Risk Of Hemorrhagic Stroke Research Articles

Hypertensive Retinopathy and the Risk of Hemorrhagic Stroke

ObjectiveHemorrhagic stroke (HS) and hypertensive retinopathy are known end organ damage of the brain and eye respectively, with HS having deleterious consequence to the patients. This study is to correlate between hypertensive retinopathy and HS in hypertensive disease. MethodsA control group of hypertensive patients only, and an investigated group of hypertensive HS patients. Fundoscopic examination to determine the grade of retinopathy was performed and then divided into low or high severity hypertensive retinopathy. Clinical and radiological parameter included are demography, vital signs, Glasgow coma scale (GCS) on admission, clot volume, site of clot, Intracerebral hemorrhage (ICH) score and Glasgow outcome scale (GOS). Data were correlated with the severity of hypertensive retinopathy. ResultsFifty patient in the control group and 51 patients in the investigated group were recruited. In the hypertensive HS group, 21 had low severity retinopathy (no or mild retinopathy) accounting for 41.2% and 30 patients had high severity (moderate or severe retinopathy). In the hypertensive patients 49 had low severity and one had high severity (p-value of 0.001). In HS group low severity showed better GCS score of 9–15 on admission (p-value of 0.003), clot volume less than 30 mL (p-value 0.001), and also a better 30 days mortality rate by using the ICH score (p-value 0.006), GOS score of 4 and 5 the low severity retinopathy fair better than the high severity retinopathy (p-value of 0.001), and the relative risk to develop HS in low severity and high severity retinopathy was 0.42 and 29.4, respectively. ConclusionHypertensive retinopathy screening could be used as an indicator in hypertensive patient, to evaluate the risk of developing hypertensive HS in the future.

Surgical Management of Failed Revascularization in Moyamoya Vasculopathy.

Objectives: Moyamoya vasculopathy (MMV) is a rare stenoocclusive cerebrovascular disease associated with increased risk of ischemic and hemorrhagic stroke, which can be treated using surgical revascularization techniques. Despite well-established neurosurgical procedures performed in experienced centers, bypass failure associated with neurological symptoms can occur. The current study therefore aims at characterizing the cases of bypass failure and repeat revascularization at a single center.Methods: A single-center retrospective analysis of all patients treated with revascularization surgery for MMV between January 2007 and December 2019 was performed. Angiographic data, cerebral blood flow analysis [H2O PET or single-photon emission CT (SPECT)], MRI, and clinical/operative data including follow-up assessments were reviewed.Results: We identified 308 MMV patients with 405 surgically treated hemispheres. Of the 405 hemispheres treated, 15 patients (3.7%) underwent repeat revascularization (median age 38, time to repeat revascularization in 60% of patients was within 1 year of first surgery). The most common cause of repeat revascularization was a symptomatic bypass occlusion (80%). New ischemic lesions were found in 13% of patients prior to repeat revascularization. Persistence of reduced or progressive worsening of cerebrovascular reserve capacity (CVRC) compared with preoperative status was observed in 85% of repeat revascularization cases. Intermediate-flow bypass using a radial artery graft was most commonly used for repeat revascularization (60%) followed by re-superficial temporal artery to middle cerebral artery (re-STA-MCA) bypass (26%). High-flow bypass using a saphenous vein graft and using an occipital artery to MCA bypass was each used once. Following repeat revascularization, no new ischemic events were recorded.Conclusion: Overall, repeat revascularization is needed only in a small percentage of the cases in MMV. A rescue surgery should be considered in those with neurological symptoms and decreased CVRC. Intermediate-flow bypass using a radial artery graft is a reliable technique for patients requiring repeat revascularization. Based on our institutional experience, we propose an algorithm for guiding the decision process in cases of bypass failure.

