ORIGINAL CONTRIBUTION

Dairy products and the risk of stroke and coronary heart disease:the Rotterdam Study

Jaike Praagman • Oscar H. Franco • M. Arfan Ikram •

Sabita S. Soedamah-Muthu • Marielle F. Engberink •

Frank J. A. van Rooij • Albert Hofman • Johanna M. Geleijnse

Received: 30 April 2014 / Accepted: 23 September 2014

� Springer-Verlag Berlin Heidelberg 2014

Abstract

Purpose We examined whether consumption of total

dairy and dairy subgroups was related to incident stroke

and coronary heart disease (CHD) in a general older Dutch

population.

Methods The study involved 4,235 participants of the

Rotterdam Study aged 55 and over who were free of car-

diovascular disease (CVD) and diabetes at baseline

(1990–1993). Multivariable Cox proportional hazards

models were used to calculate hazard ratios (HRs) for the

intake of total dairy and dairy subgroups in relation to

incident CVD events.

Results Median intake of total dairy was 397 g/day,

which mainly comprised low-fat dairy products (median

intake of 247 g/day). During a median follow-up time of

17.3 years, 564 strokes (182 fatal) and 567 CHD events

(350 fatal) occurred. Total dairy, milk, low-fat dairy, and

fermented dairy were not significantly related to incident

stroke or fatal stroke (p [ 0.2 for upper vs. lower intake

categories). High-fat dairy was significantly inversely

related to fatal stroke (HR of 0.88 per 100 g/day; 95 % CI

0.79, 0.99), but not to incident stroke (HR of 0.96 per

100 g/day; 95 % CI 0.90, 1.02). Total dairy or dairy sub-

groups were not significantly related to incident CHD or

fatal CHD (HRs between 0.98 and 1.05 per 100 g/day, all

p [ 0.35).

Conclusions In this long-term follow-up study of older

Dutch subjects, total dairy consumption or the intake of

specific dairy products was not related to the occurrence of

CVD events. The observed inverse association between

high-fat dairy and fatal stroke warrants confirmation in

other studies.

Keywords Dairy � Milk � Coronary heart disease �Stroke � Population-based study

Abbreviations

ATC Anatomical therapeutic chemical

CHD Coronary heart disease

CVD Cardiovascular disease

GP General practitioner

MI Myocardial infarction

SFFQ Semiquantitative food frequency questionnaire

Introduction

A diet rich in saturated and industrial trans fats has been

linked to an increased risk of cardiovascular disease

(CVD), in particular coronary heart disease (CHD). This

potential adverse effect is supported by well-controlled

human intervention studies that showed consistent reduc-

tions in blood LDL cholesterol levels when saturated fat

was replaced by unsaturated fat [1]. Although dairy pro-

ducts are a major food source of saturated fat, their con-

sumption was not consistently associated with a higher

Electronic supplementary material The online version of thisarticle (doi:10.1007/s00394-014-0774-0) contains supplementarymaterial, which is available to authorized users.

J. Praagman � S. S. Soedamah-Muthu �M. F. Engberink � J. M. Geleijnse (&)

Division of Human Nutrition, Wageningen University,

P.O. Box 8129, 6700 EV Wageningen, The Netherlands

e-mail: marianne.geleijnse@wur.nl

O. H. Franco � M. A. Ikram � F. J. A. van Rooij � A. Hofman

Department of Epidemiology, Erasmus Medical Center,

Rotterdam, The Netherlands

123

Eur J Nutr

DOI 10.1007/s00394-014-0774-0

CVD risk in cohort studies. A dose–response meta-analysis

of 17 prospective cohort studies (ten from Europe, five

from USA, and two from Asia) showed no relation between

intake of total dairy (four studies RR 1.02; 95 % CI

0.93–1.11) or milk (six studies RR 1.00; 0.96–1.04) and

CHD mortality [2]. This meta-analysis also showed that a

higher intake of milk was related to a 13 % lower risk of

fatal stroke, although this was not statistically significant

(six studies: RR 0.87; 95 % CI 0.72–1.05).

