Management of hypertensive disorders in pregnancy: a Position Statement of the European Society of Hypertension Working Group 'Hypertension in Women'.

Hypertensive disorders in pregnancy (HDP), remain the leading cause of adverse maternal, fetal, and neonatal outcomes. Epidemiological factors, comorbidities, assisted reproduction techniques, placental disorders, and genetic predisposition determine the burden of the disease. The pathophysiological substrate and the clinical presentation of HDP are multifarious. The latter and the lack of well designed clinical trials in the field explain the absence of consensus on disease management among relevant international societies. Thus, the usual clinical management of HDP is largely empirical. The current position statement of the Working Group 'Hypertension in Women' of the European Society of Hypertension (ESH) aims to employ the current evidence for the management of HDP, discuss the recommendations made in the 2023 ESH guidelines for the management of hypertension, and shed light on controversial issues in the field to stimulate future research.

Atrial fibrillation in the setting of cardiac amyloidosis - A review of the literature.

Cardiac amyloidosis (CA) is related to the aggregation of insoluble fibrous deposits of misfolded proteins within the myocardium. Transthyretin amyloidosis (ATTR) and immunoglobulin light-chain amyloidosis are the main forms of CA. Atrial fibrillation (AF) is a common arrhythmia in CA patients, especially in those with ATTR amyloidosis. Increased atrial preload and afterload, atrial enlargement, enhanced atrial wall stress, and autonomic dysfunction are the main mechanisms of AF in CA patients. CA is associated with the formation of endocardial thrombi and systemic embolism. The promoters of thrombogenesis include endomyocardial damage, blood stasis, and hypercoagulability. The prevalence of thrombi in patients with AF remains elevated despite long-term anticoagulation. Consequently, transesophageal ultrasound examinations before cardioversion should be performed to exclude endocardiac thrombi despite anticoagulation. Furthermore, the CHA2DS2-VASc score should not be used to assess the thromboembolic risk in CA patients with AF. Rate control is challenging in patients with CA, while rhythm control is the preferred treatment option, especially in the early stages of the disease process. Although catheter ablation is an effective treatment option, more data are needed to explore the role of the procedure in CA patients.

Rationale for the Inclusion of ß-Blockers Among Major Antihypertensive Drugs in the 2023 European Society of Hypertension Guidelines.

We address the reasons why, unlike other guidelines, in the 2023 guidelines of the European Society of Hypertension ß-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.

Revisiting Cardiovascular Benefits of Blood Pressure Reduction in Primary and Secondary Prevention: Focus on Targets and Residual Risk-A Systematic Review and Meta-Analysis.

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.

Anti-ischemic and pleiotropic effects of ranolazine in chronic coronary syndromes.

The vast majority of antianginal drugs decrease heart rate and or blood pressure levels or the inotropic status of the left ventricle to decrease myocardial oxygen consumption (MVO2) and thus anginal symptoms. Ranolazine presents a completely different mechanism of action, which reduces the sodium-dependent calcium overload inhibiting the late sodium current. Current European Society of Cardiology (ESC) guidelines for the management of angina in patients with chronic coronary symptoms recommend the use of several drugs such as ranolazine, b-blockers, calcium channel blockers, long-acting nitrates, ivabradine, nicorandil and trimetazidine for angina relief. However, ranolazine, in addition to symptom relief properties, is an antianginal drug showing favorable effects in decreasing the arrhythmic burden and in ameliorating the glycemic profile of these patients. In this review, we summarize the available data regarding the antianginal and pleiotropic effects of this drug.

One-year outcomes following a hypertensive urgency or emergency.