Effect of BMI on Central Arterial Reflected Wave Augmentation Index, Toe-Brachial Index, Brachial-Ankle Pulse Wave Velocity and Ankle-Brachial Index in Chinese Elderly Hypertensive Patients with Hemorrhagic Stroke

BackgroundHypertensive cerebral hemorrhage seriously endangers the health of the elderly. However, the relationship between obesity and arterial elasticity in hypertensive cerebral hemorrhage remains to be clarified. The purpose of our study is to explore the associations between body mass index (BMI) and central arterial reflected wave augmentation index (cAIx), toe-brachial index (TBI), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI) in the elderly hypertensive patients with hemorrhagic stroke. Materials and MethodsA total of 502 elderly hypertensive patients with hemorrhagic stroke and 100 healthy controls were collected. According to the BMI, patients were divided into normal BMI, overweight, obesity, and obese groups. The multivariate logistic regression model was used to establish a risk model for elderly hypertensive hemorrhagic stroke. ResultsCompared with the normal BMI group, systolic blood pressure (SBP), diastolic blood pressure (DBP), cAIx, and baPWV in the abnormal BMI group were significantly increased (P < 0.05), while TBI and ABI were significantly decreased (P < 0.05). Logistic regression showed that BMI (OR = 1.031, 95%CI: 1.009–1.262), cAIx (OR = 1.214, 95%CI: 1.105–1.964), TBI (OR = 0.913, 95%CI: 0.885–0.967), baPWV (OR = 1.344, 95%CI: 1.142–2.147), and ABI (OR = 0.896, 95%CI: 0.811–0.989) are important factors for the occurrence of hemorrhagic stroke in the elderly hypertensive patients. ROC curve analysis showed that the AUC of cAIx, TBI, baPWV, ABI, and BMI were 0.914, 0.797, 0.934, 0.833, and 0.608, respectively. The final prediction model of hemorrhagic stroke elderly hypertensive patients was Y(P)= 65.424 + 0.307(cAIx) - 13.831(TBI) + 0.012(baPWV) - 0.110(ABI) + 0.339(BMI). ConclusionsObesity is associated with decreased arterial elasticity. Therefore, reasonable weight management of the elderly may be of great significance for reducing the risk of hemorrhagic stroke in patients with hypertension.

Erythropoietin Use and the Risk of Stroke in Patients on Hemodialysis: A Retrospective Cohort Study in Taiwan.

BackgroundTargeting higher hemoglobin levels with erythropoietin to treat anemia in patients with chronic kidney disease is associated with increased cardiovascular risk, including that of stroke. The risks of the subtypes of stroke, ischemic, hemorrhagic, and unspecified, following the administration of erythropoietin in patients with end‐stage renal disease receiving hemodialysis remain unclear.Methods and resultsOverall, 12 948 adult patients with end‐stage renal disease treated during 1999 to 2010 who had undergone hemodialysis were included. The study end points were the incidences of stroke and its subtypes. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) of stroke and its subtypes in erythropoietin recipients compared with nonrecipients. Patients in the erythropoietin cohort did not have an increased risk of stroke compared with those in the nonerythropoietin cohort (adjusted HR, 1.03; 95% CI, 0.92–1.15). Compared with patients in the nonerythropoietin cohort, the risks of ischemic, hemorrhagic, or unspecified stroke were not higher in patients in the erythropoietin cohort (adjusted HRs, 1.08 [95% CI, 0.93–1.26], 0.96 [95% CI, 0.78–1.18], and 1.03 [95% CI, 0.80–1.32], respectively). Increased risks of stroke and its subtypes were not observed with even large annual defined daily doses of erythropoietin (>201).ConclusionsErythropoietin in patients receiving hemodialysis is not associated with increased risk of stroke or any of its subtypes.

Lipid-Lowering Therapy and Hemorrhagic Stroke Risk: Comparative Meta-Analysis of Statins and PCSK9 Inhibitors.

