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

Susanna C. Larsson; Jarmo Virtamo; Alicja Wolk

Am J Epidemiol. 2011;174(1):35-43. 

Abstract and Introduction

Abstract

The authors examined the association between dietary potassium, calcium, and magnesium intakes and the incidence of stroke among 34,670 women 49–83 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% confidence intervals. During a mean follow-up of 10.4 years (1998–2008), 1,680 stroke events were ascertained, including 1,310 cerebral infarctions, 154 intracerebral hemorrhages, 79 subarachnoid hemorrhages, and 137 unspecified 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% confidence 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 findings suggest that potassium and magnesium intakes are inversely associated with the risk of cerebral infarction among hypertensive women.

Introduction

Stroke is a leading cause of morbidity and mortality in industrialized countries.[1] Dietary factors may influence the risk of stroke through several mechanisms—for example, by effects on blood pressure, insulin resistance, systemic inflammation, 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.[3–7] 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.[8–11] Magnesium intake has also been inversely associated with markers of systemic inflammation,[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 of potassium,[15–22] calcium,[16, 17, 22–25] 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 modified 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 modified by a history of hypertension. To our knowledge, this is the largest prospective study (with regard to number 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

Details of the Swedish Mammography Cohort have been reported elsewhere.[28] In brief, the cohort was established in 1987–1990, when all women born between 1914 and 1948 and living in central Sweden (Västmanland 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 (1987–1990) 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 first 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 identification number, those with a history of stroke, coronary heart disease, or cancer before the start of follow-up, 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 49–83 years for the present analysis, which used data from 1998–2008. The study was approved by the Regional Ethical Review Board at the Karolinska Institutet, Stockholm, Sweden.

Baseline Data Collection

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]

Dietary Assessment

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 predefined 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-specific (<53, 53–65, 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 specific vitamin and mineral supplements, including calcium and magnesium. The food frequency questionnaire has been validated,[32] and the Spearman coefficients 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

Incident cases of first 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 Classification of Diseases, Tenth Revision, was used to identify stroke events. Strokes were classified as cerebral infarction (code I63), intracerebral hemorrhage (code I61), subarachnoid hemorrhage (code I60), and unspecified stroke (code I64). Dates of death were obtained from the Swedish Death Registry.

Statistical Analysis

Participants were followed from January 1, 1998, until the date of first stroke event, death, or December 31, 2008, whichever came first. 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 defined as a subject's age in months at start of follow-up, and exit time was defined as a subject's 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 stratification in the Cox model. The multivariable model included the following variables: smoking status (never, past, or current smokers), pack-years of smoking (<20, 20–39, or ≥40 pack-years), educational level (less than high school, high school, or university), body mass index (<20, 20–24.9, 25–29.9, 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, 3.4–9.9, or ≥10.0 g/day), and quintiles of protein, cholesterol, total fiber, 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 stratified analyses by history of hypertension (yes or no) to assess possible effect modification by this variable. Tests for interaction were performed using the likelihood ratio test. The statistical analyses were performed using SAS, version 9.1 (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 unspecified strokes. Baseline characteristics of the study population according to intakes of potassium, calcium, and magnesium are shown in . 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).

Table 1.  Age-Standardized Baseline Characteristics by Lowest and Highest Quintile of Energy-Adjusted Potassium, Calcium, and Magnesium Intakes in the Swedish Mammography Cohort, 1998–2008

