scholarly journals Age at Menopause and Risk of Ischemic and Hemorrhagic Stroke

Stroke ◽  
2021 ◽  
Author(s):  
Sabrina J.G.C. Welten ◽  
N. Charlotte Onland-Moret ◽  
Jolanda M.A. Boer ◽  
W.M. Monique Verschuren ◽  
Yvonne T. van der Schouw

Background and Purpose: 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. Methods: 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. Results: 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]). Conclusions: 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.

Stroke ◽  
2021 ◽  
Author(s):  
Romit Bhattacharya ◽  
Seyedeh M. Zekavat ◽  
Jeffrey Haessler ◽  
Myriam Fornage ◽  
Laura Raffield ◽  
...  

Background and Purpose: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease–related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke. Methods: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes ( DNMT3A , TET2 , and ASXL1 ) with any stroke, ischemic stroke, and hemorrhagic stroke. Results: CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03–1.27]; P =0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 [95% CI, 1.01–1.51]; P =0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke. Conclusions: CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed.


2016 ◽  
Vol 47 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Wesley T. O'Neal ◽  
Hooman Kamel ◽  
Dawn Kleindorfer ◽  
Suzanne E. Judd ◽  
George Howard ◽  
...  

Background: It is currently unknown if premature atrial contractions (PACs) detected on the routine screening electrocardiogram are associated with an increased risk of ischemic stroke. Methods: We examined the association between PACs and ischemic stroke in 22,975 (mean age 64 ± 9.2; 56% women; 40% black) participants from the Reasons for Geographic and Racial Differences in Stroke study. Participants who were free of stroke at baseline were included. PACs were detected from centrally read electrocardiograms at baseline. Cox regression was used to examine the association between PACs and ischemic stroke events through March 31, 2014. Results: PACs were present in 1,687 (7.3%) participants at baseline. In a Cox regression model adjusted for stroke risk factors and potential confounders, PACs were associated with an increased risk of ischemic stroke (hazards ratio (HR) 1.34, 95% CI 1.04-1.74). The relationship was limited to non-lacunar infarcts (HR 1.42, 95% CI 1.08-1.87), and not lacunar strokes (HR 1.01, 95% CI 0.51-2.03). An interaction by sex was detected, with the association between PACs and ischemic stroke being stronger among women (HR 1.82, 95% CI 1.29-2.56) than men (HR 1.03, 95% CI 0.69-1.52; p-interaction = 0.0095). Conclusion: PACs detected on the routine electrocardiogram are associated with an increased risk for non-lacunar ischemic strokes, especially in women.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2343
Author(s):  
Masahiro Shiozawa ◽  
Hidehiro Kaneko ◽  
Hidetaka Itoh ◽  
Kojiro Morita ◽  
Akira Okada ◽  
...  

Data on the association between body mass index (BMI) and stroke are scarce. We aimed to examine the association between BMI and incident stroke (ischemic or hemorrhagic) and to clarify the relationship between underweight, overweight, and obesity and stroke risk stratified by sex. We analyzed the JMDC Claims Database between January 2005 and April 2020 including 2,740,778 healthy individuals (Median (interquartile) age, 45 (38–53) years; 56.2% men; median (interquartile) BMI, 22.3 (20.2–24.8) kg/m2). None of the participants had a history of cardiovascular disease. Each participant was categorized as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5–24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2), or obese (BMI ≥ 30 kg/m2). We investigated the association of BMI with incidence stroke in men and women using the Cox regression model. We used restricted cubic spline (RCS) functions to identify the association of BMI as a continuous parameter with incident stroke. The incidence (95% confidence interval) of total stroke, ischemic stroke, and hemorrhagic stroke was 32.5 (32.0–32.9), 28.1 (27.6–28.5), and 5.5 (5.3–5.7) per 10,000 person-years in men, whereas 25.7 (25.1–26.2), 22.5 (22.0–23.0), and 4.0 (3.8–4.2) per 10,000 person-years in women, respectively. Multivariable Cox regression analysis showed that overweight and obesity were associated with a higher incidence of total and ischemic stroke in both men and women. Underweight, overweight, and obesity were associated with a higher hemorrhagic stroke incidence in men, but not in women. Restricted cubic spline showed that the risk of ischemic stroke increased in a BMI dose-dependent manner in both men and women, whereas there was a U-shaped relationship between BMI and the hemorrhagic stroke risk in men. In conclusion, overweight and obesity were associated with a greater incidence of stroke and ischemic stroke in both men and women. Furthermore, underweight, overweight, and obesity were associated with a higher hemorrhagic stroke risk in men. Our results would help in the risk stratification of future stroke based on BMI.


