James A. Schoenberger

Hypertension in the elderly.

The available data indicate that classical hypertension, defined here as a diastolic blood pressure greater than or equal to 95 mm Hg, is a widely prevalent and as important a risk factor for the cardiovascular diseases in those aged 65 and over as it is in those under 65. The limited available data also indicate that pure systolic hypertension, defined here as a systolic blood pressure exceeding 160 mm Hg with a diastolic pressure under 95 mm Hg, also very common at age 65 and over, is also related to excess cardiovascular morbidity and mortality in the elderly. However, it is not clear whether this latter relationship is indicative of cause and effect, or merely reflects the fact that in the elderly pure systolic hypertension is a sign of extensive sclerosis of large arteries. The results of Veterans Administration studies on antihypertensive therapy indicate that the elderly patient with classical hypertension is amenable to effective treatment, and that the benefits of such treatment significantly outweigh the risks. Great care is needed in the use of drugs for the management of hypertension in elderly patients, especially to minimize risk of hypotensive episodes and their possible harmful consequences; but with judicious and careful therapy, hypertension of this type can be controlled with reduction in excess risk of morbidity and mortality, at least for those with average diastolic pressures greater than or equal to 105 mm Hg. The lack of data on the benefits of treatment for those with pure systolic hypertension precludes any recommendations in regard to pharmacologic treatment of this condition.

Multivariate analysis of the relationship of seven variables to blood pressure: Findings of the Chicago Heart Association Detection Project in Industry, 1967–1972

Abstract 1. 1. As in the preceding cross-sectional study [1], four multivariate statistical methods —partial correlation, multiple cross classification, multiple logistical regression, and multiple linear regression—were used to evaluate the relationship between seven variables and blood pressure in over 21,000 employed men and women, white and black, ages 25–44 and 45–64 surveyed in almost 100 Chicago companies and organizations. The analyses were carried out separately for eight age-sex-race groups. The seven variables were relative weight, resting heart rate, plasma glucose one hr after 50 g oral load, serum uric acid and cholesterol, current cigarette smoking habit, and age. 2. 2. Consistent with the findings of the preceding report, the first three of these variables—relative weight, heart rate, and plasma glucose—were independently related to blood pressure with a high degree of consistency, with p values for statistical significance ≤0.01 or ≤0.001 in the great majority of analyses. 3. 3. Serum uric acid—a variable not evaluated in the preceding report—was also independently related to blood pressure in a great majority of the analyses with p values of ≤0.01 or ≤0.001. 4. 4. The findings with respect to serum cholesterol and blood pressure were generally negative, except for white males, an intriguing finding in view of a similar result from the preceding study. 5. 5. No positive relationship was found between cigarette smoking and blood pressure. 6. 6. Even within the narrow age bands studied—ages 25–44 and 45–64—age was significantly related to blood pressure in a great majority of analyses (p values ≤0.01 or ≤0.001), independent of the six other variables. 7. 7. As in the preceding paper, when multivariate regression equations and their coefficients, computed from this experience of an entire age-sex-race group, were used to calculate an expectation of elevated blood pressure for each person, and then persons were ordered from low to high in expectation, a high proportion of all persons with recorded elevations of blood pressure were in the highest decile and quintile of expected prevalence—e.g. for persons age 25–44 in the four sex-race groups, from 45 to 56 per cent of observed cases with diastolic pressure ≥95 mm Hg. were in the highest quintile (20 per cent) of expected prevalence. The observed prevalence of elevated blood pressure was many times greater for the highest quintile of expected prevalence than for the lowest. A similar but less effective concentration of cases of elevated blood pressure was obtained with the multiple cross classification method, by dichotomizing five of the independent variables and identifying the substratum with any three, four or all five high.

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.

Serum uric acid and 11.5-year mortality of middle-aged women: Findings of the Chicago heart association detection project in industry

The relationships of serum uric acid to mortality from all causes, the cardiovascular diseases, and cancer were evaluated in 6797 white women age 35-64 years followed for an average of 11.5 years in the Chicago Heart Association Detection Project in Industry (CHA). Serum uric acid levels at baseline were strongly and significantly associated with all causes mortality in this cohort, with control for multiple risk factors and with exclusion of hypertensives on treatment. When the analysis was performed on age-specific groups 35-44, 45-54, and 55-64 years of age, the association was observed primarily in women in the oldest age group. All cardiovascular deaths, deaths due to coronary heart disease, and all cancer deaths were also associated with serum uric acid levels in the 55-64 year old group. The relationships persisted with control for multiple risk factors and with exclusion of treated hypertensives. A site-specific analysis of cancer deaths demonstrated elevations in mean serum uric acid levels for nearly all sites. Differences in mean serum uric acid levels between decedents and survivors tended to be largest in the first 5 years of follow-up for the cardiovascular deaths, but for cancer decedents they tended to be larger for subsequent years of follow-up. As an initial report on the association of serum uric acid and cancer in women in this age group, the results of this study require confirmation. Although hormonal influences may play a role, pathophysiologic mechanisms relating serum uric acid to mortality in white women aged 55-64 are currently unknown.