In recent years, new evidence emerged from prospective

cohort studies on dairy subgroups in relation to CHD [3–9]

and stroke [3, 4, 6, 7, 9–11]. In line with the earlier meta-

analysis, these studies found no relation between dairy

subgroups and CHD risk [3, 6–9], except for an inverse

association between cheese consumption and risk of

myocardial infarction (MI) [5] and between low-fat milk

and incident CHD [4]. With regard to stroke, findings were

inconsistent. Several studies showed significant inverse

associations with low-fat milk [4], low-fat dairy [10] and

fermented dairy [3, 4], whereas in four other studies, the

consumption of specific dairy foods was not related to

stroke [6, 7, 9, 11].

We set up the present study to get more insight in spe-

cific dairy foods in relation to long-term risk of CVD, in

particular stroke, in a general population of older Dutch

men and women with a relatively high habitual dairy

intake.

Subjects and methods

The Rotterdam Study

The Rotterdam Study is a prospective, population-based

cohort study on risk factors for chronic diseases at older

age [12]. Starting in January 1990, all residents aged

55 years and over of a well-defined district in Rotterdam

were invited to participate. Of those, 7,983 men and

women (78 %) entered the study. Baseline data were col-

lected between August 1990 and June 1993. Subjects were

interviewed at home by a trained research assistant, after

which they were invited for physical examination and

dietary assessment at the research center. All subjects gave

written informed consent, and the study protocol was

approved by the medical ethics committee of Erasmus

University, Rotterdam. Detailed information on the design

of the Rotterdam Study can be found elsewhere [12].

Dietary assessment

Habitual dietary intake was assessed at baseline following

a two-step approach. A self-administered questionnaire

was filled out at home to collect data on types of foods and

beverages that were consumed at least twice a month

during the preceding year, as well as dietary habits, use of

supplements, and prescribed diets. Based on this ques-

tionnaire, a trained dietician interviewed the subjects at the

research center using a semiquantitative food frequency

questionnaire (SFFQ) to assess the amount and consump-

tion frequency of foods and beverages. This SFFQ con-

tained 170 food items on 13 food groups and additional

questions on prescribed diets, use of supplementation and

dietary habits. Seasonal variation was taken into account.

With regard to dairy intake, subjects were asked to indicate

the type of dairy and the frequency of consumption in times

per day, week, or month. The amount of dairy consumed

was expressed in common household units (e.g., slice of

cheese, glass of milk). The SFFQ was validated against

multiple food records and showed good correlations for

calcium (r = 0.72) and protein (r = 0.66) [13]. Dairy

products contributed *70 % of the calcium intake

and *25–30 % of the total protein intake in our

population.

The SFFQ data were linked to the Dutch food compo-

sition Table [14] to derive intake of total energy, ma-

cronutrients, and micronutrients. In the present analysis,

total dairy included milk, buttermilk, yogurt, coffee crea-

mer, curd, pudding, porridge, custard, whipped cream, ice

cream, and cheese, but not butter. Seven dairy subgroups,

which were not mutually exclusive, were created as fol-

lows: low-fat dairy (milk and milk products with a fat

content \2.0/100 g and cheese products with a fat con-

tent \20/100 g); high-fat dairy (milk and milk products

with a fat content C2.0/100 g and cheese products with a

fat content C20/100 g); total milk (all types of dairy,

excluding cheese); fermented dairy (all types of buttermilk,

yogurt, curd and cheese); cheese (all types of cheese,

excluding curd); and yogurt.

Assessment of co-variables

Information on health status, medical history, medication,

smoking behavior, and socioeconomic status was obtained

during a home interview by a trained interviewer who used

structured questionnaires. Subjects were classified as never,

former, or current smokers. Education was defined as low

(primary education), intermediate (secondary general or

vocational education), and high (higher vocational educa-

tion or university). Alcohol intake was expressed in grams

per day and divided into four categories (none; 0–10;

11–20; and [20 g/day). Medication was coded according

to the anatomical therapeutic chemical (ATC) classification

system [15].