Stroke ◽  
2020 ◽  
Vol 51 (4) ◽  
pp. 1100-1106
Author(s):  
Mitsuaki Sawano ◽  
Ya Yuan ◽  
Shun Kohsaka ◽  
Taku Inohara ◽  
Takeki Suzuki ◽  
...  

Background and Purpose— In previous studies, isolated nonspecific ST-segment and T-wave abnormalities (NSSTTAs), a common finding on ECGs, were associated with greater risk for incident coronary artery disease. Their association with incident stroke remains unclear. Methods— The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a population-based, longitudinal study of 30 239 white and black adults enrolled from 2003 to 2007 in the United States. NSSTTAs were defined from baseline ECG using the standards of Minnesota ECG Classification (Minnesota codes 4-3, 4-4, 5-3, or 5-4). Participants with prior stroke, coronary heart disease, and major and minor ECG abnormalities other than NSSTTAs were excluded from analysis. Multivariable Cox proportional hazards regression was used to examine calculate hazard ratios of incident ischemic stroke by presence of baseline NSSTTAs. Results— Among 14 077 participants, 3111 (22.1%) had NSSTTAs at baseline. With a median of 9.6 years follow-up, 106 (3.4%) with NSSTTAs had ischemic stroke compared with 258 (2.4%) without NSSTTAs. The age-adjusted incidence rates (per 1000 person-years) of stroke were 2.93 in those with NSSTTAs and 2.19 in those without them. Adjusting for baseline age, sex, race, geographic location, and education level, isolated NSSTTAs were associated with a 32% higher risk of ischemic stroke (hazard ratio, 1.32 [95% CI, 1.05–1.67]). With additional adjustment for stroke risk factors, the risk of stroke was increased 27% (hazard ratio, 1.27 [95% CI, 1.00–1.62]) and did not differ by age, race, or sex. Conclusions— Presence of NSSTTAs in persons with an otherwise normal ECG was associated with a 27% increased risk of future ischemic stroke.


Neurology ◽  
2019 ◽  
Vol 92 (21) ◽  
pp. e2432-e2443 ◽  
Author(s):  
Joan Martí-Fàbregas ◽  
Santiago Medrano-Martorell ◽  
Elisa Merino ◽  
Luis Prats-Sánchez ◽  
Rebeca Marín ◽  
...  

ObjectiveWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.MethodsPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.ResultsWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).ConclusionPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.ClinicalTrials.gov identifierNCT02238470.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Stephanie Lyden ◽  
Adam De Havenon ◽  
Vivek Reddy

Background: The systemic inflammation and oxidative stress of obstructive lung disease could promote cerebrovascular dysfunction and platelet hyperactivity, thereby increasing stroke risk 1-2 . There have been studies in the literature supporting an increased risk for stroke (ischemic and hemorrhagic) in patients with obstructive lung disease 3-4 . We aim to assess whether this association is confirmed using data collected from the Cardiovascular Health Study (CHS). Methods: This is a secondary analysis of CHS. The primary outcome is ischemic stroke and the secondary outcome is hemorrhagic stroke. The primary predictor is abnormal pulmonary function at the baseline visit, defined as FEV1<80% of predicted. We fit Cox proportional hazards models and adjusted for baseline covariates that were associated with the outcomes, which for ischemic stroke included age, race, smoking, cholesterol, diabetes, hypertension, atrial fibrillation, and history of TIA or myocardial infarction; and for hemorrhagic stroke included age, cholesterol, diabetes, and hypertension. Results: We included 5,438 patients, of whom 880 (16.2%) had ischemic stroke and 142 (2.6%) had hemorrhagic stroke. Mean (SD) days of follow-up was 4,458 (2,499). There were 331/5,438 (6.1%) of patients with abnormal pulmonary function at baseline, who had a higher risk of ischemic stroke (HR 1.36, 95% CI 1.05-1.76, p=0.019) (Figure 1). This remained significant in the adjusted multivariate model (HR 1.43, 95% CI 1.08-1.90, p=0.013). Abnormal pulmonary function was not associated with hemorrhagic stroke risk in either the unadjusted (p=0.635) or adjusted models (p=0.659). Conclusion: Patient’s with a reduced FEV1<80% were found to have an increased risk for ischemic stroke. However, this was not associated with an increased risk for hemorrhagic stroke, suggesting a less robust link between obstructive lung disease and hemorrhagic stroke risk.


