Association between intensive blood pressure lowering and stroke-free survival among patients with and without Diabetes.

This study pooled data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial to estimate the treatment effect of intensive BP on stroke prevention, and investigate whether stroke risk score impacted treatment effect. Of all the potential manifestations of the hypertension, the most severe outcomes were stroke or death. A composite endpoint of time to death or stroke (stroke-free survival [SFS]), whichever occurred first, was defined as the outcome of interest. Participants without prevalent stroke were stratified into stroke risk tertiles based on the predicted revised Framingham Stroke Risk Score. The stratified Cox model was used to calculate the hazard ratio (HR) for the intensive BP treatment. 834 (5.92%) patients had SFS events over a median follow-up of 3.68 years. A reduction in the risk for SFS was observed among the intensive BP group as compared with the standard BP group (HR: 0.76, 95% CI: 0.65, 0.89; risk difference: 0.98([0.20, 1.76]). Further analyses demonstrated the significant benefit of intensive BP treatment on SFS only among participants having a high stroke risk (risk tertile 1: 0.76 [0.52, 1.11], number needed to treat [NNT] = 861; risk tertile 2: 0.87[0.65, 1.16], NNT = 91; risk tertile 3: 0.69[0.56, 0.86], NNT = 50). Intensive BP treatment lowered the risk of SFS, particularly for those at high risk of stroke.

Estimated Pulse Wave Velocity and Cognitive Outcomes: A Post hoc Analysis of SPRINT-MIND.

BACKGROUND: Arterial stiffness has been confirmed to be associated with cognitive impairment. Carotid-femoral pulse wave velocity (cfPWV) is widely regarded as the gold standard for assessing arterial stiffness, yet it is not readily accessible. In response, the use of estimated pulse wave velocity (ePWV) has been proposed as a more accessible and cost-effective alternative. ePWV not only offers ease of calculation but also covers a broader spectrum of vascular aging processes, some of which may be distinct from those detected by cfPWV. The aim of our study was to investigate the association between ePWV and cognitive outcomes in SPRINT-MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension). METHODS: This study was a post hoc analysis of the SPRINT-MIND. The primary endpoint was a composite outcome including probable dementia and mild cognitive impairment (MCI). The calculation of ePWV was based on age and mean blood pressure. The association between ePWV and cognitive outcomes was assessed Using Cox regression analysis. The response of ePWV to antihypertensive treatment at 12 months was used to define treatment efficacy. RESULTS: 8,563 patients were enrolled. The ePWV was found to be independently associated with risk of probable dementia (Tertile 3 vs. Tertile 1: HR, 95% CI: 1.70, 1.08-2.68, P = 0.023, P for trend = 0.013), MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.35, 1.71-3.23, P < 0.001, P for trend < 0.001), and the composite outcome of probable dementia or MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.17, 1.65-2.86, P < 0.001, P for trend < 0.001). The combined effect of treatment allocation and the response of ePWV to treatment exhibited that intensive/ePWV responders had the lowest risk of the primary outcome (Log-rank P = 0.002). CONCLUSIONS: EPWV demonstrated independent predictive value for cognitive outcomes in SPRINT-MIND.

Effects of intensive blood-pressure treatment on myocardial work in elderly hypertensive patients: A subcenter study of the STEP randomized controlled trial.

BACKGROUND: The benefits and safety of intensive blood pressure treatment in elderly hypertensive patients have been proved in the STEP trial. However, relevant mechanisms for intensive treatment are lacking. HYPOTHESIS: We aimed to explore whether intensive blood pressure treatment is associated with left ventricular systolic function changes as evaluated by myocardial work (MW) parameters in elderly hypertensive patients compared to the standard. METHODS: Patients were randomized to the intensive group (n = 66, median age 66 years, 42.4% male) with a systolic blood pressure (SBP) goal of 110 to <130 mmHg or the standard treatment group (n = 50, median age 63.5 years, 30% male) with an SBP goal of 130-<150 mmHg in this subcenter study of the STEP trial. There was no pre-randomization echocardiographic collected. Echocardiographic exam was produced at 1-year (phase 1) and 3-year (phase 2) post-randomization. RESULTS: In phase 1, SBP was already significantly lower in the intensive treatment group than in the standard treatment group (126.5 vs. 132.1 mmHg, p < .05). During a median follow-up of 40 months, in phase 2, the intensive group still had a lower SBP than the standard treatment group (125.0 vs. 135.3 mmHg, p < .05). Both global work index (GWI) and global constructive work (GCW) decreased significantly in phase in the intensive treatment group but not in the standard group (p < .05). Global wasted work (GWW) increased and global work efficiency (GWE) declined in both groups from phase 1 to phase 2 while no significant difference between the treatment effects. Similarly, left ventricular ejection function (LVEF) and global longitudinal strain (GLS) decreased in the two groups. The multivariate linear regression analysis showed the intensive treatment appeared to be an independent predictor of the ΔGWI (ß = -110.92; 95% CI, -197.78 to -30.07, p = .008) and ΔGCW (ß = -135.11; 95% CI, -220.33 to -49.88, p = .002). CONCLUSIONS: In elderly hypertensive patients, lower SBP was associated with decreased GWI and GCW and intensive BP treatment did not improve global MW efficiency.

