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Hypertension is the most important, modifiable risk factor for cardiovascular disease and mortality. High salt intake may predispose children to develop hypertension later. A modest reduction in population salt intake worldwide would result in a major improvement in public health. Regarding smoking as another risk factor, there are various strategies that can be used to promote smoking cessation. Physicians are in an excellent position to help their patients stop smoking. Targeted weight loss interventions in population subgroups might be more effective for the prevention of hypertension than a general-population approach. A diet rich in high-potassium fruit and vegetables is strongly recommended. Fresh products are best; normal potassium content is reduced when foods are canned or frozen. Calcium supplementation reduces blood pressure in hypertensive individuals during chronic nitric oxide synthase inhibition and high calcium diet enhances vasorelaxation in nitric oxide-deficient hypertension. Magnesium should be considered by anyone seeking to prevent or treat high blood pressure. The foundation for a healthy blood pressure consists of a healthy diet, adequate exercise, stress reduction, and sufficient amounts of potassium and magnesium, but further investigations are required before making definitive therapeutic recommendations on magnesium use. Alcohol usage is a more frequent contributor to hypertension than is generally appreciated. For hypertensive patients in whom stress appears to be an important issue, stress management should be considered as an intervention. Individualized cognitive behavioral interventions are more likely to be effective than single-component interventions.

Nearly all of the annual 287,000 global maternal deaths are preventable. Hypertensive disorders of pregnancy (HDP) are among the major causes. A novel fixed-dose combination pill or polypill to prevent cardiovascular disease is a promising strategy for prevention of HDP. The aim of this study was to identify eligible candidates for a polypill for the prevention of HDP. A comprehensive review of systematic reviews on drug and dietary interventions to prevent HDP was conducted. Interventions were evaluated based on efficacy, dose, route of administration, and side effects. Fourteen interventions were assessed. Low-dose aspirin and calcium were identified as candidates for a polypill, with risk reduction estimations for pregnancy-induced hypertension and preeclampsia ranging between 10 and 62 %, depending on patient population characteristics including a priori risk, and gestation age at start of intervention. Their effect may be augmented through the addition of vitamin D, vitamin B12, and folic acid. The effect and optimal composition needs to be evaluated in future trials. Given the persistent burden of maternal and perinatal mortality associated with HDP, prevention of these disorders is key-especially in low-resource settings. The polypill approach with a combination of aspirin, calcium, vitamin D, vitamin B12, and folic acid is a promising strategy to improve maternal and perinatal health outcomes.

Recent evidence suggests that Ca supplements increase the risk of cardiovascular events, but the mechanism(s) by which this occurs is uncertain. In a study primarily assessing the effects of various Ca supplements on blood Ca levels, we also investigated the effects of Ca supplements on blood pressure and their acute effects on blood coagulation. We randomised 100 post-menopausal women to 1 g/d of Ca or a placebo containing no Ca. Blood pressure was measured at baseline and every 2 h up to 8 h after their first dose and after 3 months of supplementation. Blood coagulation was measured by thromboelastography (TEG) in a subgroup of participants (n 40) up to 8 h only. Blood pressure declined over 8 h in both the groups, consistent with its normal diurnal rhythm. The reduction in systolic blood pressure was smaller in the Ca group compared with the control group by >5 mmHg between 2 and 6 h (P≤0·02), and the reduction in diastolic blood pressure was smaller at 2 h (between-groups difference 4·5 mmHg, P=0·004). Blood coagulability, assessed by TEG, increased from baseline over 8 h in the calcium citrate and control groups. At 4 h, the increase in the coagulation index was greater in the calcium citrate group compared with the control group (P=0·03), which appeared to be due to a greater reduction in the time to clot initiation. These data suggest that Ca supplements may acutely influence blood pressure and blood coagulation. Further investigation of this possibility is required.

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

Background: Calcium (Ca2+) supplementation has been shown paradoxically to reduce intracellular Ca2+ and induce vascular relaxation. The aim of the study was to assess 24-h blood pressure (BP) change after Ca2+ supplementation and to investigate its relation to changes in intracellular ions and the activity of the first isoform of sodium-hydrogen exchange (NHE-1) in subjects with hypertension and type 2 diabetes., Methods: This parallel, randomized controlled, single-blinded trial, consisted of 31 patients with type 2 diabetes, and hypertension who were allocated to receive 1,500 mg of Ca2+ per day (n = 15) or no treatment (n = 16) for 8 weeks., Results: In the Ca2+ group a decrease of 1.7 +/- 2.7 mm Hg (mean +/- SE) P = 0.52 for mean 24-h systolic BP (SBP) and 2.1 +/- 1.5 mm Hg, P = 0.19 for mean 24-h diastolic BP (DBP) was recorded. Whereas in the control group an increase of 1.4 +/- 2.7 mm Hg, P = 0.59 for mean 24-h SBP and 1.2 +/- 2.8 mm Hg, P = 0.83 for mean 24-h DBP was observed. Intraplatelet Ca2+ decreased whereas intraplatelet magnesium (Mg2+) and erythrocyte K+ increased in the intervention group. Change in mean 24-h SBP in the pooled group correlated with both change in intraplatelet Ca2+ (r = 0.49, P < 0.05) and NHE-1 activity (r = 0.6, P < 0.001). The contribution of intraplatelet Ca2+ was attenuated when both parameters were entered in a multivariate regression model., Conclusions: The present study shows a weak, statistically nonsignificant trend towards association of Ca2+ supplementation on 24-h BP in hypertensive subjects with type 2 diabetes. However, our results indicated an interrelation of [Ca2+]i levels and NHE-1 activity on BP in patients with hypertension and type 2 diabetes.

