BACKGROUND:Evidence on the beneficial effects of intensive blood pressure (BP) control is still uncertain in patients with type 2 diabetes (T2D), particularly in an ethnically diverse population. OBJECTIVES:To assess whether a target of systolic BP (SBP) < 120 mm Hg reduces major cardiovascular (CV) events compared with a target of SBP < 140 mm Hg in patients with T2D and high CV risk. DESIGN:This is a multicentre, 2-arm, open-label, randomized clinical trial, in which individuals aged ≥50 years, with a SBP between 130 and 180 mm Hg, T2D and high CV risk are randomly assigned to a target SBP of <120 or <140 mm Hg. The primary endpoint is a composite of CV mortality, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, or hospitalization for heart failure. Maximum follow-up duration is 48 months. Main analysis will follow the intention-to-treat principle. RESULTS:From August 2019 through October 2021, 9,476 participants from 33 sites in Brazil were enrolled. The overall mean age was 64.74 years (standard deviation [SD], 8.16), and 5,871 (62.0%) were women. Race distribution was diverse with 4,025/9,467 (42.5%) self-described as mixed-race, 3,971/9,467 (41.9%) as White, and 1,374/9,467 (14.5%) as Black. Overall, 2,697/9,475 (28.5%) and 371 (3.9%) had established and subclinical CV disease, respectively. Antihypertensive medication was prescribed to 9,104/9,473 (96.1%) of the participants. Mean SBP is 145.89 mm Hg (SD, 12.13) and mean diastolic BP is 79.48 mm Hg (SD, 10.61). CONCLUSION:The OPTIMAL-DIABETES trial results will provide valuable evidence regarding the benefits and risks of antihypertensive treatment to an SBP < 120 vs <140 mm Hg in a diverse population of patients with T2D, elevated BP, and high CV risk. TRIAL REGISTRATION:The trial is registered at the ClinicalTrials.gov (NCT04040634).

BACKGROUND:Blood Pressure Variability (BPV) is an independent risk factor for cardiovascular events. Short-term indices of BPV, such as standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and Time Rate Index (TRI) are calculated using blood pressure (BP) measurements from 24-hour ambulatory blood pressure monitoring (ABPM). Although these indices have distinct units and amplitudes, their relationships have not been thoroughly investigated. This study aims to explore the correlation between the SD, CV, ARV, and TRI indices of short-term BPV. METHODS:Data were collected during the baseline evaluation of hypertensive participants with obstructive sleep apnoea in a randomised controlled trial. Systolic BPV indices were measured using 24-hour systolic ABPM. Pearson correlation (r) and intraclass correlation (ICC) for consistency were calculated among the BPV indices. RESULTS:Sixty-five participants aged ≥40 years were evaluated. SD, CV, and ARV showed high linear correlations, and their ICCs indicated moderate consistency between SD and CV, and between CV and ARV. In contrast, TRI exhibited weak correlations and no ICC consistency with the other indices. CONCLUSIONS:The strong linear correlations and moderate-to-high ICC consistency among SD, CV, and ARV suggest these indices may be used interchangeably in studies of short-term BPV and cardio-vascular outcomes. TRI, however, reflects a distinct construct and should be evaluated separately when assessing its prognostic value.

Summary: Background: Visceral adipose tissue (VAT) may causally contribute to cardiovascular disease (CVD); however, evidence in Latin America is limited. Here, we evaluated the association between estimated VAT (eVAT) and incident CVD among individuals without diabetes and estimated its population-attributable fraction (PAF) using data from the Cohorts Consortium of Latin America and the Caribbean (CC-LAC). Methods: We pooled data from 15 prospective cohorts across 7 countries (n = 23,097; 62% women [n = 14,383], median age 51 years). Baseline eVAT (in grams [g]) was estimated using the Metabolic Score for Visceral Fat (METS-VF) index, incorporating age, sex, an insulin resistance index, and waist-to-height ratio. The primary outcome was incident CVD events, including fatal and non-fatal outcomes. Cause-specific Cox proportional hazards models estimated adjusted hazard ratios (aHR). PAF estimates used scenario-based eVAT quartile reductions. Findings: Over a median follow-up of 4 years (113,622 person-years), 436 participants (1.9%) experienced an incident CVD event (174 fatal; 262 non-fatal). Uniformly age- and sex-standardized incidence rates were 3.8 (95% CI: 3.5–4.2) per 1000 person-years. Each 100 g increase in eVAT was associated with a 4% higher CVD hazard (aHR 1.04, 1.03–1.06). Compared with Q1 (<735 g), those in Q3 (1069–1441 g) and Q4 (≥1441 g) had a higher CVD hazard (Q3 aHR: 1.78 [1.28–2.49]; Q4 aHR: 2.03 [1.48–2.79]; p-for-trend <0.001). Associations were stronger for non-fatal events. In PAF estimates, shifting individuals from Q4 to lower quartiles could prevent 8.8% (2.8%–14.7%) of CVD events over 10 years. Interpretation: Higher eVAT was associated with increased CVD risk in Latin America, supporting the view that modest VAT reductions could decrease regional CVD burden. Funding: CC-LAC was funded by the Wellcome Trust.