The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: mediation analysis in SPRINT.

AIMS: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. METHODS AND RESULTS: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. CONCLUSION: The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.

The benefit of intensive (<120 mmHg) blood pressure (BP) treatment, reduction in all-cause mortality (ACM), was attenuated when mediated through non-fatal major adverse cardiovascular events. This was driven by cardiovascular mortality (CVM). The harm of intensive BP treatment, increase in ACM, was amplified when mediated through serious adverse events. This was driven by non-CVM. Current reporting of treatment effects in cardiovascular trials does not allow for expansion of the lens to focus on important occurrences after the index event.

Intensive Blood Pressure Treatment Goals: Evidence for Cardiovascular Protection From Observational Studies and Clinical Trials.

Epidemiologic studies have consistently identified a strong, progressive relationship between blood pressure (BP) and cardiovascular disease (CVD) events, in a range of systolic BP (SBP) from as low as 90 mm Hg to as high as 180 mm Hg. Clinical trials have demonstrated greater prevention of CVD with more compared with less intensive antihypertensive drug treatment. Meta-analyses of randomized controlled trials provide strong evidence for more intensive antihypertensive drug therapy down to an SBP of 130 mm Hg, and to an SBP 120-124 mm Hg in the meta-analysis with the greatest statistical power. In the Systolic Blood Pressure Intervention Trial (SPRINT) randomization to an SBP treatment goal of <120 mm Hg compared with <140 mm Hg in persons with high CVD risk not only reduced the rate of CVD but also all-cause mortality. These benefits were noted in all of the prestated subgroups of interest, including those ≥65 years of age at baseline. In addition, cognitive impairment was less common in those randomized to the intensive compared with standard treatment. Most clinical practice guidelines recommend an SBP treatment target <130 mm Hg in adults with a high risk of CVD, which is the norm for many patients seen in clinical practice, especially those who are older, have diabetes mellitus, or chronic kidney disease.

Effects of glucose and blood pressure reduction on subclinical cardiac damage: Results from ADVANCE.

OBJECTIVE: Observational data suggest a potential for subclinical cardiac damage from intensive blood glucose or blood pressure (BP) control, particularly in adults with very low blood glucose and BP levels. However, this has not been tested in a randomized trial. METHODS: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Research Controlled Evaluation (ADVANCE) study was a factorial, randomized trial designed to test the effects of intensive blood glucose (hemoglobin A1c ≤6.5% versus usual care) and intensive BP (combination of perindopril-indapamide versus placebo) control on vascular events in adults with diabetes. Using mixed effects tobit models, we determined the effect of the randomized interventions on change in subclinical cardiac injury (high sensitivity cardiac troponin T [hs-cTnT]) and strain (N-terminal b-type pro natriuretic peptide [NT-proBNP]), 1 year after randomization. RESULTS: Among the 682 participants, mean age was 66.1 (SD, 6.5) years; 40% were women. Mean baseline hemoglobin A1c was 7.4% (SD, 1.5) and systolic/diastolic BP was 147 (SD,21)/81 (SD,11) mmHg. After 1 year, intensive versus standard glucose control did not significantly change hs-cTnT (1.5%; 95%CI:-4.9,8.2) or NT-proBNP (-10.3%; 95%CI: -20.2%,0.9%). Intensive versus standard BP control also did not affect hs-cTnT (-2.9%; 95%CI: -8.9,3.6), but did significantly lower NT-proBNP by 21.6% (95%CI:-30.2%,-11.9%). Changes in systolic BP at 1 year (versus baseline) were strongly associated with NT-proBNP (P = 0.004), but not hs-cTnT (P = 0.95). CONCLUSIONS: In adults with diabetes, intensive BP control reduced NT-proBNP without increasing hs-cTnT, supporting the benefits and safety of intensive BP control in adults with diabetes. This trial is registered at clinicaltrials.gov, number: NCT00145925.

