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Biomedical subjects

H M Perry

Publications and source records attributed to H M Perry.

At least 19 recordsLinked to original sources

The effects of season and alcohol intake on mineral metabolism in men.

We have examined the relationship between self-reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the participants into two groups on the basis of their reported alcohol intake. Individuals with none-to-moderate intake had <8.4 oz/week of ethanol. Those with moderate or heavier intake had 8.4 oz or more of ethanol/week. Individuals with none-to-moderate SRAI had a significant seasonal increase in iPTH, osteocalcin, urine DPC/100 mg of Cr and a decrease in distal forearm bone mineral density, 25 hydroxyvitamin D (250HD), and urinary calcium/100 mg of Cr. Individuals with moderate or heavier SRAI only had significant seasonal decrease in 250HD. We have concluded that alcohol intake decreases seasonal change in serum iPTH. The biological effects of such alterations in parathyroid hormone levels include decreased seasonal loss of bone mineral density.

Adult

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.

Adult

The effect of aging on bone mineral metabolism and bone mass in Native American women.

OBJECTIVE: To examine the effect of age on mineral metabolism and bone mineral density (BMD) of the hip and spine in Native American women. DESIGN: A cross-sectional study. SETTING: The Sac and Fox Nation in rural Oklahoma MEASUREMENTS: Serum measurements were made of 25 hydroxyvitamin D (25OHD), osteocalcin, and immunoreactive parathyroid hormone. Bone mineral density of the hip and spine was assessed by dual energy X-ray absorptiometry. PARTICIPANTS: A total of 77 Native American women aged 19 to 85 years. RESULTS: Serum 25 hydroxyvitamin D was related inversely to age (r = -0.32; P < .05) and was less than 15 ng/mL in 7% of the subjects. Serum osteocalcin was higher (P < .001) in postmenopausal than in premenopausal subjects. In postmenopausal subjects, serum osteocalcin was related to age (r = .59, P < .001). BMD was lower (P < .001) in postmenopausal than in premenopausal subjects. There was no evidence of bone loss before age 50 in either the femur or the spine. Age (r > or = -0.48, P < .001) and body mass index (BMI) (r > or = 0.41, P < .005) were independent determinants of both femoral and lumbar BMD. Serum 25OHD was a significant independent determinant of both lumbar (r = .26, P < .05) and femoral (r = .41, P < .01) BMD. Age, BMI, and serum 25OHD together accounted for 70% of the variance in BMD at these sites. The use of t scores indicated femoral bone density was higher (P < .05) in premenopausal Native American women, and lower (P < 0.05) in postmenopausal subjects, compared with white women. CONCLUSIONS: In Native American women, there is a reduction in bone density and a sustained increase in bone turnover postmenopausally. BMI and serum 25OHD are significant determinants of BMD. Peak BMD may be higher, and the postmenopausal rate of bone loss greater, than that in white women.

Adult

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.

Analysis of Variance

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.

Adolescent

Effect of recent alcohol intake on parathyroid hormone and mineral metabolism in men.

The mechanisms by which alcohol intake, particularly moderate alcohol intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin (r = 0.30, p = 0.002), alkaline phosphatase (r = 0.30, p = 0.004), and aspartate aminotransferase (SGOT) (r = 0.29, p = 0.006). SRAI correlated with serum calcium corrected for albumin (r = -0.39, p < 0.001), estradiol (r = 0.43, p < 0.001), and immunoreactive parathyroid hormone (iPTH) (r = -0.51, p < 0.001), as well as urinary calcium (per 100 mg of creatinine) (r = 0.55, p < 0.001). We have arbitrarily divided the participants into two groups on the basis of their reported alcohol intake. Individuals in the first group had intakes ranging from none to moderate intake (drank 8.4 oz or less of ethanol per week, equivalent to an average of two drinks daily or less). Those in the second group had moderate or heavier intake, with >8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 +/- 3.4 and 39.9 +/- 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 +/- 0.05 vs. 8.88 +/- 0.07 mg/dl, respectively). In addition, urinary calcium (corrected per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 +/- 0.4 vs. 8.4 +/- 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 +/- 38 vs. 530 +/- 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250-hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (beta = 0.215, p = 0.025), SRAI (beta = -0.281, p = 0.003), 250-hydroxyvitamin D (beta = -0.309, p = 0.002), and testosterone (beta = -184, p = 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.

