Published online before print February 7, 2008, doi: 10.1161/HYPERTENSIONAHA.107.107821
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(Hypertension. 2008;51:1073.)
© 2008 American Heart Association, Inc.
Go Red Original Articles |
Dietary Intake of Dairy Products, Calcium, and Vitamin D and the Risk of Hypertension in Middle-Aged and Older Women
From the Division of Preventive Medicine (L.W., J.E.M., J.E.B., I.-M.L., H.D.S.) and the Division of Aging (J.E.B., H.D.S.), Department of Medicine, Brigham and Women’s Hospital, and the Department of Epidemiology (J.E.M., J.E.B., I.-M.L.), Harvard School of Public Health, Boston, Mass.
Correspondence to Lu Wang, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston MA 02215. E-mail luwang{at}rics.bwh harvard.edu
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Abstract |
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Prospective data on the associations between intake of dairy products and its nutrient components with risk of hypertension remain limited. We therefore investigated the associations of intake of dairy products, calcium, and vitamin D with the incidence of hypertension in a prospective cohort of 28 886 US women aged
45 years. Intake of dairy products, calcium, and vitamin D at baseline were assessed from semiquantitative food frequency questionnaires. Incident cases of hypertension (n=8710) were identified from annual follow-up questionnaires during 10 years of follow-up. After adjusting for major hypertension risk factors, the relative risks of incident hypertension across increasing quintiles of low-fat dairy product intake were 1.00 (reference), 0.98, 0.97, 0.95, and 0.89 (P for trend: 0.001). The risk of hypertension decreased in the higher quintiles of dietary calcium (multivariate relative risk in the highest quintile: 0.87) and dietary vitamin D (multivariate relative risk in the highest quintile: 0.95), but did not change with calcium or vitamin D supplements. Adjustment for dietary calcium significantly attenuated the inverse association of low-fat dairy intake with risk of hypertension, whereas adjustment for dietary vitamin D did not change the association. The multivariate relative risks across increasing quintiles of high-fat dairy product intake, in contrast, were 1.00, 1.02, 1.01, 1.00, and 0.97 (P for trend: 0.17). Our study found that intakes of low-fat dairy products, calcium, and vitamin D were each inversely associated with risk of hypertension in middle-aged and older women, suggesting their potential roles in the primary prevention of hypertension and cardiovascular complications.
Key Words: diet • dairy products • calcium • vitamin D • hypertension • women • population study
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Introduction |
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Previous studies have suggested an inverse association of dairy product consumption with metabolic syndrome,1 type 2 diabetes,2 and cardiovascular disease.3 These potential benefits of dairy consumption are usually attributed to major nutrients in dairy products such as calcium. High calcium intake decrease levels of parathyroid hormone and 1,25-(OH)2 vitamin D and thus reduce calcium influx from outside the cell.4 Reduced intracellular calcium may stimulate lipolysis and inhibit lipogenesis,5 promote insulin-stimulated signal transduction,4 and suppress vascular smooth muscle tone.6 Because vitamin D is critical for calcium absorption and homeostasis,7 the metabolism of these 2 nutrients are intimately interrelated.
Population studies on the associations between dairy product consumption and the incidence of hypertension or increase in blood pressure (BP) have been limited to children,8 young adults,1,9 and adults in Mediterranean countries,10 with results generally suggesting an inverse association. The Dietary Approaches to Stop Hypertension (DASH) trial has demonstrated that a combined diet rich in fruits, vegetables, and low-fat dairy products and low in total and saturated fat effectively reduced BP in subjects with and without hypertension, and the BP lowering effects of the combined diet with emphasis on dairy consumption were more profound compared with a diet rich in fruits and vegetables alone.11 To provide further evidence on the potential role of dairy consumption in prevention of hypertension, we examined the prospective associations between intake of dairy products, from both high-fat and low-fat food sources, as well as the major nutrient components in dairy products, calcium and vitamin D, with the risk of hypertension in a large cohort of middle-aged and older US women.
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Methods |
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Study Population
The Women’s Health Study (WHS) was a randomized, double-blind, placebo-controlled, 2x2 factorial trial evaluating the risks and benefits of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer.12 A third component, β-carotene, was initially included in the trial but terminated after a median treatment of 2.1 years.13 Written informed consent was obtained from all participants. The trial was approved by the institutional review board of Brigham and Women’s Hospital, Boston, Mass.