BACKGROUND:Diuretics are widely used alone or in combination with other medications to lower blood pressure (BP). The dosing ratio between hydrochlorothiazide and chlorthalidone for lowering BP, as well as the effects of different amiloride doses on BP and their ability to counteract thiazide's adverse metabolic effects, remain unclear. METHODS:In a factorial superiority randomized clinical trial with blinded participants and investigators, we compared the effects of chlorthalidone 25 mg with hydrochlorothiazide 50 mg and amiloride 5 mg with 10 mg on BP measured by office and ambulatory BP monitoring and laboratory parameters. Patients were followed for 12 weeks. RESULTS:The treatments showed no statistically significant interaction; comparisons were evaluated separately. Hydrochlorothiazide and chlorthalidone had similar effects on systolic and diastolic BP measured at the office and by ambulatory BP monitoring. The between-group δs (hydrochlorothiazide minus chlorthalidone) for systolic 24-hour and nighttime BP were -1.1 (95% CI, -8.0 to 5.9; P=0.8), and -2.3 (95% CI, -10.3 to 5.7; P=0.6), respectively. The effects of amiloride 5 mg and 10 mg on BP were similar. Laboratory parameters did not differ between hydrochlorothiazide and chlorthalidone. Comparing amiloride doses, serum sodium decreased more with 10 mg, while the remaining parameters were similar between doses. CONCLUSIONS:Chlorthalidone and hydrochlorothiazide, administered at a 1:2 dosing ratio, show similar effects on BP and laboratory parameters. Amiloride 5 and 10 mg show similar effects on BP and most metabolic parameters, with no clear dose-response relationship, suggesting that any independent BP-lowering effect of amiloride is, at best, weak. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03928145.

Pharmacological influence on nephron function has modified the clinical course of hypertension, heart failure, and chronic kidney disease. (CKD). This is a review of the efficacy of old diuretics and the incremental efficacy of new diuretics in managing hypertension, heart failure, and CKD, concluding with new evidence on the effectiveness of old agents. The efficacy of “older” diuretic agents, such as thiazide and loop diuretics, on heart failure and CKD has been primarily explored in nonrandomized studies. However, the efficacy of these agents and indapamide, a slightly newer but still “old” diuretic in preventing blood pressure-related cardiovascular disease, has been demonstrated in randomized controlled trials. Potassium-sparing agents counteract some of the adverse effects of thiazides and have been shown to prevent cardiovascular events in patients with heart failure. Newer drugs with a diuretic effect, such as gliflozins, act through a new mechanism of action in the kidney and have shown efficacy in controlling symptoms and preventing cardiovascular events in patients with heart failure, regardless of diabetes. Furthermore, gliflozins have prevented the progression of chronic kidney disease in patients with and without diabetes mellitus. New evidence detailing the efficacy of old agents has emerged. Chlorthalidone had a large blood-pressure-lowering effect in patients with stage IV CKD. Acetazolamide was effective in accelerating the clinical control of patients with acute heart failure, including patients with some reduction in kidney function. We anticipate investigating the comparative impact of combining different agents to optimize nephron function in the future.

Background: The comparison of left ventricular mass (LVM) at different BP levels and the effects of antihypertensive drug treatment on LVM are unknown. Objective: To compare the LVM of individuals with prehypertension and Stage 1 hypertension and assess the effects of treatment on LVM at these stages of hypertension. Methods: We estimated LVM in the PREVER-Prevention trial using Sokolow-Lyon and Cornell voltage and voltage-duration products before and after randomization to 18 months of treatment with low doses of chlorthalidone and amiloride or placebo in adults with JNC 7 "prehypertension" (systolic BP [SBP] of 120-139 mm Hg and diastolic BP [DBP] of 80-89 mm Hg). Similarly, in the PREVER-Treatment trial, we assessed these indices before and after randomization to 18 months of treatment with the chlorthalidone/amiloride combination or losartan in adults with JNC 7 "stage 1" hypertension (140-159 mm Hg or DBP of 90-99 mm Hg). Results: At baseline, the participants in the stage I hypertension trial exhibited higher mean LVM indices than those in the prehypertension trial. In the PREVER-Prevention trial, those randomized to the chlorthalidone/amiloride combination experienced a significant reduction in Sokolow-Lyon LVM indices compared to placebo (p = 0.02). In the PREVER-Treatment trial, those randomized to the chlorthalidone/amiloride combination or losartan experienced a similar reduction in electrocardiographic LVM during the 18 months of treatment (p < 0.01). Conclusions: The institution of low-dose antihypertensive drug therapy in prehypertension and treatment of patients with stage 1 hypertension has the potential to interrupt the progress of hypertensive cardiomyopathy.

Background: Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). Methods: In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10-40 apneas/hour of sleep) and BP within the systolic range of 140-159 mmHg or diastolic range of 90-99 mmHg. Results: The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24h, and nighttime ABP, but the two groups had no significant difference. Conclusion: Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. Trial registration clinicaltrials. gov identifier: NCT01896661.