Statins were shown to increase hemorrhagic stroke (HS) in patients with a first cerebrovascular event in 2006 (SPARCL), likely due to off-target antithrombotic effects, but continued to sometimes be used in patients with elevated HS risk due to absence of alternative medications. Recently, the PCSK9Is (proprotein convertase subtilisin kexin 9 inhibitors) have become available as a potent lipid-lowering class with potentially less hemorrhagic propensity. We performed a systematic comparative meta-analysis assessing HS rates across all completed statin and PCSK9I randomized clinical trials with treatment >3 months, following PRISMA guidelines. In addition to HS rates across all trials, causal relation was probed by evaluating for dose-response relationships by medication (low versus high medication dose/potency) and by presence and type of preceding brain vascular events at inception (none versus ischemic stroke/transient ischemic attack versus HS). The systematic review identified 36 statin randomized clinical trials (204 918 patients) and 5 PCSK9I randomized clinical trials (76 140 patients). Across all patient types and all medication doses/potencies, statins were associated with increased HS: relative risk 1.15, P=0.04; PCSK9Is were not (P=0.77). In the medication dose/potency analysis, higher dose/potency statins (7 trials, 62 204 patients) were associated with magnified HS risk: relative risk, 1.53; P=0.002; higher dose/potency PCSK9Is (1 trial, 27 564 patients) were not (P=0.99). In the type of index brain vascular injury analysis for statins (5 trials, 9772 patients), prior ischemic stroke/transient ischemic attack was associated with a magnified risk of HS: relative risk, 1.43; P=0.04; and index intracerebral hemorrhage was associated with an extremely high effect estimate of risk of recurrent HS: hazard ratio, 4.06. For PCSK9Is, prior ischemic stroke/transient ischemic attack (1 trial, 5337 patients) was not associated with increased HS risk (P=0.97). Statins increase the risk of HS in a medication dose- and type of index brain vascular injury-dependent manner; PCSK9Is do not increase HS risk. PCSK9Is may be a preferred lipid-lowering medication class in patients with elevated HS risk, including patients with prior HS.

Methamphetamine and heightened risk for early-onset stroke and Parkinson's disease: A review

IntroductionMethamphetamine users are typically young adults, placing them at risk for significant drug-related harms. Neurological harms include stroke and Parkinson's disease, both of which may develop prematurely in the context of methamphetamine use. Material and methodsWe conducted a narrative review examining the evidence first, for stroke under 45 years and second, early onset of Parkinson's disease (PD) and parkinsonism related to methamphetamine use. We summarise epidemiological factors and common clinical features, before examining in detail the underlying pathology and causal mechanisms. Results and discussionMethamphetamine use among young people (<45 years) is associated with heightened risk for haemorrhagic stroke. Compared to age-matched all-cause fatal stroke, haemorrhage secondary to aneurysmal rupture is more common among young people with methamphetamine-related stroke and is associated with significantly poorer prognosis. Aetiology is related primarily to both acute and chronic hypertension associated with methamphetamine's sympathomimetic action. Evidence from a variety of sources supports a link between methamphetamine use and increased risk for the development of PD and parkinsonism, and with their early onset in a subset of individuals. Despite this, direct evidence of degeneration of dopaminergic neurons in methamphetamine users has not been demonstrated to date. ConclusionsStroke and Parkinson's Disease/parkinsonism are neurological harms observed prematurely in methamphetamine users.

Stroke Risks in Adult Survivors of Preterm Birth: National Cohort and Cosibling Study

