Cardiovascular actions of cadmium at environmental exposure levels.

A low intake of dietary cadmium induces specific dose-dependent functional and biochemical changes in the cardiovascular tissues of rats. Maximum changes occur when the cadmium intake is 10 to 20 micrograms per kilogram of body weight per day. The changes reflect the accumulation of "critical" concentrations of cadmium in the cardiovascular tissues. The biologic activity of cadmium is demonstrated for intakes that approach those of the average American adult exposed to the usual environmental concentrations of the element but not to industrial concentrations. The sensitivity of the cardiovascular system to low doses of cadmium could not be anticipated by extrapolation from data on exposure to high concentrations of cadmium. The data support the hypothesis that ingested or inhaled environmental cadmium may contribute to essential hypertension in humans.

Screening for Vitamin D Deficiency in Black Americans: Comparison of Total, Free, Bioavailable 25 Hydroxy Vitamin D Levels with Parathyroid Hormone Levels and Bone Mineral Density.

OBJECTIVES: There is debate surrounding the adequacy of total and free 25 hydroxy vitamin D [25(OH)D] levels in black Americans who have inherently high bone mineral density [BMD] and low serum concentration of vitamin D binding proteins [VDBP]. DESIGN: Retrospective analysis of serum samples and BMD analyses from the African American Health Study [AAHS] cohort. SETTING: The AAHS is a population-based longitudinal study initiated to examine issues of disability and frailty among urban-dwelling black Americans in the city of Saint Louis, Missouri. PARTICIPANTS: 122 men and 206 women, age 60.2 ± 4.3 years. INTERVENTION: Retrospective analysis. MEASUREMENTS: Total 25(OH)D, VDBP, PTH, and BMD of the lumbar spine and hip by dual energy x-ray photometry (DXA). Free and bioavailable vitamin D levels were calculated using serum concentrations and affinity constants for the VDBP (Gc1F and Gc1S) phenotypes. RESULTS: Serum total 25(OH)D levels were 14.6 ± 8.9 ng/mL (36 ± 22 nmol/L). Vitamin D insufficiency was estimated by compensatory elevations of PTH above the normal range (> 65 pg/mL). PTH levels were within the normal reference range in > 95% of the samples at total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L). There was no difference in the correlation of the reciprocal relationship of vitamin D vs parathyroid hormone between the VDBP phenotypes. Receiver operating characteristic curve analyses indicated that serum total 25(OH)D discriminated sufficiency from insufficiency at least as well as the calculated levels of the free and bioavailable vitamin D. Very low levels of total 25(OH)D (≤ 8 ng/mL, ≤20 nmol/L) were associated with decreased BMD (p=0.02), but higher levels of 25(OH)D did not show statistical differences in BMD. CONCLUSION: Total 25(OH)D levels of ≤ 8ng/mL (≤20 nmol/L) are associated with clinically significant changes in BMD, whereas total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L) suppressed PTH and were not associated with deficiencies in BMD. Lower levels of 25(OH)D may be acceptable for bone health in black than in white Americans.

Comparison of screening questionnaires for the diagnosis of hypogonadism.

Three questionnaires, the St. Louis University Androgen Deficiency in Aging Male (ADAM), the Aging Male Survey (AMS) and the Massachusetts Male Aging Study (MMAS), have been developed as potential screening tools for hypogonadism in older males. We compared these questionnaires in 148 males aged 23-80 years using bioavailable testosterone as the "biochemical gold standard" for diagnosis of hypogonadism. The sensitivity for the ADAM was 97%, for the AMS 83% and the MMAS 60%. Specificity was 30% for the ADAM, 59% for the MMAS and 39% for AMS. Both bioavailable testosterone and the calculated free testosterone correlated significantly with a number of the individual questions. Total testosterone correlated poorly with most of the questions. In conclusion, the ADAM and AMS may be useful screening tools for hypogonadism across the adult lifespan, but both are relatively nonspecific.

Alternate calcitonin and etidronate disodium therapy for Paget's bone disease.