Elevated blood pressure (BP) remains the leading cause of mortality globally, and efforts to control it have been disappointing. Meta-analyses of antihypertensive randomized controlled trials reveal a near-exact reversal of the BP-related risks identified in cohort studies. For an observed increase in cardiovascular disease risk of 12.5%, 25%, 50%, and 75% with a 5, 10, 20, or 40 mm Hg higher level of BP, respectively, the corresponding BP reductions in antihypertensive randomized controlled trial meta-analyses document a reversal of risks by 7%, 17% of 22%, 54%, and 64%, respectively, providing almost perfect mathematical concordance between the observed and expected benefit of antihypertensive treatment. Treatment benefits have been demonstrated across a wide range of baseline BPs and in individuals with and without prior established cardiovascular disease. Meta-analyses of antihypertensive treatment randomized controlled trials also indicate that the treatment benefits far outweigh any potential risks for adverse effects. The mathematical evidence of the effectiveness of BP-lowering in reducing the incidence of BP-related cardiovascular disease without imposing relevant adverse effects should be considered by clinicians and guideline committees in defining the diagnosis of hypertension and establishing antihypertensive treatment goals. Setting lower BP values for the diagnosis and treatment of hypertension could yield a substantial reduction in the global burden of disease due to high BP.

A hipertensão arterial (HA) é um dos principais fatores de risco modificáveis para morbidade e mortalidade em todo o mundo, sendo um dos maiores fatores de risco para doença arterial coronária, acidente vascular cerebral (AVC) e insuficiência renal. Além disso, é altamente prevalente e atinge mais de um terço da população mundial. A medida da PA é procedimento OBRIGATÓRIO em qualquer atendimento médico ou realizado por diferentes profissionais de saúde. Contudo, ainda é comumente realizada sem os cuidados técnicos necessários. Como o diagnóstico se baseia na medida da PA, fica claro o cuidado que deve haver com as técnicas, os métodos e os equipamentos utilizados na sua realização. Deve-se reforçar que, feito o diagnóstico, toda a investigação e os tratamentos de curto, médio e longo prazos são feitos com base nos resultados da medida da PA. Assim, técnicas e/ou equipamentos inadequados podem levar a diagnósticos incorretos, tanto subestimando quanto superestimando valores e levando a condutas inadequadas e grandes prejuízos à saúde e à economia das pessoas e das nações. Uma vez feito o diagnóstico correto, na medida em que avança o conhecimento da importância do tratamento adequado, com a adoção de valores de normalidade mais detalhados e com objetivos de tratamento mais cuidadosos no sentido do alcance de metas de PA mais rigorosas, fica também reforçada a importância da precisão na medida da PA. A medida da PA (descrita a seguir) é habitualmente feita pelo método tradicional, a assim chamada medida casual ou de consultório. Ao longo do tempo, foram agregadas alternativas a ela, mediante o uso de equipamentos semiautomáticos ou automáticos pelo próprio paciente, nas salas de espera ou fora do consultório, em sua própria residência ou em espaços públicos. Um passo adiante foi dado com o uso de equipamentos semiautomáticos providos de memória que permitem medidas sequenciais fora do consultório (AMPA; ou MRPA) e outros automáticos que permitem medidas programadas por períodos mais prolongados (MAPA). Alguns aspectos na medida da PA podem interferir na obtenção de resultados fidedignos e, consequentemente, causar prejuízo nas condutas a serem tomadas. Entre eles, estão: a importância de serem utilizados valores médios, a variação da PA durante o dia e a variabilidade a curto prazo. Esses aspectos têm estimulado a realização de maior número de medidas em diversas situações, e as diferentes diretrizes têm preconizado o uso de equipamentos que favoreçam essas ações. Ganham cada vez mais espaço os equipamentos que realizam MRPA ou MAPA, que, além de permitirem maior precisão, se empregados em conjunto, detectam a HA do avental branco (HAB), HA mascarada (HM), alterações da PA no sono e HA resistente (HAR) (definidos no Capítulo 2 desta diretriz). Resguardados esses detalhes, devemos ressaltar que as informações relacionadas a diagnóstico, classificação e estabelecimento de metas ainda são baseadas na medida da PA de consultório e, por esse motivo, toda a atenção deve ser dada à realização desse procedimento.

In order to reduce the contamination of marine ecosystems by plastic materials, the scientific community is engaged in the development of biodegradable substitutes for conventional plastics. While certain candidates have been successfully tested in coastal marine environments, the degradation process in deep-sea environments remains poorly understood. This study examined the degradation of two industrial biopolyesters, a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and a polybutylene-succinate (PBS), in two deep marine environments of the Middle and Eastern Atlantic, at depths of 780 and 1740 m, as well as under laboratory conditions under hydrostatic pressure and without micro-organisms. The findings reveal a considerable biodeterioration of PHBV and a pronounced influence of flax fibre reinforcement on the degradation mechanisms. Conversely, PBS exhibits minimal to no indications of degradation. Additionally, the results confirm that biotic factors are the primary determinants of the degradation processes, with no degradation observed under abiotic conditions.