HIPERTENSÃO E DIABETES: CONCEITOS ATUAIS NA TERAPÊUTICA / HYPERTENSION AND DIABETES: CURRENT CONCEPTS IN THERAPEUTICS

Diabetes mellitus tipo 2 (DM) cursa com alta prevalência na população, acometendo cerca de 9,3% da população mundial (463 milhões de indivíduos). Devido ao crescimento dos casos e envelhecimento populacional, estima-se que o número de diabéticos será superior a 628 milhões em 2045. Dados de 2013 estimam que 6,2% da população brasileira acima dos 18 anos de idade tenham diabetes. Rápida urbanização, transição epidemiológica, fator nutricional, estilo de vida sedentário, excesso de peso, crescimento e envelhecimento populacional são fatores associados ao aumento da prevalência. Geralmente, ao tempo do diagnóstico do DM, a hipertensão arterial sistêmica (HAS) está presente em 50% dos diabéticos. O artigo discute aspectos relacionados à fisiopatogenia do diabetes e hipertensão, as metas de pressão arterial e as principais abordagens terapêuticas no tratamento da hipertensão arterial no paciente diabético, de acordo com as diretrizes mais recentes

Type 2 Diabetes mellitus presents high prevalence in the population, responding for about 9.3% in the world population (463 million individuals). Due to cases increase and aging, it is estimated that the number of diabetic subjects will be higher than 628 million in 2045. Data of 2013 show that 6,2% of Brazilian population higher 18 years-old have diabetes. Fast urbanization, epidemiological transition, nutritional factor, physical inactivity, overweight, population growth and aging are factors associated to increase of prevalence. Generally, when of diabetes diagnosis, hypertension is present in 50% of diabetic individuals. The article discusses aspects of pathophysiology of hypertension and diabetes, the targets of blood pressure and the principal therapeutic approaches of treatment of hypertension in the diabetic patient, in according to recenter guidelines

Blood pressure control in older adults with hypertension: A systematic review with meta-analysis and meta-regression.

BACKGROUND: Managing blood pressure reduces CVD risk, but optimal treatment thresholds remain unclear as it is a balancing act to avoid hypotension-related adverse events. OBJECTIVES: This systematic review, meta-analysis and meta-regression evaluated the benefits of intensive BP treatment in hypertensive older adults. METHODS: We systematically searched PubMed, MEDLINE, EMBASE, and the Cochrane Library of Controlled Trials until January 31, 2020. Studies comparing different BP treatments/targets and/or active BP against placebo treatment, with a minimum 12 months follow-up, were included. Risk ratios (RR) and 95% CIs were calculated using a random effects model. The primary outcome was RR of major cardiovascular events (MCEs); secondary outcomes included myocardial infarction (MI), stroke, heart failure (HF), cardiovascular (CV) mortality, and all-cause mortality. RESULTS: We included 16 studies totaling 65,890 hypertensive participants (average age 69.4 years) with a follow-up period from 1.8 to 4.9 years. Intensive BP treatment significantly reduced the relative risk of MCEs by 26% (RR:0.74, 95%CI 0.64-0.86, p = 0.000; I 2 = 79.71%). RR of MI significantly reduced by 13% (RR:0.87, 95%CI 0.76-1.00, p = 0.052; I 2 = 0.00%), stroke by 28% (RR:0.72, 95%CI 0.64-0.82, p = 0.000; I 2  = 32.45%), HF by 47% (RR:0.53, 95% CI 0.43-0.66, p = 0.000; I 2 = 1.23%), and CV mortality by 24% (RR:0.76, 95%CI 0.66-0.89, p = 0.000; I 2 = 39.74%). All-cause mortality reduced by 17% (RR:0.83, 95%CI 0.73-0.93, p = 0.001; I 2 = 53.09%). Of the participants - 61% reached BP targets and 5% withdrew; with 1 hypotension-related event per 780 people treated. CONCLUSIONS: Lower BP treatment targets are optimal for CV protection, effective, well-tolerated and safe, and support the latest hypertension guidelines.

Effectiveness of blood pressure-lowering treatment by the levels of baseline Framingham risk score: A post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT).

