The effect of supplemental oral phosphate on the bone mineral changes during prolonged bed rest.

Five healthy young men were studied during 24-30 wk of continuous bed rest. During the first 12 wk of bed rest, untreated subjects increased calcium excretion in the urine by 109 mg/day and in the feces by 147 mg/day. The rate of total body calcium loss was 0.5-0.7% per month. Losses of central calcaneus mineral, assessed by gamma ray transmission scanning, occurred at a tenfold higher rate, whereas the mineral content of the radius did not change. Changes in phosphorus balance resembled the calcium pattern, and increased excretion of nitrogen and hydroxyproline also occurred during bed rest. Upon reambulation, the subjects' calcium balance became positive in 1 month and recovery of their calcaneus mineral was complete within 10-20 wk. Treatment with potassium phosphate supplements (1327 mg P/day) entirely prevented the hypercalciuria of bed rest, but fecal calcium tended to increase. During the first 12 wk, calcium balance was slightly less negative (mean - 193 mg/day) than during bed rest without added phosphate (mean - 267 mg/day). This effect was not seen during the second 12 wk of bed rest. The patterns of magnesium excretion were similar to those of calcium. Fecal and urinary phosphorus excretions were doubled, and phosphorus balance became positive (+ 113 mg/day). Mineral loss from the central calcaneus was similar to that of untreated subjects. It is concluded that this form of phosphate supplementation reduces urinary calcium excretion but does not prevent bone loss during bed rest.

Postmenopausal hormone therapy and risk of stroke: The Heart and Estrogen-progestin Replacement Study (HERS).

BACKGROUND: Observational studies have shown that postmenopausal hormone therapy may increase, decrease, or have no effect on the risk of stroke. To date, no clinical trial has examined this question. To investigate the relation between estrogen plus progestin therapy and risk of stroke among postmenopausal women, we analyzed data collected from the Heart & Estrogen-progestin Replacement Study (HERS), a secondary coronary heart disease prevention trial. METHODS AND RESULTS: Postmenopausal women (n=2763) were randomly assigned to take conjugated estrogen plus progestin or placebo. Primary outcomes for these analyses were stroke incidence and stroke death during a mean follow-up of 4.1 years. The number of women with strokes was compared with the number of women without strokes. A total of 149 women (5%) had 1 or more strokes, 85% of which were ischemic, resulting in 26 deaths. Hormone therapy was not significantly associated with risk of nonfatal stroke (relative hazard [RH] 1.18; 95% CI 0.83 to 1.66), fatal stroke (RH 1.61; 95% CI 0.73 to 3.55), or transient ischemic attack (RH 0.90; 95% CI 0.57 to 1.42). Independent predictors of stroke events included increasing age, hypertension, diabetes, current cigarette smoking, and atrial fibrillation. Black women were at increased risk compared with white women, and unexpectedly, body mass index was inversely associated with stroke risk. CONCLUSIONS: Hormone therapy with conjugated equine estrogen and progestin had no significant effect on the risk for stroke among postmenopausal women with coronary disease.

Choice and use of blood lipid tests. An epidemiologic perspective.

Serum cholesterol is a useful test in asymptomatic adults who are interested in preventing coronary heart disease (CHD). It guides the decision to recommend a fat-controlled diet to reduce the serum cholesterol level; this intervention probably decreases the risk of CHD in patients with high levels (eg, greater than 240 mg/dL), but not in those with lower levels (the majority). The potential effect of such intervention on absolute (attributable) CHD risk is relatively large in males and in patients with other risk factors. Dietary intervention probably has less effect on CHD risk than eliminating smoking or controlling hypertension. Lipid and lipoprotein tests other than cholesterol are not generally needed, although high-density lipoprotein cholesterol may be useful in certain situations. These epidemiologic considerations, tempered by the preferences of the patient, are useful for individualizing preventive medicine decisions.

The impact of diuretic therapy on reported sexual function.

