associated cardiovascular risk factors in the region., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In the absence of outcome-based ambulatory blood pressure (BP) trails hypertension guidelines provide 24-hour mean BP values corresponding to trial-validated office BP values. Data are shown for untreated and treated patients together, but whether corresponding ambulatory values are similar in untreated and treated hypertensives and reproducible at yearly measurements during treatment is undefined., Methods: In 2397 patients of the ELSA (European Lacidipine Study on Atherosclerosis) and PHYLLIS (Plaque Hypertension Lipid-Lowering Italian Study) trials, we calculated the office and 24-hour BP relationship according to the linear regression model, with office systolic BP as the independent variable, at baseline and yearly during a 3-year treatment. Twenty-four hour BP values corresponding to clinically important office BP values (hypertension grading and treatment thresholds and targets) were calculated and compared with those provided by guidelines., Results: Office and 24-hour systolic BP or diastolic BP always exhibited a significant linear relationship, with, however, limited Pearson correlation coefficients (never >0.44).The slopes of the relationship were superimposable between different years of treatment but always significantly less steep than the slope seen in untreated individuals. Compared with the guideline-provided corresponding values, 24-hour BP showed qualitative and quantitative differences; for example, it was considerably lower and higher than the guideline-corresponding values when office BP was in the high hypertension and low treatment target ranges, respectively., Conclusions: In treated patients with hypertension the slope of the office and 24-hour BP linear regression is reproducible over time. However, the slopes are steeper in untreated individuals, indicating that information on ambulatory BP values corresponding to office BP values can be more accurate if separately estimated in these 2 conditions., Competing Interests: None.

Background: There is a paucity of data investigating the impact of antihypertensive drug classes and blood pressure (BP) treatment targets on the incidence of end-stage kidney disease (ESKD). In patients with high-risk hypertension aged 50-80 years or above, we aimed to, 1) compare effects of valsartan, an angiotensin receptor blocker, with amlodipine, a calcium channel blocker and, 2) assess the effect of achieving systolic BP <135 vs ≥135 mmHg on the ESKD incidence., Methods: The VALUE Trial was a multicenter prospective double-blinded randomized clinical trial in patients with essential hypertension and high cardiovascular risk including known coronary disease, left ventricular hypertrophy and previous stroke, in which ESKD was a secondary endpoint defined as progression to kidney transplant and/or dialysis. Patients were randomized to either valsartan or amlodipine, with other anti-hypertensive medications as add-on if needed to reach the systolic BP target of <140 mmHg. Cox proportional hazards ratio (HR) was used to compare different treatment groups and achieved systolic BP <135 with ≥135 mmHg, during 3-6 years of follow-up., Results: 15,245 patients were randomized and followed until 63,631 patient-years with only 90 patients lost to follow-up. The primary outcome, a composite of cardiac morbidity and mortality, was neutral between valsartan and amlodipine. On valsartan 47 patients (0.61 %) and on amlodipine 50 patients (0.66 %) developed ESKD (HR=1.02, 95 % CI 0.68-1.52, p =0.94). Achieved SBP <135 mmHg was strongly related to less ESKD (n =9/5036 patients, 0.2 %) compared with achieved SBP ≥135 mmHg (n =73/8766 patients, 0.8 %) (HR=0.28, CI 0.14-0.58, p <0.001)., Conclusions: In hypertensive patients with a high cardiovascular risk, valsartan and amlodipine have a similar impact on the incidence of end-stage kidney disease. Achieving SBP <135 mmHg, averaging 128.8/77.3 mm, is highly efficacious in kidney protection., Competing Interests: Declaration of competing interest R.E.S. reports honoraria from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, MSD, Menarini Group, Novartis, Recor, and Servier. G.M. reports honoraria from Astra Zeneca, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Menarini Group, Merck, Novartis, Recordati, Sandoz, Sanofi, and Servier. S.E.K. reports lecture honoraria from Emcure, Getz, J.B. Pharma, Merck Healthcare KGaA, Sanofi-Aventis and Vector-Intas. A.H. reports lecture honoraria from AZ. M.B. reports honoraria from Bayer, Menarini, Sanofi, and Servier. M.A.W. reports honoraria from Ablative Solutions, Johnson & Johnson, Medtronic, ReCor, and Urovant. No other disclosures were reported., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Accumulating evidence indicates that reducing high blood pressure (BP) prevents dementia and mild cognitive impairment (MCI). Furthermore, although diabetes is a risk factor for dementia and MCI, there is uncertainty of the effect of intensive glucose control on these endpoints. This study aimed to determine the effects of BP-lowering (vs placebo) and intensive glucose-lowering (vs standard control) treatments according to baseline cognition and other characteristics on dementia and cognitive decline (CD) in people with type 2 diabetes mellitus (T2DM)., Methods: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial involved 11,140 individuals with T2DM. The effects of BP-lowering and intensive glucose-lowering treatments were explored in subgroups of baseline Mini-Mental State Examination (MMSE), categorised as cognitively normal (scores ≥28) and cognitive impairment (scores <28). The primary outcome was a composite of dementia/CD that accounted for the competing risk of death. Multinomial regression models, adjusted for common cardiovascular risk factors, were used to estimate odds ratios (OR) with 95 % confidence intervals (CI) of the effects of the treatments on dementia/CD. Homogeneity of effects by subgroups were evaluated using interaction terms in the models. A two-sided p value <0.05 was regarded as statistically significant., Results: BP-lowering treatment (vs. placebo) was associated with a lower odds of dementia/CD in participants with cognitive impairment (OR 0.76, 95 % CI (0.59-0.99)) but not in those cognitively normal (OR 1.05, 95 % CI (0.92-1.21); p for interaction 0.03). Those with a history of cardio-renal-metabolic syndrome did not experience a benefit of active BP lowering treatment compared with placebo on dementia/CD. There were no further subgroup effects of BP-lowering treatment. The effect of intensive glucose lowering (vs standard control) on the odds of dementia/CD did not vary by baseline cognition subgroup. However, it did vary by level of blood glucose at baseline (<7.9 mmol/L OR 1.12, 95 % CI (0.96-1.30) vs ≥ 7.9 mmol/L 0.87 (0.75-1.00); p for interaction 0.02) and duration of T2DM (<10 years OR 0.92 (0.81-1.05) vs ≥10 years 1.16 (0.97-1.38); p for interaction 0.04)., Conclusions: This study suggests greater effects of BP-lowering treatment in those with early loss of cognitive function than in those cognitively normal. There were also differential effects of intensive glucose-lowering on dementia and CD according to levels of blood glucose and duration of diabetes in people with T2DM., Clinical Trial Registration: ADVANCE is registered with ClinicalTrials.gov: number NCT00145925., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.C. reports research grants from Servier and from the National Health and Medical Research Council (NHMRC) of Australia, for the ADVANCE trial and for the ADVANCE-ON study, all before 2014, and Program Grant APP1149987 from the NHMRC for 2019–2023 for “Clinical, Public Health and Policy Interventions to Combat Cardiovascular Diseases”. M.W. reports consultancy fees from Amgen, Kirin and Freeline and is supported by 10.13039/501100000925NHMRC grants APP1149987 and APP1174120. In the past 24 months G.M. has received compensations as speaker/chairman/consultant from: Berlin Chemie, IPCA Laboratories, Medtronic Inc USA, Menarini Int, Merck Healthcare KGaA, Omnicuris, Recordati, Sanofi, Servier, Sun Laboratories. N.P. has received personal speaker fees from Servier, Takeda and Novo Nordisk, and advisory board activities from AstraZeneca and Novo Nordisk, and has received grants for his research group relating to diabetes mellitus from Diabetes UK, NIHR Efficacy and Mechanism Evaluation Programme (EME), Julius Clinical and the British Heart Foundation with a pending grant from Novo Nordisk. N.P. holds no stocks or shares in any such companies. C.A. is on the Advisory Board for AstraZeneca Australia., (© 2024 The Authors.)