Characteristic Potassium Calcium Magnesium
Quintile 1 Quintile 5 Quintile 1 Quintile 5 Quintile 1 Quintile 5
Mean % Mean % Mean % Mean % Mean % Mean %
Age, years 61.6 60.7 61.0 61.9 61.6 61.0
University education 17.0 21.2 17.3 19.9 16.0 21.0
Current smoker 26.8 22.8 24.5 25.8 26.8 22.7
Body mass indexa 24.8 25.3 24.9 25.1 24.9 25.2
Total physical activity, metabolic equivalentb hours/day 42.1 43.0 42.4 42.6 42.0 43.1
Diabetes 2.2 4.5 2.7 4.3 1.5 5.9
History of hypertension 18.6 20.4 19.9 20.2 18.8 20.5
Aspirin use 50.4 48.4 49.7 49.7 50.1 47.9
Family history of myocardial infarction 16.4 17.5 17.0 16.5 15.9 17.3
Daily dietary intake
   Alcohol, g 4.3 3.8 4.8 3.6 4.0 3.9
   Protein, g 67.0 74.9 61.6 82.0 66.4 74.9
   Cholesterol, mg 243 219 227 240 252 206
   Potassium, mg 2,363 3,845 2,955 3,154 2,478 3,684
   Calcium, mg 997 1,120 669 1,484 959 1,119
   Magnesium, mg 273 369 307 331 262 381
   Sodium, mg 2,430 2,635 2,555 2,502 2,421 2,659
   Folate, μg 211 368 272 284 221 353
   Total fiber, g 18.2 26.3 23.3 20.2 17.1 27.6
Dietary supplement use
   Multivitamins with minerals 20.7 25.2 21.3 23.8 19.6 26.0
   Calcium 5.8 8.7 8.0 7.0 5.5 8.6
   Magnesium 3.2 4.9 3.9 3.9 2.8 5.1

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

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 risk factors (). 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% confidence 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).

Table 2.  Relative Risks of Total Stroke and Cerebral Infarction According to Quintiles of Potassium, Calcium, and Magnesium Intakes in the Swedish Mammography Cohort, 1998–2008

Quintile of Intake Median, mg/day Total Stroke Cerebral Infarction
Person-Years No. of Cases Age-Adjusted RR 95% CI Multivariable RRa 95% CI No. of Cases Age-Adjusted RR 95% CI Multivariable RRa 95% CI
Potassium
   1 (lowest) 2,419 70,668 373 1.00 Referent 1.00 Referent 290 1.00 Referent 1.00 Referent
   2 2,767 71,751 340 0.89 0.77, 1.03 0.90 0.77, 1.06 268 0.90 0.76, 1.06 0.91 0.76, 1.09
   3 3,021 72,067 348 0.92 0.79, 1.06 0.94 0.79, 1.11 272 0.93 0.78, 1.09 0.92 0.76, 1.12
   4 3,296 72,312 311 0.86 0.74, 0.99 0.85 0.71, 1.03 238 0.85 0.71, 1.00 0.81 0.65, 1.00
   5 (highest) 3,744 72,215 308 0.90 0.78, 1.05 0.89 0.72, 1.10 242 0.92 0.77, 1.09 0.88 0.69, 1.11
      P trend 0.16 0.26 0.25 0.22
Calcium
      1 (lowest) 698 71,495 348 1.00 Referent 1.00 Referent 272 1.00 Referent 1.00 Referent
   2 880 72,219 282 0.82 0.70, 0.96 0.88 0.75, 1.04 217 0.81 0.68, 0.97 0.88 0.73, 1.05
   3 1,012 72,096 321 0.89 0.76, 1.03 0.99 0.84, 1.16 265 0.93 0.79, 1.11 1.04 0.87, 1.26
   4 1,160 71,924 374 1.00 0.87, 1.16 1.14 0.96, 1.35 291 1.00 0.84, 1.17 1.12 0.92, 1.36
   5 (highest) 1,422 71,279 355 0.94 0.81, 1.09 1.08 0.89, 1.31 265 0.90 0.76, 1.06 1.02 0.82, 1.26
      P trend 0.75 0.14 0.74 0.47
Magnesium
   1 (lowest) 267 70,856 367 1.00 Referent 1.00 Referent 295 1.00 Referent 1.00 Referent
   2 297 71,716 351 0.96 0.83, 1.11 1.02 0.87, 1.19 268 0.91 0.77, 1.07 0.96 0.81, 1.15
   3 317 72,074 318 0.87 0.75, 1.01 0.95 0.80, 1.14 246 0.84 0.71, 1.00 0.91 0.74, 1.11
   4 339 72,271 317 0.87 0.75, 1.01 0.97 0.80, 1.17 244 0.83 0.70, 0.99 0.91 0.73, 1.13
   5 (highest) 373 72,096 327 0.92 0.80, 1.07 1.02 0.82, 1.27 257 0.91 0.77, 1.07 0.98 0.77, 1.26
      P trend 0.16 0.97 0.16 0.80

Abbreviations: CI, confidence interval; RR, relative risk.
a 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 fiber, and folate.