Relationship of education to major risk factors and death from coronary heart disease, cardiovascular diseases and all causes, Findings of three Chicago epidemiologic studies.

The relationship of education to risk factors at baseline and to long‐term mortality from coronary heart disease (CHD), cardiovascular diseases (CVD), and all causes was analyzed for three cohorts of middle‐aged employed white men in Chicago: 8047 from the Chicago Heart Association Detection Project in Industry (CHA) (entry 1967‐1973), 1250 from the Peoples Gas Company Study (PG) (entry 1958-1959) and 1730 from the Western Electric Study (WE) (entry 1957-1958). Each man was classified into one of four groups: not a high school graduate, high school graduate, some college but not a graduate, or college graduate. For all three cohorts, a graded, inverse association was observed at baseline between education and blood pressure, which was statistically significant for CHA and WE men and independent of age and relative weight. For all three cohorts, a significant, graded, inverse association was also recorded between education and cigarette use at entry. For serum cholesterol, no clear pattern was observed for the education groups in any of the three cohorts. CHA men showed a graded, inverse relationship between education and relative weight. This cohort was the only one of three showing a significant, graded inverse association between education and prevalence of ECG abnormalities at entry. For this CHA cohort, 5-year follow-up data showed a statistically significant, graded, inverse relationship between education and ageadjusted mortality rates from CHD, CVD and all causes. With adjustment for entry age, diastolic pressure, cigarettes, serum cholesterol, relative weight and ECG abnormalities, this inverse relationship remainedreduced in degree, but still statistically significant for CVD mortality. Similarly, for the pooled PG-WE cohort of 2980 with 20-21 years of follow-up, education and the three mortality end points were inversely related but not graded, with statistical significance for all three end points in the univariate analyses. The results of these studies indicate inverse relationships between education and lifestyle-related risk factors at baseline and between education and long-term risk of CHD, CVD and all-causes mortality. The inverse relationship between education and mortality is accounted for in part by the established major biomedical risk factors.

Correlates of the JAS type A behavior pattern score

Abstract The Jenkins Activity Survey (JAS), a self-administered and machine-scored questionnaire designed to assess the Type A behavior pattern described by Rosenman and Friedman, was included in an industry-based CHD risk factor screening program in the Chicago area. Data on 4108 white persons age 25–64 yr, categorized into four sex age groups, have been analyzed to investigate the relationship of the JAS Type A score to sex, age, socio-economic status (SES), CHD risk factors, prevalence of myocardial infarction, and compliance with recommendation to obtain followup medical evaluation. The following results were obtained. 1. 1. The Type A score is positively correlated with SES in all four sex age groups. 2. 2. After controlling SES, men do not differ significantly in mean Type A score from women, but both men and women age 45–64 yr have lower mean Type A scores than men and women age 25–44 yr. 3. 3. The number of cigarettes smoked per day is positively correlated with Type A score in men and younger women, but the magnitude of the correlation is very small. 4. 4. Prevalence of high blood pressure, defined as having elevated pressure or being treated medically for high blood pressure, is unrelated to Type A score in men and younger women but positively related in middle-age women after controlling for age, relative weight, and SES. 5. 5. The Type A score is weakly related to prevalence of hypercholesterolemia only in the total group of men age 25–44 yr; it is unrelated in older men and in women. Among persons not under medical treatment for CHD risk factors and without evidence of myocardial infarction, the Type A score is unrelated to concentration of serum cholesterol. 6. 6. The Type A score is unrelated to level of serum uric acid, plasma glucose after challenge, or relative weight. 7. 7. Compliance with a recommendation to obtain medical evaluation of suspect screening test results is unrelated to Type A score. 8. 8. Prevalence of myocardial infarction, as evidenced by Q-waves on the ECG or by history of physician-diagnosed heart attack, is positively related in middle-age men to Type A score after taking age, diastolic blood pressure, serum cholesterol, and cigarette smoking into account.

Serum cholesterol and risk of death from cancer and other causes in three Chicago epidemiological studies

Abstract Although hypercholesterolemia is established as a major risk factor for coronary heart disease, the finding in some epidemiological studies of no association between serum cholesterol and all causes mortality suggests that serum cholesterol may be inversely related to the risk of death from non-cardiovascular causes, e.g. cancer. This possibility led to the examination of this question in middle-aged white males from the Chicago Peoples Gas Company and Chicago Western Electric Company studies, and in middle-aged white males and females from the Chicago Heart Association Detection Project in Industry. In each of these studies, there was no significant association between initial serum cholesterol level and subsequent mortality from cancer, or from causes other than cancer and the cardiovascular diseases in men. There was, however, a significant inverse association with other causes of death in women. When the cancer deaths were examined by site, there was a significant inverse association between serum cholesterol and deaths from sarcoma, leukemia and Hodgkins disease in the Western Electric men and one that was nearly so in the Chicago Heart Association men. Serum cholesterol was not significantly related to lung cancer, colorectal cancer, oral cancer, pancreatic cancer, or to all other cancers combined in any of the three studies in men or in women. There was, however, the suggestion of a positive association for breast cancer in women. Thus, the results of these three studies do not generally support the hypothesis of an inverse association between serum cholesterol and cancer in urban middle-aged white American males and females.