The recently discovered deep-sea Capelinhos hydrothermal edifice, ~ 1.5 km of the main Lucky Strike (LS) vent field (northern Mid-Atlantic Ridge), contrasts with the other LS edifices in having poorly-altered end-member hydrothermal fluids with low pH and chlorine, and high metal concentrations. Capelinhos unique chemistry and location offer the opportunity to test the effects of local abiotic filters on faunal community structure while avoiding the often-correlated influence of dispersal limitation and depth. In this paper, we characterize for the first time the distribution patterns of the Capelinhos faunal communities, and analyze the benthic invertebrates (> 250 µm) inhabiting diffusive-flow areas and their trophic structures (δ 13 C, δ 15 N and δ 34 S). We hypothesized that faunal communities would differ from those of the nearest LS vent edifices, showing an impoverished species subset due to the potential toxicity of the chemical environment. Conversely, our results show that: (1) community distribution resembles that of other LS edifices, with assemblages visually dominated by shrimps (close to high-temperature focused-fluid areas) and mussels (at low-temperature diffuse flow areas); (2) most species from diffuse flow areas are well-known LS inhabitants, including the bed-forming and chemosymbiotic mussel Bathymodiolus azoricus and (3) communities are as diverse as those of the most diverse LS edifices. On the contrary, stable isotopes suggest different trophodynamics at Capelinhos. The high δ 15 N and, especially, δ 13 C and δ 34 S values suggest an important role of methane oxidation (i.e., methanotrophy), rather than the sulfide oxidation (i.e., thiotrophy) that predominates at most LS edifices. Our results indicate that Capelinhos shows unique environmental conditions, trophic structure and trophodynamics, yet similar fauna, compared to other LS edifices, which suggest a great environmental and trophic plasticity of the vent faunal communities at the LS.

Post-exercise hypotension (PEH) is typically reported as mean values, but a great inter-individual variation in blood pressure (BP) response after a single exercise session is expected, especially when comparing different modalities of exercise. The purpose was to evaluate the inter-individual BP responses after beach tennis, aerobic, resistance and combined exercise sessions in adults with hypertension. We conducted a post hoc analysis of pooled crossover randomized clinical trials from six previously published studies of our research group, and analyzed data from 154 participants with hypertension (≥35 years). BP was assessed using office BP, and the mean changes throughout the 60 min after recreational beach tennis (BT, n = 23), aerobic (AE, n = 18), combined (COMB, n = 18), and resistance (RES, n = 95) exercise sessions were compared to a non-exercising control session (C). To categorize the participants as responders and non-responders for PEH, the typical error (TE) was calculated as follows: TE = SDdifference/√2, where SDdifference is the standard deviation of the differences in BP measured before the interventions in the exercise and control sessions. Participants who presented PEH greater than TE were classified as responders. The TE was 7 and 6 mmHg for baseline systolic and diastolic BP, respectively. The rate of responders for systolic BP was as follows: BT: 87%; AE: 61%; COMB: 56%; and RES: 43%. For diastolic BP, the rate of responders was as follows: BT: 61%; AE: 28%; COMB: 44%; and RES: 40%. Results evidenced that there was a high inter-individual variation of BP after a single bout of different physical activity modalities in adults with hypertension, suggesting that exercise protocols with aerobic characteristics (i.e., BT, AE, and COMB sessions) presented PEH in most of its practitioners.

Chemosynthetic ecosystems are scattered in the deep ocean, harbouring highly specialized communities, among which the degree of connectivity and dispersal is scarcely studied. This gap is largely due to limited range distribution, either real or due to highly partial exploration, preventing the availability of a sufficient number of samples for population genetic analysis. For the few species that escaped this gap, large-scale panmixia was often reported, raising wonders as to the evolutionary mechanisms involved in the first steps of speciation. Vesicomyid bivalves are one of the most abundant groups of chemosynthetic fauna, for which depth was proposed as an essential driver of differentiation. Early stages of speciation are thus expected to involve genetic differentiation along depth gradients. The vesicomyid bivalve Christineconcha regab was studied across widely separated localities along the Western African margin, from the cold-seeps of Regab pockmarks located at 3150 m depth on the Congo margin to the turbiditic lobes of the Congo deep-sea fan located at 5000 m depth, using mitochondrial (COI) sequences and eight microsatellite loci. Despite rather high density in relation to high organic matter availability, results obtained showed rather low levels of genetic diversity at both mtDNA and microsatellites. The main consistent pattern of differentiation was observed across depths from Regab pockmark (South-Western part) and lobe areas (Lobe B and C). This is likely due to the largest sample sizes characterizing Regab_SW and Lobe C allowing the detection of faint genetic differentiation, and possibly to a stronger signature in the demographically declining (thus acknowledgedly under sampled) Lobe B. Other significant results were not congruent among markers, suggesting low statistical power due to limited sample size or the occurrence of chaotic genetic patchiness. Altogether, the results suggest the occurrence of effective gene flow at regional scale, and departure from equilibrium in the recently discovered lobes of the Congo River, possibly resulting from unstable environmental conditions and recurrent events of extinction recolonization.

Hypertension is highly prevalent in patients with obstructive sleep apnea (OSA), and fluid retention with its nighttime rostral distribution is one potential mechanism. We tested whether or not diuretics differ from amlodipine in their impact on echocardiographic parameters. Patients with moderate OSA and hypertension were randomized to receive diuretics (chlorthalidone plus amiloride) or amlodipine daily for 8 weeks. We compared their effects on left and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively), on LV diastolic parameters, and on LV remodeling. In the 55 participants who had echocardiographic images feasible for strain analysis, all echocardiographic parameters were within normal ranges. After 8 weeks, the 24 h blood pressure (BP) reduction values were similar, while most echocardiographic metrics were kept unchanged, except for LV-GLS and LV mass. In conclusion, the use of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension, suggesting that they do not have important effects on mediating the interaction between OSA and hypertension.

