Higher Risk Of Hemorrhagic Stroke Research Articles

Mediating effect of hypertension on risk of stroke associated with hyperuricemia

Objective: To investigate the association between hyperuricemia and the risk for stroke occurrence, as well as the mediating effect of hypertension on this association. Methods: In this study, the China Chronic Diseases and Nutrition Surveillance system in 2015 was used as baseline data. We identified hospital admissions for stroke using the electronic homepage of inpatient medical records from 2013-2020, and death data were obtained from the 2015-2020 National Mortality Surveillance System. A retrospective cohort was established after matching and linking the database. The Cox proportional hazard regression model was used to analyze the relationship between hyperuricemia and the risk of stroke and its subtypes. Restricted cubic spline analysis was conducted to examine the dose-response relationship between serum uric acid levels and the risk for stroke. Mediation analysis was performed to investigate the mediating effect of hypertension on the association between hyperuricemia and the risk for stroke and its subtypes. Subgroup analyses were conducted based on gender and age groups. Results: A total of 124 352 study subjects were included, with an accumulative follow-up time of 612 911.36 person-years. During the follow-up period, 4 638 cases of stroke were found, including 3 919 cases of ischemic stroke and 689 cases of hemorrhagic stroke. The incidence density of stroke was 756.72 per 100 000 person-years, 641.37 per 100 000 person-years for ischemic stroke, and 114.60 per 100 000 person-years for hemorrhagic stroke. Multivariable Cox proportional hazards regression models showed that after adjusting for covariates, compared to those without hyperuricemia, individuals with hyperuricemia had a 16% higher risk for stroke [hazard ratio (HR)=1.16, 95%CI: 1.06-1.27], a 12% higher risk of ischemic stroke (HR=1.12, 95%CI: 1.01-1.24), and a 39% higher risk of hemorrhagic stroke (HR=1.39, 95%CI: 1.11-1.75). Mediation analysis showed that hypertension partially mediated the associations between hyperuricemia and the risk for stroke, ischemic stroke, and hemorrhagic stroke, with mediation proportions of 36.07%, 39.98%, and 25.34%, respectively. The mediating effect is pronounced in the male population and individuals below 65. Conclusion: Hyperuricemia is a risk factor for stroke, and hypertension partially mediates the effect of hyperuricemia on stroke.

Lipid-Lowering Therapy and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin low-density lipoprotein-cholesterol (LDL-C)-and triglyceride-lowering therapies. We performed a systematic review of large randomized clinical trials (≥1000 patients with ≥2 years follow-up) of LDL-C-lowering therapy (statin, ezetimibe, and PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitor) and triglyceride-lowering therapy (omega-3 supplements and fibrate) that reported hemorrhagic stroke as an outcome. We searched MEDLINE, Embase, and Cochrane Library up to July 2, 2021 and updated a meta-analysis of cardiovascular statin trials published in 2012. Among our several subgroup analyses, we looked at difference depending on stroke status and also depending on age. We identified 37 trials for LDL-C lowering (284 301 participants) and 11 for triglyceride lowering (120 984 participants). Overall, we found a higher risk of hemorrhagic stroke for LDL-C lowering, risk ratio (RR) 1.16 (95% CI, 1.01-1.32, P=0.03). For statins (33 trials, 216 258 participants), RR=1.17 (95% CI, 1.01-1.36); for PCSK-9 inhibitors (2 trials, 46 488 participants), RR=0.86 (95% CI, 0.43-1.74); and for ezetimibe (2 trials, 21 555 participants), RR=1.14 (95% CI, 0.64-2.03). In statin trials of patients with previous stroke/transient ischemic attack, RR was 1.46 (95% CI, 1.05-2.04), and in trials with mean age ≥65 years old, RR=1.34 (95% CI, 1.04-1.73) (Pint=0.14 and Pint=0.23 respectively); for triglyceride lowering (11 trials, 120 984 participants), RR=1.05 (95% CI, 0.86-1.30). We found evidence for a small increased risk of hemorrhagic stroke events with LDL-C-lowering therapies but no clear evidence for triglyceride-lowering therapies. URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42021275363.

