Comments on a meta-analysis of the relation between dietary calcium intake and blood pressure

The role of dietary calcium in the etiology of hypertension is controversial. In 1995, Cappuccio et al. (American Journal of Epidemiology,1995;142:935-45) examined this issue in a meta-analysis of observational studies published between 1983 and 1993. The author of the present paper reviewed the original studies underlying this meta-analysis and discovered that data from one study had been inappropriately extracted and converted, leading to an understatement of the calcium-blood pressure relation by a factor of about 30. This review also raised questions about the extraction and conversion of data from several other studies and about the statistical methods used. The author repeated the meta-analyses and discovered an unadjusted regression slope between dietary calcium and systolic blood pressure of -0.34 mmHg/100 mg per day (95% confidence interval (CI) -0.46 to -0.22) for men, -0.15 mmHg/100 mg per day (95% CI -0.19 to -0.11) for women, and -0.39 mmHg/100 mg per day (95% CI -0.47 to -0.31) for men and women. For diastolic blood pressure, the pooled regression slope for men was -0.22 mmHg/100 mg per day (95% CI -0.32 to -0.13), while for women it was -0.051 mmHg/100 mg per day (95% CI -0.090 to -0.012); for men and women it was -0.35 mmHg/100 mg per day (95% CI -0.67 to -0.02). These slopes are still modest but are larger than those reported in the original analysis. However, since all of these analyses were based on zero-order correlations or regressions, extreme caution must be exercised in interpreting the results.     

Dietary protein intake and urinary excretion of calcium: a cross-sectional study in a healthy Japanese population

Efforts in dental research and training have received the contribution of individuals who had no formal training in dentistry, yet they understood the dental field and the educational needs of those who would be engaged in dental research, teaching, and service in industry and academia. Dr. Robert S. Harris (1904-1983) was such a man. What follows is a personal remembrance of his character, his research accomplishments, and his successful educational endeavors in the dental field.     

Circadian variations of the urinary excretion of catecholamines and electrolytes

Concomitant measurements of circadian variations in the urinary excretion of dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), epinephrine (E) as well as of creatinine, sodium and potassium under controlled dietary conditions during relative physical and emotional rest in 13 volunteers have shown that maximum excretion of all these substances occurred in the afternoon period between 14:30h and 18:00h, and minimum excretion in the morning between 4:00h and 5:00h. The changes were in some cases progressive from one collection period to the other, and synchronized for NE and E. DA and HVA excretions fluctuated from subject to subject. Excretory rhythms of sodium and potassium were found to be similar to those of the catecholamines. This can be explained by diurnal changes in renal blood flow and different renal excretory mechanisms of catecholamines. None of the catecholamines correlated with the urinary volume but urinary NE and E positively correlated with urinary creatinine, urinary NE and E with urinary DA and urinary sodium with urinary E. There are some common patterns in the diurnal rhythms of catecholamines and electrolytes but their interrelationship is different for individual catecholamines.     

Familial aggregation of urinary kallikrein concentration in childhood: relation to blood pressure, race and urinary electrolytes

Biochemical alterations that have been correlated with elevated blood pressure have not received extensive epidemiologic study because of the technical difficulties involved. Because the excretion of urinary kallikrein is reduced significantly in adult hypertensives, we have studied urinary kallikrein in a cohort of children in whom familial aggregation of blood pressure has been demonstrated. Casual specimens of urine were obtained in household surveys, and urinary concentration of kallikrein was determined in 601 children aged 5-18 years. The children were from 163 families, whose members also had their blood pressures measured. Familial aggregation of urinary kallikrein concentration was found by analysis of variance (F=3.45, p less than 0.001) even in these casual specimens and was demonstrable for black and white children analyzed separately. Urinary kallikrein concentration was significantly lower in black children than in white children (p less than 0.001) and was positively correlated with urinary creatinine and urinary potassium and inversely related to urinary sodium concentrations. Urinary kallikrein concentration also was being altered by season (being lowest in the summer) and by time of day (being highest in the morning). Families with the lowest mean kallikrein concentrations tended to have higher blood pressures than did families with the highest mean kallikrein concentrations, although the effect is small and subject to many variables.     

