American Journal of Epidemiology The Author 2011.

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Vol. 174, No. 1 DOI: 10.1093/aje/kwr051 Advance Access publication: May 3, 2011

Original Contribution Potassium, Calcium, and Magnesium Intakes and Risk of Stroke in Women

Susanna C. Larsson*, Jarmo Virtamo, and Alicja Wolk

* Correspondence to Dr. Susanna C. Larsson, Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-17177 Stockholm, Sweden (e-mail: susanna.larsson@ki.se).

Initially submitted October 8, 2010; accepted for publication January 28, 2011.

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The authors examined the association between dietary potassium, calcium, and magnesium intakes and the incidence of stroke among 34,670 women 4983 years of age in the Swedish Mammography Cohort who completed a food frequency questionnaire in 1997. The authors used Cox proportional hazards regression models to estimate relative risks and 95% condence intervals. During a mean follow-up of 10.4 years (19982008), 1,680 stroke events were ascertained, including 1,310 cerebral infarctions, 154 intracerebral hemorrhages, 79 subarachnoid hemorrhages, and 137 unspecied strokes. There was no overall association between potassium, calcium, or magnesium intake and the risk of any stroke or cerebral infarction. However, among women with a history of hypertension, potassium intake was inversely associated with risk of all types of stroke (for highest vs. lowest quintile, adjusted relative risk 0.64, 95% condence interval (CI): 0.45, 0.92) and cerebral infarction (corresponding adjusted relative risk 0.56, 95% CI: 0.38, 0.84), and magnesium intake was inversely associated with risk of cerebral infarction (corresponding adjusted relative risk 0.63, 95% CI: 0.42, 0.93). Calcium intake was positively associated with risk of intracerebral hemorrhage (for highest vs. lowest tertile, adjusted relative risk 2.04, 95% CI: 1.24, 3.35). These ndings suggest that potassium and magnesium intakes are inversely associated with the risk of cerebral infarction among hypertensive women. diet; nutritional sciences; population; prospective studies; stroke

Abbreviation: CI, condence interval.

Stroke is a leading cause of morbidity and mortality in industrialized countries (1). Dietary factors may inuence the risk of stroke through several mechanismsfor example, by effects on blood pressure, insulin resistance, systemic inammation, platelet function, thrombosis, and oxidation (2). Dietary intakes of potassium, calcium, and magnesium have been inversely associated with blood pressure and hypertension in several observational studies (37). In addition, some, but not all, randomized controlled trials have shown that supplementation with potassium, calcium, and magnesium alone or in combination reduced blood pressure (811). Magnesium intake has also been inversely associated with markers of systemic inammation (12), endothelial dysfunction (12), carotid artery thickness (7), fasting insulin concentrations (7), the metabolic syndrome (13), and type 2 diabetes mellitus (hereafter referred to as diabetes) (14). Findings from prospective studies of intakes
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of potassium (1522), calcium (16, 17, 2225), and/or magnesium (16, 17, 22, 26, 27) in relation to stroke incidence or mortality have been inconsistent. The relations of potassium, calcium, and magnesium intakes with the incidence of stroke could be modied by hypertension (16, 18). However, only a few studies (16, 18, 22) have examined the potential modifying effect of hypertension on the association between potassium, calcium, and magnesium intakes and the risk of stroke. We analyzed data from the Swedish Mammography Cohort, a population-based prospective cohort study of women, to assess the hypothesis that high intakes of potassium, calcium, and magnesium are associated with a reduced incidence of stroke. We examined whether the associations between intake of these minerals and risk of stroke were modied by a history of hypertension. To our knowledge, this is the largest prospective study (with regard to number
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of cases) to date that assessed the relation between potassium, calcium, and magnesium intakes and the risk of stroke in women.
MATERIALS AND METHODS Study population

