Blood Pressure is Lowered by Vitamin D (Alphacalcidol) during Long-Term Treatment of Patients with Intermittent Hypercalcaemia

ABSTRACT. There is epidemiologic evidence of a relationship between calcium deficiency and hypertension. The present study evaluated the effects of alphacalcidol, a synthetic analogue of active vitamin D, given to 29 patients with marginal, intermittent hypercalcaemia. Before therapy there was aninverse relationship between serum calcium levels and diastolic blood pressure (p<0.02). Treatment with 1 μg alphacalcidol raised the serum calcium by 0.07 mmol/l during a 6-month, double-blind, placebo-controlled trial and caused a significant reduction of diastolic blood pressure by 9.2 mmHg compared with placebo (p<0.01). The study extends previous observations, in normocalcaemic subjects, of inverse relationships between serum calcium and blood pressure indicating a primary disturbance of calcium homeostasis in hypertension. The observation that a physiologic amount of active vitamin D has hypotensive effects agrees with such a concept and suggests a new principle for the treatment of hypertension.     

Disorders of calcium homeostasis

To ensure a multitude of essential cellular functions, the extracellular concentration of calcium is maintained within a narrow physiological range. This depends on integrated regulation of calcium fluxes with respect to the intestine, kidneys and bone. The precise regulation of serum calcium is controlled by calcium itself, through a calcium receptor and several hormones, the most important of which are parathyroid hormone and 1,25(OH)(2) vitamin D. This balance can be disturbed by mutations in the calcium-sensing receptor, inappropriately high or low levels of parathyroid hormone, resistance to parathyroid hormone effects, insufficient intake or production of 1,25(OH)(2) vitamin D and inactivation of the vitamin D receptor. Mineral homeostasis is moreover influenced by many other systemic factors (e.g. sex steroid, thyroid and glucocorticoid hormones) or humoral factors (e.g. cytokines and growth factors). A specific example is the major abnormalities of mineral homeostasis in case of malignancy by excessive production of parathyroid hormone-related peptide resulting in hypercalcaemia. Several new drugs have been developed based on factors in this axis, including calcimimetics, calcilytics, vitamin D analogues and parathyroid hormone-related peptide inhibitors.     

The Effects of Calcium and Vitamin D on Blood Pressure in Conscious Sheep

ABSTRACT

The metabolic and haemodynamic effects of elevating plasma calcium levels were examined in both normal and ACTH-hypertensive sheep. Six weeks of dietary Ca⁺⁺ supplementation did not alter plasma calcium levels, blood pressure or heart rate. Five days of CaCl₂ infusion (2 mmol/h) or intravenous vitamin D injections elevated plasma ionised and total Ca⁺⁺ levels and heart rate but mean arterial pressure was unchanged. As in other species, elevation of plasma Ca⁺⁺ levels over 4 hours by infusion of CaCl₂ at 2, 5, and 10 mmol/h increased mean arterial pressure and decreased heart rate. The course of ACTH-induced hypertension was not altered in animals supplemented with CaCl₂ in their drinking water for 6 weeks nor by intravenous injection of vitamin D for 5 days. This study does not support a major role for altered plasma ionised or total Ca⁺⁺ levels in the genesis of ACTH-dependent hypertension in the sheep.     

Ambulatory Blood Pressure,Blood Pressure Variability and Antihypertensive Treatment

Ambulatory blood pressure monitoring is frequently employed in the clinical practice to improve the diagnosis of hypertension and the appropriateness of the decision regarding initiation of antihypertensive treatment. It is also frequently employed to check the efficacy of this treatment in conditions resembling daily life. This paper will describe the effect of a number of antihypertensive drugs on ambulatory blood pressure, based on data collected by our group in the past 10 years. It will then discuss the advantages of ambulatory blood pressure in studies on efficacy of antihypertensive drugs and the importance of this approach for definition of the trough-to-peak ratio of the antihypertensive effect. Some technical and clinical problems inherent to the ambulatory blood pressure monitoring approach will also be discussed.     