Clinicians will increasingly encounter adult patients who were born preterm and will need to understand their long-term sequelae. Adult survivors of preterm birth have been reported to have increased risks of hypertension and other stroke risk factors. However, their stroke risks have seldom been examined and the findings are discrepant, possibly due to small sample sizes, insufficient follow-up, or survivor bias. We examined whether preterm birth is associated with stroke in a large population-based cohort. A national cohort study was conducted of all 2 140 866 singletons born in Sweden from 1973 to 1994 who survived to age 18 years, who were followed up for first-time stroke through 2015 (maximum age 43 years). Cox regression was used to examine stroke risks associated with gestational age at birth, adjusting for other perinatal and parental factors. Cosibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. In 28.0 million person-years of follow-up, 4861 (0.2%) people were diagnosed with stroke. At ages 18 to 43 years, the adjusted hazard ratio for stroke associated with preterm birth (<37 weeks) was 1.26 (95% CI, 1.12–1.43; P<0.001), and further stratified was 1.42 (1.11–1.81; P=0.005) for early preterm (22–33 weeks) and 1.22 (1.06–1.40; P=0.004) for late preterm (34–36 weeks), compared with full-term (39–41 weeks). Positive associations were found with both hemorrhagic stroke (early preterm: adjusted hazard ratio, 1.42 [95% CI, 1.04–1.94]; any preterm: 1.15 [0.97–1.35]) and ischemic stroke (early preterm: adjusted hazard ratio, 1.33 [95% CI, 0.87–2.03]; any preterm: 1.31 [1.07–1.60]). These findings were similar in men and women and only partially explained by shared determinants of preterm birth and stroke within families. In this large national cohort, preterm birth was associated with increased risks of both hemorrhagic and ischemic stroke in adulthood. Preterm birth survivors need early preventive evaluation and long-term clinical follow-up to reduce their lifetime risk of stroke.

The risk of ischemic stroke and hemorrhagic stroke in Chinese adults with low-density lipoprotein cholesterol concentrations

BackgroundThe risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high. We sought to prioritize predictive risk factors for stroke in Chinese participants with LDL-C concentrations < 70 mg/dL using a survival conditional inference tree, a machine learning method.MethodsThe training dataset included 9327 individuals with LDL-C concentrations < 70 mg/dL who were free of cardiovascular diseases and did not use lipid-modifying drugs from the Kailuan I study (N = 101,510). We examined the validity of this algorithm in a second Chinese cohort of 1753 participants with LDL-C concentrations < 70 mg/dL from the Kailuan II study (N = 35,856).ResultsDuring a mean 8.5–9.0-year follow-up period, we identified 388 ischemic stroke cases and 145 hemorrhagic stroke cases in the training dataset and 20 ischemic stroke cases and 8 hemorrhagic stroke cases in the validation dataset. Of 15 examined predictors, poorly controlled blood pressure and very low LDL-C concentrations (≤ 40 mg/dL) were the top hierarchical predictors of both ischemic stroke risk and hemorrhagic stroke risk. The groups, characterized by the presence of 2–3 of aforementioned risk factors, were associated with a higher risk of ischemic stroke (hazard ratio (HR) 7.03; 95% confidence interval (CI) 5.01–9.85 in the training dataset; HR 4.68, 95%CI 1.58–13.9 in the validation dataset) and hemorrhagic stroke (HR 3.94, 95%CI 2.54–6.11 in the training dataset; HR 4.73, 95%CI 0.81–27.6 in the validation dataset), relative to the lowest risk groups (presence of 0–1 of these factors). There was a linear association between cumulative average LDL-C concentrations and stroke risk. LDL-C concentrations ≤ 40 mg/dL was significantly associated with increased risk of ischemic stroke (HR 2.07, 95%CI 1.53, 2.80) and hemorrhagic stroke (HR 2.70, 95%CI 1.70, 4.30) compared to LDL-C concentrations of 55–70 mg/dL, after adjustment for age, hypertension status, and other covariates.ConclusionIndividuals with extremely low LDL-C concentrations without previous lipid-modifying treatment could still be at high stroke risk.Trial registrationChinese Clinical Trial Register, ChiCTR-TNRC-11001489. Registered on 24-08-2011.

