Recent Noncardioembolic Stroke Research Articles

Abstract WP391: Post-Stroke Diastolic Blood Pressure and Risk of Recurrent Vascular Events

Background: Recent clinical trials and expert consensus guidelines have typically focused on the issue of systolic blood pressure (SBP) targets for reducing vascular risk. However, little is known about the relationship of diastolic BP (DBP) level with vascular outcomes after a stroke. Methods: We analyzed a multicenter trial dataset involving 3680 recent (<4 months) noncardioembolic stroke patients followed for 2 years. Subjects were categorized per mean DBP level (mm Hg) during follow-up: low-normal (<70), normal (70 to <80), high-normal (80 89), and high (>=90). Pulse pressure (PP) was prespecified by three categories of <60; 60 to <70; and >=70 mm Hg. Independent associations of mean DBP level with stroke, coronary heart disease, or vascular death as major vascular events (MVEs), and ischemic stroke were assessed. Results: MVEs occurred in 20.7% of the low-normal, 15.1% of the normal, 16.9% of the high-normal, and 19.2% of the high DBP groups; while stroke occurred in 9.9%, 6.8%, 8.5%, and 10.8%, respectively. Compared with the normal DBP group, risk of MVEs was higher in the low-normal DBP group (adjusted hazard ratio [AHR], 1.33; 95% CI, 1.04–1.71). Among those with SBP 120 to <140 mmHg, risk of MVEs (AHR, 1.89; 95% CI, 1.13-3.15), and stroke (AHR, 2.87; 95% CI, 1.48-5.53) was higher in subjects with PP >=70 (mean DBP, 62.4 ± 3.8) than those with the lowest PP (mean DBP, 78.0 ± 5.9); while among those with SBP <120 mm Hg, PP 60 to <70 (mean DBP, 52.7 ± 2.5) was associated with increased risk of stroke (AHR, 5.85; 95% CI, 1.25-27.5). Conclusion: DBP levels in the low-normal (<70 mm Hg) range, particularly accompanied by an increased PP of >60, confer increased future risk of MVEs and stroke, among patients with a recent noncardioembolic stroke.

Post-stroke diastolic blood pressure and risk of recurrent vascular events.

Recent clinical trials and expert consensus guidelines have typically focused on the issue of systolic blood pressure (SBP) targets for reducing vascular risk. However, little is known about the relationship of the diastolic BP (DBP) level with vascular outcomes after a stroke. A multicenter trial dataset involving 3680 recent (<4 months) non-cardioembolic stroke patients followed for 2 years was analyzed. Subjects were categorized per mean DBP level (mmHg) during follow-up: low-normal (<70), normal (70 to <80), high-normal (80-89) and high (≥90). Pulse pressure (PP) was prespecified by three categories of <60, 60 to <70, and ≥70 mmHg. Independent associations of mean DBP level with major vascular events (MVEs) and ischaemic stroke were assessed. Major vascular events occurred in 20.7% of the low-normal, 15.1% of the normal, 16.9% of the high-normal and 19.2% of the high DBP groups, whilst stroke occurred in 9.9%, 6.8%, 8.5% and 10.8%, respectively. Compared with the normal DBP group, risk of MVEs was higher in the low-normal DBP group (adjusted hazard ratio 1.33; 95% confidence interval 1.04-1.71). Amongst those with SBP 120 to <140 mmHg, risk of MVEs (1.89; 1.13-3.15) and stroke (2.87; 1.48-5.53) was higher in subjects with PP ≥70 (mean DBP 62.4 ± 3.8) than those with the lowest PP (mean DBP 78.0 ± 5.9) whilst, amongst those with SBP <120 mmHg, PP 60 to <70 (mean DBP 52.7 ± 2.5) was associated with increased risk of stroke (5.85; 1.25-27.5). Diastolic BP levels in the low-normal range, particularly accompanied by an increased PP of >60, confer increased risk of MVEs and stroke amongst patients after recent non-cardioembolic stroke.