The efficacy of salmon calcitonin and etidronate disodium was compared in the therapy of Paget's bone disease in 37 patients. Nineteen patients received etidronate for six months with a mean alkaline phosphatase reduction to 53% of initial values. Bone scintophotographs improved in 12 and were unchanged in seven. Symptoms improved in 11 subjects, were unchanged in seven, and worsened in one. Twelve of these patients were then treated with calcitonin for six months with continued improvement in alkaline phosphatase values to 36% of initial values. All bone scintophotographs improved compared with initial studies. Seven patients continued to improve symptomatically; five described no change. Eighteen individuals were treated initially with calcitonin for six months. During therapy, the alkaline phosphatase level fell to 76% of initial values. Bone scintophotographs were worse in two patients, did not change in seven, and improved in nine. Eleven patients reported improvement in symptoms and seven reported no change. Seventeen of these patients were then treated with etidronate for six months with a decrease in alkaline phosphatase levels to 64% of initial values. Compared with initial tests, bone scintophotographs were worse in three with no change in five and improvement in nine. Symptomatically, three patients reported improvement; four noted no change, and ten reported increasing pain. Although the reason for the poor response to initial calcitonin therapy and/or subsequent etidronate therapy is not apparent, we have concluded that patients fare better when treated with an etidronate calcitonin sequence when compared with those treated with a calcitonin/etidronate sequence.

Regional and racial differences in response to antihypertensive medication use in a randomized controlled trial of men with hypertension in the United States. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: Stroke incidence and mortality rates are higher in the southeastern region of the United States, which is called the "Stroke Belt." We compared the response to antihypertensive medication use in patients from different US regions. METHODS: The short-term and 1-year efficacy of the antihypertensive medications hydrochlorothiazide, atenolol, diltiazem hydrochloride (sustained release), captopril, prazosin hydrochloride, and clonidine was compared by US region in a randomized controlled trial of 1,105 men with hypertension from 15 US Veterans Affairs medical centers. RESULTS: Compared with patients outside the Stroke Belt, patients inside the Stroke Belt achieved significantly lower treatment success rates of diastolic blood pressure control at 1 year with hydrochlorothiazide (63% vs 41%), atenolol (62% vs 46%), captopril (60% vs 30%), and clonidine (69% vs 43%); there were no differences in treatment success rates with diltiazem (70% vs 71%) or prazosin (54% vs 53%). When controlling for race, patients inside the Stroke Belt had significantly lower treatment success rates with hydrochlorothiazide (P = .003) and clonidine (P = .003), and the lower success rate with atenolol approached significance (P = .15). Regardless of region, blacks were less likely than whites to achieve treatment success with atenolol (P = .02) or prazosin (P = .03) and more likely with diltiazem (P = .05). There was a trend for blacks residing inside the Stroke Belt to have a lower treatment success rate than other race-region groups when treated with captopril (P = .07). Many regional and racial differences in diet, lifestyle, and other characteristics were observed. After adjustment for these characteristics by regression analysis, the effect of residing inside the Stroke Belt remained for captopril (P = .01) and clonidine (P = .01) and approached significance for hydrochlorothiazide (P = .10). CONCLUSIONS: Hypertension in patients residing inside the Stroke Belt responded less to the use of several antihypertensive medications and important differences were shown in a number of characteristics that may affect the control of blood pressure, compared with patients residing outside the Stroke Belt.

Exogenous hyperthyroidism with osteoporosis.

Symptomatic osteopenia accompanied by subclinical hyperthyroidism developed in three women who were receiving excess thyroid hormone medication. Excessive thyroid replacement therapy resulted in mild hypercalcemia, hyperphosphatemia, and hyperphosphatasemia associated with diffuse skeletal demineralization and multiple fractures. Nondecalcified sections of double tetracycline-labeled iliac crest bone showed an accelerated rate of bone turnover with marked osteoclastosis and resorption of the cortical as well as the trabecular bone, typical of endogenous hyperthyroidism. Since thyroid hormones are among the most frequently prescribed medications, bone loss caused by exogenous hyperthyroidism may be more common than previously recognized.

Osteoporosis in young men: a syndrome of hypercalciuria and accelerated bone turnover.

Five young men had a similar syndrome of osteopenia and hypercalciuria, probably resorptive and absorptive, with histomorphometric data suggesting decreased bone mass with increased rate of bone formation. A search for causes of osteopenia, either primary or secondary, was unrewarding.

Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program.

