BP-lowering Treatment Research Articles

Association of 24-Hour Blood Pressure With Urinary Sodium Excretion in Healthy Adults.

While the positive relationship between urinary sodium excretion and blood pressure (BP) is well established for middle-aged to elderly individuals using office BP, data are limited for younger individuals and ambulatory BP measurements. Our analysis included 2,899 individuals aged 18 to 90 years from 2 population-based studies (GAPP, Swiss Kidney Project on Genes in Hypertension [SKIPOGH]). Participants with prevalent cardiovascular disease, diabetes, or on BP-lowering treatment were excluded. In SKIPOGH, 24-hour urinary sodium excretion was used as a measure of sodium intake, while in GAPP it was calculated from fasting morning urinary samples using the Kawasaki formula. Multivariable linear regression models were used to assess the relationships of 24-hour urinary salt excretion with office and ambulatory BP measurements. Mean age, ambulatory BP, sodium excretion, and estimated glomerular filtration rate in GAPP and SKIPOGH were 35 and 44 years, 123/78 and 118/77 mm Hg, 4.2 and 3.3 g/d, and 110 and 99 ml/min/1.73 m2, respectively. A weak linear association was observed between 24-hour ambulatory systolic BP and urinary sodium excretion (β (95% confidence interval [CI]) per 1 g increase in sodium excretion (0.33 % (0.09; 0.57); P = 0.008). No significant relationships were observed for 24-hour ambulatory diastolic BP (β (95% CI) (0.13 % (-0.15; 0.40) P = 0.37). When repeating the analyses in different age groups, all BP indices appeared to have stronger relationships in the older age groups (>40 years). In these large cohorts of healthy adults, urinary sodium excretion was only weakly associated with systolic 24-hour ambulatory BP.

Review: In primary prevention, BP-lowering treatment reduces major CV events in patients with SBP ≥ 140 mm Hg

Source Citation Brunstrom M, Carlberg B. Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA I...

Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels

High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated. To assess the association between BP lowering treatment and death and CVD at different BP levels. Previous systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017. Randomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included. Data were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines. Prespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease. Seventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07). Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.

Effects of blood-pressure-lowering treatment on outcome incidence. 12. Effects in individuals with high-normal and normal blood pressure: overview and meta-analyses of randomized trials.

It is currently unknown whether individuals with SBP/DBP values in the ranges 120-139/80-89 mmHg, usually defined as with prehypertension or high-normal and normal blood pressure (BP), benefit from BP-lowering treatment and whether benefits in these individuals depend on the level of their cardiovascular risk. Meta-analyzing all available data from randomized controlled trials (RCTs) about the effects on cardiovascular outcomes of BP-lowering treatment in individuals with normal or high-normal BP values in absence of baseline antihypertensive drugs and free from a recent myocardial infarction, left ventricular dysfunction and heart failure. From an available database of BP-lowering RCTs updated to end 2016, RCTs were selected only including normotensive individuals or including both hypertensive and normotensive individuals but providing separate information in normotensive individuals. Risk ratios and 95% confidence intervals, and absolute risk reduction of cardiovascular outcomes and all deaths were calculated by a random-effects model. We identified 24 RCTs providing data on 47 991 high-normal or normal BP individuals. BP-lowering treatment was found to significantly reduce cardiovascular disease risk in these individuals, but risk reduction was limited to stroke. When RCTs were stratified according to total cardiovascular risk, no significant benefits were found in RCTs including individuals at low-moderate risk (13 RCTs, 21 128 individuals), whereas a significant reduction in stroke risk (-60% to a SBP/DBP reduction of 10/5 mmHg) was found in RCTs including individuals at high-very high risk mostly because of symptomatic cardiovascular disease (11 RCTs, 26 863 individuals). In high-very high-risk normotensive individuals, BP-lowering treatment appeared to reduce stroke risk independently of the drug class used. Individuals with very high cardiovascular risk due to symptomatic cardiovascular disease should consider BP-lowering treatment even when their BP is in the high-normal and normal range.