From September 1992 to May 1995, 39 876 female US health professionals, aged 45 years and free from cardiovascular disease and cancer (except nonmelanoma skin cancer), were randomized into the WHS. Study participants reported demographic information, lifestyle characteristics, and medical history through questionnaires (please see http://hyper.ahajournals.org). A total of 39 310 participants completed a 131-item validated semiquantitative food frequency questionnaire (SFFQ). For this study, we excluded women with insufficient completion of the SFFQ or implausible total energy intake, women with missing data on dairy product intake, and women with prerandomization cardiovascular disease or cancer. We then excluded women with baseline hypertension, defined as having a self-reported physician diagnosis of hypertension, self-reported systolic BP (SBP) 140 mm Hg, diastolic BP (DBP) 90 mm Hg, or antihypertensive treatment. Self-reported BP has been highly correlated with measured SBP (r=0.72) and DBP (r=0.60) in health professionals.14 After the exclusions, 28 886 women remained for analysis.
Assessment of Dietary Intake
On the SFFQ, a commonly used unit or portion size was specified for each food item. Participants were asked how often they had consumed that amount, on average, during the previous year. Nine possible responses ranging from "never or less than once per month" to "6+ per day" were recorded. The average daily intake for each food item was calculated by multiplying the intake frequency by the portion size of the specific items. Total dairy product intake was calculated by summing the intake of individual dairy items: low-fat dairy items include skim or low-fat milk, sherbet, yogurt, and cottage/ricotta cheese, high-fat dairy items include whole milk, cream, sour cream, ice cream, cream cheese, and other cheese. Nutrient intake was computed by multiplying the intake frequency by the nutrient content of the specified portion size according to food composition tables from the Harvard School of Public Health, Boston, Mass.15 Each nutrient reported has adjusted for total energy intake using the residual method.16 Supplemental calcium and vitamin D were assessed from the self-reported use of individual and multivitamin supplements. In similar cohorts of health professionals, Pearson correlation coefficients between responses from the SFFQ and those from dietary records were 0.79 for skim milk, 0.62 for whole milk,17 and 0.51 for dietary calcium,18 and the correlation coefficient between estimated dietary vitamin D and plasma concentration of 25-OH vitamin D was 0.25.19
Ascertainment of Incident Hypertension
Incident hypertension was defined by meeting at least 1 of 4 criteria from annual follow-up questionnaires: self-reports of a new physician diagnosis of hypertension; self-reports of newly initiated antihypertensive treatment; self-reported SBP 140 mm Hg; or self-reported DBP 90 mm Hg. Women reporting a new physician diagnosis of hypertension also provided the month and year of diagnosis. A missing date for a physician diagnosis or hypertension defined by other criteria was assigned a date of incident hypertension by randomly selecting a date between the present and previous questionnaire. Individuals who developed intermediate cardiovascular disease were censored on the date of the cardiovascular disease diagnosis. The validity of self-reported hypertension in health professionals has been high in previous studies.20 In a random sample of WHS, self-reported incident hypertension was confirmed in 48 of 50 (96%) women and absence of hypertension confirmed in 45 of 50 (90%) women through telephone interviews.
Data Analyses
Statistical analyses were performed using SAS software (SAS Institute) version 9.1. Baseline hypertension risk factors were compared across quintiles of dairy product intake. Cox regression models were used to estimate the hazard ratio (presented as relative risk [RR]) of hypertension across quintiles of dairy intake, with the lowest quintile as the reference. Models first adjusted for age, race, total energy intake, and randomized treatment, and then additionally adjusted for other factors predictive of hypertension, including smoking, alcohol intake, physical activity, menopausal status, multivitamin use, body mass index (BMI), history of diabetes and hypercholesterolemia, and fruit and vegetable, whole grain, and red meat intake. We also evaluated the individual effect of adjusting for dietary calcium and vitamin D on the RRs. Analyses were further stratified by known hypertension risk factors such as BMI, alcohol intake, physical activity, and baseline BP. The above analytic approach was then repeated for dietary and supplemental calcium and vitamin D. Finally, the joint association of calcium and vitamin D with risk of hypertension was considered using a priori defined categories.
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Results |
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In 28 886 women with a mean age of 53.8 years, the median intake of total dairy products ranged from 0.56 servings/d in the lowest quintile to 3.69 servings/d in the highest quintile. The corresponding median intakes in the lowest and highest quintiles were 0.13 and 2.71 servings/d for low-fat dairy products, and 0.13 and 1.49 servings/d for high-fat dairy products. The low-fat and high-fat dairy intakes were only weakly correlated with each other (Spearman r=–0.012, P=0.05).