Dietary assessment

Details of the Swedish Mammography Cohort have been reported elsewhere (28). In brief, the cohort was established in 19871990, when all women born between 1914 and 1948 and living in central Sweden (Va stmanland and Uppsala counties) received a questionnaire on diet via the mail. In the autumn of 1997, the 56,030 participants who were still alive and residing in the study area received a new expanded questionnaire that included approximately 350 items concerning diet and other lifestyle factors; 39,227 women (70%) completed the 1997 questionnaire. Compared with women who completed the baseline (19871990) questionnaire but not the 1997 questionnaire and who were still alive in 1997, those who completed both questionnaires were on average younger and had a slightly lower incidence of all types of stroke (total stroke). The age-adjusted yearly incidence rates of total stroke per 10,000 persons between 1987 and 1997 among women who completed the 1997 questionnaire and those who did not were 9 and 10, respectively. Because information on several potential confounders (e.g., cigarette smoking, diabetes, hypertension, and physical activity) was rst obtained in 1997, only women who completed the 1997 questionnaire were included in the present study. We excluded women with an erroneous or a missing national identication number, those with a history of stroke, coronary heart disease, or cancer before the start of followup, and those with implausible values for total energy intake (i.e., 3 standard deviations from the loge-transformed mean energy intake). This left 34,670 women aged 4983 years for the present analysis, which used data from 19982008. The study was approved by the Regional Ethical Review Board at the Karolinska Institutet, Stockholm, Sweden.
Baseline data collection

A 96-item food frequency questionnaire was used to assess diet in 1997. On this questionnaire, participants indicated how often, on average, they had consumed various foods over the past year, by using 8 predened frequency categories ranging from never to 3 times per day. For commonly consumed foods such as milk, cheese, and bread, participants could indicate how often per day or week they consumed these foods (open question). Nutrient intakes were calculated by multiplying the frequency of consumption by the nutrient content of age-specic (<53, 5365, and 66 years of age) portion sizes by using composition values from the Swedish Food Administration Database (30). All nutrients, except alcohol, were adjusted for total energy intake through the use of the residual method (31). The questionnaire also asked about use of dietary supplements, including multivitamins with minerals, and some specic vitamin and mineral supplements, including calcium and magnesium. The food frequency questionnaire has been validated (32), and the Spearman coefcients for the correlations between estimates (intake in mg/day) from the dietary questionnaire and the mean of 14 24-hour recall interviews were 0.77 for calcium and 0.73 for magnesium; potassium intake has not been validated.
Case ascertainment and follow-up

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Incident cases of rst stroke that occurred between January 1, 1998, and December 31, 2008, were ascertained by linkage of the study cohort with the Swedish Hospital Discharge Registry, which provides virtually complete coverage of the discharges. The International Classication of Diseases, Tenth Revision, was used to identify stroke events. Strokes were classied as cerebral infarction (code I63), intracerebral hemorrhage (code I61), subarachnoid hemorrhage (code I60), and unspecied stroke (code I64). Dates of death were obtained from the Swedish Death Registry.
Statistical analysis

The 1997 questionnaire included questions on educational level, weight, height, cigarette smoking, physical activity level, aspirin use, medical history, family history of myocardial infarction before 60 years of age, alcohol consumption, and diet. Body mass index was calculated by dividing the weight in kilograms by the square of height in meters. Pack-years of smoking history were calculated as the number of packs of cigarettes smoked per day multiplied by the number of years of smoking. Participants reported their level of activity at work, home/housework, walking/ bicycling, and exercise in the year before study enrollment. The questionnaire also included questions on inactivity (watching television or reading) and hours per day of sleeping and sitting or lying down. The reported time spent at each activity per day was multiplied by its typical energy expenditure requirements, expressed in metabolic equivalents, and amounts for all activities were added together to create a metabolic equivalent-hours per day (24 hours) score (29).