High parathyroid hormone,but not low vitamin D concentrations,expose elderly inpatients to hypertension

Aim: Serum parathyroid hormone (PTH) and 25‐hydroxyvitamin D (25OHD) concentrations might contribute to blood pressure (BP) levels. Mixed results in previous literature could be due to the failure to consider both these hormones concurrently, despite their long‐known relationship. Our objective was to examine the association of serum intact PTH and 25OHD concentrations with BP levels amongst older inpatients, while accounting for each other. Methods: The participants were 284 Caucasian older inpatients with no suspicion of primary hyperparathyroidism (mean age 85.87 ± 5.90 years; 65.8% female) admitted to the geriatric acute care unit of Angers University Hospital, France. They were divided into two groups according to the existence of hypertension (i.e. systolic blood pressure [SBP] >140 mmHg, or diastolic blood pressure [DBP] >90 mmHg). Age, sex, numbers of chronic diseases and of drugs taken daily, use of antihypertensive or corticosteroid drugs and of calcium supplements/vitamin D, thyroid‐stimulating hormone and albumin concentrations, creatinine clearance, and season tested were used as covariables. Results: Hypertensive participants (n = 106) had higher intact PTH concentrations than normotensive patients (P = 0.044). There was a positive linear association of BP with intact PTH concentrations (adjusted β = 0.08, P = 0.015 for SBP; adjusted β = 0.05, P = 0.044 for DBP), but not with vitamin D. Serum intact PTH concentration, unlike 25OHD, was associated with hypertension (adjusted OR 1.01, P = 0.038). Conclusions: Irrespective of 25OHD, PTH was associated with hypertension by increasing both SBP and DBP. Geriatr Gerontol 2013; 13: 783–791 .     

Treatment with One-alpha-hydroxycholecalciferol in Middle-aged Men with Impaired Glucose Tolerance—A Prospective Randomized Double-blind Study

ABSTRACT Experimental evidence suggests a specific role for the active metabolite of vitamin D (1,25(OH)₂D₃) in insulin secretion. In order to evaluate the possible clinical significance, 65 middle-aged men with impaired glucose tolerance, and normal serum levels of vitamin D metabolites, were enrolled in a three-month study where they were given either 0.75 μg alpha-calcidol (1α(OH)D₃) daily or placebo. Indices of glucose and lipid metabolism were evaluated before and after treatment. There were no significant changes during the trial neither for fasting blood glucose, hemoglobin A_1C or for the intravenous glucose tolerance between the treatment and the placebo groups, nor were there any consistent changes in insulin values during the glucose tolerance test. Subjects treated with alpha-calcidol displayed a significant reduction in body weight with an average of 1.1. kg, while those receiving placebo lost no weight. Treatment did not affect the serum lipoprotein values. Thus, a modest dose of active vitamin D, which did not cause elevation of serum calcium, did not provide general improvement of glucose tolerance or of insulin secretion when given to patients with impaired glucose tolerance, but without vitamin D deficiency, over a three-month period.     

Plasma ionized calcium and cardiovascular risk factors in mild primary hyperparathyroidism: effects of long-term treatment with active vitamin D (alphacalcidol).

Primary hyperparathyroidism (HPT) has been associated with hypertension, hyperinsulinaemia, hypertriglyceridaemia and hyperuricaemia. In the present study, plasma ionized calcium (Ca2+) was studied in relation to cardiovascular risk factors in 20 subjects with mild hypertension. Plasma Ca2+ was found to be negatively correlated with fasting serum insulin, triglycerides and urate, and with diastolic blood pressure (DBP). However, after the interaction of the different risk factors had been taken into account in the multiple regression analysis, only the relationship between Ca2+ and serum insulin was significant (r = 0.55, P less than 0.01). In a previous double-blind, placebo-controlled study 1 micrograms alphacalcidol, a synthetic analogue of 1,25 dihydroxy-vitamin D3, induced a decrease in blood pressure in mild HPT subjects. In the present study, the highest dose that did not further aggravate the hypercalcaemia was given in a long-term study over a 12-month period to 18 mild HPT subjects (average dose, 1.75 micrograms daily). The treatment induced a reduction in body weight of 0.9 kg (P less than 0.05) and an increase in serum urate from 330 +/- 92 to 380 +/- 104 mmol l-1 (P less than 0.01). A reduction in blood pressure was only observed at the end of the study, from 142 +/- 17/86.6 +/- 9.1 to 139 +/- 13/82.9 +/- 8.9 mmHg (P less than 0.05 for DBP). The reduction in systolic blood pressure was significantly correlated with the reduction in body weight induced by treatment (r = 0.63, P less than 0.02). No consistent changes in glucose or lipid metabolism were induced by treatment.     

