Patterns of blood pressure response during intensive BP lowering and clinical events: results from the secondary prevention of small subcortical strokes trial.
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ABSTRACT:
SUBMITTER: Ku E
PROVIDER: S-EPMC5818304 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
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Patterns of blood pressure response during intensive BP lowering and clinical events: results from the secondary prevention of small subcortical strokes trial.
Ku Elaine E Scherzer Rebecca R Odden Michelle C MC Shlipak Michael M White Carole L CL Field Thalia S TS Benavente Oscar O Pergola Pablo E PE Peralta Carmen A CA
Blood pressure 20170927 2
<h4>Purpose</h4>We applied cluster analysis to identify discrete patterns of concomitant responses of systolic (SBP), diastolic (DBP) and pulse pressure (PP) during intensive BP lowering; and to evaluate their clinical relevance and association with risk of mortality, major vascular events (MVEs), and stroke.<h4>Material and methods</h4>We used an unsupervised cluster procedure to identify distinct patterns of BP change during the first 9 months of anti-hypertensive therapy intensification among ...[more]
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Project description:Background We aimed to determine whether cerebral white matter hyperintensities ( WMHs ) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure ( BP ) lowering. Methods and Results The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and <130 mm Hg. We included 2454 participants with WMH measured by clinical magnetic resonance imaging at baseline and serum creatinine measured during follow-up. We tested interactions between BP target and WMH burden on the incidence of rapid kidney function decline (?30% decrease from baseline estimated glomerular filtration rate at 1-year follow-up) and recurrent stroke. Rapid kidney function decline incidence was 11.0% in the lower- BP -target arm and 8.1% in the higher-target arm (odds ratio=1.40; 95% CI=1.07-1.84). Odds ratio for rapid kidney function decline between lower- and higher-target groups ranged from 1.26 in the lowest WMH tertile (95% CI , 0.80-1.98) to 1.71 in the highest tertile (95% CI , 1.05-2.80; P for interaction=0.65). Overall incidence of recurrent stroke was 7.9% in the lower-target arm and 9.6% in the higher-target arm (hazard ratio=0.80; 95% CI , 0.63-1.03). Hazard ratio for recurrent stroke in the lower-target group was 1.13 (95% CI , 0.73-1.75) within the lowest WMH tertile compared with 0.73 (95% CI , 0.49-1.09) within the highest WMH tertile ( P for interaction=0.04). Conclusions Participants with higher WMH burden appeared to experience greater benefit from intensive BP lowering in prevention of recurrent stroke. By contrast, intensive BP lowering increased the odds of kidney function decline, but WMH burden did not significantly distinguish this risk. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00059306.
| S-EPMC6405594 | biostudies-literature
Project description:ObjectiveTo determine whether cerebral small vessel disease or disability modify the effect of SBP treatment on cognitive and vascular outcomes in older patients with recent lacunar stroke.MethodsParticipants aged at least 65 years of the Secondary Prevention of Small Subcortical Strokes Trial were randomized to a higher (130-149 mmHg) or lower (<130 mmHg) SBP target. The primary outcome was change in cognitive function (Cognitive Abilities Screening Instrument); secondary outcomes were incident mild cognitive impairment, stroke, major vascular events (all-stroke, myocardial infarction), and all-cause death. Results were stratified by severity of white matter hyperintensities (WMH; none/mild, moderate, severe) on baseline MRI, and by disability (no vs. at least one limitation in activities of daily living).ResultsOne thousand, two hundred and sixty-three participants (mean age 73.8 ± 5.9 years, 40% women) were included. Participants with severe WMH or disability had worse cognitive function at baseline and after a mean follow-up of 3.9 years. No significant interactions existed between treatment group and effect modifiers (WMH, disability) for change in cognitive function (P for interaction 0.42 and 0.66, respectively). A lower SBP target appeared more beneficial among those with worse WMH burden for vascular outcomes (P for interaction = 0.01 for stroke and 0.03 for major vascular events).ConclusionThere was no difference in the effect of lowering SBP to less than 130 mmHg on cognitive function by cerebral small vessel disease or disability among older adults with a history of lacunar stroke. Those with evidence of small vessel disease may derive greater benefit from lower SBP on prevention of subsequent vascular events.Trial registrationClinicaltrials.gov Identifier: NCT00059306.