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% confidence interval: 1.24, 3.35) (). There was no association between potassium or magnesium intake and risk of intracerebral hemorrhage or subarachnoid hemorrhage.

Table 3.  Relative Risks of Intracerebral Hemorrhage and Subarachnoid Hemorrhage According to Tertiles of Potassium, Calcium, and Magnesium Intakes in the Swedish Mammography Cohort, 1998–2008

Tertile of Intake Median, mg/day Intracerebral Hemorrhage Subarachnoid Hemorrhage
No. of Cases Age-Adjusted RR 95% CI Multivariable RRa 95% CI No. of Cases Age-Adjusted RR 95% CI Multivariable RRa 95% CI
Potassium
   1 (lowest) 2,563 63 1.00 Referent 1.00 Referent 29 1.00 Referent 1.00 Referent
   2 3,015 44 0.69 0.47, 1.02 0.78 0.51, 1.20 27 0.91 0.54, 1.54 0.92 0.51, 1.66
   3 (highest) 3,541 47 0.76 0.52, 1.11 0.96 0.57, 1.61 23 0.76 0.44, 1.32 0.87 0.42, 1.80
      P trend 0.17 0.86 0.33 0.70
Calcium
   1 (lowest) 772 40 1.00 Referent 1.00 Referent 27 1.00 Referent 1.00 Referent
   2 1,009 44 1.07 0.70, 1.64 1.20 0.76, 1.88 23 0.84 0.48, 1.46 0.83 0.46, 1.51
   3 (highest) 1,300 70 1.60 1.09, 2.36 2.04 1.24, 3.35 29 1.03 0.61, 1.73 1.07 0.55, 2.09
      P trend 0.01 0.004 0.88 0.80
Magnesium
   1 (lowest) 279 58 1.00 Referent 1.00 Referent 31 1.00 Referent 1.00 Referent
   2 317 52 0.89 0.61, 1.30 1.07 0.70, 1.63 24 0.76 0.45, 1.29 0.66 0.36, 1.21
   3 (highest) 357 44 0.75 0.51, 1.11 1.02 0.59, 1.75 24 0.74 0.43, 1.26 0.68 0.33, 1.42
      P trend 0.15 0.94 0.27 0.30

Abbreviations: CI, confidence interval; RR, relative risk.
a 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 fiber, and folate.

Because hypertension is an important risk factor for stroke, we performed analyses stratified by history of hypertension at baseline (). Potassium intake was statistically significantly 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 significant 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 significant 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 significantly by stratum of hypertension.

Table 4.  Relative Risks of Total Stroke and Cerebral Infarction According to Quintiles of Potassium, Calcium, and Magnesium Intakes, Stratified by History of Hypertension, in the Swedish Mammography Cohort, 1998–2008