Indices of Mineral Metabolism in Relation to Blood Pressure in a Sample of a Healthy Population

Indices of mineral metabolism in blood and urine were analysed in relation to blood pressure in 97 healthy subjects aged 16–82 years. In a multivariate analysis, after allowing for the effects of sex, body mass index (BMI) and age, there was an inverse relationship between plasma level of ionized calcium and mean blood pressure (MBP) (β=-50.0 mmHg/mmol/l P-ionized calcium, p= 0.0005). In univariate analyses MBP also showed statistically significant inverse relationships with plasma ionized calcium, serum phosphate and renal threshold concentration of phosphate; positive relationships to MBP were found for fasting urinary excretion of calcium and cyclic adenosine monophosphate. However, when examined multivariately, only the relation between MBP and plasma ionized calcium persisted. This study supports previous findings of an inverse relationship between blood pressure and serum ionized calcium and extends the observations to the physiological range. It is further evident from this study that BMI and age should be taken into account in analyses of the relationship between blood pressure and mineral metabolism.     

Dietary Calcium Intake and Blood Pressure in Normotensive Subjects

ABSTRACT. Epidemiological and prospective studies in man and animals have indicated an inverse relationship between calcium intake and cardiovascular mortality and blood pressure (BP). We have therefore studied the effect of dietary calcium on blood pressure in two groups of women. In a cross-sectional study 103 early postmenopausal women were stratified into three groups according to daily calcium intake calculated from a questionnaire. Both diastolic and systolic blood pressures were identical in the three groups. We thereafter conducted a prospective placebo-controlled trial on the effect of calcium supplementation. Twenty-eight healthy women were randomized to placebo treatment (n=14) or calcium supplementation 2000 mg daily (n=14) for one year. In both groups BP remained at initial levels throughout the study and was identical in the two groups at measurements every three months. We thus conclude that calcium supplementation has no effect on BP in normotensive subjects on a high calcium diet.     

Vitamin D status and parathyroid hormone levels in relation to blood pressure: a population-based study in older men and women

BACKGROUND: Evidence is accumulating that the vitamin D endocrine system has physiological functions beyond bone health including a role in the regulation of blood pressure. Effects of poor vitamin D status on blood pressure may be mediated by elevated parathyroid hormone (PTH) levels. AIM: To evaluate whether serum 25-hydroxyvitamin D [25(OH)D] and PTH levels are independently associated with blood pressure in a population-based study of older men and women. METHODS: Subjects were participants of the Longitudinal Aging Study Amsterdam, aged 65 years and older. In 1205 participants, serum 25(OH)D and PTH levels were determined and diastolic and systolic blood pressure were measured. Linear and logistic regression analyses were performed with adjustments for age, sex, region, season, lifestyle factors (physical activity, smoking, alcohol intake), and waist circumference. RESULTS: Serum 25(OH)D was not significantly associated with diastolic (beta 0.00, P = 0.98) or systolic (beta 0.06, P = 0.11) blood pressure. In contrast, higher ln-PTH levels were significantly associated with higher diastolic (beta 1.93, P = 0.03) and systolic (beta 4.67, P = 0.01) blood pressure. Higher PTH levels were associated with a substantially higher prevalence of hypertension (OR 2.00, 95% CI 1.31-3.06 for the highest versus the lowest quartile), whereas 25(OH)D showed no significant association (OR 0.89, 95% CI 0.47-1.69 for the lowest versus the highest 25(OH)D category). CONCLUSION: These results indicate that PTH is a potentially modifiable determinant of blood pressure in the general elderly population. Serum 25(OH)D, however, was not associated with blood pressure, possibly due to the relatively high levels in our population.     

Glomerular filtration rate and parathyroid hormone are associated with 1,25-dihydroxyvitamin D in men without chronic kidney disease

