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This report, the third in a series on pulse pressure and pure systolic hypertension, examines the associations between blood pressure and the cardiovascular diseases and coronary heart disease, both cross-sectionally and prospectively, utilizing data from four Chicago epidemiologic studies, in an effort to determine whether or not a widened pulse pressure, or pure systolic hypertension, is an independent risk factor. In these analyses, blood pressure is divided into two components, one related to level and the other to pulse pressure, with pulse pressure redefined so that the association between pulse pressure and the prevalence of ECG abnormalities or mortality, indicates whether the endpoint is more strongly related to systolic or diastolic blood pressure. In these studies, blood pressure level is significantly related to both ECG abnormalities and mortality. In the cross-sectional analyses, pulse pressure is generally positively related to the prevalence of ECG abnormalities, indicating a stronger association for systolic blood pressure, and thus a possible association with pure systolic hypertension. However, in the prospective analyses, pulse pressure is generally not related to mortality, indicating an equal association with mortality for systolic and diastolic blood pressure in these studies. Thus, although the cross-sectional analyses generally support the hypothesis that a widened pulse pressure, or pure systolic hypertension, is an independent risk factor for the cardiovascular diseases and coronary heart disease, the prospective analyses do not.

Two methodological problems in characterizing an individual's plasma glucose level are examined in this study. First, how large is the intra-individual variation of an individual's 1-hr post-load glucose level and for this estimated intra-individual variation what are the probabilities of misclassifying individuals based on a one-time measurement only of glucose level? Second, do different tests—i.e. fasting, 1-hr, 2-hr post-load, GTT—yield consistent ranking for the same individual? The first of these was explored with data on subsamples from the Chicago Peoples Gas Company (PG) study and the Chicago Heart Association Detection Project in Industry (CHA) study; the second, with data from the Chicago Coronary Prevention Evaluation Program (CPEP). For both the PG and CHA studies, the estimated ratios of the intra- to inter-individual variances were generally higher for post-load plasma glucose than blood pressure, heart rate, weight and serum uric acid. The conditional probabilities of misclassifying individuals into quintiles or deciles based on one measurement of 1-hr post-load glucose were also estimated from these data. These estimated probabilities indicate that the possible attenuation due to intraindividual variation cannot abolish a strong association; however, it may create some problem if the relationship is not very strong. Furthermore, both rank correlation and quintile classification analyses show that fasting, 1-hr and 2-hr plasma glucose level characterize individuals differently. Thus it is possible that the inconsistent results of previous studies, all using a one-time measure of plasma glucose, are partially due to the large intra-individual variation of this variable, and the use of methods that are not highly consistent in their classification of individuals.

With advancing age from youth on, there is an increase in mean serum cholesterol level of populations in "western" industrialized countries. Since serum cholesterol is one of the established major risk factors for premature coronary heart disease, it is important to explore the degree to which this age trend is physiologic or due to modern life styles. This study used cross-sectional data for 19,730 white men and 13,872 white women from the Chicago Heart Association Detection Project in Industry to investigate one aspect of this question: does weight explain the association between age and serum cholesterol, in particular whether older age is associated with higher serum cholesterol in the absence of overweight. The relationships among age, relative weight, and serum cholesterol were examined through assessment of mean serum cholesterol levels in 25 subgroups stratified by age (18-24, 25-34, 35-44, 45-54, 55-64) and by relative weight (less than 100, 100-109, 110-119, 120-134, greater than or equal to 135). Age and serum cholesterol were positively associated with each other. In women, it was a simple, linear relationship. In men, the degree of this positive association was less in people over age 35-44 than people in younger ages. These age-cholesterol patterns were present in men and women at desirable weight. However, in men aged 18-54, the positive association between age and prevalence of marked hypercholesterolemia (serum cholesterol greater than or equal to 250) was lower in people at desirable relative weight in comparison to those at higher relative weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Because systolic blood pressure rises more sharply than diastolic blood pressure for those middle aged and beyond, leading to an increasing prevalence with advancing age of elevated systolic blood pressure without elevated diastolic pressure, i.e. so-called pure systolic hypertension, the question arises as to whether or not factors that have been shown to be related to blood pressure and hypertension are related to pure systolic hypertension or to 'classical' hypertension, i.e. hypertension defined solely by the level of the diastolic pressure. This question was examined in four Chicago epidemiologic studies by examining the associations between several variables and pulse pressure, with pulse pressure redefined so that the association between a variable and pulse pressure indicated whether the variable was more strongly related to systolic or diastolic blood pressure. In these four studies, glucose, heart rate and cigarette use tended to show a stronger association with systolic pressure, suggesting a possible association with pure systolic hypertension, while hematocrit, serum cholesterol, and uric acid tended to be more strongly associated with diastolic pressure, or equally associated with systolic and diastolic pressure, suggesting an association with 'classical' hypertension. Relative weight tended to be more strongly associated with systolic pressure under the age of 35 and more strongly associated with diastolic pressure after age 45.

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.