Association of black race with recurrent stroke risk

BackgroundThe significantly higher risk of primary stroke in Black vs. Whites is very well established. However, very few studies have specifically examined the presence of this racial disparity in recurrent stroke risk. MethodsWe conducted an analysis of a clinical trial dataset comprising 3470 recent non-cardioembolic stroke patients aged ≥35years and followed for 2years. Subjects were categorized by race into Whites and Blacks. Cox regression analysis was used to evaluate the associations between Black (vs. White) and ischemic stroke (primary outcome); and stroke/coronary heart disease (CHD)/vascular death as major vascular events (secondary outcome) with and without adjustment for comorbid conditions associated with stroke. ResultsAmong participants (2925 Whites and 545 Blacks), a total of 287 (8.3%) incident stroke and 582 (16.8%) major vascular events occurred. Compared with Whites, Blacks had higher frequencies of prior stroke, hypertension, diabetes mellitus, and smoking; but were younger with lower prevalence of CHD. Frequency of stroke was higher in Blacks vs. Whites (11.4% vs. 7.7%; P=0.004), but there was no difference in major vascular events (16.9% vs. 16.8%). Compared with Whites, Blacks experienced a significantly higher risk of recurrent stroke (HR 1.58; 95% CI, 1.19–2.09), but the stroke risk was not significant after multivariable adjustment (1.13; 0.81–1.59). ConclusionBlacks are ~60% more likely to experience a recurrent stroke within 2years than their Whites, but this risk is likely mediated via stroke risk factors. These results underscore a need to optimize and sustain risk factor control in Black stroke populations.

Optimal combination treatment and vascular outcomes in recent ischemic stroke patients by premorbid risk level

BackgroundOptimal combination of secondary stroke prevention treatment including antihypertensives, antithrombotic agents, and lipid modifiers is associated with reduced recurrent vascular risk including stroke. It is unclear whether optimal combination treatment has a differential impact on stroke patients based on level of vascular risk. MethodsWe analyzed a clinical trial dataset comprising 3680 recent non-cardioembolic stroke patients aged ≥35years and followed for 2years. Patients were categorized by appropriateness levels 0 to III depending on the number of the drugs prescribed divided by the number of drugs potentially indicated for each patient (0=none of the indicated medications prescribed and III=all indicated medications prescribed [optimal combination treatment]). High-risk was defined as having a history of stroke or coronary heart disease (CHD) prior to the index stroke event. Independent associations of medication appropriateness level with a major vascular event (stroke, CHD, or vascular death), ischemic stroke, and all-cause death were analyzed. ResultsCompared with level 0, for major vascular events, the HR of level III in the low-risk group was 0.51 (95% CI: 0.20–1.28) and 0.32 (0.14–0.70) in the high-risk group; for stroke, the HR of level III in the low-risk group was 0.54 (0.16–1.77) and 0.25 (0.08–0.85) in the high-risk group; and for all-cause death, the HR of level III in the low-risk group was 0.66 (0.09–5.00) and 0.22 (0.06–0.78) in the high-risk group. ConclusionOptimal combination treatment is related to a significantly lower risk of future vascular events and death among high-risk patients after a recent non-cardioembolic stroke.

Neurologic Symptom Severity after a Recent Noncardioembolic Stroke and Recurrent Vascular Risk

There is a well-established relation of symptom severity with functional status and mortality after an index stroke. However, little is known about the impact of symptom severity of a recent index stroke on risk of recurrent vascular events. We reviewed the data set of a multicenter trial involving 3680 recent noncardioembolic stroke patients aged 35 years or older and followed for 2 years. Independent associations of stroke severity (as measured by National Institutes of Health Stroke Scale [NIHSS] score) with recurrent stroke (primary outcome) and stroke/coronary heart disease (CHD)/vascular death (secondary outcome) were analyzed. NIHSS score was analyzed as a dichotomous (<4 versus ≥4) and a continuous variable. Among study subjects, 550 (15%) had NIHSS scores of 4 or more (overall scores ranged from 0 to 18, median score was 1 [25th-75th percentile 0-2]). NIHSS was measured at a median of 35 days after the index stroke. After adjusting for multiple covariates, NIHSS of 4 or more was independently linked to a higher risk of recurrent stroke (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.01-1.84) and risk of stroke/CHD/vascular death (HR, 1.32; 95% CI, 1.07-1.64). Analysis of NIHSS score as a continuous variable also showed a higher risk of recurrent stroke (HR, 1.06; 95% CI, 1.00-1.12) and stroke/CHD/vascular death (HR, 1.05; 95% CI, 1.01-1.09) with increasing index stroke symptom severity. Greater residual symptom severity after a recent stroke is associated with higher risk of recurrent vascular events. Future studies are needed to confirm this relationship and to clarify its underlying mechanisms.

Abstract T P166: Is Functional Disability after an Index Stroke a Risk Factor for Recurrent Vascular Events?