Abstract. Karhapää P, Pihlajamäki J, Pörsti I, Kastarinen M, Mustonen J, Niemelä O, Tuomi H, Kuusisto J (University of Eastern Finland, Kuopio; University of Tampere, Tampere; Finnish Medical Agency, Kuopio; and University of Tampere, Tampere, Finland). Glomerular filtration rate and parathyroid hormone are associated with 1,25‐dihydroxyvitamin D in men without chronic kidney disease. J Intern Med 2012; 271 : 573–580. Background and aim. Vitamin D, estimated glomerular filtration rate (eGFR) and parathyroid hormone (PTH) are related to cardiovascular disease risk. We examined the associations between the levels of 25‐hydroxyvitamin D (25‐D) and 1,25‐dihydroxyvitamin D (1,25‐D) and both eGFR and PTH. Design and setting. Cross‐sectional population‐based study in Kuopio, Eastern Finland. Subjects. A total of 909 men without known chronic kidney disease (CKD) and not receiving antidiabetic medication, aged from 45 to 73 years, were included in the study. Main outcome measures. Fasting levels of 25‐D, 1,25‐D, creatinine and PTH were measured, and an oral glucose tolerance test (OGTT) was performed. Results. High levels of 25‐D were associated with low levels of eGFR and PTH (β = ?0.17, P = 9 × 10^?7 and β = ?0.28, P = 6 × 10^?17, respectively, adjusted for age, body mass index and levels of calcium, phosphorus and glucose in a 2‐h OGTT, and also for either eGFR or PTH). By contrast, high 1,25‐D levels were associated with high levels of eGFR and PTH (β = 0.17, P = 2 × 10^?6 and β = 0.19, P = 5 × 10^?8, respectively, adjusted as mentioned earlier and additionally for 25‐D). Eighteen per cent of men in the highest 25‐D quartile were in the lowest 1,25‐D quartile and also had a lower eGFR than men with high levels of both 25‐D and 1,25‐D (P = 4 × 10^?5). Finally, 15% of men in the lowest 25‐D quartile were in the highest 1,25‐D quartile and also had higher PTH levels than men with low levels of both 25‐D and 1,25‐D (P = 2 × 10^?3). Conclusion. Our findings suggest that both eGFR and PTH are significantly associated with vitamin D metabolism in men without known CKD.     

老年高血压病病人血糖水平与动态脉压相关性探讨

目的探讨老年原发性高血压病人血糖水平与动态脉压的相关性。方法对455例老年高血压病（EH）病人进行体检，检测空腹血糖（FBG）、餐后2h（2hBG）血糖及其他指标，比较不同血糖水平组间脉压大小。结果老年高血压病病人血糖水平与脉压密切相关，3组间比较有统计学意义（P〈0．01）。年龄、收缩压、舒张压、2hBG与PP有显著相关性（r分别为0．108、0．111、0．097、0．777，P〈0．001）。结论合并糖尿病的老年高血压病病人应加强脉压的监控。     

Factors associated with elevated or blunted PTH response in vitamin D insufficient adults

Objectives. The purpose of this study was to examine factors associated with high or low parathyroid hormone (PTH) levels in relationship to vitamin D insufficiency. Design. This was a cross‐sectional study consisting of 516 healthy men and women, aged 30–85, all Caucasians with vitamin D insufficiency [serum 25(OH)D < 45 nmol L^?1]. The group was divided into quartiles by PTH levels and the highest and lowest quartiles were compared with regard to various factors likely to affect calcium metabolism. We used stepwise multivariable logistic regression to determine the independent association between PTH levels and other variables for men and women separately. Results. We found that men in the lowest PTH quartile were significantly younger, had less energy intake, lower body mass index (BMI) and better kidney function compared with the highest PTH quartile. They had also higher ionized calcium, insulin‐like growth factor (IGF1) and testosterone and were more likely to smoke. Women within the lowest PTH quartile were younger, had lower BMI and magnesium values and higher IGF1 levels and were more likely to smoke. Stepwise multivariate regression showed that IGF1, testosterone and BMI were significantly associated with PTH in men (R² = 0.472) but smoking, BMI and kidney function in women (R² = 0.362). Conclusions. Our results indicate that during vitamin D insufficiency, factors other than calcium and vitamin D may modify PTH response. These factors may be different between sexes and we have identified novel factors, IGF1 and testosterone in men which may be compensatory in nature and confirmed previous factors such as smoking, BMI and kidney function in women.     

长期补钙对儿童血压的影响

55名4～5岁健康儿童分两组（A组34名，平均4.45±0．5岁；B组21名，平均4岁）进行长期口服补钙的自身交叉对比试验，结果显示两组儿童补钙前后各自的平均24h尿钙排泄量均无显著变化，未提供补钙对儿童血压影响的证据。本研究提示尿钠、钠／钾的增加对血压水平的升高有显著影响。     

Influence of Partial Pressure of Oxygen in Blood Samples on Measurement Performance in Glucose-Oxidase-Based Systems for Self-Monitoring of Blood Glucose

Background

Partial pressure of oxygen (pO₂) in blood samples can affect blood glucose (BG) measurements, particularly in systems that employ the glucose oxidase (GOx) enzyme reaction on test strips. In this study, we assessed the impact of different pO₂ values on the performance of five GOx systems and one glucose dehydrogenase (GDH) system. Two of the GOx systems are labeled by the manufacturers to be sensitive to increased blood oxygen content, while the other three GOx systems are not.

