Effect of Alcohol-Mediated Renal Denervation on Blood Pressure in the Presence of Antihypertensive Medications: Primary Results From the TARGET BP I Randomized Clinical Trial.

BACKGROUND: Renal denervation (RDN) has demonstrated clinically relevant reductions in blood pressure (BP) among individuals with uncontrolled hypertension despite lifestyle intervention and medications. The safety and effectiveness of alcohol-mediated RDN have not been formally studied in this indication. METHODS: TARGET BP I is a prospective, international, sham-controlled, randomized, patient- and assessor-blinded trial investigating the safety and efficacy of alcohol-mediated RDN. Patients with office systolic BP (SBP) ≥150 and ≤180 mm Hg, office diastolic BP ≥90 mm Hg, and mean 24-hour ambulatory SBP ≥135 and ≤170 mm Hg despite prescription of 2 to 5 antihypertensive medications were enrolled. The primary end point was the baseline-adjusted change in mean 24-hour ambulatory SBP 3 months after the procedure. Secondary end points included mean between-group differences in office and ambulatory BP at additional time points. RESULTS: Among 301 patients randomized 1:1 to RDN or sham control, RDN was associated with a significant reduction in 24-hour ambulatory SBP at 3 months (mean±SD, -10.0±14.2 mm Hg versus -6.8±12.1 mm Hg; treatment difference, -3.2 mm Hg [95% CI, -6.3 to 0.0]; P=0.0487). Subgroup analysis of the primary end point revealed no significant interaction across predefined subgroups. At 3 months, the mean change in office SBP was -12.7±18.3 and -9.7±17.3 mm Hg (difference, -3.0 [95% CI, -7.0 to 1.0]; P=0.173) for RDN and sham, respectively. No significant differences in ambulatory or office diastolic BP were observed. Adverse safety events through 6 months were uncommon, with one instance of accessory renal artery dissection in the RDN group (0.7%). No significant between-group differences in medication changes or patient adherence were identified. CONCLUSIONS: Alcohol-mediated RDN was associated with a modest but statistically significant reduction in 24-hour ambulatory SBP compared with sham control. No significant differences between groups in office BP or 6-month major adverse events were observed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02910414.

Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial.

BACKGROUND: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China. METHODS: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months. RESULTS: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P<0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P<0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up. CONCLUSIONS: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02901704.

Association Between Hematoma Volume and Risk of Subsequent Ischemic Stroke: A MISTIE III and ATACH-2 Analysis.

BACKGROUND: Nontraumatic intracerebral hemorrhage (ICH) is independently associated with a long-term increased risk of major arterial ischemic events. While the relationship between ICH location and ischemic risk has been studied, whether hematoma volume influences this risk is poorly understood. METHODS: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was hematoma volume, treated as a continuous measure in the primary analysis, and dichotomized by the median in the secondary analyses. The outcome was a symptomatic, clinically overt ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. RESULTS: Of 1470 patients with ICH, the mean age was 61.7 (SD, 12.8) years, and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (interquartile range, 7.2-35.7). During a median follow-up of 107 days (interquartile range, 91-140), a total of 30 ischemic strokes occurred, of which 22 were in patients with a median ICH volume of ≥17.3 mL and a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with a median ICH volume <17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). In primary analyses using adjusted Cox regression models, ICH volume was associated with an increased risk of ischemic stroke (hazard ratio, 1.02 per mL increase [95% CI, 1.01-1.04]). In secondary analyses, ICH volume of ≥17.3 mL was associated with an increased risk of ischemic stroke (hazard ratio, 2.5 [95% CI, 1.1-7.2]), compared with those with an ICH volume <17.3 mL. CONCLUSIONS: In a heterogeneous cohort of patients with ICH, initial hematoma volume was associated with a heightened short-term risk of ischemic stroke.

Trends in Black-White Differences of Antihypertensive Treatment in Individuals With and Without History of Stroke.