Background: Consumption of dairy foods has been associated with lower blood pressure in certain populations., Objective: This study examined the effects of dairy foods on blood pressure (BP) and intracellular calcium ((Ca)(i)) and the dependence of BP changes on changes in (Ca)(i)., Design: Twenty-three stage 1 hypertensive adults were fed the following 3 experimental diets (5 wk each) in a randomized cross-over design study; a dairy-rich, high fruits and vegetables diet (D-FandV; 30% fat, 7% saturated fat (SFA), 3.4 servings/d dairy), a high fruits and vegetables diet (FandV; 30% fat, 7% SFA, 0.4 servings/d dairy), and an average Western diet (control; 36% fat, 15% SFA, 0.4 servings/d dairy). Systolic (SBP) and diastolic (DBP) BP, calcium regulatory hormones, and erythrocyte (Ca)(i) were determined., Results: SBP and DBP were significantly reduced by approximately 2 mm Hg following both D-F&V and F&V diets vs. the control (P < 0.05). The D-F&V diet significantly lowered 1,25-dihydroxyvitaminD compared with the F&V and control diets (P < 0.01). Serum calcium, parathyroid hormone, calcitonin, and renin activity were unchanged. The D-F&V diet lowered (Ca)(i) vs. the other two diets (P < 0.01), and this change correlated with the fall in DBP (r = 0.52, P < 0.05). Subjects who responded to the D-F&V diet by significantly reducing (Ca)(i) exhibited significantly greater net decreases in DBP on the D-F&V vs. the F&V (-2.8 +/- 1.0 mm Hg) and control diets (-5.4 +/-1.0 mm Hg; diet x group interaction, P < 0.02)., Conclusion: Consumption of dairy foods beneficially affects (Ca)(i), resulting in improved BP in a subgroup defined by (Ca)(i) response.

Aims/hypothesis: To investigate the effect of oral calcium (Ca(2+)) supplementation on insulin sensitivity measured by the euglycaemic hyperinsulinaemic clamp, intraplatelet cationic concentration of Ca(2+) ([Ca(2+)](i)) and the transmembrane sodium-hydrogen exchanger (NHE) activity in erythrocytes in subjects with Type 2 diabetes and hypertension., Patients and Methods: In this parallel randomized controlled single-blinded trial, 31 patients were allocated to receive either 1500 mg of Ca(2+) orally, daily (n = 15) or no treatment (n = 16) for 8 weeks. At baseline and at the end of the 8-week period insulin sensitivity, [Ca(2+)](i) and the first isoform of NHE (NHE-1) activity were measured., Results: At the end of the study, subjects who received Ca(2+) supplementation showed higher insulin sensitivity (Delta M-value 0.32 +/- 0.5 mmol/min P < 0.05) and lower [Ca(2+)](i) (125.0 +/- 24.7 to 80.4 +/- 10.6 nmol/l, P < 0.05, mean +/- sem) and NHE-1 activity (79.5 +/- 10.0 to 52.1 +/- 6.4 mmol Na/l red cell/h, P < 0.05). None of the above parameters were changed in the control group. Simple regression analysis demonstrated the change in [Ca(2+)](i) significantly determined insulin sensitivity change (beta = -0.36, P < 0.05)., Conclusions/interpretation: Oral Ca(2+) supplementation improves insulin sensitivity in patients with Type 2 diabetes and hypertension. These changes are likely to be mediated by changes in intracellular ionic Ca(2+). NHE-1 activity was also reduced after Ca(2+) supplementation but its role in insulin sensitivity requires further investigation.

Despite advances in the prevention and treatment of hypertension over the past decade, hypertension remains an important public health challenge. Recent efforts to reduce the prevalence of hypertension have focused on nonpharmacologic means, specifically diet. An increased intake of minerals such as potassium, magnesium, and calcium by dietary means has been shown in some but not all studies to reduce blood pressure in patients with hypertension. This review will discuss the roles of potassium, magnesium, and calcium in the prevention and treatment of essential hypertension with specific emphasis on clinical trial evidence, mechanism of action, and recommendations for dietary intake of these minerals. A high intake of these minerals through increased consumption of fruits and vegetables may improve blood pressure levels and reduce coronary heart disease and stroke.

Background: Follow up of participants in trials of antenatal calcium supplementation has reported an impact on blood pressure among mothers and children., Aims: To determine whether blood pressure at 4-7 years follow up would be lower for calcium-supplemented mothers in the Australian Calcium Trial (ACT) and for their children., Methods: This follow up targeted 414 of the original ACT participants with liveborn infants who lived in South Australia. Mothers and their children attended the Women's and Children's Hospital for anthropomorphic examination. Information on lifestyle factors was collected by questionnaire. Descriptive statistics examined differences between respondents and non-respondents and multiple regression models examined associations with blood pressure., Results: Blood pressure and body measurements were available on 45 and 43% of eligible women and children, respectively; questionnaire data were available on 50% of this cohort. At follow up, there were no differences between treatment groups in blood pressure in the women or their children. Both children of women who had high blood in pregnancy (pre-eclampsia or pregnancy-induced hypertension) and the women themselves had higher systolic and diastolic blood pressure at follow up. Among children, there was a trend towards an interaction with the treatment group with both systolic and diastolic blood pressure at follow up., Conclusion: There is no evidence that the impact of calcium supplementation in reducing the risk of high blood pressure in pregnancy is sustained 4-7 years after the index pregnancy either in woman or in their children; however, calcium supplementation may lower blood pressure in children of pregnant women with hypertension.

The labeling of health claims that meet the significant scientific agreement (SSA) standard (authorized health claims) and qualified health claims on conventional foods and dietary supplements requires premarket approval by the US Food and Drug Administration (FDA). FDA conducts an evidence-based review to determine whether there is sufficient evidence to support an authorized or qualified health claim. An evidence-based review was conducted on the human intervention and observational studies evaluating the role of supplemental calcium in reducing the risk of hypertension, pregnancy-induced hypertension, and preeclampsia. This review provides FDA's evaluation of the current scientific evidence on the role of supplemental calcium in reducing the risk of these three end points. Based on this evidence-based review, the agency concluded that the relationship between calcium and risk of hypertension is inconsistent and inconclusive, and the relationship between calcium and risk of pregnancy-induced hypertension and preeclampsia is highly unlikely.