Moderate alcohol consumption on the risk of stroke in the Million Veteran Program

BackgroundThere is inconsistent evidence on the association of moderate alcohol consumption and stroke risk in the general population and is not well studied among U.S. Veterans. Furthermore, it is unclear whether primarily drinking beer, wine, or liquor is associated with a difference in stroke risk.MethodsThe study included 185,323 Million Veteran Program participants who self-reported alcohol consumption on the Lifestyle Survey. Moderate consumption was defined as 1–2 drinks/day and beverage preference of beer, wine or liquor was defined if ≥ 50% of total drinks consumed were from a single type of beverage. Strokes were defined using ICD-9 and ICD-10 codes from the participants’ electronic health record.ResultsThe mean (sd) age of the sample was 64 (13) years and 11% were women. We observed 4,339 (94% ischemic; 6% hemorrhagic) strokes over a median follow-up of 5.2 years. In Cox models adjusted for age, sex, race, education, income, body mass index, smoking, exercise, diet, cholesterol, prevalent diabetes, prevalent hypertension, lipid-lowering medication, antihypertensive medication, and diabetes medication, moderate alcohol consumption (1–2 drinks/day) was associated with a 22% lower risk of total stroke compared with never drinking [Hazards ratio (HR) 95% confidence interval (CI): 0.78 (0.67, 0.92)]. When stratifying by stroke type, we observed a similar protective association with moderate consumption and ischemic stroke [HR (95% CI): 0.76 (0.65, 0.90)], but a non-statistically significant higher risk of hemorrhagic stroke [HR (95% CI): 1.29 (0.64, 2.61)]. We did not observe a difference in ischemic or hemorrhagic stroke risk among those who preferred beer, liquor or wine vs. no beverage preference. When stratifying by prior number of hospital visits (≤ 15, 16–33, 34–64, ≥ 65) as a proxy for health status, we observed attenuation of the protective association with greater number of visits [HR (95% CI): 0.87 (0.63, 1.19) for ≥ 65 visits vs. 0.80 (0.59, 1.08) for ≤ 15 visits].ConclusionsWe observed a lower risk of ischemic stroke, but not hemorrhagic stroke with moderate alcohol consumption and did not observe substantial differences in risk by beverage preference among a sample of U.S. Veterans. Healthy user bias of moderate alcohol consumption may be driving some of the observed protective association.

Association of MMP3, MMP14, and MMP25 gene polymorphisms with cerebral stroke risk: a case-control study

BackgroundCerebral stroke (CS) is the leading cause of death in China, and a complex disease caused by both alterable risk factors and genetic factors. This study intended to investigate the association of MMP3, MMP14, and MMP25 single nucleotide polymorphisms (SNPs) with CS risk in a Chinese Han population.MethodsA total of 1,348 Han Chinese were recruited in this case-control study. Four candidate loci including rs520540 A/G and rs679620 T/C of MMP3, rs2236302 G/C of MMP14, and rs10431961 T/C of MMP25 were successfully screened. The correlation between the four SNPs and CS risk was assessed by logistic regression analysis. The results were analyzed by false-positive report probability (FPRP) for chance or significance. The interactions between four SNPs associated with CS risk were assessed by multifactor dimensionality reduction (MDR).Resultsrs520540 A/G and rs679620 C/T SNP in MMP3 were associated with risk of CS in allele, codominant, dominant and log-additive models. Ischemic stroke risk were significantly lower in carriers with rs520540-A allele and rs679620-T allele than those with G/G or C/C genotypes. However, rs520540-A allele and rs679620-T allele were associated with higher risk of hemorrhagic stroke. Stratified analysis showed that these two SNPs were associated with reduced risk of CS in aged < 55 years, non-smoking and non-drinking participants, and rs679620 SNP also reduced CS risk in male participants. The levels of uric acid, high-density lipoprotein cholesterol, and eosinophil were different among patients with different genotypes of rs520540 and rs679620. No statistically significant association was found between MMP14 rs2236302 G/C or MMP25 rs10431961 T/C with CS even after stratification by stroke subtypes, age, gender as well as smoking and drinking conditions in all the genetic models.ConclusionMMP3 rs520540 A/G and rs679620 C/T polymorphisms were associated with CS risk in the Chinese Han population, which provides useful information for the prevention and diagnosis of CS.