Participants were followed from January 1, 1998, until the date of rst stroke event, death, or December 31, 2008, whichever came rst. We used Cox proportional hazards regression models with age as the time scale to estimate the relative risks of stroke by category of potassium, calcium, and magnesium intake. Participants were categorized into quintiles (for total stroke and cerebral infarction) or tertiles (for hemorrhage strokes because of the smaller number of cases) of potassium, calcium, and magnesium intakes based on the distribution in the whole cohort. Entry time was dened as a subjects age in months at start of follow-up, and exit time was dened as a subjects age in months at stroke event or censoring. The proportional hazards assumption was tested and was found to be met for all variables except diabetes. We adjusted for diabetes by stratication in the Cox model. The multivariable model included the following variables: smoking status (never, past, or current smokers), pack-years of smoking (<20, 2039, or 40 pack-years), educational level (less than high school, high school, or
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Potassium, Calcium, and Magnesium Intakes and Stroke

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Table 1. Age-Standardized Baseline Characteristics by Lowest and Highest Quintile of Energy-Adjusted Potassium, Calcium, and Magnesium Intakes in the Swedish Mammography Cohort, 19982008
Potassium Characteristic Quintile 1 Mean % Quintile 5 Mean % Quintile 1 Mean % Calcium Quintile 5 Mean % Magnesium Quintile 1 Mean % Quintile 5 Mean %

Age, years University education Current smoker Body mass index

a

61.6 17.0 26.8 24.8 42.1

60.7 21.2 22.8 25.3 43.0

61.0 17.3 24.5 24.9 42.4

61.9 19.9 25.8 25.1 42.6

61.6 16.0 26.8 24.9 42.0

61.0 21.0 22.7 25.2 43.1

Total physical activity, metabolic equivalentb hours/day Diabetes History of hypertension Aspirin use Family history of myocardial infarction Daily dietary intake Alcohol, g Protein, g Cholesterol, mg Potassium, mg Calcium, mg Magnesium, mg Sodium, mg Folate, lg Total ber, g Dietary supplement use Multivitamins with minerals Calcium Magnesium
a b

2.2 18.6 50.4 16.4

4.5 20.4 48.4 17.5

2.7 19.9 49.7 17.0

4.3 20.2 49.7 16.5

1.5 18.8 50.1 15.9

5.9 20.5 47.9

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17.3

4.3 67.0 243 2,363 997 273 2,430 211 18.2 20.7 5.8 3.2

3.8 74.9 219 3,845 1,120 369 2,635 368 26.3 25.2 8.7 4.9

4.8 61.6 227 2,955 669 307 2,555 272 23.3 21.3 8.0 3.9

3.6 82.0 240 3,154 1,484 331 2,502 284 20.2 23.8 7.0 3.9

4.0 66.4 252 2,478 959 262 2,421 221 17.1 19.6 5.5 2.8

3.9 74.9 206 3,684 1,119 381 2,659 353 27.6 26.0 8.6 5.1

Body mass index was calculated by dividing weight in kilograms by the square of height in meters. Metabolic equivalents were calculated as kcal divided by weight in kilograms times the number of hours.

university), body mass index (<20, 2024.9, 2529.9, or 30), total physical activity level (quartiles), self-reported history of hypertension (yes or no), aspirin use (yes or no), family history of myocardial infarction before 60 years of age (yes or no), and intakes of total energy (in kcal/day, as a continuous variable), alcohol consumption (nondrinkers or <3.4, 3.49.9, or 10.0 g/day), and quintiles of protein, cholesterol, total ber, and folate. The selection of variables for inclusion in the multivariable model was based on the association between the variable and potassium, calcium, or magnesium intake, as well as the association between the variable and risk of stroke observed in the present cohort study or reported in the literature. Tests for linear trends were conducted by modeling the minerals as continuous variables by using the median value of each category. We conducted stratied analyses by history of hypertension (yes or no) to assess possible effect modication by this variable. Tests for interaction were performed using the likelihood ratio test. The statistical analyses were performed using SAS, version 9.1
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(SAS Institute Inc., Cary, North Carolina). All P values were 2-sided.

