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Background. There is considerable interest in the possible role of nitrate in gastric carcinogenesis, but little information on nitrate intake around the world. This is the first study to give comprehensive standardized data on nitrate excretion as a marker of intake, using 48 worldwide population samples. Methods. Urinary nitrate excretion has been shown to be a valid measure of nitrate intake in people under 50. This report presents data on 24-hour urinary nitrate excretion from urine collections obtained in the INTERSALT study, based on random samples of men and women aged 20-49 from each of 48 population samples in 30 countries. Results. There was large variation in urinary nitrate excretion both within and between samples ; within-sample (individual) distributions tended to be skewed towards higher values. Median values of the samples ranged from 0.42 mmol/day (Labrador, Canada) to 3.52 (Beijing, People's Republic of China) in men and 0.44 mmol/day (Colombia) to 3.44 (Beijing) in women. Overall, median values were higher in men than women by 11% on average (higher in men in 37 of 48 population samples). Comparison by geographical region of median values for men and women combined showed relatively low values in the samples in North America and Northern Europe (range 0.46-0.88 mmollday), slightly higher values in Western Europe and Africa (0.68-1.11), and intermediate to high values in Southern Europe, Eastern and Central Europe and India (0.86-2.47). The highest median values were found in the Far Eastern samples (up to 3.48). Median values in the Central and South American samples ranged from 0.48 mmol/day (Colombia) to 1.37 (Xingu Indians of Brazil, and Argentina). Conclusions. For the first time, these data give standardized information on urinary nitrate excretion from different geographical regions of the world, and provide a basis for the further exploration of the role of nitrate in the aetiology of disease in human populations.

The National High Blood Pressure Education Program (NHBPEP) was launched 20 years ago based on data from population studies and clinical trials that showed high blood pressure (HBP) was a major unsolved--but soluble--mass public health problem. The present review summarizes recent data from US prospective population studies on blood pressure--systolic (SBP), diastolic (DBP)--and cardiovascular risk. The outcome variables include blood pressure-related risks, primarily incidence and mortality from coronary heart disease, stroke, other and all cardiovascular diseases (CVD); also cardiac abnormalities (roentgenographic, electrocardiographic, echocardiographic); also, all-cause mortality and life expectancy. Data accrued during the past 20 years confirm that SBP and DBP have continuous, graded, strong, independent, etiologically significant relationships to the outcome variables. These relationships are documented for young, middle-aged, and older men and for middle-aged and older women of varying socioeconomic backgrounds and ethnicity. Among persons aged 35 years or more, most have SBP/DBP above optimal (120/80 mm Hg); hence, they are at increased CVD risk, ie, the blood pressure problem involves most of the population, not only the substantial minority with clinical HBP. For middle-aged and older persons, SBP relates even more strongly to risk than DBP; at every DBP level, higher SBP results in greater CVD risk and curtailment of life expectancy. A great potential exists for improved health and increased longevity through control of the blood pressure problem. Its realization requires a strategy combining population wide and high-risk approaches, the former to prevent rise of blood pressure with age and to achieve primary prevention of HBP by nutritional-hygienic means; the latter to enhance detection, treatment, and control of HBP. The newly expanded goals of the NHBPEP, aimed at implementing this broader strategy for the solution of the blood pressure problem, merit active support from physicians and all health professionals.

