Nurses' Health Study (Cardiovascular Component)

September 15, 2023 updated by: JoAnn E. Manson, MD, Brigham and Women's Hospital
To determine the relationships of hormonal, reproductive, dietary, and lifestyle factors, as well as biochemical and genetic factors, with the subsequent risk of coronary heart disease and other cardiovascular events in a cohort of female registered nurses. The current funding cycle involves comprehensive metabolomic profiling of coronary heart disease cases and controls and development of metabolomic risk scores for coronary heart disease.

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

BACKGROUND:

The Nurses' Health Study began in 1976, when 121,700 female registered nurses living in eleven states completed a mailed questionnaire that included items about their medical history, diet, and other risk factors for cancer. The National Cancer Institute funded the first three years of the study and subsequent years on data pertaining to cancer. In 1980 the National Heart, Lung, and Blood Institute began funding the cardiovascular portion of the study. Follow-up questionnaires have been administered every two years subsequently. Blood samples were collected on a subsample of the women between 1989-1990 and stored for analysis of germline DNA and circulating biomarkers.

The cardiovascular component is currently funded through March 2022.

DESIGN NARRATIVE:

In 1976, 121,700 nurses ages 30-55 completed and returned the initial Nurses' Health Study questionnaire and comprise the Nurses' Health Study cohort. The cohort has been followed by means of biennial mailed questionnaires. A total of 109,413 participants responded to the 1978 questionnaire. In addition, 400 women who replied in 1976 stated that they did not wish to continue in the study and 390 women died. In 1980, the first major dietary assessment was added to the questionnaire. In the 1978-1980 interval, there were 624 deaths, 300 women declined further participation, approximately 99,000 completed the full questionnaire including the dietary questionnaire, and another 4,000 completed an abbreviated questionnaire, for a total of about 103,000 responses. In 1982, the overall response was 101,174. The approximately 19,000 living non-respondents were followed by telephone, yielding 71 percent of the non-respondents. Thus, at the end of 1982, current information was available on 116,150 or 95.4 percent of the original cohort. A subset of 32,826 women provided blood samples between 1989 and 1990. Genotyping on 1,186 women (382 with coronary heart disease and 804 matched controls) was performed using Affymetrix 6.0 platform.

Deaths in the cohort were usually reported by next-of-kin or postal authorities. At the completion of each mailing cycle, the National Death Index was searched for names of non-respondents who might have died. By comparing deaths ascertained from independent sources, the study ascertained an estimated 98 percent of deaths. Death certificates were obtained from state vital statistics departments to confirm all reported deaths. For all death certificates indicating possible cardiovascular disease, permission to obtain further information was requested from family members. Confirmed coronary heart disease death required additional information beyond the death certificate such as autopsy reports, ECG and enzyme changes of myocardial infarction prior to death, classical chest pain immediately prior to death, prior documented myocardial infarction or angina, or prior cardiac catheterization showing severe coronary disease.

Data were collected on date of birth, weight, cigarette smoking, menopausal status and current interim use of menopausal hormone therapy. Data were also collected on incident cases of nonfatal myocardial infarction, stroke, pulmonary embolism, and angina pectoris. These items appeared on each questionnaire. In addition, nutritional parameters were assessed by a self-administered semi-quantitative food frequency questionnaire in 1986 and again in 1990.

The study was renewed in 1993 with particular attention given to dietary antioxidants, other nutritional factors, physical activity, regional fat distribution, menopausal estrogen and progestin therapy, and biochemical markers including plasma lipids and apoproteins. Follow-up for nonfatal cardiovascular disease events is over 92 percent for the original 121,700 participants. Fatal cardiovascular events are documented by death certificates and confirmed and classified by review of hospital records, autopsy reports, and interviews with next of kin. Searches of the National Death Index for all nonrespondents ensure the identification of remaining deaths, resulting in mortality follow-up that is more than 98 percent complete.

The study was renewed in FY 2002 to continue follow-up till March 2007. A major aim of that renewal was to compare the predictive capability of several biochemical and genetic markers of inflammation and endothelial activation for coronary heart disease versus stroke in women: C-reactive protein (CRP), E-selectin, intercellular adhesion molecule-1, endothelin-1, and polymorphisms of the CRP and E-selectin genes. The study also continues the investigation of lifestyle determinants of cardiovascular disease, including menopausal hormone therapy (dose, formulation, and duration of use) and alcohol consumption (dose and beverage type), in the full cohort, and interactions of these exposures with the above biomarkers and with novel genetic markers (prothrombin and alcohol dehydrogenase-3 gene polymorphisms). Genotypes from 1,186 women typed as part of a genome-wide association study of coronary heart disease were used to study genetic factors associated with cardiovascular disease and the interplay of genes and diet on cardiovascular risk. Subsequent renewal cycles included study of plasma adipokines and metabolomic predictors, including gut flora metabolites such as trimethylamine N-oxide, choline, and L-carnitine, of coronary heart disease. The current funding cycle involves comprehensive metabolomic profiling of coronary heart disease cases and controls and development of metabolomic risk scores for coronary heart disease, with funding through March 2022.

Study Type

Observational

Enrollment (Actual)

121700

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

See "Detailed Description"

Description

See "Detailed Description"

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Coronary heart disease (CHD)
Time Frame: The primary outcome measure time frame is first CHD event during person-time of follow-up for each participant from study enrollment through March 2022.
CHD is defined as nonfatal myocardial infarction and death from coronary heart disease. Information on the outcome is assessed by medical record review of events reported on biennial questionnaires or by searches of the National Death Index, and the date of the CHD event or CHD death is ascertained from these sources.
The primary outcome measure time frame is first CHD event during person-time of follow-up for each participant from study enrollment through March 2022.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: JoAnn E Manson, MD, DrPH, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 1980

Primary Completion (Estimated)

March 31, 2024

Study Completion (Estimated)

March 31, 2024

Study Registration Dates

First Submitted

May 25, 2000

First Submitted That Met QC Criteria

May 25, 2000

First Posted (Estimated)

May 26, 2000

Study Record Updates

Last Update Posted (Actual)

September 18, 2023

Last Update Submitted That Met QC Criteria

September 15, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2008P000327
  • R01HL034594-28 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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