Background and Purpose— The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of <70 mg/dL to reduce the risk of cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature or aortic arch plaque >4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods— One thousand seventy-three French patients were assigned to <70 mg/dL (1.8 mmol/L) and 1075 to 100±10 mg/dL (90–110 mg/dL, 2.3–2.8 mmol/L). To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe on top if needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. Results— After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57–0.94]; P =0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% ( P =0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% ( P =0.023). The primary outcome or intracranial hemorrhage was reduced by 25% ( P =0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53–2.62]; P =0.70). Conclusions— After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of <70 mg/dL during 5.3 years avoided 1 subsequent major vascular event in 4 (number needed to treat of 30) and no increase in intracranial hemorrhage. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875.

BACKGROUND: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. METHODS: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. RESULTS: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). CONCLUSIONS: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

No abstract