Background: Metabolic studies suggest calcium may have a role in the regulation of blood pressure. Some epidemiological studies have reported that people with a higher intake of calcium tend to have lower blood pressure. Previous systematic reviews and meta-analyses have reached conflicting conclusions about whether oral calcium supplementation can reduce blood pressure., Objectives: To evaluate the effects of oral calcium supplementation as a treatment for primary hypertension in adults., Search Strategy: We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review., Selection Criteria: Inclusion criteria were: 1) RCTs comparing oral calcium supplementation with placebo, no treatment, or usual care; 2) treatment and follow-up >/=8 weeks; 3) participants over 18 years old, with raised systolic blood pressure (SBP) >/=140 mmHg or diastolic blood pressure (DBP) >/=85 mmHg; 4) SBP and DBP reported at end of follow-up. We excluded trials where: participants were pregnant; received antihypertensive medication which changed during the study; or calcium supplementation was combined with other interventions., Data Collection and Analysis: Two reviewers independently abstracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted., Main Results: We included 13 RCTs (n=485), with between eight and 15 weeks follow-up. The results of the individual trials were heterogeneous. Combining all trials, participants receiving calcium supplementation as compared to control had a statistically significant reduction in SBP (mean difference: -2.5 mmHg, 95% CI: -4.5 to -0.6, I(2 )= 42%), but not DBP (mean difference: -0.8 mmHg, 95% CI: -2.1 to 0.4, I(2) = 48%). Sub-group analyses indicated that heterogeneity between trials could not be explained by dose of calcium or baseline blood pressure. Heterogeneity was reduced when poor quality trials were excluded. The one trial reporting adequate concealment of allocation and the one trial reporting adequate blinding yielded results consistent with the primary meta-analysis., Authors' Conclusions: In view of the poor quality of included trials and the heterogeneity between trials, the evidence in favour of causal association between calcium supplementation and blood pressure reduction is weak and is probably due to bias. This is because poor quality studies generally tend to over-estimate the effects of treatment. Larger, longer duration and better quality double-blind placebo controlled trials are needed to assess the effect of calcium supplementation on blood pressure and cardiovascular outcomes.

Although supplemental calcium typically lowers blood pressure in subjects with salt-sensitive, low-renin hypertension - presumably by down-regulating increased production of parathyroid hormone (PTH) and/or parathyroid hypertensive factor (PHF) - its impact on the blood pressure of unselected hypertensive or normotensive subjects, as assessed by meta-analyses, appears to be trivial at best. This suggests that calcium may actually raise blood pressure a bit in some patients with high-renin hypertension, a prediction that is borne out in rodent models of this disorder. There is limited clinical evidence that long-term calcium supplementation tends to raise plasma renin activity; this finding, if valid, could evidently rationalize the equivocal clinical impact of calcium on blood pressure. Salt restriction likewise boosts renin production, and this effect tends to most notable in subjects whose blood pressure fails to decline during low-salt diets. Two clinical groups have demonstrated that salt restriction has a larger and more consistently beneficial impact on the blood pressure of hypertensives when they concurrently are treated with ACE inhibitors - evidently because the physiological impact of the associated rise in renin is blunted. Analogous logic suggests that calcium supplementation may be more beneficial for hypertensives in the context of ACE inhibition or blockade of angiotensin II receptors; this supposition that can readily be tested clinically. The imminent availability of safe nutraceutical ACE inhibitors may make it more feasible for the general public to benefit from these therapeutic/preventive possibilities.

It has been shown that calcium-enriched diets cause a decrease in arterial blood pressure in hypertensive patients and animals. Moreover, it has been suggested that the combination of dietary calcium and calcium antagonists could paradoxically have a synergistic effect in order to decrease arterial blood pressure. The combination of these treatments may also have potential therapeutic benefit in the attenuation of cardiac hypertrophy. In this study, after being weaned at three weeks, male spontaneously hypertensive rats (SHR) were randomized in four groups of animals. Two of these groups were fed on a normal calcium diet (Ca 1%) and another two groups were fed on a calcium-enriched diet (Ca 2.5%). One of the groups fed on each diet also received amlodipine (1 mg/kg/day) in the drinking water after being weaned. Body weight was measured weekly in all the groups, and arterial blood pressure was also measured in all the 10-, 15-, 20-, and 25-week-old SHR by the tail cuff method. We established the ratio heart weight/body weight x 1000 (R), and we weighed the left ventricle in the 25-week-old animals at the end of the different treatments. The Ca 2.5% diet caused a delay in the development of hypertension in SHR. This effect could not be correlated with alterations in body weight since this diet improved growth in these rats. Amlodipine did not alter growth in SHR. This pharmacological treatment caused a decrease in the arterial blood pressure of the SHR and it intensified the antihypertensive effect of the Ca 2.5% diet. Nevertheless, this drug attenuated the effect of dietary calcium on body weight and when the treatment was prolonged, almodipine also antagonized the effect of dietary calcium on arterial blood pressure. At the end of the different treatments the ratio R and the left ventricular weight were similar in all the groups of animals. Therefore, the use of dietary calcium with a calcium antagonist to control arterial blood pressure seems not to be advisable, and the present data do not prove the usefulness of the mentioned antihypertensive treatments in preventing cardiac hypertrophy.

This 8-week study investigated the effects of increasing dietary Ca2+ content from 1.0% to 3.0% and hypercalcemia induced by oral 1alpha-OH vitamin D3 (1OH-D3, 1.2 microg/kg), on arterial tone in NaCl-hypertensive rats. The high-Ca2+ diet completely prevented the increase in blood pressure induced by the 6.0% NaCl chow, while plasma total Ca2+ and body weight were not different from controls. The 1OH-D3 treatment moderately elevated plasma total Ca2+ and attenuated the NaCl-induced rise in blood pressure, but also impaired weight gain. The tone of isolated mesenteric arterial rings was examined at the end of study. The endothelium-independent relaxations to nitroprusside, isoproterenol, and cromakalim were impaired in NaCl-hypertension. Experiments with NG-nitro-l-arginine methyl ester and tetraethylammonium in vitro suggested that both the nitric oxide- and hyperpolarization-mediated components of endothelium-dependent relaxation to acetylcholine were reduced in NaCl-hypertensive rats. All of the impaired relaxations in NaCl hypertension were normalized by concomitant Ca2+ supplementation. The 1OH-D3 treatment did not affect vascular relaxation, but it attenuated maximal contractile responses induced by norepinephrine and KCl by more than 50%. The reduced vasoconstrictor responses could not be explained by increased apoptosis in the vessel wall, but calcification may have played a role, since moderate signs of medial or adventitial calcification were observed in the aortic preparations after the 1OH-D3 treatment. In conclusion, a high-Ca2+ diet, which did not cause hypercalcemia, normalized blood pressure and endothelium-dependent and endothelium-independent vasorelaxation in NaCl-hypertensive rats. In contrast, chronic hypercalcemia induced by 1OH-D3 was associated with moderately lowered blood pressure, possibly because of reduced vasoconstrictor responses in arterial smooth muscle.