There are scarce data on the comparative prognosis between patients with hypertensive emergencies (HE), urgencies (HU), and those without HU or HE (HP). Our study aimed to compare cardiovascular (CV) outcomes of HE, HU, and HP during a 12-month follow-up period. The population consisted of 353 consecutive patients presenting with HE or HU in a third-care emergency department and subsequently referred to our hypertension center for follow-up. After both groups completed scheduled follow-up visits, patients with HU were matched one-to-one by age, sex, and hypertension history with HP who attended our hypertension center during the same period. Primary outcomes were 1) a recurrent hypertensive HU or HE event and 2) non-fatal CV events (coronary heart disease, stroke, heart failure, or CV interventions), while secondary outcomes were 1) all-cause death, 2) CV death, 3) non-CV death, and 4) any-cause hospitalization. Events were prospectively registered for all three groups. During the study period, 81 patients were excluded for not completing follow-up. Among eligible patients(HE = 94; HU = 178), a total of 90 hospitalizations and 14 deaths were recorded; HE registered greater CV morbidity when compared with HU (29 vs. 9, HR 3.43, 95 % CI 1.7-6.9, p = 0.001), and increased CV mortality (8 vs. 1, HR 13.2, 95 % CI 1.57-110.8, p = 0.017). When opposing HU to HP, events did not differ substantially. Cox regression models were adjusted for age, sex, CV and chronic kidney disease, diabetes mellitus, and smoking. During 1-year follow-up, the prognosis of HU was better than HE but not different compared to HP. These results highlight the need for improved care of HU and HE.

DASH vs. Mediterranean diet on a salt restriction background in adults with high normal blood pressure or grade 1 hypertension: A randomized controlled trial.

BACKGROUND & AIMS: Non-pharmacological measures are recommended as the first-line treatment for individuals with high-normal blood pressure (BP) or mild hypertension. Studies directly comparing the BP effects of the Dietary Approaches to Stop Hypertension (DASH) vs. the Mediterranean diet (MedDiet) on a salt restriction background are currently lacking. Thus, our purpose was to assess the BP effects of a 3-month intensive dietary intervention implementing salt restriction either alone or in the context of the DASH, and the MedDiet compared to no/minimal intervention in adults with high normal BP or grade 1 hypertension. METHODS: We randomly assigned never drug-treated individuals to a control group (CG, n = 60), a salt restriction group (SRG, n = 60), a DASH diet with salt restriction group (DDG, n = 60), or a MedDiet with salt restriction group (MDG, n = 60). The primary outcome was the attained office systolic BP difference among the randomized arms during follow-up. RESULTS: A total of 240 patients were enrolled, while 204 (85%) completed the study. According to the intention-to-treat analysis, compared to the CG, office and 24 h ambulatory systolic and diastolic BP were reduced in all intervention groups. A greater reduction in the mean office systolic BP was observed in the MDG compared to all other study groups (MDG vs. CG: mean difference = -15.1 mmHg; MDG vs. SRG: mean difference = -7.5 mmHg, and MDG vs. DDG: mean difference = -3.2 mmHg, all P-values <0.001). The DDG and the MDG did not differ concerning the office diastolic BP and the 24 h ambulatory systolic and diastolic BP; however, both diets were more efficient in BP-lowering compared to the SRG. CONCLUSIONS: On a background of salt restriction, the MedDiet was superior in office systolic BP-lowering, but the DASH and MedDiet reduced BP to an extent higher than salt restriction alone.

Distinct Features of Vascular Diseases in COVID-19.

The Coronavirus Disease 2019 (COVID-19) pandemic was declared in early 2020 after several unexplained pneumonia cases were first reported in Wuhan, China, and subsequently in other parts of the world. Commonly, the disease comprises several clinical features, including high temperature, dry cough, shortness of breath, and hypoxia, associated with findings of interstitial pneumonia on chest X-ray and computer tomography. Nevertheless, severe forms of acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are not limited to the respiratory tract but also may be extended to other systems, including the cardiovascular system. The bi-directional relationship between atherosclerosis and COVID-19 is accompanied by poor prognosis. The immune response hyperactivation due to SARS-CoV-2 infection causes an increased secretion of cytokines, endothelial dysfunction, and arterial stiffness, which promotes the development of atherosclerosis. Also, due to the COVID-19 pandemic, access to healthcare amenities was reduced, resulting in increased morbidity and mortality in patients at risk. Furthermore, as lockdown measures were largely adopted worldwide, the sedentary lifestyle and the increased consumption of processed nutrients or unhealthy food increased, and in the consequence, we might observe even 70% of overweight and obese population. Altogether, with the relatively low ratio of vaccinated people in many countries, and important health debt appeared, which is now and will be for next decade a large healthcare challenge. However, the experience gained in the COVID-19 pandemic and the new methods of patients' approaching have helped the medical system to overcome this crisis and will hopefully help in the case of new possible epidemics.