BACKGROUND: Recent hypertension guidelines for the general population have included race-specific recommendations for antihypertensives, whereas current stroke-specific recommendations for antihypertensives do not vary by race. The impact of these guidelines on antihypertensive regimen changes over time, and if this has varied by prevalent stroke status, is unclear. METHODS: The use of antihypertensive medications was studied cross-sectionally among self-identified Black and White participants, aged ≥45 years, with and without history of stroke, from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Participants completed an in-home examination in 2003-2007 (visit 1) with/without an examination in 2013-2016 (visit 2). Stratified by prevalent stroke status, logistic regression mixed models examined associations between antihypertensive class use for visit 2 versus visit 1 and Black versus White individuals with an interaction adjusted for demographics, socioeconomic status, and vascular risk factors/vital signs. RESULTS: Of 17 244 stroke-free participants at visit 1, Black participants had greater adjusted odds of angiotensin-converting enzyme inhibitor usage than White participants (odds ratio [OR], 1.51 [95% CI, 1.30-1.77]). This difference was smaller in the 7476 stroke-free participants at visit 2 (OR, 1.16 [95% CI, 1.08-1.25]). In stroke-free participants at visit 1, Black participants had lower odds of calcium channel blocker (CCB) usage than White participants (OR, 0.47 [95% CI, 0.41-0.55]), but CCB usage did not differ significantly between Black and White stroke-free participants at visit 2 (OR, 1.02 [95% CI, 0.95-1.09]). Among 1437 stroke survivor participants at visit 1, Black participants had lower odds of CCB use than White participants (OR, 0.34 [95% CI, 0.26-0.45]). In 689 stroke survivor participants at visit 2, CCB use did not differ between Black and White participants (OR, 0.80 [95% CI, 0.61-1.06]). CONCLUSIONS: Racial differences in the use of guideline-recommended antihypertensives decreased between 2003-2007 and 2013-2016 in stroke-free individuals. In stroke survivors, racial differences in CCB usage narrowed over the time periods. These findings suggest there is still a mismatch between race-specific hypertension guidelines and recent clinical practice.

Code ICH: A Call to Action.

Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.

Effect of the Blood Pressure and Antihypertensive Drugs on Cerebral Small Vessel Disease: A Mendelian Randomization Study.

BACKGROUND: Previous studies yielded conflicting results about the influence of blood pressure (BP) and antihypertensive treatment on cerebral small vessel disease. Here, we conducted a Mendelian randomization study to investigate the effect of BP and antihypertensive drugs on cerebral small vessel disease. METHODS: We extracted single-nucleotide polymorphisms for systolic BP and diastolic BP from a genome-wide association study (N=757 601) and screened single-nucleotide polymorphisms associated with calcium channel blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers from public resources as instrumental variables. Then, we chose the genome-wide association study of white matter hyperintensity (WMH; N=18 381), cerebral microbleed (3556 cases, 22 306 controls), white matter perivascular space (9317 cases, 29 281 controls), basal ganglia perivascular space (BGPVS; 8950 cases, 29 953 controls), hippocampal perivascular space (HIPPVS; 9163 cases, 29 708 controls), and lacunar stroke (6030 cases, 248 929 controls) as outcome data sets. Subsequently, we conducted a 2-sample Mendelian randomization analysis. RESULTS: We found that elevated systolic BP significantly increases the risk of BGPVS (odds ratio [OR], 1.05 [95% CI, 1.04-1.07]; P=1.72×10-12), HIPPVS (OR, 1.04 [95% CI, 1.02-1.05]; P=2.71×10-7), and lacunar stroke (OR, 1.41 [95% CI, 1.30-1.54]; P=4.97×10-15). There was suggestive evidence indicating that elevated systolic BP is associated with higher WMH volume (ß=0.061 [95% CI, 0.018-0.105]; P=5.58×10-3) and leads to an increased risk of cerebral microbleed (OR, 1.16 [95% CI, 1.04-1.29]; P=7.17×10-3). Elevated diastolic BP was significantly associated with higher WMH volume (ß=0.087 [95% CI, 0.049-0.124]; P=5.23×10-6) and significantly increased the risk of BGPVS (OR, 1.05 [95% CI, 1.04-1.06]; P=1.20×10-16), HIPPVS (OR, 1.03 [95% CI, 1.02-1.04]; P=2.96×10-6), and lacunar stroke (OR, 1.31 [95% CI, 1.21-1.41]; P=2.67×10-12). The use of calcium channel blocker to lower BP was significantly associated with lower WMH volume (ß=-0.287 [95% CI, -0.408 to -0.165]; P=4.05×10-6) and significantly reduced the risk of BGPVS (OR, 0.85 [95% CI, 0.81-0.89]; P=8.41×10-19) and HIPPVS (OR, 0.88 [95% CI, 0.85-0.92]; P=6.72×10-9). CONCLUSIONS: Our findings contribute to a better understanding of the pathogenesis of cerebral small vessel disease. Additionally, the utilization of calcium channel blockers to decrease BP can effectively reduce the likelihood of WMH, BGPVS, and HIPPVS. These findings offer valuable insights for the management and prevention of cerebral small vessel disease.