This was a post hoc analysis of Systolic Blood Pressure Intervention Trial (SPRINT), aimed to investigate whether intensive blood pressure treatment has differential therapeutic outcomes on patients with different baseline Framingham risk score (FRS). The 9298 SPRINT participants were categorized into low-risk (baseline FRS < 10%), intermediate-risk (FRS = 10%-20%), or high-risk (FRS > 20%) arms. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Serious adverse events were defined as hypotension, syncope, and bradycardia. Multiple Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these three groups. After a median follow-up time of 3.26 years, the primary outcome hazard ratio (HR) for intensive versus standard treatment was 0.73 (95% CI: 0.61-0.88, P = .0044) in the high-risk arm. And, for all-cause mortality, the hazard ratio with intensive SBP treatment was 1.58 (95% CI: 0.55-1.06), 0.9 (95% CI: 0.26-9.50), and 0.53 (95% CI: 0.34-0.82) in three arms (all P values for interaction > 0.05). Effects of intensive versus standard SBP control on serious adverse events were similar among patients with different FRS. Our results suggested that regardless of the FRS level, the intensive blood pressure control was beneficial.

Unintended consequences of the new ACC/AHA blood pressure treatment guidelines.

Hypertension is a major risk factor for cardiovascular disease, heart failure, chronic kidney disease and stroke. Therefore, its early detection and treatment are very important according to blood pressure (BP) treatment guidelines issued by the various scientific societies. Over the years, BP treatment guidelines have changed from strict control of BP to more relaxed control, and lately to a strict BP control influenced by the results of the SPRINT trial. The recently published BP treatment guidelines by the American College of Cardiology/American Heart Association (ACC/AHA) recommend a systolic BP (SBP) and diastolic BP reduction to less than 130 mmHg and less than 80 mmHg, respectively, for all ages, and have also changed the classification of hypertension by changing the term "prehypertension" of the JNC 7 (7th Joint National Committee) guidelines to "stage 1 hypertension". These changes could have significant social and economic consequences for the patients. In order to get a better perspective of the current status of SBP control, we conducted a MEDLINE search of the English language literature from 2014 to 2018 in connection with recent (2014-2018) BP treatment guidelines, using the terms 'hypertension', 'blood pressure control', 'intensive blood pressure control', 'blood pressure treatment guidelines', and 'benefits and risks of intensive blood pressure control', and 26 pertinent papers were retrieved. These papers together with collateral literature, which goes beyond the year 2014, will be discussed in this review.

[Positioning for the management of arterial hypertension in Primary Care from the critical analysis of the American (2017) and European (2018) guidelines. Spanish Society of Primary Care Physicians (SEMERGEN)]. / Posicionamiento para el manejo de la hipertensión arterial en atención primaria a partir del análisis crítico de las guías americana (2017) y europea (2018). Sociedad Española de Médicos de Atención Primaria (SEMERGEN).

The Scientific Societies of Primary Care, being the area in which there is a considerable prevalence of Arterial Hypertension (AHT), need to periodically evaluate the international guidelines for its management. This is particularly relevant when disparate guidelines make it difficult to make decisions in daily clinical practice. The present document has as its aim to analyse the changes and new developments proposed in the guidelines of the American College of Cardiology and the American Heart Association (ACC/AHA 2017), as well as in the guidelines of the European Society of Cardiology and European Society of Hypertension (ESC/ESH 2018). An analysis will be made of any differences, limitations, and their applicability to Primary Care in Spain. Finally, the most relevant available and appropriate information is extracted and integrated in order to homogenise the care of the hypertensive patient, from a critical, but also a reasoned, perspective. The discrepancies between the recommendations in such essential aspects as the management of the disease, require the compiling and critical analysis of the information that enables us as scientific society, interested in providing all PC physicians with the most relevant, and at the same time, sensible, recommendations of all the guidelines.

2018 Practice Guidelines for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension.

These practice guidelines on the management of arterial hypertension are a concise summary of the more extensive ones prepared by the Task Force jointly appointed by the European Society of Hypertension and the European Society of Cardiology. These guidelines have been prepared on the basis of the best available evidence on all issues deserving recommendations; their role must be educational and not prescriptive or coercive for the management of individual subjects who may differ widely in their personal, medical and cultural characteristics. The members of the Task Force have participated independently in the preparation of these guidelines, drawing on their academic and clinical experience and by objective examination and interpretation of all available literature. A disclosure of their potential conflict of interest is reported on the websites of the ESH and the ESC.

[Management of arterial hypertension : ESC/ESH guidelines 2018]. / Management der arteriellen Hypertonie : ESC/ESH-Leitlinien 2018.

The ESC/ESH guidelines 2018 for the treatment of arterial hypertension are designed for adults with hypertension, i. e. ≥18 years. The guidelines reflect new findings and assess them for the recommendations. The specific objectives of these guidelines were to develop pragmatic guidance on how to improve the detection and treatment of hypertension and to improve poor blood pressure control rates by promoting simple and effective treatment strategies. This overview also presents the differences to the last guidelines on hypertension from the year 2013.

