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Dairy Consumption and Incidence of Hypertension

A Dose-Response Meta-Analysis of Prospective Cohort Studies
Originally publishedhttps://doi.org/10.1161/HYPERTENSIONAHA.112.195206Hypertension. 2012;60:1131–1137

Abstract

Observational and clinical studies suggest that dairy intake, particularly low-fat dairy, could have a beneficial effect on blood pressure. We performed a dose-response meta-analysis of prospective cohort studies on dairy intake and risk of hypertension in the general population. A systematic literature search for eligible studies was conducted until July 2011, using literature databases and hand search. Study-specific dose-response associations were computed according to the generalized least squares for trend estimation method, and linear and piecewise regression models were created. Random-effects models were performed with summarized dose-response data. We included 9 studies with a sample size of 57 256, a total of 15 367 incident hypertension cases, and a follow-up time between 2 and 15 years. Total dairy (9 studies; range of intake, ≈100–700 g/d), low-fat dairy (6 studies; ≈100–500 g/d), and milk (7 studies; ≈100–500 g/d) were inversely and linearly associated with a lower risk of hypertension. The pooled relative risks per 200 g/d were 0.97 (95% CI, 0.95–0.99) for total dairy, 0.96 (95% CI, 0.93–0.99) for low-fat dairy, and 0.96 (95% CI, 0.94–0.98) for milk. High-fat dairy (6 studies), total fermented dairy (4 studies), yogurt (5 studies), and cheese (8 studies) were not significantly associated with hypertension incidence (pooled relative risks of ≈1). This meta-analysis of prospective cohort studies suggests that low-fat dairy and milk could contribute to the prevention of hypertension, which needs confirmation in randomized controlled trials.

Introduction

Hypertension (HTN) contributes to approximately half of all cardiovascular diseases.1 In 2000, the worldwide prevalence of HTN was estimated to be 26%, affecting ≈1 billion people. It is expected that 29% of the world population will be experiencing HTN in 2025, mainly because of the expected increase in hypertensive people in economically developing regions.2

American and European guidelines emphasize the importance of weight control, regular physical activity, moderate alcohol intake, and reduced sodium intake for the prevention of HTN and cardiovascular diseases.3,4 A diet low in saturated and total fat and rich in fruit, vegetables, and low-fat dairy products substantially lowered blood pressure (BP) in the Dietary Approaches to Stop Hypertension (DASH) Trial.5 Dairy products contain protein, minerals (eg, calcium, potassium, magnesium, and phosphorus), and vitamins (eg, folate and vitamin D, if fortified) that may individually or in combination reduce BP.68

A recent meta-analysis of 5 prospective cohort studies showed significant inverse associations of total dairy, low-fat dairy, and fluid dairy foods with BP.9 However, large variation in the types of dairy intake and serving sizes exists among populations, which has not yet been fully explored. Therefore, we conducted a dose-response meta-analysis of 9 population-based cohort studies in which we examined total dairy, low-fat dairy, high-fat dairy, and different types of dairy products in relation to incidence of HTN.

Methods

Study Selection

A systematic literature search was conducted for articles on dairy consumption and BP or HTN, which were published until July 2011, using the databases of PubMed (www.ncbi.nlm.nih.gov/pubmed), Embase (www.embase.com), and Scopus (www.scopus.com). Titles and abstracts were screened to select prospective studies on dairy intake and HTN or BP changes over time. We identified a total of 1709 unique articles, from which we excluded animal studies, in vitro studies, comments, letters, editorials, ecological studies, and randomized controlled trials. Studies in children, adolescents and pregnant women, patients, and hypertensive populations were also excluded. Additional articles were found by checking bibliographies of cohort studies and reviews.