Ischemic and non-ischemic stroke reported in DOAC treated patients with atrial fibrillation and levetiracetam drug interaction: a real-world study

Abstract Background To date, the combination of direct oral anti coagulants and some anticonvulsants remain controversial. Therefore, the European Heart Rhythm recommendations do not support using levetiracetam with DOACs. Objectives This study sought to investigate reports on ischemic and hemorrhagic stroke with DOACs and the effect of levetiracetam on the rate of reporting in atrial fibrillation patients. Methods In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify adverse events associated with DOACs with and without concomitant use of levetiracetam. The authors evaluated disproportionate reporting by the reporting odds ratio adjusted to age and sex (adjROR) and the lower bound of the shrinkage 95% confidence interval (Ω025 &amp;gt; 0 is deemed significant). Results The authors identified 1723 (1.3%), 1841 (1.5%), and 3731 (5.3%) MedDRA preferred terms for ischemic stroke in AF patients treated with rivaroxaban, apixaban, and dabigatran, respectively. Whereas reports that described hemorrhagic stroke included, 3016 (2.2%), 1346 (1.1%), and 1256 (1.8%) for rivaroxaban, apixaban and dabigatran. Significant disproportionality signal was identified for ischemic stroke in dabigatran AF patients, (adjROR 3.10; 95%CI, 2.94-3.28). Rivaroxaban demonstrated the lowest adjROR for ischemic stroke when compared to apixaban and dabigatran, (adjROR 0.38; 95%CI, 0.36-0.41). A reciprocal image was noticed for hemorrhagic stroke with a higher reporting odds ratio for rivaroxaban (adjROR 1.46; 95%CI, 1.38-1.55) and a lower reporting odds ratio for dabigatran (adjROR 0.75; 95%CI 0.70-0.78). With regards to the DOAC-levetiracetam-ischemic stroke triplet; rivaroxaban, apixaban and dabigatran illustrated a significant signal in the regression and shrinkage analysis models. The exp(B) 95%CI for the interaction was highest with dabigatran, (exp(B) 3.92; 95%CI, 3.08-3.98). Conclusions In this large post-marketing study to date, the authors identified an interaction resulting in decreased effectiveness between levetiracetam and the DOACs. The greatest strength of association was found to be with dabigatran, supporting a P-glycoprotein induction mechanism. The interaction does not seem to influence the risk of hemorrhagic stroke. In line with current studies, ischemic stroke was lowest for rivaroxaban compared to dabigatran and apixaban on account of a higher risk for hemorrhagic stroke. Dabigatran demonstrated significantly lower reporting on hemorrhagic stroke but on account of a higher risk of ischemic stroke. We highly recommend pharmacodynamic monitoring, either anti-Xa for apixaban and rivaroxaban or plasma diluted thrombin time for dabigatran while concomitantly prescribing anticonvulsants with the DOACs.ResultsSensitivity Analysis

Lower-adherence direct oral anticoagulant use is associated with increased risk of thromboembolic events than warfarin.

Real-world data have suggested inconsistent adherence to oral anticoagulation for thromboembolic event (TE) prevention in patients with Non valvular atrial fibrillation (NVAF), yet it remains unclear if event risk is elevated during gaps of non-adherence. To compare difference in outcomes between direct oral anticoagulant (DOAC) and warfarin based on adherence to the therapy in patients with NVAF. Using the MarketScan claims data, patients receiving prescription of warfarin or a DOAC for NVAF from January 2015 to June 2016 were included. Outcomes included hospitalization for TE (ischemic stroke or systemic embolism), hemorrhagic stroke, stroke of any kind, and major bleeding. Event rates were reported for warfarin and DOACs at a higher-adherence proportion of days covered (PDC > 80%) and lower-adherence (PDC 40-80%). The cohort included 83,168 patients prescribed warfarin (51% [n = 42,639]) or DOAC (49% [n = 40,529]). Lower adherence occurred in 36% (n = 15,330) of patients prescribed warfarin and 26% (n = 10,956) prescribed DOAC. As compared to higher-adherence warfarin after multivariable adjustment, the risk of TE was highest in lower-adherence DOAC (HR 1.26; 95% CI, 1.14-1.33), and lowest in higher-adherence DOAC (HR, 0.93; 95% CI, 0.88-0.99). There was a significantly higher risk of hemorrhagic stroke and stroke of any kind in the lower-adherence groups. Major bleeding was more common with lower-adherence DOAC (HR, 1.43, 95% CI, 1.35-1.52) and lower-adherence warfarin (HR, 1.32, 95% CI, 1.26-1.39). In this large real-world study, low adherence DOAC was associated with higher risk of TE events as compared to high and low adherence warfarin.

Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations.

