Prevention and treatment of ischaemic and haemorrhagic stroke in people with diabetes mellitus: a focus on glucose control and comorbidities.

Diabetes mellitus is a significant risk factor for both ischaemic and haemorrhagic stroke, affecting up to a third of individuals with cerebrovascular diseases. Beyond being a risk factor for stroke, diabetes and hyperglycaemia have a negative impact on outcomes after ischaemic and haemorrhagic stroke. Hyperglycaemia during the acute ischaemic stroke phase is associated with a higher risk of haemorrhagic transformation and poor functional outcome, with evidence in favour of early intervention to limit and manage severe hyperglycaemia. Similarly, intensive glucose control nested in a broader bundle of care, including blood pressure, coagulation and temperature control, can provide substantial benefit for clinical outcomes after haemorrhagic stroke. As micro- and macrovascular complications are frequent in people with diabetes, cardiovascular prevention strategies also need to consider tailored treatment. In this regard, the broader availability of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists can allow tailored treatments, particularly for those with heart failure and chronic kidney disease as comorbidities. Here, we review the main concepts of hyperacute stroke management and CVD prevention among people with diabetes, capitalising on results from large studies and RCTs to inform clinicians on preferred treatments.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Global, Regional, and National Burdens of Stroke in Children and Adolescents From 1990 to 2019: A Population-Based Study.

BACKGROUND: Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels. METHODS: The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019. RESULTS: The global age-standardized incidence of stroke increased (average annual percentage change, 0.15% [95% uncertainty interval, 0.09%-0.21%]), while YLLs decreased substantially (average annual percentage change, -3.33% [95% uncertainty interval, -3.38% to -3.28%]) among children and adolescents between 1990 and 2019. Ischemic stroke accounted for 70% of incident cases, and intracerebral hemorrhage accounted for 63% of YLLs. Children under 5 years of age had the highest incidence of ischemic stroke, while adolescents aged 15 to 19 years had the highest incidence of hemorrhagic stroke. In 2019, low-income and middle-income countries were responsible for 84% of incident cases and 93% of YLLs due to childhood stroke. High-sociodemographic index countries had a reduction in YLLs due to stroke that was more than twice as fast as that of low-income and middle-income. CONCLUSIONS: Globally, the burden of childhood stroke continues to increase, especially among females, children aged <5 years, and low-sociodemographic index countries, such as sub-Saharan Africa. The burden of childhood stroke is likely undergoing a significant transition from being fatal to causing disability. Global public health policies and the deployment of health resources need to respond rapidly and actively to this shift.

Discordant High Remnant Cholesterol With LDL-C Increases the Risk of Stroke: A Chinese Prospective Cohort Study.

BACKGROUND: Previous studies focusing on assessing the effects of remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) on stroke may not consider their mutual influence. We aimed to explore the associations of RC and discordant high RC with LDL-C with stroke, ischemic stroke (IS), and hemorrhagic stroke. METHODS: This prospective cohort study was conducted based on 3 cohorts of the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project. RC was calculated as non-high-density lipoprotein cholesterol minus LDL-C estimated by Martin/Hopkins equations. Concordant/discordant categories for RC versus LDL-C were determined based on cut-points of 130 mg/dL for LDL-C and equivalent percentile (32.50 mg/dL) for RC. Cox models were used to estimate adjusted hazard ratios and 95% CIs for incident stroke. RESULTS: Among 113 448 participants recruited at baseline, a total of 98 967 participants were eligible for the final analysis (mean age of 51.44 years; 40.45% were men). During 728 776.87 person-years of follow-up, 2859 stroke cases, 1811 IS cases, and 849 hemorrhagic stroke cases were observed. RC was positively associated with stroke and IS, but not hemorrhagic stroke, with adjusted hazard ratios (95% CIs) of 1.06 (1.02-1.10), 1.09 (1.04-1.13), and 0.95 (0.88-1.03) for per SD increase in RC. Compared with low LDL-C/low RC group, low LDL-C/high RC group had higher risks of stroke (adjusted hazard ratio, 1.15 [95% CI, 1.02-1.30]) and IS (1.19, 1.03-1.38), while high LDL-C/low RC group had no increased risk of stroke (1.07 [0.95-1.20]) and IS (1.09 [0.94-1.25]). CONCLUSIONS: Higher RC was associated with increased risks of stroke and IS but not hemorrhagic stroke. Discordantly high RC, not discordantly high LDL-C, conferred higher risks of stroke and IS. Our findings support further lowering RC by interventions to reduce residual IS risk.