Blood Pressure Management in Intracerebral Haemorrhage: when, how much, and for how long?

PURPOSE OF REVIEW: When compared to ischaemic stroke, there have been limited advances in acute management of intracerebral haemorrhage. Blood pressure control in the acute period is an intervention commonly implemented and recommended in guidelines, as elevated systolic blood pressure is common and associated with haematoma expansion, poor functional outcomes, and mortality. This review addresses the uncertainty around the optimal blood pressure intervention, specifically timing and length of intervention, intensity of blood pressure reduction and agent used. RECENT FINDINGS: Recent pivotal trials have shown that acute blood pressure intervention, to a systolic target of 140mmHg, does appear to be beneficial in ICH, particularly when bundled with other therapies such as neurosurgery in selected cases, access to critical care units, blood glucose control, temperature management and reversal of coagulopathy. Systolic blood pressure should be lowered acutely in intracerebral haemorrhage to a target of approximately 140mmHg, and that this intervention is generally safe in the ICH population.

Prescription of non-steroidal anti-inflammatory and antirheumatic drugs in outpatient hypertensive patients.

BACKGROUND: It has been documented that NSAIDs (nonsteroidal anti-inflammatory and antirheumatic drugs) reduce the effectiveness of some antihypertensive drugs. OBJECTIVE: Analyze the prescription of NSAID and the variables associated in outpatients with hypertension and explore some characteristics of the physicians. MATERIAL AND METHODS: Cross-sectional study, included patients with hypertension from the Family Medicine Unit No. 24 in Mante, Tamaulipas. From the patients, sociodemographic data, clinical history and pharmacological treatments were obtained. From the physicians, sociodemographic and academic information were collected. RESULTS: Mean age of the patients was 63 ± 11 years and 31.7% were prescribed NSAIDs. When compare exposed versus non-exposed to NSAIDs, being in uncontrolled high blood pressure, uncontrolled hypertension, multimorbidity and polypharmacy. The variables associated to the prescription of NSAIDs were: uncontrolled hypertension, multimorbidity and polypharmacy. The 56.7% of the physicians were women, 83.3% with experience >10 years and 33.3% with current certification by the Council in Family Medicine. CONCLUSIONS: The inappropriate prescription of NSAIDs revealed the need to implement actions to mitigate the potential risk for the hypertension patients to present a complication.

