AS126 - Stroke risk factors and molecular markers in postmenopausal women

Investigator Names and Contact Information

Sylvia Smoller (Sylvia.Smoller@einsteinmed.edu)

Introduction/Intent

The goal of this research is to determine whether blood-based biomarkers and polymorphisms in candidate genes can be used to characterize individuals at high risk for future stroke. The study will use a population based nested case-control of 1100 stroke cases and 1100 controls to investigate the associations of selected biomarkers, genetic factors, and lifestyle variables, with risk of stroke among participants in the Observational Study component of WHI.

The molecular and genetic markers to be examined in this study are hypothesized to participant in the etiology of stroke through the pathways of inflammation and thromboisis/atherocsclerosis/hemostasis.

Aim 1: Determine whether genetic factors and serologic markers related to inflammation are associated with increased risk of stroke in postmenopausal women.
Aim 2: Compare incident cases of stroke with controls with regard to baseline measures of markers of blood coagulation and fibrinolysis, lipid and glucose metabolism, antioxidants and other blood analytes. Compare allelic frequencies within race group of candidate genes involved in thrombosis/atherosclerosis.
Aim 3: determine the effects of use of exogenous estrogen on risk of stroke and on markers of inflammation and thromboisis/atherocsclerosis/hemostasis.
Aim 4: Determine whether allelic variations in candidate genes involved in hypertension are associated with risk of stroke.
Aim 5: Determine whether the effects on stroke risk of established risk factors and use of specific medications, will be modified in the presence of markers of inflammation and/or thromboisis/atherocsclerosis/hemostasis.

Results/Findings

Some of the publications related to this ancillary study are:

Ms602 - Kaplan RC, McGinn AP, Baird AE, Hendrix SL, Kooperberg C, Lynch J, Rosenbaum DM, Johnson KC, Strickler HD, Wassertheil-Smoller S. Inflammation and hemostasis biomarkers for predicting stroke in postmenopausal women: the Women's Health Initiative Observational Study. J Stroke Cerebrovasc Dis. 2008 Nov-Dec;17(6):344-55.

Ms603 - Wassertheil-Smoller S, Kooperberg C, McGinn AP, Kaplan RC, Hsia J, Hendrix SL, Manson JE, Berger JS, Kuller LH, Allison MA, Baird AE. Lipoprotein-associated phospholipase A2, hormone use, and the risk of ischemic stroke in postmenopausal women. Hypertension. 2008 Apr;51(4):1115-22. Epub 2008 Feb 7.

Ms672 - Wildman RP, Kaplan R, Manson JE, Rajkovic A, Connelly SA, Mackey RH, Tinker LF, Curb JD, Eaton CB and Wassertheil-Smoller S. Body size phenotypes and inflammation in the Women’s Health Initiative Observational Study. Obesity. 2011 Jan 13. [Epub ahead of print]

Ms829 - Berger JS, McGinn AP, Howard BV, Kuller L, Manson JE, Otvos J, Curb JD, Eaton CB, Kaplan RC, Lynch JK, Rosenbaum DM, Wassertheil-Smoller S. Lipid and lipoprotein biomarkers and the risk of ischemic stroke in postmenopausal women. Stroke. 2012 Feb 2. [Epub ahead of print]

Ms869 - Ogorodnikova AD, Wassertheil-Smoller S, Mancuso P, Sowers MR, Rajpathak SN, Allison MA, Baird AE, Rodriguez B, and Wildman RP. High-molecular-weight adiponectin and incident ischemic stroke in postmenopausal women. A Women’s Health Initiative Study. Stroke. 2010 May 27. [Epub ahead of print]

Ms872 - Wassertheil-Smoller S, McGinn A, Allison M, Ca T, Curb D, Eaton C, Hendrix S, Kaplan R, Ko M, Martin LW, Xue X. Improvement in stroke risk prediction: role of C-reactive protein and lipoprotein-associated phospholipase A(2) in the Women's Health Initiative. Int J Stroke. 2012 Oct 23. [Epub ahead of print]

Ms944 - Yaemsiri S, Sen S, Tinker L, Rosamond W, Wassertheil-Smoller S, He K. Trans fat, aspirin, and ischemic stroke in postmenopausal women. Ann Neurol. 2012 March 1 [Epub ahead of print]

For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.

Data Dictionaries and Study Documentation

This section displays all study-related data dictionaries and study-related files. The investigators for this study will upload the datasets, data dictionaries, and other study-related files. Study-related files will be made available to the public one year after the completion of the ancillary study, with the exception of the datasets, which will only be available to those with a Data Distribution Agreement. Those will be available to those with permission to download and will appear as a download link next to the data dictionary

Data Dictionaries

Name	Description
No results found

Study Documents

Name	Description
NameAS126 matching_report summary.pdf.pdf	Description
NameAS126 matching_report updated 6-11-13 for SP.doc	Description

Related Papers

Lipid and lipoprotein biomarkers and the risk of ischemic stroke in postmenopausal women

Jeffrey Berger et al., 2012/2 PubMed #22308251 MSID: 829

Few studies simultaneously investigated lipids and lipoprotein biomarkers as predictors of ischemic stroke. The value of these biomarkers as independent predictors of ischemic stroke remains controversial.We conducted a prospective nested case-control study among postmenopausal women from the Women's Health Initiative Observational Study to assess the relationship between fasting lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C],...