Age- and Sex-Specific Analysis of Stroke Hospitalization Rates, Risk Factors, and Outcomes From German Nationwide Data.

BACKGROUND: Significant age and sex differences have been reported at each stage of the stroke pathway, from risk factors to outcomes. However, there is some uncertainty in previous studies with regard to the role of potential confounders and selection bias. Therefore, using German nationwide administrative data, we aimed to determine the magnitude and direction of trends in age- or sex-specific differences with respect to admission rates, risk factors, and acute treatments of ischemic and hemorrhagic stroke. METHODS: We obtained and analyzed data from the Research Data Centres of the Federal Statistical Office for the years 2010 to 2020 with regard to all acute stroke hospitalizations, risk factors, treatments, and in-hospital mortality, stratified by sex and stroke subtype. This database provides a complete national-level census of stroke hospitalizations combined with population census counts. All hospitalized patients ≥15 years with an acute stroke (diagnosis code: I60-64) were included in the analysis. RESULTS: Over the 11-year study period, there were 3 375 157 stroke events; 51.2% (n=1 728 954) occurred in men. There were higher rates of stroke admissions in men compared with women for both ischemic (378.1 versus 346.7/100 000 population) and hemorrhagic subtypes (75.6 versus 65.5/100 000 population) across all age groups. The incidence of ischemic stroke admissions peaked in 2016 among women (354.0/100 000 population) and in 2017 among men (395.8/100 000 population), followed by a consistent decline from 2018 onward. There was a recent decline in hemorrhagic stroke admissions observed for both sexes, reaching its nadir in 2020 (68.9/100 000 for men; 59.5/100 000 for women). Female sex was associated with in-hospital mortality for both ischemic (adjusted odds ratio, 1.11 [1.09-1.12]; P<0.001) and hemorrhagic stroke (adjusted odds ratio, 1.18 [95% CI, 1.16-1.20]; P<0.001). CONCLUSIONS: Despite improvements in stroke prevention and treatment pathways in the past decade, sex-specific differences remain with regard to hospitalization rates, risk factors, and mortality. Better understanding the mechanisms for these differences may allow us to develop a sex-stratified approach to stroke care.

Stroke incidence increases with diabetic retinopathy severity and macular edema in type 1 diabetes.

BACKGROUND: As the retina is suggested to mirror the brain, we hypothesized that diabetic retinopathy and macular edema are indicative of stroke risk in type 1 diabetes and sought to assess this association in individuals with type 1 diabetes. METHODS: We included 1,268 adult FinnDiane Study participants with type 1 diabetes (age 38.7 ± 11.8 years, 51.7% men vs. 48.3% women, and 31.5% had diabetic kidney disease), data on baseline diabetic retinopathy severity, and first stroke during our observational follow-up. Retinopathy was graded by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and macular edema as clinically significant (CSME) or not. Strokes identified from registries were confirmed from medical files. Adjusted hazard ratios (HR) for stroke by retinopathy severity and CSME were calculated by Cox models adjusted for clinical confounders, including diabetic kidney disease. RESULTS: During median 18.0 (14.1-19.3) follow-up years, 130 strokes (96 ischemic, 34 hemorrhagic) occurred. With no-very mild (ETDRS 10-20) retinopathy as reference, the adjusted HR for stroke was 1.79 (95%CI 1.02-3.15) in non-proliferative (ETDRS 35-53), and 1.69 (1.02-2.82) in proliferative (ETDRS 61-85) retinopathy. Corresponding adjusted HR for ischemic stroke was 1.68 (0.91-3.10) in non-proliferative and 1.35 (0.77-2.36) in proliferative retinopathy. The adjusted HR for hemorrhagic stroke was 2.84 (0.66-12.28) in non-proliferative and 4.31 (1.16-16.10) in proliferative retinopathy. CSME did not increase HR for any stroke type after adjustment for clinical confounders (data not shown). CONCLUSIONS: Stroke incidence increases with the severity of diabetic retinopathy independently of comorbid conditions, including diabetic kidney disease.

Incidence of stroke, subsequent clinical outcomes and health care resource utilization in people with type 2 diabetes: a real-world database study in France: "INSIST" study.

BACKGROUND: People with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France. METHODS: We conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs. RESULTS: Among 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 [95% confidence interval (CI) 6.47-7.15] versus 1.38 [1.24-1.54]). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 [107.7-159.0] versus 126.4 [117.2-136.4]; stroke recurrence: 86.7 [66.4-113.4] versus 66.5 [59.2-74.6]; mortality 291.5 [259.1-327.9] versus 144.1 [134.3-154.6]). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 [95% CI 1.66-2.92]). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378). CONCLUSIONS: The high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D.

Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association.

The objective of this scientific statement is to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive low-density lipoprotein cholesterol lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke. The writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize existing evidence and to identify gaps in current knowledge. Although some retrospective, case control, and prospective longitudinal studies suggest that statins and low-density lipoprotein cholesterol lowering are associated with cognitive impairment or dementia, the preponderance of observational studies and data from randomized trials do not support this conclusion. The risk of a hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is nonsignificant, and achieving very low levels of low-density lipoprotein cholesterol does not increase that risk. Data reflecting the risk of hemorrhagic stroke with lipid-lowering treatment among patients with a history of hemorrhagic stroke are not robust and require additional focused study.

Etiological Subclassification of Stroke in Older People ≥80 Years Compared to Younger People: A Systematic Review and Meta-Analysis.

BACKGROUND: Due to the rapid growth of the world´s oldest population, the number of older persons with stroke is expected to rise. Knowledge of stroke etiology is essential to offer personalized and equal health care across age groups. The present systematic review aimed to investigate the prevalence of etiological subtypes of ischemic and hemorrhagic stroke in older compared to younger people. METHODS: MEDLINE, Embase, Cochrane, Epistemonikos, and Cinahl were systematically searched for studies regarding etiological classification in people ≥80 years compared to those <80 years with ischemic or hemorrhagic stroke. RESULTS: Out of 28 441 identified articles, eight met the inclusion criteria. In total, 8223 individuals were included in meta-analyses, of whom 2997 were 80 years or older. We demonstrated a higher prevalence of cardioembolic stroke in people ≥80 years OR 1.68 (95% CI, 1.12-2.53). Small vessel disease was significantly less common in older people OR .64 (95% CI, .50-.81). Regarding large vessel disease, no statistically significant difference between the two groups was shown OR 1.05 (95% CI, .77-1.43). CONCLUSION: In people ≥80 years, cardioembolic stroke is more common, and small vessel disease less common compared to people <80 years. Overall, the results have to be interpreted with caution due to few studies. Large studies using validated classification systems are needed.

Greenness mitigate cause-specific mortality associated with air pollutants in ischemic and hemorrhagic stroke patients: An ecological health cohort study.

BACKGROUND: Air pollution is one of the most serious environmental risks to mortality of stroke. However, there exists a noteworthy knowledge gap concerning the different stroke subtypes, causes of death, the susceptibility of stroke patient, and the role of greenness in this context. METHODS: We analyzed data from an ecological health cohort, which included 334,261 patients aged ≥40 years with stroke (comprising 288,490 ischemic stroke and 45,771 hemorrhagic stroke) during the period 2013-2019. We used Cox proportional hazards models with time-varying exposure to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the associations of annual average fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) with both all-cause and cause-specific mortality. Additionally, we conducted analyses to examine the effect modification by greenness and identify potential susceptibility factors through subgroup analyses. RESULT: In multivariable-adjusted models, long-term exposure to PM2.5 and NO2 was associated with increased risk of all-cause mortality (HR: 1.038, 95% CI: 1.029-1.047 for PM2.5; HR: 1.055, 95% CI: 1.026-1.085 for NO2, per 10 µg/m3, for ischemic stroke patients; similar for hemorrhagic stroke patients). Gradually increasing effect sizes were shown for CVD mortality and stroke mortality. The HRs of mortality were slightly weaker with high versus low vegetation exposure. Cumulative exposures increased the HRs of pollutant-related mortality, and greater greenness decreased this risk. Two subtypes of stroke patients exhibited diverse patterns of benefit. CONCLUSION: Increasing residential greenness attenuates the increased risk of mortality with different patterns due to chronic air pollutants for ischemic and hemorrhagic stroke, offering valuable insights for precise tertiary stroke prevention strategies.

Association of traditional and novel obesity indicators with stroke risk: Findings from the Rural Chinese cohort study.