Adult

Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP Cooperative Research Group.

CONTEXT: Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known. OBJECTIVE: To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension. DESIGN: Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial. PARTICIPANTS: A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP). INTERVENTION: Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo. MAIN OUTCOME MEASURES: Fatal and nonfatal heart failure. RESULTS: During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71; P<.001; number needed to treat to prevent 1 event [NNT], 48). Among patients with a history of or electrocardiographic evidence of prior myocardial infarction (MI), the RR was 0.19 (95% CI, 0.06-0.53; P=.002; NNT, 15). Older patients, men, and those with higher systolic blood pressure or a history of or electrocardiographic evidence of MI at baseline had higher risk of developing heart failure. CONCLUSION: In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.

Aged

Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone.

A cross-sectional survey was made in 56 exceptionally healthy males, ranging in age from 20 to 84 years. Measurements were made of selected steroidal components and peptidic hormones in blood serum, and cognitive and physical tests were performed. Of those blood serum variables that gave highly significant negative correlations with age (r > -0.6), bioavailable testosterone (BT), dehydroepiandrosterone sulfate (DHEAS), and the ratio of insulin-like growth factor 1 (IGF-1) to growth hormone (GH) showed a stepwise pattern of age-related changes most closely resembling those of the age steps themselves. Of these, BT correlated best with significantly age-correlated cognitive and physical measures. Because DHEAS correlated well with BT and considerably less well than BT with the cognitive and physical measures, it seems likely that BT and/or substances to which BT gives rise in tissues play a more direct role in whatever processes are rate-limiting in the functions measured and that DHEAS relates more indirectly to these functions. The high correlation of IGF-1/GH with age, its relatively low correlation with BT, and the patterns of correlations of IGF-1/GH and BT with significantly age-correlated cognitive and physical measures suggest that the GH-IGF-1 axis and BT play independent roles in affecting these functions. Serial determinations made after oral ingestion of pregnenolone and data from the literature suggest there is interdependence of steroid metabolic systems with those operational in control of interrelations in the GH-IGF-1 axis. Longitudinal concurrent measurements of serum levels of BT, DHEAS, and IGF-1/GH together with detailed studies of their correlations with age-correlated functional measures may be useful in detecting early age-related dysregulations and may be helpful in devising ameliorative approaches.

Adult

Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men.

Cross-sectional studies have demonstrated a decline in testosterone and free and bioavailable testosterone with age. This occurs in a majority of older persons without an increase in luteinizing hormone (LH), suggesting that a component of the testosterone decrease is due to secondary hypogonadism. To determine whether these findings could be duplicated in a longitudinal study, we measured testosterone, LH, follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) levels in 77 men participating in the New Mexico Aging Process Study who had sera available in 1980 or 1981 and two or more serial samples in 1982, 1984, 1989, and/or 1994. Thirty-nine subjects had samples available from both 1980 and 1994. The age at entry into the study ranged from 61 to 87 years. Testosterone levels decreased over the 15 years of the study. In persons who were alive for the duration of the study, testosterone levels were significantly lower 5 years before termination of the study (P < .05). Testosterone levels did not differ at entry into the study among those who died and those who were alive at the end of the study period. Eight of 77 subjects (10%) had LH levels above the normal range at some time during the study. In contrast, 43% of subjects had elevated FSH levels. Both LH and FSH increased significantly with age. SHBG levels were measured in 1980 and 1994 and increased significantly with age (P < .0001). LH and FSH were highly correlated with one another, but neither correlated with testosterone. This study demonstrated a longitudinal decline in testosterone and an increase in LH and FSH in older men. The average rate of decrement in testosterone concentration was 110 ng/dL every decade.

Aged

Body composition and age in African-American and Caucasian women: relationship to plasma leptin levels.