Background: The modified Rankin Scale (mRS) is widely used as an index for measuring degree of functional disability following a recent stroke. However, greater degree of disability after stroke may unfavorably influence adherence to recommended medical and lifestyle practices shown to lower recurrent vascular event risk. We are unaware of published studies that have examined the possible association of post-stroke disability with occurrence of future vascular events. Methods: We reviewed the dataset of a multicenter trial involving 3680 recent non-cardioembolic stroke patients aged ≥35 years and followed for 2 years. Independent associations of post-stroke disability (as measured by modified Rankin Scale [mRS] score) with recurrent stroke (primary outcome), stroke, coronary heart disease (CHD), or vascular death as major vascular events (secondary outcome), and all-cause death (tertiary outcome) were analyzed. mRS score was analyzed as a dichotomous (≥2 vs. ≤1) and a dose dependent manner. Results: Among study participants, 1336 (36.3%) had a baseline mRS ≥2 (overall scores ranged from 0 to 3). Baseline mRS was measured at a median 35 days after the index stroke. Compared to mRS ≤1, mRS ≥2 was associated with higher risk of recurrent stroke (HR 1.26, 95% CI: 0.99-1.60), major vascular events (HR 1.17; 95% CI: 0.98–1.38), and all-cause death (HR 1.62; 95% CI: 1.21–2.16). Compared with mRS 0, there was progressively higher risk for stroke: mRS 1 (HR 1.40; 95% CI, 0.97-2.01), mRS 2 (HR 1.45; 95% CI, 0.98-2.14), mRS 3 (HR 1.99; 95% CI, 1.30-3.05). Compared with mRS 0, there was progressively higher risk for major vascular events: mRS 1 (HR 1.26; 95% CI, 0.99-1.61), mRS 2 (HR 1.30; 95% CI, 1.00-1.69), mRS 3 (HR 1.55 (95% CI, 1.15-2.09). Compared with mRS 0, there was progressively higher risk for all-cause death: mRS 1 (HR 1.50; 95% CI, 0.94-2.39), mRS 2 (HR 2.06; 95% CI, 1.27-3.35), mRS 3 (HR 2.41; 95% CI, 1.42-4.09). Conclusions: Greater functional disability after a recent stroke is linked to a higher risk of recurrent vascular events including stroke and all-cause death. Future studies with a wider range of mRS are needed to confirm this relationship and to clarify its underlying mechanisms.

Abstract W P373: Symptom Severity of Recent Stroke and Risk of Recurrent Vascular Events

Background: Symptom severity of an index stroke is a powerful prognosticator of short term outcomes, especially functional status and mortality. It is widely recognized that stroke patients with greater initial symptom severity tend to have more unfavorable prognoses. However, little is relatively known about the possible association of symptom severity and risk of recurrent vascular events after a recent index stroke, particularly over the longer term. On one hand, stroke patients with greater baseline symptom severity may be at higher risk for recurrent vascular events due to reactive depression or impaired mobility leading to overall poorer regimen adherence; while on the other hand stroke patients that recover with minimal deficit or no deficit may be more vulnerable to a future events due to underlying unstable pathophysiology (i.e. ongoing thrombosis-thrombolysis). Methods: We reviewed the dataset of a multicenter trial involving 3680 recent non-cardioembolic stroke patients aged ≥35 years and followed for 2 years. Independent associations of stroke severity (as measured by National Institutes of Health Stroke Scale [NIHSS] score) with recurrent stroke (primary outcome) and stroke/coronary heart disease (CHD)/vascular death (secondary outcome) were analyzed. NIHSS score was analyzed as a dichotomous (&lt;4 vs. ≥4) and a continuous variable. Results: Among trial participants, 550 (15%) had NIHSS scores ≥4 (overall scores ranged from 0 to 18, median score was 1 [25 th to 75 th percentile 0 to 2]). NIHSS was measured median 35 days after the qualifying stroke. Scores ≥4 were independently linked to higher risk of recurrent stroke (HR 1.43, 95% CI: 1.06-1.92) and risk of stroke/CHD/vascular death (1.32; 1.07–1.64). Analysis of NIHSS score as a continuous variable also showed a higher risk of events with increasing symptom severity (recurrent stroke: 1.07; 1.01–1.13) and stroke/CHD/vascular death: 1.05; 1.01-1.09) Conclusions: Greater symptom severity of a recent stroke is associated with higher risk of recurrent vascular events including stroke. Future studies are needed to confirm this relationship and to clarify its underlying mechanisms.