ANTECEDENTES: Los antiinflamatorios y los antirreumáticos no esteroideos (AINE) disminuyen la eficacia de algunos antihipertensivos. OBJETIVO: Analizar el patrón de prescripción de AINE y las variables asociadas en pacientes ambulatorios con diagnóstico de hipertensión arterial, así como explorar algunas características de los médicos prescriptores. MATERIAL Y MÉTODOS: Estudio transversal de pacientes con hipertensión de la Unidad de Medicina Familiar 24 en Ciudad Mante, Tamaulipas. De los pacientes se registraron datos sociodemográficos, antecedentes patológicos y tratamientos farmacológicos; y de los médicos, información sociodemográfica y académica. RESULTADOS: La edad promedio de los pacientes fue de 63 ± 11 años, 31.7 % recibía AINE y al contrastarlos con quienes no los recibían, se identificó mayor proporción de obesidad, presión arterial más elevada, más casos en descontrol de la hipertensión arterial, multimorbilidad y polimedicación. Las variables asociadas a la prescripción de AINE fueron estar en descontrol de la hipertensión arterial, multimorbilidad y polimedicación; 56.7 % de los médicos prescriptores fue del sexo femenino, 83.3 % con antigüedad superior a 10 años y 33.3 % con certificación vigente. CONCLUSIONES: La prescripción inapropiada de AINE reveló la necesidad de implementar acciones para mitigar el riesgo potencial de los pacientes hipertensos de presentar una complicación.

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines: Comparisons, Reflections, and Recommendations.

The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.

Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association.

Cardiovascular disease remains the leading cause of death in patients with diabetes. Cardiovascular disease in diabetes is multifactorial, and control of the cardiovascular risk factors leads to substantial reductions in cardiovascular events. The 2015 American Heart Association and American Diabetes Association scientific statement, "Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence," highlighted the importance of modifying various risk factors responsible for cardiovascular disease in diabetes. At the time, there was limited evidence to suggest that glucose-lowering medications reduce the risk of cardiovascular events. At present, several large randomized controlled trials with newer antihyperglycemic agents have been completed, demonstrating cardiovascular safety and reduction in cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and heart failure. This AHA scientific statement update focuses on (1) the evidence and clinical utility of newer antihyperglycemic agents in improving glycemic control and reducing cardiovascular events in diabetes; (2) the impact of blood pressure control on cardiovascular events in diabetes; and (3) the role of newer lipid-lowering therapies in comprehensive cardiovascular risk management in adults with diabetes. This scientific statement addresses the continued importance of lifestyle interventions, pharmacological therapy, and surgical interventions to curb the epidemic of obesity and metabolic syndrome, important precursors of prediabetes, diabetes, and comorbid cardiovascular disease. Last, this scientific statement explores the critical importance of the social determinants of health and health equity in the continuum of care in diabetes and cardiovascular disease.

Nonselective beta-adrenoceptor blocker use and risk of Parkinson's disease: from multiple real-world evidence.

BACKGROUND: People with hypertension have a higher risk of developing Parkinson's disease (PD), epidemiological evidence suggests that multiple antihypertensives may affect the occurrence and development of PD with inconsistent results. With multisource data, we sought to determine whether specific antihypertensive classes elevated or reduced the risk for PD. METHODS: We used a mixed methods approach that combines 4 methodologies. First, we conducted a disproportionality analysis using the reports causing adverse events in the US Food and Drug Administration Adverse Events Reporting System (FAERS) to explore the effect of different classes of antihypertensive medications on the risk of PD; based on the findings from FAERS, a meta-analysis and a UK Biobank cohort analysis were used to further assess the association of drug use with PD; finally, we employed Mendelian randomization (MR) analysis to validate the causal relationship between the drug target and the occurrence of PD. RESULTS: In the disproportionality analysis using the FAERS (N = 187,266), nonselective beta-adrenoceptor blockers (NBBs) were demonstrated to have a significant association with PD (reporting odds ratio (ROR) = 3.13; 95% CI 2.33-4.22). In the meta-analysis of 12 studies with 12,183,809 participants, PD risk was elevated in NBBs (RR, 1.64; 95% CI, 1.19-2.09) when stratified by subtypes of BBs. Among the 105,763 participants included in the cohort analysis using data from the UK Biobank, individuals who used NBBs had a significantly increased risk of PD compared to nonusers (HR, 1.47; 95% CI 1.04-2.06). The MR analysis revealed a significant association between higher expression of the ß2 adrenergic receptor (ADRB2) gene, a drug target blocked by NBBs, and a reduced risk of PD (OR, 0.85; 95% CI 0.73-0.99). CONCLUSIONS: Our comprehensive study indicated that regular NBB use is associated with an increased risk of PD. In light of the detrimental effects of NBBs on PD, some people should choose alternative antihypertensive treatments.