BACKGROUND: --Thiazide diuretics are the most commonly prescribed antihypertensive agent in the treatment of hypertension. No studies to date have isolated conclusively the effect of diuretic therapy on patient quality of life, and particularly on sexual dysfunction. METHODS: --We carried out a randomized placebo-controlled trial of the effect of thiazide diuretics on quality of life in mildly hypertensive men between the ages of 35 and 70 years. After a 1-month washout period off diuretic therapy, the men were randomized to a 2-month trial of a thiazide treatment or placebo. At the end of the trial, 176 men completed a confidential self-administered questionnaire assessing aspects of social performance, general well-being, and emotional and physiologic states. RESULTS: --Patients taking diuretics reported significantly greater sexual dysfunction than control subjects, including decreased libido, difficulty in gaining and maintaining an erection, and difficulty with ejaculation. Multivariate analysis suggested that the findings were not mediated by low serum potassium levels or by low blood pressure. Sexual dysfunction was noted more often in the confidential self-report questionnaire than in response to direct questions from clinicians. We found no differences between diuretic and placebo groups in measures of mood, general sense of well-being, ability to work, alertness, and social/recreational activities. CONCLUSIONS: --Thiazide diuretic use is associated with male sexual dysfunction but does not appear to adversely affect other aspects of quality of life.

Postural hypotension and postural dizziness in elderly women. The study of osteoporotic fractures. The Study of Osteoporotic Fractures Research Group.

BACKGROUND: Postural hypotension and dizziness are common findings in elderly individuals. Although postural hypotension and postural dizziness are often perceived to be strongly associated entities, evidence to support this view in sparse. In addition, there is a lack of knowledge regarding the relationship of postural hypotension and postural dizziness to potential clinical outcomes, such as falls, syncope, and restricted activity. METHODS: We utilized a cross-sectional examination to study the prevalence and correlates of postural hypotension (drop in systolic blood pressure of greater than or equal to 20 mm Hg after 1 minute of standing) and postural dizziness (self-reported dizziness on standing) in 9704 nonblack, ambulatory women aged 65 years and older enrolled in the multicenter Study of Osteoporotic Fractures. First, we examined postural hypotension and postural dizziness as outcomes of risk factors that included medical conditions, medications, and physical findings. Then, we examined falls, syncope, and impaired functional status as outcomes of postural hypotension and postural dizziness. RESULTS: Postural hypotension and postural dizziness were common findings, noted in 14% and 19% of subjects, respectively. However, they were not highly correlated with each other and did not share the same risk factors or associated outcomes. Postural dizziness was more strongly associated than was postural hypotension with history of falling (age-adjusted odds ratios, 1.32 vs 1.02), history of syncope (1.94 vs 1.35), and impaired functional status (1.95 vs 0.76). CONCLUSION: Assessment of dizziness on standing appears to be more important than measurement of postural blood pressure change in ascertaining functional status and risk of falls and syncope in elderly individuals. Future prospective studies of postural dizziness are needed to confirm its value as a predictor of clinical outcomes.

HIV antibody testing in young, urban adults.

We surveyed men and women aged 21 to 34 years to determine the rates of human immunodeficiency virus (HIV) antibody testing in blacks and whites of diverse education levels in four US cities. Responses to the anonymous, mailed questionnaire were received from 90% of 777 white women, 64% of 734 black women, 79% of 677 white men, and 48% of 541 black men. The percentages reporting HIV testing for these four race-gender groups were 29%, 22%, 30%, and 38%, respectively. The percentages reporting testing that was voluntarily sought (ie, not in connection with blood donation, military service) were 16%, 14%, 18%, and 22%, respectively. In each race-gender group, roughly half of those who had not been tested said they "might have a blood test for the AIDS virus in the future". Education level was not correlated with HIV-testing frequency. Blacks were significantly less likely than whites to be aware of "a blood test that can detect the AIDS virus infection" (58% vs 77%), but blacks who knew of the test were more likely than whites to have been tested (47% vs 37%). Eleven percent of subjects reported at least one major risk factor for HIV infection. In these people, HIV testing was most common among homosexually active men (56% tested; 52% voluntarily sought), intermediate among injection drug users (40% tested; 31% voluntarily sought), and least common among the sexual partners of injection-drug users (21% tested; 11% voluntarily sought). Health education programs need to communicate the availability of, and need for, anonymous HIV testing.

Estrogen replacement therapy and mortality among older women. The study of osteoporotic fractures.