Preexisting hypertension and cancer therapy: evidence, pathophysiology, and management recommendation.

Cancer is considered one of the leading causes of mortality worldwide. At the same time, hypertension is recognized as one of the most common comorbidities in cancer patients. Antineoplastic therapies, mainly tyrosine kinase and vascular endothelial growth factor inhibitors, have been associated with new-onset hypertension by activation of different pathophysiological pathways. However, the role of preexisting hypertension in cancer patients under treatment has not been thoroughly studied. According to this review, preexisting hypertension is an independent risk factor for increased blood pressure during anticancer therapy. Therefore, physicians should recognize hypertension and its phenotypes (i.e., masked hypertension) as an important modifiable risk factor that should be properly managed prior to the initiation of cancer therapy to avoid premature chemotherapy cessation. The development of onco-hypertension will help establish specific guidelines for managing hypertension in cancer patients.

Sex-related cardiovascular prognosis in patients with hypertensive emergencies: a 12-month study.

Current evidence on the prognosis of patients with a hypertensive crisis and predisposing factors is limited. We registered the clinical phenotype of patients with HC admitted to the emergency department, while those with a hypertensive emergency (HE) were hospitalized. One-year outcomes, i.e., composite of death or cardiovascular hospitalizations, were determined in patients with HE after hospital discharge. Out of 38,589 patients assessed in the emergency department, 256 hypertensive urgencies and 97 HE was registered. After stratification of the HE by sex, 48 men and 46 women completed the one-year follow-up. Men had more events than women (27 vs. 13, Ηazard Ratio 2.2, 95% Confidence Interval 1.03-4.7, p = 0.042) after adjustment for age, cardiovascular or chronic kidney disease, and diabetes mellitus. Our study raises the hypothesis that the male sex is an independent risk factor for cardiovascular outcomes in HE patients. CV Cardiovascular, BP blood pressure. The diagram presents the groups of comparison, men versus women in hypertensive emergencies that completed the 1-year follow-up for outcomes, in terms of hospitalizations or deaths.

Sex and gender in hypertension guidelines.

This paper reviews 11 current and previous international and some selected national hypertension guidelines regarding sex and gender-related differences. Those differences can be attributed to biological sex and to gender differences that are determined by socially constructed norms. All reviewed guidelines agree on a higher hypertension prevalence in men than in women. They also concur that evidence does not support different blood pressure thresholds and targets for treatment between men and women. Differences refer in addition to the differences in epidemiological aspects to differences in some morphometric diagnostic indices, e.g., left ventricular mass or the limits for daily alcohol intake. Concerning practical management, there are hardly any clear statements on different procedures that go beyond the consensus that blockers of the renin-angiotensin system should not be used in women of childbearing age wishing to become pregnant. Some further sex-specific aspects are related to differences in tolerability or drug-specific side effects of BP-lowering drugs. There is also a consensus about the need for blood pressure monitoring before and during the use of contraceptive pills. For management of pregnancy, several guidelines still recommend no active treatment in pregnant women without severe forms of hypertension, despite a wide consensus about the definition of hypertension in pregnancy. A disparity in treatment targets when treating severe and non-severe hypertension in pregnancy is also observed. Overall, sex-specific aspects are only very sparsely considered or documented in the evaluated guidelines highlighting an unmet need for future clinical research on this topic.

Net clinical benefit of PFO closure versus medical treatment in patients with cryptogenic stroke: A systematic review and meta-analysis.