HomeJournal of the American Heart AssociationAhead of PrintIs it Time to Retire the Diagnosis “Hypertensive Emergency”? Open AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessEditorialPDF/EPUBIs it Time to Retire the Diagnosis “Hypertensive Emergency”? Flávio Danni Fuchs, MD, Miguel Gus, MD, Sandro Cadaval Gonçalves, MD and Sandra Costa Fuchs, MD Flávio Danni FuchsFlávio Danni Fuchs *Correspondence to: Flávio Danni Fuchs, MD, Division of Cardiology Hospital de Clínicas de Porto Alegre Ramiro Barcelos 2350 90035‐903, Porto Alegre, Rio Grande do Sul, Brazil. Email: E-mail Address: [email protected] https://orcid.org/0000-0002-1191-0523 , Division of Cardiology, , Hospital de Clínicas de Porto Alegre, , Porto Alegre, , Rio Grande do Sul, , Brazil, , Graduate Program in Cardiology, School of Medicine, , Universidade Federal do Rio Grande do Sul, , Porto Alegre, , Rio Grande do Sul, , Brazil, Search for more papers by this author , Miguel GusMiguel Gus https://orcid.org/0000-0003-4635-9003 , Division of Cardiology, , Hospital Moinhos de Vento, , Porto Alegre, , Rio Grande do Sul, , Brazil, Search for more papers by this author , Sandro Cadaval GonçalvesSandro Cadaval Gonçalves , Division of Cardiology, , Hospital de Clínicas de Porto Alegre, , Porto Alegre, , Rio Grande do Sul, , Brazil, , Graduate Program in Cardiology, School of Medicine, , Universidade Federal do Rio Grande do Sul, , Porto Alegre, , Rio Grande do Sul, , Brazil, Search for more papers by this author and Sandra Costa FuchsSandra Costa Fuchs https://orcid.org/0000-0001-6351-9588 , Graduate Program in Cardiology, School of Medicine, , Universidade Federal do Rio Grande do Sul, , Porto Alegre, , Rio Grande do Sul, , Brazil, Search for more papers by this author Originally published25 Jan 2023https://doi.org/10.1161/JAHA.122.028494Journal of the American Heart Association. 2023;0:e028494The recognition of the risks of high blood pressure (BP) in the last century was highlighted by observing the acute association between very high BP and medical catastrophes in emergency settings, including stroke, acute left ventricular failure, and myocardial infarction. Edward Freis was among the first authors to propose the concept of “hypertensive crisis,” which he characterized as a life‐threatening disorder caused by acute or severe elevation of BP and clinical manifestations secondary to hypertension.1 According to Freis, the clinical manifestations included encephalopathy, neuroretinitis, evidence of rapidly advancing renal impairment, and acute heart failure.Hypertension guidelines incorporated the diagnosis of hypertensive crisis, and the 1984 Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure report proposed the classification of hypertensive emergencies and urgencies.2 Hypertensive emergencies were characterized by hypertensive encephalopathy, intracranial hemorrhage, acute left ventricular failure, dissecting aortic aneurysm, severe hypertension, toxemia, head trauma, extensive burns, unstable angina pectoris, and acute myocardial infarction, in which BP should be lowered within 1 hour. Urgencies were defined as situations in which BP should be controlled within 24 hours, including accelerated or malignant hypertension, perioperative hypertension, and patients requiring emergency surgeries.With slight variations in the criteria for the definition of urgencies and emergencies, these recommendations have been repeatedly copied and pasted into the Joint National Committee guidelines and the guidelines from Europe and other countries. The 2017 American Heart Association/American College of Cardiology hypertension guidelines3 defined hypertensive emergencies as severe BP elevations (>180/120 mm Hg) associated with evidence of hypertensive encephalopathy, intracerebral hemorrhage, acute ischemic stroke, acute myocardial infarction, acute left ventricular failure, unstable angina pectoris, dissecting aortic aneurysm, acute renal failure, and eclampsia. The guideline defined hypertensive urgencies as situations associated with severe BP elevation in patients without an acute or impending change in target organ damage or dysfunction. The 2018 European Society of Cardiology/European Society of Hypertension guidelines of hypertension4 included the diagnosis of malignant hypertension (characterized by funduscopic changes or disseminated intravascular coagulation), excluded any presentation of stroke from the criteria to characterize hypertensive emergencies, and proposed a similar definition for hypertensive urgencies.Patients with high BP in emergency departments have worse long‐term cardiovascular outcomes than those with lower BP.5 This consequence is expected because these patients already have high BP levels and a longer duration of hypertension. The diagnoses of urgency and emergency would be justified if short‐term outcomes were influenced by prompt therapy in emergency departments. Nevertheless, there is no clinical trial in patients diagnosed as having hypertensive urgencies and emergencies showing the short‐term reduction in the incidence of cardiovascular events. The long‐term benefits would depend of the management after the discharge of the emergency department.The denomination of hypertensive urgency for the isolated elevation of BP in the emergency room has been questioned.6 There is no evidence that lowering BP in a short period prevents major cardiovascular events and the prognosis was not different in patients referred to an emergency service.7 The resumption of medication for the chronic management of hypertension in this context can be considered.The utility of the diagnosis of hypertensive emergencies to guide the treatment of patients in emergency departments should also be questioned. There is a clear difference between the dangerous long‐term elevation of BP, the major cause of cardiovascular diseases,8 and the acute elevation of BP, even if accompanied by target organ damage or dysfunction. Delayed therapy for primary clinical conditions, and treating high BP instead, continues to occur in emergency settings. Here, we propose reasons to abandon the diagnosis of hypertensive emergency (Table), which had been useful to characterize the risks of high BP but now deserves an honorable retirement.Table 1. Reasons to Discard the Diagnosis of Hypertensive Emergencies1. Misguided importance attributed to high blood pressure in emergency care.2. Absence of clinical trials with cardiovascular outcomes in patients with hypertensive emergencies.3. Broader coverage of diagnostic and therapeutic aspects by guidelines and protocols proposed for the primary clinical conditions.Misguided Importance Attributed to High BP in Emergency CareThe concept that sustained high BP was associated with a higher incidence of cardiovascular events was consolidated. The idea that high BP was also the cause of immediate consequences was a corollary of this knowledge, creating the theoretical grounds to propose immediate intervention over BP in patients presenting with acute clinical conditions.Most patients with stroke, acute pulmonary edema, aortic dissection, encephalopathy, and others present with high BP in emergency rooms. These clinical conditions were then recognized as a consequence of acute BP rising. The perception of reversal causality, for example, BP increasing as a response to the damage or dysfunction of organs, particularly the brain and heart, was missed because the diagnosis of high BP and those clinical conditions was concurrent. This misguided interpretation also occurred with more trivial clinical conditions, such as headache and epistaxis.The recommendation to treat high BP as a means to interrupt a worse clinical course of the clinical conditions that characterize hypertensive emergencies was included in medical textbooks and guidelines. This notion still prevails in emergency care worldwide and may eventually give primacy to measures to lower BP, delaying the treatment the primary clinical diagnosis.Absence of Clinical Trials With Cardiovascular Outcomes in Patients With Hypertensive EmergenciesPatients presenting with the diagnosis of hypertensive emergency have already a diagnosis of an acute cardiovascular event on course. Therefore, treatments would aim to reduce complications of the clinical conditions that characterize the occurrence of hypertensive emergencies, particularly the evolution to fatal outcomes or more severe complications. The strategy to reach these goals should be tested in randomized clinical trials, which should depart from the definition of the disease to be treated. Hypertensive emergencies do not fill this criterion because various clinical conditions define it. The simple decision to treat or not treat is naturally different in patients with stroke, acute left ventricular failure, angina, and others. Moreover, there is no common denominator among the different clinical conditions to justify a similar BP‐lowering strategy for all.The use of BP‐lowering drugs in the absence of such trials could be eventually justified because the hypertensive response worsens the clinical condition, such as acute pulmonary edema. In this case, however, the treatment should be tailored to the underlining diagnosis, which is better defined by guidelines and protocols specific to each clinical condition.Broader Coverage of Diagnostic and Therapeutic Aspects by Guidelines and Protocols Proposed for the Primary Clinical ConditionsThe natural diagnosis sequence in patients with hypertensive emergencies is usually from the typical manifestations of the primary clinical diagnosis and not from the detection of high BP. The management of BP is one among several steps of care in such conditions, and frequently the intervention over BP is secondary or even not considered in guidelines for the primary diagnoses.StrokeThe management of high BP in patients presenting with acute stroke in emergency departments is the more controversial among the diagnosis that characterizes a hypertensive emergency. The 2017 American Heart Association/American College of Cardiology hypertension guidelines divide the management by the diagnoses of acute ischemic stroke and intracerebral hemorrhage.3 The 2018 European Society of Cardiology/European Society of Hypertension guidelines for hypertension do not include any presentation of stroke as a criterion for diagnosing hypertensive emergencies because the beneficial effects of BP reduction in these conditions are unclear.4The management of high BP is among several steps proposed by the specific guidelines for acute cerebrovascular events.9, 10 The recommendations unfold in ischemic and hemorrhagic strokes, several BP levels, and by the possibility of carrying out thrombolysis or mechanical thrombectomy. The classes of recommendations and the corresponding level of evidence in all guidelines that address the management of BP during acute stroke are mostly low (or weak) (IIa or IIb and B and C, respectively). Nonetheless, there is high uncertainty over the benefits and risks of intensive BP lowering on functional outcomes.11, 12The various nuances of BP management during acute cerebrovascular events suggest that neurovascular specialists (or trained intensivists and emergency physicians) are needed to achieve better outcomes in these patients. The recommendations for nonspecialists should be restricted to the recognition of a cerebrovascular event in patients with acute elevation of BP and the immediate referral to a tertiary care hospital. If it is impossible to transfer a patient within the time window for thrombolysis or thrombectomy, a better alternative would be to avoid modulating BP. This option has been associated with better neurologic outcomes in patients who are not candidates for pharmacological or mechanical reperfusion.13Acute Coronary SyndromesAccording to hypertension guidelines, unstable angina and acute myocardial infarction are traditionally listed as criteria to diagnose a hypertensive emergency.3, 4 Unlike the detailed recommendations for managing high BP in patients with stroke, the hypertension guidelines superficially address BP management in patients with acute cardiac ischemia.There are no clinical trials of major cardiovascular outcomes assessing the benefits of different strategies to reduce BP in the context of acute coronary syndromes. Differently from guidelines for hypertension, guidelines for acute coronary syndromes focus on revascularization therapies, which are firmly based on the results of randomized clinical trials and do not include BP in the flow charts and algorithms for the management.14, 15Physicians are more often concerned with low BP values in patients presenting with acute coronary syndromes, which can signal incipient cardiogenic shock. High BP is usually secondary to pain (reversal causality), particularly in patients with previous hypertension, and is evidence of preserved cardiac output. These patients are treated with nitrates, drugs that have a BP‐lowering effect as one of their mechanisms to reduce myocardial ischemia, while the procedures to promote coronary reperfusion are prepared.Acute Left Ventricular FailureAcute cardiogenic pulmonary edema is a self‐evident clinical condition with short‐term resolution in most patients and is another clinical condition that does not have its management primarily oriented by BP values. The management is based on the physiopathology of the syndrome and the clinical experience. BP is elevated in many patients, particularly those with hypertensive cardiomyopathy, because of the sympathetic discharge promoted by hypoxemia and the fear of imminent death. The rationale for treatment indicates drugs that reduce preload and afterload, such as nitrates.Guidelines for managing heart failure superficially address on the management of acute cardiogenic pulmonary edema,16, 17 a condition that was specifically focused by a complementary statement from the European Society of Cardiology.18 It recommends vasodilators, preferentially nitrates, and oxygen and loop diuretics as the first step for treatment. Pulmonary edema secondary to acute left ventricular failure is another clinical condition that does not have its management primarily oriented by BP values in most patients.Aortic DissectionThe short‐term risk of dying immediately after the onset of dissection (particularly the type A) characterizes an aortic dissection as a medical emergency. BP is frequently high at presentation in the emergency setting because of the intense pain and because most patients have chronic hypertension, the primary cause of aortic syndromes. The rationale to lower BP in this context aims to reduce the wall tension and the shear stress, which promotes endothelial tearing and enhances the disruption of the media layer of the aorta.Hypertension guidelines3, 4 and a recent review19 recommend lowering systolic BP below 120 mm Hg in patients with aortic dissection, accompanied by heart rate reduction. These strategies were not and will not be tested in randomized controlled trials with major cardiovascular outcomes. Specific guideline provides a broader coverage of diagnostic and therapeutic strategies, focusing primarily on the criteria to recommend medical, surgical, or percutaneous therapies.19Preeclampsia and EclampsiaGuidelines for hypertension3, 4 recommend lowering BP to values lower than 140/90 mm Hg. Preeclampsia and eclampsia, however, are self‐evident conditions usually managed in an obstetric department and not in emergency departments. There are many randomized clinical trials comparing the effect of different drugs over BP in patients with eclampsia, but none comparing the effect of different BP targets in maternal‐fetal outcomes. The treatment of pregnant women with high BP should follow guidelines that cover BP and other conditions in patients with preeclampsia/eclampsia.20Hypertensive EncephalopathyHypertensive encephalopathy is primarily a diagnosis of exclusion after other causes of central nervous system dysfunction are ruled out, particularly stroke. It was probably more frequent at the time when the BP of the whole population was higher than currently, and patients were not treated intensively. According to old reports, it characteristically responds dramatically to acute lowering of BP. Guidelines of hypertension cover superficially the diagnosis and conduct in patients with hypertensive encephalopathy,3, 4 a very rare condition nowadays.ConclusionThe recognition of high BP in patients in emergency settings requires the diagnosis of the causes of the elevation. The diversity of clinical conditions that lead to the diagnosis of hypertensive emergency does not have a common denominator to justify a similar BP‐lowering strategy for all. The clinical conditions are usually self‐evident and should be managed according to their specific guidelines, which include several aspects of diagnosis and treatment. Treating elevated BP rather than the primary clinical condition can be harmful. The diagnosis of hypertensive emergency provided good services to doctors and patients, but given the contemporary reality, it should have a well‐deserved retirement.Sources of FundingF.D.F. and S.C.F. are recipients of research grants from the National Council of Research (Conselho Nacional de Pesquisas – CNPq), Brazil.DisclosuresNone.Footnotes*Correspondence to: Flávio Danni Fuchs, MD, Division of Cardiology Hospital de Clínicas de Porto Alegre Ramiro Barcelos 2350 90035‐903, Porto Alegre, Rio Grande do Sul, Brazil. Email: [email protected]edu.brFor Sources of Funding and Disclosures, see page 4.REFERENCES1 Freis ED. Hypertensive crisis. JAMA.1969; 208:338–342.CrossrefMedlineGoogle Scholar2 The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. 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Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.122.028494PMID: 36695314 Manuscript receivedOctober 13, 2022Manuscript acceptedJanuary 5, 2023Originally publishedJanuary 25, 2023Manuscript revisedDecember 2, 2022 Keywordshigh blood pressure in emergency settingshypertensive urgencieshypertensive emergenciesPDF download SubjectsHypertension