Blood pressure target in 2017

The issue of how far blood pressure (BP) should be lowered under antihypertensive treatment is still an important matter of scientific debate. The aim of the present review is to consider the clinical relevance of individualized BP goal under treatment in hypertensive patients according to their age, comorbidities or established cardio-vascular (CV) disease. The French and European recommendations propose a systolic BP target between 130 and 139mmHg (<150mmHg after 80 years) and diastolic BP target <90mmHg in hypertensive patients whatever their level of risk. The results of the recent SPRINT study suggest that a more ambitious systolic BP target, <120mmHg, significantly reduces CV morbidity and mortality, but with an increased iatrogenic risk. Several questions in everyday practice have to be considered. An important issue concerns BP measurement methods in this clinical trial (Dinamap) versus in routine clinical practice and the implications on BP treatment targets. In addition, close monitoring of participants in clinical trials and active orthostatic hypotension research limit the incidence of adverse events related to intensive treatement. Finally, in the presence of an established CV disease, an intensive therapeutic approach could be associated with a J-curve relationship between BP level and CV events. An early and strict BP control in young or middle-aged hypertensive patients in primary prevention should be a priority. In this hypertensive population with low to moderate CV risk, without established CV or renal diseases, more stringent than recommended BP-lowering treatment could potentially prevent hypertensive arterial damage and thus correct the increased residual CV risk later in life. The tolerance of an intensive therapeutic approach should remain a concern in elderly patients and in patients with established CV disease.

LB.03.08] SERUM CHLORIDE AND ADVERSE CARDIOVASCULAR EVENTS IN THE ANGLO SCANDINAVIAN CARDIAC OUTCOMES TRIAL (ASCOT)

Objective: Data suggests that lower serum chloride (Cl-) is associated with higher mortality and cardiovascular risk in populations with hypertension or heart failure. In this study, we tested the association between serum Cl- and cardiovascular outcomes in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Blood Pressure-Lowering Arm. Design and method: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized a subset of 6549 patients at risk with no history of coronary heart disease to either atenolol-based or amlodipine-based BP lowering treatment and followed-up for 5.5 years. Serum Cl- was measured at baseline in 319 participants who had a cardiovascular event and 1361 controls, matched for age and sex. The primary outcome was a composite of fatal and non-fatal myocardial infarction, stroke and heart failure. Subjects were grouped into four categories based on Serum Cl- levels (Cl-< = 95; 95.1–105; 105.1–115; >115.1 mmol/L). The characteristics of the study population across these groups were compared using 1-way ANOVA for continuous variables and X2 test for categorical variables. Kaplan-Meier (KM) and Cox Proportional Hazard models (Cox-PH), adjusted for age, sex, body mass index, systolic blood pressure, smoking, diabetes, cholesterol, serum Na+, use of diuretics and randomisation group, were used to explore the multivariate adjusted association between baseline serum Cl- and cardiovascular events. Results: Participants with Cl- <95 mmol/L had a greater proportion of females (24.1 vs 11.9%; p 0.02) than those with Cl- >115.1, were slightly older (67.8[7.7] vs 65.3[7.5] years; p 0.01), had lower sodium (139[5] vs 142[3] mmol/L; p <0.01), and were more likely to be taking a diuretic (66.3 vs 28.9%; p < 0.01). Serum Cl- <95 mmol/L was associated with an increased risk of a cardiovascular event (HR 4.09[95% CI 1.17–14.32; p 0.03] independent of serum Na+ (1.01[0.97–1.5]; p 0.80) or diuretic use (1.13[0.89–1.42]; p 0.31) compared to those with serum Cl->115.1 mmol/L (figure). Conclusions: In the ASCOT study, serum chloride less than 95 mmol/L was associated with greater risk of cardiovascular events, independent of serum sodium or diuretic use.

Intensive versus standard lowering of blood pressure in the acute phase of intracranial haemorrhage: a systematic review and meta-analysis.