Cerebral cavernous malformations (CCMs) are abnormally dilated intracranial capillaries that form cerebrovascular lesions with a high risk of hemorrhagic stroke. Recently, several somatic "activating" gain-of-function (GOF) point mutations in PIK3CA (phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit p110α) were discovered as a dominant mutation in the lesions of sporadic forms of cerebral cavernous malformation (sCCM), raising the possibility that CCMs, like other types of vascular malformations, fall in the PIK3CA-related overgrowth spectrum (PROS). However, this possibility has been challenged with different interpretations. In this review, we will continue our efforts to expound the phenomenon of the coexistence of gain-of-function (GOF) point mutations in the PIK3CA gene and loss-of-function (LOF) mutations in CCM genes in the CCM lesions of sCCM and try to delineate the relationship between mutagenic events with CCM lesions in a temporospatial manner. Since GOF PIK3CA point mutations have been well studied in reproductive cancers, especially breast cancer as a driver oncogene, we will perform a comparative meta-analysis for GOF PIK3CA point mutations in an attempt to demonstrate the genetic similarities shared by both cancers and vascular anomalies.

ALDH2 rs671 Polymorphism Likely a Risk Factor for Hemorrhagic Stroke: A Hospital-Based Study.

Hypertension is the main risk factor for hemorrhagic stroke. Aldehyde dehydrogenase 2 (ALDH2) may inhibit the occurrence of hypertension by anti-oxidative stress and vascular dilation. The purpose was to investigate the relationship of ALDH2 polymorphisms with hemorrhagic stroke in Hakka Chinese. A total of 329 patients with hemorrhagic stroke and 515 controls were enrolled, and medical records (smoking and drinking history, hypertension, and diabetes) were collected. The genotypes of ALDH2 rs671 of the two groups were detected and analyzed. The proportion of the ALDH2 rs671 G/G, G/A, and A/A genotype in patients with hemorrhagic stroke was 55.9%, 37.4%, and 6.7%, respectively, while those were 65.0%, 30.7%, and 4.3% in controls, respectively. There was statistically significant difference in ALDH2 rs671 genotypes distribution (P=0.021) and alleles distribution (P=0.005) between patients and controls. Among hemorrhagic stroke patients, no statistically significant differences were observed between patients with ALDH2 different genotypes. Logistic regression analysis showed that there was significantly high risk of hemorrhagic stroke in men (male vs female: adjusted OR 1.711, 95% CI 1.154-2.538, P=0.008), the presence of hypertension (with vs without hypertension: adjusted OR 16.095, 95% CI 10.958-23.641, P<0.001), and the presence of ALDH2 rs671 G/A genotype (G/A vs G/G: adjusted OR 1.679, 95% CI 1.151-2.450, P=0.007) or A/A genotype (A/A vs G/G: adjusted OR 2.516, 95% CI 1.132-5.591, P=0.024). ALDH2 rs671 polymorphism likely a risk factor for hemorrhagic stroke.

Association of serum uric acid to lymphocyte ratio, a novel inflammatory biomarker, with risk of stroke: A prospective cohort study.

Inflammation plays an important role in the pathological progress associated with stroke. Serum uric acid (SUA) to lymphocyte ratio (ULR), a novel inflammatory biomarker, has been considered as a better risk stratification tool of adverse outcomes than SUA or lymphocyte alone. This study aimed to investigate whether ULR produced more predictive value for stroke and explore the potential mediators of the associations. This study enrolled 93,023 Chinese participants without stroke and myocardial infarction at baseline. Cox proportional hazard models were used to analyze the associations of ULR with stroke and subtypes. Mediation analyses were conducted to explore potential mediators of the associations. During a median follow-up of 13.00 years, 6081 cases of incident stroke occurred, including 5048 cases of ischemic stroke (IS) and 900 cases of hemorrhagic stroke (HS). After adjustment for confounders, the Q4 group was associated with a higher risk of HS (HR, 1.25; 95% CI, 1.03-1.50), but not with total stroke (HR, 1.07; 95% CI, 1.03-1.13) or IS (HR, 1.04; 95% CI, 0.97-1.12). No significant associations were found between SUA or lymphocyte and any stroke. ULR outperformed SUA or lymphocytes alone in predicting stroke. Additionally, the significant association between ULR and HS was partially mediated by systolic blood pressure (20.32%), diastolic blood pressure (11.18%) and estimated glomerular filtration rate (9.19%). ULR was significantly associated with the risk of HS, but not with IS. Systolic blood pressure, diastolic blood pressure and estimated glomerular filtration rate were potential mediators for the association.