Resumo Fundamento A prevenção secundária é recomendada a pacientes com evidência de doença arterial coronariana (DAC) independentemente da indicação de tratamento por cirurgia de bypass da artéria coronária (CABG) ou intervenção coronária percutânea (ICP). Objetivos Este estudo avaliou se o tratamento clínico, a ICP ou o CABG teve influência na adesão à prevenção secundária farmacológica em pacientes com DAC estável. Métodos Esta coorte incluiu pacientes com idade ≥40 anos com DAC estável confirmada por angiografia coronária estável. A decisão por tratamento clínico isolado, ou combinado com ICP ou CABG foi feita por médicos assistentes. A adesão às drogas prescritas recomendadas pelas diretrizes de prevenção secundária (tratamento farmacológico ótimo), incluindo agentes antiplaquetários, drogas hipolipemianetes, betabloqueadores, e bloqueadores do sistema angiotensina aldosterona, foi avaliada no acompanhamento. Diferenças com valores de p < 0,05 foram consideradas estatisticamente significativas. Resultados Dos 928 pacientes incluídos inicialmente, 415 apresentaram DAC leve e 66 apresentaram DAC leve a moderada. O período médio de seguimento foi 5,2 ± 1,5 anos. Os pacientes submetidos ao CABG apresentaram maior probabilidade de receberem tratamento farmacológico ótimo que aqueles submetidos à ICP ou tratamento clínico (63,5% versus 39,1% versus 45,7% respectivamente, p=0,003). Fatores basais independentemente associados com maior probabilidade de prescrição de tratamento ótimo foram CABG [39% maior (6% - 83%, p=0,017)] em comparação a outros tratamentos e diabetes [25% maior (1% - 56%), p=0,042] em comparação à ausência de diabetes. Conclusões Pacientes com DAC submetidos ao CABG são mais frequentemente tratados com prevenção secundária farmacológica ótima que pacientes tratados com ICP ou exclusivamente com tratamento clínico.