BACKGROUND: Little information has been published on the impact of antihypertensive medications on quality of life in older persons. Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition, mood, or leisure activities. METHODS: A multicenter double-blind randomized controlled trial was conducted over an average of 5 years' followup involving 16 academic clinical trial clinics. Participants consisted of 4736 persons (1.06%) selected from 447,921 screenees aged 60 years and older. Systolic blood pressure at baseline ranged from 160 to 219 mm Hg, while diastolic blood pressure was less than 90 mm Hg. Participants were randomized to active antihypertensive drug therapy or matching placebo. Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1, while step 2 consisted of 25 to 50 mg of atenolol. If atenolol was contraindicated, 0.05 to 0.10 mg of reserpine could be used for the second-step drug. The impact of drug treatment on measures of cognitive, emotional, and physical function and leisure activities was assessed. RESULTS: Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and, for some measures, a slight positive effect on cognitive, physical, and leisure function. The positive findings in favor of the treatment group were small. There was no effect on measures related to emotional state. Measures of cognitive and emotional function were stable in both groups for the duration of the study. Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period. CONCLUSIONS: The overall study cohort exhibited decline over time in activities of daily living, particularly the more strenuous ones, and some decline in certain leisure activities. However, mood, cognitive function, basic self-care, and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study. Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition, emotional state, physical function, or leisure activities.

Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol treatment program on blood pressure.

OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized controlled trial. METHODS: Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS: Reduction in average weekly self-reported alcohol intake was significantly greater (P<.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = .17 and P = .18) for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P = .44). CONCLUSIONS: The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension.

Parathyroid hormone-lymphocyte interactions modulate bone resorption.

The biologically active PTH fragment 1-34 induces mononuclear leukocytes to produce a substance(s) capable of increasing bone resorption, as assayed in an organ culture system. The onset of the effect is evident at 2 days and lasts at least 7 days. The cell responsible for this effect appears to be an activated nonadherent lymphocyte (probably T-cell). PTH-(1-34) induces these cells to secrete this factor(s). The presence of adherent mononuclear leukocytes or appropriate conditioned medium appears to augment this response. Secretion of this factor(s) is specific for PTH-(1-34); it is not induced by biologically inactive PTH fragments, nor can it be induced by incubating mononuclear leukocytes with other hormones, including human PRL or lysine vasopressin. On the other hand, PTH-(1-34), human PRL, and lysine vasopressin all activate mononuclear leukocytes, as determined by [3H]thymidine incorporation. Biologically inactive PTH fragments do not. Thus, while lymphocyte activation may be a necessary prerequisite to lymphocyte modulation of bone resorption, it is not sufficient of itself. The PTH fragment 1-34 activates mononuclear leukocytes and specifically induces nonadherent lymphocytes to produce a substance(s) capable of increasing bone resorption. Preliminary characterization of this substance(s) shows that cellular components of the organ culture are necessary to demonstrate the increased resorptive capacity of PTH-stimulated lymphocyte supernatants. Secondly, this resorptive capacity is heat sensitive. Finally, this substance(s) appears to have a nominal molecular radius greater than 14,000 daltons, but less than 50,000 daltons.

Partial characterization of a parathyroid hormone-stimulated resorption factor(s) from osteoblast-like cells.

PTH stimulates osteoblast-like cells to produce a product(s) capable of increasing cellular bone resorption. We have investigated this phenomenon using primary cultures of osteoblasts and the clonal osteoblast-like cell line ROS 17/2. Conditioned medium from PTH-stimulated populations of either culture increases bone resorption compared to conditioned medium measured in three independent assay systems; the isolated osteoclast assay system, elicited macrophages, and the fetal bone rudiment system. Characterization of the factor(s) of PTH-stimulated osteoblast-like cell (ROS 17/2) suggests that the compound(s) is not prostaglandin (no inhibition by indomethacin; not extractable in diethylacetate). Rather, it is heat and protease sensitive. In addition, secretion of the product is sensitive to cycloheximide. These findings lead us to the conclusion that the factor(s) is protein. Further work demonstrates the necessity for a divalent cation for retention of factor activity. Finally, we have estimated the molecular radius of the factor as about 110,000 daltons and perhaps a second at about 70,000 daltons using a sizing column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of [35S]methionine-labeled PTH-stimulated ROS culture supernatants reveals relatively increased secretion of proteins with these approximate molecular radii.

Calcitonin response in circulating human lymphocytes.

The concentration of cAMP increases in human mononuclear leukocytes after exposure to salmon calcitonin (SCT). This response is lost when the cells are separated into adherent (monocytic) and nonadherent (lymphocytic) cells, although the appropriate response to prostaglandin E2 remains in both groups. Adherent and nonadherent cells, each cultured alone for 16 h, do not regain the SCT response. Coculturing adherent and nonadherent cells together for 16 h restores the SCT response in the lymphocytes. The addition of a cyclooxygenase inhibitor to this culture system prevents development of the SCT response. The SCT response may be induced in nonadherent cells by culturing them for 16 h in medium previously conditioned by the growth of mixed mononuclear leukocytes.