During physical examination at the research center,

height and weight of the participants were measured while

wearing indoor clothes without shoes. Body mass index

Eur J Nutr

123

(BMI) was calculated as weight divided by height squared

(kg/m2). Blood pressure was calculated as the mean of two

consecutive measurements with a random-zero sphygmo-

manometer while subjects were in sitting position and had

rested for 5 min. Subjects were classified as hypertensive

when they fulfilled one or more of the following criteria:

(1) systolic blood pressure C140 mmHg; (2) diastolic

blood pressure C90 mmHg; and (3) use of antihyperten-

sive medication. Information on the prevalence of CVD at

baseline was assessed during the home interview and ver-

ified by study physicians using medical records and/or

physical examination at the research center. During the

physical examination, several tests were performed,

including an ECG. Besides this examination, information

on prevalent diseases was obtained through linkage with

data from the Nationwide Medical Registry (LMR, Utr-

echt, the Netherlands) [16]. Diabetes was considered

present when the participant used anti-diabetic medication

(ATC code A010) or when they had a non-fasting or post-

load glucose concentration C11.1 mmol/L [17].

Outcome assessment

For the present analysis, follow-up information until Jan-

uary 1, 2011, was used. Information on vital status and the

date of death was obtained from municipality records at

regular intervals. Causes of death were independently

determined by a research physician using information from

medical records and subsequently validated by a medical

specialist in the relevant field (e.g., cardiologist or neu-

rologist), whose judgment was considered decisive. Fatal

stroke events were classified according to the 10th revision

of the International Classification of Diseases (ICD-10)

[18, 19], and fatal CHD was classified according to the

definitions based on recommendations from widely

endorsed international guidelines [16, 20]. Codes which the

physicians disagreed on were discussed to reach consensus.

Information on incident stroke and CHD was obtained

through digital record linkage with general practitioners

(GP) and medical specialists in the research area. Trained

research assistants checked medical records for informa-

tion about the CVD events, including ECGs and hospital-

ization discharge letters.

Incident stroke comprised all non-fatal and fatal stroke

(ICD-10 codes I60–I69) events and was defined as rapidly

developing clinical signs or symptoms of vascular origin

lasting 24 h or more or leading to death [18]. Information

on potential strokes was reviewed by research physicians

and verified by an experienced stroke neurologist.

Incident CHD comprised non-fatal and fatal myocardial

infarctions (MI) and fatal CHD [16]. MI was defined on

basis of typical changes in cardiac biomarkers and/or

indicative ECG changes and preferably the presence of

symptoms or signs such as cardiac pain or cardiogenic

shock [16]. For fatal MI, pathology findings of an acute MI

within 28 days of death were taken into account. MI was

further classified as definite (diagnosis by medical spe-

cialist), probable (diagnosis by GP or nursing home phy-

sician), possible, or unlikely. For the present analysis, we

used definite and probable cases of CHD.

Population for analysis

Non-institutionalized subjects who visited the study center

at baseline (n = 6,521, 82 % of the cohort) were eligible

for a dietary interview with a dietician. Diet was not

assessed in 874 subjects, mainly because of logistic reasons

and problems with dietary recall in subjects suspected from

dementia. Furthermore, 212 dietary reports were consid-

ered unreliable by the dietician and excluded. Dietary data

were thus available for 5,435 subjects.

We excluded 39 subjects who provided no informed

consent for the collection of follow-up data or of whom

follow-up data were missing. Furthermore, subjects with a

history of CHD (n = 694), stroke (n = 75), or clinically

diagnosed diabetes mellitus (n = 392) were excluded,

leaving 4,235 subjects for the present analysis.