Background Secondary prevention is recommended for patients with evidence of coronary artery disease (CAD) regardless of the indication for treatment by coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). Objectives This study evaluated whether clinical treatment, PCI or CABG had an influence on adherence to the pharmacological secondary prevention in patients with stable CAD. Methods This cohort included patients aged ≥40 years with stable CAD confirmed by coronary angiography. The decision for medical treatment alone, or additionally with PCI or CABG, was made by the attending physicians. Adherence to the prescribed drugs recommended by the guidelines for secondary prevention (optimal pharmacological treatment), including antiplatelet agents, lipid-lowering drugs, beta-blockers, and renin-angiotensin-aldosterone system blockers, was assessed at follow-up. Differences were considered significant for p values <0.05. Results From 928 patients enrolled at baseline, 415 had mild CAD and 66 moderate to severe CAD. The average follow-up was 5.2 ± 1.5 years. Patients submitted to CABG were more likely to receive the optimal pharmacological treatment than those submitted to PCI or treated clinically (63.5% versus 39.1% versus 45.7% respectively, p=0.003). Baseline factors independently associated with greater probability of having a prescription of optimal treatment at follow-up were CABG [39% higher (6% - 83%, p=0.017) and diabetes [25% higher (1% - 56%), p=0.042] than their counterparts treated by other methods and participants without diabetes, respectively. Conclusions Patients with CAD submitted to CABG are more commonly treated with optimal pharmacological secondary prevention than patients treated by PCI or exclusively with medical therapy.

