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Journal of the American College of Nutrition, Vol. 17, No. 1, 59-64 (1998)
Published by the American College of Nutrition

Original Paper

Dietary Calcium and Blood Pressure in a Native American Population

K.M. Venkat Narayan, MD, Robert L. Hanson, MD, Cynthia J. Smith, PhD, Robert G. Nelson, MD, Stacey B. Gyenizse, RD, David J. Pettitt, MD and William C. Knowler, MD

Diabetes and Arthritis Epidemiology Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Objective: To assess the relationship between dietary calcium and blood pressure.

Methods: Cross-sectional study of 404 adult Pima Indians of Arizona. Dietary variables were assessed by the 24-hour recall. Hypertension (HTN) was defined as systolic blood pressure (SBP) >=140 mmHg or diastolic blood pressure (DBP) >=90 mmHg or drug treatment.

Results: Controlled for age and sex, dietary calcium intake was higher in subjects with HTN than in those without (p<0.01), and higher dietary calcium was associated with a higher prevalence of HTN (odds ratio comparing highest with lowest tertile group of calcium=2.6, 95% CI 1.4–4.8). Age-sex-adjusted mean DBP in low, middle and high tertiles of calcium was 74, 76, and 79 mmHg, respectively (p<0.001). SBP was not significantly different in the three tertiles (p=0.07). Multiple regression analyses that controlled for age, sex, body mass index, sodium, potassium and alcohol also suggested a positive association between DBP and dietary calcium (p<0.01), an association which was stronger at higher glucose concentrations (p<0.01 for the calcium-glucose interaction).

Conclusion: In Pima Indians, a population with a high incidence of diabetes, the inverse association between dietary calcium and blood pressure reported in other populations was not found.

Key words: blood pressure, hypertension, calcium, dietary, diabetes mellitus, Pima Indians


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Most epidemiologic studies investigating the relationship between dietary calcium intake and blood pressure have reported an inverse association, and data from a meta-analysis of published observations were also consistent with such an association [1]. However, substantial heterogeneity across studies was observed, and the authors could not exclude publication bias as an explanation of such heterogeneity [1]. Such bias may occur where there is a tendency for papers that report an association in one direction to be preferentially published over those that report no association or one in an opposite direction [2]. Furthermore, there may be true heterogeneity in the effect of calcium among populations due to unexplained clinical and biological factors [1]. Although the relationship between calcium and blood pressure has been studied in a variety of ethnic groups, there have not been any published reports from Native American populations.

We report here an absence of an inverse association between dietary calcium and blood pressure among Pima Indians, a Native American population with a high incidence and prevalence of non-insulin-dependent diabetes mellitus [3,4].


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
Since 1965, a prospective study of diabetes and its complications has been conducted in the Gila River Indian Community, where most residents are Pima or Tohono O’odham Indians [3]. All residents of the Community who are >=5 years old are invited to attend biennial research examinations, which include a medical history, a physical examination and laboratory tests. A 75 g oral glucose tolerance test is performed and diabetes is diagnosed if the 2-hour post-load plasma glucose concentration is >=200 mg/dl [5] or if diabetes is detected in the course of routine medical care [4]. Systolic (SBP) and diastolic (DBP) blood pressures are measured by a physician or a nurse with a mercury manometer while the subject is supine. DBP is determined at the fourth Korotkoff sound (the usual practice when the study began). Height and weight are measured with the subject wearing light clothes and no shoes. Body mass index (BMI), a measure of obesity, is calculated as weight in kg divided by height in m squared [6].

During 1989, a sample of 599 community members aged 18 to 74 years participated in a dietary survey [7]. Subjects were selected, without regard to health or presence of diabetes, from a register of persons residing within the community. Excluded from participation in this survey were pregnant women, non-lactating women less than 6 weeks postpartum and lactating women less than 6 months postpartum. 404 subjects who completed the dietary survey and attended a biennial research examination within a year of the dietary assessment were included in the present study.