Statistical analysis

Intakes of total dairy and dairy subgroups were divided into

three categories on basis of their range of intake. The

categories for total dairy, total milk, and low-fat dairy

corresponded to \200, 200–400, and [400 g/day. High-fat

dairy, fermented dairy, and yogurt were categorized

as \50, 50–100, and [100 g/day, and cheese as \20,

20–40, and [40 g/day. Baseline characteristics were cal-

culated within intake categories of total dairy and were

reported as means with standard deviations (SD), medians

with interquartile ranges (IQR), or percentages.

Cox regression analysis was used to calculate hazard

ratios (HRs) with 95 % confidence intervals (CI) for CHD

and stroke incidence within intake categories of total dairy

and dairy subgroups, using the lowest category as the ref-

erence. Similarly, HRs were obtained for mortality due to

CHD and stroke. Person-years were calculated as years

from baseline date to the first CHD or stroke event, last

contact (if lost to follow-up), death or January 1, 2011,

whichever came first.

Three multivariate Cox regression models were con-

structed to adjust for potential confounders. Confounders

were selected based on the literature and former compa-

rable studies. Since we examined intake of dairy groups,

we also adjusted for food groups. Model 1 adjusted for age

(continuous), gender, and total energy intake (continuous).

Model 2 additionally adjusted for BMI (continuous),

Eur J Nutr

123

smoking (current, former, never), educational level (low,

intermediate, high), and alcohol use (none; 0–10;

11–20; [20 g/day). Model 3 also adjusted for intakes of

vegetables, fruit, meat, fish, bread, coffee, and tea (all

continuous, in g/day). The proportional hazards assumption

was tested by calculating Schoenfeld residuals. Visual

examination of log–log plots showed no significant

deviations.

Total dairy and dairy subgroups were also analyzed as

continuous variables, expressed per 100 g/day (for cheese:

per 20 g/day), and HRs with 95 % CI and a p value for

linear trend were obtained for the relation with incident

events. Additional adjustment for the use of cardiovascular

medication (n = 1,067) did not change any of the HRs and

was therefore not included in the final model. In sensitivity

analyses, we repeated the analyses in a population

excluding all 1,067 subjects who used CVD medication

(serum lipid reducing or antihypertensive agents), since

these subjects may have had a less stable diet because of

awareness of their higher CVD risk. Data on physical

activity were obtained through a questionnaire in 1997 and

available in only 30 % (n = 1,289) of our study popula-

tion. The effect of physical activity on the HRs was

therefore examined in this subpopulation by comparing the

HRs of the full model with HRs after additional adjustment

for physical activity. To minimize the possibility of

reversed causation, we performed a sensitivity analysis in

which we excluded the first 2 years of follow-up. To check

whether hypertension could be an intermediary factor in

the relation between dairy intake and CVD outcomes, we

added this variable in the multivariable model and checked

the change in HRs. We also included total calcium, mag-

nesium, vitamin D, and protein intake one by one to the

final model to examine whether these nutrients could

explain part of the observed associations. All analyses were

executed in SAS version 9.2 (SAS Institute, Cary, NC,

USA), and results were considered to be statistically sig-

nificant if p \ 0.05 (two-sided).

Results

Table 1 shows the baseline characteristics of the study

population, which consisted of 2,632 women and 1,603

men with a mean age of 66.9 (± 7.7) years. The median

total dairy intake was 397 g/day (IQR 257–559 g/day).

About half of the subjects consumed more than 400 g/day

and fell in the highest intake category. With a median

intake of 247 g/day (IQR 99–416 g/day), low-fat dairy

represented the largest amount of consumed dairy foods,

whereas the median intake of high-fat dairy was 94 g/day

(IQR 52–179 g/day). About 32 % of the median high-fat

dairy intake consisted of high-fat cheese (median intake:

30 g/day (IQR 20–44 g/day). Median intakes for other

subgroups were as follows: 147 g/day (IQR 58–250) for

fermented dairy, 33 g/day (IQR 22–46) for cheese, and

43 g/day (IQR 0–107) for yogurt. During 62,701 person-

years of follow-up since baseline (median follow-up

13.3 years, IQR 11.8–18.2), 564 strokes (182 fatal) and 567

CHD events (350 fatal) occurred.