Early standardized treatment of critical blood pressure elevations is associated with a reduction in eclampsia and severe maternal morbidity.

BACKGROUND: Hypertensive disorders of pregnancy result in significant maternal morbidity and mortality. State and national guidelines have been proposed to increase treatment of patients with hypertensive emergencies or critically elevated blood pressures. There are limited data available to assess the impact of these recommendations on maternal morbidity. OBJECTIVE: The purpose of this prospective quality improvement project was to determine if maternal morbidity would be improved using a standardized approach for treatment of critically elevated blood pressures. STUDY DESIGN: In all, 23 hospitals participated in this project. Treatment recommendations included the use of an intravenous blood pressure medication and magnesium sulfate when there was a sustained blood pressure of ≥160 mm Hg systolic and/or ≥110 mm Hg diastolic. Compliance with the metric recommendations was monitored based on the number of patients treated with an intravenous blood pressure medication, use of magnesium sulfate, and if they received a timely postpartum follow-up appointment. The metric was scored as all or none; missing any of the 3 metric components was considered noncompliant. From January through June 2015 baseline data were collected and hospitals were made aware that ongoing monitoring of compliance would begin in July 2015 through June 2016. The primary outcomes were composite metric compliance, the incidence of eclampsia per 1000 births, and severe maternal morbidity. RESULTS: During the 18 months of this study there were 69,449 births. Within this population, 2034 met criteria for a critically elevated blood pressure, preeclampsia, or superimposed preeclampsia with severe features. Of this group, 1520 had a sustained critical blood elevation. Initial compliance with treatment recommendations was low (50.5%) and increased to >90% after April 2016 (P < .001). Compliance with utilization of intravenous blood pressure medication increased by 33.2%, from a baseline of 57.1-90.3% (P < .01) during the last 6 months of monitoring. Compliance with utilization of magnesium sulfate increased by 10.8%, from a baseline of 85.4-96.2% (P < .01). The incidence of eclampsia declined by 42.6% (1.15 ± 0.15/1000 to 0.62 ± 0.09/1000 births). Severe maternal morbidity decreased by 16.7% from 2.4 ± 0.10% to 2.0 ± 0.15% (P < .01). CONCLUSION: We noted 3 important findings: (1) compliance with state and national treatment guidelines is low without monitoring; (2) high levels of compliance can be achieved in a relatively short period of time; and (3) early intervention with intravenous blood pressure medication and magnesium sulfate for verified sustained critical maternal blood pressures resulted in a significant reduction in the rate of eclampsia and severe maternal morbidity. The reduction in the rate of eclampsia could only partially be attributed to the increase in the use of magnesium sulfate, suggesting an additive or synergistic effect of the combined treatment of an antihypertensive medication and magnesium sulfate on the rate of eclampsia and severe maternal morbidity.

BP Targets in Hypertension: What Should We Do Now That SPRINT Is Out?

Systolic blood pressure (SBP) is an important predictor of cardiovascular disease (CVD) outcomes. Lowering SBP has been shown to reduce CVD morbidity and mortality, but the optimal SBP target continues to be a topic of intense debate. The Systolic Blood Pressure Intervention Trial (SPRINT) reported a significantly lower risk for CVD outcomes and all-cause mortality by targeting SBP <120 mmHg compared with <140 mmHg in a population of hypertensive persons at high CV risk. In this review, we discuss the strengths, limitations, and generalizability of SPRINT findings to other hypertensive populations that were excluded from the trial, including those with diabetes or prior stroke, <50 years old, and at lower CVD risk. We will focus on the implications of SPRINT findings for appropriate BP targets in high-risk groups of hypertensive persons, including the elderly and those with chronic kidney disease (CKD). We will also address the cost-effectiveness of intensive BP treatment as implemented in SPRINT and the implications of SPRINT for health care policy and future BP guidelines.

2014 Guideline for the Management of High Blood Pressure (Eighth Joint National Committee): Take-Home Messages.

The JNC 8 guidelines focus on 3 highest-ranked clinical questions that include BP thresholds for starting therapy, specific BP goals, and risks and benefits of specific antihypertensive drugs. Only randomized controlled trial data were used and JNC 8 panel did not include observational studies, systematic reviews, or meta-analyses. The investigators also suggested that benefit of lowering BP to less than 140/90 is not clear. Lifestyle modifications were considered very important for all patients with hypertension. These recommendations are not alternatives for clinical judgment, and decisions about medical care must be individualized to each patient.