Dietary Assessment
A standard 24-hour recall [8], adapted to suit Pima Indian diet, was used to measure nutrient intake as described elsewhere [7]. Measurement of calcium intake included calcium supplements. Intrainterviewer reproducibility was evaluated with repeat interviews in 24 subjects selected at random. Pearson correlation was used to measure the reproducibility in duplicate data pairs. Interviews were conducted by four Pima women who were trained by a research dietitian according to methods recommended by the Nutrition Coordinating Center of the University of Minnesota in Minneapolis. Intake of 102 nutrients was calculated using a specific computerized database developed by the Nutrition Coordinating Center [9]. This database was expanded to include specific Pima foods, the nutrient composition of which was determined prior to the survey by a combination of laboratory analysis and computer-based recipe calculation [7,10].

Statistical Analysis
The association between calcium intake and blood pressure was first examined with Spearman partial correlation coefficients adjusted for age, sex, and total energy intake. Hypertension (HTN) was defined as SBP >=140 mm Hg or DBP >=90 mm Hg or treatment with antihypertensive drugs [11]. Differences between hypertensive and normotensive subjects for each sex were compared using analysis of variance (ANOVA), controlled for age. The prevalence of HTN by tertiles of calcium intake was calculated for men and women, stratified into three age groups: 18 to 34 years, 35 to 54 years, 55 to 74 years. The age-sex-BMI-energy-adjusted prevalence of HTN for tertiles of calcium intake was also calculated from multiple logistic regression models. Age-sex-BMI-energy-adjusted means of SBP and DBP for tertiles of calcium intake for subjects not taking antihypertensive drugs were also computed. Statistical significance was tested by ANOVA. Because the relationship between calcium intake and blood pressure may be different between diabetic and nondiabetic subjects, interactions of calcium intake with diabetes and 2-hour glucose were evaluated [12], and these groups were also analyzed separately.

The association between calcium intake and blood pressure, controlled for potentially confounding factors, was assessed by multiple linear regression. To evaluate multicollinearity, each predictor variable was in turn treated as the response variable in multiple regression models in which the remaining predictor variables were the independent variables [13]. Multiple R2 was thus calculated for each predictor variable and not more than one variable with an R2 of >=0.90 was included in any regression model. As potassium, magnesium, phosphorus, fat and total energy intakes had multiple R2 >=0.90, a number of separate models were generated. Stepwise, forward and backward selection models including age, sex, BMI, alcohol, calcium, sodium, potassium, magnesium, phosphorus, vitamin D, fat and energy were also assessed. Residual analysis was used to confirm multiple regression model assumptions of linearity, homogeneity of variance, independence and normality were satisfied [13]. Two-tailed p-values were reported.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
404 subjects (176 men and 228 women) completed the dietary and blood pressure measurements. The median calcium intake was 760 mg (25th and 75th percentiles 486 and 1079, respectively), and age-specific means were at least as high as the average calcium intake of low income groups in the United States (unpublished data). Based on a random sample of 24 duplicate interviews, Pearson correlation coefficients of 24-h recall for repeat interviews by the same interviewer were 0.77 for total energy, 0.50 for protein, 0.67 for fat, 0.78 for carbohydrate, and 0.52 for calcium. As shown in Table 1, adjusted for age, sex and energy intake, there was a weak positive correlation between calcium intake and both systolic and diastolic blood pressures. The correlation between calcium intake and DBP was 0.17 (p<0.01) among women and 0.14 (p<0.05) among men; 0.19 (p<0.01) among diabetic and 0.12 (p>0.05) among non-diabetic subjects. Adjusted for age, sex and energy intake, calcium intake was positively associated with intakes of sodium, potassium, magnesium, phosphorus, vitamin D, fat and fiber, and negatively associated with alcohol intake. SBP and DBP were not associated with intakes of sodium, potassium, magnesium, phosphorus, alcohol, fat or fiber (data not shown).


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  		Table 1. Spearman Partial Correlations with Dietary Calcium Intake*

 
Of the 404 people, 85 (48%) men and 70 (31%) women had HTN. Adjusted for age and sex, people with HTN had higher intakes of calcium, phosphorus and energy than those with normal blood pressure (p<0.05 for each). Data comparing people with HTN with those with normal blood pressure are shown in Table 2. Adjusted for age, both men and women with HTN had higher dietary calcium intake than those with normal blood pressure, but this was significant only among women.