Aim: Whether apolipoproteins (apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 [ApoB/ApoA1] ratio) or very-low-density lipoprotein (VLDL) cholesterol are better risk predictors than established lipid risk markers, and whether there are sex differences, is uncertain, both in general populations and in patients with diabetes. The aim of this study was to assess the association between established risk markers, apolipoproteins and the risk of macro- and microvascular disease and death in a large study of women and men with diabetes and to assess the potential sex differences in the associations., Materials and Methods: Established lipid risk markers were studied in 11 140 individuals with type 2 diabetes from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial, and apolipoproteins (A1, B, ApoB/ApoA1 ratio) and VLDL cholesterol from nuclear magnetic resonance (NMR) lipid analyses in biobanked samples from 3586 individuals included in the ADVANCE case-cohort study (ADVANCE CC). Primary outcomes were major macro- and microvascular events and death. Cox proportional hazards models adjusted for confounders were used to quantify the associations (hazard ratio [HR] and 95% confidence intervals [CIs]) between established lipid risk markers and apolipoproteins with study outcomes. To address potential effect modification by sex, we investigated the association between the lipid risk markers and outcomes in subgroup analyses by sex., Results: There was a lower risk of macrovascular complications for high-density lipoprotein (HDL) cholesterol (HR [95%CI] 0.88 [0.82-0.95]), a higher risk for total cholesterol (1.10 [1.04-1.17]), low-density lipoprotein (LDL) cholesterol (1.15 [1.08-1.22]), non-HDL cholesterol (1.13 [1.07-1.20]) and the total cholesterol/HDL ratio (1.20 [1.14-1.27]) but no significant associations with triglycerides from ADVANCE. There was a higher risk of macrovascular complications for the ApoB/ApoA1 ratio (1.13 [1.03-1.24]) from the ADVANCE CC. Only the ApoB/ApoA1 ratio (1.19 [1.06-1.34]), but none of the established lipid risk markers, was associated with a higher risk of microvascular complications. There were no statistically significant sex differences for any of the established lipid risk markers or apolipoproteins with any outcome. Using C-statistics and net reclassification improvement (NRI) did not detect significant improvement in predicting all outcomes by adding lipids or apolipoproteins to the models with confounding factors only., Conclusions/interpretation: All established lipid risk markers, except triglycerides, were predictors of macrovascular complications, but not microvascular complications, in patients with type 2 diabetes. The ApoB/ApoA1 ratio was associated with major macro- and microvascular complications, but there was no evidence that apolipoproteins are better than established lipid risk markers in predicting cardiovascular complications in patients with type 2 diabetes., (© 2024 John Wiley & Sons Ltd.)

The Action in Diabetes and Vascular disease: preterAx and diamicroN Controlled Evaluation (ADVANCE) trial investigated the effects of intensive blood pressure (BP) lowering using a fixed combination of perindopril-indapamide versus placebo in type 2 diabetes (T2D). The study showed that combination perindopril-indapamide had significant benefits in reducing cardiovascular, renal, and mortality events, with consistent relative risk reductions across different patient subgroups. Secondary analyses of ADVANCE have identified novel risk markers in T2D including cessation of BP lowering therapy, absent peripheral pulses and cardiac biomarkers to name a few. ADVANCE also shed light on practical aspects of hypertension management, including the limitations of office BP, tolerability of combination BP lowering therapy across the range of BP levels and the interpretation of changes in serum creatinine after treatment initiation. This review article summarizes the findings of ADVANCE and its subsequent substudies, which have been foundational in our understanding of BP management and the use of combination BP lowering therapy in T2D., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Despite dramatic medical advances over the last few decades, cardiovascular disease remains a leading cause of death globally. High BP is clearly established, but modifiable, risk factor for early disability and death. Although most of the adverse outcomes occur in adulthood it has become clear that high BP is a life course problem that can become evident in early life however, relatively little attention has been paid to the problem of high BP in children and adolescents. Materials and methods: Being aware of the problem and the needs, the Task Force of the ESH Guidelines in children and adolescents took the initiative to move forward in the field, identifying the COST Action program. A proposal, HyperChildNET, was submitted, approved and funded for 4 years starting in October 2020. Results: The aim of the Action has been to establish a European sustainable and multidisciplinary network of researchers, clinicians, early career investigators, health economists, decision-makers, regulatory bodies, and medical devices manufacturers under the umbrella of the European Commission in order to acquire a holistic understanding of those factors affecting high BP in children and adolescents in order to propose and implement preventive and corrective actions. All the activities carried out during the 4 years are described. Conclusions: HyperChildNET offers a European perspective of the issue giving us the opportunity to develop new strategies and objectives moving forward in the field.