Rational Design of a Highly Specific Prolyl Endopeptidase To Activate the Antihypertensive Effect of Peptides.

Enzymatic hydrolysis of food-derived proteins to produce bioactive peptides could activate food functions such as antihypertension. However, the diversity of enzymatic hydrolysis products can reduce bioactive peptides' efficacy. Highly specific proteases can homogenize the hydrolysis products to reduce the production of impotent peptides. In this study, we successfully obtained M. xanthus prolyl endopeptidase mutant Y451M by constraint/free molecular dynamics simulations and binding energy calculations. The specificity of Y451M for proline was increased by 286 % compared to WT, while its activity was almost unchanged. Milk-derived substrates processed with Y451M showed an antihypertensive effect that was 567 % higher than without enzymes. The ability to activate food antihypertension increased 152 % and the use of enzyme by 192 % compared with WT. Specific proteases are thus valuable tools in the processing of complex substrates to obtain bioactive peptides.

Guideline-Driven Management of Hypertension: An Evidence-Based Update.

Several important findings bearing on the prevention, detection, and management of hypertension have been reported since publication of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline. This review summarizes and places in context the results of relevant observational studies, randomized clinical trials, and meta-analyses published between January 2018 and March 2021. Topics covered include blood pressure measurement, patient evaluation for secondary hypertension, cardiovascular disease risk assessment and blood pressure threshold for drug therapy, lifestyle and pharmacological management, treatment target blood pressure goal, management of hypertension in older adults, diabetes, chronic kidney disease, resistant hypertension, and optimization of care using patient, provider, and health system approaches. Presenting new information in each of these areas has the potential to increase hypertension awareness, treatment, and control which remain essential for the prevention of cardiovascular disease and mortality in the future.

Adherence to Established Blood Pressure Targets and Associated Complications in Patients Presenting with Acute Intracerebral Hemorrhage.

BACKGROUND: Conflicting evidence exists surrounding systolic blood pressure (SBP) control in patients with acute intracerebral hemorrhage (ICH). The 2022 American Heart Association and American Stroke Association guidelines recommend targeting a SBP of 140 mm Hg while maintaining the range of 130-150 mm Hg. The current practice at our health system is to titrate antihypertensives to a SBP goal of < 160 mm Hg, which aligns with previous recommendations. We hypothesized that the prior lack of guidance to a specific SBP target range predisposed patients to hypotension leading to an increased risk of brain and renal adverse events. METHODS: This retrospective, multicenter, single health system cohort study included adults admitted to the neurointensive care unit or intermediate unit with acute ICH from June 2019 to June 2021. The primary objective evaluated the frequency of time within SBP range (140-160 mm Hg) in the first 48 h. Secondary and safety end points included the frequency of time above and below the established SBP range, episodes of hypotension (defined as a decrease in SBP < 140 mm Hg prompting discontinuation in antihypertensive[s] or the initiation of vasopressor[s]), the incidence of new brain or renal adverse events within 7 days, and modified Rankin Scale at discharge. RESULTS: A total of 80 patients (59% men; median age 62 years) were included. The majority of ICHs in this cohort were intraparenchymal (70%). Nearly one third were attributed to systemic hypertension (31%). During the first 48 h of admission, the frequency of time spent above, within, and below the target SBP range were 6 h (12%), 16 h (34%), and 26 h (54%), respectively. Hypotension was associated with renal adverse events (odds ratio [OR] 3.36, 95% confidence interval [CI] 1.10-11.44, p = 0.023). A relative SBP reduction > 20% in the first 48 h was associated with renal adverse events (OR 8.99, 95% CI 2.57-35.25, p < 0.001), brain ischemia (OR 22.5, 95% CI 1.92-300.11, p = 0.005), and an increased odd of a modified Rankin Scale of 4-6 at discharge (OR 11.79, 95% CI 2.79-57.02, p < 0.001). CONCLUSIONS: In individuals with nontraumatic/nonaneurysmal ICH, SBP measurements were observed to be < 140 mm Hg for > 50% of the initial 48 h following admission. Hypotension and relative SBP reduction > 20% were also independent predictors of renal adverse events. SBP reduction > 20% was also an independent predictor of brain ischemia. These data indicate that intensive SBP reduction following ICH predispose patients to secondary organ injury that may impact long-term outcomes. Our data suggest that a more modest lowering of the SBP within 48 h, as recommended in the most recent guidelines, may minimize the risk of further adverse events.