Respiratory symptoms and bronchial responsiveness are related to dietary salt intake and urinary potassium excretion in male children

Six men were accidentally exposed to NO2 when they were changing a propeller using a gas burner in the poorly ventilated hold of a ship. All of them were admitted to hospital with shortness of breath and cough. Chest X-ray on admission revealed diffuse, patchy and infiltrative shadows, leading to the diagnosis of pulmonary edema in all five patients. Steroid therapy was effective and followed by a quick recovery in all patients. None developed third phase manifestations characterized pathologically by bronchiolitis obliterans.     

The effects of dietary sodium on the diurnal activity of the renin-angiotensin-aldosterone system and the excretion of urinary electrolytes

Diurnal variations of five normal men were tested over three 24 h consecutive periods. The first experiment began at 0900 h after the subjects had fasted for 12 h and a normal sodium diet of about 70-80 mEq was given at 0900 h, 1200h, and 1630 h (total of about 220 mEq of Na). Significant variations in the plasma renin activity (PRA), in the plasma aldosterone (PA), and in the urinary Na and K outputs were found. The second experiment began at 1200 h with the first feeding time at 2100 h after fasting about 24 h and the subjects were given a normal sodium diet as in the first experiment, but with the meals given at 2100 h, 2400 h, and 0430 h. The diurnal variations in PRA, plasma aldosterone, and urinary electrolytes disappeared. From this study, it appears that the diurnal variation in urinary electrolyte excretion is a factor of the diurnal variation in PRA and plasma aldosterone. The diurnal variation in PRA and plasma aldosterone are related to the timing of sodium ingestion.     

Association between blood pressure and dietary factors in the dietary and nutritional survey of British adults

During the last few decades, the industrial production and use of Cd resulted in the release of significant quantities of Cd into the environment. Concern about health risks of human exposure to this toxic metal, which may be contained in soil and other environmental compartments, has increased significantly in recent years. Soil ingestion is a potentially important pathway of exposure to soil-absorbed environmental contaminants, especially for young children exhibiting hand-to-mouth behavior. Health risk assessments are usually based on unchanged bioavailability of soil-absorbed pollutants, e.g., heavy metals, neglecting interactions of metals with the soil matrix, which may lead to relatively lower bioavailability. This study was conducted to determine the bioavailability of Cd absorbed to soil in rats. Eight-week-old male Lewis rats were given either a soil polluted with CdCl2 (150 micrograms Cd/rat) dissolved in 5% gun acacia or an equal amount of Cd as CdCl2 dissolved in saline. Control rats were gavaged with isotonic saline. Cd concentrations in liver, kidney, brain, heart, and blood, as well as Cd content of urine and feces were analyzed using graphite furnace atomic absorption spectrometry. Tissue Cd concentrations in soil-treated animals were significantly lower than the tissue concentrations in the Cd-saline group; in the liver and kidneys of the Cd-saline and Cd-soil groups, 4 and 2.7% respectively, of the original doses were recovered. Relative bioavailability, calculated on the basis of blood Cd levels for the Cd-soil group as compared to the Cd-saline group, appeared to be 43%. No differences in the excretion pattern of Cd into feces were observed between the Cd-saline and Cd-soil groups. After 6 days, over 91% of the original dose was recovered in the feces of both Cd-treated groups. Cd excretion via urine was very low, but in the Cd-soil group a significant increase in urinary Cd was observed as compared to the control group. However, the amount of Cd excreted into urine of the Cd-soil group during the experimental period corresponded to only 0.01% of the original dose. In the Cd-saline group, no additional Cd was excreted into urine as compared to the control group. These results indicate that the soil matrix significantly reduced the absorption of Cd in the gastrointestinal tract. Consequently, exposure assessment models, assuming an unaffected bioavailability of soil-absorbed Cd, overestimate the internal dose and thereby overestimate health risks associated with direct ingestion of soil particles.     