Methods

Aliquots of 20 venous samples were adjusted to the following pO₂ values: <45, ~70, and ≥150 mmHg. For each system, five consecutive measurements on each sample aliquot were performed using the same test strip lot. Relative differences between the mean BG results at pO₂ ~70 mmHg, which is considered to be similar to pO₂ in capillary blood samples, and the mean BG result at pO₂ <45 and ≥150 mmHg were calculated.

Results

For all tested GOx systems, mean relative differences in the BG measurement results were between 6.1% and 22.6% at pO₂ <45 mmHg and between -7.9% and -14.9% at pO₂ ≥150 mmHg. For both pO₂ levels, relative differences of all tested GOx systems were significant (p < .0001). The GDH system showed mean relative differences of -1.0% and -0.4% at pO₂ values <45 and ≥150 mmHg, respectively, which were not significant.

Conclusions

These data suggest that capillary blood pO₂ variations lead to clinically relevant BG measurement deviations in GOx systems, even in GOx systems that are not labeled as being oxygen sensitive.     

Serum concentrations of vitamin D and parathyroid hormone and prevalent metabolic syndrome among adults in the United States

Background: Some reports suggest that concentrations of vitamin D are inversely, whereas concentrations of parathyroid hormone (PTH) are directly, associated with prevalent metabolic syndrome. Because of lingering uncertainty about these associations, we examined the cross‐sectional associations between serum concentrations of 25‐hydroxyvitamin D₃ and PTH with metabolic syndrome in a representative sample of adults in the US. Methods: We used data from 1705 participants in the 2005–2006 National Health and Nutrition Examination Survey. Vitamin D was measured by radioimmunoassay, whereas PTH was measured using an electrochemiluminescent process. Results: The mean concentration of vitamin D for participants with and without metabolic syndrome was 20.3 and 22.9 ng/mL, respectively (P = 0.001). The mean concentration of PTH for participants with and without metabolic syndrome was 44.5 and 41.0 pg/mL, respectively (P = 0.002). The age‐adjusted mean concentrations of vitamin D (P for linear trend <0.001) decreased linearly, whereas PTH (P for linear trend = 0.002) increased linearly, as the number of components of metabolic syndrome increased. After adjusting for age, gender, physical activity, urinary albumin creatinine ratio, and concentrations of C‐reactive protein and calcium, concentrations in the highest quintile of vitamin D [prevalence ratio (PR) = 0.59; 95% confidence interval (CI) 0.44–0.79], but not PTH (PR = 1.18; 95% CI 0.97–1.43), was significantly associated with prevalent metabolic syndrome. Conclusion: Concentrations of vitamin D, but not PTH, were significantly associated with prevalent metabolic syndrome among US adults.     

动态血压监测评价贝尼地平治疗原发性高血压的疗效观察

目的　应用动态血压监测 (ABPM )的方法评价贝尼地平治疗原发性高血压的降压疗效、谷 /峰比值及不良反应。方法　采用开放的方法 ,2 0例研究对象经 2周洗脱期 ,服用贝尼地平 4mg/d一次 ,2周末坐位舒张压 (SeDBP)≥ 90mmHg者加量至贝尼地平 8mg/d一次 ,继续服用 6周。于洗脱期末及治疗 8周末各行ABPM和实验室检查一次。结果　ABPM显示 8周末 2 4h、日间、夜间收缩压 (SBP/DBP)较洗脱期末分别下降 (9.4± 5 .4 / 6 .2± 4 .1)mmHg、(10 7± 6 .7/ 6 8± 3 8)mmHg、(6 9± 9 0 / 5 1± 7 7)mmHg。降压T/P值SBP为 5 8% ,DBP为 5 9%。无严重不良反应。 结论　贝尼地平 4～ 8mg/d一次为疗效确切的降压药物。     

美托洛尔治疗高血压对血脂及糖代谢的影响

对37例原发性高血压患者进行美托洛尔治疗前后心率、血压、总胆固醇、甘油三酯、糖耐量试验、胰岛素、24h尿钾、钠、钙、肌酐测定，结果表明：服用美托洛尔后心率、血压下降，尿钠排泄增加，糖负荷曲线略增高，胰岛素水平及胰岛素抗性（ISR）降低（P＜0．01），血脂无改变（P＞0．05）。提示美托洛尔对原发性高血压Ⅰ，Ⅱ期者，在改善血压、心率同时，不影响脂肪代谢，可增加尿纳排泄，对糖代谢、胰岛素及胰岛素抵抗影响较小。