Sharon E. Carmody

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)

THE WASHINGTON UNIVERSITY- EPRI VETERANS' COHORT MORTALITY STUDY: Preliminary Results

This article presents the design of and some results from a new prospective mortality study of a national cohort of about 50,000 U.S. veterans who were diagnosed as hypertensive in the mid 1970s, based on approximately 21 yr of follow-up. This national cohort is male with an average age at recruitment of 51 ± 12 yr; 35% were black and 81% had been smokers at one time. Because the subjects have been receiving care at various U.S. Veterans Administration (VA) hospitals, access to and quality of medical care are relatively homogeneous. The health endpoints available for analysis include all-cause mortality and specific diagnoses for morbidity during VA hospitalizations; only the mortality results are discussed here. Nonpollution predictor variables in the baseline model include race, smoking (ever or at recruitment), age, systolic and diastolic blood pressure (BP), and body mass index (BMI). Interactions of BP and BMI with age were also considered. Although this study essentially controls for socioeconomic status by design because of the homogeneity of the cohort, selected ecological variables were also considered at the ZIP code and county levels, some of which were found to be significant predictors. Pollutants were averaged by year and county for TSP, PM10, CO, O3, and NO2; SO2 and Pb were considered less thoroughly. Both mean and peak levels were considered for gases. SO42 data from the AIRS database and PM2.5, coarse particles, PM15, and SO42 from the U.S. EPA Inhalable Particulate (IP) Network were also considered. Four relevant exposure periods were defined: 1974 and earlier (back to 1953 for TSP), 1975–1981, 1982–1988, and 1989–1996. Deaths during each of the three most recent exposure periods were considered separately, yielding up to 12 combinations of exposure and mortality periods for each pollutant. Associations between concurrent air quality and mortality periods were considered to relate to acute responses; delayed associations with prior exposures were considered to be emblematic of initiation of chronic disease. Preexposure mortality associations were considered to be indirect (noncausal). The implied mortality risks of long-term exposure to air pollution were found to be sensitive to the details of the regression model, the time period of exposure, the locations included, and the inclusion of ecological as well as personal variables. Both positive and negative statistically significant mortality responses were found. Fine particles as measured in the 1979–1984 U.S. EPA Inhalable Particulate Network indicated no significant (positive) excess mortality risk for this cohort in any of the models considered. Among the positive responses, indications of concurrent mortality risks were seen for NO2 and peak O3, with a similar indication of delayed risks only for NO2. The mean levels of these excess risks were in the range of 5–9%;. Peak O3 was dominant in two-pollutant models and there was some indication of a threshold in response. However, it is likely that standard errors of the regression coefficients may have been underestimated because of spatial autocorrelation among the model residuals. The significant variability of responses by period of death cohort suggests that aggregation over the entire period of follow-up obscures important aspects of the implied pollution–mortality relationships, such as early depletion of the available pool of those subjects who may be most susceptible to air pollution effects.

Air Pollution, Blood Pressure, and Their Long-Term Associations with Mortality

This article addresses the importance of blood pressure as a covariate in studies of long-term associations between air quality and mortality. We focus on a cohort of about 50,000 U.S. veterans who had been diagnosed as hypertensive at some time and whose survival rates were predicted by blood pressure (BP) and ambient air quality, among other factors. The relationship between BP and air quality is considered by reviewing the literature, by deleting variables from the proportional hazards regression model, and by stratifying the cohort by diastolic blood pressure (DBP) level. The literature review shows BP to be an important predictor of survival and finds small transient associations between air quality and BP that may be either positive or negative. The regression model sensitivity runs showed that the associations with air pollution are robust to the deletion of the BP variables, for the entire cohort. For stratified regressions, the confidence intervals for the air pollution-mortality associations overlap for the two DBP groups. We conclude that associations between mortality and air quality are not mediated through blood pressure, nor vice versa.