In most hypertensive rat models, serum total cholesterol is typically low and the cholesterol is primarily in the HDL rather than the LDL fraction. This difference from humans usually makes these animals unsuitable for experimental atherosclerosis studies. In the present study, we induced severe hypercholesterolemia including a 10-fold increase in serum LDL cholesterol, endothelial dysfunction and hypertension as well as vascular and renal damage in obese Zucker rats by feeding a human-type high fat, high cholesterol and high salt diet (butter 18, cholesterol 1 and NaCl 6 g/100 g dry weight). Supplementation of this atherogenic diet with plant sterols (1 g/100 g) and replacing the NaCl partially by calcium, magnesium and potassium effectively prevented the diet-induced increases in total and LDL cholesterols and 24-h systolic and mean blood pressures, and markedly improved endothelial function. Plant sterols and the minerals also protected against vascular and renal damage and extended the life span of the obese Zucker rats by 60% compared with the rats fed the atherogenic diet. Our findings suggest that human-type cardiovascular disorders can be induced in obese Zucker rats by feeding a human-type atherogenic diet. This seems to be a suitable animal model for experimental studies on atherosclerosis and hypertension as well as for evaluating new dietary approaches to reducing cardiovascular risk.

Federal health goals for the public have focused on reducing health disparities that exist between whites and various racial and ethnic groups. Many of the chronic diseases for which African Americans are at greater risk- hypertension, stroke, colon cancer, and obesity-may be exacerbated by a low intake of calcium and/or other dairy-related nutrients. For example, a low intake of dairy food nutrients, such as calcium, potassium, and magnesium, may contribute to the high risk of hypertension seen in African Americans. The Dietary Approaches to Stop Hypertension (DASH) study demonstrated that a low-fat diet rich in fruits and vegetables (8 to 10 servings) and low-fat dairy foods (3 servings) significantly reduced blood pressure-and was twice as effective in African-American participants. Calcium and dairy food consumption is particularly low among African-American, Hispanic, and Asian populations. Average intakes are near the threshold of 600 to 700 mg/day, below which bone loss and hypertension can result. Although lactose intolerance may be partly to blame for the low calcium intakes due to reduced dairy food consumption by minority populations, culturally determined food preferences and dietary practices learned early in life also play a role. The high incidence figures for primary lactose maldigestion among minority groups grossly overestimates the number who will experience intolerance symptoms after drinking a glass of milk with a meal. Randomized, double-blind, controlled clinical trials have demonstrated that by using a few simple dietary strategies, those who maldigest lactose (have low levels of the lactase enzyme) can easily tolerate a dairy-rich diet that meets calcium intake recommendations. Physicians and other health professionals can help their minority patients and the general public understand how to improve calcium nutrition by overcoming the surmountable barrier of lactose intolerance. At the same time they will be helping to reduce the incidence of calcium-related chronic diseases for which minority populations are at high risk.

Regulation of intracellular calcium plays a key role in hypertension and obesity. Dysregulation of calcium homeostasis appears to be a fundamental factor linking these conditions. Regulation of intracellular calcium in key disease-related target tissues by calcitrophic hormones provides the opportunity to modulate disease risk with dietary calcium. Overall, sub-optimal calcium intakes contribute to the etiology of salt-sensitivity and hypertension. High salt diets exert a calciuretic effect, serving to exacerbate the physiological consequences of sub-optimal calcium diets. Among these are increases in 1,25-dihydroxyvitamin D, which increases vascular smooth muscle intracellular calcium, thereby increasing peripheral vascular resistance and blood pressure. Dietary calcium reduces blood pressure in large part via suppression of 1,25-dihydroxyvitamin D, thereby normalizing intracellular calcium. The practical relevance of this approach has been confirmed in the DASH (Dietary Approaches to Stop Hypertension) trial, which demonstrated that increasing low-fat dairy product and fruit and vegetable consumption exerted profound blood pressure-lowering effects. The magnitude of this effect among hypertensives was comparable to that typically found in pharmacological trials of mild hypertension. 1,25-dihydroxyvitamin D also stimulates calcium influx in human adipocytes, resulting in stimulation of lipogenesis, inhibition of lipolysis and expansion of triglyceride stores. Accordingly, suppression of 1,25-dihydroxyvitamin D by dietary calcium has been identified as a target, which may contribute to the prevention and management of obesity. Indeed, laboratory, clinical and population data all indicate a significant anti-obesity effect of dietary calcium, although large-scale prospective clinical trials have not yet been conducted to definitively demonstrate the scope of this effect. Thus, available evidence indicates that increasing dietary calcium intakes may result in reductions in fat mass as well as in blood pressure.

Because the effects of calcium supplementation on arterial tone in nitric oxide-deficient hypertension are unknown, we investigated the influence of elevating dietary calcium from 1.1 to 3.0% in Wistar rats treated with N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg. kg(-1). day(-1)) for 8 wk. A high-calcium diet attenuated the development of hypertension induced by L-NAME and abrogated the associated impairments of endothelium-independent mesenteric arterial relaxations to nitroprusside, isoproterenol, and cromakalim. Endothelium-dependent relaxations to acetylcholine during nitric oxide synthase inhibition in vitro were decreased in L-NAME rats and improved by calcium supplementation. The inhibition of cyclooxygenase by diclofenac augmented the responses to acetylcholine in L-NAME rats but not in calcium + L-NAME rats. When hyperpolarization of smooth muscle was prevented by KCl precontraction, the responses to acetylcholine during combined nitric oxide synthase and cyclooxygenase inhibition were similar in all groups. Furthermore, superoxide dismutase enhanced the acetylcholine-induced relaxations in L-NAME rats but not in calcium + L-NAME rats. In conclusion, calcium supplementation reduced blood pressure during chronic nitric oxide synthase inhibition and abrogated the associated impairments in endothelium-dependent and -independent arterial relaxation. The augmented vasorelaxation after increased calcium intake in L-NAME hypertension may be explained by enhanced hyperpolarization and increased sensitivity to nitric oxide in arterial smooth muscle and decreased vascular production of superoxide and vasoconstrictor prostanoids.

No single study or avenue of investigation can resolve the scientific controversies that entangle efforts to determine the effects of specific nutrients on medical conditions. To reach consensus in this area requires a substantial body of plausible, reproducible and consistent data from various investigative approaches--such as the data that now exist regarding the relationship between dietary calcium and blood pressure. In this paper we describe the plethora of epidemiological and clinical studies and analyses that have been published in the last two years and which cumulatively reveal the consistency of the available data regarding the influence of dietary calcium on blood pressure regulation. Nearly 20 years of investigation in this area has culminated in remarkable and compelling agreement in the data, confirming the need for and benefit of regular consumption of the recommended daily levels of dietary calcium.