BACKGROUND AND AIMS: Few researchers have compared the effectiveness of traditional and novel obesity indicators in predicting stroke incidence. We aimed to evaluate the associations between six obesity indices and stroke risk, and to further identify the optimal indicator. METHODS AND RESULTS: A total of 14,539 individuals from the Rural Chinese Cohort Study were included in the analyses. We used the Cox proportional hazards regression models to evaluate the association between six obesity indices (including body mass index [BMI], waist circumference [WC], conicity index [C-index], lipid accumulation product [LAP], visceral adiposity index [VAI], and Chinese visceral adiposity index [CVAI]) and stroke risk. Receiver operating characteristic curves were employed to compare their predictive ability on stroke risk. During a median follow-up period of 11.13 years, a total of 1257 cases of stroke occurred. In the multiple-adjusted Cox regression model, WC, BMI, C-index, and CVAI were positively associated with ischemic stroke (P < 0.01) rather than hemorrhagic stroke risk. Dose-response analyses showed a linear correlation of WC, BMI, C-index, and LAP (Poverall <0.05, and Pnonlinear >0.05), but a non-linear correlation of CVAI (Poverall <0.05, and Pnonlinear <0.05) with the risk of ischemic stroke. CVAI demonstrates the highest areas under the curves (AUC: 0.661, 95% CI: 0.653-0.668), indicating a superior predictive ability for ischemic stroke occurrence compared to other five indices (P < 0.001). CONCLUSION: WC, BMI, C-index, LAP, and CVAI were all positively related to the risk of ischemic stroke, among which CVAI exhibited stronger predictive ability for ischemic stroke.

Stroke outcomes following durable left ventricular assist device implant in patients bridged with micro-axial flow pump: Insights from a large registry.

BACKGROUND: Stroke after durable left ventricular assist device (d-LVAD) implantation portends high mortality. The incidence of ischemic and hemorrhagic stroke and the impact on stroke outcomes of temporary mechanical circulatory support (tMCS) management among patients requiring bridge to d-LVAD with micro-axial flow-pump (mAFP, Abiomed) is unsettled. METHODS: Consecutive patients, who underwent d-LVAD implantation after being bridged with mAFP at 19 institutions, were retrospectively included. The incidence of early ischemic and hemorrhagic stroke after d-LVAD implantation (<60 days) and association of pre-d-LVAD characteristics and peri-procedural management with a specific focus on tMCS strategies were studied. RESULTS: Among 341 patients, who underwent d-LVAD implantation after mAFP implantation (male gender 83.6%, age 58 [48-65] years, mAFP 5.0/5.5 72.4%), the early ischemic stroke incidence was 10.8% and early hemorrhagic stroke 2.9%. The tMCS characteristics (type of mAFP device and access, support duration, upgrade from intra-aortic balloon pump, ECMELLA, ECMELLA at d-LVAD implantation, hemolysis, and bleeding) were not associated with ischemic stroke after d-LVAD implant. Conversely, the device model (mAFP 2.5/CP vs. mAFP 5.0/5.5: HR 5.6, 95%CI 1.4-22.7, p = 0.015), hemolysis on mAFP support (HR 10.5, 95% CI 1.3-85.3, p = 0.028) and ECMELLA at d-LVAD implantation (HR 5.0, 95% CI 1.4-18.7, p = 0.016) were associated with increased risk of hemorrhagic stroke after d-LVAD implantation. Both early ischemic (HR 2.7, 95% CI 1.9-4.5, p < 0.001) and hemorrhagic (HR 3.43, 95% CI 1.49-7.88, p = 0.004) stroke were associated with increased 1-year mortality. CONCLUSIONS: Among patients undergoing d-LVAD implantation following mAFP support, tMCS characteristics do not impact ischemic stroke occurrence, while several factors are associated with hemorrhagic stroke suggesting a proactive treatment target to reduce this complication.

Trend analysis of stroke subtypes mortality attributable to high body-mass index in China from 1990 to 2019.

BACKGROUND: The prevalence of stroke disability associated with high BMI has significantly increased over the past three decades. However, it remains uncertain whether high body-mass index (BMI) exerts a similar impact on the disease burden of different stroke subtypes. The aim of this study is to assess the long-term trends of stroke and subtypes mortality attributable to high BMI in China between 1990 and 2019. METHODS: Data on stroke and subtypes mortality attributable to high BMI in China was extracted in the Global Burden of Disease (GBD) 2019. The trends of age-standardized mortality rate (ASMR) were calculated using the linear regression and age-period-cohort framework. RESULTS: The changing trend of ASMR on stroke attributable to high BMI in China differed among subtypes, with an estimated annual percentage change (EAPC) and 95%CI of 2.04 (1.86 to 2.21) for ischemic stroke (IS), 0.36 (-0.03 to 0.75) for intracerebral hemorrhage (ICH), and - 4.62 (-5.44 to -3.78) for subarachnoid hemorrhage (SAH). Net and local drift analyses revealed a gradual increase in the proportion of older people with IS and a gradual increase in the proportion of younger people with hemorrhagic strokes. The cohort and period rate ratios varied by subtype, showing an increasing trend for IS and ICH but a decreasing trend for SAH. The stroke mortality attributable to high BMI increased significantly with age for IS and ICH, peaking between ages 50-70 for SAH. Notably, males had higher ASMR related to stroke but exhibited slighter declines or higher growth compared to females in China. Moreover, the population affected by fatal strokes tended to be older among females but more evenly distributed across a wider age range encompassing both younger and older individuals. CONCLUSION: The research findings indicate a rising trend in the ASMR of stroke and subtypes attributable to high BMI in China from 1990 to 2019, with different patterns of change for different subtypes, genders and ages. Consequently, it is imperative for public health authorities in China to formulate guidelines for specific stroke subtypes, genders and ages to prevent the burden of stroke attributable to high BMI.