The optimal target of blood pressure (BP) in the acute phase of intracranial haemorrhage (ICH) is still controversial. Our aim was to evaluate safety and efficacy of intensive BP lowering compared to standard BP treatment in ICH. We conducted a systematic review and meta-analysis of all available randomized controlled trials recruiting patients with elevated BP in acute spontaneous ICH to intensive or standard BP-lowering treatment. Our primary outcomes were 3-month mortality, disability (modified Rankin Scale 3-5) and combined death or disability. Secondary outcomes were early neurological deterioration at 24h, substantial haematoma enlargement within 24-72h and 3-month non-fatal serious adverse events. We included six studies for a total of 4385 patients (mean age 62years, 62.3% men). No differences were detected between the two treatment groups in 3-month mortality (RR=0.99, 95% CI 0.83-1.17), disability (RR=0.96, 95% CI 0.89-1.03) and combined death and disability (RR=0.97, 95% CI 0.90-1.03). The rate of patients with early neurological deterioration, substantial haematoma enlargement and non-fatal serious adverse events was similar in the two treatment groups (RR=1.03, 95% CI 0.88-1.19, RR=0.85, 95% CI 0.70-1.03, RR=1.07, 95% CI 0.90-1.28, respectively). An intensive BP control in the acute phase of ICH is not beneficial and should not be recommended. Therefore, the systolic BP target of less than 140mmHg that is now suggested by guidelines needs to be reconsidered.

Isometric Handgrip as an Adjunct for Blood Pressure Control: a Primer for Clinicians.

Considered a global health crisis by the World Health Organization, hypertension (HTN) is the leading risk factor for death and disability. The majority of treated patients do not attain evidence-based clinical targets, which increases the risk of potentially fatal complications. HTN is the most common chronic condition seen in primary care; thus, implementing therapies that lower and maintain BP to within-target ranges is of tremendous public health importance. Isometric handgrip (IHG) training is a simple intervention endorsed by the American Heart Association as a potential adjuvant BP-lowering treatment. With larger reductions noted in HTN patients, IHG training may be especially beneficial for those who (a) have difficulties continuing or increasing drug-based treatment; (b) are unable to attain BP control despite optimal treatment; (c) have pre-HTN or low-risk stage I mild HTN; and (d) wish to avoid medications or have less pill burden. IHG training is not routinely prescribed in clinical practice. To shift this paradigm, we focus on (1) the challenges of current HTN management strategies; (2) the effect of IHG training; (3) IHG prescription; (4) characterizing the population for whom it works best; (5) clinical relevance; and (6) important next steps to foster broader implementation by clinical practitioners.

Association of Intensive Blood Pressure Control and Kidney Disease Progression in Nondiabetic Patients With Chronic Kidney Disease

The optimal blood pressure (BP) target remains debated in nondiabetic patients with chronic kidney disease (CKD). To compare intensive BP control (<130/80 mm Hg) with standard BP control (<140/90 mm Hg) on major renal outcomes in patients with CKD without diabetes. Searches of PubMed, MEDLINE, Embase, and Cochrane Library for publications up to March 24, 2016. Randomized clinical trials that compared an intensive vs a standard BP target in nondiabetic adults with CKD, reporting changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, end-stage renal disease (ESRD), or all-cause mortality. Random-effects meta-analyses for pooling effect measures. Meta-regression and subgroup analyses for exploring heterogeneity. Differences in annual rate of change in GFR were expressed as mean differences with 95% CIs. Differences in doubling of serum creatinine or 50% reduction in GFR, ESRD, composite renal outcome, and all-cause mortality were expressed as risk ratios (RRs) with 95% CIs. We identified 9 trials with 8127 patients and a median follow-up of 3.3 years. Compared with standard BP control, intensive BP control did not show a significant difference on the annual rate of change in GFR (mean difference, 0.07; 95% CI, -0.16 to 0.29 mL/min/1.73 m2/y), doubling of serum creatinine level or 50% reduction in GFR (RR, 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), composite renal outcome (RR, 0.99; 95% CI, 0.81-1.21), or all-cause mortality (RR, 0.95; 95% CI, 0.66-1.37). Nonblacks and patients with higher levels of proteinuria showed a trend of lower risk of kidney disease progression with intensive BP control. Targeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive BP-lowering treatments.