BACKGROUND: Most previous studies of estrogen replacement therapy (ERT) and mortality have focused on younger women. Recently, it has been suggested that the effect of ERT on mortality may represent a "healthy-user" effect, ie, those with healthier lifestyles having a greater likelihood of receiving ERT. METHODS: Nine thousand seven hundred four women, 65 years or older, participated; 1258 (14.1%) reported current use of ERT for at least 1 year at entry. During an average follow-up of 6.0 years, 1054 women (11.8%) died. RESULTS: After adjusting for multiple variables, mortality rate was lower among current (relative risk [RR], 0.69; 95% confidence interval [CI], 0.54-0.87) and past users (RR, 0.79; 95% CI, 0.66-0.95), mainly due to reductions in deaths due to cardiovascular disease. The protective effect of ERT was greatest among women younger than 75 years (RR, 0.55; 95% CI, 0.40-0.76) compared with women from 75 to 84 years of age (RR, 0.93; 95% CI, 0.62-1.41) and 85 years or older (RR, 1.33; 95% CI, 0.43-4.12). The RR for overall mortality was 0.95 (95% CI, 0.68-1.32) among short-term users (1-9 years) compared with 0.55 (95% CI, 0.40-0.75) among long-term users (> or = 10 years). Deaths considered unrelated to ERT tended also to be reduced in current users younger than 75 years (RR, 0.72; 95% CI, 0.49-1.06) and current long-term users (RR, 0.75; 95% CI, 0.51-1.10). CONCLUSIONS: Estrogen replacement therapy is associated with lower overall mortality rates and reduced deaths due to cardiovascular disease. Women using ERT had healthier lifestyles, and the risk for death thought to be unrelated to ERT also tended to be lower in ERT users, suggesting in part a healthy-user effect.

Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study.

OBJECTIVES: To describe recent temporal patterns of cholesterol-lowering medication use and the characteristics that may have influenced the initiation of cholesterol-lowering therapy among those aged 65 years or older. SUBJECTS AND METHODS: A cohort of 5201 adults 65 years or older were examined annually between June 1989 and May 1996. We added 687 African American adults to the cohort in 1992-1993. We measured blood lipid levels at baseline and for the original cohort in the third year of follow-up. We assessed the use of cholesterol-lowering drugs at each visit. RESULTS: The prevalence of cholesterol-lowering drug use in 1989-1990 was 4.5% among the men and 5.9% among the women; these figures increased over the next 6 years to 8.1% and 10.0%, respectively, in 1995-1996. There was a 4-fold increase in the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors during the 6 years of follow-up, from 1.9% of all participants in 1989-1990 to 7.5% in 1995-1996. The use of bile acid sequestrants, nicotinic acid, and probucol declined from initial levels of less than 1% each. Among the participants who were untreated in 1989-1990, but eligible for cholesterol-lowering therapy after a trial of dietary therapy according to the 1993 guidelines of the National Cholesterol Education Panel, less than 20% initiated drug therapy in the 6 years of follow-up, even among subjects with a history of coronary heart disease. Among participants untreated at baseline but eligible for either cholesterol-lowering therapy or dietary therapy, initiation of cholesterol-lowering drug therapy was directly associated with total cholesterol levels, hypertension, and a history of coronary heart disease, and was inversely related to age, high-density lipoprotein cholesterol levels, and difficulties with activities of daily living. Other characteristics that form the basis of the 1993 National Cholesterol Education Panel guidelines-diabetes, smoking, family history of premature coronary heart disease, and total number of risk factors-were not associated with the initiation of cholesterol-lowering drug therapy. CONCLUSIONS: Given the clinical trial evidence for benefit, those aged 65 to 75 years and with prior coronary heart disease appeared undertreated with cholesterol-lowering drug therapy.

A novel use of the link-file system for longitudinal studies of HIV infection: a practical solution to an ethical dilemma.

BACKGROUND: Longitudinal studies that collect sensitive data, such as test results for HIV antibodies, present difficult ethical problems for investigators. Personal identifiers are needed for longitudinal follow-up, but current regulations in the United States require that all subjects be informed of their HIV test results when identifiers are retained. Therefore, subjects who do not wish to learn their HIV status must be excluded from prospective research. Because these subjects may be at particularly high risk for HIV infection, this situation may lead to substantial bias. METHODS: We describe a new application of a methodology for blinding such studies, based on the link-file system used for protecting subjects' sensitive research data. This design enables investigators to hold each subject's HIV test result and survey data for multiple ascertainments over time while effectively severing any link between this information and the subject's identity. This objective is achieved by a process of sequential coding, using at least two coders who are not associated with the study. CONCLUSIONS: The method described in this paper permits investigators in the United States to perform important prospective epidemiologic studies while adhering to current regulations for the conduct of such investigations.

Levels of HIV testing and low validity of self-reported test results among alcoholics and drug users.