Risk of Hemorrhagic Stroke among Patients Treated with High-Intensity Statins versus Pitavastatin-Ezetimibe: A Population Based Study.

High-intensity statin (HIS) is recommended for high-risk patients in current guidelines. However, the risk of hemorrhagic stroke (HS) with HIS is a concern for Asians. Pitavastatin carries pharmacological differences compared with other statins. We compared the risk of HS in patients treated with pitavastatin-ezetimibe vs. HIS. We conducted a population-based, propensity score-matched cohort study using data from the Taiwan National Health Insurance Research Database. From January 2013 to December 2018, adults (≥ 18 years) who received pitavastatin 2-4 mg/day plus ezetimibe 10 mg/day (combination group, N = 3,767) and those who received atorvastatin 40 mg/day or rosuvastatin 20 mg/day (HIS group, N = 37,670) were enrolled. The primary endpoint was HS. We also assessed the difference of a composite safety endpoint of hepatitis or myopathy requiring hospitalization and new-onset diabetes mellitus. Multivariable Cox proportional hazards model was used to evaluate the relationship between study endpoints and different treatment. After a mean follow-up of 3.05 ± 1.66 years, less HS occurred in combination group (0.74%) than in HIS group (1.35%) [adjusted hazard ratio (aHR) 0.65, 95% confidence interval (CI) 0.44-0.95]. In subgroup analysis, the lower risk of HS in combination group was consistent among all pre-specified subgroups. There was no significant difference of the composite safety endpoint between the 2 groups (aHR 0.91, 95% CI 0.81-1.02). In conclusion, pitavastatin-ezetimibe combination treatment had less HS compared with high-intensity atorvastatin and rosuvastatin. Pitavastatin-ezetimibe may be a favorable choice for Asians who need strict lipid control but with concern of HS.

Stroke Risk After COVID-19 Bivalent Vaccination Among US Older Adults.

Importance: In January 2023, the US Centers for Disease Control and Prevention and the US Food and Drug Administration noted a safety concern for ischemic stroke among adults aged 65 years or older who received the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine. Objective: To evaluate stroke risk after administration of (1) either brand of the COVID-19 bivalent vaccine, (2) either brand of the COVID-19 bivalent plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant administration), and (3) a high-dose or adjuvanted influenza vaccine. Design, Setting, and Participants: Self-controlled case series including 11 001 Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine (among 5 397 278 vaccinated individuals). The study period was August 31, 2022, through February 4, 2023. Exposures: Receipt of (1) either brand of the COVID-19 bivalent vaccine (primary) or (2) a high-dose or adjuvanted influenza vaccine (secondary). Main Outcomes and Measures: Stroke risk (nonhemorrhagic stroke, transient ischemic attack, combined outcome of nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day risk window after vaccination vs the 43- to 90-day control window. Results: There were 5 397 278 Medicare beneficiaries who received either brand of the COVID-19 bivalent vaccine (median age, 74 years [IQR, 70-80 years]; 56% were women). Among the 11 001 beneficiaries who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there were no statistically significant associations between either brand of the COVID-19 bivalent vaccine and the outcomes of nonhemorrhagic stroke, transient ischemic attack, nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke during the 1- to 21-day or 22- to 42-day risk window vs the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12). Among the 4596 beneficiaries who experienced stroke after concomitant administration of either brand of the COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window for the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine (IRR, 1.20 [95% CI, 1.01-1.42]; risk difference/100 000 doses, 3.13 [95% CI, 0.05-6.22]) and a statistically significant association between vaccination and transient ischemic attack during the 1- to 21-day risk window for the Moderna mRNA-1273.222 COVID-19 bivalent vaccine (IRR, 1.35 [95% CI, 1.06-1.74]; risk difference/100 000 doses, 3.33 [95% CI, 0.46-6.20]). Among the 21 345 beneficiaries who experienced stroke after administration of a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window (IRR, 1.09 [95% CI, 1.02-1.17]; risk difference/100 000 doses, 1.65 [95% CI, 0.43-2.87]). Conclusions and Relevance: Among Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there was no evidence of a significantly elevated risk for stroke during the days immediately after vaccination.

