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  • 1.
    Johansson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Risk markers and incidence of atrial fibrillation in northern Sweden2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Atrial fibrillation (AF) is the most common clinically significant arrythmia with a prevalence of approximately 3% in the general population. Less is known about the incidence of AF. In order to reduce the incidence of AF, it is of essence to identify modifiable risk factors for the disease.

    Aims: The aims of this thesis were (1) to estimate the incidence of AF and to assess the prevalence of provoking factors and risk factors for stroke and systemic embolism at the time of AF diagnosis, (2) to study the association between alcohol consumption and risk of AF, (3) to study the association between weight, height, weight change, and risk of AF, and (4) to study the association between normal or high normal blood pressure (BP), compared to optimal BP, and risk of AF.

    Methods: To determine the incidence of AF and the prevalence of provoking factors and risk factors for stroke and systemic embolism at AF diagnosis, an observational study was performed between January 1, 2011, and December 31, 2012, in the municipalities of Skellefteå and Norsjö, Västerbotten, Sweden. Diagnosis registries were searched for cases of incident AF. All AF diagnoses were verified by electrocardiogram. Data regarding provoking factors, type of AF and presence of risk factors for stroke and systemic embolism (as assessed by the CHA2DS2-VASc score) was obtained from medical records. Incidence was calculated by dividing the number of incident AF cases by the time at risk for the population.

    The association between alcohol consumption, weight, height, weight change, normal BP, high normal BP, and risk of AF was investigated in a population-based cohort study of participants of the Västerbotten Intervention Programme (VIP). Residents of Västerbotten County aged 30, 40, 50 and 60 years who had participated in the VIP health examinations between January 1, 1988, and September 5, 2014, were included. Individuals who had been diagnosed with AF before participating in the VIP were excluded. Study participants were followed until a diagnosis of AF, death, migration from the study area, or the end of the study on September 5, 2014. Incident AF cases were identified using the Swedish National Patient Registry. The health examinations included measurements of height and weight, systolic BP, diastolic BP, fasting glucose, oral glucose tolerance, and cholesterol. 

    Participants also answered a questionnaire addressing any history of diabetes and myocardial infarction, alcohol use, education level, smoking habits, medications, and physical activity. Optimal BP was defined as BP < 120/80 mm Hg. Normal BP was defined as BP 120–129/80–84 mm Hg. High normal BP was defined as BP 130–139/85–89 mm Hg. Hypertension was defined as BP ≥ 140/90 mm Hg. Cox proportional hazards regression analysis was used to assess the associations between alcohol consumption, weight, height, weight change, normal BP, high normal BP, and risk of AF. These were performed with crude, age-adjusted, and multivariable models adjusted for other cardiovascular risk factors (age, sex, body mass index, hypertension, cholesterol, previous myocardial infarction, diabetes, problem drinking, smoking, education level, and leisure-time physical activity).

    Results: The incidence of AF was 4.0 cases of AF per 1000 person-years. In approximately one fifth of participants, a provoking factor was present at the first episode of AF. The CHA2DS2-VASc score was 2 or higher in 81% of participants. Permanent AF was the most common type of AF and was seen in about one third of the participants.

    When studying the association between alcohol consumption and risk of AF, 109,230 health examination participants were included in the study cohort and were followed for 1,484,547 person-years. During the study period, 5230 participants developed incident AF. Men with alcohol consumption in the highest quartile (≥ 4.83 standard drinks weekly) had a hazard ratio (HR) of 1.21 (95% confidence interval [CI] 1.09-1.34) for AF in a multivariable model when compared to men with an alcohol consumption in the lowest quartile (< 0.90 standard drinks weekly). In men, problem drinking was also associated with an increased risk of AF (HR 1.24, 95% CI 1.10–1.39 in a multivariable model). Among women, no significant association between alcohol consumption, problem drinking, and risk of AF was identified.

    In a fully adjusted model, height, weight, body mass index, and body surface area were positively associated with risk of incident AF. Among participants who underwent two health examinations 10 years apart, 1142 persons developed AF. The mean weight change from baseline was a weight gain of 4.8%. There was no significant association between either weight gain or weight loss and risk of AF.

    In the study of the association between normal BP, high normal BP, and risk of AF, 109,697 persons with a total of 162,982 health examinations were included. Incident AF was diagnosed in 5260 participants. There was an increased risk of incident AF in persons with normal BP (HR 1.11, 95% CI 1.01–1.27) and in persons with high normal BP (HR 1.23, 95% CI 1.10–1.38) compared to optimal BP in a multivariable model. Systolic BP and diastolic BP were associated with risk of incident AF, with HRs of 1.11 (95% CI 1.10–1.13) and 1.13 (95% CI 1.09–1.16) per 10 mmHg, respectively, in multivariable models. A restricted cubic spline analysis indicated a gradually increasing risk of AF with increasing systolic BP and diastolic BP.

