Dairy Consumption and Incidence of Hypertension
Transcript
Dairy Consumption and Incidence of Hypertension
Dairy Consumption and Incidence of Hypertension A Dose-Response Meta-Analysis of Prospective Cohort Studies Sabita S. Soedamah-Muthu,* Lisa D.M. Verberne,* Eric L. Ding, Mariëlle F. Engberink, Johanna M. Geleijnse 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. (Hypertension. 2012;60:1131-1137.) ● Online Data Supplement Key Words: dairy products ◼ milk ◼ hypertension ◼ blood pressure ◼ meta-analysis ◼ prospective studies H ypertension (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.6–8 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 populationbased 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. Received March 12, 2012; first decision March 21, 2012; revision accepted August 14, 2012. From the Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands (S.S.S.-M., L.D.M.V., M.F.E., J.M.G.); Department of Nutrition, Harvard School of Public Health, Boston, MA (E.L.D.); and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (E.L.D.). 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 [email protected] © 2012 American Heart Association, Inc. Hypertension is available at http://hyper.ahajournals.org DOI:10.1161/HYPERTENSIONAHA.112.195206 1131 1132 Hypertension November 2012 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,10–12 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.19–23 Eventually, 9 studies19–27 were included in the meta-analysis. For 3 of these studies that used BP change as the primary outcome,20–22 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. types of dairy and incident HTN, where each noodle of the Spaghetti Plot represents the data contribution of each study. Study-specific doseresponse 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 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 Results Study Characteristics The Table shows the characteristics of the 9 prospective cohort studies that were included in the meta-analysis. In total, data Table. Characteristics of 9 Prospective Cohort Studies That Were Included in a Meta-Analysis of Dairy Intake and Incident Hypertension Study Population Reference Country Men, Mean Mean BMI, % Age, y kg/m2 Follow-Up Time, y Subjects (Cases) Dietary Assessment Baseline Period HTN Assessment 19 Alonso et al SUN cohort Spain 39 37 23.1 2 5880 (180) 136-item FFQ 1999–2002 Self-report* Alonso et al20 ARIC Study United States 43 53 26.4 9 8204 (2399) 66-item FFQ 1987–1989 Physical examination* Dauchet et al21 SU.VI.MAX cohort France 36 50 24.8 5 2341 (606) 6-d dietary records 1994 Physical examination* Engberink et al24 MORGEN Study The Netherlands 45 50 24.9 5 3454 (713) 178-item FFQ 1993–1997 Physical examination* Engberink et al25 Rotterdam Study The Netherlands 43 65 25.7 6 2245 (984) 170-item FFQ 1990–1993 Physical examination* Snijder et al22 Hoorn Study The Netherlands 46 59 25.4 5 755 (319) 92-item FFQ 1989 Physical examination* Steffen et al27 CARDIA Study United States 43 25 25.2 15 4304 (997) Dietary history, average y 0 and 7 1985–1986, 1992–1993 Physical examination† Wang et al23 Women’s United States Health Study 0 54 25.1 10 28 886 (8 710) 131-item FFQ 1992–1995 Self-report* 47 43 24.8 10 1187 (459) 5-day dietary records 1989 Physical examination* Heraclides et al26 1946 National United Kingdom Birth Cohort BMI indicates body mass index; HTN, hypertension; FFQ, food-frequency questionnaire; SUN, Seguimiento University of Navarra; ARIC, Atherosclerosis Risk in Communities Study; SU.VI.MAX, SUpplementation en VItamines et Mineraux Anti-oXydants; MORGEN, Monitoring van Risicofactoren en Gezondheid in Nederland; CARDIA, Coronary Artery Risk Development in Young Adults. *Definition of HTN was SBP ≥140 mm Hg or DBP ≥90 mm Hg or use of antihypertensive medication. †Definition of HTN was SBP ≥130 mm Hg or DBP ≥85 mm Hg or use of antihypertensive medication. Soedamah-Muthu et al Meta-Analysis of Dairy and Hypertension 1133 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.19,21,22,24–26 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 metaanalyses per dairy category . Total Dairy Nine studies assessed the