Keywords: Lipoprotein Particle; Cholesterol; Stroke

Related Studies: 126

Body size phenotypes and inflammation in the Women’s Health Initiative Observational Study

Rachel Wildman et al., 2011/1 PubMed #21233809 MSID: 672

Individuals with ''metabolically benign'' obesity (obesity unaccompanied by hypertension, dyslipidemia, and diabetes) are not at elevated 10-year risk of cardiovascular disease (CVD) compared to normal weight individuals. It remains unclear whether these obese individuals or normal weight individuals with clustering of cardiometabolic factors display heightened immune activity. Therefore, we characterized levels of acute-phase reactants (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necr...

Keywords: Obesity; Metabolic Syndrome; Inflammatory Biomarkers

Related Studies: 126

Resistin, but not adiponectin and leptin, is associated with the risk of ischemic stroke among postmenopausal women

Swapnil Rajpathak et al., 2011/5 PubMed #21546486 MSID: 893

Adipose tissue is considered an endocrine organ that secretes adipokines, which possibly mediate the effects of obesity on the risk of cardiovascular disease. However, there are yet limited prospective data on the association between circulating adipokine levels and the risk of ischemic stroke. We aimed to examine the associations of 3 adipokines (adiponectin, leptin, and resistin) with the risk of ischemic stroke.We conducted a prospective nested case-control study (972 stroke cases and 972 mat...

Keywords: None Provided

Related Studies: 126, BA10

High-molecular-weight adiponectin and incident ischemic stroke in postmenopausal women. A Women’s Health Initiative Study

Alexandra Ogorodnikova et al., 2010/5 PubMed #20508194 MSID: 869

Although low levels of adiponectin are associated with coronary heart disease and cardiovascular disease risk factors, it is unclear whether adiponectin levels are related to the risk of developing ischemic stroke.We examined the relationship between baseline high-molecular-weight (HMW) adiponectin levels and incident ischemic stroke in postmenopausal women using data and specimens from the Hormones and Biomarkers Predicting Stroke Study, a case-control study nested within the Women's Health Ini...

Keywords: Obesity; High Molecular Weight Adiponectin; Stroke

Related Studies: 126

Improvement in stroke risk prediction: role of C-reactive protein and lipoprotein-associated phospholipase A2 in the Women's Health Initiative

Sylvia Smoller et al., 2012/10 PubMed #23088183 MSID: 872

Classification of risk of ischemic stroke is important for medical care and public health reasons. Whether addition of biomarkers adds to predictive power of the Framingham Stroke Risk or other traditional risk factors has not been studied in older women.The Hormones and Biomarkers Predicting Stroke Study is a case-control study of blood biomarkers assayed in 972 ischemic stroke cases and 972 controls, nested in the Women's Health Initiative Observational Study of 93, 676 postmenopausal women fo...

Keywords: Stroke; Framingham Stroke Risk; Biomarkers; Crp; Lp-Pla2

Related Studies: 126

Inflammation and hemostasis biomarkers for predicting stroke in postmenopausal women: the Women's Health Initiative Observational Study

Robert Kaplan et al., 2008/11 PubMed #18984425 MSID: 602

Inflammatory and hemostasis-related biomarkers may identify women at risk of stroke.Hormones and Biomarkers Predicting Stroke is a study of ischemic stroke among postmenopausal women participating in the Women's Health Initiative observational study (n = 972 case-control pairs). A Biomarker Risk Score (BRS) was derived from levels of 7 inflammatory and hemostasis-related biomarkers that appeared individually to predict risk of ischemic stroke: C-reactive protein (CRP), interleukin-6, tissue plas...

Keywords: Stroke; Inflammation; Coagulation; Fibrinolysis; Postmenopausal Women; Stroke Biomarkers

Related Studies: 126

Lipoprotein-associated phospholipase A2, hormone use, and the risk of ischemic stroke in postmenopausal women

Sylvia Smoller et al., 2008/2 PubMed #18259035 MSID: 603

Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA(2)) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA(2) and stroke. We assessed the relationship between Lp-PLA(2) and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study...

Keywords: Stroke; Lp-Pla2; Postmenopausal Women; Stroke Biomarkers

Related Studies: 126

Circulating adipokines and inflammatory markers and postmenopausal breast cancer risk

Marc Gunter et al., 2015/7 PubMed #26185195 MSID: 1061

Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited.In a case-cohort analysis nested within the Women's Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, ...

Keywords: Breast Cancer; Adipokine; Insulin; Obesity

Related Studies: 126, 129, BA10

The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: The Women’s Health Initiative Observational Study

Unab Khan et al., 2013/12 PubMed #24357553 MSID: 1223

OBJECTIVE: Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors. METHODS: In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponectin, leptin, an...