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  		Table 2. Characteristics of Subjects with and without Hypertension

 
The age-sex-BMI-energy-adjusted prevalence of HTN was higher in higher tertile groups of calcium intake (Table 3). Odds ratio for HTN comparing tertile group 3 with tertile group 1 was 2.1 (95% CI 1.1, 4.2). The age-sex-BMI-energy-adjusted prevalence of HTN was lowest in the lowest tertile group of calcium intake and highest in the highest tertile group for all subjects and for diabetic subjects, but in non-diabetic subjects the trend was not linear. The prevalence of HTN was greater with higher calcium intake in all age groups and in both sexes except among men aged 55 to 74 years and women aged 18 to 34 years (Fig. 1). Age-BMI-energy-adjusted prevalence of HTN was higher in higher tertile groups of calcium intake in both sexes (HTN prevalence in low, middle and high tertiles of calcium were: 34.3%, 35.3% and 37.3% for men, {chi}2=1.2, 2 d.f., p=0.54, and 20.6%, 27.4% and 33.5% for women, {chi}2=4.1, 2 d.f., p=0.12, respectively).


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  		Table 3. Prevalence (%) of Hypertension, Adjusted for Age, Sex, BMI and Energy, by Tertile Groups of Calcium Intake

 


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  		Fig. 1. Prevalence of hypertension by tertile groups of dietary calcium for different age groups. Calcium measured by 24-hour recall and HTN defined as SBP>=140 mmHg or DBP>=90 mmHg or drug treatment.

 
Age-sex-BMI-energy-adjusted means of SBP and DBP by tertile group of calcium intake are presented in Figs. 2 and 3. The 61 individuals taking anti-hypertensive drugs were excluded from this analyses. DBP (p<0.05) was significantly positively associated with calcium intake (Fig. 2). When analyzed separately by diabetes status, the mean SBP and DBP were higher with higher calcium intake, but the association was statistically significant only for DBP among the diabetic subjects (p<0.05). There was no interaction between sex and calcium on the relationship between calcium and blood pressure.



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  		Fig. 2. Age-sex-BMI-energy-adjusted mean (S.E.) systolic and diastolic blood pressures by tertile groups of dietary calcium. Subjects taking anti-hypertensive drugs excluded.

 


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  		Fig. 3. Age-sex-BMI-energy-adjusted mean (S.E.) systolic and diastolic blood pressures by tertile groups of dietary calcium in nondiabetic and diabetic subjects. Subjects taking anti-hypertensive drugs excluded.

 
The estimated effects of a 100 mg/day difference in dietary calcium intake on SBP and DBP, calculated from multiple linear regression models (excluding subjects taking antihypertensive drugs) are presented in Table 4. Calcium intake, controlled for various potentially confounding variables, was consistently and positively associated with SBP and DBP. However, the association was significant only for DBP, which was approximately 0.3 mm Hg higher for every 100 mg/day difference in dietary calcium. When age, sex, BMI, alcohol, calcium, potassium, sodium, magnesium, energy and fat were included in stepwise, backward and forward selection models, age, sex, BMI (p<0.001 for each) and calcium (p<0.1) were selected as the best predictors of SBP. Age, sex, BMI (p<0.001 for each) and calcium (p<0.01) were selected for DBP. When these analyses were repeated including subjects taking anti-hypertensive drugs, similar results were obtained (data not shown). In sub-group analyses, the relationship between calcium intake and blood pressure was positive in both hypertensive and normotensive subjects, but the association was statistically significant only for DBP (p<0.05) in normotensive subjects. As seen in Table 4, the association was generally stronger among diabetic than non-diabetic subjects even when data on diabetic subjects were controlled for diabetes duration and glycemia. The association between calcium intake and DBP was stronger at higher glucose concentrations (p<0.01 for the interaction between calcium intake and glucose concentration).


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  		Table 4. Multiple Linear Regression Coefficients for 100 mg/Day Difference in Calcium Intake (Subjects Taking Anti-Hypertensive Drugs Excluded)

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
A weak but direct association was found between dietary calcium intake and blood pressure in Pima Indians. This association was more evident for DBP and among diabetic subjects. The direction of the association remained unchanged when controlled for age, sex, and BMI. Other potential confounders, namely, intakes of alcohol [14,15], sodium [16], potassium [17], magnesium [18,19], phosphorus [18–20], vitamin D [21], energy and fat did not alter the relationship between calcium intake and blood pressure. However, in addressing the potential confounding factors, as in all previous studies, the problem of multicollinearity was faced [22]. Correlations between variables may preclude evaluation of the independent effect of a specific nutrient on blood pressure in multivariable analyses [22,23].