Intensive blood pressure lowering in patients with acute intracerebral haemorrhage: clinical outcomes and haemorrhage expansion. Systematic review and meta-analysis of randomised trials

IntroductionIt is unclear whether intensive lowering of blood pressure (BP) at the acute phase of intracerebral haemorrhage (ICH) is beneficial. We performed a meta-analysis of randomised controlled trials (RCTs) to...

Abstract WP349: Updated Meta-Analysis of Randomized Controlled Trials Investigating Blood-Pressure Lowering for Acute Intracerebral Hemorrhage

Objective: We performed a meta-analysis of randomized controlled trials (RCTs) to assess whether intensive blood pressure (BP) lowering in acute intracerebral haemorrhage (ICH) patients is safe and effective in improving clinical outcomes. Methods: We searched PubMed, EMBASE and the Cochrane databases for relevant RCTs and calculated pooled odds ratios (OR) for 3-month mortality (safety outcome) and 3-month death or dependency (efficacy outcome), in acute ICH patients randomized to either intensive BP-lowering vs. standard BP lowering treatment protocols. We also investigated the association between treatment arm and significant ICH expansion at 24h. Random effects models with DerSimonian-Laird weights were used. Results: Five eligible studies including 4360 acute ICH patients were pooled in meta-analysis. The risk of 3-month mortality was similar between patients randomized to intensive BP-lowering treatment vs. standard BP-lowering treatment (OR: 0.99; 95%CI: 0.82-1.20, p=0.909). Intensive BP-lowering treatment showed a (non-significant) trend for an association with lower 3-month death or dependency risk compared to standard treatment (OR: 0.91; 95%CI: 0.80-1.02), p=0.106). Intensive BP-reduction was associated with a trend for lower risk of significant ICH expansion compared to standard treatment (OR: 0.82; 95%CI: 0.68-1.00, p=0.056), especially in larger RCTs. Conclusion: For acute ICH patients similar to those included in RCTs and without contraindication to acute BP treatment, intensive acute BP-lowering is safe (Class I; Level of Evidence A), but does not seem to provide an incremental clinical benefit in terms of functional outcomes (Class I; Level of Evidence B). The effect of intensive BP-lowering on significant hematoma expansion at 24 hours warrants further investigation.

Abstract WP348: Blood Pressure Lowering in Patients With Intracerebral Haemorrhage: Data from the Ongoing Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH-2) Trial

Background: Intensive lowering of blood pressure in the hyperacute phase after intracerebral haemorrhage may improve outcome (as observed in the INTERACT-2 trial) or have no effect (ATACH-2). Clinical guidelines recommend BP lowering. Methods: We investigated the relationship between BP, and BP lowering treatment on functional outcome, death and serious adverse events at day 90. Statistical models were adjusted for baseline characteristics. Results: As at 18 th July 2016, 1161 (71.4%) of patients were on BP lowering treatment by day 2; these patients were younger (mean (SD): 67.7 (13.9) vs 71.9 (12.9) years, p-value&lt;0.0001), more likely to be male (660/1161 (56.9%) vs 241/466 (51.7%), p-value=0.0598) and had lower NIHSS at baseline (12.5 (7.2) vs 14.2 (8.0), p-value&lt;0.0001). Patients on BP lowering were found to have significantly better mRS and Barthel Index by day 90 (p-values: 0.0171, 0.0482, respectively) as compared to those not on treatment, and fewer of these patients died or suffered an SAE (p-values: 0.0074, 0.0002, respectively). However, there was no relationship between systolic BP levels (&lt;140 vs &gt;= 140 mmHg) on day 2, and outcome at day 90. Conclusion: Early BP lowering is associated with improved functional outcome, and fewer deaths and SAEs, at day 90. Those achieving a BP target of &lt;140mmHg by day 2 did not have a better outcome, suggesting that the optimal BP target may need more investigation.