Specific causes of death were analyzed for 10,908 participants in the Hypertension Detection and Follow-up Program, to explore possible explanations for the observed excess 8.3-year mortality from all causes in hypertensives with low body mass. Although the cardiovascular mortality rate among men in the lowest decile of body mass (body mass index 21.96 or less) was 50% higher than that of men in the median class (body mass index 26.4-28.8), death rate for noncardiovascular deaths was more than 2 1/2 times higher in men with lean versus median body mass. The pattern was similar among women. Among noncardiovascular causes, striking differences in mortality rates between lean hypertensives and those of average body mass were observed for cirrhotic death (relative risk of 12+ in men and 11+ in women), for nonmalignant respiratory disease in men (relative risk of 7+), for violent death (both sexes), and for malignant neoplasms in men. Prevalence of smoking was almost twice as high in the lowest compared with the median body mass group; among the lean, excess deaths, particularly noncardiovascular deaths, were concentrated among smokers. Thus, male smokers in the lowest decile of body mass constituted only 3% of the study population, but contributed 8% of all deaths, 11% of all noncardiovascular deaths, and 22% of all cirrhotic deaths. A larger proportion of deaths occurred early in follow-up in the lean versus other hypertensives, suggesting occult disease among the lean at baseline. There was no evidence that more severe or treatment-resistant hypertension was present in or could explain excess mortality among the hypertensives with low body mass. The inference from the findings is not that overweight is protective for hypertensives nor that excess risk is due to leanness per se. Rather, a reasonable hypothesis, particularly from findings on specific causes of death, is that excess mortality in lean hypertensives is due to deleterious lifestyles, particularly smoking and excess alcohol intake, contributing to both leanness and risk of death.

The association between hypertension and a number of cardiovascular disease risk factors was assessed in the large population sample of Gubbio, a town in central Italy that dates back to medieval times. The data confirm those of previous studies showing that hypertension is strongly associated with other metabolic abnormalities, such as markedly overweight subjects, hyperuricaemia, hyperglycaemia, hypercholesterolaemia, that may be related to the aetiopathogenesis of high blood pressure and, in addition, compound the risk of major clinical cardiovascular events in people with hypertension. The findings are therefore relevant for prevention strategies. In addition, the association between erythrocyte sodium-stimulated lithium countertransport and hypertension is being studied.

ContextThree major coronary risk factors—serum cholesterol level, blood pressure, and smoking—increase incidence of coronary heart disease (CHD) and related end points. In previous investigations, risks for low-risk reference groups were estimated statistically because samples contained too few such people to measure risk.ObjectiveTo measure long-term mortality rates for individuals with favorable levels for all 3 major risk factors, compared with others.DesignTwo prospective studies, involving 5 cohorts based on age and sex, that enrolled persons with a range of risk factors. Low risk was defined as serum cholesterol level less than 5.17 mmol/L (

The appropriateness of current cardiovascular disease (CVD) risk factor guidelines in women continues to be debated.To present new data on the appropriateness of current CVD risk factor guidelines, for women and men, from long-term follow-up of a large population sample.Cardiovascular disease risk factor status according to current clinical guidelines and long-term impact on mortality were determined in 8686 women and 10503 men aged 40 to 64 years at baseline from the Chicago Heart Association Detection Project in Industry; average follow-up was 22 years.At baseline, only 6.6% of women and 4.8% of men had desirable levels for all 3 major risk factors (cholesterol level,5.20 mmol/L [200 mg/dL]; systolic and diastolic blood pressure,120 and80 mm Hg, respectively; and nonsmoking). With control for age, race, and other risk factors, each major risk factor considered separately was associated with increased risk of death for women and men. In analyses of combinations of major risk factors, risk increased with number of risk factors. Relative risks (RRs) associated with any 2 or all 3 risk factors were similar: for coronary heart disease mortality in women, RR= 5.72 (95% confidence interval [CI], 2.35-13.93), and in men, RR = 5.51 (95% CI, 3.10-9.77); for CVD mortality in women, RR = 4.54 (95% CI, 2.33-8.84), and in men, RR = 4.12 (95% CI, 2.56-6.37); and for all-cause mortality in women, RR = 2.34 (95% CI, 1.73-3.15), and in men, RR = 3.20 (95% CI, 2.47-4.14). Absolute excess risks were high in women and men with any 2 or all 3 major risk factors.Combinations of major CVD risk factors place women and men at high relative, absolute, and absolute excess risk of coronary heart disease, CVD, and all-cause mortality. These findings support the value of (1) measurement of major CVD risk factors, especially in combination, for assessing long-term mortality risk and (2) current advice to match treatment intensity to the level of CVD risk in both women and men.