The relationship between blood pressure and biochemical risk factors in a general population

The relationship between blood pressure, ponderal index, sex, blood glucose, haemoglobin, serum uric acid, calcium cholesterol and creatinine, and albumin has been examined in 698 subjects aged between 44 and 49 years from the register of a group general practice. Sixty per cent of the variation in systolic pressure could be explained by statistically significant associations with diastolic pressure, sex, blood glucose, serum calcium, and cholesterol. The diastolic blood pressure (not corrected for systolic pressure) was significantly related only to ponderal index, haemoglobin in men, and cholesterol in women. Pulse pressure was also positively related to the risk factors blood glucose, serum cholesterol, and calcium. The possibility is discussed that one or more of these variables reduce aortic compliance and that the serum calcium contributes to this end. Diastolic, but not systolic pressure, had a prime association with relative weight, obesity being only basically associated with an increase in diastolic pressure.     

Normal values for ambulatory blood pressure and differences between casual blood pressure and ambulatory blood pressure: results from a Danish population survey

Oncogenic forms of the Abl and Src tyrosine kinases trigger the destruction of the Abi proteins, a family of Abl-interacting proteins that antagonize the oncogenic potential of Abl after overexpression in fibroblasts. The destruction of the Abi proteins requires tyrosine kinase activity and is dependent on the ubiquitin-proteasome pathway. We show that degradation of the Abi proteins occurs through a Ras-independent pathway. Significantly, expression of the Abi proteins is lost in cell lines and bone marrow cells isolated from patients with aggressive Bcr-Abl-positive leukemias. These findings suggest that loss of Abi proteins may be a component in the progression of Bcr-Abl-positive leukemias and identify a novel pathway linking activated nonreceptor protein tyrosine kinases to the destruction of specific target proteins through the ubiquitin-proteasome pathway.     

Associations of urinary albumin excretion rate with vascular disease in europid nondiabetic subjects

Microalbuminuria and its association with vascular disease has previously been reported in nondiabetic individuals. The aims of this study were to determine whether there is a cross-sectional relationship between urinary albumin excretion rate and cardiovascular disease in nondiabetic subjects and to investigate hereditary predisposition to microalbuminuria by studying offspring of the main study population. Europid patients, aged 40-70 years, were randomly selected from a large inner-city general practice; there was a 62.6% attendance rate, and a study population of 959 remained after exclusions. Blood pressure, ankle systolic pressure, height, and weight were measured. Albumin excretion rate was calculated from overnight and morning urine collections. Venous blood was taken for lipids, fibrinogen, and factor VII; and resting electrocardiograms were carried out. Offspring (aged 15-40 years) of those found to be microalbuminuric were invited to attend for the same tests, and controls were selected by age and sex matching the parents. There was no association between parents' albumin excretion rate with that of their offspring, and there were no significant differences in albumin excretion rate between offspring subjects and their controls. There were no statistically significant associations of prevalent coronary heart disease (CHD) with albumin excretion rate or microalbuminuria in either sex [CHD in women: odds ratio (OR) 1.85; 95% confidence interval (CI) 0.19,9.0] [CHD in men: OR 2.13; 95% CI (0.64, 6.59)]. In women, there were significant associations between albumin excretion rate and peripheral vascular disease (positive) and fibrinogen (negative). Because established risk factors may not be as strongly associated with CHD in cross-sectional studies, we intend to follow this group prospectively.     

Accelerating effect of chitosan intake on urinary calcium excretion by rats

The effect of chitosan on calcium (47Ca) metabolism was investigated in rats. The whole-body retention of 47Ca by rats fed on a 5% chitosan diet was significantly decreased when compared with that of rats fed on a cellulose diet, but showed no significant difference from that of rats fed on a fiber-free diet. Although there was no significant difference in the fecal excretion of 47Ca between the chitosan group and the cellulose or fiber-free group, the urinary excretion of 47Ca was significantly increased in the chitosan group when compared with the cellulose group. These results suggest that dietary chitosan would affect the calcium metabolism in animals.     