Abstract WP364: Impaired Renal Function and Outcome After Intracerebral Haemorrhage: Data From the Ongoing Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH-2) Trial

Background: Trends between renal failure at presentation and poor outcome in intracerebral haemorrhage (ICH) have been investigated; however, few studies have examined this relationship. Methods: TICH-2 records estimated glomerular filtration rate (eGFR) at baseline. Renal function was categorised as; normal (&gt;60 mL/min), moderate (30-60) and low (&lt;30). Baseline characteristics were compared across all three groups. Moderate and low eGFR was compared to normal for day 90 outcomes and adjusted for baseline covariates. Results: Of 1514 participants in TICH-2 with baseline eGFR recorded, 1277 (84.4%) had a normal eGFR, 214 (14.1%) a moderate eGFR and 23 (1.5%) a low eGFR. Systolic blood pressure was highest in the severe group (normal: 173.4, moderate: 172.0, low: 194.4 mmHg; p-value=0.0078), as was pre-morbid mRS (normal: 0.49, moderate: 0.81, severe: 0.87; p-value=0.0001); however, the moderate group had the highest average age (normal: 68.0, moderate: 75.8, low: 66.9 years; p-value=0.0178) and NIHSS (normal: 12.8, moderate: 14.1, low: 12.4; non-significant) at baseline. Proportionally, the severe group had more previous strokes or TIAs and higher historical rates of heart disease, diabetes and haemorrhagic stroke (see figure); although these differences were not all significant. After accounting for the varied results at baseline; no significant differences were found between the groups when looking at day 90 outcomes, SAEs, deaths, do not attempt resuscitation rates, BP lowering treatment, or length of stay in hospital. Conclusion: Patients with renal impairment had more severe strokes and co-morbidities; however, outcomes did not differ once other prognostic factors were accounted for.

Intensive Care Unit Admission for Patients in the INTERACT2 ICH Blood Pressure Treatment Trial: Characteristics, Predictors, and Outcomes.

Wide variation exists in criteria for accessing intensive care unit (ICU) facilities for managing patients with critical illnesses such as acute intracerebral hemorrhage (ICH). We aimed to determine the predictors of admission, length of stay, and outcome for ICU among participants of the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of 2839 ICH patients (<6h) and elevated systolic blood pressure (SBP) allocated to receive intensive (target SBP <140mmHg within 1h) or guideline-recommended (target SBP <180mmHg) BP-lowering treatment. The primary outcome was death or major disability, defined by modified Rankin scale scores 3-6 at 90days. Logistic regression and propensity score analyses were used to determine independent associations. Predictors of ICU admission included younger age, recruitment in China, prior ischemic/undetermined stroke, high SBP, severe stroke [National Institute of Health stroke scale (NIHSS) score ≥15], large ICH volume (≥15mL), intraventricular hemorrhage (IVH) extension, early neurological deterioration, intubation and surgery. Determinants of prolonged ICU stay (≥5days) were prior antihypertensive use, NIHSS ≥15, large ICH volume, lobar ICH location, IVH, early neurological deterioration, intubation and surgery. ICU admission was associated with higher-risk major disability at 90-day assessment compared to those without ICU admission. This study presents prognostic variables for ICU management and outcome of ICH patients included in a large international cohort. These data may assist in the selection and counseling of patients and families concerning ICU admission.

Effects of blood-pressure-lowering treatment in hypertension: 9. Discontinuations for adverse events attributed to different classes of antihypertensive drugs: meta-analyses of randomized trials.

Choice of antihypertensive drugs is also based on the expected burden of adverse events associated with each class of agents, and we have recently identified treatment discontinuation for adverse events as a measure of treatment tolerability frequently reported in randomized controlled trials (RCTs). To investigate whether all classes of blood pressure (BP) lowering drugs increase discontinuations for adverse events when compared with placebo and whether risk of discontinuation is similar for all classes when compared in head-to-head RCTs. RCTs of BP-lowering treatment were subdivided in groups according to class of drug compared with placebo or with other classes. Risk ratios and 95% confidence intervals of major cardiovascular events and of treatment discontinuations for adverse events were calculated (random-effects model). Thirty-eight placebo-controlled RCTs (147 788 patients) and 37 head-to-head RCTs (242 481 patients) provided comparative information on discontinuations for adverse events. All classes of drugs significantly increased discontinuations for adverse events over those occurring on placebo: risk ratio diuretics 2.23 (1.32-3.76), beta-blockers 2.88 (1.58-5.28), calcium antagonists 2.03 (1.17-3.56), angiotensin-converting enzyme inhibitors 2.78 (1.37-5.47), central agents 1.74 (1.24-2.45), with the single exception of angiotensin receptor blockers, which did not significantly increase adverse events over placebo [risk ratio 1.13 (0.78-1.62)]. Similarly, in head-to-head comparison RCTs with other classes, angiotensin receptor blockers were the only class associated with a significantly lower risk of adverse events [risk ratio 0.71 (0.58-0.87)] when head-to-head compared with other classes. Regression analysis also shows that incidence of discontinuations for adverse events is proportional to the number of antihypertensive and other cardiovascular drugs, which accounts for the high incidence of this outcome often found in groups randomized to placebo. Reduction of cardiovascular events by all classes of BP-lowering drugs is accompanied by increased treatment discontinuations for adverse events, except when angiotensin receptor blockers are used. Treatment discontinuations are also related to treatment often accompanying antihypertensive agents.