We updated our previous systematic review of the effect of supplemental calcium on blood pressure. We extended our previous searches on MEDLINE and EMBASE to May 1997 and examined citations from relevant articles. We contacted the authors of eligible trials to ensure the accuracy and completeness of data, and to identify unpublished trials. We included any study in which investigators randomized hypertensive or normotensive people to calcium supplementation or alternative therapy and measured blood pressure for at least 2 weeks. In addition to 32 trials included in the prior metaanalysis, 10 new trials contributed to this metaanalysis. Two pairs of independent reviewers abstracted data and assessed the validity of the study data according to six quality criteria. We calculated the differences in blood pressure change between the calcium supplementation and control groups and pooled the estimates with each trial weighted with the inverse of the variance using a random effects model. The predictors of blood pressure reduction that we examined included method of supplementation, baseline blood pressure, and the methodologic quality of the studies. The pooled analysis shows a reduction in systolic blood pressure of -1.44 mm Hg (95% confidence interval -2.20 to -0.68; P < .001) and in diastolic blood pressure of -0.84 mm Hg (95% confidence interval -1.44 to -0.24; P < .001). We found statistically significant heterogeneity of results across trials (P < or = .02), which persisted when we looked at the nondietary trials alone, but not when we restricted our analysis to dietary trials. Although there was a trend toward larger effects with dietary interventions, none of the possible mediators of blood pressure reduction explained differences in treatment effect. We conclude that calcium supplementation leads to a small reduction in systolic and diastolic blood pressure. The effect of supplemental calcium in the diet is at least as great as nondietary supplementation.

During the past decade, a credible body of evidence has emerged supporting the concept that maintaining an adequate dietary mineral intake, specifically of calcium, magnesium, and potassium, protects against high blood pressure in humans. Observational and interventional studies in humans and extensive use of laboratory models showed that a significant portion of blood pressure variability in response to sodium chloride can be linked to the adequacy of the mineral content of the diet. This review summarizes the observational data from several large databases showing that when adults meet or exceed the recommended dietary allowances of calcium, potassium, and magnesium, the simultaneous ingestion of a diet high in sodium chloride is not associated with elevated arterial pressure. In fact, a higher sodium chloride intake in these adults is most likely associated with the lowest blood pressure in the society. This interaction between adequacy of mineral intake and protection against salt sensitivity in humans provides an important opportunity for further improving blood pressure control in our society. Educating individuals to maintain, on a daily basis, adequate intakes of calcium, potassium, and magnesium rather than limit their sodium chloride is a viable health recommendation that individuals can implement to reduce their risk of sodium chloride-induced hypertension.

The effects of dietary salt-loading and concurrent administration of dietary calcium on water and electrolyte excretion in Sprague-Dawley rats have been studied. The total salt consumed by salt-loaded rats was significantly higher than that of control rats (P < 0.05). The total salt consumed by salt-loaded calcium fed rats was also higher (P < 0.05) than that of control rats but it was slightly lower (P < 0.05) than the consumption by the salt-loaded. Rats fed only high calcium diet had the least salt consumption. The total water intake was also highest (P < 0.05) in the salt-loaded rats when compared with either control rats, salt-loaded-calcium-fed rats or calcium-fed rats. Urinary water excretion was highest (P < 0.05) in salt-loaded-calcium-fed rats followed by salt-loaded rats and calcium-fed rats while the control rats had the least. Similarly, the sodium excretion was highest in salt-loaded-calcium-fed rats followed by salt-loaded rats and calcium-fed rats and control rats respectively. Potassium excretion was highest in salt-loaded-calcium-fed rats followed by salt-loaded rats and calcium-fed rats while the control rats had the least excretion of potassium. Serum sodium concentrations were identical in all the groups although in salt-loaded rats and salt-loaded-calcium-fed rats the values were slightly higher than those of controls. However, serum potassium concentration was lowest in salt-loaded rats and calcium-fed rats while the values for salt-loaded-calcium-fed rats was not significantly different from that of control. The results of this study suggest that increase in dietary calcium intake reduces the increase in blood pressure resulting from salt-loading and this is accompanied by an increase in water and sodium excretion.

Oral calcium (Ca) supplementation mildly reduces blood pressure. The authors studied the effects of Ca supplementation on the cardiovascular system in patients with mild to moderate essential hypertension. Twelve patients aged forty-nine to seventy years (7 men and 5 women, mean age with 60.3 +/- 7.2 years) participated. The investigators orally administered Ca (1.0 g/day for one week) under hospitalization, adding to a dietary intake of Ca (0.6 g/day). Left ventricular function and systemic arterial compliance were evaluated by M-mode and pulsed Doppler echocardiographies before and after seven days of Ca supplementation. Left ventricular contractility and afterload were not changed. Preload indicated by end-diastolic volume was significantly decreased after Ca supplementation (109.6 +/- 8.5 vs 107.3 +/- 8.2 mL, P < 0.05). Myocardial relaxation evaluated by IIa-mitral valve opening time (87.7 +/- 6.7 vs 82.1 +/- 6.2 ms, P < 0.01) and maximum descending rate of the left ventricular posterior wall (10.6 +/- 1.0 vs 12.4 +/- 1.0 cm/s, P < 0.01), and atrioventricular net compliance assessed by the descending slope of rapid filling flow in the left ventricular inflow tract (2.63 +/- 0.24 vs 2.26 +/- 0.17 m/s2, P <0.05), as well as systemic arterial compliance (2.05 +/- 0.20 vs 2.73 +/- 0.26 mL/mmHg, P < 0.01) were significantly improved by Ca supplementation. Oral Ca supplementation improved the disturbed left ventricular diastolic function and systemic arterial compliance.