    Conclusions: AF has an incidence of 4.0 per 1000 person-years. Alcohol consumption and problem drinking were associated with higher risk of AF in men, but not in women. Weight, height, body mass index, and body surface area were associated with increased risk of incident AF. Normal BP and high normal BP, when compared to optimal BP, were associated with increased risk of incident AF.

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  • 2.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Dahlqvist, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Incidence, type of atrial fibrillation and risk factors for stroke: a population-based cohort study2017In: Clinical Epidemiology, E-ISSN 1179-1349, Vol. 9, p. 53-62Article in journal (Refereed)
    Abstract [en]

    Purpose: The aims of this study were to estimate the incidence of atrial fibrillation and atrial flutter (AF), to assess the presence of provoking factors and risk factors for stroke and systemic embolism, and to determine the type of AF in patients with first-diagnosed AF. Patients and methods: This cohort study was performed in northern Sweden between January 1, 2011 and December 31, 2012. Diagnosis registries were searched for the International Classification of Diseases-10 code for AF (I48) to identify cases of incident AF. All AF diagnoses were electrocardiogram-verified. Data pertaining to provoking factors, type of AF and presence of risk factors for stroke and systemic embolism according to the CHA(2)DS(2)-VASc score were obtained from medical records. Results: The incidence of AF in the entire population was 4.0 per 1,000 person-years. The incidence was 27.5 per 1,000 person-years in patients aged >= 80 years. A total of 21% of all patients had a provoking factor in association with the first-diagnosed episode of AF. The CHA(2)DS(2)-VASc score was 2 or higher in 81% of the patients. Permanent AF was the most common type of AF (29%). Conclusion: There was a considerable increase in the incidence of AF with age, and a provoking factor was found in one-fifth. The most common type of AF was permanent AF. Four in five patients had a CHA(2)DS(2)-VASc score of 2 or more.

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  • 3.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Andersson, Jonas
    Lind, Marcus M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Normal blood pressure, high normal blood pressure, and risk of incident atrial fibrillation: a population-based cohort studyManuscript (preprint) (Other academic)
  • 4.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Weight, height, weight change, and risk of incident atrial fibrillation in middle-aged men and women2020In: Journal of Arrhythmia, ISSN 1880-4276, Vol. 36, no 6, p. 974-981Article in journal (Refereed)
    Abstract [en]

    Background: Anthropometric factors are reported to be risk factors for atrial fibrillation (AF), but it is unclear whether weight change in mid‐life is associated with AF. We aimed to study the possible associations of weight, height, and weight change with the risk of incident AF in men and women.

    Methods: Our study cohort included 108 417 persons (51% women) who participated in a population‐based health examination in northern Sweden at 30, 40, 50, or 60 years of age. The health examination included weight and height measurement and collection of data regarding cardiovascular risk factors. Within this cohort, 40 275 participants underwent two health examinations with a 10‐year interval. We identified cases with a first‐ever diagnosis of AF through the Swedish National Patient Registry.

    Results: During a total follow‐up of 1 469 820 person‐years, 5154 participants developed incident AF. The mean age at inclusion was 46.3 years, and mean age at AF diagnosis was 66.6 years. After adjustment for potential confounders, height, weight, body mass index (BMI), and body surface area (BSA) were positively associated with risk of incident AF in both men and women. Among participants who underwent two health examinations 10 years apart, 1142 persons developed AF. The mean weight change from baseline was a gain of 4.8%. Weight gain or weight loss was not significantly associated with risk of incident AF.

    Conclusions: Height, weight, BMI, and BSA showed positive associations with risk of incident AF in both men and women. Midlife weight change was not significantly associated with AF risk.

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  • 5.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Alcohol consumption and risk of incident atrial fibrillation: a population-based cohort study2020In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 76, p. 50-57Article in journal (Refereed)
    Abstract [en]

    AIMS: Atrial fibrillation (AF) is a common tachyarrhythmia. High alcohol consumption is associated with increased AF risk. It remains unclear whether lower levels of alcohol consumption are also associated with AF risk, and whether the association differs between men and women. In this study, we investigated the association between low to moderate levels of alcohol consumption and AF risk in men and women.

    METHODS: We performed a population-based cohort study of 109,230 health examination participants in northern Sweden. Data regarding alcohol intake were obtained using a questionnaire administered at the health examination. Incident AF cases were identified from the Swedish National Patient Registry.