Leptin is a recently isolated peptide hormone released from adipocytes that has been postulated to play a role in appetite regulation and energy metabolism. Aging affects both food intake and body composition. Body composition is also affected by ethnicity. We have evaluated the relationships between serum leptin levels, age, body composition (by dual-energy x-ray absorptiometry), and hormonal parameters in a cross-sectional study of 94 women, 53 African-American (AAF) and 41 Caucasian (CF). Our hypotheses were as follows: (1) changes in body composition would be related to age in a sinusoidal pattern, (2) changes in serum leptin would parallel changes in body fat, (3) serum leptin levels would be influenced by body fat distribution, and (4) serum leptin would be related to serum concentrations of sex hormones. Serum leptin paralleled changes in body fat and body mass index (BMI) with age. In the entire group, serum leptin correlated closely with measures of body fat, including BMI and total fat mass, and there was no difference in leptin levels between the two ethnic groups. In simple regression analysis, serum leptin was related to both serum estradiol and testosterone. The relationship between serum leptin and trunk fat was linear in both groups, but significantly different in AAF and CF (P = .014). Serum leptin was associated with the trunk to lower-extremity fat ratio in CF (r = .67, P = .001) but not in AAF. Body fat was increased with advancing age until about 65 years and then declined. Measures of lean body mass declined linearly with age in the entire group, as well as both subgroups. In the entire group, total lean body mass and lean body mass corrected for BMI (lean body mass/BMI) were inversely related to age. In subjects aged less than 60 years AAF were stronger (P < .05) and had both a larger BMI and fat mass (P < .05) than CF. However, the patterns of age-related changes in fat body mass, lean body mass, and BMI were similar in both groups. In the entire group, multiple regression analysis indicated that the age, free thyroxine index (FTI), and leptin concentration were predictors of the body composition and distribution of trunk to lower-body fat. These observations indicate that there is a sinusoidal relationship between body fat and age, with a decline in body fat in extreme old age in both AAF and CF, and that serum leptin concentrations are more closely related to body fat and BMI than to age or ethnicity.

Absorptiometry, Photon

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.

Aged

Testosterone and frailty.

Although estrogen replacement therapy has become well established in the management of postmenopausal women, most physicians pay much less attention to the testosterone status of their older male patients. There is now increasing evidence that testosterone deficiency-Low Testosterone Syndrome-occurs in older men and is associated with decreased muscle strength and bone density, as well as memory problems. This article reviews the evidence for the existence of Low Testosterone Syndrome, often characterized as the male menopause or viropause, and the emerging evidence that testosterone therapy may ameliorate some of the symptoms and signs of frailty in men beyond 50 years of age.

Aged

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.

Adult

Age-related changes in amylin secretion.

Amylin (islet amyloid polypeptide) is a recently identified pancreatic peptide. It has been shown to affect glucose metabolism both in vitro and in vivo. A cross sectional analysis of the effects of age on amylin secretion following a 75 g glucose tolerance test in a young (20-40 years), middle aged (41-60 years) and older (61-90 years) group was performed. Thirty lean (BMI less than 25) non-diabetic individuals were studied. Amylin secretion exhibited a U-shaped curve with greater secretion in young and old subjects than in middle aged persons. Baseline levels were 7.2 +/- 1, 4.7 +/- 1, and 5.3 +/- 0.75 pM respectively, at 60 min 9.5 +/- 0.9 (y), 5.5 +/- 1 (m), 8.6 +/- 1 (o) pM; and at 120 min 10.3 +/- 2 (y), 4.4 +/- 0.5 (m), 10.9 +/- 1.5 (o) pM. Amylin production (area under the curve) was 1102 +/- 131, 619.5 +/- 79 and 1043 +/- 120 pM per min respectively (P < 0.05). Amylin secretion was similar in both sexes. Variability in the insulin to amylin ratio for each of the age groups at different time points following a glucose load was found, suggesting that insulin and amylin are not co-secreted in a fixed ratio. A significant association was found between both maximum amylin and rise in amylin (delta) and a glucose greater than 120 mg/dl at 2 h. (P < 0.001, P < 0.001). This correlation of glucose and amylin may be interpreted as suggestive of a counterregulatory role for amylin. However, aging is also associated with changes in glucose metabolism and amylin may merely be acting as a marker of impaired glucose metabolism.

Adult

Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group.

Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.

Antihypertensive Agents

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.

Adolescent

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)

Adult