Myocardial injury (MI) is frequent in critically ill patients with COVID-19, but its pathogenesis remains unclear. We hypothesized that MI is not solely due to viral infection by SARS-CoV-2 but rather due to the common pathophysiological mechanisms associated with severe pulmonary infections and respiratory failure. This contemporary cohort study was designed to compare the incidence of MI in patients with acute respiratory failure caused by COVID-19 to patients with other pulmonary infections. In addition, we aimed to investigate whether MI was a distinct risk factor for in-hospital mortality in patients with COVID-19 compared to those with non-COVID-19 infections. This study included 1444 patients with COVID-19 (55.5% men; age 58 (46;68) years) and 182 patients with other pulmonary infections (46.9% men; age 62 (44;73) years). The incidence of MI at ICU admission was lower in COVID-19 patients (36.4%) compared to non-COVID-19 patients (56%), and this difference persisted after adjusting for age, sex, coronary artery disease, heart failure, SOFA score, lactate, and C-reactive protein (RR 0.84 (95% CI, 0.71-0.99)). MI at ICU admission was associated with a 59% increase in mortality (RR 1.59 (1.36-1.86); p < 0.001), and there was no significant difference in the mortality between patients with COVID-19 and those with other pulmonary infections (p = 0.271). We concluded that MI is less frequent in patients with critical COVID-19 pneumonia and respiratory failure compared to those with other types of pneumonia. The occurrence of MI is a significant risk factor for in-hospital mortality, regardless of the etiology of the pulmonary infection.