BACKGROUND: The ideal treatment for patent foramen ovale (PFO) in patients with cryptogenic stroke remains controversial and is being evaluated. The objective of this study was to evaluate the net clinical benefit (NCB) between PFO closure and medical treatment. METHODS: We searched three electronic databases from inception until January 2022. The primary outcomes were the NCB-1, defined as the cumulative incidence of stroke, major bleeding, atrial fibrillation/flutter, and serious procedural or device complications; the NCB-2 and NCB-3 were defined as NCB1 but using a weighted factor of 0.5 and 0.25 for atrial fibrillation/flutter events, respectively. We also evaluated each component outcome of NCB as a secondary outcome. Risk ratios (RR) and 95% confidence intervals (CI) of each outcome were calculated (random-effects model). RESULTS: Our analysis included six RCTs (n = 3750 patients). The rates of NCB-1, NCB-2, and NCB-3 were not different between PFO closure and medical treatment. The heterogeneity between trials was low to moderate. Stroke showed a significant relative decrease of 44% (95% CI, 21-60%), favoring the PFO closure arm. Atrial fibrillation/flutter increased by 4.04 times (95% CI, 1.57-8.89) in the PFO closure compared with the medical treatment group. In a meta-regression analysis, the reduction in NCB-1 with PFO closure increased as the proportion of patients treated with the Amplatzer device increased (p = 0.02), and the reduction in NCB-1, NCB-2, and NCB-3 with PFO closure increased as the proportion of patients treated with substantial PFO size increased (p = 0.03). CONCLUSION: The NCB between PFO closure and medical treatment was not different, suggesting individualized treatment to maximize benefit.

Fatty liver index and cardiovascular outcomes in never-treated hypertensive patients: a prospective cohort.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing rapidly worldwide, affecting 25-30% of the population. Fatty liver index (FLI) is a validated marker of NAFLD and can be used as a screening tool for hepatic steatosis. The purpose of the study was to evaluate the relationship between FLI and the risk of major cardiovascular events in never treated hypertensive patients. We included 903 hypertensive patients without a history of cardiovascular disease (mean age 52.7 ± 11.4 years; men 55%; baseline clinic BP 149.8 ± 15.2/95.5 ± 10.1 mmHg). Participants were prospectively evaluated for a mean follow-up period of 5.2 ± 3.2 years with at least one annual visit. Patients were also categorized into two groups using an FLI of 60 units. The incidence of cardiovascular events during follow-up was 8.5% (n = 77). Patients with FLI < 60 (n = 625) had a better BP control compared to their counterparts with FLI ≥ 60 (n = 278) during follow up (43% vs 33%, p = 0.02). Cox-regression analysis indicated that FLI (Hazard Ratio [HR], 1.05; 95% Confidence Interval [CI], 1.03-1.07, p < 0.001), FLI z-scores (HR, 3.66; 95% CI, 2.22-6.04) and high-risk FLI (HR, 7.5; 95% CI, 3.12-18.04) were independent determinants of the outcome after adjustment for baseline and follow-up variables. Stratification by diabetes mellitus indicated that FLI predicted the outcome to a greater extent in those with than those without diabetes (P-interaction < 0.001). In conclusion, FLI has an independent prognostic value for the incidence of cardiovascular events in newly diagnosed, never-treated hypertensive patients. Therefore, FLI might identify higher-risk patients in the primary prevention of hypertension.

Net clinical benefit of DOACs vs. usual anticoagulation treatment in venous thromboembolism and active cancer: systematic review and meta-analysis.