RESULTS

Among the 34,670 women, who were followed for a mean of 10.4 years, we ascertained 1,680 incident stroke events, including 1,310 cerebral infarctions, 154 intracerebral hemorrhages, 79 subarachnoid hemorrhages, and 137 unspecied strokes. Baseline characteristics of the study population according to intakes of potassium, calcium, and magnesium are shown in Table 1. Potassium intake was strongly positively correlated with magnesium intake (r 0.81) and weakly correlated with calcium intake (r 0.15). Intakes of calcium and magnesium were weakly positively correlated (r 0.20). We observed no overall association between dietary intakes of potassium, calcium, and magnesium and risk of total stroke or cerebral infarction after adjustment for other

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risk factors (Table 2). Results were similar when potassium, calcium, and magnesium were included in the same multivariable model. Excluding women who reported use of dietary supplements containing calcium or magnesium (including multivitamins with minerals) did not change the results appreciably. After excluding supplement users, the multivariable relative risks of total stroke for the highest quintile of intake compared with the lowest were 0.92 (95% condence interval (CI): 0.74, 1.14) for calcium and 0.94 (95% CI: 0.75, 1.19) for magnesium (data not shown). Excluding women with a low body mass index (<15) did not change the results (data not shown). We examined more extreme intakes of the minerals by categorizing women into deciles of potassium, calcium, and magnesium intakes. Compared with women in the lowest decile of intake, the multivariable relative risks of total stroke for those in the highest decile were 0.71 (95% CI: 0.54, 0.94) for potassium, 1.17 (95% CI: 0.92, 1.50) for calcium, and 0.85 (95% CI: 0.64, 1.12) for magnesium. Calcium intake was positively associated with risk of intracerebral hemorrhage (relative risk for the highest tertile (vs. lowest) 2.04, 95% condence interval: 1.24, 3.35) (Table 3). There was no association between potassium or magnesium intake and risk of intracerebral hemorrhage or subarachnoid hemorrhage. Because hypertension is an important risk factor for stroke, we performed analyses stratied by history of hypertension at baseline (Table 4). Potassium intake was statistically signicantly inversely associated with risk of total stroke and cerebral infarction among women with a history of hypertension but not among women with no history of hypertension. There was a suggestion of an interaction between potassium intake and history of hypertension in relation to the risk of cerebral infarction (P 0.07) but not of total stroke (P 0.26). We also observed a statistically signicant inverse association between magnesium intake and the risk of cerebral infarction among women with a history of hypertension, but no association was observed among those without hypertension. There was a statistically signicant interaction between magnesium intake and hypertension in relation to risk of cerebral infarction (P 0.03). The association between calcium intake and stroke risk did not vary signicantly by stratum of hypertension.
DISCUSSION

In the present prospective cohort study of Swedish women, we found no overall associations between potassium, calcium, and magnesium intakes and the risk of total stroke or cerebral infarction. However, potassium and magnesium intakes were signicantly inversely associated with the risk of cerebral infarction among women with a history of hypertension. In contrast to the hypothesis, calcium intake was positively associated with risk of intracerebral hemorrhage. Rich food sources of potassium include fruits, vegetables (especially root vegetables), and legumes. Foods high in magnesium include whole grains, legumes, nuts, bananas, and green leafy vegetables.