From the 18 studies that met the inclusion criteria, the full text was retrieved. Of these, we excluded 9 articles for the following reasons: no specific exposure data presented for dairy but only dairy included in dietary patterns or dairy micronutrients,1012 data on metabolic syndrome and not HTN or BP,13,14 no relative risks (RRs) available for incident HTN by type of dairy,15 cross-sectional design,16 hypertensive population,17 and 1 article for the same study population, Coronary Artery Risk Development in Young Adults (CARDIA) Study.18 If insufficient data were reported in the article (eg, no specific risk estimates for different dairy products and HTN incidence), additional information was requested from the authors.1923 Eventually, 9 studies1927 were included in the meta-analysis. For 3 of these studies that used BP change as the primary outcome,2022 additional data on HTN incidence during follow-up were supplied by the authors. Figure S1 in the online-only Data Supplement provides a flow chart for the selection of studies for meta-analysis.

Figure 1.

Figure 1. A, Forest plot for the linear dose-response relationship between total dairy intake (per increment of 200 g/d) and hypertension (HTN) incidence from 9 studies. Shown are author names, year of publication, country, study population, relative risks (RRs), 95% CIs, and weight to the overall meta-analysis. Study-specific RRs and 95% CIs are visualized in squares. The area of the squares is proportional to the specific study weight to the overall meta-analysis. The diamond presents the pooled RR and a 95% CI. The percentage of heterogeneity because of between-study variation is shown by I2. B, Ding Spaghetti plot for the linear dose-response relationship between total dairy intake and HTN incidence from 9 studies. Each gray (thin) line represents a study. The circles are placed at the study-specific RRs that are related to the corresponding quantity of intake. The area of the circle is proportional to the study-specific weight. The solid black line represents the pooled RR at each quantity of intake and the dashed line the corresponding 95% CI. SUN indicates Seguimiento University of Navarra; CARDIA, Coronary Artery Risk Development in Young Adults; ARIC, Atherosclerosis Risk in Communities Study; MORGEN, Monitoring van Risicofactoren en Gezondheid in Nederland; SU.VI.MAX, SUpplementation en VItamines et Mineraux Anti-oXydants (trial with daily supplementation with antioxidant vitamins and minerals).

Statistical Methods

We defined 7 dairy categories for the present meta-analysis, namely total dairy, milk, low-fat dairy, high-fat dairy, total fermented dairy, yogurt, and cheese. For each category of dairy intake, the total number of subjects, number of cases, dairy intake data, and RR with SE or 95% CI were extracted from the selected articles. In 3 studies, findings were presented as odds ratios, whereas incident HTN occurred in >10% of the study participants.21,24,26 Because of the high HTN incidence, the odds ratios may present an overestimation of the true RR in these studies, and we, therefore, attenuated the odds ratios using a previously published correction method.28 In the American studies, dairy intakes were presented in servings per day20,23 or in times per day.27 To convert these intakes in grams per day, conversions from the US Food Guide Pyramid were used (eg, 247 g for 1 serving of milk and 245 g for 1 serving of yogurt).29 From each publication, results from the final multivariable model was used, which included adjustments for lifestyle and dietary variables (Table S1 in the online-only Data Supplement). We used STATA version 11.0 (STATA Corp, College Station, TX) for statistical analyses.

For visualizing dose-response relationships across all data, Spaghetti Plots, developed by coauthor Eric L. Ding, were created to illustrate the direction and shape of the associations between the intake of different types of dairy and incident HTN, where each noodle of the Spaghetti Plot represents the data contribution of each study. Study-specific dose-response associations were computed for all types of dairy according to the generalized least squares for trend estimation method of Greenland and Longnecker.30 Random-effects weighted pooling was conducted using DerSimonian and Laird random-effects models.31 Forest plots were made to visualize and summarize the associations of the different types of dairy and HTN incidence. Pooled estimates were expressed in round numbers that approximated a normal portion size and fitted within the range of dairy intake of all studies (ie, 200 g for milk, total, low-fat, and high-fat dairy; 150 g for fermented dairy; 50 g for yogurt; and 30 g for cheese). In addition, spline knots were created to check for potential nonlinear dose-response associations between the intake of different types of dairy and HTN incidence. In case of a nonlinear association, piecewise spline regression models were used to express varying dose-response relationships within different intake intervals. We assessed the I2 statistic to represent the percentage of total variation attributable to between-study heterogeneity.32