Patients with active cancer are at high risk of recurrent venous thromboembolism (VTE). Usual treatment includes low molecular weight heparin (LMWH), while vitamin K antagonists (VKAs) have also been used as substitutes for LMWH. Direct oral anticoagulants (DOACs) are considered a beneficial alternative to the usual treatment but are accompanied by an increased rate of bleeding compared to LMWH. We conducted a meta-analysis to evaluate the benefits and harms under a common denomination, namely the net clinical benefit (NCB), between DOACs and usual anticoagulation. The primary outcome was NCB-1, defined as non-fatal VTE, major non-fatal bleedings, and all-cause mortality). Co-primary outcomes were 1) NCB-2 (i.e., NCB-1 and clinically relevant non-major bleedings) and 2) NCB-3 (i.e., fatal or non-fatal VTE and major bleedings). A random-effects model was used to calculate outcome risk ratios and 95% confidence intervals (CI). Prospective Register of Systematic Reviews identification number CRD42021284238. We selected 8 studies (n = 4,4461 patients; mean follow-up, 6 months). The NCB-1 and -2 were not different between DOACs and usual anticoagulation, while the NCB-3 showed a reduction of 28% (95% CI, 10-42%), favoring DOACs. Recurrent VTE was reduced by 40% (95% CI, 25-53%) with DOACs than the usual treatment. Different bleeding outcomes and all-cause mortality were not different between treatments. All primary outcomes did not differ between DOACs and LMWH, while NCB-2 and NCB-3 were reduced with DOACs than VKAs. The NCB of DOACs was similar or more favorable to usual anticoagulation in patients with active cancer due to a substantial reduction of VTE and no bleeding excess.

Effects of ranolazine on various outcomes in patients with stable angina: an updated meta-analysis.

OBJECTIVE: We determined the effect of ranolazine vs. placebo in angina patients on 1) selective measures of the ischemic burden, 2) cardiovascular outcomes, including atrial fibrillation incidence, 3) the in-treatment glycohemoglobin levels and the permanent discontinuations because of side effects, and 4) the achieved between-arms blood pressure and heart rate difference. METHODS: PubMed and Cochrane Collaboration Library databases were searched for eligible trials until end of September 2020. Trial quality was assessed by the Rob2 tool. Risk ratios or achieved mean differences during follow-up and 95% confidence interval (CI) of categorical or continuous outcomes, respectively, were calculated (random-effects model). The relationship between discontinuation rates and ranolazine's mean dose was investigated by meta-regression analysis. RESULTS: We selected 18 trials (n = 12,995 patients in patients with macro or microvascular coronary heart disease. Achieved blood pressure and heart rate at rest were not different between randomized arms. Ranolazine administration compared to placebo was associated with an increase of 1) total exercise duration by 30 seconds (95% CI, 18-42), 2) time to 1 mm ST-segment depression by 44 seconds (95% CI, 30-54), and 3) time to angina onset by 40 seconds (95% CI, 30-54). On average, the incidence of atrial fibrillation was reduced by 25% following ranolazine treatment compared to placebo, while glycohemoglobin showed a mean decrease of 0.4% (95% CI, 0.3-0.5%). DISCUSSION: Ranolazine remains an effective anti-ischemic drug, increases the angina-free exercise duration, delays the onset of ST-segment depression. The beneficial effects of ranolazine are extended to atrial fibrillation reduction rates and better glycemic control.

Air Pollution and Home Blood Pressure: The 2021 Athens Wildfires.

INTRODUCTION: Fine particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5) in the ambient air has been associated with increased blood pressure (BP) levels and new-onset hypertension. However, the association of BP with a sudden upsurge of PM2.5 in extreme conditions has not yet been demonstrated. AIM: To evaluate the association between PM2.5 pollutants the week before, during, and the week after the 2021 wildfires in Athens (Greece) and home BP measurements. METHODS: Home BP measurements were performed, and the readings were transferred to the doctor's office through a telemonitoring system on the patient's Smartphone application. Data from a calibrated, sensor-based PM2.5 monitoring network assessed PM2.5 exposure. RESULTS: PM2.5 pollutants demonstrated a gradual surge while the particle concentration was not different in the selected air pollution measurement stations. A total of 20 consecutive patients with controlled hypertension, mean age 61 ± 9 years, were included in the analysis. For one unit in µg/m3 increase of PM2.5 particle concentration, an average of 2.1 mmHg increment in systolic BP was observed after adjustment for confounders (P = 0.023). CONCLUSIONS: Our findings raise the hypothesis that short-term exposure to raised PM2.5 concentrations in the air appears to be associated with increases in systolic home BP." Telemonitoring systems of home BP recordings may provide important information for the clinical management of hypertensive patients, at least in conditions of major environmental disturbances, such as wildfires.