Background: Dietary calcium intake has been suggested to correlate inversely with blood pressure in humans and experimental animals. However, the effects of calcium supplementation on hypertensive disturbances of the endothelium have not been well characterized., Methods and Results: Wistar-Kyoto rats made hypertensive by deoxycorticosterone (DOC)-NaCl treatment, but a concurrent increase in chow calcium content from 1.1% to 2.5% markedly attenuated the rise in blood pressure. The function of isolated mesenteric arterial rings in vitro was investigated at the close of the 10-week study. In norepinephrine-precontracted rings, the relaxations to acetylcholine (ACh) and ADP, as well as to nitroprusside, 3-morpholinosydnonimine, and isoproterenol were attenuated in hypertensive rats on 1.1% calcium supplementation. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), the relaxations to ACh in hypertensive animals on normal calcium were practically absent, whereas in normotensive rats and calcium-supplemented hypertensive rats, distinct relaxations to higher concentrations of ACh were still present. These responses were reduced by 30% to 50% with apamin, a blocker of Ca2+-activated K+ channels, and were further inhibited by blockade of ATP-dependent K+ channels with glyburide. Interestingly, relaxations elicited by ACh and ADP during precontraction with 60 mmol/L KCl (preventing endothelium-dependent hyperpolarization) were not impaired in hypertensive animals. The contractile sensitivity of endothelium-intact arterial rings to 5-hydroxytryptamine and norepinephrine was higher in hypertensive rats on either normal or high-calcium diet, whereas the increase in contractile sensitivity caused by L-NAME corresponded in all groups., Conclusion: High-calcium diet markedly opposed experimental DOC-NaCl hypertension, an effect associated with improved arterial relaxation, while abnormalities of vascular contractile properties remained unaffected. In particular, the hyperpolarization-related component of endothelium-dependent arterial relaxation, mediated via opening of arterial K+ channels, could be augmented by calcium supplementation in DOC-NaCl hypertension.

Manipulations of dietary calcium have been repeatedly shown to alter blood pressure in animal models of human essential hypertension. Supplemental dietary calcium lowers blood pressure, whereas restricted calcium diets tend to elevate blood pressure. The mechanisms responsible have not been identified, but numerous possibilities have been proposed. Many of the proposals have attempted to relate dietary calcium to calcium metabolism in vascular smooth muscle and altered vascular tone. Other proposals have focused on neural, hormonal, and renal effects of dietary calcium. In this article, mechanisms through which elevations in extracellular calcium levels might influence intracellular calcium levels are explored. Also examined are the potential roles of calcium regulating hormones, sympathetic nervous system, and electrolyte interactions in modifying blood pressure.

Calcium homeostasis is an important aspect of maternal and fetal physiology during gestation, and recent evidence implicates alterations in calcium metabolism in the pathogenesis of hypertension during pregnancy. Deficiencies in calcium intake have been linked to preeclampsia/eclampsia, and hypocalciuria and deviations in both 1,25(OH)2D3 and PTH have been shown in women with preeclampsia. Preliminary studies also suggest that calcium supplementation may lower blood pressure and prevent preeclampsia in pregnant women.

Despite years of investigative effort, the role of calcium in preventing or treating hypertension remains unclear. Comprehensive analyses have provided inconclusive results due to variations in methodology and/or design and, similar to the individual studies, to inconsistent, often conflicting results. However, what these studies have shown is that there are individuals or certain population groups who will benefit from increased calcium use, and that although it may not be the solution to the high prevalence of hypertension or a first-line treatment for hypertension, adequate calcium intake, in conjunction with other nutrients, may be associated with a reduced risk of developing hypertension. Further, based on the available data, it can be recommended that clinical and investigative efforts should be directed at identifying those persons at greater risk who will benefit from increased intake of dietary calcium.

Calcium intake has been implicated as being an important factor in the development and treatment of hypertension. The mechanisms underlying the relationship between calcium and blood pressure are not yet clearly defined. Experimental studies have documented an inverse association between calcium intake and blood pressure level. For 15 years it has been shown that calcium supplementation is effective in lowering blood pressure in hypertensive rats and, on the other hand, calcium deprivation results in increased blood pressure levels. Enriched calcium diets decrease blood pressure in genetic hypertension displayed by spontaneously hypertensive rats (SHR), stroke-prone SHR, Lyon hypertensive rats or Dahl salt-sensitive rats and, in volume-dependent hypertension induced by saline and mineralocorticoid or angiotensin II administration in Wistar or Sprague-Dawley rats. Efficacy is observed with calcium carbonate added in the diet and with calcium chloride or calcium gluconate in drinking water. Compared with the normal level in the diet (0.5% to 1%), calcium supplementation represents mainly a fourfold increase whose effect is more intense in young weaning animals treated for a long-lasting period (4 to 10 weeks).

Low dietary intake of calcium has been found to be a risk factor for the development of hypertension in a number of epidemiological studies. Moreover, increased dietary calcium intake has been reported to beneficially influence on blood pressure in both humans and animal models of hypertension, suggesting the relative calcium deficiency may indeed be present in these conditions. The underlying mechanisms for the beneficial effect of positive calcium balance on blood pressure have been a subject for extensive research in essential and experimental hypertension. In this article, the possible beneficial effects of increased dietary calcium intake on central blood pressure control are reviewed.

The objective of this study was to assess whether the epidemiological data support a relation between dietary calcium intake and blood pressure (BP). Fifty three published reports of observational studies relating intake of calcium or calcium-rich foods to BP in the USA (n = 33), Canada (n = 3), Puerto Rico (n = 1), Europe (n = 9), Asia (n = 5), Australia (n = 1) and South Africa (n = 1) were identified including a Medline search (January 1983-November 1993). Sample size ranged from 55 to over 58,000 (median 885). Five studies were prospective, 48 cross-sectional, of which four also contained a longitudinal component. Various dietary methodologies were used; the most common was the 24 h dietary recall. Most studies controlled for age, sex and body mass index, with variable control for other confounders. Many reports also allowed identification of subgroups by sex, age and race. One hundred and eight population samples and subgroups could then be identified. There was inconsistency in results both within and between studies. In 12 of the 53 published reports simple regression coefficients were reported. Median regression coefficients were -0.033 mm Hg/100 mg Ca (range -4.90 to +/- 0.47; n = 12) for systolic blood pressure (SBP) and -0.140 mm Hg/100 mg Ca (range -9.40 to +1.63; n = 10) for diastolic blood pressure (DBP). The association between dietary calcium intake and BP could not be assessed in all 108 population samples and subgroups because of design features, incompleteness of reported results and methods of analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The purpose of this study is to clarify whether the taking of a calcium dietary supplement is able to prevent the development of pregnancy-induced hypertension (PIH) in Japanese people., Study Design: Forty-five nulliparous women (Ca-group) with various high-risk factors for PIH started to take a calcium supplement (1 g/day in the form of calcium salts) from the 12th gestational week (GW). Obstetrical outcome of Ca-group was compared to that of the nullipara (n = 453) who did not take a calcium supplement during pregnancy (Non-Ca Group) and that of the nullipara (n = 413) who did not develop PIH among Non-Ca group (normotensive group)., Results: The incidence of PIH in the Ca-group was 2.2%, compared to 8.8% of Non-Ca group. The decrease in blood pressure after taking calcium during the first half of the pregnancy was much greater in Ca-group than in the normotensive group. The urinary excretion of sodium and calcium and serum free calcium at the 28th GW were much lower in a woman with PIH, despite of the taking of a calcium supplement, than in the normotensive calcium group. Also, the parathyroid hormone level at the 28th GW was higher in the calcium-taking woman with PIH than in the normotensive calcium group., Conclusion: Our preliminary study suggests that among the possible effects of taking a calcium supplement are a decrease in blood pressure and the prevention of PIH in Japanese people, and that calcium metabolism might be related to the development of PIH. However, more study is needed before it will be possible to reach a final conclusion.