Genetically proxied appendicular lean mass and stroke risk: A two-step mendelian randomization study.

BACKGROUND AND PURPOSE: Prior observational studies have suggested a strong correlation between sarcopenia and stroke, but the causal link between them remains uncertain. This study aims to investigate the associations between genetically predicted sarcopenia-related traits and stroke using a two-step Mendelian randomization (MR) approach. METHODS: Genome-wide association study (GWAS) summary data for sarcopenia-related traits were acquired from the UK Biobank. Genetic associations for ischemic stroke (IS) and its subtypes were selected from the MEGASTROKE consortium comprising European ancestry participants. GWAS summary data for cerebral hemorrhage were obtained from the FinnGen consortium, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). MR estimates were calculated using the inverse-variance weighted (IVW) method. The robustness of results was assessed for heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs). RESULTS: Higher appendicular lean mass (ALM) exhibited a potential causal association with a reduced incidence of large artery atherosclerosis (LAA) (odds ratio [OR] = 0.81, 95% confidence interval [CI]:0.71-0.93; P = 0.003) and small vessel disease (SVD) (OR = 0.83, 95% CI:0.74-0.94; P = 0.002). The associations of ALM with IS and ICH were compromised after adjusting for body fat and physical activity with multivariable MR. Two-step MR mediation analysis explored 33 candidate mediators, among which hypertension and SBP accounted for more than 10% of the mediation proportion in the relationship between ALM and stroke and its subtypes. CONCLUSION: Our research findings indicate that lower ALM is associated with a increased risk of stroke . It is necessary to explore the specific protective mechanisms of higher ALM for preventing stroke occurrence.

A systematic review of the epidemiology and the public health implications of stroke in Sub-Saharan Africa.

BACKGROUND: With approximately 11 million strokes occurring annually worldwide, and over 6.5 million deaths annually, stroke has made its place as one of the major killers in the world. Although developing countries make up more than 4/5 of the global stroke burden, well-grounded information on stroke epidemiology remains lacking there. AIMS: This systematic review study aimed to provide a synthesis of studies on the incidence and prevalence of stroke among adults in sub-Saharan Africa (SSA), subsequently deduce the associated risk factors and public health implications (mortality rates and economic costs) of the disease on the population of this region. METHODS: A systematic review of studies carried out in the region and published on PUBMED. Eligibility criteria were established using the PEO (Population/Patient, Exposure, Outcome) format. Research articles investigating either (or all) of the following: ischemic or haemorrhagic stroke, incidence, prevalence, and risk factors of stroke in adults (≥ 18 years old), in at least one region of SSA were included. Exclusion criteria comprised studies involving populations younger than 18 years old, research conducted outside the designated research region, and articles inaccessible in full text. The PRISMA guidelines were used for the search strategy. RESULTS: Fifty-two studies were included review. Among them, over 11 studies investigated the prevalence of the disease. Some older studies within the continent (Nigeria, 2011) showed a prevalence of 1.3 per 100 while more recent studies (Zambia, 2021) showed a prevalence of 4.3 per 1000. The highest prevalence noted in this region was in Madagascar (2017) with 48.17 per 100, while the lowest was recorded in (Zimbabwe, 2017) with 0.61 per 100. The study in Tanzania showed a crude incidence of 94·5 per 100 000 (76·0-115·0) while the study in Ghana in 2018 showed an incidence of 14.19 events per 1000 person-years [10.77-18.38]. The identified risk factors included hypertension, diabetes, smoking, alcohol consumption, physical inactivity, poor diets (more salt, less vegetables), dyslipidaemia, HIV/AIDS co-infection, heart disease (cardiomyopathies, cardiac arrhythmias), obesity, previous stroke and/or family history of stroke. Over 21 studies investigated the mortality rates due to stroke in SSA, with most of the studies being in West Africa. These studies revealed mortality rates as high as 43.3% in Ghana, and as low as 10.9% in Cameroon. Few studies reported on the economic costs of stroke in the region; two in Benin, two in Nigeria and one in Tanzania. CONCLUSION: The increasing incidence/prevalence, lifestyle factors and interactions with other diseases, including major communicable diseases, stroke is becoming a pressing public health problem for SSA. Reducing the incidence of stroke in Africa will surely lower mortality, morbidity, disability, and the neurological as well as cognitive aftereffects of stroke, as is clear from the experience of higher-income nations. We recommend a collective intervention involving the governments of nations, international organizations, civil society, and the private sector for greater impact and sustainable outcomes reducing the epidemiology and implications of stroke in SSA.

