January 2005
John P. Forman, MD; Eric B. Rimm, ScD; Meir J. Stampfer, MD, DrPH; et al

 

Abstract

Context: Folate has important beneficial effects on endothelial function, but there is limited information about folate intake and risk of incident hypertension.

Objective: To determine whether higher folate intake is associated with a lower risk of incident hypertension.

Design, Setting, and Participants: Two prospective cohort studies of 93 803 younger women aged 27 to 44 years in the Nurses’ Health Study II (1991-1999) and 62 260 older women aged 43 to 70 years in the Nurses’ Health Study I (1990-1998), who did not have a history of hypertension. Baseline information on dietary folate and supplemental folic acid intake was derived from semiquantitative food frequency questionnaires and was updated every 4 years.

Main Outcome: Measure Relative risk of incident self-reported hypertension during 8 years of follow-up.

Results: We identified 7373 incident cases of hypertension in younger women and 12 347 cases in older women. After adjusting for multiple potential confounders, younger women who consumed at least 1000 μg/d of total folate (dietary plus supplemental) had a decreased risk of hypertension (relative risk [RR], 0.54; 95% confidence interval [CI], 0.45-0.66; P for trend <.001) compared with those who consumed less than 200 μg/d. Younger women’s absolute risk reduction (ARR) was approximately 8 cases per 1000 person-years (6.7 vs 14.8 cases).

The multivariable RR for the same comparison in older women was 0.82 (95% CI, 0.69-0.97; P for trend = .05). Older women’s ARR was approximately 6 cases per 1000 person-years (34.7 vs 40.4 cases). When the analysis was restricted to women with low dietary folate intake (<200 μg/d), the multivariable RR for younger women with total folate intake at least 800 μg/d compared with less than 200 μg/d was 0.55 (95% CI, 0.32-0.94; P for trend = .03), and 0.61 (95% CI, 0.34-1.11; P for trend = .05) in the older cohort.

Among women who did not take folic acid–containing supplements, dietary folate intake of 400 μg/d or more was not significantly associated with risk of hypertension.

Conclusion: Higher total folate intake was associated with a decreased risk of incident hypertension, particularly in younger women.

Hypertension affects an estimated 65 million individuals in the United States and many more worldwide. Because the risk of hypertension increases with age, the prevalence is growing along with the aging population. Hypertension is a potent independent risk factor for cardiovascular disease3-6 and renal failure. Therefore, identifying risk factors for hypertension could lead to specific preventive interventions that may favorably affect public health.

Folate may have beneficial effects on blood pressure by increasing nitric oxide synthesis in endothelial cells, or by reducing plasma homocysteine, which itself can cause endothelial cell injury. Oral folic acid supplementation improves endothelial function in vivo.

Although there are no published studies on the association between folate intake and risk of incident hypertension, 2 small randomized trials have demonstrated that high-dose folic acid supplementation may lower systolic and diastolic blood pressure. Taken together, these data suggest that a higher intake of folate may reduce an individual’s risk of hypertension. We prospectively examined the association between folate intake and risk of incident hypertension in 2 large studies of younger and older women who were followed up for 8 years.