An evaluation of canagliflozin for the treatment of type 2 diabetes: an update

ABSTRACT Introduction Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proven to ameliorate kidney and heart failure in patients with type 2 diabetes (T2D), in addition to improving glycemic controls. Canagliflozin is a SGLT2i and has proved beneficial for kidney and heart diseases in addition to decreasing the incidence of the composite outcomes of cardiovascular diseases and stroke. Areas covered This paper reviews the development of canagliflozin and its effects on renal dysfunction, heart failure, and vascular diseases. Expert opinion Canagliflozin contributes to the inhibition of renal function, decline progression and, therefore, is effective for T2D patients with chronic kidney dysfunction and albuminuria. The Canagliflozin Cardiovascular Assessment Study (CANVAS) revealed that patients showed increased incidence of amputation via unknown mechanisms, which has not been observed in other studies that used real-world data. Moreover, canagliflozin has been proven effective for anemia-associated outcomes of chronic kidney failure. Meta-analyses have revealed that canagliflozin contributed to lower diastolic blood pressure when compared with other SGLT2is. A subanalysis of CANVAS data proved that canagliflozin reduced the risk of hemorrhagic stroke. Canagliflozin should be used for T2D patients with chronic kidney failure and/or albuminuria and those with vascular diseases, with monitoring for ulcers and/or the pulse on the lower limb.

Age at Menopause and Risk of Ischemic and Hemorrhagic Stroke.

The few epidemiological studies that addressed the association between age at menopause and ischemic and hemorrhagic stroke risk in women had conflicting findings. We aimed to investigate whether age at (natural and surgical) menopause is a risk factor for total, ischemic, and hemorrhagic stroke in women. We analyzed data from 16 244 postmenopausal women, aged 26 to 70 years at recruitment who were enrolled in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort between 1993 and 1997. Participants were followed for the occurrence of stroke until January 1, 2011. At baseline, participants filled in questionnaires about health, reproductive history including age at menopause, diet, and lifestyle. Cox regression was used to investigate the association between age at menopause and stroke. All analyses were adjusted for age, smoking, systolic blood pressure, and body mass index. Mean age of menopause was 46.4 (7.0) years. A total of 830 strokes (571 ischemic, 162 hemorrhagic, 97 unclassified) were identified. Earlier menopause was associated with an increased risk of total stroke. Compared with women who experienced menopause between 50 and 54 years old, women who underwent menopause before age 40 years had 1.48× higher risk (95% CI, 1.19-1.85) of total stroke. In continuous analyses, we observed a 2% lower total stroke risk for each year menopause was delayed (hazard ratio, 0.98 [95% CI, 0.97-0.99]). The risk between earlier menopause and stroke was confined to ischemic stroke, earlier menopause was not associated with hemorrhagic stroke. The association with age at menopause was stronger for natural menopause (hazard ratio <40 versus 50-54 years, 1.74 [95% CI, 1.12-2.70]) than for surgical menopause (hazard ratio <40 versus 50-54 years, 1.26 [95% CI, 0.84-1.89]). The risk of total and ischemic stroke decreased with an increase in age at menopause. Whether this should have clinical consequences such as intensified risk factor control should be subject of further studies.

Sex difference in the association between plasma selenium and first stroke: a community-based nested case-control study

BackgroundTo date, there is no clearly defined association between plasma selenium levels and first stroke. We aimed to investigate the association between baseline plasma selenium and first stroke risk in a community-based Chinese population.MethodsUsing a nested case-control study design, a total of 1255 first stroke cases and 1255 matched controls were analyzed. Participant plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), and the association of plasma selenium with first stroke risk was estimated by conditional logistic regression models.ResultsOverall, a non-linear negative association between plasma selenium and first total stroke and first ischemic stroke risks was found in males but not in females. Compared with participants with lower selenium levels (tertile 1–2, < 94.1 ng/mL), participants with higher selenium levels (tertile 3, ≥ 94.1 ng/mL) had significantly lower risks of first total stroke (OR 0.63; 95% CI 0.48, 0.83) and first ischemic stroke (OR 0.61; 95% CI 0.45, 0.83) in males but not in females with first total stroke (OR 0.92; 95% CI 0.69, 1.22) and first ischemic stroke (OR 0.89; 95% CI 0.65, 1.22). Furthermore, a stronger association between plasma selenium and first total stroke was found in males with higher vitamin E levels (≥ 13.5 μg/mL vs. < 13.5 μg/mL P-interaction = 0.007). No significant association was observed between plasma selenium and first hemorrhagic stroke risk in either males or females.ConclusionOur study indicated a significant, non-linear, negative association between plasma selenium and first stroke in males but not in females.Trial registrationChiCTR1800017274.

Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

BackgroundAlcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10–20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption.MethodsData were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean ± SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p < 0.0001). ALDH2 rs671 was not associated with either hemorrhagic or ischemic stroke among alcohol drinkers. However, the risk of developing hemorrhagic stroke was significantly higher among ADH1B rs1229984 TC + CC individuals who drank alcohol (odds ratio (OR), 4.85; 95% confidence interval (CI) 1.92–12.21). We found that the test for interaction was significant for alcohol exposure and rs1229984 genotypes (p for interaction = 0.016). Stratification by alcohol exposure and ADH1B rs1229984 genotypes showed that the risk of developing hemorrhagic stroke remained significantly higher among alcohol drinkers with TC + CC genotype relative to those with the TT genotype (OR, 4.43, 95% CI 1.19–16.52).ConclusionsOur study suggests that the ADH1B rs1229984 TC + CC genotype and alcohol exposure of at least 150 ml/week may increase the risk of developing hemorrhagic stroke among Taiwanese adults.

Association of Initial Potassium Levels with the Type of Stroke in the Emergency Department

Serum potassium levels are considered as a marker of cerebrovascular emergencies but there is less clarity on the association between initial serum potassium levels recorded on patient's arrival at the emergency department with the type of stroke. This is a case-control study using data of a tertiary care hospital in Japan from April 2018 to September 2019. We identified adult patients with hemorrhagic stroke including subarachnoid hemorrhage (cases) and those with ischemic stroke (controls). Data on age, sex, chief complaints, vital signs, and initial blood tests were collected. We analyzed the association between serum potassium levels and the type of stroke by drawing a LOWESS curve. Additionally, we fitted a logistic regression model to examine the association of interest. There were 416 stroke patients (158 hemorrhagic and 258 ischemic). The median age was 77 years (IQR: 68, 84), and 54% were male. The mean potassium level was 3.69 ± 0.55 mEq/L for hemorrhagic stroke and 4.08 ± 0.65 mEq/L for ischemic stroke. The LOWESS curve showed that the lower initial potassium level was linearly associated with a greater likelihood of hemorrhagic stroke. In the logistic regression model, the odds ratio for the risk of hemorrhagic stroke per 1 mEq/L lower potassium level was 3.31 (95% confidence interval [CI]: 2.24–5.04). This association remained significant in a multivariable model adjusting for other covariates (OR: 2.62 [95% CI: 1.70–4.16]). Initial potassium level was lower in patients with hemorrhagic stroke compared to those with ischemic stroke.

Low LDL-C levels are associated with risk of mortality in a Chinese cohort study.

Although low-density lipoprotein cholesterol (LDL-C) has been considered as a risk factor of atherosclerotic cardiovascular disease, limited studies can be available to evaluate the association of LDL-C with risk of mortality in the general population. This study aimed to examine the association of LDL-C level with risk of mortality using a propensity-score weighting method in a Chinese population, based on the health examination data. We performed a retrospective cohort study with 65,517 participants aged 40 years or older in Ningbo city, Zhejiang. LDL-C levels were categorized as five groups according to the Chinese dyslipidemia guidelines in adults. To minimize potential biases resulting from a complex array of covariates, we implemented a generalized boosted model to generate propensity-score weights on covariates. Then, we used Cox proportional hazard regression models with all-cause and cause-specific mortality as the dependent variables to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During the 439,186.5 person years of follow-up, 2403 deaths occurred. Compared with the median LDL-C group (100-130 mg/dL), subjects with extremely low LDL-C levels (group 1) had a higher risk of deaths from all-cause (HR = 2.53, 95% CI:1.80-3.53), CVD (HR = 1.84, 95% CI: 1.28-2.61), ischemic stroke (HR = 2.29, 95% CI:1.32-3.94), hemorrhagic stroke (HR = 3.49, 95% CI: 1.57-7.85), and cancer (HR = 2.12, 95% CI: 1.04-4.31) while the corresponding HRs in LDL-C group 2 were relatively lower than that in group 1. Low LDL-C levels were associated with an increased risk of all-cause, CVD, ischemic stroke, hemorrhagic stroke, and cancer mortality in the Chinese population.