Objective: Available data on the association between antihypertensive drugs and cancer are characterized by a few years follow-up. Our aim has been to evaluate the association between long-term exposure to antihypertensive drugs and the risk of cancer occurrence., Methods: Using the healthcare utilization databases of the Lombardy region (Italy), individuals aged 40-85 years who had no previous history of cancer and were newly dispensed with at least one antihypertensive drug from the major drug classes between 2009 and 2011 were followed from the first drug dispensation to December 31, 2020. Data were analyzed according to the first drug used and the intention to treat principle, but also via an "as treated" approach, that is, by considering changes of and exposure to drugs during follow-up. The association between the duration of exposure to each drug class and the risk of cancer occurrence was evaluated using the adjusted Cox regression models., Results: The study cohort included 338 910 new drug users (median age, 59 years; 49.5% males). During a median follow-up of 10.2 years, 36 556 cancers occurred. There was no consistent significant association between the risk of cancer occurrence and angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or thiazides. A progressive, weak increase in cancer occurrence was associated with progressive exposure to calcium channel blockers and, limited to long-term exposure, to beta-blockers. A modest progressive increase in risk was observed also for thiazide-like and loop diuretics in the as treated, although not in the intention to treat approach., Conclusions: Long-term evaluation of exposure to antihypertensive drugs did not show consistent associations between thiazides, angiotensin-receptor blockers, or angiotensin-converting-enzyme inhibitors and the risk of cancer occurrence. A weak association was observed between cancer and the duration of exposure to calcium channel blockers and beta-blockers., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: We aimed to determine the influence of coronavirus disease 2019 (COVID-19) pandemic on blood pressure (BP) control assessed by ambulatory blood pressure monitoring (ABPM)., Methods: Office BP and ABPM data from two visits conducted within a 9-15 months interval were collected from patients treated for hypertension. In the prepandemic group, both visits took place before, while in the pandemic group, Visit-1 was done before and Visit-2 during the pandemic period., Results: Of 1811 collected patients 191 were excluded because they did not meet the required ABPM time frames. Thus, the study comprised 704 patients from the pandemic and 916 from the prepandemic group. Groups did not differ in sex, age, duration of hypertension, frequency of first line antihypertensive drug use and mean 24 h BP on Visit-1. The prevalence of sustained uncontrolled hypertension was similar in both groups. On Visit-2 mean 24 h BP, daytime and nighttime systolic BP and diastolic BP were higher in the pandemic compared to the prepandemic group ( P  < 0.034). The prevalence of sustained uncontrolled hypertension on Visit-2 was higher in the pandemic than in the prepandemic group [0.29 (95% confidence interval (95% CI): 0.26-0.33) vs. 0.25 (95% CI: 0.22-0.28), P  < 0.037]. In multivariable adjusted analyses a significant difference in BP visit-to-visit change was observed, with a more profound decline in BP between visits in the prepandemic group., Conclusions: This study using ABPM indicates a negative impact of the COVID-19 pandemic on BP control. It emphasizes the need of developing strategies to maintain BP control during a pandemic such as the one induced by COVID-19., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Evidence on the association of arterial stiffness and left ventricular (LV) concentric remodelling/LVH assessed by echocardiography, with abnormal blood pressure (BP) phenotypes, defined by office and ambulatory BP monitoring (ABPM) in the community is scanty. Thus, we investigated this issue in the participants to the Pressioni Monitorate E Loro Associazioni (PAMELA) study., Methods: The present study included 491 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, blood examinations, office, ABPM, echocardiographic and Cardio-Ankle Vascular Index (CAVI) measurements., Results: In the whole study sample (age 66+10 years, 50% males), the prevalence rates of sustained normotension (NT), white coat hypertension (WCH), masked hypertension (MH), sustained hypertension (SH) and non-dipping (ND) were 31.2, 10.0, 24.2, 34.6, and 35.8% and respectively. The likelihood of having SH, the BP phenotype carrying the greatest CV risk, was four times higher (OR= 4.31, CI:2.39-7.76, p<0.0001) in participants with increased CAVI and LV remodelling/LVH compared to their counterparts without organ damage. This association showed an incremental value in discriminating SH compared to both isolated markers of organ damage (OR=1.92,p=0.03 for increased CAVI and OR= 2.02, p=0.02 for LV remodelling/LVH). The presence of isolated but also combined organ damage was unrelated to ND., Conclusions: Our study provides new evidence of the incremental value of looking for both vascular and cardiac target organ damage to optimize the identification and clinical management of SH in the general population., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Background and Aims: Evidence has been provided that in the normotensive population chronic coffee consumption does not adversely affect cardiovascular and total mortality. Whether and to what extent this is the case also in high risk cardiovascular patients such as those with elevated blood pressure (BP) is largely debated., Methods and Results: We analyzed data collected in 943 hypertensive patients belonging to the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, which were classified as coffee consumers and non-consumers (self report). Cardiovascular and total mortality were evaluated at the 25 year follow-up taking into account a number of variables including office and 24-h ambulatory BP. When data were analyzed as unadjusted values no significant difference in hazard ratios for cardiovascular and total mortality was detected in coffee consumers and non-consumers considering office (0.85 and 0.83 respectively, PNS) or 24-h (1.08 vs 0.80 respectively, PNS) BP. This was the case also when the data were adjusted for confounders (age, sex, BP, lipid profile, plasma glucose and cholesterol levels, renal function, previous cardiovascular events) or when analyzed according to presence or absence of antihypertensive treatment., Conclusions: Thus in mild-to-moderate hypertensive patients chronic coffee consumption does not