Quintile of Intake Median, mg/day Total Stroke Cerebral Infarction
No History of Hypertension History of Hypertension No History of Hypertension History of Hypertension
No. of Cases Multivariable RRa 95% CI No. of Cases Multivariable RRa 95% CI No. of Cases Multivariable RRa 95% CI No. of Cases Multivariable RRa 95% CI
Potassium
   1 (lowest) 2,419 239 1.00 Referent 134 1.00 Referent 174 1.00 Referent 116 1.00 Referent
   2 2,767 225 1.02 0.84, 1.24 115 0.72 0.55, 0.94 168 1.05 0.84, 1.32 100 0.71 0.53, 0.95
   3 3,021 223 1.01 0.81, 1.25 125 0.77 0.58, 1.03 170 1.05 0.82, 1.34 102 0.71 0.51, 0.97
   4 3,296 198 0.94 0.74, 1.18 113 0.68 0.49, 0.92 150 0.96 0.73, 1.25 88 0.58 0.41, 0.82
   5 (highest) 3,744 212 1.00 0.78, 1.28 96 0.64 0.45, 0.92 166 1.04 0.78, 1.40 76 0.56 0.38, 0.84
      P trend 0.84 0.02 0.94 0.004
      P interaction 0.26 0.07
Calcium
   1 (lowest) 698 221 1.00 Referent 127 1.00 Referent 166 1.00 Referent 106 1.00 Referent
   2 880 177 0.87 0.71, 1.07 105 0.92 0.71, 1.21 132 0.88 0.69, 1.11 85 0.90 0.67, 1.20
   3 1,012 216 1.02 0.83, 1.25 105 0.89 0.68, 1.18 175 1.10 0.87, 1.38 90 0.91 0.67, 1.24
   4 1,160 246 1.02 0.83, 1.25 128 1.07 0.80, 1.43 186 1.13 0.89, 1.44 105 1.02 0.74, 1.40
   5 (highest) 1,422 237 1.13 0.92, 1.40 118 0.99 0.72, 1.36 169 0.99 0.76, 1.29 96 0.93 0.65, 1.31
      P trend 0.26 0.83 0.68 0.86
      P interaction 0.28 0.37
Magnesium
   1 (lowest) 267 234 1.00 Referent 133 1.00 Referent 177 1.00 Referent 118 1.00 Referent
   2 297 236 1.10 0.91, 1.34 115 0.83 0.63, 1.09 169 1.06 0.84, 1.33 99 0.77 0.58, 1.04
   3 317 207 1.00 0.81, 1.24 111 0.79 0.59, 1.06 160 1.04 0.81, 1.33 86 0.65 0.47, 0.90
   4 339 196 0.95 0.75, 1.20 121 0.89 0.65, 1.21 146 0.94 0.71, 1.23 98 0.75 0.53, 1.05
   5 (highest) 373 224 1.08 0.84, 1.41 103 0.76 0.53, 1.09 176 1.12 0.83, 1.51 81 0.63 0.42, 0.93
      P trend 0.82 0.24 0.63 0.03
      P interaction 0.14 0.03

Abbreviations: CI, confidence interval; RR, relative risk.
a 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 fiber, and folate.

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 significantly 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,[15–22] 4 showed a significant inverse association.[15, 16, 18, 20] Of the 6 studies of calcium intake in relation to stroke incidence or mortality,[16, 17, 22–25] 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 significantly 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, Beta-Carotene Cancer Prevention Study, intake of magnesium but not potassium or calcium was inversely associated with risk of cerebral infarction, but the associations were not modified 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 significant 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 specific 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, 23–25] 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 finding was due to chance. No previous study has reported a positive association between calcium intake and intracerebral hemorrhage.

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 population-based 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 misclassification 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, findings 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.

References

  1. Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation 2010;121(7):e46–e215.

  2. Ding EL, Mozaffarian D. Optimal dietary habits for the prevention of stroke. Semin Neurol 2006;26(1):11–23.

  3. Ascherio A, Hennekens C, Willett WC, et al. Prospective study of nutritional factors, blood pressure, and hypertension among US women. Hypertension 1996;27(5):1065–1072.

  4. Ascherio A, Rimm EB, Giovannucci EL, et al. A prospective study of nutritional factors and hypertension among US men. Circulation 1992;86(5):1475–1484.

  5. Song Y, Sesso HD, Manson JE, et al. Dietary magnesium intake and risk of incident hypertension among middle-aged and older US women in a 10-year follow-up study. Am J Cardiol 2006;98(12):1616–1621.

  6. Van Leer EM, Seidell JC, Kromhout D. Dietary calcium, potassium, magnesium and blood pressure in the Netherlands. Int J Epidemiol 1995;24(6):1117–1123.

  7. Ma J, Folsom AR, Melnick SL, et al. Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. J Clin Epidemiol 1995;48(7):927–940.

  8. Beyer FR, Dickinson HO, Nicolson DJ, et al. Combined calcium, magnesium and potassium supplementation for the management of primary hypertension in adults. Cochrane Database Syst Rev. 2006;3.

  9. Dickinson HO, Nicolson DJ, Campbell F, et al. Potassium supplementation for the management of primary hypertension in adults. Cochrane Database Syst Rev. 2006;3.

  10. Dickinson HO, Nicolson DJ, Campbell F, et al. Magnesium supplementation for the management of essential hypertension in adults. Cochrane Database Syst Rev. 2006;3.

  11. van Mierlo LA, Arends LR, Streppel MT, et al. Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials. J Hum Hypertens 2006;20(8):571–580.