Stratified analyses were performed (only linearly) by mean age of study cohorts (<50 and >50 years), continent (Europe and United States), mean body mass index (BMI) of study cohorts (normal weight and overweight; BMI <25 and ≥25 kg/m2), and follow-up duration (<6 and >6 years), if ≥3 studies were available per subgroup. Meta-regression was used to examine effect measure modification for these subgroup variables, and P values for interaction are presented. An additional sensitivity analysis was performed excluding the large Women’s Health Study,23 because that study included only women and provided no data on total cheese and total milk (but only cottage cheese and skim milk). The funnel plot was made for total dairy intake and HTN incidence to visualize publication bias, and the Egger test was used to assess publication bias.33

Results

Study Characteristics

The Table shows the characteristics of the 9 prospective cohort studies that were included in the meta-analysis. In total, data from 57 256 individuals were available for analysis. Apart from the Women’s Health Study,23 studies were performed in both sexes, with the percentage of men ranging from 39% to 47%. The mean age of study populations was 48±12 years (range, 25–65 years), and follow-up lasted 5 to 15 years. Three studies were conducted in the United States20,23,27 and 6 in Europe.19,21,22,2426 The types of dairy intake that were examined and definitions of dairy categories differed across studies, as described in Table S2.

Apart from 1 study,27 all studies used the same definition for HTN, that is, systolic BP (SBP) ≥140 mm Hg or diastolic BP (DBP) ≥90 mm Hg or use of antihypertensive medication. In the CARDIA Study, HTN was defined as SBP ≥130 mm Hg or DBP ≥85 mm Hg or use of antihypertensive medication.27 In 2 studies, HTN incidence was based on self-report.19,23 In the remaining studies, HTN cases were confirmed during physical examination. Table S3 shows the characteristics of meta-analyses per dairy category.

Total Dairy

Nine studies assessed the association between total dairy intake and HTN incidence.1927 These studies included a total of 57 256 individuals, of whom 15 367 developed HTN, and mean (or median) dairy intakes in the different studies varied between 257 and 458 g/d. Total dairy intake was linearly associated with HTN incidence (Figure 1A and 1B), with a pooled RR for HTN of 0.97 (95% CI, 0.95–0.99) per 200 g/d and no significant statistical heterogeneity (I2=28%; P=0.19). Excluding the Women’s Health Study and stratification by continent, age, and follow-up time did not alter the results. Stratification by BMI showed a slightly stronger association in overweight versus normal-weight populations. The pooled RR per intake of 200 g/d was 1.00 (95% CI, 0.96–1.04) for the 4 studies, with a mean BMI <25 kg/m2,19,21,24,26 and 0.96 (95% CI, 0.94–0.98) for the 5 studies, with a mean BMI ≥25 kg/m2.20,22,23,25,27 The funnel plot for the studies of total dairy with HTN incidence showed reasonable symmetry (Figure S2), with no evidence for publication bias (P=0.17).

Figure 2.

