Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke: Meta-Analysis of Population-Based Studies Involving 17 180 Individuals.

Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01-1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02-1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82-1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00-1.42]; third quartile: 1.35 [1.14-1.59]; fourth quartile: 1.38 [1.07-1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.

In-hospital outcomes of acute ischaemic stroke patients with atrial septal defect. A national inpatient sample study.

BACKGROUND AND AIMS: Atrial septal defects (ASD) are a well-recognised risk factor for acute ischaemic stroke (AIS). We aimed to delineate the relationship between ASD and in-hospital AIS outcomes (mortality, severe stroke (National Institutes of Health Stroke Scale (NIHSS) > 15), prolonged hospitalisation > 4 days and routine home discharge) in contemporary practice using data from the United States National Inpatient Sample. METHODS: NIS admissions with a primary diagnosis of AIS between 2016-2018 were extracted. The NIHSS variable had 75% missing data, which were imputed using multiple imputations by chained equations. The relationship between ASD and the main outcomes was modelled using multivariable logistic regressions, adjusting for age, sex, comorbidities, stroke severity and revascularisation therapies. RESULTS: 245,859 records representative of 1,229,295 AIS admissions were included, 35,840 (2.91%) of whom had ASD. ASD patients were younger (median age 63 years versus 72 years) and less likely to have traditional cardiovascular risk factors than their counterparts without ASD. ASD was independently associated with 58% lower odds of in-hospital mortality (hazard ratio (95% confidence interval) = 0.42 (0.33-0.54)), 18% lower odds of severe stroke (0.82 (0.71-0.94)), 20% higher odds of routine home discharge (1.20 (1.14-1.28)) and 28% higher odds of prolonged hospitalisation (1.28 (1.21-1.35)). CONCLUSIONS: ASD was associated with better in-hospital outcomes, which were likely driven by younger age, lower prevalence of traditional cardiovascular risk factors, and lower stroke severity. Further research is warranted to clarify the ASD anatomical characteristics which are most strongly associated with these associations.