Background Sodium-lithium countertransport (Na-Li CT) activity is high in persons with hypertension. This study investigated whether high Na-Li CT relates to development of hypertension. Methods and Results At the baseline visit of the Gubbio Population Study, 4210 people of the 5376 surveyed were 18 to 74 years old; of these, 1599 were hypertensive (systolic pressure ≥140 mm Hg, or diastolic pressure ≥90 mm Hg, or on antihypertensive drug therapy). Of the 2611 nonhypertensives, 302 did not have Na-Li CT measured and 580 did not participate in 6-year follow-up. This analysis, therefore, deals with data collected on 1729 men 18 to 74 years old and women 18 to 74 years old who at baseline were nonhypertensive and had Na-Li CT measurement. Compared with individuals who were nonhypertensive at baseline and follow-up, individuals with incident hypertension at follow-up (systolic pressure ≥140 mm Hg, or diastolic pressure ≥90 mm Hg, or on antihypertensive drug therapy) had higher baseline values of Na-Li CT, blood pressure, age, body mass index, plasma cholesterol, and alcohol intake ( P P −1 ·h −1 ). In univariate logistic regression, incidence of hypertension was related to baseline value of Na-Li CT, blood pressure, age, body mass index, plasma cholesterol, and alcohol intake ( P P Conclusions Na-Li CT is a predictor of hypertension risk in adults.

Abstract Sodium-lithium countertransport activity in red blood cells relates to blood pressure (BP) and the prevalence of hypertension. This study investigated in adults the relation of sodium-lithium (Na-Li) countertransport to BP change from baseline to 6-year follow-up. In the Gubbio Population Study, 4210 men and women were 18 to 74 years old at baseline (1983-1986), and 3766 had a valid baseline Na-Li countertransport measurement; of these, 2729 were reexamined at 6 years of follow-up (1989-1992) and made up the study cohort. At baseline, data collection included age, height, weight, BP, pulse rate, drug treatment, alcohol intake, ratio of sodium to potassium in spot urine, plasma cholesterol, and Na-Li countertransport in red blood cells. At 6-year follow-up, data for age, BP, and drug treatment were collected as at baseline. From baseline, average BP declined for people on antihypertensive medication at follow-up and for those with baseline BP greater than or equal to 140/90 mm Hg (systolic/diastolic) and did not change or increased for the remaining participants. In quartile and correlation analyses controlled for sex, baseline BP, and antihypertensive treatment, BP change related significantly and directly to baseline Na-Li countertransport. In multiple linear regression analyses done for the entire cohort with control for other confounders, the regression coefficient of baseline Na-Li countertransport to BP change over time was positive and borderline significant. The Na-Li countertransport coefficient was positive and significant when analyses were done with the use of a categorical value of baseline Na-Li countertransport (quartile 4 and quartiles 1 through 3 combined). In both models, the Na-Li countertransport coefficient was the strongest for people with baseline BP greater than or equal to 120/80 mm Hg or for people with baseline age of 45 years or older. In conclusion, Na-Li countertransport significantly relates to BP change over time in adults.

This report further examines the relation of body mass index (BMI) to associations of 24-hour urinary sodium, potassium, and sodium-potassium ratio with blood pressure in INTERSALT, a 52-center international study of electrolytes and blood pressure. Analyses without adjustment for BMI indicated average systolic pressure greater by 6.00 mm Hg per 100 mmol higher sodium and diastolic by 2.52 mm Hg. With adjustment for BMI, these values were reduced to 3.14 and 0.14 mm Hg, respectively. For the sodium-potassium ratio, blood pressure associations were stronger when not adjusted for BMI, and for potassium, adjustment generally had little effect. To explore possible interactions of these variables with BMI in relation to blood pressure, the 52 centers were divided into two groups of 26 based on whether the center median for BMI was less than or greater than or equal to 24.5 kg/m2, and individuals within each of the 52 centers were classified into lower- or higher-BMI groups based on individual BMI less than or greater than or equal to 24.1 kg/m2. Sodium and the sodium-potassium ratio were positively and significantly and potassium inversely and significantly related to systolic pressure in all four of these subgroups, and the sodium-potassium ratio and potassium were related to diastolic pressure in two and three subgroups, respectively. Electrolyte-blood pressure associations did not differ significantly between the two subgroups of centers or between the two subgroups based on individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