exert deleterious long-term effects on cardiovascular and total mortality. This is the case in both genders and in treated and untreated hypertensive patients., Competing Interests: Declaration of competing interest The Authors of the paper “Habitual coffee consumption and risk of cardiovascular and all-cause mortality in the PAMELA hypertensive population” submitted to Nutrition metabolism and Cardioavscular Diseases report no conflict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: We evaluated whether chronic coffee consumption affects arterial stiffness, assessed by cardio-ankle vascular index (CAVI)., Methods: In 514 subjects, aged 66.6 ± 9.9 years (mean ± SD), recruited in the 3rd follow-up of the PAMELA study, subdivided into 3 groups according to the daily intake of regular coffee (0, 1-2, and ≥3 cups/day), we measured CAVI and clinic, ambulatory blood pressure (BP), and other variables., Results: The 3 groups displayed similar age, gender, metabolic, and renal profile. Clinic and ambulatory BPs were similar in the 3 groups, this being the case for CAVI (0 cup: 9.1 ± 1.8, 1-2 cups: 9.5 ± 2.3, and ≥3 cups: 9.2 ± 2.1 m/s, P = NS). No significant gender difference in CAVI and in participants under antihypertensive treatment was detected., Conclusions: Our data show that chronic coffee consumption leaves unaffected arterial stiffness in the general population, this being the case in subgroups. The neutral vascular impact of coffee may favor the absence of any significant BP effect of habitual coffee intake., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Limited data exist on the relationship between declining kidney function and cardiovascular events, dementia, and mortality in patients with a history of stroke.Thus the aims of the study were to investigate functional relationships between dynamic kidney function change and cardiovascular outcomes, and clarify whether adding kidney parameters to conventional cardiovascular risk factors improves model discrimination., Methods: Post hoc analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) clinical trial of blood pressure lowering for the secondary prevention of stroke. We examined the association between dynamic kidney function defined as percentage change (declines of >30%, and >0 to ≤30%, and increases of ≥0 to <30%, and ≥30%) in estimated glomerular filtration rate (eGFR) over 2 years and recurrent stroke, major cardiovascular events, dementia and all-cause death over the next 2 years using Cox proportional hazard models controlling for eGFR at registration and potential confounders. Restricted cubic splines were used to assess the functional relationships. C-statistics and Net Reclassification Improvement (NRI) at 2 years were used to assess model discrimination., Results: In 4591 patients followed for a mean of approximately 2 years, 254 (5.5%) developed recurrent stroke, 391 (8.5%) had a major cardiovascular event, 221 (4.8%) developed dementia, and 271 (5.9%) died. Reverse J-like or U-like relationships were observed for percent declines in eGFR and outcomes. Using declines in eGFR of >0 to ≤30% as a reference, increased risks were evident for a greater decline (>30%) in relation to recurrent stroke [adjusted hazard ratio 1.85, 95% confidence interval (CI) 1.20-2.85], major cardiovascular event (2.24, 1.62-3.10) and all-cause death (2.09, 1.39-3.15). A larger increase (≥30%) in eGFR was also associated with a greater risk of all-cause death (1.96, 1.14-3.37). Improvements in the C-statistic were found by adding baseline eGFR and percent change compared with a model with conventional cardiovascular risk factors alone, for major cardiovascular events, dementia, and all-cause mortality., Conclusion: Declining kidney function following an incident cerebrovascular event is associated with additional risk of a major cardiovascular events, dementia, and 2-year mortality. However, a large increase in kidney function was also found to be associated with a higher risk of mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Clinical trials have shown that in type 2 diabetes mellitus (T2D) resting office heart rate (HR) values > 70 beats/minute are associated with an increased cardiovascular risk, a worse prognosis and an unfavorable outcome. The present study was aimed at investigating whether the above mentioned treshold HR values reflect a sympathetic overdrive of marked degree., Methods: In 58 T2D patients (age range: 39-57 years) without signs of autonomic neuropathy and in 52 age-matched healthy controls, we assessed muscle sympathetic nerve activity (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC), subdividing the study population in different subgroups according to their clinic and 24-h HR values., Results: In T2D progressively greater clinic and 24-h HR values were accompanied by progressive increases in MSNA and NE. HR cutoff values indicated by clinical trials as associated with an increased cardiovascular risk (> 70 beats/minute) were accompanied by MSNA values significantly higher than those detected in patients with lower HR, this being the case also for NE. In T2D both MSNA and NE were significantly related to clinic (r = 0.93, P < 0.0001 and r = 0.87, P < 0.0001, respectively) and 24-h (r = 0.92, P < 0.0001 and r = 0.84, P < 0.0001, respectively) HR. The MSNA and NE behaviour observed in T2D was not detected in healthy controls., Conclusions: In T2D clinic HR values allow to detect patients with a greater sympathetic overactivity. Considering the adverse clinical impact of the sympathetic overdrive on prognosis, our data emphasize the need of future studies investigating the potential usefulness of lifestyle and pharmacological interventions exerting sympathomodulatory effects., (© 2024. The Author(s).)

Competing Interests: Declaration of competing interest The conflict of interest declaration of authors are compiled into one file that can be found on the ESH website: https://www.eshonline.org/guidelines/2023-guidelines/. ESH received no financial support for the generation of this guidelines.

Background: Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective., Methods: A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty., Results: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61-1.14), with a mean cost differential of -€12 (95% CI -9,719-8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871-€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17-7,813) and €2,027 (95% CI 19-8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574-10,640 vs. €3,710, 95% CI 263-11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status., Conclusions: The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system., (© 2024. The Author(s).)