OBJECTIVES: To evaluate HIV testing behavior, validity of self-reported serostatus, and intention to test among alcoholics and drug users entering treatment. DESIGN: Longitudinal cohort study. METHODS: A total of 952 clients voluntarily entering three outpatient and two inpatient public alcohol treatment centers in San Francisco were enrolled. Seventy-six per cent were men, 50% black, 81% had used both alcohol and drugs during the last year, 43% had injected drugs and 9% of the men were homosexual. Subjects completed an interviewer-administered questionnaire and blindly-linked HIV-antibody test at entry and after 1 year (81% follow-up). RESULTS: Fifty-seven per cent of subjects reported that they had previously sought HIV testing. Factors associated with HIV testing included homosexual contact, injecting drug use, having a partner who had been tested, and using condoms. Hispanics were the least likely of all ethnic groups to report testing. Of 60 subjects with HIV antibodies, 47 (78%) said they had already been tested; however, 19 (40%) inaccurately reported that their serostatus was negative and another four (9%) had no collected their test results. Blacks were much more likely than other groups to misreport or be unaware of their HIV status. Only half of the 68% who said they planned to be tested during the following year did so. Five (42%) out of 12 HIV-positive individuals who were unaware of, or misreported their serostatus at baseline, and who sought another HIV test during the follow-up year continued to report themselves as uninfected. CONCLUSIONS: A large proportion of clients attending public alcohol treatment centers report having been HIV tested, much greater than that observed in other populations. However, misreporting of HIV test results was very common among seropositive subjects. Alcohol and drug treatment programs for this high-risk population should include interventions to optimize use of HIV testing for prevention and treatment, and improve understanding of test results.

Effect of risk status on treatment criteria. Implications of hypertension trials.

When deciding whether to treat a patient with hypertension, clinicians must balance the benefit of treatment against its adverse effects. In the absence of an interaction, the multiplicative model of risk implies that the absolute benefit of treatment is related to the underlying risk of an adverse outcome. Thus, each additional risk factor multiplies the absolute benefit of treating hypertension. Analyses of data from subgroups in clinical trials of hypertension treatment suggest that this model is usually valid. In contrast, the adverse effects of treatment are usually unrelated to other risk factors. Thus, the cutoff point for treatment differs in different individuals: setting a single treatment threshold and goal for the entire population is not appropriate. Patients who are at high absolute risk because of prior coronary artery disease or other risk factors have a greater potential absolute benefit, and such patients deserve a low threshold and goal, such as a diastolic blood pressure of 90 mm Hg. Conversely, persons at low risk, such as white women without other risk factors, do not require such aggressive management.

Effect of the diphosphonate EHDP on bone mineral metabolism during prolonged bed rest.

The effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDPTM) on bone mineral metabolism was tested in 4 healthy young men during 20 weeks of continuous bed rest. Two subjects received an oral dose of 5 mg/kg/day and the other 2 20 mg/kg/day. The low dose had two minor effects: the increase in bone accretion rate which usually occurs during bed rest was prevented, and there was an accentuation of the bed rest induced increase in hydroxyproline excretion. Skeletal mineral loss, assessed by calcium balance measurements and gamma ray absorptiometry of the calcaneus, occurred at the rate previously noted in untreated control subjects. Two types of drug effect were apparent at the higher dosage: one was immediate and sustained--a rise in serum phosphorus concentration and a fall in serum alkaline phosphatase activity. The other was delayed and progressive--a decline in urinary hydroxyproline excretion and in the rates of bone accretion and resorption. Skeletal mineral loss may have been affected; the usual negative mineral balance developed during the first half of the study, then disappeared during the last few weeks. However, gamma ray absorptiometry revealed no attenuation of the calcaneal mineral losses.

Effect of health education on dietary behavior: the Stanford Three Community Study.

A 2-yr mass media cardiovascular health education program in two communities was followed by a 3rd, maintenance yr of reduced effort. In each community, a representative cohort reported its dietary behavior annually to an interviewer using a questionnaire which estimated daily consumption of cholesterol and fat. Relative weight and plasma cholesterol were also measured annually. Both men and women in the treatment towns reported reductions in dietary cholesterol (23 to 34%) and saturated fat (25 to 30%) which were significantly larger than those reported in a 3rd, control community. Relative weight was increased in the control community when compared to the treatment towns, perhaps as a result of the aging of the cohorts. Similar patterns were observed for plasma cholesterol changes. The 2-yr changes were maintained or increased during the 3rd, maintenance yr. The changes in individual values for plasma cholesterol showed low level correlations with dietary cholesterol and saturated fat, but the association with weight change was more important. These results suggest that mass media health education can achieve lasting changes in diet, obesity, and plasma cholesterol on a community level.