Impact of surface ultraviolet radiation intensity on hospital admissions for ischemic and hemorrhagic stroke: A large-scale database study using distributed lag nonlinear analysis, 2015-2022, in Harbin, China.

OBJECTIVES: Our aim is to evaluate the impact of surface ultraviolet radiation intensity on hospital admissions for stroke and to compare the correlation and differences among different subtypes of strokes. MATERIALS AND METHODS: We collected daily data on surface ultraviolet radiation intensity, temperature, air pollution, and hospital admissions for stroke in Harbin from 2015 to 2022. Using a distributed lag non-linear model, we determined the correlation between daily surface ultraviolet radiation intensity and the stroke admission rate. Relative risks (RR) with 95% confidence intervals (CI) and attributable fractions (AF) with 95% CI were calculated based on stroke subtypes, gender, and age groups. RESULTS: A total of 132,952 hospitalized stroke cases (including hemorrhagic and ischemic strokes) were included in the study. We assessed the non-linear effects of ultraviolet intensity on hospitalized patients with ischemic and hemorrhagic strokes. Compared to the maximum morbidity benchmark ultraviolet intensity (19.2 × 10^5 for ischemic stroke and 20.25 for hemorrhagic stroke), over the 0-10 day lag period, the RR for extreme low radiation (1st percentile) was 0.86 (95% CI: 0.77, 0.96), and the RR for extreme high radiation (99th percentile) was 0.86 (95% CI: 0.77, 0.96). In summary, -4.842% (95% CI: -7.721%, -2.167%) and -1.668% (95% CI: -3.061%, -0.33%) of ischemic strokes were attributed to extreme low radiation intensity with a lag of 0 to 10 days and extreme high radiation intensity with a lag of 0 to 5 days, respectively. The reduction in stroke hospitalization rates due to low or high ultraviolet intensity was more pronounced in females and younger individuals compared to males and older individuals. None of the mentioned ultraviolet intensity intensities and lag days had a statistically significant impact on hemorrhagic stroke. CONCLUSIONS: Our study fundamentally suggests that both lower and higher levels of surface ultraviolet radiation intensity in Harbin, China, contribute to a reduced incidence of ischemic stroke, with this effect lasting approximately 10 days. This finding holds significant potential for public health and clinical relevance.

The Prevalence and Pattern of Admission Mortality among Acute Stroke Patients Managed at a Tertiary Hospital in Abakaliki, Nigeria: A Retrospective Study.

BACKGROUND: Stroke ranks as the second leading cause of mortality worldwide, following ischemic heart disease, and is expected to maintain this position through 2030. This neurological ailment is profoundly impactful, imposing a significant burden on health and the economy. In 2019 alone, it was responsible for 6.6 million fatalities and the loss of 143 million disability-adjusted life years (DALYs) across the globe. OBJECTIVES: This study highlighted the prevalence and pattern of admission mortality among acute stroke patients managed over 9 years in a private tertiary hospital in Abakaliki, Nigeria. METHODOLOGY: This was a retrospective hospital-based study conducted at a tertiary hospital in Abakaliki, Nigeria from January 2014 to December 2022. Relevant data were extracted from the patients' case notes and the sociodemographic, clinical and laboratory parameters of acute stroke survivors were compared with those of their dead counterparts. RESULTS: Out of the 172 (males - 57%; females - 43%) patients that fulfilled the inclusion criteria, 53 (30.81%) had haemorrhagic stroke while 119 (69.19%) had ischaemic stroke. The overall admission mortality rate was 15.12%, and it was more common in patients with haemorrhagic stroke, advancing age, severe hypertension, severe stroke, impairment of consciousness, renal dysfunction, hypernatremia, neutrophilic leucocytosis, and short admission duration. CONCLUSIONS: High mortality rates are linked to acute stroke admissions, particularly in cases involving haemorrhagic stroke, increasing age, severe hypertension, substantial stroke severity, impaired consciousness, renal dysfunction, hypernatremia, neutrophilic leukocytosis, and brief admission duration.