Women who consumed more low-fat dairy products were older, less likely to smoke and drink alcohol, more likely to be physically active, use multivitamins, and had a higher prevalence of diabetes and hypercholesterolemia (Table 1). Low-fat dairy intake was also positively associated with fruit and vegetable and whole grain intake and energy-adjusted potassium, fiber, calcium, and vitamin D intake, while inversely associated with red meat intake and cholesterol intake. Women who consumed more high-fat dairy products had generally less favorable lifestyle and diet profile. Low-fat dairy intake was not associated with baseline BP, whereas high-fat dairy intake was positively associated with baseline DBP. The associations for total dairy intake with baseline characteristics reflected the differential associations for low-fat and high-fat dairy intake.
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During 10 years of follow-up, we identified 8710 cases of incident hypertension. After adjusting for age, race, randomized treatment, and total energy intake, the RRs of hypertension across increasing quintiles of low-fat dairy intake were 1.00, 0.96, 0.93, 0.90, and 0.84 (P for trend: <0.0001; Table 2). Successive multivariate model adjusting for lifestyle factors, clinical factors, and other dietary factors only slightly attenuated the highly significant inverse association (please see the online data supplement). Additional adjustment for dietary calcium did substantially attenuate the association to a RR of 0.97 [95%CI: 0.85 to 1.10] in the highest quintile of low-fat dairy intake, whereas adjustment for dietary vitamin D did not change the RRs. The multivariate adjusted RRs of hypertension across increasing quintiles of high-fat dairy intake were 1.00, 1.02, 1.01, 1.00, and 0.97 (P for trend: 0.17). The RRs remained unchanged with additional adjustment for dietary calcium and vitamin D. Primarily driven by the association for low-fat dairy intake, there was an inverse association between total dairy intake and risk of hypertension, which was attenuated with additional adjustment for dietary calcium.
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For all 4 major low-fat dairy products, a reduction of 10% to 15% in hypertension risk comparing the highest to the lowest intake category was observed in the initial model, although the reduction was statistically significant only for skim milk and yogurt (Table 3). Multivariate adjustment substantially attenuated the inverse association for yogurt, but did not materially change the RRs for the other low-fat dairy products. No significant interaction was found between total, individual low-fat dairy intake and BMI, alcohol intake, physical activity, or baseline BP (data not shown).
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After multivariate adjustment, the RRs of hypertension across increasing quintiles of dietary calcium were 1.00, 0.96, 0.89, 0.89, and 0.87 (P for trend: <0.0001; Table 4). In contrast, the risk of hypertension did not appreciably change with intake of supplemental calcium. As with calcium, the risk of hypertension decreased moderately in the higher quintiles of dietary vitamin D, but did not change with supplemental vitamin D. When the RRs were calculated for categories defined jointly by dietary calcium and dietary vitamin D (Figure), the inverse association between dietary calcium and risk of hypertension appeared to be stronger with lower intake of dietary vitamin D, and vice versa. However, the interaction was not statistically significant (P for interaction=0.92).
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Discussion |
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In this large prospective cohort study of middle-aged and older women, we found an inverse association between low-fat dairy product intake and the subsequent risk of hypertension. The association was moderate, graded, and independent of known risk factors for hypertension. In contrast, we found no association between high-fat dairy intake and the risk of hypertension. Calcium and vitamin D intake in diet, but not in supplements, were also inversely associated with risk of hypertension. The association between low-fat dairy intake and a reduced risk of hypertension was substantially attenuated by adjustment for dietary calcium.
The association between dairy product intake and BP, hypertension have been examined more in cross-sectional studies21–24 than in prospective studies.8–10 The Framingham Children’s Study found that children who consumed 2 or more servings/d dairy products during preschool years had smaller SBP gain throughout childhood and lower SBP by early adolescence.8 In the Coronary Artery Risk Development In young Adults (CARDIA) Study, risk of elevated BP, defined as incident SBP 130 mm Hg, DBP 85 mm Hg, or use of antihypertensive medication, was inversely associated with milk, dairy dessert, and total dairy intakes.9 The University of Navarra Follow-up Study assessed total, low-fat, and whole-fat dairy consumption using SFFQ among 5880 Spanish adult men and women, and found that the highest quintile of low-fat dairy consumption was associated with a 54% reduction in hypertension risk, whereas whole-fat dairy consumption was not associated with incident hypertension.10 Our study findings largely agree with these earlier reports.