Pretreatment blood pressure as a predictor of 21-year mortality

Our objective was to evaluate pretreatment predictors of longevity, particularly blood pressure, in a large cohort of hypertensive men. During 1974 to 1976, 10,367 male hypertensive veterans (47% black) were identified at screening and subsequently characterized in 32 special Veterans Administration (VA) hypertension clinics. Their mean age was 52 years and mean blood pressure (BP) 154/100 mm Hg. During an average of 21 years of follow-up, 61% died. Risk ratios for all-cause mortality as functions of BP and other risk factors are presented for each variable alone; for each variable controlling for age, race, and BP; and for a multivariate model. We observed that when the entire cohort was divided into deciles by systolic blood pressure (SBP) and by diastolic blood pressure (DBP), the risk ratios for 21-year mortality increased from lowest to highest decile by 178% for SBP and 16% for DBP. When the deciles were computed separately by age group, increases from lowest to highest decile for those less than 40 years of age were 138% for SBP and 263% for DBP. For those over 60 years, the increases were 154% and -10%, respectively. Although blacks were younger and had more severe diastolic hypertension than whites, the risk ratios were similar within each race group. Risk patterns for mean arterial pressure and pulse pressure resembled those for SBP but had smaller gradients. Survival curves for BP groups suggested constant mortality rates during follow-up. Other significant observations included decreasing mortality with increasing body mass index and increased mortality in the Stroke Belt. We concluded that pretreatment SBP strongly predicted all-cause mortality during 21-year follow-up. For the young, both SBP and DBP were strong predictors; for the elderly, only SBP was predictive.

Community volunteers as recruitment staff in a clinical trial: The systolic hypertension in the elderly program (SHEP) experience

During the recruitment phase of a trial it is often found that recruitment is not proceeding as quickly as projected. Budget limitations require innovative methods, such as use of volunteers, to increase recruitment yields without increasing cost. In the Systolic Hypertension in the Elderly Program (SHEP), volunteer staff at 12 of the 16 clinical centers (CCs) performed a range of tasks such as mailings, telephoning, and clerical work. SHEP volunteers donated almost 40,000 hours, at an estimated cost savings to the program of more than

Erythropoietin activity and protein-protein interactions in human urine

368,000. Staff volunteers appear to require more training and supervision than regular staff and may require flexible work schedules. These limitations can be obviated by careful planning. This paper describes the SHEP experience with staff volunteers and provides suggestions for their use in other trials.

Survival in hydralazine-treated hypertensive patients with and without late toxicity.

Abstract 1. 1. Urine containing erythropoietin was chromatogrpahed, and the proteins associated with its activity were characterized physicochemically. Protein-protein interactions between acidic and basic proteins were observed, and the specific activity of the erythropoietin decreased as the basic protein was removed. 2. 2. Erythropoietin was associated with acidic-basic protein complexes. Two acidic proteins having isoionic points at pH 2.8–2.9 and 2.6–2.7 were isolated. 3. 3. The electrophoretic mobilities of the partially purified acidic proteins were influenced by the presence of a basic protein. Under the conditions described, the most anionic protein had a moblity of −7.6·10 −5 cm 2 V −1 sec −1 ; the most cationic protein had a mobility of +2.7·10 −5 cm 2 V −1 sec −1 . 4. 4. The sedimentation coefficients of the isolated acidic-basic protein complexes were 2.7 S and 1.2 S.

Relationship of acetyl transferase activity to antinuclear antibodies and toxic symptoms in hypertensive patients treated with hydralazine

Abstract Part I, Average diastolic pressure was examined in two groups of white patients during 10 yr of treatment with hydralazine for significant hypertension. The first group consisted of 42 patients who developed late toxic reactions to hydralazine. The control group consisted of 42 similarly treated non-toxic patients matched for age, sex, and pre-treatment severity of hypertension. The average diastolic pressure was lower for the toxic patients throughout the period of hydralazine exposure. The effect was evident within a month of starting treatment; it was maximal during toxicity, and it apparently persisted long after the toxic patients discontinued ingesting hydralazine. More importantly, the once-toxic patients survived almost a third longer than their ‘matches’, and the number of survivors at both 10 and 15 yr after starting therapy was significantly greater for toxic than non-toxic patients. Finally, there was a marked difference in survival within the group of once-toxic patients, with those who continued markedly reduced doses of hydralazine for 18 months or more after toxic symptoms appeared, surviving more than twice as long as those who discontinued hydralazine within two months of their first toxic symptom. Part II, For 168 non-toxic white patients, whose hypertension was treated with hydralazine plus ganglioplegic agent, long-term survival was significantly related to therapeutic response as follows: (1) Patients with ‘controlled’ hypertension survived 60% longer than those with ‘partly controlled’ hypertension. (2) Patients who required 2 3 or less of their initial dose of hydralazine after a year of treatment survived 85% longer than those who required 3 2 or more of their initial dose. (3) Patients without leucopenia, anemia, or dysglobulinemia survived 50% longer than those with such changes. (4) Patients whose cholesterol levels fell more than 50 mg/100 ml of plasma below their pre-treatment values survived 70% longer than those whose levels increased.