Clinical significance of “periventricular collateral enhancement sign” in symptomatic moyamoya disease: A vessel wall imaging study

BackgroundPeriventricular collaterals are associated with high risk of hemorrhagic stroke in adult moyamoya disease (MMD). However, the clinical significance of the periventricular collateral enhancement sign (PCES), which indicates wall enhancement of periventricular collaterals on contrast-enhanced vessel wall imaging (VWI), has yet to be determined. MethodsThirty-seven patients with MMD with acute neurological symptoms were consecutively recruited. Periventricular collaterals including lenticulostriatal artery, thalamic artery, and choroidal artery collaterals were evaluated on digital subtraction angiography, and then PCES was detected on pre- and postcontrast VWI. First, the association between PCES and hemorrhagic presentation was evaluated using multivariate analyses. Second, two raters investigated the culprit vessels responsible for bleeding in hemorrhagic MMD using the Cohen kappa statistic. ResultsFifteen sites of PCES on postcontrast VWI were observed in 15 patients. Multivariate analysis revealed that hemorrhagic presentation was the only independent factor for PCES (OR = 37.3, 95%CI = 3.9–113, p =.002). In patients with hemorrhagic presentation (n = 20), the identification rate of the ruptured vessel was 80% by rater 1, with excellent agreement. (inter-rater, κ = 0.86, 95%CI = 0.59–1.00; intra-rater, κ = 0.83, 95%CI = 0.50–1.00). Choroidal (50%) and thalamic artery collaterals (15%) were the most common and the second most common types of culprit vessels. Inter-rater and intra-rater reliabilities for the classification of culprit vessels were also excellent (intra-rater, κ = 0.86, 95%CI = 0.67–1.00; inter-rater, κ = 0.93, 95%CI = 0.79–1). ConclusionAcute hemorrhagic stroke in MMD is independently associated with PCES on postcontrast VWI. PCES can help to detect the culprit vessels that are responsible for hemorrhage in patients with MMD.

Menopausal hormone therapy with conjugated equine estrogen is associated with a higher risk of hemorrhagic stroke than therapy with estradiol: a retrospective population-based cohort study

BackgroundSeveral studies have shown that menopausal hormone therapy (MHT) reduces the risk of hemorrhagic stroke (HS), but there are no studies comparing the effect of different estrogen types (conjugated equine estrogen [CEE] and estradiol [E2]). MethodsThis retrospective cohort study included menopausal women aged 40–65 years diagnosed between 2000 and 2016 who received MHT with oral CEE or E2 and were registered in Taiwan's National Health Insurance Research Database. The primary outcome was HS. Propensity score matching with menopausal age and comorbidities was performed. Cox proportional hazard regression models were used to calculate the incidence and hazard ratios (HRs) of HS. ResultsA total of 14,586 pairs of women were included. The mean menopausal ages of the CEE and E2 groups were 50.45 ± 5.31 and 50.31 ± 4.99 years, respectively. After adjusting for age and comorbidities, the incidence of HS was 1.23-fold higher in women treated with CEE than in those treated with E2 (8.04 vs. 6.49/10,000 person-years), with an adjusted HR of 1.50 (95 % confidence interval [CI] 1.04–2.17). MHT with CEE initiated within 5 years of menopause was associated with a higher risk of HS than MHT with E2 (HR = 1.47, 95 % CI: 1.01–2.14). ConclusionsIn postmenopausal Taiwanese women, MHT with CEE was associated with an increased risk of HS compared to MHT with E2, a risk that women using CEE should discuss with their clinicians. Further large-scale investigations of this population are warranted.

Sex-Based Differences in Clinical Outcomes of Stroke Related to LVAD

<h3>Purpose</h3> Sex-based differences among patients with left ventricular assist devices (LVAD) having stroke are uncertain. We aimed to compare demographic and clinical characteristics, inpatient outcomes, and measures of health care utilization among men and women who had stroke while undergoing LVAD implantation. <h3>Methods</h3> We analyzed the National Inpatient Sample from 2009 and 2019) to identify patients with stroke while on LVAD utilizing ICD Codes. The data were weighted to reflect national estimates. Outcomes of interest include inpatient mortality, clinical complications, length of stay (LOS), and inflation-adjusted care costs among men vs. women. <h3>Results</h3> A total of 2192 hospitalizations (556 females and 1636 males) were included in this analysis. Most strokes occurred in men vs. women (75% vs. 25%). Women patients were younger (51 y vs. 59 yr); Black women had a higher likelihood of stroke than Black men (32.4% vs. 15.6%). Men had a higher burden of cardiometabolic comorbidities (hypertension, diabetes, ischemic heart disease) than women. While there were no significant differences regarding ischemic stroke, women had higher odds of hemorrhagic stroke than men (1.49 [CI: 1.02-2.18]). Between 2010 and 2019, stroke rates have significantly increased among men, while the trend remained stable in women (<b>Figure</b>). There was no significant difference in all-cause mortality or clinical complications (cardiac arrest, invasive mechanical ventilation, pressors, dialysis). <h3>Conclusion</h3> In this national analysis, men had a higher comorbidity burden, translating into worsening stroke trends over the last 10 years than women with LVAD and stroke. In contrast, women were younger, exhibited racial disparities, and had a higher risk of hemorrhagic stroke. A deeper understanding of factors influencing sex-related outcomes may explain diverging trends among men and women.