Figure 2. A, Forest plot for the linear dose-response relationship between low-fat dairy intake (per increment of 200 g/d) and hypertension (HTN) incidence from 6 studies. Shown are author names, year of publication, country, study population, relative risks (RRs), 95%CIs, and weight to the overall meta-analysis. Study-specific RRs and 95% CIs are visualized in squares. The area of the squares is proportional to the specific study weight to the overall meta-analysis. The diamond presents the pooled RR and a 95% CI. The percentage of heterogeneity because of between-study variation is shown by I2. B, Ding Spaghetti plot for the linear dose-response relationship between low-fat dairy intake and HTN incidence from 6 studies. Each gray (thin) line represents a study. The circles are placed at the study-specific RRs that are related to the corresponding quantity of intake. The area of the circle is proportional to the study-specific weight. The solid black line represents the pooled RR at each quantity of intake and the dashed line the corresponding 95% CI. SUN indicates Seguimiento University of Navarra; MORGEN, Monitoring van Risicofactoren en Gezondheid in Nederland (study set up to examine risk factors and health in the Netherlands)

Low- and High-Fat Dairy

Intake of low-fat dairy and high-fat dairy was assessed in 6 studies,19,2226 including a total of 42 407 individuals (11 365 HTN cases). Mean intakes in the different studies were 205 to 271 g/d for low-fat dairy and 98 to 228 g/d for high-fat dairy. Low-fat dairy was linearly and inversely associated with HTN incidence, with a pooled RR of 0.96 (95% CI, 0.93–0.99) per intake of 200 g/d (Figure 2A and 2B). Intake of high-fat dairy was not associated with HTN incidence (RR per 200 g/d, 0.99; 95% CI, 0.95–1.03) (Figure S3A and S3B). There was no significant heterogeneity for the associations with low-fat (I2=25%; P=0.25) or high-fat dairy (I2=0%; P=0.44). Excluding the Women’s Health Study did not change the pooled RR for low-fat dairy but yielded a slightly different estimate for high-fat dairy (RR per 200 g/d, 1.03; 95% CI, 0.95–1.11). Stratification by age or BMI did not change the results. For continent and follow-up time, subgroups were too small to perform stratified analyses.

Milk

Seven studies2023,25–27 assessed the intake of milk and incident HTN, including 47 647 individuals (14 398 HTN cases), with mean milk intakes of 117 to 264 g/d. A significant inverse linear association was found, with a pooled RR of 0.96 (95% CI, 0.94–0.98) per increment of 200 g/d (Figure S4A and S4B). Spline models did not reveal significant nonlinearity. Excluding the Women’s Health Study (data for skim milk only) and stratification by continent and follow-up time did not alter the results. For age and BMI, subgroups were too small to perform stratified analyses.

Total Fermented Dairy, Cheese, and Yogurt

Four studies reported data for total fermented dairy intake.22,2426 These studies were composed of 7641 individuals (2475 HTN cases) and mean total fermented dairy intake of 84 to 201 g/d. The pooled RR for HTN incidence was 0.99 (95% CI, 0.94–1.04) per 150 g/d. Stratified analyses could not be performed because of the limited number of studies.

Associations with yogurt intake were assessed in 5 studies20,2224,27 that included 45 088 individuals (12 959 HTN cases), with mean yogurt intakes of 10 to 79 g/d. Yogurt intake was not associated with HTN incidence. The pooled RR for HTN incidence was 0.99 (95% CI, 0.96–1.01) per 50 g/d (Figure S5A). Stratified analyses could not be performed because of the limited number of studies. Excluding the Women’s Health Study did not essentially change the results.

Associations with cheese intake were assessed in 8 studies,2027 which included 51 007 individuals (15 066 HTN cases) with mean cheese intakes of 10 to 43 g/d. The pooled RR for association of cheese intake with HTN incidence was 1.00 (95% CI, 0.98–1.03) per 30 g/d (Figure S6A and S6B). After exclusion of the Women’s Health Study (assessing cottage cheese only), the RR for HTN incidence increased to 1.02 (95% CI, 0.99–1.05) per 30 g/d. Stratification by continent, age, BMI, and follow-up time did not change the results.

No heterogeneity was observed in the analyses of total fermented dairy, yogurt, and cheese.

Discussion

This meta-analysis showed that total dairy intake was associated with a 3% lower risk of HTN per 200 g/d. When examining different types of dairy products in relation to HTN risk, we found significant inverse associations with low-fat dairy and milk. For high-fat dairy, total fermented dairy products, yogurt, and cheese, no significant associations with HTN were found.

