Background and Purpose
Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke.
Methods
Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a Phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment, and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (HR, 95%CI) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use.
Results
Among 1244 lacunar stroke patients (mean 63.3 ± 10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes), and 115 major vascular events (stroke, myocardial infarction, vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP >4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR 2.54, 95%CI 1.30–4.96), even after adjusting for demographics and risk factors (adjusted HR 2.32, 95%CI 1.15–4.68). HsCRP predicted increased risk of major vascular events (top quartile adjusted HR 2.04, 95%CI 1.14–3.67). There was no interaction with randomized antiplatelet treatment.
Conclusions
Among recent lacunar stroke patients, hsCRP levels predict risk of recurrent strokes and other vascular events. HsCRP did not predict response to dual antiplatelets.
Background: Little is known about post-stroke depression in patients with lacunar stroke due to cerebral small vessel disease. Our objectives were to describe the prevalence of depression, its correlates and to examine the course of depression over time in a cohort of patients with lacunar stroke, the majority of whom had mild functional disability. Methods: Depression was determined in participants in the international Secondary Prevention of Small Subcortical Strokes (SPS3) trial which is testing antiplatelet therapies and targets of blood pressure control in patients with lacunar strokes and assessing stroke recurrence and cognitive decline. Depression was evaluated using the Patient Health Questionnaire. Multivariable logistic regression models were fitted to examine the relationship between the covariates of interest and depression. Generalized estimating equations were used to examine the likelihood of depression over time, while accounting for the multiple measurements within each subject. Results: The prevalence of depression in 2,477 participants at approximately 4 months after stroke was 19%. Older age (OR 0.97; 95% CI 0.96–0.99), male gender (OR 0.62; 95% CI 0.48–0.80) and less cognitive impairment (OR 0.99; 95% CI 0.98–1.00) were independently associated with a lower risk of depression. Functional disability (OR 1.8; 95% CI 1.3–2.4), living with a spouse/family (OR 1.6; 95% CI 1.1–2.3) and risk factors for stroke (OR 1.2; 95% CI 1.0–1.3) were each independently associated with a higher risk of depression. Longitudinal modeling indicated that the likelihood of depression decreased by 1.12 times (95% CI 1.06–1.17) for each 1-year increase in time. Conclusions: One fifth of those in the SPS3 trial cohort reported depression that is sustained over time. Although this is lower than the prevalence reported for stroke in general, these results underscore the importance of early screening for post-stroke depression, treatment and follow-up to minimize the negative consequences associated with depression.
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