The BP lowering effect of low-fat dairy intake has been observed in intervention trials. Earlier feeding studies have shown that supplementation of usual diet with dairy products may reduce BP.25–27 In the DASH trial, a combination diet that was rich in fruits and vegetables and low-fat dairy products with low saturated and total fat reduced SBP and DBP by 5.5 and 3.0 mm Hg more, respectively, compared to the control diet, whereas the corresponding BP reduction were 2.8 and 1.1 mm Hg more for the fruits and vegetables diet alone.11 A more profound BP reduction with the addition of 2 servings/d of low-fat dairy products, along with other aspects of the combination diet, was observed both in subjects with hypertension and in those without hypertension. Other intervention studies built on DASH trial findings continue to support the potential effects of low-fat dairy consumption on BP control28–30; however, these studies were originally designed to test the effect of multiple dietary interventions but not the specific effect of any individual dietary factor.
Calcium is one major nutritional component in dairy products. Dietary calcium may lower the activity of renin-angiotensin system,31 improve sodium-potassium balance,32 and inhibit vascular smooth muscle cell (VSMC) constriction.6 High calcium intake facilitates weight loss5 and enhances insulin sensitivity,4 which also contribute to BP reduction. Compelling evidence from epidemiological studies has supported an association between adequate calcium intake and lower BP or reduced hypertension risk.33,34 Intervention trials have shown greater consistency for the BP lowering effects of whole foods compared with nondietary supplement used as the source,33,35,36 suggesting the importance of a complete nutritional profile for the BP effects.36 In our study, higher dietary intake of calcium, but not calcium supplement, was associated with reduced risk of hypertension, and adjustment for dietary calcium substantially attenuated the inverse association of dairy intake with risk of hypertension. Because dairy products account for nearly 80% of total calcium intake in American diet, our findings on total dietary calcium suggested a major role of this nutrient in mediating the beneficial effects of dairy products in the prevention of hypertension.
Milk fortified with vitamin D is the main source of vitamin D intake in the American diet. Vitamin D maintain calcium homeostasis by regulating calcium absorption from the gastrointestinal tract and interacting with parathyroid hormone.37 Vitamin D deficiency/insufficiency may also be directly associated with development of hypertension through inappropriate stimulation of the renin-angiotensin system.38 Compared with calcium, there were fewer studies of vitamin D intake and BP,37,39 which, along with the present study, have suggested that dietary vitamin D may reduce BP or risk of hypertension. A moderate impact on the association between low-fat dairy intake and risk of hypertension indicated that vitamin D only partially explains the BP effects of low-fat dairy products. Our findings on vitamin D are limited, however, by the lack of information on sun exposure that induces endogenous synthesis of vitamin D. Besides calcium and vitamin D, other potentially hypotensive components of dairy products include lactose, dairy protein and derivative peptides, and other minerals such as potassium and magnesium.
It remains unclear why benefits are observed for low-fat dairy products but not for high-fat dairy products. A similar phenomenon has been observed for type 2 diabetes2 and coronary heart disease.3 It is postulated that saturated fats in high-fat dairy products may mitigate the beneficial effects of other components of dairy products, including calcium.10 The capacity of calcium to form soaps is higher when fat intake is increased.10 Therefore high fat in foods might hinder calcium absorption and reduce the bioavailability of calcium. Another speculated explanation is that changes in the nutritional composition of skim milk and whole milk during the product processing and preparation may be responsible for the different effects, which cannot be confirmed with available data.
Several limitations of this study deserve comment. First, dietary intake was assessed from a single measurement of SFFQ, which is subject to random error that would tend to underestimate the true association. Second, incident hypertension was identified based on self-reported information. However, we performed sensitivity analyses using varied definitions of hypertension (elevated BP only, physician diagnosis or antihypertensive treatment only, or multiple indications), and the RRs were similar. Third, because our observed associations remained significant after adjusting for related dietary factors, we believe that the association could not necessarily be explained by an overall healthier dietary pattern. Nevertheless, residual confounding cannot be completely ruled out, despite a comprehensive set of available covariates. Finally, our study results apply primarily to white health professional women and may not be directly generalizable to other populations.
Perspectives
The 2005 Dietary Guideline from the US Department of Agriculture recommend that the majority of Americans increase their intake of milk and milk products to 3 servings per day. Our study findings offer additional support to this recommendation from the perspective of hypertension prevention and emphasize on the importance of low-fat dairy products. Because hypertension remains a highly prevalent disease in the US, even a modest reduction in hypertension risk on individual level will substantially lower the disease burden in the population.
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Acknowledgments |
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Sources of Funding
This work was supported by research grants CA-047988 and HL-080467 from the National Institutes of Health, Bethesda, Md.
Disclosures
None.
Received December 3, 2007; first decision December 21, 2007; accepted January 11, 2008.
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