2020 ◽  
Vol 35 (8) ◽  
pp. 1933-1943 ◽  
Author(s):  
Dongshan Zhu ◽  
Hsin-Fang Chung ◽  
Annette J Dobson ◽  
Nirmala Pandeya ◽  
Eric J Brunner ◽  
...  

Abstract STUDY QUESTION How does the risk of cardiovascular disease (CVD) vary with type and age of menopause? SUMMARY ANSWER Earlier surgical menopause (e.g. &lt;45 years) poses additional increased risk of incident CVD events, compared to women with natural menopause at the same age, and HRT use reduced the risk of CVD in women with early surgical menopause. WHAT IS KNOWN ALREADY Earlier age at menopause has been linked to an increased risk of CVD mortality and all-cause mortality, but the extent that this risk of CVD varies by type of menopause and the role of postmenopausal HRT use in reducing this risk is unclear. STUDY DESIGN, SIZE, DURATION Pooled individual-level data of 203 767 postmenopausal women from 10 observational studies that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) consortium were included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Postmenopausal women who had reported menopause (type and age of menopause) and information on non-fatal CVD events were included. Type of menopause (natural menopause and surgical menopause) and age at menopause (categorised as &lt;35, 35–39, 40–44, 45–49, 50–54 and ≥55 years) were exposures of interest. Natural menopause was defined as absence of menstruation over a period of 12 months (no hysterectomy and/or oophorectomy) and surgical menopause as removal of both ovaries. The study outcome was the first non-fatal CVD (defined as either incident coronary heart disease (CHD) or stroke) event ascertained from hospital medical records or self-reported. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CI for non-fatal CVD events associated with natural menopause and surgical menopause. MAIN RESULTS AND THE ROLE OF CHANCE Compared with natural menopause, surgical menopause was associated with over 20% higher risk of CVD (HR 1.22, 95% CI 1.16–1.28). After the stratified analysis by age at menopause, a graded relationship for incident CVD was observed with lower age at menopause in both types of natural and surgical menopause. There was also a significant interaction between type of menopause and age at menopause (P &lt; 0.001). Compared with natural menopause at 50–54 years, women with surgical menopause before 35 (2.55, 2.22–2.94) and 35–39 years (1.91, 1.71–2.14) had higher risk of CVD than those with natural menopause (1.59, 1.23–2.05 and 1.51, 1.33–1.72, respectively). Women who experienced surgical menopause at earlier age (&lt;50 years) and took HRT had lower risk of incident CHD than those who were not users of HRT. LIMITATIONS, REASONS FOR CAUTION Self-reported data on type and age of menopause, no information on indication for the surgery (e.g. endometriosis and fibroids) and the exclusion of fatal CVD events may bias our results. WIDER IMPLICATIONS OF THE FINDINGS In clinical practice, women who experienced natural menopause or had surgical menopause at an earlier age need close monitoring and engagement for preventive health measures and early diagnosis of CVD. Our findings also suggested that timing of menopause should be considered as an important factor in risk assessment of CVD for women. The findings on CVD lend some support to the position that elective bilateral oophorectomy (surgical menopause) at hysterectomy for benign diseases should be discouraged based on an increased risk of CVD. STUDY FUNDING/COMPETING INTEREST(S) InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). GDM is supported by Australian National Health and Medical Research Council Principal Research Fellowship (APP1121844). There are no competing interests.


Stroke ◽  
2021 ◽  
Author(s):  
Shadi Yaghi ◽  
Adam de Havenon ◽  
Sara Rostanski ◽  
Alexandra Kvernland ◽  
Brian Mac Grory ◽  
...  