| S-EPMC8302036 | biostudies-literature
Project description:BackgroundSmall subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events.MethodsSecondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n = 3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 × 2 factorial design, to antiplatelet therapy--325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind--and to one of two levels of systolic blood pressure targets--'intensive' (<130 mmHg) vs. 'usual' (130-149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.ConclusionsSecondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder.
| S-EPMC4214141 | biostudies-literature
Project description:BackgroundHypertension is the most powerful risk factor for stroke. The aim of this study was to characterize baseline blood pressure in participants in the Secondary Prevention of Small Subcortical Strokes trial.MethodsFor this cross-sectional analysis, participants were categorized by baseline systolic blood pressure (SBP) < 120, 120-139, 140-159, 160-179, and ≥ 180 mm Hg and compared on demographic and clinical characteristics. Predictors of SBP < 140 mm Hg were examined.ResultsMean SBP was 143±19 mm Hg while receiving an average of 1.7 antihypertensive medications; SBP ≥ 140 mm Hg for 53% and ≥ 160 mm Hg for 18% of the 3,020 participants. Higher SBP was associated with a history of hypertension and hypertension for longer duration (both P < 0.0001). Higher SBPs were associated with more extensive white matter disease on magnetic resonance imaging (P < 0.0001). There were significant differences in entry-level SBP when participants were categorized by race and region (both P < 0.0001). Black participants were more likely to have SBP ≥ 140 mm Hg. Multivariable logistic regression showed an independent effect for region with those from Canada more likely (odds ratio = 1.7; 95% confidence interval, 1.29, 2.32) to have SBP < 140 mm Hg compared with participants from United States.ConclusionsIn this cohort with symptomatic lacunar stroke, more than half had uncontrolled hypertension at approximately 2.5 months after stroke. Regional, racial, and clinical differences should be considered to improve control and prevent recurrent stroke.
| S-EPMC3816319 | biostudies-literature
Project description:ObjectivesTo determine whether vascular and demographic factors predict worsening disability up to 8 years after lacunar stroke.MethodsSPS3 (Secondary Prevention of Small Subcortical Strokes) was a clinical trial in lacunar stroke patients with annual assessment of disability using the Older Americans Resources and Survey instrumental activities of daily living (IADL) scale (range 0-14). Generalized estimating equations modeled the likelihood of disability (IADL <14) over time, adjusting for demographics, medical risk factors, cognition, mood, stroke location, and geographic region in univariate and multivariable models. IADL assessments after recurrent stroke were censored. We stratified by study region and age quartile.ResultsAmong 2,820 participants, mean age was 63.4 years (SD 10.8), 63% were male, 36% had diabetes, 90% hypertension, and 10% prior stroke. Mean follow-up was 3.7 years. In multivariable models, female sex, education, diabetes, nonregular alcohol use, prior stroke, Cognitive Abilities Screening Instrument score, depression, mild cognitive impairment, and stroke location were associated with disability. The youngest age quartile had decreased odds of disability over time (odds ratio 0.90 per year, 95% confidence interval 0.85-0.95), whereas the oldest age quartile had increased odds (2.20, 95% confidence interval 1.75-2.75). Americans and Latin Americans had >2-fold greater odds of disability per year compared with Spaniards (p < 0.0001).ConclusionsIn lacunar stroke patients, older age was associated with worsening long-term disability, even without recurrence. Worse long-term function was associated with diabetes, cognitive status, and prior stroke, and regional differences may be attributable to variations in health care delivery or scale interpretation.