  12. Song Y, Li TY, van Dam RM, et al. Magnesium intake and plasma concentrations of markers of systemic inflammation and endothelial dysfunction in women. Am J Clin Nutr 2007;85(4):1068–1074.

  13. Song Y, Ridker PM, Manson JE, et al. Magnesium intake, C-reactive protein, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Diabetes Care 2005;28(6):1438–1444.

  14. Larsson SC, Wolk A. Magnesium intake and risk of type 2 diabetes: a meta-analysis. J Intern Med 2007;262(2):208–214.

  15. Khaw KT, Barrett-Connor E. Dietary potassium and stroke-associated mortality. A 12-year prospective population study. N Engl J Med 1987;316(5):235–240.

  16. Ascherio A, Rimm EB, Hernán MA, et al. Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men. Circulation 1998;98(12):1198–1204.

  17. Iso H, Stampfer MJ, Manson JE, et al. Prospective study of calcium, potassium, and magnesium intake and risk of stroke in women. Stroke 1999;30(9):1772–1779.

  18. Fang J, Madhavan S, Alderman MH. Dietary potassium intake and stroke mortality. Stroke 2000;31(7):1532–1537.

  19. Bazzano LA, He J, Ogden LG, et al. Dietary potassium intake and risk of stroke in US men and women: National Health and Nutrition Examination Survey I epidemiologic follow-up study. Stroke 2001;32(7):1473–1480.

  20. Green DM, Ropper AH, Kronmal RA, et al. Serum potassium level and dietary potassium intake as risk factors for stroke. Cardiovascular Health Study. Neurology 2002;59(3):314–320.

  21. Umesawa M, Iso H, Date C, et al. Relations between dietary sodium and potassium intakes and mortality from cardiovascular disease: the Japan Collaborative Cohort Study for Evaluation of Cancer Risks. JACC Study Group. Am J Clin Nutr 2008;88(1):195–202.

  22. Larsson SC, Virtanen MJ, Mars M, et al. Magnesium, calcium, potassium, and sodium intakes and risk of stroke in male smokers. Arch Intern Med 2008;168(5):459–465.

  23. Abbott RD, Curb JD, Rodriguez BL, et al. Effect of dietary calcium and milk consumption on risk of thromboembolic stroke in older middle-aged men. The Honolulu Heart Program. Stroke 1996;27(5):813–818.

  24. Umesawa M, Iso H, Date C, et al. Dietary intake of calcium in relation to mortality from cardiovascular disease: the JACC Study. Stroke 2006;37(1):20–26.

  25. Umesawa M, Iso H, Ishihara J, et al. Dietary calcium intake and risks of stroke, its subtypes, and coronary heart disease in Japanese: the JPHC Study Cohort I. JPHC Study Group. Stroke 2008;39(9):2449–2456.

  26. Song Y, Manson JE, Cook NR, et al. Dietary magnesium intake and risk of cardiovascular disease among women. Am J Cardiol 2005;96(8):1135–1141.

  27. Ohira T, Peacock JM, Iso H, et al. Serum and dietary magnesium and risk of ischemic stroke: the Atherosclerosis Risk in Communities Study. Am J Epidemiol 2009;169(12):1437–1444.

  28. Wolk A, Bergström R, Hunter D, et al. A prospective study of association of monounsaturated fat and other types of fat with risk of breast cancer. Arch Intern Med 1998;158(1):41–45.

  29. Norman A, Bellocco R, Bergström A, et al. Validity and reproducibility of self-reported total physical activity—differences by relative weight. Int J Obes Relat Metab Disord 2001;25(5):682–688.

  30. Bergström L, Kylberg E, Hagman U, et al. The food composition database KOST: the National Administration's information system for nutritive values of food. Vår Föda 1991;43:439–447.

  31. Willett W, Stampfer MJ. Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 1986;124(1):17–27.

  32. Messerer M, Johansson SE, Wolk A. The validity of questionnaire-based micronutrient intake estimates is increased by including dietary supplement use in Swedish men. J Nutr 2004;134(7):1800–1805.

  33. Hsia J, Heiss G, Ren H, et al. Calcium/vitamin D supplementation and cardiovascular events. Women's Health Initiative Investigators. Circulation 2007;115(7):846–854.