Background: Findings regarding the association between Cardio-Ankle Vascular Index (CAVI) and the extent of nocturnal blood pressure (BP) fall in the general population are scanty. We sought to investigate this issue in the participants enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study., Methods: The study included 491 participants who attended the second and third surveys of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure BP monitoring (ABPM), blood examinations, echocardiography, and CAVI measurements., Results: In the whole study, both CAVI and left ventricular mass index (LVMI) were inversely correlated with nocturnal SBP fall, expressed as day-night percent change (r =  - 0.152, p = 0.0007, and r =  - 0.213, p < 0.0001, respectively). However, after adjustment for sex and age, the correlation remained significant only for LVMI (r =  - 0.124, p = 0.006). Non-dipper participants exhibited significantly higher sex-age adjusted LVMI (91 ± 22 vs 82 ± 18 g/m 2 (p < 0.0001)), but not of CAVI (9.07 ± 2.0 and 9.57 ± 2.2 m/s, p = ns). Similar results were found when classifying participants into quartiles of nocturnal SBP drop. Finally, both sex-age adjusted CAVI and LVMI were positively correlated with mean nocturnal SBP (r = 0.181, p < 0.001, and r = 0.240, p < 0.0001)., Conclusions: Although arterial stiffness assessed by CAVI, unlike LVMI, is unrelated with the degree of nocturnal BP drop, this marker is useful in identifying nocturnal hypertension and optimizing cardiovascular risk stratification in the community., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

In resistant hypertensive patients acute carotid baroreflex stimulation is associated with a blood pressure (BP) reduction, believed to be mediated by a central sympathoinhbition.The evidence for this sympathomodulatory effect is limited, however. This meta-analysis is the first to examine the sympathomodulatory effects of acute carotid baroreflex stimulation in drug-resistant and uncontrolled hypertension, based on the results of microneurographic studies. The analysis included 3 studies assessing muscle sympathetic nerve activity (MSNA) and examining 41 resistant uncontrolled hypertensives. The evaluation included assessment of the relationships between MSNA and clinic heart rate and BP changes associated with the procedure. Carotid baroreflex stimulation induced an acute reduction in clinic systolic and diastolic BP which achieved statistical significance for the former variable only [systolic BP: -19.98 mmHg (90% CI, -30.52, -9.43), P < 0.002], [diastolic BP: -5.49 mmHg (90% CI, -11.38, 0.39), P = NS]. These BP changes were accompanied by a significant MSNA reduction [-4.28 bursts/min (90% CI, -8.62, 0.06), P < 0.07], and by a significant heart rate decrease [-3.65 beats/min (90% CI, -5.49, -1.81), P < 0.001]. No significant relationship was detected beween the MSNA, systolic and diastolic BP changes induced by the procedure, this being the case also for heart rate. Our data show that the acute BP lowering responses to carotid baroreflex stimulation, although associated with a significant MSNA reduction, are not quantitatively related to the sympathomoderating effects of the procedure. This may suggest that these BP effects depend only in part on central sympathoinhibition, at least in the acute phase following the intervention., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Visit-to-visit blood pressure (BP) variability associates with an increased risk of cardiovascular events. We investigated the role of seasonal BP modifications on the magnitude of BP variability and its impact on cardiovascular risk., Methods: In 25 390 patients included in the ONTARGET and TRANSCEND trials, the on-treatment systolic (S) BP values obtained by five visits during the first two years of the trials were grouped according to the month in which they were obtained. SBP differences between winter and summer months were calculated for BP variability quintiles (Qs), as quantified by the coefficient of variation (CV) of on-treatment mean SBP from the five visits. The relationship of BP variability with the risk of cardiovascular events and mortality was assessed by the Cox regression model., Results: SBP was approximately 4 mmHg lower in summer than in winter regardless of confounders. Winter/summer SBP differences contributed significantly to each SBP-CV quintile. Increase of SBP-CV from Q1 to Q5 was associated with a progressive increase in the adjusted hazard ratio (HR) of the primary endpoint of the trials, i.e. morbid and fatal cardiovascular events. This association was even stronger after removal of the effect of seasonality from the calculation of SBP-CV. A similar trend was observed for secondary endpoints., Conclusions: Winter/summer SBP differences significantly contribute to visit-to-visit BP variability. However, this contribution does not participate in the adverse prognostic significance of visit-to-visit BP variations, which seems to be more evident after removal of the BP effects of seasonality from visit-to-visit BP variations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Systolic blood pressure (BP) is a key predictor of cardiovascular events, but patients with peripheral artery disease (PAD) are rarely included in hypertension trials. The VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation) investigated the long-term effects of valsartan- or amlodipine-based treatments on cardiovascular outcomes in patients with hypertension with a high cardiovascular risk. The aim of this subanalysis was to clarify the relationship between achieved BP on treatment and cardiovascular outcomes in patients with hypertension with PAD., Methods: Patients were followed for 4 to 6 years, and BP was measured regularly. The primary end point was time to the first major adverse cardiovascular event, including myocardial infarction, stroke, cardiovascular death, and heart failure requiring hospitalization. Statistical analyses were performed using Cox regression, adjusting for various baseline covariates., Results: Of the 13 803 participants, 1898 (13.8%) had PAD. During a median follow-up of 4.5 years, patients with PAD had a 23% increased risk of major adverse cardiovascular events compared with patients without PAD. Patients with an achieved systolic BP <130 mm Hg and 130 to 139 mm Hg, compared with those with systolic BP ≥140 mm Hg, were associated with a decreased risk of a major adverse cardiovascular event (hazard ratio, 0.65 [95% CI, 0.43-0.97]; P =0.037; 0.85 [95% CI, 0.74-0.97]; P =0.016, respectively). Additionally, systolic BP <130 mm Hg was associated with a decreased risk of cardiovascular death (hazard ratio, 0.33 [95% CI, 0.12-0.92]; P =0.034). The incidence of the primary outcome did not differ between antihypertensive treatment regimens ( P =0.365)., Conclusions: Our results indicate that more intensive BP control is associated with a reduction in cardiovascular morbidity and mortality in patients with hypertensive PAD., Competing Interests: Disclosures G. Mancia reports honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Menarini Group, Merck, Novartis, Recordati, Sandoz, Sanofi, and Servier outside the present work. S.E. Kjeldsen reports lecture honoraria from Emcure, Getz, JB Pharma, Merck Healthcare KGaA, Sanofi-Aventis, and Vector-Intas. M.A. Weber reports honoraria from Abbvie, Johnson & Johnson, Idorsia, Roche, Medtronic, ReCor, Ablative Solutions, Verve, and Omron. M. Vrsalovic reports honoraria from AstraZeneca, Viatris, and Berlin Chemie Menarini. The other authors report no conflicts.