Findings from previous prospective studies of potassium, calcium, and magnesium intakes in relation to risk of stroke have been inconsistent (Web Table 1, available at http:// aje.oxfordjournals.org/). Of the 8 prospective studies that have assessed the association between potassium intake and stroke incidence or mortality (1522), 4 showed a signicant inverse association (15, 16, 18, 20). Of the 6 studies of calcium intake in relation to stroke incidence or mortality (16, 17, 2225), 4 found an inverse association between stroke and intake of dairy calcium but not nondairy calcium (17, 23, 25, 26). No association was observed for total calcium intake from both dairy and nondairy foods (16, 22). A randomized trial that included 36,282 postmenopausal women found no effect of combined calcium and vitamin D supplementation on risk of stroke over a 7-year period (33). Dietary magnesium intake has been inversely associated with stroke incidence, either overall or in subgroups, in 3 (16, 22, 27) of 5 (16, 17, 22, 26, 27) previous studies. Of previous studies that have examined a potential interaction between potassium, calcium, or magnesium intake and history of hypertension in relation to risk of stroke (16, 18, 22), 2 showed an interaction (16, 18). In the Health Professionals Follow-up Study, intake of potassium and magnesium but not of calcium was signicantly inversely associated with the risk of stroke among men with a history of hypertension but not among men with no history of hypertension (16). Similarly, a low potassium intake was associated with an increased risk of stroke in hypertensive men but not in nonhypertensive men in the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (18). However, no association was observed in women (18). In the Alpha-Tocopherol, BetaCarotene Cancer Prevention Study, intake of magnesium but not potassium or calcium was inversely associated with risk of cerebral infarction, but the associations were not modied by hypertension (22). The reason for the inconsistent results for potassium, magnesium, and calcium intakes in relation to stroke may be differences in the range of exposure or the lack of adjustment for potential confounders. An association may not be seen if the difference in intake between the lowest and highest intake categories is too small. In fact, we observed a statistically signicant inverse association between potassium intake and risk of stroke in women in the highest decile of potassium intake compared with those in the lowest decile. Moreover, an association may only be seen in specic subgroups of the population, such as hypertensive individuals, as suggested in the present study and 2 previous studies (16, 18). The inverse association of intake of calcium from dairy foods but not from nondairy sources with stroke incidence or mortality observed in some studies (17, 2325) could suggest that factors other than the calcium in dairy foods account for the observed association. We observed an unexpected positive association between dietary calcium intake and the risk of intracerebral hemorrhage. This association was in opposition to the one assumed in the hypothesis. Because many analyses were performed, it is possible that this nding was due to chance. No previous study has reported a positive association between calcium intake and intracerebral hemorrhage.
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Table 2. Relative Risks of Total Stroke and Cerebral Infarction According to Quintiles of Potassium, Calcium, and Magnesium Intakes in the Swedish Mammography Cohort, 19982008
Total Stroke Quintile of Intake Median, mg/day PersonYears No. of Cases Age-Adjusted RR 95% CI Multivariable RRa 95% CI No. of Cases Age-Adjusted RR Cerebral Infarction 95% CI Multivariable RRa 95% CI

Potassium 1 (lowest) 2 3 4 5 (highest) Ptrend Calcium 1 (lowest) 2 3 4 5 (highest) Ptrend Magnesium 1 (lowest) 2 3 4 5 (highest) Ptrend
a