Conference report on stroke mortality in the southeastern United States.

A workshop to describe and then seek possible causes for the increased stroke mortality in the southeastern United States briefly considered 30 suspected correlates and discussed in more detail the 10 thought to be most likely. Recent age-adjusted stroke mortality rates in adults from industrialized countries reveal marked geographic differences. Age-adjusted statewide stroke mortality rates also differ, and they are higher in the Southeast than elsewhere in the United States. For five southeastern coastal states in the heart of the "Stroke Belt," excess stroke mortality has been present at least since 1930. In a 20-year follow-up of 10,000 veterans, the Stroke Belt had a 25% increase in all-cause mortality and congestive heart failure. A potential cause of increased fatal stroke included hypertension, which was more frequent in the Stroke Belt. No consistent patterns of lifestyle differences or of differences in potassium or calcium intake seemed to explain the higher rates of fatal strokes in the Stroke Belt; however, detailed investigations of smaller populations in localized areas seem warranted. Some data suggest a relationship between socioeconomic status and the Stroke Belt effect. Other differences in the Southeast that could explain, at least partially, the Stroke Belt effect include presence of soft water throughout most of the area, decreased antioxidant intake, and differences in the use of medical care and in the response to antihypertensive drugs. On the basis of available information, the three most likely explanations or partial explanations for the Stroke Belt are increased levels of blood pressure, localized differences in socioeconomic status, and toxic environmental factor(s). Two major recommendations were made: (1) to encourage both patient and caregiver to use all currently available means of decreasing morbidity and mortality by controlling blood pressures at or below normal levels and by reducing other risk factors and (2) to seek precise information about relationships of identified possible causes of increased morbidity and mortality in the Stroke Belt.

Department of Veterans Affairs hypertension meeting : a proposal for improved care.

A major invitational hypertension meeting was hosted by the Department of Veterans Affairs (VA) in Washington, DC, on May 26 to 28, 1999. It followed a report that only 25% of hypertensive veterans had adequate levels of treated blood pressure and focused on how control of hypertension could be improved both immediately and in the future. After the presentation of brief outlines of 5 unresolved basic science questions, 2 general topics were considered: (1) 30 years of change in hypertension and its treatment and (2) current healthcare delivery mechanisms and how to improve them. Since 1970, the severity of hypertension has decreased, malignant hypertension has disappeared, and the prognostic roles of systolic and diastolic blood pressure have been reversed as hypertension became milder. Five VA Cooperative Studies have provided important data: the 1970 Freis Trial report demonstrated the value of treatment, 2 trials showed that some controlled patients can decrease or even discontinue pharmacological treatment without recrudescent hypertension, a blinded trial was performed on the efficacy of different antihypertensive drugs, and an unblinded trial showed that diuretics and beta-blockers are the most effective agents when caregivers choose the agent and dose. Two healthcare models were considered: (1) the patient-friendly VA Hypertension Screening and Treatment Program that was introduced in 1972, which controls 80% of patients at the goal of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure with diuretics and keeps patients in the program an average of 7.5 years, and (2) the newer primary care health maintenance organization-like model in the VA and throughout the United States. Choosing a regimen and monitoring control of blood pressure and compliance with therapy were discussed. The meeting was closed with 6 general recommendations for improving the care of hypertensive patients.

Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial.

A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population. Fifteen hypogonadal men (mean age 68 +/- 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65 +/- 7 yr) were randomly assigned to receive testosterone. Hypogonadism was defined as a bioavailable testosterone <60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months. The main outcomes measured included grip strength, hemoglobin, prostate-specific antigen, leptin, and memory. Testosterone improved bilateral grip strength (P < 0.05 by ANOVA) and increased hemoglobin (P < 0.001 by ANOVA). The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean +/- SEM: -2.0 +/- 0.9 ng/dL vs. 0.8 +/- 0.7 ng/dL; P < 0.02). There were no significant changes in prostate-specific antigen or memory. Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study. Three of those seven withdrew because of an abnormal elevation in hematocrit. Testosterone supplementation improved strength, increased hemoglobin, and lowered leptin levels in older hypogonadal men. Testosterone may have a role in the treatment of frailty in males with hypogonadism; however, older men receiving testosterone must be carefully monitored because of its potential risks.