Objectives: Heterogeneous are the results of the published studies aimed at determining the long-term effects of habitual coffee consumption on blood pressure (BP). Specifically, no data are available on the longitudinal association between habitual coffee consumption and office, home and 24 h BP profile and variability., Methods: In 1408 subjects recruited in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, followed for a 10 year follow-up period and classified as coffee consumers and nonconsumers (self-reporting), we prospectically investigated the association between habitual coffee consumption and office, home and 24-h ambulatory BP; 24-h BP variability; and development of a new hypertensive state. Data were also analysed according to gender., Results: When data were adjusted for confounders habitual coffee nonconsumers and consumers displayed similar long-term BP changes during the follow-up in office, home, and ambulatory BP. No difference was found between heavy and moderate coffee consumers. Furthermore, also new-onset hypertension and patterns of BP variability were superimposable in coffee nonconsumers and consumers, independently on confounders including gender, number, and characteristics of the antihypertensive drug treatment., Conclusion: The present study, which is the first longitudinal investigation never performed examining in a prospective fashion the long-term (10 year) effects of coffee consumption on office, home, and ambulatory BP, provides conclusive evidence that habitual coffee consumption is associated with neutral effects on in-office and out-of-office BP values and related variabilities. This is the also the case for the new-onset hypertensive state., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Recent evidence suggests that an exaggerated blood pressure (BP) response to standing (ERTS) is associated with an increased risk of adverse outcomes, both in young and old individuals. In addition, ERTS has been shown to be an independent predictor of masked hypertension. In the vast majority of studies reporting on the prognostic value of orthostatic hypertension (OHT), the definition was based only on systolic office BP measurements. This consensus statement provides recommendations on the assessment and management of individuals with ERTS and/or OHT. ERTS is defined as an orthostatic increase in SBP at least 20 mmHg and OHT as an ERTS with standing SBP at least 140 mmHg. This statement recommends a standardized methodology to assess ERTS, by considering body and arm position, and the number and timing of BP measurements. ERTS/OHT should be confirmed in a second visit, to account for its limited reproducibility. The second assessment should evaluate BP changes from the supine to the standing posture. Ambulatory BP monitoring is recommended in most individuals with ERTS/OHT, especially if they have high-normal seated office BP. Implementation of lifestyle changes and close follow-up are recommended in individuals with ERTS/OHT and normotensive seated office BP. Whether antihypertensive treatment should be administered in the latter is unknown. Hypertensive patients with ERTS/OHT should be managed as any other hypertensive patient. Standardized standing BP measurement should be implemented in future epidemiological and interventional studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office blood pressure (BP) <130/80 mmHg in most and against target office BP <120/70 mmHg in all patients with CKD; recommendations for use of spironolactone or chlorthalidone for patients with resistant hypertension with estimated glomerular filtration rate (eGFR) higher or lower than 30 mL/min/1.73 m2, respectively; use of a sodium-glucose cotransporter 2 inhibitor for patients with CKD and estimated eGFR ≥20 mL/min/1.73 m2; use of finerenone for patients with CKD, type 2 diabetes mellitus, albuminuria, eGFR ≥25 mL/min/1.73 m2 and serum potassium <5.0 mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis ≥70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts from ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Findings regarding the association between Cardio-Ankle Vascular Index (CAVI) and cardiac hypertension-mediated organ damage (HMOD), such as left ventricular hypertrophy (LVH) assessed by echocardiography, in elderly hypertensive patients are scanty. We sought to investigate this issue in the hypertensive fraction of the general population treated with anti-hypertensive drugs enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study., Methods: The study included 239 out of 562 participants who attended the second and third surveys of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure (BP), blood examinations, echocardiography, and CAVI measurements., Results: In the whole study sample (age 69 ± 9 years, 54% males), CAVI was positively correlated with age, office, home, ambulatory systolic BP, LV mass (LVM) index, and negatively associated with body mass index (BMI). In multivariate analysis, CAVI was associated with the LVM index (P < 0.05) independently of major confounders. The participants with LVH exhibited significantly higher CAVI (10.6 ± 2.8 vs. 9.2 ± 1.8 m/s P < 0.001), larger left atrial diameter, and lower LV ejection fraction values than their counterparts without it. The CAVI value of 9.4 m/s was the best cut-off for prediction of LVH in the whole sample., Conclusions: Our study provides new evidence of an independent association between CAVI and LVH in treated elderly hypertensive patients and suggests that the use of this metric of arterial stiffness could not only be used to evaluate vascular damage but also to stratify the risk of LVH., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We address the reasons why, unlike other guidelines, in the 2023 guidelines of the European Society of Hypertension β-blockers (BBs) have been regarded as major drugs for the treatment of hypertension, at the same level as diuretics, calcium channel blockers, and blockers of the renin-angiotensin system. We argue that BBs, (1) reduce blood pressure (the main factor responsible for treatment-related protection) not less than other drugs, (2) reduce pooled cardiovascular outcomes and mortality in placebo-controlled trials, in which there has also been a sizeable reduction of all major cause-specific cardiovascular outcomes, (3) have been associated with a lower global cardiovascular protection in 2 but not in several other comparison trials, in which the protective effect of BBs versus the other major drugs has been similar or even greater, with a slightly smaller or no difference of global benefit in large trial meta-analyses and a similar protective effect when comparisons extend to BBs in combination versus other drug combinations. We mention the large number of cardiac and other comorbidities for which BBs are elective drugs, and we express criticism against the exclusion of BBs because of their lower protective effect against stroke in comparison trials, because, for still uncertain reasons, differences in protection against cause-specific events (stroke, heart failure, and coronary disease) have been reported for other major drugs. These partial data cannot replace global benefits as the main deciding factor for drug choice, also because in the general hypertensive population whether and which type of event might occur is unknown., Competing Interests: Disclosures G. Mancia has received honoraria from Astra Zeneca, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Menarini, Merck, Novartis, Recordati, Sandoz, Sanofi, and Servier. M. Brunström reports lecture honoraria from Amarin, AstraZeneca and Medtronic. M. Burnier has received honoraria from Servier, Menarini, Cincor, Bayer, and Boehringer Ingelheim. G. Grassi has received lecture honoraria from Berlin-Chemie, Gedeon-Richter, Menarini, Merck Healthcare, and Servier. A. Januszewicz has received honoraria from Servier, Gedeon-Richter, Medtronic, KRKA, Novartis, AstraZeneca, Adamed, Bausch, Polfarma; Novartis; Berlin-Chemie; Termedia; ViaMedica; Medycyna Praktyczna. S.E. Kjeldsen reports lecture honoraria from Getz Pharma, J.B. Pharma, Merck Healthcare KGaA, Vector-Intas, and Zydus. M.L. Muiesan reports honoraria from Novartis and Merck-Serono. C. Thomopoulos reports lecture honoraria from Astra Zeneca, Menarini, Medtronic, Krka, Sanofi, and Servier. K. Tsioufis reports honoraria from Medtronic, St. Jude Medical, Bayer, Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer, Chiesi, Pharmanel, Sanofi, Vianex, Win-Medica, Elpen, Recordati, Servier. R. Kreutz reports support for research by Bayer, honoraria for lectures from Bayer, Berlin-Chemie/Menarini, Daiichi Sankyo, Ferrer, Merck, Sanofi, and Servier.