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines.

The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.

Moving toward improved access to medicines and health technologies for cardiovascular disease.

The objectives of this article are to describe the interventions carried out by the Strategic Fund of the Pan American Health Organization to facilitate access to and availability of antihypertensive medicines and devices for measuring blood pressure across the Region of the Americas as part of the HEARTS initiative, and to present the preliminary results of price analyses of antihypertensive medicines. The study methodology included a review of reports made by the Strategic Fund between 2019 and 2020, an evaluation of modalities of procurement, a review of the public procurement databases for five antihypertensive medicines, and a comparison with the price obtained by the Strategic Fund. Differences in price ranging from 20% to 99% were identified, indicating significant opportunities for savings. The study also presents interprogrammatic actions that can support the HEARTS initiative, such as the inclusion of antihypertensive medicines recommended by the World Health Organization, consolidation of regional demand and competitively-priced long-term agreements to manage the procurement of quality generic products, and the definition of technical specifications and regulatory requirements to support the procurement of devices to measure blood pressure. This mechanism will enable Member States to reduce their costs significantly, while extending treatment and diagnostic coverage to more people.

Los objetivos del presente artículo son describir las intervenciones realizadas por el Fondo Estratégico de Organización Panamericana de la Salud, para facilitar el acceso y disponibilidad de medicamentos antihipertensivos y dispositivos para la medición de la presión arterial a los países de la Región de las Américas en apoyo a la implementación de la Iniciativa HEARTS; y presentar los resultados preliminares de los análisis de los precios de los medicamentos antihipertensivos. La metodología del estudio incluyó la revisión de informes realizados por el Fondo Estratégico durante los años 2019-2020, la evaluación de las modalidades de adquisición y revisión de las bases de datos de compras públicas para 5 medicamentos antihipertensivos, y el análisis comparativo con el precio obtenido por el Fondo Estratégico. Se identificaron diferencias que oscilaron entre 20% y 99%, lo que evidencia oportunidades de ahorro significativas. Asimismo, se presentan las acciones interprogramáticas desarrolladas en apoyo a la Iniciativa HEARTS, entre las que se destacan la inclusión de medicamentos antihipertensivos recomendados por la Organización Mundial de la Salud; la consolidación de la demanda regional y el establecimiento de precios competitivos con acuerdos a largo plazo para gestionar la adquisición de productos genéricos de calidad; y la definición de especificaciones técnicas y requisitos regulatorios para apoyar con la adquisición de dispositivos para la medición de la presión arterial. A través de este mecanismo, los Estados Miembros pueden disminuir sus costos significativamente, extendiendo cobertura del tratamiento y diagnóstico a más personas.

