The Nurses' Health Study Hypertension & Stroke Substudy - Nurses' Health Study Hypertension & Stroke Substudy


Nutritional factors and BMI measurements for hypertension and stroke.


There may be nonpharmacologic approaches to prevent and control hypertension; women who are obese or who have gained considerable weight since age 18 years are more likely to suffer strokes.

Study Design

Study Design:

Patients Screened: 121,700
Patients Enrolled: (1) 58,218; (2) 116,759
Mean Follow Up: (1) 4 years; (2) 16 years
Mean Patient Age: ~45 years
Female: 100

Patient Populations:

Female registered nurses living in the United States.
Complete the writing of personal information on periodically mailed questionnaires regarding risk factors for cardiovascular disease and cancer.


Participants responding with 10 or more blank items on the questionnaire.

Participants self-reporting one or more of the following diagnoses on the 1980 or previous questionnaires: high blood pressure, myocardial infarction, angina pectoris, diabetes mellitus, and all cancers (except nonmelanoma skin cancer).

Participants self-reporting on the 1980 questionnaire that they were currently using antihypertensive medication, on a special diet, or had been pregnant for at least six months since 1978.

Questionnaire nonrespondents.

Primary Endpoints:

Hypertension, stroke (total, ischemic, or hemorrhagic [subarachnoid or intraparenchymal]).

Secondary Endpoints:

Quetelet's index, alcohol consumption, consumption of calcium, magnesium, potassium, fiber, saturated fatty acids, linoleic acid, trans-unsaturated fatty acids, total fat.

Drug/Procedures Used:

Not applicable

Concomitant Medications:

Not applicable

Principal Findings:

During 4 years of follow-up, 3,275 women reported a diagnosis of hypertension; the validity of the self-report was shown in a subsample.

Age, relative weight, and alcohol consumption were the strongest predictors for the development of hypertension.

Dietary calcium and magnesium had independent and significant inverse associations with hypertension. For women with a calcium intake of at least 800 mg/day, the relative risk of hypertension was 0.78 (95% confidence interval [CI], 0.69-0.88) when compared with an intake of less than 400 mg/day. The relative risk for magnesium intake of 300 mg/day or more compared with an intake of less than 200 mg/day was 0.77 (95% CI, 0.67-0.88). For women with high intakes of both calcium and magnesium compared with those having low intakes of both, the relative risk of hypertension was 0.65 (95% CI, 0.53-0.80).

No independent associations with hypertension were observed for intakes of potassium, fiber, and saturated and polyunsaturated fatty acids.

During 16 years of follow-up, 866 total strokes (including 403 ischemic strokes and 269 hemorrhagic strokes) were documented. In multivariate analyses adjusted for age, smoking, postmenopausal hormone use, and menopausal status, women with increased body mass index (BMI) (>27 kg/m2) had significantly increased risk of ischemic stroke, with relative risks (RRs) of 1.75 (95% CI, 1.17-2.59) for BMI of 27 to 28.9 kg/m2; 1.90 (95% CI, 1.28-2.82) for BMI of 29 to 31.9 kg/m2; and 2.37 (95% CI, 1.60-3.50) for BMI of 32 kg/m2 or more (P for trend<.001), as compared with those with a BMI of less than 21 kg/m2.
For hemorrhagic stroke, there was a nonsignificant inverse relation between obesity and hemorrhagic stroke, with the highest risk among women in the leanest BMI category (P for trend=.20).

For total stroke, the RRs were somewhat attenuated compared with those for ischemic stroke, but remained elevated for women with higher BMI (P for trend<.001). In multivariate analyses that also adjusted for BMI at age 18 years, weight gain from age 18 years until 1976 was associated with an RR for ischemic stroke of 1.69 (95% CI, 1.26-2.29) for a gain of 11 to 19.9 kg and 2.52 (95% CI, 1.80-3.52) for a gain of 20 kg or more (P for trend<.001), as compared with women who maintained stable weight (loss or gain <5 kg). Although weight change was not related to risk of hemorrhagic stroke (P for trend=.20), a direct relationship was observed between weight gain and total stroke risk (P for trend<.001).

Compared with women in the lowest fifth of the cohort with respect to vitamin E intake, those in the top fifth had a relative risk of major coronary disease of 0.66 (95% CI, 0.50-0.87) after adjusting for age and smoking. Further adjustment for a variety of other coronary risk factors and nutrients, including other antioxidants, had little effect on the results. Most of the variability in intake and reduction in risk was attributable to vitamin E consumed as supplements. Women who took vitamin E supplements for short periods had little apparent benefit, but those who took them for more than two years had a relative risk of major coronary disease of 0.59 (95% CI, 0.38-0.91) after adjustment for age, smoking status, risk factors for coronary disease, and use of other antioxidant nutrients (including multivitamins).


These prospective findings add to the growing evidence to support the need for randomized trials to determine whether there is a protective role of dietary calcium and magnesium in the regulation of blood pressure.

A large weight gain since the age of 18 also increased the risk for stroke. After adjusting for age, smoking, postmenopausal hormone use and menopausal status, women who gained 11 to 19.9kg (24 to 44 pounds) were 1.7 times more likely to suffer an ischemic stroke, and women who gained 20kg (44 pounds) or more were more than two-and-a-half times more likely to suffer an ischemic stroke than women who maintained a stable weight since age 18.

These prospective data indicate that both obesity and weight gain in women are important risk factors for ischemic and total stroke but not hemorrhagic stroke. The relationship between obesity and total stroke depends on the distribution of stroke subtypes in the population.


1. Circulation 1989;80:1320-7. Nutrition and hypertension
2. N Engl J Med 1990;322:882-9. Obesity and CAD
3. N Engl J Med 1993;328:1444-9. Vitamin E and CAD risk
4. JAMA 1997;277:1539-45. Body mass and weight change
5. Circulation 1998;97:1540-8. Calcium channel blockade

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Hypertension, Smoking

Keywords: Magnesium, Writing, Neoplasms, Stroke, Follow-Up Studies, Vitamin E, Multivariate Analysis, Coronary Disease, Risk Factors, Weight Gain, Calcium Channel Blockers, Smoking, Potassium, Calcium, Dietary, Body Mass Index, Fatty Acids, Unsaturated, Obesity, Confidence Intervals, Questionnaires, Hypertension

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