Early Blood Pressure Lowering Does Not Reduce Growth of Intraventricular Hemorrhage following Acute Intracerebral Hemorrhage: Results of the INTERACT Studies

Background: Intraventricular hemorrhage (IVH) extension is common following acute intracerebral hemorrhage (ICH) and is associated with poor prognosis. Aim: To determine whether intensive blood pressure (BP)-lowering therapy reduces IVH growth. Methods: Pooled analyses of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and INTERACT2) computed tomography (CT) substudies; multicenter, open, controlled, randomized trials of patients with acute spontaneous ICH and elevated systolic BP, randomly assigned to intensive (<140 mm Hg) or guideline-based (<180 mm Hg) BP management. Participants had blinded central analyses of baseline and 24-hour CT. Association of BP lowering to IVH growth was assessed in analysis of covariance. Results: There was no significant difference in adjusted mean IVH growth following intensive (n = 228) compared to guideline-recommended (n = 228) BP treatment (1.6 versus 2.2 ml, respectively; p = 0.56). Adjusted mean IVH growth was nonsignificantly greater in patients with a mean achieved systolic BP ≥160 mm Hg over 24 h (3.94 ml; p trend = 0.26). Conclusions: Early intensive BP-lowering treatment had no clear effect on IVH in acute ICH.

MPS 03-08 ON-TREATMENT BLOOD PRESSURE AND CARDIOVASCULAR OUTCOMES IN OLDER ADULTS WITH ISOLATED SYSTOLIC HYPERTENSION

Objective: Data are sparse regarding on-treatment blood pressure (BP) levels at which cardiovascular disease (CVD) and all-cause mortality risks are minimized in older adults with isolated systolic hypertension (ISH). Our aim was to assess optimal on-treatment BP in older Japanese adults with ISH. Design and Method: We used data from the Valsartan in Elderly Isolated Systolic Hypertension (VALISH) Study, which recruited older adults (n = 3,035; mean age: 76 years) with systolic BP (SBP)>160 mmHg and diastolic BP (DBP) < 90 mmHg. Patients were randomly assigned to receive intensive (SBP target < 140 mmHg) or moderate (>140 and < 150 mmHg) BP-lowering treatment with Valsartan, and were also categorized into three groups based on their achieved on-treatment SBP: those with SBP < 130 mmHg (n = 317), 130 to <145 mmHg (n = 2,025), or >145 mmHg (n = 693). The primary outcome was composite CVD (coronary heart disease, stroke, heart failure, cardiovascular deaths, other vascular diseases, and kidney diseases) and the secondary outcome was all-cause mortality. Cox proportional hazards models were used to assess the CVD risk for each group. Results: Over a median 3-year follow-up (8022.13 person-years), 93 CVD events and 52 deaths occurred. With on-treatment SBP of 130 to <145 mmHg as the reference stratum, the multivariable-adjusted hazard ratios and 95% confidence intervals of CVD and all-cause mortality risks for those with on-treatment SBP<130 were 2.08 (1.12–3.83) and 2.09 (0.93–4.71), and for those with on-treatment SBP>145 mmHg were 2.29 (1.44–3.62) and 2.51 (1.35–4.66), respectively (Figure 1). Results were similar by baseline clinical characteristics (i.e., sex, <80 years and >80 years, and prevalent diabetes or CVD). On-treatment DBP yielded no relationships with CVD or all-cause mortality risk. Conclusions: A J-shaped relationship was observed between on-treatment SBP and CVD and all-cause mortality risk in older adults with ISH. On-treatment SBP of 130 to <145 mmHg was associated with minimal adverse outcomes.