    RESULTS: AF was diagnosed in 5,230 individuals during a total follow-up of 1,484,547 person-years. Among men, AF risk increased over quartiles of weekly alcohol consumption (P for trend 0.001). Men with alcohol consumption in the highest quartile (≥4.83 standard drinks [each drink containing 12 gs of ethanol] per week; SDW) had a HR of 1.21 (95% CI 1.09-1.34) for AF compared to men in the lowest quartile (<0.90 SDW). In men, problem drinking was also associated with an increased AF risk (HR: 1.24; 95% CI: 1.10-1.39). Among women, AF risk was not significantly associated with alcohol consumption (P for trend 0.09 for decreasing risk of AF over quartiles of weekly alcohol consumption) or problem drinking (HR: 1.00; 95% CI 0.70-1.42).

    CONCLUSION: Self-reported alcohol consumption and problem drinking were associated with an increased risk of AF among men, but not in women.

  • 6.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Örtendahl, Lina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lind, Marcus M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Brunström, Mattias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Diabetes, prediabetes, and atrial fibrillation: a population-based cohort study based on national and regional registers2023In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 294, no 5, p. 605-615Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this increase in AF risk is independent of other risk factors for AF.

    Objective: To investigate the association between diabetes and different prediabetic states, as independent risk factors for the onset of AF.

    Methods: We performed a population-based cohort study in Northern Sweden, including data on fasting plasma glucose, oral glucose tolerance test, major cardiovascular risk factors, medical history, and lifestyle factors. Participants were divided into six groups depending on glycemic status and followed through national registers for AF diagnosis. Cox proportional hazard model was used to assess the association between glycemic status and AF, using normoglycemia as reference.

    Results: The cohort consisted of 88,889 participants who underwent a total of 139,661 health examinations. In the model adjusted for age and sex, there was a significant association between glycemic status and development of AF in all groups except the impaired glucose tolerance group, with the strongest association for the group with known diabetes (p-value <0.001). In a model adjusted for sex, age, systolic blood pressure, body mass index, antihypertensive drugs, cholesterol, alcohol, smoking, education level, marital status, and physical activity, there was no significant association between glycemic status and AF.

    Conclusions/interpretation: The association between glycemic status and AF disappears upon adjustment for potential confounders. Diabetes and prediabetes do not appear to be independent risk factors for AF.

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  • 7.
    Tschiderer, Lena
    et al.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Institute of Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
    Peters, Sanne A. E.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; The George Institute for Global Health, School of Public Health, Imperial College London, London, United Kingdom; The George Institute for Global Health, University of New South Wales, NSW, Sydney, Australia.
    van der Schouw, Yvonne T.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
    van Westing, Anniek C.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Division of Human Nutrition and Health, Wageningen University, Wageningen, Netherlands.
    Tong, Tammy Y. N.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Willeit, Peter
    Institute of Health Economics, Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Seekircher, Lisa
    Institute of Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
    Moreno-Iribas, Conchi
    Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Huerta, José María
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council-IMIB, Murcia, Spain.
    Crous-Bou, Marta
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)– Bellvitge Biomedical Research Institute, (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States.
    Söderholm, Martin
    Department of Neurology, Skåne University Hospital, Malmö, Lund and Malmö, Sweden; Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Johansson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Själander, Sara
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Heath, Alicia K.
    SwedenDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Macciotta, Alessandra
    Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Ibsen, Daniel B.
    Department of Public Health, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus, Denmark; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark.
    Pala, Valeria
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    Mellemkjær, Lene
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Burgess, Stephen
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom; MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
    Wood, Angela
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, Germany.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, Germany.
    Amiano, Pilar
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastian, Spain.
    Rodriguez-Barranco, Miguel
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.
    Engström, Gunnar
    Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, Section of Environmental Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Halkjær, Jytte
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Panico, Salvatore
    School of Medicine, Federico II University, Naples, Italy.
    Danesh, John
    BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge, United Kingdom; The National Institute for Health and Care Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom; Human Genetics, Wellcome Sanger Institute, Saffron Walden, United Kingdom; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, United Kingdom; British Heart Foundation Centre of Research Excellence, Division of Cardiovascular Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom.
    Butterworth, Adam
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, United Kingdom; NIHR Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, United Kingdom; BHF Centre of Research Excellence, School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom.
    Onland-Moret, N. Charlotte
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
    Age at menopause and the risk of stroke: observational and mendelian randomization analysis in 204 244 postmenopausal women2023In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, E-ISSN 2047-9980, Vol. 12, no 18, article id e030280Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear.

    METHODS AND RESULTS: We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8–13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07–1.12) for stroke, 1.09 (95% CI, 1.06–1.13) for ischemic stroke, 1.10 (95% CI, 1.04–1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08–1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84–1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke.

    CONCLUSIONS: In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.

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