Keywords: Metabolically Benign Obesity; Adipokines; Postmenopausal Women

Related Studies: 126

Trans fat, aspirin, and ischemic stroke in postmenopausal women

Sirin Yaemsiri et al., 2012/2 PubMed #22383309 MSID: 944

To examine the associations between dietary fat intake and ischemic stroke among postmenopausal women.We conducted a prospective cohort study of 87,025 generally healthy postmenopausal women (age, 50-79 years) enrolled in the Women's Health Initiative Observational Study. Repeated and validated dietary assessments were done using a self-administered food frequency questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HRs) of ischemic stroke based on quintiles of the c...

Keywords: Ischemic Stroke; Ischemic Stroke Subtype; Lacunar Infarction; Atherosclerotic Infarction; Cardioembolic Infarction; Saturated Fat Intake; Trans Fat Intake; N-3 Polyunsaturated Fat Intake; N-6 Polyunsaturated Fat Intake

Related Studies: 126, 187

Stroke Genetics Network (SiGN) study: design and rationale for a genome-wide association study of ischemic stroke subtypes

James Meschia et al., 2013/9 PubMed #24021684 MSID: 2112

BACKGROUND AND PURPOSE: Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke. METHODS: The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from E...

Keywords: Cerebral Infarct; Genetics; Genomics

Related Studies: 126, M16

Biomarkers of inflammation, pregnancy loss, and cardiovascular disease risk

Approved Proposal, Wright, Catherine et al., 2021/1 MSID: 4354

Keywords: Inflammation; Biomarkers; Reproductive History; Miscarriage; Cardiovascular Disease

Related Studies: 83, 126, 132, 133, 191, 362, BA6, BA10, BA11, BA13, BA20

Evaluation of the association between circulating IL-1β and related cytokines and incident atrial fibrillation in a cohort of postmenopausal women

Marco Perez et al., 2023/1 PubMed #36646198 MSID: 2432

Background: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1β, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF. Methods: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluate the association between log-transformed baseline cytokine levels and future AF incidence. Models were adjusted for body mass index, age, race, educatio...

Keywords: Atrial Fibrillation; Myocytokines; Il-6; Crp; Biomarkers; Inflammation

Related Studies: 83, 126, 132, 133, 179, 191, 207, 214, 266, BA10, BA11, BA13, BA20, W6, W35

Inflammation and hemostasis-related biomarkers and clonal hematopoiesis of indeterminate potential

Approved Proposal, Haring, Bernhard et al., 2022/8 MSID: 4716

Keywords: Inflammatory Biomarkers; Hemostasis Biomarkers; Clonal Hematopoiesis Of Indeterminate Potential; Chd; Stroke; Heart Failure

Related Studies: 126

Lipid and lipoprotein biomarkers and clonal hematopoiesis of indeterminate potential

Approved Proposal, Haring, Bernhard et al., 2022/8 MSID: 4729

Keywords: Lipids; Lipoprotein Biomarkers; Clonal Hematopoiesis Of Indeterminate Potential; Chip; Stroke

Related Studies: 126

Genetic interleukin-6 receptor blockade, chronic disease risk and longevity

Approved Manuscript, Haring, Bernhard et al., 2024/12 MSID: 5099

Keywords: Inflammation; Ageing; Longevity; Chronic Disease Risk; Chd; Dementia; Chf

Related Studies: 126, 132

Inflammation, body weight change, CVD and mortality risk. Results from the Women’s Health Initiative

Approved Proposal, Haring, Bernhard et al., 2025/1 MSID: 5257

Keywords: Inflammation; Weight Change; Il-6; Il-6 Inhibition; Hscrp

Related Studies: 126, 132

Work characteristics associated with physical functioning in women

Aimee Palumbo et al., 2017/3 PubMed #28420131 MSID: 2635

Women make up almost half of the labor force with older women becoming a growing segment of the population. Work characteristics influence physical functioning and women are at particular risk for physical limitations. However, little research has explored the effects of work characteristics on women's physical functioning. U.S. women between the ages of 50 and 79 were enrolled in the Women's Health Initiative Observational Study between 1993 and 1998. Women provided job titles and years worked ...

Keywords: Physical Function; Social Environment; Workplace

Related Studies: 126

Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Angela Wood et al., 2018/4 PubMed #29676281 MSID: 3708

BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaborat...

Related Studies: 126

Agreement between TOAST and CCS ischemic stroke classification: the NINDS SiGN study

Patrick McArdle et al., 2014/9 PubMed #25261504 MSID: 1869

OBJECTIVE: The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems. METHODS: Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently clas...

Related Studies: 126, M16

Understanding the relation between socioeconomic position and inflammation in post-menopausal women: education, income and occupational prestige

Jolene Masters Pedersen et al., 2017/12 PubMed #29186460 MSID: 1738

BACKGROUND: The role of occupational prestige, a direct measure of the perceived status of job and job holder, in inflammation is unknown. To contribute to understanding the pathways by which socioeconomic position (SEP) is associated with inflammation, we aimed to estimate the direct effects of education, income and occupational prestige on C-reactive protein (CRP) and to describe the relationship between these markers and CRP. METHODS: The study was based on 2026 post-menopausal women enrolled...

Keywords: Occupation; Socioeconomic Position; Low Grade Inflammation

Related Studies: 126, 132