Background and Purpose: Randomized trials demonstrated the benefit of dual antiplatelet therapy in patients with minor ischemic stroke or high-risk transient ischemic attack. We sought to determine whether the presence of carotid stenosis was associated with increased risk of ischemic stroke and whether the addition of clopidogrel to aspirin was associated with more benefit in patients with versus without carotid stenosis. Methods: This is a post-hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) that randomized patients with minor ischemic stroke or high-risk transient ischemic attack within 12 hours from last known normal to receive either clopidogrel plus aspirin or aspirin alone. The primary predictor was the presence of ≥50% stenosis in either cervical internal carotid artery. The primary outcome was ischemic stroke. We built Cox regression models to determine the association between carotid stenosis and ischemic stroke and whether the effect of clopidogrel was modified by ≥50% carotid stenosis. Results: Among 4881 patients enrolled POINT, 3941 patients met the inclusion criteria. In adjusted models, ≥50% carotid stenosis was associated with ischemic stroke risk (hazard ratio, 2.45 [95% CI, 1.68–3.57], P <0.001). The effect of clopidogrel (versus placebo) on ischemic stroke risk was not significantly different in patients with <50% carotid stenosis (adjusted hazard ratio, 0.68 [95% CI, 0.50–0.93], P =0.014) versus those with ≥50% carotid stenosis (adjusted hazard ratio, 0.88 [95% CI, 0.45–1.72], P =0.703), P value for interaction=0.573. Conclusions: The presence of carotid stenosis was associated with increased risk of ischemic stroke during follow-up. The effect of added clopidogrel was not significantly different in patients with versus without carotid stenosis. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03354429.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Oluwaseun Fashanu ◽  
Anas Bizanti ◽  
Ahmad Al-Abdouh ◽  
Di Zhao ◽  
Matthew J Budoff ◽  
...  

Introduction: Stroke is a leading cause of morbidity and mortality in the United States. Identification of individuals at risk for stroke is important for implementation of preventive therapies. Prevalent valvular calcification (VC) has been shown to be associated with stroke but less is known about associations of VC progression with stroke. Methods: Progression (interval increase >0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors. Results: We studied 5,606 multiethnic participants (39.6% White, 26.9% Black, 21.4% Hispanic, 12.2% Chinese) free of baseline CVD enrolled in MESA. Baseline mean ± SD age was 62 ± 10 years; 53% were women; 12% had prevalent AVC and 9% prevalent MAC at the baseline visit; 83% had no progression of VC, 14%, progression at one site (AVC or MAC), and 3% progression at both sites (AVC and MAC) at follow-up. Over a median of 12 years, 214 total and 170 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p>0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratios (95% CI) 1.59 (1.11 - 2.27)] and ischemic stroke [1.64 (1.10 - 2.43)] in the whole cohort (model 3) and after further adjustment for baseline coronary artery calcification (model 4) ( Table ). Results remained significant for total stroke risk after excluding participants with interim atrial fibrillation or coronary heart disease [1.60 (1.01 - 2.54)]. In women, AVC progression was associated with ischemic stroke [1.87 (1.04 - 3.36)] (p-for-interaction=0.03). Conclusion: Progression of MAC over 2.4 years is associated with increased risk of total and ischemic stroke, and in women, AVC progression with higher ischemic stroke risk.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Charles D Nicoli ◽  
Nicholas Wettersten ◽  
George Howard ◽  
Virginia J Howard ◽  
Suzanne E Judd ◽  
...  

Introduction: The neuropeptide neurotensin (NT) has been linked to cardiovascular and metabolic disease risk. Through measurement of its stable equimolar precursor, pro-neurotensin/neuromedin N (pro-NT/NMN), hyperactivity of NT has been associated with aggregate cardiovascular outcomes that include stroke. However, the exclusive association of pro-NT/NMN with incident ischemic or hemorrhagic stroke has not been studied. Hypothesis: Higher serum pro-NT/NMN is associated with incident ischemic and hemorrhagic stroke. Methods: Prospective case-cohort study in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. From 2003-2007, REGARDS enrolled 30,239 White or Black adults aged ≥45. Pro-NT/NMN was measured by immunoassay in 464 ischemic stroke cases, 49 hemorrhagic stroke cases, and 800 non-cases from a random cohort. Cox proportional-hazards models were used to calculate hazard ratios (HR) of stroke by pro-NT/NMN quartiles and per standard deviation (SD) of log pro-NT/NMN. Model 1 (both stroke types) included demographic factors as covariates, Model 2A (ischemic only) added ischemic stroke risk factors, and Model 2B (hemorrhagic only) added hemorrhagic stroke risk factors. Results: The table shows an increased HR of ischemic stroke for those in the 4th vs 1st-quartile pro-NT/NMN in Model 1 with a trend of increased risk across quartiles; this was attenuated in Model 2A. Prebaseline diabetes and coronary artery disease were the largest confounders of ischemic stroke risk, with each accounting for 19% of the association observed in Model 1. There was no association of pro-NT/NMN with hemorrhagic stroke in either model. There were no interactions of race or sex with log pro-NT/NMN. Conclusions: Higher pro-NT/NMN is associated with increased risk of ischemic stroke after adjusting for demographics, but this was not independent of stroke risk factors. No significant association with hemorrhagic stroke was observed; this analysis was limited by a small number of events.


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