1. 1. Four multivariate statistical methods—partial correlation, multiple cross classification, multiple logistic regression, and multiple linear regression—were used to study the relationship between six variables and blood pressure in over 13,000 men and women, white and black, ages 30–44 and 45–64 surveyed in two low-income Chicago communities. The analyses were carried out separately for eight age-sex-race groups. The six variables were relative weight, resting heart rate, plasma glucose 1 hr after 100 g oral load, hematocrit, serum cholesterol and age. 2. 2. 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 ≤0.001. 3. 3. Hematocrit was independently and additively related to diastolic—but not to systolic—pressure for the four age-race groups of women, but only for one of the four age-race groups of men. 4. 4. The findings with respect to serum cholesterol and blood pressure were generally negative. 5. 5. Even within the narrow age groups studied—ages 30–44 and 45–64—age was significantly related to systolic level particularly ( p values ≤0.01 or ≤0.001), independent of the five other variables. 6. 6. When multivariate regression equations and their coefficients, computed from the 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 30–44 in the four sex-race groups, from 47–69 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 as much as 20 times as high for the highest quintile of expected prevalence as 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 four of the independent variables and identifying the substratum with any two, three or all four high.

Studies of possible association between asymptomatic hyperglycemia and coronary disease were conducted among middle-aged employed men in Chicago. In one cohort, frequency of ECG abnormalities at baseline was examined among men at different glucose levels. In univariate analysis, those at the highest glucose levels had higher rates of ECG evidence of CHD, but this association did not remain when such factors as age, blood pressure, weight, cholesterol and cigarettes were taken into account in multivariate analysis. Among the studies, long-term follow-up to mortality (10, 13 and 15 yr) showed inconsistent findings on association of hyperglycemia and subsequent death. In one cohort (Gas Company men followed for 10 yr after a 1-hr post-load glucose determination) a positive glucose-mortality association was found in both univariate and multivariate analysis. But in the two remaining cohorts (Gas Company 13 yr after casual glucose determination and Western Electric 15 yr after 2-hr post-load determination), no such association was found. While differences in method and sample size as well as other limitations may have contributed to the differences observed, the inconsistency of the findings do not permit a conclusion that asymptomatic hyperglycemia is a positive coronary risk factor.

This report, the second in a series on pulse pressure and pure systolic hypertension, examined in prospective analyses the associations between both the initial values of five variables and the changes in these variables and pulse pressure, utilizing data from three Chicago epidemiologic studies, in order to determine whether variables known to be related to blood pressure and hypertension are related to pure systolic hypertension or ‘classical’ hypertension. In these analyses, follow-up pulse pressure, which was measured from 2–5 years after the initial measurement of the other variables, was redefined so that the association between the initial value or change and pulse pressure indicated whether the initial value or change was more strongly related to follow-up systolic or diastolic blood pressure. In these three studies, only the initial value for cigarette use had a consistent positive association with follow-up pulse pressure. Change in heart rate was generally positively related to follow-up pulse pressure, while the initial value was not. For relative weight and serum cholesterol, both the change and the initial value tended to be negatively related. For glucose, the association was not consistent for either the initial value or the change. The results from these prospective analyses thus suggest that cigarette use is related to pure systolic hypertension, rather than ‘classical’ hypertension.

Because systolic blood pressure rises more sharply with age than diastolic blood pressure, leading to an increasing prevalence with advancing age of elevated systolic blood pressure without elevated diastolic pressure, i.e. so-called pure systolic hypertension, the question arises as to whether or not pure systolic hypertension has its own etiology and pathogenesis. Since pure systolic hypertension is characterized by a widened pulse pressure, the present report examined the association between relative weight and pulse pressure, both cross-sectionally and prospectively, in addition, to the association between relative weight and the level of blood pressure, in four Chicago epidemiologic studies. The positive association between relative weight and the level of blood pressure in these studies, in both cross-sectional and prospective analyses, reaffirms the finding in previous studies of a positive association between weight and blood pressure and the prevalence and incidence of hypertension. However, the results of these studies did not generally support the hypothesis that relative weight is related to pulse pressure, and thus possibly to pure systolic hypertension.

Among the 40,000 employed men and women screened in Chicago industry, 7841 white men age 40–59 formed the cohort studied to determine significance of asymptomatic hyperglycemia for coronary disease. In cross-sectional analysis of frequency of ECG abnormalities, those in the upper 2 1 2 % of the glucose distribution had higher rates of such abnormalities than the rest of the group, and men in the highest quintile likewise had higher rates of ECG abnormalities than were seen in the lowest quintile. Analysis of these data using the multiple logistic showed inconsistent positive association of glucose with prevalence of ECG abnormalities defined by the Whitehall and Pooling Project criteria, but no association with definite MI, on ECG. In 5-yr mortality follow-up, while men with overt diabetes experienced coronary death rates 2–3 times higher than those without such a diagnosis, similar univariate analysis that excluded diagnosed diabetics showed no association between glucose level and coronary mortality. In multivariate analysis as well, no association between initial glucose and subsequent coronary or cardiovascular mortality was seen, although all causes mortality rates were significantly related to glucose levels. The inconsistent results between univariate and multivariate analyses, as well as between cross-sectional and prospective findings, do not support a conclusion that asymptomatic hyperglycemia is a major coronary risk factor.