Os objetivos deste artigo são descrever as intervenções realizadas pelo Fundo Estratégico da Organização Pan-Americana da Saúde para facilitar o acesso e a disponibilidade de medicamentos anti-hipertensivos e aparelhos de medição de pressão arterial aos países da Região das Américas, em apoio à implementação da iniciativa HEARTS; e apresentar os resultados preliminares da análise dos preços dos medicamentos anti-hipertensivos. A metodologia do estudo incluiu a revisão de relatórios feitos pelo Fundo Estratégico durante os anos de 2019 e 2020, a avaliação das modalidades de aquisição e revisão dos dados de compras públicas de 5 medicamentos anti-hipertensivos e uma análise comparativa com o preço obtido pelo Fundo Estratégico. Foram identificadas diferenças que oscilaram entre 20% e 99%, o que evidencia oportunidades de economia significativas. Da mesma forma, são apresentadas as ações interprogramáticas desenvolvidas em apoio à iniciativa HEARTS, entre as quais se destacam a inclusão de medicamentos anti-hipertensivos recomendados pela Organização Mundial da Saúde; a consolidação da demanda regional e o estabelecimento de preços competitivos com acordos de longo prazo para gerenciar a aquisição de genéricos de qualidade; e a definição de especificações técnicas e requisitos regulatórios para subsidiar a aquisição de aparelhos de medição de pressão arterial. Por meio desse mecanismo, os Estados Membros podem reduzir seus custos significativamente, ampliando a cobertura de tratamento e diagnóstico para atingir mais pessoas.

Synthesis of Dihydropyrimidines: Isosteres of Nifedipine and Evaluation of Their Calcium Channel Blocking Efficiency.

Hypertension and cardiovascular diseases related to it remain the leading medical challenges globally. Several drugs have been synthesized and commercialized to manage hypertension. Some of these drugs have a dihydropyrimidine skeleton structure, act as efficient calcium channel blockers, and affect the calcium ions' intake in vascular smooth muscle, hence managing hypertension. The synthesis of such moieties is crucial, and documenting their structure-activity relationship, their evolved and advanced synthetic procedures, and future opportunities in this area is currently a priority. Tremendous efforts have been made after the discovery of the Biginelli condensation reaction in the synthesis of dihydropyrimidines. From the specific selection of Biginelli adducts to the variation in the formed intermediates to achieve target compounds containing heterocylic rings, aldehydes, a variety of ketones, halogens, and many other desired functionalities, extensive studies have been carried out. Several substitutions at the C3, C4, and C5 positions of dihydropyrimidines have been explored, aiming to produce feasible derivatives with acceptable yields as well as antihypertensive activity. The current review aims to cover this requirement in detail.

More Than Just the Target: Blood Pressure, Stroke, and Vascular Cognitive Impairment.

Despite effective treatments, hypertension remains a leading risk factor of any stroke, stroke recurrence, and vascular cognitive impairment. Hypertension is underdiagnosed and undertreated, both in the primary and secondary prevention setting. The current issue of Stroke includes a Focused Update series of 6 review articles covering differing aspects of hypertension and cerebrovascular disease. Traditionally, the goal of antihypertensive treatment has been risk reduction through reaching defined targets, a "one-size-fits-all" approach, both in the acute stroke and in secondary prevention. In this series, there is a shift toward a more individualized approach to blood pressure management in patients suffering from stroke or vascular cognitive impairment, taking several factors in addition to a defined target into account.

Effect of Antihypertensives by Class on Cerebral Small Vessel Disease: A Post Hoc Analysis of SPRINT-MIND.