2,419 2,767 3,021 3,296 3,744

70,668 71,751 72,067 72,312 72,215

373 340 348 311 308

1.00 0.89 0.92 0.86 0.90 0.16

Referent 0.77, 1.03 0.79, 1.06 0.74, 0.99 0.78, 1.05

1.00 0.90 0.94 0.85 0.89 0.26

Referent 0.77, 1.06 0.79, 1.11 0.71, 1.03 0.72, 1.10

290 268 272 238 242

1.00 0.90 0.93 0.85 0.92 0.25

Referent 0.76, 1.06 0.78, 1.09 0.71, 1.00 0.77, 1.09

1.00 0.91 0.92 0.81 0.88 0.22

Referent 0.76, 1.09 0.76, 1.12 0.65, 1.00 0.69, 1.11

698 880 1,012 1,160 1,422

71,495 72,219 72,096 71,924 71,279

348 282 321 374 355

1.00 0.82 0.89 1.00 0.94 0.75

Referent 0.70, 0.96 0.76, 1.03 0.87, 1.16 0.81, 1.09

1.00 0.88 0.99 1.14 1.08 0.14

Referent 0.75, 1.04 0.84, 1.16 0.96, 1.35 0.89, 1.31

272 217 265 291 265

1.00 0.81 0.93 1.00 0.90 0.74

Referent 0.68, 0.97 0.79, 1.11 0.84, 1.17 0.76, 1.06

1.00 0.88 1.04 1.12 1.02 0.47

Referent 0.73, 1.05 0.87, 1.26 0.92, 1.36 0.82, 1.26

Potassium, Calcium, and Magnesium Intakes and Stroke

267 297 317 339 373

70,856 71,716 72,074 72,271 72,096

367 351 318 317 327

1.00 0.96 0.87 0.87 0.92 0.16

Referent 0.83, 1.11 0.75, 1.01 0.75, 1.01 0.80, 1.07

1.00 1.02 0.95 0.97 1.02 0.97

Referent 0.87, 1.19 0.80, 1.14 0.80, 1.17 0.82, 1.27

295 268 246 244 257

1.00 0.91 0.84 0.83 0.91 0.16

Referent 0.77, 1.07 0.71, 1.00 0.70, 0.99 0.77, 1.07

1.00 0.96 0.91 0.91 0.98 0.80

Referent 0.81, 1.15 0.74, 1.11 0.73, 1.13 0.77, 1.26

Abbreviations: CI, condence interval; RR, relative risk. Multivariable relative risks were adjusted for age, smoking status, pack-years of smoking, educational level, body mass index, total physical activity level, history of diabetes, history of hypertension, aspirin use, family history of myocardial infarction, and intakes of total energy, alcohol, protein, cholesterol, total ber, and folate.

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Table 3. Relative Risks of Intracerebral Hemorrhage and Subarachnoid Hemorrhage According to Tertiles of Potassium, Calcium, and Magnesium Intakes in the Swedish Mammography Cohort, 19982008
Intracerebral Hemorrhage Tertile of Intake Median, mg/day No. of Cases Age-Adjusted RR 95% CI Multivariable RRa 95% CI No. of Cases Subarachnoid Hemorrhage Age-Adjusted RR 95% CI Multivariable RRa 95% CI

Potassium 1 (lowest) 2 3 (highest) Ptrend Calcium 1 (lowest) 2 3 (highest) Ptrend Magnesium 1 (lowest) 2 3 (highest) Ptrend
a

2,563 3,015 3,541

63 44 47

1.00 0.69 0.76 0.17

Referent 0.47, 1.02 0.52, 1.11

1.00 0.78 0.96 0.86

Referent 0.51, 1.20 0.57, 1.61

29 27 23

1.00 0.91 0.76 0.33

Referent 0.54, 1.54 0.44, 1.32

1.00 0.92 0.87 0.70

Referent 0.51, 1.66 0.42, 1.80

772 1,009 1,300

40 44 70

1.00 1.07 1.60 0.01

Referent 0.70, 1.64 1.09, 2.36

1.00 1.20 2.04 0.004

Referent 0.76, 1.88 1.24, 3.35

27 23 29

1.00 0.84 1.03 0.88

Referent 0.48, 1.46 0.61, 1.73

1.00 0.83 1.07 0.80

Referent 0.46, 1.51 0.55, 2.09

279 317 357

58 52 44

1.00 0.89 0.75 0.15

Referent 0.61, 1.30 0.51, 1.11

1.00 1.07 1.02 0.94

Referent 0.70, 1.63 0.59, 1.75

31 24 24

1.00 0.76 0.74 0.27

Referent 0.45, 1.29 0.43, 1.26

1.00 0.66 0.68 0.30

Referent 0.36, 1.21 0.33, 1.42

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Abbreviations: CI, condence interval; RR, relative risk. Multivariable relative risks were adjusted for age, smoking status, pack-years of smoking, educational level, body mass index, total physical activity level, history of diabetes, history of hypertension, aspirin use, family history of myocardial infarction, and intakes of total energy, alcohol, protein, cholesterol, total ber, and folate.

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Table 4 Relative Risks of Total Stroke and Cerebral Infarction According to Quintiles of Potassium, Calcium, and Magnesium Intakes, Stratied by History of Hypertension, in the Swedish Mammography Cohort, 19982008
Total Stroke Quintile of Intake Median, mg/day No History of Hypertension No. of Cases Multivariable RRa 95% CI No. of Cases History of Hypertension Multivariable RRa 95% CI Cerebral Infarction No History of Hypertension No. of Cases Multivariable RRa 95% CI No. of Cases History of Hypertension Multivariable RRa 95% CI

Potassium 1 (lowest) 2 3 4 5 (highest) Ptrend Pinteraction Calcium 1 (lowest) 2 3 4 5 (highest) Ptrend Pinteraction Magnesium 1 (lowest) 2 3 4 5 (highest) Ptrend Pinteraction
a