Stroke incidence

Table 2 presents the HRs for the associations between

stroke incidence and total dairy and dairy subgroups in

categories of intake. After adjustment for lifestyle and

dietary confounders, total dairy intake was not related to

stroke incidence (HR of 0.99; 95 % CI 0.76–1.27 for highest

vs. lowest category) or stroke mortality (HR of 0.90; 95 % CI

0.56–1.45). High-fat dairy intake of [100 g/day compared

to \50 g/day was not associated with incident stroke (HR of

0.83; 95 % CI 0.66–1.04, p = 0.11), but was associated with

fatal stroke (HR of 0.64; 95 % CI 0.43–0.96, p = 0.03). No

consistent significant associations were found between

intakes of total milk, low-fat milk, fermented dairy, cheese or

yogurt, and stroke incidence or stroke mortality (in upper

categories: all p [ 0.2).

Analyses expressed per 100 g/day (Table 3) were in line

with the results within categories. Low-fat dairy was not

associated with fatal stroke (HR of 1.00, p = 0.99), and

high-fat dairy intake was associated with a significant 12 %

fatal stroke risk reduction (p = 0.026). Total dairy and all

other dairy subgroups were not significantly associated

with stroke incidence or stroke mortality.

In a sensitivity analysis in subjects free of CVD med-

ication (supplemental Table 1), a non-significant 10 %

lower risk of fatal stroke (based on 120 events) was found

per 100 g/day increase in high-fat dairy. When analyzed

in categories (data not in table), high-fat dairy inta-

kes [100 g/day were associated with a borderline sig-

nificantly 37 % lower risk of fatal stroke (p = 0.07),

compared to intakes \50 g/day. For stroke incidence

(based on 350 events) in subjects without CVD medica-

tion, the associations with high-fat dairy were not statis-

tically significant (HR of 0.96 per 100 g/day, p = 0.3;

supplemental Table 1). All HRs remained similar after

additional adjustment for hypertension (supplemental

Table 2) and after additional adjustment for physical

activity level among 1,289 subjects with complete data on

physical activity (supplemental Table 3). Furthermore,

exclusion of the first 2 years of follow-up and additional

adjustment for intake of calcium, magnesium, vitamin D,

and protein did not alter any of the results either (data not

shown).

Eur J Nutr

123

CHD incidence

The HRs for the associations between dairy and dairy

subgroups with incident and fatal CHD are presented in

Table 4. No significant associations of total dairy, high-fat

dairy, low-fat dairy, and total milk with CHD incidence or

CHD mortality were observed (in upper categories: all

p [ 0.3). Intakes of yogurt and cheese were not related to

CHD incidence or CHD mortality (all p [ 0.3). In con-

tinuous analyses, HRs for the associations of total dairy and

dairy subgroups (low-fat dairy, high-fat dairy, milk, fer-

mented dairy) with CHD incidence and CHD mortality

were all non-significant (Table 3). In subjects free of CVD

medication (supplemental Table 1), also no significant HRs

for total dairy or dairy subgroups were found.

Discussion

In this prospective cohort study of 4,235 Dutch persons, we

observed no significant associations between consumption

of total dairy or dairy subgroups with risk of stroke or

CHD, except for an inverse association between high-fat

dairy and stroke mortality.

Strengths of this study include its prospective study

design with a long follow-up period and extensive data

Table 1 Baseline

characteristics of 4,235 persons

(C55 years) of the Rotterdam

Study across categories of total

dairy intake

a Education is defined as low

(primary education),

intermediate (secondary general

or vocational education), and

high (higher vocational

education or university)b Median with interquartile

range (IQR)c Hypertension defined as

systolic blood

pressure C140 mmHg or

diastolic blood

pressure C90 mmHg or use of

antihypertensive medicationd Corresponding ATC codes

were b04 (lipid lowering

agents), c02 (antihypertensives),

c03 (diuretics), and c07 (beta-

blockers)e Values are means (SD) or

percentages, unless stated

otherwise

\200 g/day 200–400 g/day [400 g/day p value

n = 689 n = 1,452 n = 2,094

Age (years) 66.2 ± 7.3 67.1 ± 7.5 67.2 ± 8.0 0.02

Gender (% male) 44 37 36 0.002

Education (%)a

Low 34 32 35 0.11

Intermediate 52 57 53 0.04

High 14 11 12 0.1

Smoking (%)