Intensive or standard blood pressure control in patients with a history of ischemic stroke: RESPECT post hoc analysis.

The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study and its pooled analysis showed that intensive blood pressure (BP) lowering reduced recurrent stroke risk by 22% in patients with a history of stroke. Here, we report the effect of intensive BP lowering on the risk of recurrent stroke subtypes in patients with a history of ischemic stroke. RESPECT was a randomized clinical trial among 1280 people with a history of cerebral infarction or intracerebral hemorrhage. Participants were assigned to the intensive blood pressure control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg). In this post hoc analysis, we analyzed 1074 patients with a history of cerebral infarction. The mean BP at baseline was 140.7/81.4 mmHg. Throughout the follow-up period, the mean BP was 133.4/77.5 (95% CI, 132.7-134.1/76.9-78.2) mmHg in the standard group and 126.7/74.1 (95% CI, 126.0-127.4/73.5-74.8) mmHg in the intensive group. During a mean follow-up of 3.9 years, 78 first recurrent strokes occurred. Intensive treatment tended to reduce overall annual stroke recurrence (1.74% in intensive vs. 2.17% in standard; P = 0.351 by log-rank test) and did not change the risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999) but markedly reduced the risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effects of intensive BP control were observed for the risk of hemorrhagic stroke in patients with a history of ischemic stroke. The findings of this study indicate the benefit of intensive BP control for patients with a history of ischemic stroke at high risk of hemorrhagic stroke.

Abstract 153: Long-Term Risk Of Stroke After Posterior Reversible Encephalopathy Syndrome

Introduction: Posterior reversible encephalopathy syndrome (PRES) can cause brain infarction and hemorrhage in the acute phase. We hypothesized that PRES is also associated with an increased long-term risk of stroke. Methods: We performed a retrospective cohort study using statewide all-payer claims data from 2016-2018 for all admissions to nonfederal hospitals in 11 states. Adult patients with PRES were compared to patients with TIA (positive control) and renal colic (negative control), as done in prior studies. The primary outcome was any stroke, and secondary outcomes were ischemic and hemorrhagic stroke. Diagnoses were ascertained using ICD-10-CM codes. We excluded patients with stroke before and during index admissions for PRES and controls. We used Cox proportional hazards analyses to evaluate associations between PRES and stroke, adjusting for demographics, stroke risk factors, and factors associated with PRES (cancer, kidney disease, rheumatological disease). In a sensitivity analysis, stroke events within 4 weeks of index admissions were excluded. Results: We identified 3,086 patients with PRES, 85,189 with TIA, and 3,094 with renal colic. Patients with PRES (55±17 years) and renal colic (54±18 years) were younger than those with TIA (72±14 years). Median follow-up was 1.1 years and similar between groups. Stroke incidence was 3.2 per 100 person-years after PRES, 3.8 per 100 person-years after TIA, and 0.4 per 100 person-years after renal colic (Figure). After adjustment, patients with PRES had a similar stroke risk as patients with TIA (HR, 0.9; 95% CI, 0.8-1.2), and a higher stroke risk than patients with renal colic (HR, 2.6; 95% CI, 2.0-3.5). Compared to TIA, PRES had a higher risk of hemorrhagic stroke (HR, 2.9; 95% CI, 2.2-3.9) and a lower risk of ischemic stroke (HR, 0.7; 95% CI, 0.6-0.9). Results were similar with a 4-week washout period. Conclusions: PRES is associated with an increased risk of future stroke, specifically hemorrhagic stroke.