2,419 2,767 3,021 3,296 3,744

239 225 223 198 212

1.00 1.02 1.01 0.94 1.00 0.84 0.26

Referent 0.84, 1.24 0.81, 1.25 0.74, 1.18 0.78, 1.28

134 115 125 113 96

1.00 0.72 0.77 0.68 0.64

Referent 0.55, 0.94 0.58, 1.03 0.49, 0.92 0.45, 0.92 0.02

174 168 170 150 166

1.00 1.05 1.05 0.96 1.04 0.94 0.07

Referent 0.84, 1.32 0.82, 1.34 0.73, 1.25 0.78, 1.40

116 100 102 88 76

1.00 0.71 0.71 0.58 0.56 0.004

Referent 0.53, 0.95 0.51, 0.97 0.41, 0.82 0.38, 0.84

698 880 1,012 1,160 1,422

221 177 216 246 237

1.00 0.87 1.02 1.02 1.13 0.26 0.28

Referent 0.71, 1.07 0.83, 1.25 0.83, 1.25 0.92, 1.40

127 105 105 128 118

1.00 0.92 0.89 1.07 0.99 0.83

Referent 0.71, 1.21 0.68, 1.18 0.80, 1.43 0.72, 1.36

166 132 175 186 169

1.00 0.88 1.10 1.13 0.99 0.68 0.37

Referent 0.69, 1.11 0.87, 1.38 0.89, 1.44 0.76, 1.29

106 85 90 105 96

1.00 0.90 0.91 1.02 0.93 0.86

Referent 0.67, 1.20

Potassium, Calcium, and Magnesium Intakes and Stroke

0.67, 1.24 0.74, 1.40 0.65, 1.31

267 297 317 339 373

234 236 207 196 224

1.00 1.10 1.00 0.95 1.08 0.82 0.14

Referent 0.91, 1.34 0.81, 1.24 0.75, 1.20 0.84, 1.41

133 115 111 121 103

1.00 0.83 0.79 0.89 0.76 0.24

Referent 0.63, 1.09 0.59, 1.06 0.65, 1.21 0.53, 1.09

177 169 160 146 176

1.00 1.06 1.04 0.94 1.12 0.63

Referent 0.84, 1.33 0.81, 1.33 0.71, 1.23 0.83, 1.51

118 99 86 98 81

1.00 0.77 0.65 0.75 0.63 0.03 0.03

Referent 0.58, 1.04 0.47, 0.90 0.53, 1.05 0.42, 0.93

Abbreviations: CI, condence interval; RR, relative risk. Multivariable relative risks were adjusted for age, smoking status, pack-years of smoking, educational level, body mass index, total physical activity level, history of diabetes, history of hypertension, aspirin use, family history of myocardial infarction, and intakes of total energy, alcohol, protein, cholesterol, total ber, and folate.

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The strengths of this study include the prospective and population-based design and the almost complete follow-up of study participants by linkage with various populationbased Swedish registries. Additionally, this study included a large number of incident stroke cases, which led to high statistical power in the analysis. A limitation of this study is that diet was assessed with a self-administered questionnaire, which inevitably led to some measurement error in dietary intake. Thus, we cannot rule out the possibility that the lack of observed association is due to misclassication of exposure, leading to attenuated risk estimates. Another limitation is that our assessment of hypertension was based on self-report, which is less reliable than clinical measurement. Finally, although we controlled for other risk factors for stroke, we cannot exclude the possibility that our results have been affected by residual confounding by imprecisely or unmeasured risk factors. In conclusion, ndings from this prospective cohort study of women suggest that potassium and magnesium intakes are inversely associated with risk of cerebral infarction among women with hypertension. We observed no protective effect of calcium intake on stroke risk.

ACKNOWLEDGMENTS

Author afliations: Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (Susanna C. Larsson, Alicja Wolk); and Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (Jarmo Virtamo). This study was supported by a research grant from the Swedish Council for Working Life and Social Research and the Swedish Research Council for Infrastructure. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Conict of interest: none declared.

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