Background: Previous meta-analyses resurrected the debated statement "the lower, the better" following blood pressure (BP)-lowering treatment. We investigated the benefits of BP-lowering treatment at different BP targets by prevention category., Methods: The meta-analysis protocol was registered at the International Prospective Register of Systematic Reviews (CRD42022379249). The database included 115 BP-lowering or comparison trials from patients with (n=241 089) or without (n=198 937) previous cardiovascular events. Prevention disease groups were stratified by in-treatment achieved BP, drug class versus placebo, and drug class versus other classes. Risk ratios and 95% CIs of major adverse cardiovascular events were calculated., Results: Following a standard (10/5 mm Hg) BP reduction, major adverse cardiovascular event relative risk reductions were not different between prevention groups (primary, 25% [95% CI, 18%-31%]; secondary, 28% [95% CI, 20%-37%]). For achieved systolic BP of at least 140 mm Hg, between 130 and 140 mm Hg, and <130 mm Hg (nadir, 125 mm Hg), (1) risk ratios of major adverse cardiovascular events and absolute risk reductions were not different between prevention groups across systolic BP strata, and (2) residual risk, though 4.1× greater in secondary than primary prevention, decreased in primary prevention from higher to lower systolic BP targets. The effect of separate drugs versus others on the primary outcome was not different between prevention groups., Conclusions: BP-lowering treatment benefits did not differ by prevention group to a nadir of 125 mm Hg for systolic BP. Although residual risk in secondary prevention is higher than in primary prevention, it gradually decreases at progressively lower systolic BP targets in primary prevention., Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022379249., Competing Interests: Disclosures C. Thomopoulos and K. Tsioufis have received speaker fees from Menarini, Sanofi, Medtronic, and Servier. C. Thomopoulos reports consulting fees from Sanofi and Menarini. The other authors report no conflicts.

Objective: Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies., Research Design and Methods: Haptoglobin phenotype was measured in available samples from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) biomarker case-cohort study. Weighted multivariable-adjusted Cox regression models were used to evaluate the association between intensive glycemic control (HbA1c target of ≤6.5%) versus standard therapy (based on local guidelines) and major CAD events among participants with (n = 1,327) and without (n = 2,077) the Hp2-2 phenotype separately and within prespecified stratifications by sex, race, previous cardiovascular disease (CVD), diabetes duration, and HDL-cholesterol., Results: While the hazard ratios (HRs) were in the hypothesized differing directions, compared with standard therapy, intensive glycemic control was not significantly associated with risk of CAD events among participants without (1.04, 95% CI 0.82-1.32) or with (0.84, 0.63-1.14, Pinteraction = 0.27) the Hp2-2 phenotype overall. Intensive therapy was associated with lower CAD risk among participants with the Hp2-2 phenotype who had no previous CVD (0.47, 0.29-0.76, Pinteraction = 0.01)., Conclusions: Our findings suggest that intensive glycemic control contributes to the prevention of major CAD events among ADVANCE participants with the Hp2-2 phenotype and no previous CVD and are in alignment with our hypothesis that intensive glycemic control may be beneficial in a subset of people with the Hp2-2 phenotype., (© 2024 by the American Diabetes Association.)

Background: Evidence exists that lowering high blood pressure reduces the risk of dementia. However, the generalizability of this evidence to old patients from the general population remains uncertain., Objectives: This study sought to evaluate the effect of antihypertensive drug treatment on the risk of dementia in a heterogeneous group of new users of antihypertensive drugs., Methods: A nested case-control study was carried out by including the cohort of 215,547 patients from Lombardy, Italy, aged ≥65 years, who started taking antihypertensive drugs between 2009 and 2012. Cases were the 13,812 patients (age 77.5 ± 6.6 years; 40% men) who developed dementia or Alzheimer's disease during follow-up (up to 2019). For each case, 5 control subjects were selected to be matched for sex, age, and clinical status. Exposure to drug therapy was measured by the proportion of the follow-up covered by antihypertensive drugs. Conditional logistic regression was used to model the outcome risk associated with exposure to antihypertensive drugs., Results: Exposure to treatment was inversely associated with the risk of dementia. Compared with patients with very low exposure, those with low, intermediate, and high exposure exhibited a 2% (95% CI: -4% to 7%), 12% (95% CI: 6%-17%), and 24% (95% CI: 19%-28%) risk reduction, respectively. This was also the case for very old (aged ≥85 years) and frail patients (ie, those characterized by a high mortality risk at 1 year)., Conclusions: In the old fraction of the general population, antihypertensive drug treatment is associated with a lower risk of dementia. This was also the case in very old and frail patients., Competing Interests: Funding Support and Author Disclosures This study was supported by a grant from the Italian Ministry of Health (Ricerca Finalizzata 2016, NET-2016-02363853). The funding source had no role in the design of the study, the collection, analysis and interpretation of the data, or the decision to approve publication of the finished manuscript. Dr Corrao has received research support from the European Community, the Italian Medicines Agency, the Italian Ministry of Health, and the Italian Ministry of Education, University, and Research; has participated in various projects that were funded by Novartis, GSK, Roche, Amgen, Bristol Myers Squibb, and Servier; and has received honoraria from Roche as a member of its advisory board. Dr Mancia has received honoraria for participation as speaker or chairman in national or international meetings from Bayer, Boehringer Ingelheim, CVRx, Daiichi-Sankyo, Ferrer, Medtronic, Menarini Int, Merck, Novartis, Recordati, and Servier. Dr Rea has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hypertension urgency and emergency represents a challenging condition in which clinicians should determine the assessment and/or treatment of these patients. Whether the elevation of blood pressure (BP) levels is temporary, in need of treatment, or reflects a chronic hypertensive state is not always easy to unravel. Unfortunately, current guidelines provide few recommendations concerning the diagnostic approach and treatment of emergency department patients presenting with severe hypertension. Target organ damage determines: the timeframe in which BP should be lowered, target BP levels as well as the drug of choice to use. It's important to distinguish hypertensive emergency from hypertensive urgency, usually a benign condition that requires more likely an outpatient visit and treatment., Competing Interests: Declaration of Competing Interest None declared, (Copyright © 2023. Published by Elsevier B.V.)