Role of nutritional status and weight loss in HIV seroconversion among Rwandan women.

To investigate nutritional status and heterosexual human immunodeficiency virus (HIV) transmission, we performed a nested case-control study of sexually active, adult women in Kigali, Rwanda. Forty-five women who seroconverted during the 24-month study period were compared to 74 women who remained seronegative throughout the study. Seroconvertors and nonseroconvertors did not differ in preseroconversion serum levels of vitamin A, carotenoids, vitamin E, selenium, albumin, ferritin, or cholesterol. Weight loss, however, was a significant predictor of eventual HIV seroconversion. Subsequent seroconvertors lost an average of 1.5 kg during the first 6 months of the study compared with a 1.0-kg gain (p = 0.001) for nonconvertors. Nine of 27 (33%) seroconvertors, compared with one of 44 (2%) controls, lost at least 5 kg in the 6-month period beginning 1 year before their seroconversion (odds ratio, 21.5, 95% confidence interval 4.1-112). The association between weight loss and seroconversion was independent of other potential risk factors such as socioeconomic status, pregnancy, and genital ulcer disease. In addition to these findings for measured weight loss during follow-up, reported weight loss before enrollment was also a risk factor for subsequent seroconversion. Additional studies of heterosexual HIV transmission are needed to determine whether or not weight loss is causally related to susceptibility for HIV infection.

Health policy for treating hyperlipidemia: analogy with hypertension and prospects for the next decade.

Over the past 15 years, efforts by the health profession to detect and treat high blood pressure have grown remarkably successful. A similar growth now seems likely for high blood cholesterol. Three factors are responsible: the continuing emergence of scientific evidence corroborating the benefit of lowering high blood cholesterol levels by diet or drugs, the formulation in 1984 of more specific health policy guidelines by the Consensus Development Conference on Lowering Blood Cholesterol and the creation in 1985 of the National Cholesterol Education Program. This program has been designed to enhance preventive activities by the public and by health care professionals. Its success will depend in part on resolving problems with the efficacy and acceptability of life-style and drug interventions for lowering blood cholesterol levels.

Circadian variation in ventricular arrhythmias in hypertensive men.

Circadian patterns have been observed for various cardiovascular functions and events including sudden cardiac death. This study examined whether ventricular arrhythmias could be a pathophysiologic explanation for the increase in prevalence of sudden cardiac death observed between 6 A.M. and noon. Hypertensive men 35 to 70 years of age and without a history of symptomatic cardiac disease were withdrawn from diuretic treatment and received 1 month of oral electrolyte repletion with both 40 mmol of potassium chloride and 400 mg of magnesium oxide daily. Then continuous 24-hour Holter monitoring was performed and ventricular arrhythmias were classified by 6-hour time intervals. The interval from 6 A.M. to noon revealed a higher prevalence of complex or frequent ventricular arrhythmias than the interval from midnight to 6 A.M., as well as a higher mean number of ventricular premature complexes per hour. The differences were statistically significant (p less than 0.01) and amounted to increases of about one third. Ventricular arrhythmias during the other two 6-hour periods were intermediary in frequency. It is concluded that the increase in sudden cardiac death noted in the morning might be related, at least in part, to an increase in frequency of ventricular arrhythmias; the implications of this observation for preventive cardiology deserve further investigation.

Risk of ventricular arrhythmias in hypertensive men with left ventricular hypertrophy.

The echocardiographic predictors of ventricular arrhythmias are reported for the Hypertension Arrhythmia Reduction Trial. Men with mild hypertension were withdrawn from their diuretic therapy and repleted with 40 mEq/day of oral potassium and 20 mEq/day of oral magnesium for 1 month. M-mode echocardiography and 24-hour continuous ambulatory electrocardiography were performed on 123 men, mean age 62 years. Forty-eight men (39%) had echocardiographic evidence of left ventricular (LV) hypertrophy defined as an LV mass index greater than 134 g/m2 and this finding was not related to the presence of LV hypertrophy on electrocardiogram or to age. Men who had echocardiographic LV hypertrophy were more likely than men without echocardiographic LV hypertrophy to have greater than or equal to 30 ventricular premature complexes (VPCs)/hr (odds ratio = 2.7; 95% confidence interval = 0.9, 8.0), multiform extrasystoles (odds ratio = 1.7; confidence interval = 0.8, 3.7), episodes of ventricular tachycardia (odds ratio = 2.3; confidence interval = 0.7, 7.1) and the combination of frequent (greater than or equal to 30 VPCs/hr) or complex (ventricular couplets, multiform extrasystoles or episodes of ventricular tachycardia) ventricular arrhythmia (odds ratio = 1.7; confidence interval = 0.8, 3.5). Similar associations between echocardiographic LV hypertrophy and ventricular arrhythmias were observed on 24-hour tracings obtained on entry to the study (before electrolyte repletion) in the 96 men who were taking diuretics at this time. The combination of a frequent or complex arrhythmia was also more common in men aged 60 to 70 compared to men aged 35 to 59 (odds ratio = 3.4; confidence interval = 1.4, 8.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Silent myocardial ischemia in men with systemic hypertension and without clinical evidence of coronary artery disease.