New Pooled Cohort Risk equations: Application to a recent stroke patient population

BackgroundRecently, Pooled Cohort Risk (PCR) equations, which incorporate new sex- and race-specific estimates of the 10-year risk for atherosclerotic cardiovascular disease (ASCVD) including stroke, for ASCVD-free adults were introduced. Given the importance of secondary stroke prevention and benefit of a potential tool to readily identify stroke patients at high intermediate-term vascular risk for appropriate treatment, we evaluated the prediction and discrimination of the PCR and Framingham Cardiovascular Risk (FCR) equations after a recent stroke. MethodWe conducted an analysis of Vitamin Intervention for Stroke Prevention dataset of 3555 recent non-cardioembolic stroke patients aged ≥35years and followed for 2years. Subjects were categorized as having low-PCR/low-FCR (<20%), high-PCR/high-FCR (≥20%), and known-ASCVD. Independent associations of high-PCR/high-FCR with recurrent stroke (primary outcome) and stroke/coronary heart disease (CHD)/vascular death (secondary outcomes) were assessed. ResultsBoth PCR and FCR were independently related to both outcomes: compared with low-PCR, high-PCR was associated with stroke (adjusted hazard ratio, 1.79; 95% CI, 1.25–2.57) and stroke/CHD/vascular death (2.05; 1.55–2.70). Compared with low-FCR, high-FCR was associated with stroke (2.06; 1.34–3.16) and stroke/CHD/vascular death (1.57; 1.12–2.20). The c-statistic of PCR/FCR as a continuous variable for stroke was 0.56 (95% CI, 0.54–0.58) and 0.56 (0.54–0.57), respectively and for stroke/CHD/vascular death was 0.62 (0.60–0.63) and 0.61 (0.59–0.63), respectively. ConclusionsBoth PCR and FCR are significant predictors of recurrent vascular events among patients after a recent non-cardioembolic stroke, but neither one of them is an optimal model for discriminating intermediate-term ASCVD prediction among stroke patients already receiving secondary stroke prevention.

Optimal combination secondary prevention drug treatment and stroke outcomes.

To investigate the effect of optimal combination of evidence-based drug therapies including antihypertensive agents, lipid modifiers, and antithrombotic agents on risk of recurrent vascular events after stroke. We analyzed the database of a multicenter trial involving 3,680 recent noncardioembolic stroke patients aged 35 years or older and followed for 2 years. Patients were categorized by appropriateness level 0 to III depending on the number of drugs prescribed divided by the number of drugs potentially indicated for each patient (0 = none of the indicated medications prescribed and III = all indicated medications prescribed). Independent associations of medication appropriateness level with recurrent stroke (primary outcome), stroke/coronary heart disease/vascular death as major vascular events (secondary outcome), and death (tertiary outcome) were assessed. The unadjusted rate of stroke declined with increasing medication appropriateness level (15.9% for level 0, 10.3% for level I, 8.6% for level II, and 7.3% for level III). Compared with level 0: the adjusted hazard ratio of stroke for level I was 0.51 (95% confidence interval, 0.21-1.25), level II 0.50 (0.23-1.09), and level III 0.39 (0.18-0.84); of stroke/coronary heart disease/vascular death for level I 0.60 (0.32-1.14), level II 0.45 (0.25-0.80), and level III 0.39 (0.22-0.69); and of death for level I 0.89 (0.30-2.64), level II 0.71 (0.26-1.93), and level III 0.35 (0.13-0.96). Optimal combination of secondary prevention medication classes after a recent noncardioembolic stroke is associated with a significantly lower risk of stroke, major vascular events, and death.

Risk of Recurrent Stroke in Patients With Silent Brain Infarction in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) Imaging Substudy

Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent noncardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality. The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age- and sex-matched patients with stroke without SBI. Secondary outcomes were a combined vascular end point, other vascular events, and mortality. The 2 groups were compared using conditional logistic regression. Silent brain infarction was detected in 207 (20.4%) of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (OR, 1.42; 95% CI, 0.79-2.56; P=0.24) during a mean follow-up of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI. The presence of SBI in patients with recent mild noncardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality rate. URL: http://clinicaltrials.gov. Unique identifier: NCT00153062.

Editorial What should the optimal blood pressure goal be in patients with diabetes mellitus or chronic kidney disease?

Editorial What should the optimal blood pressure goal be in patients with diabetes mellitus or chronic kidney disease?