The focus here is on relationships between major risk factors and long-term mortality from coronary heart disease (CHD) and all causes, and on longevity, in Chicago cohorts: 25-year follow-up for Peoples Gas (PG) men aged 25-39 (n = 1,119), 30-year follow-up for PG men aged 40-59 (n = 1,235), 24-year follow-up for Western Electric (WE) men aged 40-55 (n = 1,882); also 15-year follow-up for five cohorts of the Chicago Heart Association (CHA) Study: men aged 25-39 (n = 7,873), 40-59 (n = 8,515), 60-74 (n = 1,490), and women aged 40-59 (n = 7,082) and 60-74 (n = 1,243); also 12-year findings for very low risk men (n = 11,098) and other men (n = 350,564) screened for the Multiple Risk Factor Intervention Trial (MRFIT). With a high degree of consistency, multivariate analyses showed independent positive relationships of baseline serum cholesterol, blood pressure and cigarette use to risk of death from CHD and all causes. For the WE cohort, with baseline nutrient data, dietary cholesterol was also independently related to these mortality risks. Combined risk factor impact was strong for both men and women of all baseline ages. Thus, for WE men, favorable compared to observed levels of serum cholesterol, blood pressure, cigarette use and dietary cholesterol were estimated to result in 24-year risk of CHD death 69% lower, all-cause death 42% lower and longevity 9 years greater. For CHA middle-aged and older women, favorable baseline levels of serum cholesterol, blood pressure and cigarette use were estimated to yield 15-year-CHD risk lower by about 60% and longevity greater by about 5 years. For MRFIT, very low risk men (serum cholesterol182 mg/dl, systolic/diastolic blood pressure120/80), nonsmokers, nondiabetic, no previous heart attack), compared to all others, observed 12-year death rates were lower by 89% for CHD, 79% for stroke, 86% for all cardiovascular diseases, 30% for cancers, 21% for other causes, 53% for all causes, and longevity was estimated to be more than 9 years longer. These findings indicate great potentials for prevention of the CHD epidemic and for increased longevity with health for men and women, through improved life-styles and consequent lower risk factor levels.

Population based data on 24-h urinary excretion of calcium, oxalate, magnesium, phosphate, uric acid and creatinine were collected from 220 children (aged 3-16 years) living in Cimitile, Campania, southern Italy. Mean excretion rates for 7 days were correlated with age, body weight, body mass index and height. The prevalence of hypercalciuria (greater than 4 mg/kg body weight) and of hyperoxaluria (greater than 60 mg/day) were 9.1% and 1.8%, respectively. The same 20 children were also identified as hypercalciuric when a calcium/creatinine ratio of greater than 0.15 was considered. No significant differences between boys and girls were found in the urinary excretion of the five constituents implicated in urolithiasis. The study data provide additional childhood reference values for urinary excretion of compounds related to stone formation.

An inverse association between social class and disease has frequently been reported; education, an indicator of social class, was negatively related to blood pressure in several studies. Reasons are not clear. INTERSALT, an international study on electrolytes and blood pressure, obtained data on years of education for 10,079 adults in 52 centers in 32 countries. Data presented here are for 47 centers, omitting five where the population in the sample had no education or no differences in educational level. Regression coefficients were calculated for the education-blood pressure association in each center. An inverse association was found for men in 28 centers and for women in 38. Center coefficients were combined to give a studywide estimate of that association. When adjusted only for age, systolic pressure in men was 1.3 mm Hg higher for 10 fewer years of education (p less than 0.05) and for women 4.5 mm Hg higher (p less than 0.001). However, when adjusted also for five lifestyle factors (24-hour sodium and potassium excretion, body mass index, alcohol intake, and smoking), these estimates were reduced by about one half, and the inverse association was no longer significant for men. Similar findings were obtained for diastolic pressure. Those with less education had on average higher sodium excretion, lower potassium excretion, greater body mass, and higher alcohol intake, all factors tending to increase blood pressure. Improvement of these factors, which help explain the differences in blood pressure related to years of education, has the potential to reduce the blood pressure disadvantage associated with lower socioeconomic status.