Association between statin adherence and the risk of stroke among South Korean adults with hyperlipidemia

Background and aimsThe effectiveness of statins commonly used to prevent stroke may depend on adherence to treatment. We examined the association between statin adherence and stroke risk among South Korean adults with hyperlipidemia. Methods and resultsThe data of 128,052 and 129,390 participants with hyperlipidemia for the purpose of studying the risks of ischemic and hemorrhagic stroke, respectively, were collected from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013. Participants were divided into groups according to statin adherence, calculated as the proportion of days covered (PDC; poor, moderate, good). The risk of ischemic and hemorrhagic stroke were analyzed using a Cox proportional hazards model. Individuals with poor PDC exhibited higher risks of ischemic and hemorrhagic stroke than those with good PDC (ischemic stroke: hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 1.03–1.15, hemorrhagic stroke: HR = 1.37, 95% CI = 1.22–1.54). Women with poor PDC were at higher risk of ischemic stroke than those with good PDC (HR = 1.17, 95% CI = 1.09–1.26), while men with poor PDC exhibited a higher risk of hemorrhagic stroke than those with good PDC (HR = 1.55, 95% CI = 1.27–1.90). Individuals with disabilities who had poor PDC were at higher risk of ischemic stroke than those with good PDC (HR = 1.55, 95% CI = 1.24–1.93). ConclusionsWe detected a significant association between statin adherence and ischemic and hemorrhagic stroke risk. Therefore, hyperlipidemia patients should adhere to statin treatment; such interventions are required to reduce the stroke risk.

Risk of stroke with antivenom usage after venomous snakebite in Taiwan: a population-based cohort study.

Stroke is a rare complication of snakebites, but may lead to serious sequelae. We aimed to explore the relationship between venomous snakebite and the risk for acute stroke, in a nationwide population-based cohort study. This retrospective cohort study used claims data between 1 January 2000 and 31 December 2012, from the Taiwan National Health Insurance Research Database. The study included data of patients aged 18 years or older with venomous snakebite (n = 535), matched for propensity score with controls without venomous snakebite (n = 2140). The follow-up period was the duration from the initial diagnosis of venomous snakebite and administration of antivenom to the date of an acute stroke, or until 31 December 2013. The competing risk model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of stroke, ischemic stroke and hemorrhagic stroke, after adjusting for demographic and other possible stroke risk factors. The adjusted HR for the venomous snakebite group compared with the control group was 2.68 for hemorrhagic stroke (95% CI = 1.35-5.33). Stratified analysis showed that the older age group (>65 years old) had a higher risk of hemorrhagic stroke. A 2.72-fold significant increase in the risk for hemorrhagic stroke was observed following venomous snakebite with antivenom usage (95% CI = 1.41-5.26). Venomous snakebite is associated with an increased risk of hemorrhagic stroke after the use of antivenom. Further study of the underlying mechanism is warranted.

Effect of changes in serum uric acid on the risk of stroke and its subtypes

Background and aimsThe role of serum uric acid (SUA) in stroke remains controversial and analyses of changes in SUA and stroke are limited. The objective of the study was to investigate the associations of changes in SUA with stroke and its subtypes (ischemic and hemorrhagic stroke). Methods and resultsA total of 51 441 participants (mean age 52.69 ± 11.71 years) without history of myocardial infarction or stroke were enrolled. Participants were divided into four groups based on SUA level changes during 2006 and 2010: stable low, increasing, decreasing, and stable high. SUA score was quantified on a 3-point scale with 1 point awarded for hyperuricemia at either year 2006, 2008 or 2010. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs). During 7.03-year follow up, 1611 stroke (1410 ischemic stroke, 199 hemorrhagic stroke, and 47 subarachnoid hemorrhage) were identified. Participants with stable high SUA had higher risk of hemorrhagic stroke, the HR was 1.93 (95% CI: 1.06–3.51), compared to those with stable low SUA. Furthermore, cumulative high SUA exposure also increased the risk of hemorrhagic stroke, the HR (95%CI) was 2.99 (1.55–5.74), compared with cumulative low SUA exposure. However, no significant evidence indicated changes in SUA was associated with the risk of total and ischemic stroke, the HRs (95% CIs) were 0.98 (0.74–1.29) and 0.88 (0.65–1.19), respectively. ConclusionsStable high SUA was positively associated with the risk of hemorrhagic stroke, but not with total and ischemic stroke risk.