| S-EPMC4352098 | biostudies-literature
Project description:Background and purposeInfarct size and location are thought to correlate with different mechanisms of lacunar infarcts. We examined the relationship between the size and shape of lacunar infarcts and vascular risk factors and outcomes.MethodsWe studied 1679 participants in the Secondary Prevention of Small Subcortical Stroke trial with a lacunar infarct visualized on diffusion-weighted imaging. Infarct volume was measured planimetrically, and shape was classified based on visual analysis after 3-dimensional reconstruction of axial MRI slices.ResultsInfarct shape was ovoid/spheroid in 63%, slab in 12%, stick in 7%, and multicomponent in 17%. Median infarct volume was smallest in ovoid/spheroid relative to other shapes: 0.46, 0.65, 0.54, and 0.90 mL, respectively (P<0.001). Distributions of vascular risk factors were similar across the 4 groups except that patients in the ovoid/spheroid and stick groups were more often diabetic and those with multicomponent had significantly higher blood pressure at study entry. Intracranial stenosis did not differ among groups (P=0.2). Infarct volume was not associated with vascular risk factors. Increased volume was associated with worse functional status at baseline and 3 months. Overall, 162 recurrent strokes occurred during an average of 3.4 years of follow-up with no difference in recurrent ischemic stroke rate by shape or volume.ConclusionsIn patients with recent lacunar stroke, vascular risk factor profile was similar among the different infarct shapes and sizes. Infarct size correlated with worse short-term functional outcome. Neither shape nor volume was predictive of stroke recurrence.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00059306.
| S-EPMC4198938 | biostudies-literature
Project description:To determine safety and tolerability of lowering blood pressure in older adults with lacunar stroke.Cohort study.The Secondary Prevention of Small Subcortical Strokes (SPS3) Trial, which compared the efficacy of two systolic blood pressure (SBP) targets (<130 mmHg and 130-149 mmHg) for secondary stroke prevention.Of 3,020 SPS3 participants, 494 aged 75 and older at baseline were used in these analyses.Rates of side effects related to lowering SBP and clinical outcomes, including stroke recurrence and vascular death, were examined.Older participants achieved SBP levels similar to those of younger participants (mean SBP of 125 mmHg and 137 mmHg in lower and higher SBP target groups, respectively). At least once during the approximately 3.5 years of follow-up, 21% reported dizziness, and 15% reported lightheadedness when standing; the only significant difference between the younger and older groups was unsteadiness when standing (23% vs 32% respectively, P < .001). There was no difference according to treatment group. In younger adults, recurrent stroke was less likely in the lower than the higher SBP group (hazard ratio (HR) = 0.77, 95% confidence interval (CI) = 0.59-1.01) but not in older participants (HR = 1.01, 95% CI = 0.59-1.73), although the interaction was not significant (P = .39). The lower SBP target was associated with a significant reduction in vascular death in older participants (HR = 0.42, 95% CI = 0.18-0.98), with a significant interaction between age and SBP group (P = .049).Except for unsteadiness when standing, there was no difference according to age in individuals with lacunar stroke with respect to side effects potentially related to lowering blood pressure. Although the lower SBP target was not associated with lower likelihood of recurrent stroke, these exploratory analyses suggested a possible benefit related to vascular death.
| S-EPMC4582779 | biostudies-literature
Project description:To characterize cerebral microbleeds (CMBs) in lacunar stroke patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to assess their relationship with recurrent stroke and death, and response to assigned treatment.SPS3 is a randomized, clinical trial conducted between 2003 and 2011. Patients with recent magnetic resonance imaging (MRI)-documented lacunar infarcts were randomly assigned in a factorial design to target levels of systolic blood pressure (130-149mmHg vs <130mmHg; open label) and to antiplatelet treatment (aspirin/clopidogrel vs aspirin/placebo; double-blinded). The current analysis involves 1,278 trial participants who had a baseline axial T2*-weighted gradient echo MRI sequence allowing for CMB detection.CMBs were present in 30% of 1,278 patients (mean age?=?63 years). Male gender (odds ratio [OR]?=?1.7, 95% confidence interval [CI]?=?1.3-2.3), history of hypertension (OR?=?1.6, 95% CI?=?1.2-2.3), increased systolic blood pressure (1.2 per 20mmHg, 95% CI?=?1.1-1.4), nondiabetic status (OR?=?1.4, 95% CI?=?1.1-1.9), multiple old lacunar infarcts (OR?=?1.9, 95% CI?=?1.5-2.5), and moderate (OR?=?1.7, 95% CI?=?1.2-2.3) or severe (OR?=?4.2, 95% CI?=?3.0-5.9) white matter hyperintensities on MRI were independently associated with CMBs. During a mean follow-up of 3.3 years, overall stroke recurrence was 2.5% per patient-year. Patients with CMBs had an adjusted 2-fold increased risk of recurrent stroke (hazard ratio?=?2.1, 95% CI?=?1.4-3.1). CMBs were not a risk factor for death. There were no statistically significant interactions between CMBs and treatment assignments.Patients with lacunar stroke and CMBs likely harbor a more advanced form of cerebral small vessel disease in need of efficacious therapeutic strategies. Ann Neurol 2017;82:196-207.