BACKGROUND: Treatment of uncontrolled arterial hypertension reduces the risk of cerebral small vessel disease (CSVD) progression, although it is unclear whether this reduction occurs due to blood pressure control or class-specific pleiotropic effects, such as improved beat-to-beat arterial pressure variability with calcium channel blockers. The goal of this study was to investigate the influence of antihypertensive medication class, particularly with calcium channel blocker, on accumulation of white matter hyperintensities (WMH), a radiographic marker of CSVD, within a cohort with well-controlled hypertension. METHODS: We completed an observational cohort analysis of the SPRINT-MIND trial (Systolic Blood Pressure Trial Memory and Cognition in Decreased Hypertension), a large randomized controlled trial of participants who completed a baseline and 4-year follow-up brain magnetic resonance image with volumetric WMH data. Antihypertensive medication data were recorded at follow-up visits between the magnetic resonance images. A percentage of follow-up time participants were prescribed each of the 11 classes of antihypertensive was then derived. Progression of CSVD was calculated as the difference in WMH volume between 2 scans and, to address skew, dichotomized into a top tertile of the distribution compared with the remaining. RESULTS: Among 448 individuals, vascular risk profiles were similar across WMH progression subgroups except age (70.1±7.9 versus 65.7±7.3 years; P<0.001) and systolic blood pressure (128.3±11.0 versus 126.2±9.4 mm Hg; P=0.039). Seventy-two (48.3%) of the top tertile cohort and 177 (59.2%) of the remaining cohort were in the intensive blood pressure arm. Those within the top tertile of progression had a mean WMH progression of 4.7±4.3 mL compared with 0.13±1.0 mL (P<0.001). Use of angiotensin-converting enzyme inhibitors (odds ratio, 0.36 [95% CI, 0.16-0.79]; P=0.011) and dihydropyridine calcium channel blockers (odds ratio, 0.39 [95% CI, 0.19-0.80]; P=0.011) was associated with less WMH progression, although dihydropyridine calcium channel blockers lost significance when WMH was treated as a continuous variable. CONCLUSIONS: Among participants of SPRINT-MIND trial, angiotensin-converting enzyme inhibitor was most consistently associated with less WMH progression independent of blood pressure control and age.

Temporal Trajectory of Systolic Blood Pressure and Outcomes in Acute Intracerebral Hemorrhage: ATACH-2 Trial Cohort.

BACKGROUND: To highlight the heterogeneity of acute temporal blood pressure (BP) changes in the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) and associations with the outcomes of intracerebral hemorrhage. METHODS: One thousand patients with acute intracerebral hemorrhage, who had been randomized to intensive (110-139 mm Hg) or standard (140-179 mm Hg) systolic BP (SBP) lowering with intravenous nicardipine in ATACH-2 from 2011 to 2015, were analyzed about temporal changes in hourly maximum SBP up to 24 hours after randomization using group-based trajectory modeling. Outcomes included death or disability (modified Rankin Scale score 4-6) at 3 months, neurological deterioration within 24 hours (≥2-point decrease in Glasgow Coma Scale score or ≥4-point increase in National Institutes of Health Stroke Scale score), and acute kidney injury (≥0.3 mg/dL within 48 hours or ≥1.5-fold increase in serum creatinine) within 7 days after onset. RESULTS: Group-based trajectory modeling revealed 4 SBP trajectory groups: moderate SBP (from ≈190 mm Hg at hospital arrival to 150-160 mm Hg after randomization; n=298), moderate-to-low SBP (from ≈190 mm Hg to <140 mm Hg; n=395), high-to-low SBP (from >210 mm Hg to <140 mm Hg; n=134), and high SBP (from >210 mm Hg to 160-170 mm Hg; n=173). Patients with intensive treatment accounted for 11.1%, 88.6%, 85.1%, and 1.7% of each group, respectively. Compared with the moderate-to-low SBP group, the high-to-low SBP group showed increased risks of death or disability at 3 months (adjusted odds ratio, 2.29 [95% CI, 1.24-4.26]) and acute kidney injury (adjusted odds ratio, 3.50 [95% CI, 1.83-6.69]), while no increase in neurological deterioration was seen in this group (adjusted odds ratio, 0.48 [95% CI, 0.20-1.13]). The moderate SBP and high SBP groups showed no significant risk differences for such outcomes. CONCLUSIONS: Data-driven observation using a group-based trajectory modeling approach may be useful to clarify the relationship between antihypertensive treatment, temporal SBP changes, and outcomes in acute intracerebral hemorrhage. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01176565.