Aims: The triglyceride-glucose index (TyG) has been proposed as an alternative to insulin resistance and as a predictor of cardiovascular outcomes. Little is known on its role in chronic stable cardiovascular disease and its predictive power at controlled low density lipoprotein (LDL) levels., Methods and Results: Our study population consisted of 29 960 participants in the ONTARGET and TRANSCEND trials that enrolled patients with known atherosclerotic disease. Triglycerides and glucose were measured at baseline. TyG was calculated as the logarithmized product of fasting triglycerides and glucose divided by 2. The primary endpoint of both trials was a composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. The secondary endpoint was all-cause death and the components of the primary endpoint. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) with extensive covariate adjustment for demographic, medical history, and lifestyle factors. During a mean follow-up of 4.3 years, 4895 primary endpoints and 3571 all-cause deaths occurred. In fully adjusted models, individuals in the highest compared to the lowest quartile of the TyG index were at higher risk for the primary endpoint (HR 1.14; 95% CI 1.05-1.25) and for myocardial infarction (HR 1.30; 95% CI 1.11-1.53). A higher TyG index did not associate with the primary endpoint in individuals with LDL levels < 100 mg/dL., Conclusion: A higher TyG index is associated with a modestly increased cardiovascular risk in chronic stable cardiovascular disease. This association is largely attenuated when LDL levels are controlled., Registration: www.clinicaltrials.gov: NCT00153101., Competing Interests: Conflict of interest: M.B. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939) and reports personal fees from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Servier, and Vifor during the conduct of the study. B.H. reports no conflicts. F.M. reports grants and personal fees from Medtronic and personal fees from Recor, Boehringer Ingelheim, and Berlin Chemie. He is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, project number 322900939), and Deutsche Herzstiftung, has received scientific support and/or speaker honoraria from Ablative Solutions, Medtronic, and ReCor Medical, and speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. G.M. reports no conflicts. J.F.E.M. reports no conflicts. R.S. reports no conflicts. H.S. reports personal fees from Boehringer Ingelheim. K.K.T. reports no conflicts. E.M.L. reports no conflicts. S.Y. reports institutional grants for the ONTARGET and TRANSCEND trials but not related to the current analysis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

More than 90 % of patients developing heart failure (HF) have hypertension. The most frequent concomitant conditions are type-2 diabetes mellitus, obesity, atrial fibrillation, and coronary disease. HF outcome research focuses on decreasing mortality and preventing hospitalization for worsening HF syndrome. All drugs that decrease these HF endpoints lower blood pressure. Current drug treatments for HF are (i) angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, (ii) selected beta-blockers, (iii) steroidal and non-steroidal mineralocorticoid receptor antagonists, and (iv) sodium-glucose cotransporter 2 inhibitors. For various reasons, these drug treatments were first studied in HF patients with a reduced ejection fraction (HFrEF). Subsequently, they have been investigated in HF patients with a preserved left ventricular ejection fraction (LVEF, HFpEF) of mostly hypertensive etiology, and with modest benefits largely assessed on top of background treatment with the drugs already proven effective in HFrEF. Additionally, diuretics are given on symptomatic indications. Patients with HFpEF may have diastolic dysfunction but also systolic dysfunction visualized by lack of longitudinal shortening. Considering the totality of evidence and the overall need for antihypertensive treatment and/or treatment of hypertensive complications in almost all HF patients, the principal drug treatment of HF appears to be the same regardless of LVEF. Rather than LVEF-guided treatment of HF, treatment of HF should be directed by symptoms (related to the level of fluid retention), signs (tachycardia), severity (NYHA functional class), and concomitant diseases and conditions. All HF patients should be given all the drug classes mentioned above if well tolerated., Competing Interests: Declaration of Competing Interest SEK reports lecture honoraria from Getz, Emcure, JB Pharma, Merck KGaA, Vector-Intas, and Zydus. BP is receiving consulting fees from and owning stock options in Relypsa/Vifor, KBP Pharmaceuticals, Sarfez, SCPharmaceuticals, SQinnovations, G3 Pharmaceuticals, and Tricida, receiving consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, and PhaseBio, and holding patent US 9,931,412 on site-specific delivery of eplerenone to the myocardium and pending patent US 63/045,784 on histone-acetylation modulating agents for the treatment and prevention of organ damage. MB reports honoraria from Bayer, Menarini, Sanofi, and Servier. RK reports support for research by Bayer, and honoraria for lectures from Bayer, Berlin-Chemie, Daiichi Sankyo, Ferrer, Merck, Menarini, Sanofi, and Servier. GM reports honoraria from Astra Zeneca, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Menarini, Merck, Novartis, Recordati, Sandoz, Sanofi, and Servier. FZ reports personal fees from Boehringer Ingelheim, Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer, and Cellprothera, other than from CVCT, and Cardiorenal. AR, KS, KW, RBD, GPA, OAS, SJ, and SO declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures G. Mancia reports honoraria from Astra Zeneca, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Menarini, Merck Healthcare KGaA, Novartis, Recordati, Sandoz, Sanofi, and Servier. S.E. Kjeldsen reports lecture honoraria from Getz, J.B. Pharma, Merck Healthcare KGaA, Vector-Intas, and Zydus.