INTERSALT, an international cooperative study on electrolytes and other factors related to blood pressure, found, in within-population analyses involving 10,079 persons, a significant positive association between 24-hour urinary sodium excretion and systolic blood pressure and between the sodium/potassium ratio and systolic blood pressure. These significant findings were derived from analyses for individuals from all 52 centers and from the 48 centers remaining when persons from four low sodium centers were excluded. Potassium excretion of individuals was significantly and independently related inversely to their systolic blood pressure. For men and women, both separate and combined, the relation between sodium and systolic blood pressure was stronger for older than younger adults, perhaps reflecting the result of longer exposure with age or diminished capacity to handle a sodium load. Relations between electrolyte excretion and diastolic blood pressure in individuals were weaker than for systolic blood pressure. Body mass index and heavy alcohol consumption of individuals were strongly and independently related to blood pressure. In cross-population analyses with n = 52 or n = 48, sample median sodium excretion was significantly and independently related to the slope of systolic blood pressure and diastolic blood pressure with age. Other ecological analyses yielded inconsistent results. Four isolated populations showed low sodium excretion, low sodium/potassium excretion, low body mass index, and low alcohol consumption; sample median blood pressures were low, there was little or no upward slope of blood pressure with age, and high blood pressure was rare or nonexistent.

Background Evidence exists that cardiovascular risk factors influence progression toward end-stage renal failure. We tested the hypothesis that in nondiabetic middle-aged adults without macroalbuminuria, cardiovascular risk factors are related to urinary albumin excretion and prevalence of microalbuminuria, a sign of early nephropathy. Methods Cross-sectional analysis of data for 1567 participants in The Gubbio Population Study (677 men and 890 women), aged 45 to 64 years, without macroalbuminuria, without diabetes mellitus, and with fasting plasma glucose levels of less than 7.8 mmol/L (140 mg/dL). Data collection included albumin and creatinine excretion in timed overnight urine collection; levels of fasting plasma cholesterol, glucose, triglycerides, creatinine, and uric acid; creatinine clearance; red blood cell sodium-lithium countertransport; blood pressure; weight; height; medical history; smoking status; and alcohol intake. Urinary albumin excretion and prevalence of microalbuminuria were the dependent variables. Results Blood pressure, plasma cholesterol levels, smoking, and body mass index significantly related to urinary albumin excretion and prevalence of microalbuminuria. In analyses with control for multiple variables, relative risk for microalbuminuria (urinary albumin excretion, 20-199 µg/min) in men and women was 2.51 and 1.62, respectively, with 18 mm Hg higher (1 SD) systolic blood pressure; 2.25 and 2.10, respectively, with 1.0-mmol/L (40 mg/dL) higher plasma cholesterol level; 1.99 and 1.91, respectively, for smokers vs nonsmokers; and 1.83 and 1.33, respectively, with 4 kg/m 2 higher body mass index. Findings were similar for microalbuminuria defined as urinary albumin excretion of at least 25 µg/dL glomerular filtration rate. Conclusion Major cardiovascular risk factors are independent correlates of microalbuminuria in nondiabetic middle-aged adults.