In adults ≥75 years of age with hypertension, intensive vs standard BP-lowering treatment reduced CV events.

Source Citation Williamson JD, Supiano MA, Applegate WB, et al; SPRINT Research Group. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥ 75 years: a ...

Moderator's view: Salt, cardiovascular risk, observational research and recommendations for clinical practice.

In observational studies, blood pressure (BP), cholesterol and nutritional status biomarkers, including sodium intake, coherently show a J- or U-shaped relationship with health outcomes. Yet these data may reflect a stable sodium intake or a reduced intake due to comorbidities or intercurrent disease, or an intentional decrease in salt intake. Adjusting for comorbidities and risk factors may fail to eliminate confounding. For cholesterol and BP, we base our recommendations for prevention and treatment on interventional (experimental) studies. For sodium, we lack the perfect large-scale trial we would need, but substantial circumstantial information derived from interventional studies cannot be ignored. The objection that modelling the risk of salt excess for cardiovascular disease events based on the effect of salt intake on BP is unjustified fails to consider a recent meta-analysis showing that, independently of the intervention applied, intensive BP-lowering treatment (average BP 133/76 mmHg), compared with the less intensive treatment (140/81 mmHg), is associated with a 14% risk reduction for major cardiovascular events. In this knowledge context, inertia, i.e. awaiting the 'mother trial', is not justified. While recognizing that this trial may still be needed and that actual data, rather than modelled data, are the ideal solution, for now, the World Health Organization recommendation of reducing salt intake to <2 g/day of sodium (5 g/day of salt) in adults stands.

Effects of blood pressure lowering treatment in hypertension: 8. Outcome reductions vs. discontinuations because of adverse drug events - meta-analyses of randomized trials.

Previous meta-analyses of randomized controlled trials (RCTs) of blood pressure (BP)-lowering treatment provided overwhelming evidence that treatment markedly reduces risk of cardiovascular outcomes in hypertensive patients. However, adverse events associated with BP-lowering treatment have never been surveyed systematically. Identifying among BP-lowering RCTs those reporting a common and meaningful index of treatment-attributed adverse events, and describing the burden of these adverse events accompanying the benefits of mortality and morbidity reduction induced by treatment. The database consisted of the BP-lowering RCTs (active vs. placebo or less active treatment) we have described (70 RCTs, 255 970 participants, 1 091 964 patient-years). A common index of relevant adverse events was identified as permanent treatment discontinuation attributed to treatment adverse events. Risk ratios and 95% confidence intervals, standardized to a SBP/DBP reduction of 10/5 mmHg, of seven fatal and nonfatal outcomes and of treatment discontinuations for adverse events were calculated (random-effects model). The relationships of outcome reductions and discontinuation excess to SBP and DBP reductions were investigated by meta-regressions. Forty-four RCTs provided data on treatment discontinuations for adverse events and six more on serious adverse events because of treatment (179 949 patients, 719 796 patient-years). In these 50 RCTs, a significant 24% reduction of major cardiovascular event risk was associated with a significant 89% increase in the risk of discontinuations (33 major cardiovascular effects prevented and 84 excess discontinuations/1000 patients for 5 years). Metaregression analysis indicated that both outcome reductions and treatment discontinuation excess were significantly related to the extent of SBP and DBP reduction, but absolute treatment discontinuation excess disproportionally increased with larger BP reductions than increase in outcome risk reduction. Furthermore, a standard SBP reduction was found associated with a constant relative reduction, but a smaller absolute reduction of cardiovascular events, and a greater relative excess of treatment discontinuations when the achieved SBP was below 130 mmHg rather than in higher ranges. The burden of adverse events associated with BP-lowering treatment should be considered not to deny patients the overwhelming benefits of BP lowering, but whenever the extent of the BP lowering or the BP target to be achieved are discussed.