Current 29 23 21 \0.001

Former 42 43 40 0.27

Never 28 34 39 \0.001

Alcohol users (%) 83 82 79 0.02

Intake among users (g/day)b 10.7 (2.5–24.7) 8.2 (1.9–20.9) 5.6 (1.0–14.2) \0.001

BMI (kg/m2) 26.1 ± 4.0 26.3 ± 3.5 26.1 ± 3.5 0.2

Hypertensive (% yes)c 53 56 54 0.5

CVD medication (% users)d 25.9 26.9 22.8 0.3

Blood pressure (mmHg)

Systolic 136.4 ± 21.5 138.2 ± 21.9 137.1 ± 21.4 0.17

Diastolic 74.4 ± 11.1 73.9 ± 11.1 73.4 ± 11.1 0.13

Dietary variablese

Total energy (kJ/d) 7,564 ± 2,094 8,024 ± 1,960 8,664 ± 2,153 \0.001

Total dairy (g/day)b 121 (66–169) 308 (256–354) 561 (474–694) \0.001

Low fat (g/day)b 23 (0–85) 198 (125–259) 419 (302–551) \0.001

High fat (g/day)b 59 (34–96) 89 (52–165) 117 (65–237) \0.001

Total milk (g/day)b 85 (32–137) 271 (221–321) 524 (434–659) \0.001

Fermented dairy (g/day)b 45 (23–90) 134 (60–205) 200 (104–352) \0.001

Cheese (g/day)b 27 (19–42) 32 (22–46) 35 (22–48) \0.001

Yogurt (g/day)b 0 (0–21) 43 (0–96) 71 (12–150) \0.001

Vegetables (g/day) 353 ± 148 342 ± 115 350 ± 142 0.11

Fruit (g/day)b 182 (105–286) 213 (131–299) 232 (154–311) \0.001

Meat (g/day) 118 ± 55 110 ± 46 103 ± 48 \0.001

Fish (g/day)b 7 (0–21) 10 (0–28) 11 (0–28) 0.04

Bread (g/day) 128 ± 55 133 ± 51 137 ± 55 \0.001

Coffee (ml/d) 484 ± 263 481 ± 231 485 ± 237 0.9

Tea (ml/d)b 375 (125–500) 375 (250–500) 375 (250–500) 0.5

Eur J Nutr

123

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Eur J Nutr

123

collection, which allowed adjustment for many potential

confounders. Data on physical activity, however, were

available for only 30 % of our cohort. Adjustment for this

potential confounder in the subsample did not affect the

association between high-fat dairy intake and stroke mor-

tality or any of the other associations. We had no data on

total sodium intake in the Rotterdam Study because the

FFQ was not suitable for assessing discretionary salt use.

High salt intake is considered a risk factor for CVD, and

the lack of adjustment for sodium from non-dairy sources

may have caused some bias toward the null in the observed

associations.

A wide variety of dairy products was consumed on a

daily basis which allowed investigation of intake up to

more than 400 g/day for total dairy and low-fat dairy.

Intake of high-fat dairy and fermented dairy products,

however, was rather low, which limited the analyses of

these specific subgroups. Other limitations include the use

of an SFFQ, which relies on self-report. Nevertheless, this

method is considered appropriate for ranking of individuals

in epidemiological studies, and a validation study in Rot-

terdam Study participants showed good correlations

(R = 0.6-0.7) [13] for nutrients that are present in dairy.