This paper examines the evidence that connects calcium intake and vitamin D status to bone fragility, hypertension, colon cancer, and breast cancer. Human calcium physiology, with an intestinal absorptive barrier and inefficient conservation, reflects the abundance of calcium in the primordial human food supply. The calcium intake of stone-age adults is estimated at 50 to 75 mmol/d, three to five times the median calcium intake of present-day U.S. adults. Long-term calcium restriction and/or insufficient vitamin D may promote the development of bone fragility, high blood pressure, colon cancer, and breast cancer in susceptible individuals. Conversely, improvement in calcium intake and/or in vitamin D status may help to prevent these serious health problems. At least 12 intervention studies have established the skeletal benefit of increased calcium intake among women in the late postmenopause. Other reports suggest that adequate calcium may protect against salt-sensitive and pregnancy-associated hypertension. High intakes of both dietary calcium and vitamin D are associated with reduced development of precancerous changes in colonic mucosa. Preliminary findings also suggest that vitamin D has a protective effect against breast cancer.

More than 80 studies have reported lowered blood pressure after dietary calcium enrichment in experimental models of hypertension. The evidence presented here suggests that dietary calcium may act concurrently through a number of physiological mechanisms to influence blood pressure. The importance of any given mechanism may vary depending on the experimental model under consideration. Supplemental dietary calcium is associated with reduced membrane permeability, increased Ca(2+)-ATPase and Na,K-ATPase, and reduced intracellular calcium. These results suggest that supplemental calcium may limit calcium influx into the cell and improve the ability of the VSMC to extrude calcium. This could be a direct effect of calcium on the VSMC or an indirect effect mediated hormonally. The calcium-regulating hormones have all been found to have vasoactive properties and therefore may influence blood pressure. Furthermore, CGRP and the proposed parathyroid hypertensive factor are both vasoactive substances that are responsive to dietary calcium. Therefore, diet-induced variations in calcium-regulating hormones may influence blood pressure. Modulation of the sympathetic nervous system is another important way that dietary calcium can influence blood pressure. There is evidence of altered norepinephrine levels in the hypothalamus as a consequence of manipulations of dietary calcium as well as changes in central sympathetic nervous system outflow. Dietary calcium has also been shown to specifically modify alpha 1-adrenergic receptor activity in the periphery. In some experimental models of hypertension, dietary calcium may alter blood pressure by changing the metabolism of other electrolytes. For example, the ability of calcium to prevent sodium chloride-induced elevations in blood pressure may be attributed to natriuresis. However, natriuresis does not account for all of the interactive effects of calcium and sodium chloride on blood pressure. Sodium chloride-induced hypertension may be due in part to calcium wasting and subsequent elevation of calcium-regulating hormones. Chloride is an important mediator of this effect because it appears that sodium does not cause calcium wasting when it is not combined with chloride. More attention to the central nervous system effects of dietary calcium is needed. Not only can calcium itself influence neural function, but many of the calcium-regulating hormones appear to affect the central nervous system. The influence of calcium and calcium-regulating hormones on central nervous system activity may have important implications for blood pressure regulation and also may extend to other aspects of physiology and behavior.

We studied the effects of a high Ca (4.07%) diet on mean arterial pressure (MAP) and renal hemodynamics in young (6 weeks) spontaneously hypertensive rats (SHR) fed a normal (0.66%) or a high-salt (8.00%) diet for 4 weeks. The high-salt diet accelerated development of hypertension (213 +/- 5 vs. 159 +/- 2 mm Hg, p < 0.01) and increased renal vascular resistance (RVR) (26.4 +/- 2.3 vs. 18.2 +/- 1.2 U, p < 0.01) in young SHR. Simultaneous Ca supplementation prevented the salt-induced increase in MAP (158 +/- 3 mm Hg, p < 0.01) and in RVR (17.3 +/- 1.1 U, p < 0.01). The high-Ca diet did not affect MAP (151 +/- 3 mm Hg, NS) and RVR (17.4 +/- 1.3 U, NS) in young SHR fed a normal salt diet. RVR and MAP were positively correlated in all rats (r = 0.634, n = 38, p < 0.001). The high-Ca diet also prevented salt-induced left ventricular (LV) hypertrophy. Dietary Ca supplementation attenuated the increased salt sensitivity of arterial pressure, possibly by normalizing renal hemodynamics, in salt-loaded young SHR.

To determine the clinical significance of parathyroid hypertensive factor (PHF), physiological studies previously performed in animal models of hypertension were parallelled by human studies. These studies revealed that PHF-like activity is present in human hypertension, where it correlates with the salt-sensitive, low-renin state. As in spontaneously hypertensive rats, both supplemental calcium and calcium-channel blockers appear to be useful in the treatment of PHF-related hypertension. In primary hyperparathyroid patients, PHF presence is linked with the presence of hypertension. Postparathyroidectomy blood pressure falls in parallel with PHF levels. These preliminary human studies suggest that PHF may be a useful marker in the treatment of hypertension.