Inadequate management of blood pressure in a hypertensive population

BACKGROUND: Many patients with hypertension have inadequate control of their blood pressure. Improving the treatment of hypertension requires an understanding of the ways in which physicians manage this condition and a means of assessing the efficacy of this care. METHODS: We examined the care of 800 hypertensive men at five Department of Veterans Affairs sites in New England over a two-year period. Their mean (+/-SD) age was 65.5+/-9.1 years, and the average duration of hypertension was 12.6+/-5.3 years. We used recursive partitioning to assess the probability that antihypertensive therapy would be increased at a given clinic visit using several variables. We then used these predictions to define the intensity of treatment for each patient during the study period, and we examined the associations between the intensity of treatment and the degree of control of blood pressure. RESULTS: Approximately 40 percent of the patients had a blood pressure of > or =160/90 mm Hg despite an average of more than six hypertension-related visits per year. Increases in therapy occurred during 6.7 percent of visits. Characteristics associated with an increase in antihypertensive therapy included increased levels of both systolic and diastolic blood pressure at that visit (but not previous visits), a previous change in therapy, the presence of coronary artery disease, and a scheduled visit. Patients who had more intensive therapy had significantly (P<0.01) better control of blood pressure. During the two-year period, systolic blood pressure declined by 6.3 mm Hg among patients with the most intensive treatment, but increased by 4.8 mm Hg among the patients with the least intensive treatment. CONCLUSIONS: In a selected population of older men, blood pressure was poorly controlled in many. Those who received more intensive medical therapy had better control. Many physicians are not aggressive enough in their approach to hypertension.     

The relationship between free and total hydroxyproline concentration in blood serum and urinary excretion of hydroxyproline in healthy individuals

The quantitative measurement of the IgG subclass composition of the sera from sixteen patients with cystic fibrosis has revealed grossly elevated levels of IgG4 in seven patients. The possible significance of this observation is discussed in relation to recent reports of a high incidence of immediate-type hypersensitivity in such patients.     

The effect of dietary sodium intake on the blood pressure and cardiac output responses to angiotensin II in unanaesthetized rats

1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium and administered in various sequences. 2. Dose-response curves were shifted to the left in rats on a high-, compared with a low-, sodium intake. This response was maintained for 7 days on changing from high to low sodium. 3. There was no difference in the relation between the fall of cardiac output and the rise of blood pressure in any of the experimental groups. 4. Dose-response curves for peripheral resistance showed the same directional change as seen for the pressor response in rats on high- and low-sodium diets. Since depression of cardiac output was proportional to the pressure rise, the absolute change in peripheral resistance was greater than the blood pressure response. The proportional changes were similar. 5. It is concluded that alterations in the pressor response to angiotensin caused by changes in sodium loading are attributable to changes in peripheral resistance and not to changes in the cardiac output response to the acute rise in blood pressure.     

The association of blood lead and blood pressure in population surveys

The association of age, body weight, body mass index (BMI) and glycosylated hemoglobin A1c (HbA1c) to blood pressure in the general population of the Ho-long area in Taiwan was examined. A total of 1341 subjects, 746 men and 595 women, aged 40-90 years, were studied. Sex-specific multiple regression analyses were carried out on variables both univariately and significantly associated with blood pressure. Results show HbA1c to be significantly associated with SBP in both males and females before age, weight and/or BMI are adjusted (p < 0.05). After controlling for these confounders, the strength of SBP-HbA1c association was slightly reduced in males, but remained significant. In contrast, there was no significance in females. Moreover, no significant relationship in DBP-HbA1c was found in either sex group. These findings suggest that although a positive correlation was found between HbA1c and SBP, HbA1c or glucose status appeared to be a less important contributing factor in hypertension than age or body weight.     

Time-course changes in blood pressure, urinary excretion of norepinephrine and dopamine after administration of fusaric acid in a single dose in elderly hypertensive patients