Uric acid: a risk factor for coronary heart disease?

The association between serum uric acid the prevalence of ECG abnormalities was analyzed for 24,997 employed men women, white black, age 18–64 years, from the Chicago Heart Association (CHA) Detection Project in Industry. In addition, the relationships between uric acid 5-year mortality from all causes, from cardiovascular diseases (CVD), from coronary heart disease (CHD) were analyzed for 7804 white men women age 45-64 years from this study 967 white men age 44–63 years from the Chicago Peoples Gas Company Study. For men, the associations between uric acid the prevalence of ECG abnormalities with mortality appear to be secondary to associations between uric acid other risk factors. For women, however, the associations could not be explained by other risk factors.

Psychosocial predictors of mortality in the Cardiac Arrhythmia Suppression Trial-1 (CAST-1).

Psychosocial variables predict the recurrence of clinical events in symptomatic patients, controlling for measures of disease severity. The Cardiac Arrhythmia Suppression Trial-1, a pharmacologic test of the arrhythmia suppression and mortality hypothesis among postmyocardial infarction patients, allowed a prospective test of the relationship of distress, perceived support, social interaction, life stress, and other variables, to mortality, adjusting statistically for ejection fraction, arrhythmia rates, and other known risk factors for coronary heart disease. Results indicated that the treatment medications, encainide and flecainide, were powerful predictors of mortality. Although the psychosocial variables were significant as univariate predictors, these variables were not significant as predictors in a multivariate model that included drug treatment. When the data analysis was restricted to patients randomized to placebo, thereby eliminating the antiarrhythmic drug effect, the level of perceived social support was a significant multivariate predictor of mortality, adjusting for measures of disease severity. The adjusted hazards ratio for a 1-point decrease in the perceived support score is equal to 1.46, based on the multivariate model.

Long-term effects on plasma lipids of diet and drugs to treat hypertension. Treatment of Mild Hypertension Study (TOMHS) Research Group

OBJECTIVE - To compare long-term plasma lipid changes among 6 antihypertensive treatment interventions for stage I (mild) hypertension. DESIGN - Multicenter, randomized, double-blind, parallel-group clinical trial. SETTING - Four academic clinical research units in the United States. PARTICIPANTS - A total of 902 men and women, aged 45 to 69 years, with stage I diastolic hypertension (diastolic blood pressure <100 mm Hg), recruited from 11914 persons screened in their communities. INTERVENTIONS - Participants were randomized to 1 of 6 treatment groups: (1) placebo, (2) beta-blocker (acebutolol), (3) calcium antagonist (amlodipine), (4) diuretic (chlorthalidone), (5) alpha1-antagonist (doxazosin), and (6) angiotensin-converting enzyme inhibitor (enalapril). All groups received intensive lifestyle counseling to achieve weight loss, dietary sodium and alcohol reduction, and increased physical activity. MAIN OUTCOME MEASURES - Changes in plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides from baseline to annual visits through 4 years. RESULTS - Mean changes in all plasma lipids were favorable in all groups. The degree of weight loss with fat-modified diet and exercise was significantly related to favorable lipid changes. Significant differences (P<.01) among groups for average changes during follow-up in each lipid were observed. Decreases in plasma total cholesterol and LDL cholesterol were greater with doxazosin and acebutolol (for plasma total cholesterol, 0.36 and 0.30 mmol/L [13.8 and 11.7 mg/dL], respectively), less with chlorthalidone and placebo (0.12 and 0.13 mmol/L [4.5 and 5.1 mg/dL], respectively). Decreases in triglycerides were greater with doxazosin and enalapril, least with acebutolol. Increases in HDL cholesterol were greater with enalapril and doxazosin, least with acebutolol. Significant relative increases in plasma total cholesterol with chlorthalidone compared with placebo at 12 months were no longer present at 24 months and beyond, when mean plasma total cholesterol for the chlorthalidone group fell below baseline. Analyses of participants continuing to receive chlorthalidone throughout the 4 years of follow-up indicated this was not due solely to an increasing percentage of participants changing or discontinuing use of medication during follow-up. CONCLUSIONS - Weight loss with a fat-modified diet plus increased exercise produces favorable long-term effects on blood pressure and all plasma lipid fractions of adults with stage I hypertension; blood pressure reduction is enhanced to a similar degree by addition of a drug from any one of 5 classes of antihypertensive medication. These drugs differ quantitatively in influencing the degree of long-term favorable effects on blood lipids obtained with nutritional-hygienic treatment.