The prevalence, characteristics and circadian pattern of silent myocardial ischemia, and its association with ventricular arrhythmias was studied in hypertensive men aged 35 to 70 years (mean 61) without clinical cardiac disease. Participants were withdrawn from diuretic treatment and received 1 month of oral electrolyte repletion with 40 mmol of potassium chloride, and 400 mg of magnesium oxide daily. Twenty-four-hour Holter monitoring was then performed. Episodes of silent myocardial ischemia occurred in 50 of 186 men (27%) and lasted from 2 to 289 minutes (mean 30 and median 18). Statistical analysis comparing the interval from midnight to 6 A.M. with each of the other three 6-hour time intervals revealed that participants were less likely to have silent myocardial ischemia in this period (p less than 0.01 for each comparison) than at other times of the day. There was little difference in the proportion of men with a frequent or complex ventricular arrhythmia during the entire day or within 1 hour of the silent myocardial ischemic episode (or during a comparable time period) comparing those with to those without silent myocardial ischemia. These findings indicate that silent myocardial ischemia occurs in approximately 25% of an older population of hypertensive men without history of symptomatic cardiac disease. The circadian pattern of frequency of silent ischemic events in men free of clinical cardiac disease is similar to that reported for patients with cardiac disease and coincides with that reported for sudden death. There was no significant association between silent myocardial ischemia and ventricular arrhythmias.

Systolic Hypertension in the Elderly Program (SHEP): antihypertensive efficacy of chlorthalidone.

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, blinded test of the efficacy of antihypertensive drug treatment. In a large feasibility trial, 551 men and women who had isolated systolic hypertension and were at least 60 years old received chlorthalidone (25 to 50 mg/day) or matching placebo as the step I drug. After 1 year, 83% of the chlorthalidone group and 80% of the placebo group were still taking SHEP medications. Of those still taking chlorthalidone, 88% had reached goal blood pressure (BP) without requiring a step II drug, and most had responded to the lower dose (25 mg/day). The BP response was similar in all age, sex and race subgroups, with an overall mean difference between randomized groups of 17 mm Hg for systolic BP (p less than 0.001) and 6 mm Hg for diastolic BP (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum levels of potassium (0.5 mEq/liter lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001) and creatinine (0.08 mg/dl higher, p = 0.02). This study indicates that chlorthalidone is effective for lowering BP in elderly patients with systolic hypertension and sets the stage for a larger trial of the effects of such treatment on the incidence of cardiovascular disease.

Risk factors for coronary heart disease. Selected recent epidemiological advances.

Several recent advances in our understanding of the epidemiology and prevention of coronary artery disease are presented, highlighting the current status of the 3 major risk factors: blood cholesterol, blood pressure and cigarette smoking. There is a striking analogy between serum cholesterol and diastolic blood pressure in the pattern of the association with coronary heart disease (CHD). Mortality follow-up of the 361,662 middle-aged men screened for the Multiple Risk Factor Intervention Trial (MRFIT) shows that each of these risk factors identifies a large group of patients (the top 15% of the population distribution) who have a 4-fold higher risk of CHD death than those in the bottom 15%, and that each has a continuously rising gradient of risk for people with intermediary levels. The implication from these findings, and from the clinical trial data, is that public health and clinical policies directed at blood cholesterol should be made similar to those that have become widespread for blood pressure in the past 2 decades; i.e. measuring the level periodically in all adults and intervening to prevent CHD in those at highest risk. The public health campaign to reduce cigarette smoking has been bolstered by new evidence on the hazards of ambient smoke. One example comes from the clinical trial cohort of the MRFIT, in which non-smoking men who were married to smoking wives had nearly twice the all-cause mortality rate of non-smoking men who were married to non-smoking wives.(ABSTRACT TRUNCATED AT 250 WORDS)