| S-EPMC5568949 | biostudies-literature
Project description:BackgroundOrthostatic hypotension (OH) has been independently associated with increased risk of stroke and other cardiovascular events. We sought to investigate the relationship between OH at follow-up and recurrent stroke risk in SPS3 (Secondary Prevention of Small Subcortical Strokes) trial patient cohort. This is a retrospective cohort analysis.MethodsWe included all SPS3 trial participants with blood pressure measurements in both sitting and standing position per protocol at baseline, with at least 1 follow-up visit to establish the relationship between OH at follow-up and recurrent stroke risk (primary outcome). Secondary outcomes included major vascular events, myocardial infarction, all-cause mortality, and, ischemic and hemorrhagic stroke subtypes. Participants were classified as having OH at baseline and at each follow-up visit based on a systolic BP decline ≥20 mm Hg or a diastolic BP decline ≥10 mm Hg on position change from sitting to standing. We used Cox proportional hazards regression modeling to compare the risk of outcomes among those with and without OH.ResultsA total of 2275 patients were included with a mean follow up time 3.2 years (standard deviation = 1.6 years). 39% (881/2275) had OH at some point during their follow-up. Of these, 41% (366/881) had orthostatic symptoms accompanying the BP drop. In a fully adjusted model, those with OH had a 1.8 times higher risk of recurrent stroke than those without OH (95% confidence interval: 1.1-3.0). The risk of ischemic stroke, major vascular events, and all-cause mortality was similarly elevated among the OH group.ConclusionOH was associated with increased recurrent stroke risk, vascular events, and all-cause death in this large cohort of lacunar stroke patients. Whether minimizing OH in the management of poststroke hypertension in patients with lacunar stroke reduces recurrent stroke risk deserves further study.
| S-EPMC6679756 | biostudies-literature
Project description:BackgroundThe clinical implications of vertebrobasilar ectasia (VBE) in patients with cerebral small-artery disease are not well defined. We investigated whether VBE is associated with recurrent stroke, major hemorrhage, and death in a large cohort of patients with recent lacunar stroke.MethodsMaximum diameters of the vertebral and basilar arteries were measured by magnetic resonance angiography and computed tomographic angiography in 2621 participants in the Secondary Prevention of Small Subcortical Strokes trial. VBE was defined a priori as basilar artery greater than 4.5 mm and/or vertebral artery greater than 4.0 mm. Patient characteristics and risks of stroke recurrence and mortality during follow-up (median, 3.5 years) were compared between patients with and without VBE.ResultsVBE affecting 1 or more arteries was present in 200 (7.6%) patients. Patient features independently associated with VBE were increasing age, male sex, white race ethnicity, hypertension, and higher baseline diastolic blood pressure. Baseline systolic blood pressure was inversely associated with VBE. After adjustment for other risk factors, VBE was not predictive of recurrent stroke (hazard ratio [HR], 1.3; 95% confidence interval [CI], .85-1.9) or major hemorrhage (HR, 1.5; CI, .94-2.6), but was of death (HR, 1.7; CI, 1.1-2.7).ConclusionsIn this large well-characterized cohort of patients with recent lacunar stroke, VBE was predictive of death but not of recurrent stroke or major hemorrhage. In these exploratory analyses, the frequency of VBE was directly related to diastolic blood pressure but inversely related to systolic blood pressure.
| S-EPMC4408219 | biostudies-literature