Despite a small number of null findings [21,24,25], most cross-sectional epidemiological studies have suggested an inverse association of calcium intake with blood pressure or HTN [1]. However, heterogeneity across populations was observed, which may reflect either true biological differences, publication bias or both [1]. It has also been suggested that the association may be affected by the presence of diabetes [26]. The present findings may simply be spurious or they may represent true biologic heterogeneity in the effect of calcium intake on blood pressure on some unknown basis. A drawback of most studies, including the present one, is that they were cross-sectional and thus may reflect dietary alterations in response to high blood pressure. Results of clinical trials testing the effect of oral calcium on blood pressure have also not produced consistent findings. Cutler and Brittain [27], in a meta-analyses of reported clinical trials, concluded that the effect on SBP was small (-1.8 mm Hg, 95% CI -3.0, -0.6), and on DBP was not significant (-0.7 mm Hg, 95% CI -1.5, +0.2). A more recent meta-analysis of clinical trials also reported similar findings for SBP (-1.27 mm Hg, 95% CI -2.25, -0.29) and for DBP (-0.24 mm Hg, 95% CI -0.92, 0.44) [28]. Although the latter meta-analysis attempted to identify unpublished trials, the extent to which publication bias (the tendency not to publish negative results) may have contributed to the findings in either of the meta-analysis is not known.

Most previous studies of this relationship have used the 24-hour recall and this method is accepted as representative of the dietary intake of groups of subjects [29]. The 24-hour recall method for measuring nutrient intake is subject to substantial intra-individual variation, however, and the use of a single 24-hour recall to estimate usual intake of calcium for individuals may therefore be problematic [30,31]. However, there was reasonable intraobserver correlation, and there is no reason to believe that this variation differs by HTN status.

Sources of dietary calcium may affect the relationship between calcium intake and blood pressure. Calcium from dairy products has been more closely linked with blood pressure in several reports [19–22,32,33]. Based on a subsequent sample of 24-hour records, there was very little use of supplementary calcium, and water was an important source in this population contributing almost 25% of dietary calcium. This is higher than in most other populations where water contributes approximately 5 to 10% of total calcium intake [34]. The most powerful inverse association for calcium and blood pressure have been reported for dietary sources, but our data did not permit analysis according to the source of calcium. Whether and how the source of calcium contributes to the relationship found in the present study remains to be determined. It is not known whether the presence of an unknown confounder in water may be responsible for the findings, but routine surveillance has not demonstrated unacceptable amounts of fluoride, arsenic, barium, cadmium, chromium, copper, iron, lead, magnesium, mercury, selenium, silver, sodium or zinc in the drinking water consumed in the Community (Personal communication, Gila River Indian Community Environmental Health Department).

Calcium-induced natriuresis is one of the proposed mechanisms for the inverse effect of calcium on blood pressure [35]. This is also thought to be amplified in the presence of a high sodium intake in susceptible individuals [18,36]. Further, patients with low-renin HTN and salt-sensitive HTN are more responsive to the blood pressure lowering effect of calcium [37–41]. In the present study, dietary sodium measured by 24-hour recall was not associated with blood pressure and it may be that this population is not susceptible to salt-sensitive HTN, although a better method of estimating dietary sodium is needed to make this conclusion. There was also no interaction between sodium intake and calcium’s relation to blood pressure. Genetic bases for salt-sensitivity [42,43] and altered calcium metabolism [18] are both plausible and could explain the findings in the Pima Indians. Since the Pimas are a population with a very high prevalence of diabetes [3,4], a different set of factors may play a major role in the development of HTN. Indeed, the finding of a significant interaction between calcium intake and glucose concentration suggests that calcium may have a different effect in hyperglycemic subjects than in normoglycemic ones.

In summary, this study in Pima Indians has not found the inverse association between dietary calcium and blood pressure reported in other populations. Further investigations would be required to determine if there are true biological differences between populations in the relationship of calcium intake to blood pressure.


   ACKNOWLEDGMENTS
 
The authors thank the members of the Gila River Indian Community who have participated in the longitudinal study over nearly 30 years. This work was supported in part by NIH Contract N01-DK-6-2285 from the National Institute of Diabetes and Digestive and Kidney Diseases.


   FOOTNOTES
 
Reprints not available from author.

Received March 1, 1997. Accepted May 1, 1997.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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