High levels of dietary calcium attenuate the elevation of arterial pressure induced by deoxycorticosterone (DOC)-salt in trained, conscious dogs. This response resulted primarily from the failure of the expected rise in peripheral vascular resistance to develop. In addition, the enhanced pressor sensitivity to norepinephrine and angiotensin II associated with DOC-salt hypertension was normalized by high levels of dietary calcium. These changes could not be explained by changes in serum potassium concentration, plasma catecholamines concentration, or plasma volume. A possible explanation is that high levels of dietary calcium inhibit a parathyroid hypertensive factor that has been observed to be elevated in mineralocorticoid-induced hypertension. This hypothesis requires further studies.

In this brief review, we have not been able to address all of the various dietary factors which have been implicated as causal in hypertension. Because of the heterogeneity of hypertension, it is quite difficult to find a simple answer to the question of how important dietary factors are in causing hypertension and even more difficult to answer the question of how diet should be therapeutically altered in treating a hypertensive patient. Given the difficulties in achieving good compliance to almost any dietary prescription and the lifestyle changes these therapies often require, significant benefit must be demonstrated to justify the efforts. It is worth emphasizing that many of the dietary alterations which have been proposed for treating hypertension have even better established preventative health rationales which justify their use. Although salt intake is a factor in the genesis of hypertension, the effectiveness of salt restriction varies between patients. Despite the absence of good predictors of response, moderate sodium reduction is a reasonable first step when dealing with a hypertensive patient. In obese hypertensive patients, weight loss provides a modest but significant BP reduction. Added benefit may be obtained by lowering total fat content and increasing the ratio of polyunsaturated to saturated fats. The reduction in cardiovascular risk with these changes in dietary fat, over and above the lowering of BP, make this approach appropriate in all hypertensive patients. Potassium supplementation, while sometimes effective, is more difficult to recommend broadly. Calcium supplementation is certainly reasonable in women, for whom such therapy should be seen as good dietary advice for the prevention of osteoporosis. Moderate alcohol intake probably has little deleterious effect, whereas heavy alcoholism does contribute to increased BP. Again, reduction of alcohol intake is important for reasons other than the modest BP reduction attained.

To investigate the role of parathyroid hormone (PTH) in the development of hypertension, the long-term administration of human PTH (hPTH) was performed in 7-week-old male spontaneously hypertensive rats maintained on a standard calcium diet (1.1% calcium) or a high calcium diet (2.8% calcium). The hPTH was infused subcutaneously at 0.9 U/h over 2 weeks using a minipump. Two weeks after minipump implantation, rat PTH (rPTH) and 1,25-dihydroxy vitamin D (1,25-D) levels were measured and the pressor response to norepinephrine (NE) was examined. Calcium loading both attenuated the development of hypertension and reduced the pressor response to norepinephrine. Chronic hPTH administration accelerated the development of hypertension and increased the pressor response to norepinephrine in rats fed a high calcium diet, but did not affect either parameter in rats fed a standard calcium diet. The serum concentrations of rat PTH and 1,25-D were significantly lower in rats fed a high calcium diet than in those fed a standard calcium diet (rat PTH: 351 +/- 16 v 430 +/- 1 pmol/L; 1,25-D: 125 +/- 19 v 206 +/- 31 pg/mL). Chronic administration of hPTH increased the serum 1,25-D concentration in rats fed a high calcium diet (186 +/- 35 pg/mL), but did not affect that of rats fed a standard calcium diet (165 +/- 16 pg/mL). It is concluded that PTH prevented the antihypertensive effect of calcium loading in young SHR, perhaps by enhancing blood pressure reactivity through causing an increase of 1,25-D.

The effect of consumption of 400 mg vs 1,500 mg of dietary calcium per day was examined in 13 male volunteers who had been diagnosed as hypertensive. Dietary calcium consumption was varied by manipulation of the intake of dairy products over 4-week periods. Caffeine intake (mean = 500 mg/day) was monitored. Neither laboratory blood pressure measured by standard sphygmomanometry nor ambulatory blood pressure monitored by automated sphygmomanometry varied significantly among men consuming baseline, low-calcium, or high-calcium diets (laboratory blood pressure = 136/83, 133/83, and 137/84 mm Hg, respectively; ambulatory blood pressure = 136/86, 138/87, and 138/87 mm Hg, respectively). Serum ionized calcium values did not vary with the three diets (1.25, 1.26, and 1.25 mmol/L, respectively). The parathyroid hormone level decreased (39 mmol/L vs 37 mmol/L) and the urinary calcium:creatinine ratio was elevated (0.41 vs 0.50) in the high-calcium diet. Consumption of a diet containing 1,500 mg calcium per day over 4 weeks did not produce a significant decrease in blood pressure or alterations in calcium metabolic indexes.

Epidemiologic findings continue to add to the body of evidence supporting a relationship between calcium intake and blood pressure. These findings also indicate that there is a threshold of the potential protective effect of adequate calcium intake, below which the risk of hypertension increases at a greater rate. The set point of this threshold, estimated at 700-800 mg/d, may be modified by a variety of factors including dietary patterns and components, lifestyle, and genetics. This may explain, at least in part, the heterogeneous response observed in dietary-intervention studies. In animal models of hypertension it was shown that greater amounts of calcium must be given to cause a blood pressure change comparable with that in normal animals, suggesting that in high-risk human populations in which calcium metabolism may be disordered, calcium intake may have to be increased to amounts greater than 700-800 mg/d to demonstrate the blood-pressure-lowering effect. Calcium intake at or above the currently recommended daily allowance of 800 mg could be of potential benefit to certain racial groups, individuals ingesting excessive alcohol, and pregnant women, all of whom generally consume low amounts of calcium and who are at higher risk of developing hypertension.

Considerable interest has developed regarding the role of calcium in the regulation of blood pressure. Epidemiologic investigations, laboratory evaluations, and clinical trials all confirm that the relationship between calcium and blood pressure extends to include the pregnant state. On the basis of current information it is clear that calcium supplementation during pregnancy lowers blood pressure. Additionally, the effect of calcium on blood pressure may influence the incidence and/or gestational age of development of preeclampsia. Additionally, the effect on smooth-muscle relaxation detected in calcium-supplemented patients may affect the incidence of prematurity. Although the mechanism for these effects has not been entirely elucidated, calcium supplementation appears to affect circulating concentrations of parathyroid hormone and renin, which may modulate intracellular ionized calcium, resulting in the observed effect on smooth-muscle relaxation. This effect may also be responsible for reduced uterine activity and for a lowering of the incidence of prematurity.