Cerebral Microbleeds: Relationship to Antithrombotic Medications.

Cerebral microbleeds (CMBs) are represented by small areas of hemosiderin deposition, detected on brain magnetic resonance imaging (MRI), and found in ≈23% of the cognitively normal population over age of 60 years. CMBs predict risk of hemorrhagic and ischemic stroke. They correlate with increased cardiovascular mortality. In this article, we sought to determine in a population-based study whether antithrombotic medications correlate with CMBs and, if present, whether the association was direct or mediated by another variable. The study consisted of 1253 participants from the population-based Mayo Clinic Study of Aging who underwent T2* gradient-recalled echo magnetic resonance imaging. We tested the relationship between antithrombotic medications and CMB presence and location, using multivariable logistic-regression models. Ordinal logistic models tested the relationship between antithrombotics and CMB frequency. Using structural equation models, we assessed the effect of antithrombotic medications on presence/absence of CMBs and count of CMBs in the CMB-positive group, after considering the effects of age, sex, vascular risk factors, amyloid load by positron emission tomography, and apoE. Two hundred ninety-five participants (26.3%) had CMBs. Among 678 participants taking only antiplatelet medications, 185 (27.3%) had CMBs. Among 95 participants taking only an anticoagulant, 43 (45.3%) had CMBs. Among 44 participants taking an anticoagulant and antiplatelet therapy, 21 (48.8%) had CMBs. Anticoagulants correlated with the presence and frequency of CMBs, whereas antiplatelet agents were not. Structural equation models showed that predictors for presence/absence of CMBs included older age at magnetic resonance imaging, male sex, and anticoagulant use. Predictors of CMB count in the CMB-positive group were male sex and amyloid load. Anticoagulant use correlated with presence of CMBs in the general population. Amyloid positron emission tomography correlated with the count of CMBs in the CMB-positive group.

Preterm Delivery and Long-Term Risk of Stroke in Women: A National Cohort and Cosibling Study.

Stroke has a high burden of disease in women, and adverse pregnancy outcomes have been identified as important risk factors for stroke later in life. However, long-term risks of stroke associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment and stroke prevention in women. A national cohort study was conducted of all 2 188 043 women with a singleton delivery in Sweden in 1973 through 2015 who were followed up for stroke identified from nationwide diagnoses through 2015. Cox regression was used to compute adjusted hazard ratios (aHRs) for stroke associated with pregnancy duration, and cosibling analyses assessed for confounding by shared familial (genetic or environmental) factors. In 48.0 million person-years of follow-up, 36 372 (1.7%) women were diagnosed with stroke. In the 10 years after delivery, the aHR for stroke associated with preterm delivery (gestational age <37 weeks) was 1.61 (95% CI, 1.45-1.79) and further stratified was 2.81 (95% CI, 2.02-3.91) for extremely preterm (22-27 weeks), 2.07 (95% CI, 1.74-2.46) for very preterm (28-33 weeks), 1.38 (95% CI, 1.21-1.57) for late preterm (34-36 weeks), and 1.15 (95% CI, 1.06-1.24) for early term (37-38 weeks), compared with full-term (39-41 weeks) delivery. These risks remained similarly elevated at 10 to 19 years after delivery (preterm versus full-term: aHR, 1.61 [95% CI, 1.50-1.74]) and then declined but remained significantly elevated at 20 to 29 years (aHR, 1.35 [95% CI, 1.28-1.44]) and 30 to 43 years (aHR, 1.35 [95% CI, 1.27-1.42]). Preterm delivery was associated with both hemorrhagic (aHR, 1.31 [95% CI, 1.25-1.38]) and ischemic (aHR, 1.54 [95% CI, 1.47-1.61]) stroke across the entire follow-up period (up to 43 years). These findings were not explained by shared determinants of preterm delivery and stroke within families. Stroke risks were higher after either spontaneous or medically indicated preterm delivery, and recurrent preterm delivery was associated with further increases in risk. In this large national cohort, preterm delivery was associated with higher future risks of both hemorrhagic and ischemic stroke. These associations remained substantially elevated at least 40 years later, and were largely independent of covariates and shared familial factors. Preterm delivery should be recognized as a risk factor for stroke in women across the life course.