Another limitation is the single (baseline) measurement of

dairy intake, ignoring possible changes during the median

follow-up of 17 years. Intake of total dairy and cheese,

however, remained at a stable level in older Dutch men and

women in the past two decades [21]. The contribution of

high-fat dairy to total dairy intake, on the other hand,

declined from around 30 % in the early 1990s to \15 % in

2010 [21]. Therefore, we cannot exclude the possibility of

misclassification in the analyses of high- and low-fat dairy,

which may have diluted the associations with these product

subgroups. Also, part of the Rotterdam Study cohort was

excluded from our analysis. Diet was not assessed in

nursing home residents and in those with impaired cogni-

tive function. We additionally excluded subjects with a

history of CVD. As expected, the incidence of stroke and

CHD was twice as high subjects who were excluded

compared to the study population for the present analysis.

The findings for dairy intake and CVD risk can therefore

only be generalized to a relatively healthy, non-institu-

tionalized older population.

In the present study, no association was observed

between total dairy intake and stroke, which is in line with

results from former cohort studies [3, 6, 7, 9, 10]. A cohort

study from Japan (n = 63,947) found a lower risk of fatal

stroke for a food pattern high in dairy in both men (HR

0.65; 95 % CI 0.49–0.86) and women (HR: 0.70; 95 % CI

0.51–0.97) [22]. It should be noted, however, that Japanese

subjects with a high dairy intake also consumed more fruits

and less salt which may be responsible for the observed

inverse associations. A meta-analysis of six cohort studies

conducted by our group showed a non-significant inverse

association between total milk intake and stroke incidence

with a 6–7 % risk reduction per 100 g/day [2]. The present

analysis in the Rotterdam Study showed no relation of total

milk with incident stroke and a non-significant inverse

association with stroke mortality (5 % reduction per 100 g/

day, p = 0.17). The latter finding is in line with the meta-

analysis, but power in the present study was insufficient to

detect significant changes in fatal stroke risk of \10 %.

Table 3 Hazard ratiosa (95 % CI) of the relationship of intakes of total dairy and dairy subgroups per 100 g/day with incidence of stroke and

CHD (total and fatal) among 4,235 persons of the Rotterdam Study

Incident stroke (n = 564) Fatal stroke (n = 182) Incident CHD (n = 567) Fatal CHD (n = 350)

HR (95 % CI) P value HR (95 % CI) P value HR (95 % CI) P value HR (95 % CI) P value

Total dairyb 1.01 (0.97–1.04) 0.66 0.95 (0.89–1.02) 0.16 0.99 (0.96–1.03) 0.75 0.98 (0.94–1.03) 0.48

Low-fat dairyc 1.02 (0.99–1.06) 0.18 1.00 (0.94–1.06) 0.99 1.00 (0.97–1.04) 0.89 0.99 (0.95–1.04) 0.80

High-fat dairyd 0.96 (0.90–1.02) 0.17 0.88 (0.79–0.99) 0.03 0.98 (0.93–1.04) 0.47 0.97 (0.91–1.05) 0.48

Total milke 1.01 (0.97–1.04) 0.68 0.95 (0.89–1.02) 0.17 0.99 (0.96–1.03) 0.72 0.98 (0.94–1.03) 0.43

Fermented dairyf 1.02 (0.97–1.08) 0.41 0.99 (0.90–1.09) 0.85 1.01 (0.96–1.06) 0.73 0.98 (0.91–1.05) 0.55

Yogurt 1.04 (0.92–1.18) 0.50 0.99 (0.79–1.24) 0.93 1.04 (0.92–1.17) 0.51 0.98 (0.84–1.15) 0.84

Cheeseg 1.01 (0.93–1.10) 0.75 0.98 (0.84–1.14) 0.79 1.02 (0.94–1.10) 0.66 1.05 (0.95–1.15) 0.36

a All HRs are adjusted for age, gender, total energy intake, BMI, smoking, education level and intakes of alcohol, vegetables, fruit, meat, bread,

fish coffee, and teab Contains milk, buttermilk, yogurt, coffee creamer, curd, pudding, porridge, custard, whipped cream, ice cream, and cheesec Milk products with a fat content \2/100 g and cheese with a fat content \20/100 gd Milk products with a fat content C2/100 g and cheese with a fat content C20/100 ge All types of dairy except for cheesef All types of buttermilk, yogurt, curd, and cheeseg Analyzed per 20 g/day