Formulation of Tablets in Capsule system: Statistical optimization for chronotherapeutic drug delivery of propranolol hydrochloride

Chronic diseases like asthma, hypertension and rheumatoid arthritis requires prompt release of drug as per the disease condition. Conversely, extended release systems can only maintains the drug concentration with in therapeutic range for prolonged period of time, which not be the primary requisite for the foresaid diseases. The early morning surge of blood pressure was reported to be associated with a high risk of hemorrhagic stroke and cardiac death. This can be overcomeby programmed lag time, through designing of chronotherapeutic drug delivery systems (CDDS), that can be beneficial for the delivery of Propranolol hydrochloride at required time. The goal of the present study is to explore and optimize various parameters in designing Tablets in Capsule system (TCS) using response surface methodology to release the medication as per the chronological conditions of the disease. Initially, coating of capsule body was optimized in order to maintain its integrity for more than 12 h. Subsequently, erodible tablet formulation was optimized via a face-centered central composite design. Concentration of guar gum (X1) and total erodible tablet weight (X2) were selected as independent variables and these were studied at five different levels (±1 - factorial points, ± 1.141- axial points and center point −0) to optimize the cumulative drug release at the end of 5 h [CDR (6 h)- Y1] and time taken to release 98% of drug [T 98% - Y2], using Design Expert 11. On basis of Global desirability function (D) criteria, formulation with guar gum concentration of 35.589 mg and total tablet weight of 150 mg can accomplish the prerequisites of optimum formulation and the use of such combination shows, 6.946% of CDR at the end of 5 h and time taken to release 98% of Propranolol hydrochloride was found to be 12 h. Chronotherapeutic system requires of at least 5–6 h of lag time and followed by the complete drug release within 12 h, that matches with the optimized formulation. However, this work should extend to in vivo pharmacokinetic studies to conform the in vitro in vivo correlation.

Comparison of risk of cardiovascular disease related adverse events between selective serotonin reuptake inhibitor users and serotonin norepinephrine reuptake inhibitor users in Korean adult patients with depression: retrospective cohort study.

Serotonin norepinephrine reuptake inhibitor (SNRI) has been increasingly administered, but the associated cardiovascular disease (CVD) related adverse events risk is not clearly understood. So, we conducted a cohort study to identified CVD-related adverse events risk of SNRI comparing to selective serotonin reuptake inhibitor (SSRI). We used Korea Health Insurance Review and Assessment data. During the period from April 2009 to March 2011, patients who were prescribed SSRI or SNRI for depression, who were followed up till March 2018, were the subjects. Hemorrhagic stroke, ischemic stroke, and myocardial infarction were selected as the outcomes. High-dimensional propensity scores were used to adjust the unmeasured confounders. the cox proportional hazard model was used for the statistical analysis. A total of 1,016,136 patients diagnosed with depression over the age of 20 were screened and there were 64,739 SSRI users and 3,711 SNRI users in the group of patients. The adjusted hazard ratio did not differ between the two groups, but the subgroup analysis according to comorbidities showed a high risk of hemorrhagic stroke in SNRI users with hypertension or diabetes mellitus.

Alcohol and risk of non-traumatic bleeding events requiring hospital care in the general population: A prospective cohort study.

Alcohol has a direct effect on blood coagulation and fibrinolysis. We studied how alcohol is related to common bleeding events (e.g., nose bleeding), as well as life-threatening bleeding events (e.g., hemorrhagic stroke) that required hospital care in the general population. We used data from The Copenhagen City Heart Study, 1991 to 1994 and 2001 to 2003. Baseline information on alcohol consumption and potential confounders was obtained by questionnaires, and participants were followed for incident bleeding events with nationwide registers until 2013. Among the 10,259 included participants, we observed 366 nose or other respiratory organ bleeding events, 149 hemorrhagic stroke events, 470 gastrointestinal bleeding events, 266 unspecified bleeding events, and 1088 any-bleeding events (composite endpoint) during follow-up. Compared to drinkers of 1-6 drinks per week, those drinking ≥35 drinks per week had a higher risk of hemorrhagic stroke [hazard ratio, 2.27 (1.14-4.55)] and non-variceal gastrointestinal bleeding [hazard ratio 2.04 (1.37-3.05)], whereas non-drinkers and drinkers of 7-13, 14-20, 21-27, and 28-34 drinks per week had not. Alcohol consumption was not associated with risk of nose or other respiratory organ bleeding or unspecified bleeding. For non-drinkers and drinkers of 7-13, 14-20, 21-27, 28-34, and 35 or more drinks per week, hazard ratios for the composite endpoint of any bleeding were 1.17 (95% CI: 0.99-1.37), 0.97 (95% CI: 0.81-1.15), 1.00 (95% CI: 0.80-1.26), 0.93 (95% CI: 0.69-1.25), 1.39 (95% CI: 1.00-1.94), and 1.83 (95% CI: 1.39-2.41) compared to drinkers of 1-6 drinks per week. In conclusion, drinking 35 or more drinks per week may be associated with a higher risk of hemorrhagic stroke and non-variceal gastrointestinal bleeding in the general population.