Association between Angiotensin Converting Enzyme Insertion/Deletion gene polymorphism with the risk of Hemorrhagic Stroke: A systematic review and Meta-Analysis of 53 studies.

Hemorrhagic stroke (HS) results in significant mortality and disability worldwide. Angiotensin Converting Enzyme (ACE) is responsible for blood pressure regulation and vascular homeostasis. Our objective was to conduct a comprehensive meta-analysis for ascertaining the association of ACE I/D polymorphism with HS since a number of studies depicted inconclusive evidence. Literature search was performed till July 10, 2020 in PubMed, EMBASE, Cochrane, Chinese National Knowledge Information and Google Scholar databases with keywords: ('Angiotensin Converting Enzyme' OR 'ACE') AND ('Single Nucleotide polymorphisms' OR 'SNP') AND ('Hemorrhagic stroke or 'HS'). Pooled Odds Ratio (OR) and 95% Confidence Interval (CI) were determined for gene-disease association using either fixed (when I2<50%) or random effect (when I2>50%) models. Risk of bias in studies was assessed using funnel plots and sensitivity analyses. Statistical analysis was performed using STATA version 13.0 software. A total of 53 studies having 5186 HS and 7347 healthy control subjects were included in our meta-analysis. Pooled analyses showed that ACE I/D gene polymorphism had significant association with risk of HS in overall study population [(dominant model: OR=1.29, 95% CI=1.12-1.50 & recessive model: OR=1.79, 95% CI=1.46-2.20)]. Population subgroup analyses further revealed significant relationship of ACE I/D polymorphism with ICH in Asians (recessive: OR 1.97, 95% CI=1.57-2.47) but not in Caucasians (recessive: OR 1.02, 95% CI=0.76-1.36). This meta-analysis suggests that ACE I/D polymorphism may lead to risk of HS and can be a potential biomarker for HS susceptibility especially in Asian population.

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.

Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.

The effect of PCSK9 inhibitors on brain stroke prevention: A systematic review and meta-analysis

Background and aimsAlthough proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention. Methods and resultsWe searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67–0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84–1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66–1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81–1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times. ConclusionsPCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment.

Serum/Plasma Zinc Is Apparently Increased in Ischemic Stroke: a Meta-analysis.

Zinc (Zn) is found in many neuronal pathways in the brain and has implications for neuromodulation and cerebrovascular disease. However, the association between Zn levels and stroke risk remains controversial. Therefore, we conducted a meta-analysis to explore these relationships. A systematic literature search using PubMed, EMBASE database, and Google Scholar was performed for relevant articles from inception to August 2020. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were considered the effect sizes and statistical analyses were performed using Stata 12.0. A total of 12 studies involving 1878 cases of stroke and 1754 controls were enrolled. Overall, the meta-analysis demonstrated no significant difference in Zn levels between the stroke group and control group (SMD =-0.18, 95% CI =-0.69 to 0.32, P = 0.480). Subgroup analysis showed that type of stroke had an influence on the Zn levels. A meta-analysis of nine ischemic stroke (IS) studies, which included 1645 cases and 1585 controls, revealed that the Zn levels were significantly higher in IS patients than in controls (SMD (95% CI): 0.61(0.04, 1.19), P = 0.036), but no significant association was found between Zn levels and risk of hemorrhagic stroke (P = 0.113). Egger's test indicated no significant publication bias. This meta-analysis indicates that higher Zn levels may be associated with increased risk of IS; however, these findings should be further confirmed.