Background and Purpose— Our study aim was to assess whether high-sensitivity cardiac troponin T (hs-cTnT), a specific biomarker for myocardial injury, is associated with cognitive function in patients after mild-to-moderate first-ever ischemic stroke. Methods— We used data from PROSCIS-B (Prospective Cohort With Incident Stroke Berlin). Cognitive function was assessed by Mini-Mental-State-Examination at baseline, and Telephone Interview for Cognitive Status–modified after 1 to 3 years of follow-up. Patients were categorized according to hs-cTnT quartiles. We performed generalized linear regression to calculate risk ratios of cognitive impairment (Mini-Mental-State-Examination <27; Telephone Interview for Cognitive Status–modified <32). Association of hs-cTnT with cognitive function over time was estimated using a linear mixed model. Results— We included 555 patients (mean age, 67 years, 62% male, median National Institutes of Health Stroke Scale 2 [interquartile range, 1–5], hs-cTnT above upper reference limit 40%, baseline cognitive impairment 28%). Baseline Mini-Mental-State-Examination score and rate of cognitive impairment were lower in patients in the highest versus lowest hs-cTnT quartile (median Mini-Mental-State-Examination 27 versus 29, and 15.3% versus 43.0%, adjusted risk ratio, 1.76 [95% CI, 1.07–2.90], respectively). If anything, cognition seemed to improve in all groups, yet Telephone Interview for Cognitive Status–modified scores were consistently lower in patients within the highest versus lowest hs-cTnT quartile (adjusted β, −1.33 [95% CI, −2.65 to −0.02]), without difference in the rate of change over time. Conclusions— In patients with mild-to-moderate first-ever ischemic stroke without dementia, higher hs-cTnT was associated with higher prevalence of cognitive impairment at baseline and lower Telephone Interview for Cognitive Status–modified during 3-year follow-up. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01363856.

Clonal hematopoiesis (CH) is common among older people and associated with an increased risk of atherosclerosis, inflammation, and shorter overall survival. Age and inflammation are major risk factors for ischemic stroke, yet the association of CH with risk of secondary vascular events and death is unknown. We investigated CH in peripheral blood DNA from 581 patients with first-ever ischemic stroke from the Prospective Cohort with Incident Stroke-Berlin study (PROSCIS-B) using error-corrected targeted sequencing. The primary composite endpoint (CEP) consisted of recurrent stroke, myocardial infarction, and all-cause mortality. 348 somatic mutations with a variant allele frequency ≥ 1% were identified in 236/581 patients (41%). CH was associated with large-artery atherosclerosis stroke (P = 0.01) and white matter lesion (P &lt; 0.001). CH-positive patients showed increased levels of pro-inflammatory cytokines such as IL-6, IFN-γ, hsCRP, and VCAM-1. CH-positive patients had a higher risk for the primary CEP (HR: 1.55, 95%-CI 1.04 - 2.31, P = 0.03), which was more pronounced in patients with larger clones. CH clone size remained an independent risk factor (HR 1.30, 95%-CI 1.04 - 1.62, P = 0.022) in multivariable Cox regression. While our data show that in particular larger and TET2- or PPM1D-mutated clones are associated with increased risk of recurrent vascular events and death, this risk is partially mitigated by a common germline variant of the IL-6 receptor (IL-6R p.D358A). The CH mutation profile is accompanied by a pro-inflammatory profile opening new avenues for preventive precision medicine approaches to resolve the self-perpetuating cycle of inflammation and clonal expansion.