Our results are based on data from prospective cohort studies, in which dairy intake was mostly assessed by food-frequency questionnaires. In several studies, validation of the food-frequency questionnaires showed good correlations of ≈0.7 for milk or (if not assessed) for protein and calcium, which are good indicators for milk intake.19,2224 Dietary intake data in the different studies were collected between 1985 and 2002. In earlier studies,20,22,26,27 high-fat milk was a major contributor to total milk intake, whereas in later studies19,21,2325 this was more often low-fat milk. In spite of variations in types of dairy intake between populations (Table S2) and over time, no statistical heterogeneity was present, and stratified analysis by continent, age, BMI, and follow-up time did not show substantially different results.

Our meta-analyses covered a broad range of dairy products. Data on dairy intake were converted into grams per day for all studies, using country-specific conversions, and pooled RRs for incident HTN were obtained using an advanced statistical approach.30 For zero intakes and intakes >700 g/d (total dairy) or >500 g/d (milk, low-fat dairy), we had insufficient data to draw conclusions. Our results are in line with the results from a recent systematic review8 and with a pooled meta-analysis by Ralston et al,9 which showed significant inverse associations for high versus low intake of total dairy (RR, 0.87), low-fat dairy (RR, 0.84), and fluid dairy (ie, milk and yogurt; RR, 0.92) with incident HTN, whereas no significant associations were found for high-fat dairy and cheese.

Our results also corroborate data from a prospective study of 2290 older participants at high cardiovascular risk by Toledo et al,17 which was excluded from our meta-analysis, because 80% of their participants already had HTN at baseline. They found an inverse association of low-fat dairy, but not high-fat dairy, with BP change during 1 year of follow-up, with a significant −4.2 mm Hg difference in SBP for the highest versus lowest quintile of low-fat dairy. Low-fat and high-fat dairy intakes were also examined in relation to 4-year incidence of HTN in 30 681 predominantly white US men who participated in the Health Professionals Study, and it was reported that no statistically significant associations were found.10 Specific data on dairy intake, however, could not be obtained, and we, therefore, had to exclude this study. If RRs for increasing levels of dairy intake in the Health Professionals Study were close to or >1, the beneficial associations as reported in the present meta-analysis could be overestimated.

Randomized trials of dairy intake and BP in healthy individuals, with follow-up periods ranging from 8 to 40 weeks, showed inconsistent results.3440 In overweight and obese subjects, dairy intake (combining milk, cheese, and yogurt) lowered SBP only,34 DBP only,35 both,36 or none.3739 In a study of young normal-weight adults (mean BP, 118/69 mm Hg), high-fat dairy increased SBP but not DBP, and no benefit was found for low-fat dairy.40 The DASH trial among 459 US adults, on the other hand, showed that BP can be substantially reduced by an 8-week diet rich in fruits, vegetables, and low-fat dairy products compared with a typical US diet, with reductions in SBP up to −11 mm Hg in hypertensive participants. Because of the multifactorial intervention, it is, however, not clear to what extent the inclusion of low-fat dairy products contributed to the DASH effect.5 To the best of our knowledge, no long-term trials (>1 year) of dairy intake and incident HTN have been conducted.

Dairy is a major source of dietary calcium and potassium, 2 minerals that could lower BP. An intake of 200 g of nonfortified milk provides ≈250 mg of calcium and 300 mg of potassium.41,42 A meta-analysis of 40 randomized controlled trials showed a small but significant effect of ≈1 g/d of calcium supplementation on SBP and DBP (−1.9/−1.0 mm Hg).43 Significant reductions in BP (−2.4/−1.6 mm Hg) were also found for ≈2 g/d of potassium supplementation in a meta-analysis of 27 trials.44 In addition, it has been suggested that other nutrients in dairy, such as magnesium, phosphorus, and proteins, could improve BP.8 From our observational data, we cannot conclude to what extent these different components in dairy contributed to the inverse associations with incident HTN and whether the relationship is causal.