Antihypertensive efficacy of treatment regimens used in Veterans Administration hypertension clinics. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

There is continuing uncertainty about whether morbidity and mortality of treated hypertensive patients depends on the drug(s) used to treat or only on the level of blood pressure achieved. This study was undertaken in a sample of special Veterans Administration hypertension clinics to determine which antihypertensive drugs were selected by the involved healthcare providers and how effective they were in achieving normotension. Hypertensive veterans (n = 6100) were followed in six VA Hypertension Screening and Treatment Program clinics for 46 months beginning in May 1989. Their average age was 60.7 years; 53% lived in the Stroke Belt; 46% had target organ damage, 36% were black, 23% smoked, and 10% had diabetes mellitus. Antihypertensive regimens were divided into 12 all-inclusive categories. Blood pressures were averaged at the last study visit for all patients on a regimen. The regimens of diuretic or diuretic plus beta-blocker gave the lowest average pressures (140.6/82.3 mm Hg) and calcium antagonist the highest (149.0/86.5 mm Hg). ANOVA indicated that differences between seven common regimens and also between the four single drug regimens were highly significant (P<.0001). This pattern of low treated pressure with the "old" agents and higher treated pressure with newer agents was reflected in the percentage of patients controlled below 140/90 mm Hg and the percentage uncontrolled above 159/94 mm Hg. Blacks and patients with target organ damage resembled the entire cohort in average treated diastolic blood pressure, but the former had lower and the latter had higher treated systolic blood pressure than the entire cohort.

Early predictors of 15-year end-stage renal disease in hypertensive patients.

There has been a continuing increase in the incidence of end-stage renal disease (ESRD) in the United States, including the fraction that has been attributed to hypertension. This study was done to seek relationships between ESRD and pretreatment clinical data and between ESRD and early treated blood pressure data in a population of hypertensive veterans. We identified a total of 5730 black and 6182 nonblack male veterans as hypertensive from 1974 through 1976 in 32 Veterans Administration Hypertension Screening and Treatment Program clinics. Their mean age was 52.5 +/- 10.2 years, and their mean pretreatment blood pressure was 154.3 +/- 19.0/100.8 +/- 9.8 mm Hg. During a minimum of 13.9 years of follow-up, 5337 (44.8%) of these patients died and 245 developed ESRD. For 1055 of these subjects, pretreatment systolic blood pressure (SBP) was greater than 180 mm Hg; 901 were diabetic; 1471 had a history of urinary tract problems; and 2358 of the 9644 who were treated had an early fall in SBP of more than 20 mm Hg. We used proportional hazards modeling to fit multivariate survival models to determine the effect of the available pretreatment data and early treated blood pressure levels on ESRD. This model demonstrated the independent increased risk of ESRD associated with being black or diabetic (risk ratio, 2.2 or 1.8), having a history of urinary tract problems (risk ratio, 2.2), or having high pretreatment SBP (for SBP 165 to 180 mm Hg, risk ratio was 2.8; for SBP > 180 mm Hg, risk ratio was 7.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional differences in mortality during 15-year follow-up of 11,936 hypertensive veterans.

Several different investigators have reported increased stroke mortality in the southeastern United States, leading to the introduction of the term "Stroke Belt." The results presented here from the Veterans Administration Hypertension Screening and Treatment Program (HSTP) demonstrate an increased all-cause mortality among hypertensive patients seen in HSTP clinics in the southeastern United States when compared with similar patients from other HSTP clinics. Several different groupings of southeastern states were examined and compared with nine states west of the Mississippi River. A total of 11,936 male veterans, 5737 of whom were black, were identified as hypertensive during 1974-1976 in 32 HSTP clinics. Their mean age was 52.4 +/- 10.4 years, and their mean pretreatment blood pressure was 153.8 +/- 19.1/100.4 +/- 9.8 mm Hg. During a minimum of 13.9 years of follow-up, 5360 (44.9%) of these patients died. Proportional hazards modeling was used to fit a basic survival model with terms representing race, age, blood pressure, smoking, and obesity. Risk was increased with higher blood pressure, age, and smoking and with lower body mass index. For 6 HSTP clinics in an 11-state Stroke Belt (defined as states with stroke mortality > 10% above the United States average), the relative risk of death was 1.226 (95% confidence interval, 1.106-1.358) when compared with 9 states west of the Mississippi River. For two different groupings of southeastern states with 10 and 8 HSTP clinics the relative risk of death was 1.231 and 1.295.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging and bone metabolism in African American and Caucasian women.