Data from 10,559 men and women, age 30–64, participating in the morning and afternoon in a Chicago Health Department multiphasic screening project, were used to determine the effects of time of day and time since last meal on the values for plasma glucose one and two hours following oral challenge with 100 gm. of glucose. Mean plasma glucose values and rates of suspect glucose intolerance (based on several cutpoints) were sizeably higher in the afternoon than in the morning. In addition, plasma glucose values increased with time elapsed since the last meal, up to 10 hours postprandially. Thereafter, both one- and two-hour plasma glucose values tended to exhibit a decline. Analysis of covariance confirmed that fluctuations in glucose tolerance were related to time of day and time since last meal, but the effects of each parameter were exerted independently.

A four-year trial assessed whether less severe hypertensives could discontinue antihypertensive drug therapy, using nutritional means to control blood pressure. Randomization was to three groups: group 1—discontinue drug therapy and reduce overweight, excess salt, and alcohol; group 2—discontinue drug therapy, with no nutritional program; or group 3—continue drug therapy, with no nutritional program. In groups 1 and 2 patients resumed drug therapy if pressure rose to hypertensive levels. Loss of at least 4.5 kg (10+ lb) was maintained by 30% of group 1, with a group mean loss of 1.8 kg (4 lb); sodium intake fell 36% and modest alcohol intake reduction was reported. At four years, 39% in group 1 remained normotensive without drug therapy, compared with 5% in group 2. Study findings demonstrated that nutritional therapy may substitute for drugs in a sizable proportion of hypertensives or, if drugs are still needed, can lessen some unwanted biochemical effects of drug treatment. ( JAMA 1987;257:1484-1491)

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.

Data from 10,559 men and women, aged 30–64, participating in the morning and afternoon in a Chicago Health Department multiphasic screening project, were used to evaluate the relationship of time of day and time since last meal to group mean serum cholesterol, hematocrit, systolic and diastolic blood pressure, and heart rate. Serum cholesterol showed no definable differences with time of day and time since last meal. Hematocrit values tended to be slightly higher in the morning than in the afternoon and showed no consistent differences with time since last meal. Systolic blood pressure values, but not diastolic, were slightly higher in the afternoon than in the morning. Mean heart rates tended to be slightly higher in the afternoon and lower with time elapsed since last meal. All these differences were small and not of an order to present significant problems with regard to carrying out mass screening for these variables over the course of the day.

SUMMARY 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.

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.

This epidemiologic study explored the sex differential in risk of death from coronary heart disease in persons with or without clinically diagnosed diabetes or asymptomatic hyperglycemia. Use was made of 9-year follow-up data from the Chicago Heart Association Detection Project in Industry for 11,220 white men and 8,030 white women aged 35-64 years at entry to the Project (November 1967-January 1973). Both clinically diagnosed diabetes and asymptomatic hyperglycemia were associated with an increased risk of death from coronary heart disease. The extent of this association was greater in women than in men in regard to relative risk. However, absolute excess risk for both diabetics and those with asymptomatic hyperglycemia was larger for men than for women. Clinical diabetes appeared to be an independent risk factor for coronary heart disease in both men and women based on multivariate Cox regression analyses. On the other hand, for men, no significant independent effect of asymptomatic hyperglycemia was apparent. Women with asymptomatic hyperglycemia had significantly higher coronary heart disease death rates than normoglycemic women, with adjustment for major coronary heart disease risk factors; in multivariate analyses, the relationship of asymptomatic hyperglycemia to risk of coronary heart disease was of borderline significance (p = 0.054). This study indicates the independent associations of diabetes and possibly asymptomatic hyperglycemia with coronary heart disease mortality, with greater relative significance in women than in men.