Time-course changes in blood pressure, urinary norepinephrine and dopamine excretion after administration in a single dose of fusaric acid calcium salt were examined in 8 elderly hypertensive patients. Eight elderly hypertensive patients served as controls receiving placebo administration in a single dose. The dose of fusaric acid calcium salt ranged from 5.1 mg/Kg to 6.0 mg/Kg. The results obtained are as follows: 1) Both systolic and diastolic blood pressure showed a significant reduction in fusaric acid calcium salt group, the lowest value of systolic blood pressure being observed from 4 to 8 hrs. and that of diastolic blood pressure being observed from 4 to 6 hrs. after administration of this agent, respectively. Systolic blood pressure returned more slowly to the level before fusaric acid calcium salt administration than diatolic blood pressure did. In placebo group, however, no significant reduction of both systolic and diastolic blood pressures was noted. 2) In fusaric acid calcium salt group, norepinephrine excretion in the urine did not show a diurnal change. In placebo group, however, a tendency of diurnal change was noted. These results would suggest that noepinephrine synthesis might be inhibited temporalily by fusaric acid calcijm salt. 3) In fusaric acid calcium salt group, dopamine excretion in the urine did hardly show a diurnal change. In placebo group, however, a fairly evident diurnal change was observed. The interpretation of these results seems to be difficult in the present state of knowledge of the action of fusaric acid calcium salt in humans.     

Relation between passive smoking at home and dietary intake

Recent attempts to protect hematopoietic progenitor cells from cytarabine (ara-C)-induced toxicity by transfer of the cytidine deaminase (CDD) gene resulted in efficient in vitro inducibility of ara-C resistance. Another enzyme involved in intracellular ara-CTP inactivation is the deoxycytidylate deaminase (dCMPD). We therefore transfected the human dCMPD cDNA gene into murine fibroblasts and investigated the relationship of forced dCMPD expression and resistance induction to ara-C. Several cell lines were established which demonstrated a 1.7-3.5-fold increase in cellular dCMPD activity and an up to 2-fold increase in the IC50 value of ara-C. However, increases in dCMPD activities did not show a positive linear correlation with the induction of ara-C resistance. In addition, CD34 + hematopoietic progenitor cells revealed the highest endogenous dCMPD enzyme levels among different human hematopoietic cells. Thus, despite the documented role for dCMPD in ara-CTP inactivation of certain cell types, these results suggest that the dCMPD gene may prove less useful than the CDD gene as a therapeutic target in attempts to attenuate ara-C-induced bone marrow toxicity.     

Salt intake, blood pressure, and cardiovascular structure

Epidemiologic data revealed that a low sodium intake might have a favorable influence on blood pressure throughout an individual's lifetime. Sodium restriction was reported to lead to a modest fall in blood pressure in some studies, although a few groups of hypertensive patients experienced a rise in blood pressure. Left ventricular hypertrophy has been demonstrated to be related to cardiovascular morbidity and mortality independent of other risk factors. Dietary salt intake participates in the hypertrophic process independent of other determinants. Thus, 24-hour urinary sodium excretion has been reported to correlate with left ventricular mass independent of levels of arterial pressure. Three different mechanisms may link dietary salt intake to myocardial hypertrophy: the renin-angiotensin-aldosterone system, the sympathetic nervous system, and fluid volume homeostasis. Whether salt restriction reduces cardiovascular structural damage independent of arterial pressure has not been determined.     

Associations between self-assessed masticatory ability and some general health factors in a Swedish population

BACKGROUND: A phase III, randomized, double-blind, multi-institutional trial was performed evaluating active specific immunotherapy using vaccinia melanoma oncolysate (VMO) in the surgical adjuvant setting in patients with stage II melanoma (UICC staging). The first interim analysis showed no significant difference in disease-free and overall survival. The data were further analyzed to identify subsets of patients with improved outcome when treated with VMO. METHODS: Patients received either VMO or placebo of live vaccinia vaccine virus (V), once a week for 13 weeks and then once every 2 weeks for an additional 39 weeks or until recurrence. Having stratified patients according to sex, age, number of positive nodes, tumor thickness, and clinical stage, data were analyzed for disease-free survival and overall survival. RESULTS: Male patients showed a 17% difference in overall survival at 4 years when treated with VMO (p = 0.19). A subset of male patients < 57 years of age with one to five positive nodes showed a 30% difference at 4 years with VMO (p = 0.06). Patients with clinical stage I but pathological stage II disease (both male and female), who had undergone prophylactic node dissection, showed a 23% difference in survival at 3 years with VMO (p = 0.11). CONCLUSIONS: This subset analysis shows encouraging survival benefit in certain subsets of patients and an increasing trend in overall survival. Further follow-up of this phase III trial from a second interim analysis will be forthcoming.