Eur J Nutr

123

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Eur J Nutr

123

We found no consistent relationship between low-fat

dairy and incident stroke, in contrast to a Swedish cohort

study in which individuals in the upper quintile of low-fat

dairy intake (4 servings/day) had a 12 % lower stroke risk

compared to those who consumed no low-fat dairy [10].

Unlike low-fat dairy foods in Sweden, dairy products in the

Netherlands are not fortified with vitamin D, which may be

a possible explanation for the discrepant findings. Vitamin

D has been linked to a reduced risk of fatal stroke [23]. In

accordance, in another Swedish cohort, low-fat dairy intake

was associated with a 24 % lower risk of incident stroke

[4], whereas similar to our results, two previous Dutch

cohort studies [3, 9] also found no significant association

between low-fat dairy and stroke.

In our study, high-fat dairy intake ([100 vs. \50 g/day)

was significantly associated with a 36 % lower risk of fatal

stroke, overall as well as in subjects not using CVD med-

ication. However, other cohort studies [3, 6] on high-fat

dairy intake and stroke mortality, including a Dutch study

with 1,054 fatal stroke cases [3], reported no significant

associations. For total stroke incidence in the Rotterdam

Study, we found a much smaller risk reduction of 17 %,

which was not statistically significant. This finding is in

agreement with other cohort studies [9–11], including one

from the Netherlands [9], that found no significant relation

between high-fat dairy and incident stroke. In line with

these absent associations, a recent meta-analysis of six

cohort studies found no relation between high-fat dairy

intake and incident hypertension [24], a major risk factor

for stroke [25]. When considering the totality of evidence,

it may be possible that the reduction in stroke mortality that

we observed for high-fat dairy is due to chance, resulting

from multiple testing of dairy subgroups. Confirmation of

this association in other prospective cohort studies, pref-

erably with a larger range of high-fat dairy intake, is

therefore warranted.

The lack of association between total dairy or milk

consumption with CHD in our study is in line with the

results from a dose–response meta-analysis by our group

[2] and several recent cohort studies [3, 6, 8, 9, 26]. With

regard to cheese, a Swedish cohort study among 33,363

women showed a 26 % lower CHD risk of high (6 serv-

ings/day) versus low (0.7 servings/day) intake [5]. Apart

from no association being present in our study, the range of

cheese intake in our older Dutch cohort with rather

homogeneous dietary habits may have been too small to

detect associations with CVD outcomes. Three other cohort

studies, with a range of cheese intake comparable to ours,

also reported no association with CHD risk [3, 8, 9].

To conclude, our study showed no consistent associa-

tions of dairy food consumption with stroke or CHD risk,

except for an inverse relationship of high-fat dairy intake

(*1 serving/day) with stroke mortality which needs con-

firmation in other prospective studies.

Acknowledgments This study was supported by an unrestricted

grant from the Dutch Dairy Organization (NZO) for epidemiological

analyses on dairy intake and cardiovascular diseases. The Rotterdam

Study was funded by the Erasmus Medical Center and Erasmus

University Rotterdam; The Netherlands Organization for Scientific

Research; The Netherlands Organization for Health Research and

Development; the Research Institute for Diseases in the Elderly; The

Netherlands Genomics Initiative; the Ministry of Education, Culture

and Science; the Ministry of Health, Welfare and Sports; the Euro-

pean Commission (DG XII); and the Municipality of Rotterdam.

Conflict of interest J.M.G and S.S.S.M received an unrestricted

grant from the Dutch Dairy Organization (NZO) for epidemiological

analyses on dairy intake and cardiovascular diseases. The other

authors declare that they have no conflict of interest.

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