We found a small inverse association of low-fat, but not high-fat dairy, with HTN incidence. People who consume low-fat dairy may be more health conscious and have a healthier eating and lifestyle pattern. In all studies included in our meta-analysis, adjustment was performed for smoking, alcohol intake, total energy intake, and several dietary confounders. However, residual confounding cannot be ruled out in observational studies. One study did not adjust for BMI,27 and 3 studies did not adjust for physical activity,22,24,25 which are important determinants of HTN risk. Exclusion of studies that did not adjust for physical activity,22,24,25 however, yielded similar results for total, low-fat, and high-fat dairy. Alternatively, the lower risk of HTN in those consuming low-fat dairy could be because of replacement of other beverages, for example, sugar-containing soft drinks that have been associated with increased BP.45,46 The intake of high-fat dairy was not inversely associated with HTN in our meta-analysis, in contrast to intake of low-fat dairy. Apart from residual confounding by factors related to a more unhealthy diet or lifestyle, we have no ready explanation for this finding. High-fat dairy products are a source of saturated and trans fatty acids, although there has been little convincing evidence to date that dairy fat increases the risk of HTN.4749 Furthermore DASH diet, low in saturated fat (rich in low-fat dairy, fruits, and vegetables), has been shown to lower BP.5 We also found no relationship with cheese, which may partly be explained by its relatively high content of salt that is known to raise BP.44

Overall, this meta-analysis of prospective cohort studies showed an inverse association of low-fat dairy and milk with risk of HTN, which needs confirmation in randomized controlled trials.

Perspectives

US dietary guidelines recommend consumption of 3 cups of dairy per day, preferably fat-free or low-fat milk or yogurt. The results from our meta-analysis of prospective cohort studies showed that intake of dairy, in particular low-fat dairy and milk, could reduce the risk of HTN with 3% per 200 g/d within the range of intakes that we studied (100–700 g/d). These findings warrant confirmation in randomized, controlled trials.

Acknowledgments

We thank the authors who contributed data to this meta-analysis: M.A. Martínez-González (SUN cohort, data on high-fat dairy intake), A. Alonso (ARIC Study, data on the associations of total dairy, total milk, total cheese, and yogurt with HTN incidence), E. Kesse-Guyot and S. Hercberg (SU.VI.MAX Study, data on the associations of total dairy, milk, and cheese with HTN incidence), M.B. Snijder and J.M. Dekker (Hoorn Study, provision of the data set), L. Wang (Women’s Health Study, data on milk, yogurt, and cheese intake), and A. Heraclides (1946 National Birth Cohort, provision of his prepublication). We thank Dione Bouchaut (Wageningen University, Netherlands) for graphical work on the Figures for this article.

Footnotes

The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA.112.195206/-/DC1.

*S.S.S.-M. and L.D.M.V. contributed equally to this study.

Correspondence to Dr Sabita S. Soedamah-Muthu, Wageningen University, Division of Human Nutrition, PO Box 8129, 6700 EV Wageningen, the Netherlands. E-mail

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Novelty and Significance

What Is New?

  • Assessment of different types of dairy in relation to hypertension risk

  • Standardization among studies for levels of intake and examination of dose-response associations by means of an advanced meta-analysis technique

What Is Relevant?

  • Low-fat dairy and milk were inversely related to risk of hypertension, whereas high-fat dairy and fermented dairy were not.

  • Dairy is frequently consumed in Western societies, and the burden of hypertension is high; therefore, the results of this study could have a substantial public health impact.

Summary

The results from this meta-analysis based on data from 9 prospective cohort studies showed a small beneficial association between dairy intake, especially low-fat dairy and milk, and hypertension risk.

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