There is limited information concerning bone mineral density (BMD) and its determinants across a wide spectrum of ages in African American females (AAF). Therefore, we have performed a cross-sectional study of 54 AAF and 39 Caucasian females (CF), aged 20-90 yr, to quantify femoral and lumbar bone mineral density, total body calcium, as well as the potential determinants of bone density. BMD decreased with age in all sites after age 40 yr in both racial groups. Bone density was greater in AAF than in CF, although there was considerable overlap between the two groups. There was no significant difference in the rate of age-related bone loss between the two groups. At the femoral neck, BMD was below the fracture threshold in 28% of the postmenopausal AAF compared to 47% of postmenopausal CF. L1-L4 BMD was below the fracture threshold in 8% of postmenopausal AAF and 11% of postmenopausal CF. Serum-25 hydroxyvitamin D (25OHD) was inversely related to age in both othnic groups and lower (P < 0.05) in premenopausal AAF than CF. Twenty-four percent of the AAF and 22% of the CF had serum 25OHD levels of 8 ng/L or less. Serum PTH was directly related to age (r = 0.43; P = 0.003 in AAF and r = 0.55; P = 0.002 in CF), and 25OHD was inversely related to age (r = -0.43; P = 0.003 in AAF and r = -0.65; P < 0.001 in CF). PTH was higher (P < 0.05) in postmenopausal AAF than in CF. Serum testosterone was greater in AAF than in CF (P < 0.05). Serum estradiol was greater in premenopausal AAF than in CF. Serum dehydroepiandrosterone sulfate was inversely related to age (r = 0.42; P = 0.004 in AAF and r = 0.51; P = 0.005 in CF). Serum osteocalcin was related to age in AAF (r = 0.47; P = 0.001), but not in CF. There was also a trend for an increase in urinary dipyridinoline (expressed per 100 mg urinary creatinine) with age (r = 0.31; P = 0.055 in AAF and r = 0.37; P = 0.066 in CF). Both lean and fat mass were major determinants of femoral neck BMD in AAF. Femoral BMD was directly related to body weight and body mass index in both races. Serum 25OHD and dehydroepiandrosterone sulfate approached statistical significance as independent predictors of femoral BMD in AAF. We conclude that in AAF, 1) bone density is higher than in CF, but there is a significant risk of fracture in a substantial number of subjects on the basis of BMD; 2) there is no difference in rates of age-related bone loss compared to those in CF; 3) both lean and fat mass are significant determinants of bone density; 4) serum estradiol and testosterone were higher than those in CF; and 5) aging is associated with increased bone turnover, 25OHD deficiency, and secondary hyperparathyroidism in both races. The absence of a difference in rates of bone loss between AAF and CF despite higher serum levels of PTH is compatible with the concept of a relative skeletal resistance to PTH in AAF.

Relationship of age and calcitonin gene-related peptide to postprandial hypotension.

Falls following a meal occur commonly in older persons. These falls have been related to a decrease in postprandial blood pressure due to carbohydrates in the meal. The mechanism by which this occurs is not known. In this study, we examined the possible role of a vasodilatory peptide, calcitonin gene-related peptide (CGRP), which is released following carbohydrate loading in the pathophysiology of postprandial hypotension. Levels were assessed in 29 community-dwelling individuals aged 20-83 years during an oral glucose tolerance test, and heart rate and blood pressure were measured. Five subjects exhibited a postprandial reduction in systolic blood pressure (SBP) greater than 15 mmHg (mean reduction -30 +/- 4 mmHg). Four were aged over 60 (40% of the individuals in that group) and one was middle aged (11%). One individual in the older group was temporarily symptomatic, complaining of light-headedness. Linear regression analysis showed a significant association between the changes in CGRP and in blood pressure: SBP (r = 0.39, P = 0.037), and mean blood pressure (MBP) (r = 0.356, P = 0.06) in the oldest group. Individuals in this group with a greater than 15 mmHg drop in blood pressure, exhibited significantly greater changes in CGRP (SBP: P = 0.001, diastolic blood pressure (DBP): P = 0.05, MBP: P = 0.006). This association of log CGRP delta and BP change was not present in young or middle aged individuals. Thus, increases in CGRP levels were associated with blood pressure reduction, with older individuals more susceptible to these changes than younger individuals. CGRP may play a role in the pathogenesis of postprandial hypotension.