association between total dairy intake and HTN incidence.19–27 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). Low- and High-Fat Dairy Intake of low-fat dairy and high-fat dairy was assessed in 6 studies,19,22–26 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 studies20–23,25–27 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.22,24–26 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 studies20,22–24,27 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,20–27 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 foodfrequency 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.19,22–24 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 studies19,21,23–25 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 1134 Hypertension November 2012 A Author Year Country Study Population Relative Risk % Weight (95% CI) Alonso 2005 ES SUN cohort 0.91 (0.80–1.03) 2.83 Steffen 2005 USA CARDIA Study 0.93 (0.88–0.99) 9.80 Engberink 2009 NL Rotterdam Study 0.94 (0.89–0.99) 12.65 Wang 2008 USA Women’s Health Study 0.96 (0.94–0.98) 30.81 Alonso 2009 USA ARIC Study 0.97 (0.93–1.01) 18.06 Heraclides 2012 UK 1946 National Birth Cohort 1.01 (0.92–1.12) 4.25 Engberink 2009 NL MORGEN Study 1.01 (0.96–1.07) 12.18 Dauchet 2007 FR SU.VI.MAX cohort 1.02 (0.93–1.12) 4.88 Snijder 2008 NL Hoorn Study 1.04 (0.95–1.14) 4.54 Overall 0.97 (0.95–0.99) 100.00 (I2=28.3%, P=0.193) NOTE: Weights are from random-effects analysis 0.1 B Relative Risk 0.5 1.0 2.0 Relative Risk 1.2 1.0 0.8 0.6 0 200 400 600 800 Total Dairy (grams per day) 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 studyspecific 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). 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), lowfat 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 Soedamah-Muthu et al Meta-Analysis of Dairy and Hypertension 1135 A Author Year Country Study population Alonso 2005 ES SUN cohort 0.81 (0.68–0.97) 3.43 Engberink 2009 NL Rotterdam Study 0.94 (0.88–1.00) 19.28 Engberink 2009 NL MORGEN Study 0.94 (0.87–1.02) 14.22 Wang 2008 USA Women’s Health Study 0.96 (0.93–0.98) 45.73 Snijder 2008 NL Hoorn Study 1.01 (0.92–1.10) 11.32 Heraclides 2012 UK 1946 National Birth Cohort 1.03 (0.91–1.18) 6.01 Relative Risk (95% CI) Overall % Weight 0.96 (0.93–0.99) 100.00 2 (I =25.1%, P=0.246) NOTE: Weights are from random-effects analysis 0.1 B Relative Risk 0.5 1.0 2.0 1.2 Relative Risk 1.0 0.8 0.6 0.4 0 200 400 Low−Fat Dairy (grams per day) 600 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) 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.34–40 In overweight and obese subjects, dairy intake (combining milk, cheese, and yogurt) lowered SBP only,34 DBP only,35 both,36 or none.37–39 In a study of young normal-weight adults (mean BP, 118/69 mm Hg), highfat 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 metaanalysis 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. 1136 Hypertension November 2012 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 lowfat 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.47–49 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. KesseGuyot 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. Sources of Funding S.S. Soedamah-Muthu and J.M. Geleijnse obtained an unrestricted grant from the Dutch Dairy Association (NZO) for meta-analyses of dairy products and cardiovascular diseases. S.S. Soedamah-Muthu recently (May 2012) obtained a project grant from Global Dairy Platform for meta-analyses on cheese and blood lipids. These funding organizations were not involved in the design, data collection, data interpretation, or reporting of the present study. Disclosures E.L. Ding has consulted for Dairy Research Institute, unrelated to this study. The other authors have no conflicts to report. References 1.Mackay J, Mensah GA. Risk factors. In: The Atlas of Heart Disease and Stroke. Geneva, Switzerland: World Health Organization; 2004. http://www.who.int/cardiovascular_diseases/en/cvd_atlas_01_types.pdf. Accessed June 13, 2012. 2. 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Novelty and Significance What Is New? • A ssessment 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.