CONTEXTE: L'accident vasculaire cérébral (AVC) est la deuxième cause de mortalité dans le monde, après la cardiopathie ischémique, et devrait conserver cette position jusqu'en 2030. Cette affection neurologique a un impact profond, imposant une charge significative sur la santé et l'économie. En 2019 seulement, elle a été responsable de 6,6 millions de décès et de la perte de 143 millions d'années de vie ajustées sur l'incapacité (DALYs) dans le monde. OBJECTIFS: Cette étude a mis en évidence la prévalence et le modèle de la mortalité à l'admission chez les patients victimes d'AVC aigu gérés pendant 9 ans dans un hôpital privé tertiaire à Abakaliki, Nigéria. MÉTHODOLOGIE: Il s'agissait d'une étude rétrospective en milieu hospitalier menée dans un hôpital tertiaire à Abakaliki, Nigéria, de janvier 2014 à décembre 2022. Les données pertinentes ont été extraites des dossiers des patients et les paramètres sociodémographiques, cliniques et de laboratoire des survivants d'un AVC aigu ont été comparés à ceux de leurs homologues décédés. RÉSULTATS: Parmi les 172 patients (hommes - 57 % ; femmes - 43 %) qui remplissaient les critères d'inclusion, 53 (30,81 %) avaient un AVC hémorragique tandis que 119 (69,19 %) avaient un AVC ischémique. Le taux global de mortalité à l'admission était de 15,12 % et était plus fréquent chez les patients ayant un AVC hémorragique, un âge avancé, une hypertension sévère, un AVC sévère, une altération de la conscience, une dysfoncti on rénal e, une hyper natrémie, une l eucocytose neutrophilique et une courte durée d'admission. CONCLUSIONS: Les taux de mortalité élevés sont liés aux admissions pour AVC aigu, en particulier dans les cas d'AVC hémorragique, d'âge avancé, d'hypertension sévère, de sévérité importante de l'AVC, d'altération de la conscience, de dysfonction rénale, d'hypernatrémie, de leucocytose neutrophilique et de courte durée d'admission. MOTS-CLÉS: Facteurs de risque, Mortalité à l'admission, AVC aigu, Étude rétrospective.

Chronic Hepatitis B Virus Infection and Risk of Stroke Types: A Prospective Cohort Study of 500†000 Chinese Adults.

BACKGROUND: Stroke is a leading cause of mortality and permanent disability in China, with large and unexplained geographic variations in rates of different stroke types. Chronic hepatitis B virus infection is prevalent among Chinese adults and may play a role in stroke cause. METHODS: The prospective China Kadoorie Biobank included >500 000 adults aged 30 to 79 years who were recruited from 10 (5 urban and 5 rural) geographically diverse areas of China from 2004 to 2008, with determination of hepatitis B surface antigen (HBsAg) positivity at baseline. During 11 years of follow-up, a total of 59 117 incident stroke cases occurred, including 11 318 intracerebral hemorrhage (ICH), 49 971 ischemic stroke, 995 subarachnoid hemorrhage, and 3036 other/unspecified stroke. Cox regression models were used to estimate adjusted hazard ratios (HRs) for risk of stroke types associated with HBsAg positivity. In a subset of 17 833 participants, liver enzymes and lipids levels were measured and compared by HBsAg status. RESULTS: Overall, 3.0% of participants were positive for HBsAg. HBsAg positivity was associated with an increased risk of ICH (adjusted HR, 1.29 [95% CI, 1.16-1.44]), similarly for fatal (n=5982; adjusted HR, 1.36 [95% CI, 1.16-1.59]) and nonfatal (n=5336; adjusted HR, 1.23 [95% CI, 1.06-1.44]) ICH. There were no significant associations of HBsAg positivity with risks of ischemic stroke (adjusted HR, 0.97 [95% CI, 0.92-1.03]), subarachnoid hemorrhage (adjusted HR, 0.87 [95% CI, 0.57-1.33]), or other/unspecified stroke (adjusted HR, 1.12 [95% CI, 0.89-1.42]). Compared with HBsAg-negative counterparts, HBsAg-positive individuals had lower lipid and albumin levels and higher liver enzyme levels. After adjustment for liver enzymes and albumin, the association with ICH from HBsAg positivity attenuated to 1.15 (0.90-1.48), suggesting possible mediation by abnormal liver function. CONCLUSIONS: Among Chinese adults, chronic hepatitis B virus infection is associated with an increased risk of ICH but not other stroke types, which may be mediated through liver dysfunction and altered lipid metabolism.