We compared the effect on serum lipids of an alpha-blocker (prazosin) and a diuretic (hydrochlorothiazide) used as initial antihypertensive drug treatment for 102 men and women with less severe hypertension (average entry blood pressure, 148/97 mm Hg, with no major organ system damage). A two-center trial randomized patients to treatment with either prazosin or hydrochlorothiazide; the alternate drug was added if adequate blood pressure control was not achieved with the originally assigned drug, and patients were removed from any drug they were not able to tolerate. After an average of 40 weeks on the assigned drug regimen, a decline was observed in prazosin-treated patients in both serum total cholesterol (-9.3 mg/dl) and serum triglycerides (-33.9 mg/dl). In contrast, an increase in both these lipids was seen in hydrochlorothiazide-treated patients (+5.0 mg/dl for serum total cholesterol and +18.6 mg/dl for serum triglycerides). The net trial differences between the groups were 14.3 mg/dl for total cholesterol and 52.5 mg/dl for triglycerides, in favor of prazosin (p less than 0.001 for both comparisons). These differences in lipids between the two groups persisted into the second year of the trial (p less than 0.05). There were no significant differences between the drug groups in regard to the level of high density lipoprotein cholesterol or its subfractions or low density lipoprotein cholesterol. In patients who required a combination of the two drugs to achieve blood pressure control, the alpha-blocker diminished or eliminated the lipid-raising effects of the diuretic. Both drugs were similar in their ability to control the elevation of diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Intervention to control hypertension and prevent coronary heart disease was initially undertaken in the United States in the late 1950s. It was conducted along three lines: randomized controlled trials, community demonstration projects, and broad public health and medical care efforts involving both the general population and its high-risk strata. This article reviews findings from the United States trials, particularly those on the primary prevention of coronary heart disease by unifactorial means (such as fat-modified diet, serum cholesterol-lowering drugs, antihypertensive drug treatment) and by multifactorial interventions. Results of unifactorial and multi-factorial trials are discussed with reference to the prevention of high blood pressure. Studies in the United States are compared with research abroad, and current research needs are reviewed together with the implications for medical practice and public health. The United States population as a whole has a large high-risk segment. Since the late 1950s, significant population-wide changes have occurred in life-styles (diet, smoking, exercise habits), and this is especially true of the more educated. The proportion of persons with detected, treated, and controlled high blood pressure has risen markedly in all population strata. Consequently, a favorable shift has occurred in the population distribution of the major established risk factors: "rich" diet, hypercholesterolemia, high blood pressure, and cigarette smoking. It can be reasonably inferred that the steady and marked declines in death rates in the United States from coronary heart disease, stroke, all cardiovascular diseases, and all causes since 1968 are related to reductions in these risk factors.

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.

Ability to safely withdraw well-controlled mild hypertensives from drugs is being tested in a three-group randomized trial. Group I (intervention) was removed from drugs after the first 2 months of nutrition counseling. Counseling is continuing through the remaining years of the trial to achieve a minimum weight loss of 10 lb if overweight, reduction of sodium intake to less than 1,800 mg, and reduction of alcohol intake to not more than two drinks per day. Group II (the first control group) was also removed from drugs to see if previous long-term blood pressure control had a carryover effect without dietary change. Blood pressure is monitored frequently in both groups, with return to drug treatment in the event of specified blood pressure rise. Group III (the second control group) has remained on drugs for comparison of blood pressure and biochemical variables. In Group I mean 30-month weight loss was 8 lb, with 35% losing 10+ lb; sodium intake was reduced by 38%. Blood pressure control without drugs was maintained for 47% of Group I patients but only 16% of group II patients (P less than 0.05). These findings indicate it may be possible, after establishing good blood pressure control, to maintain control in a sizable proportion without medication, when reduction of weight, sodium, and alcohol intake is achieved.

Red blood cell membrane cation transport was measured in five population-based surveys and two randomized, controlled, dietary intervention studies to examine its associations with demographic, biological, and dietary variables in free-living individuals. A total of 508 individuals, 255 with high blood pressure, were studied. Both sexes, blacks and whites, and several age groups were represented. The intervention studies included short-term dietary sodium restriction in normotensive adolescents, and a 4-year multifactorial trial on weight, sodium, and alcohol in hypertensive adults. The findings from these surveys and intervention studies are summarized in this report. Sodium-stimulated lithium countertransport was significantly related to diastolic blood pressure in white adults (r = 0.28, p less than 0.001), and to systolic blood pressure in black children (r = 0.50, p less than 0.005) and white adolescents (r = 0.31, p less than 0.05). Lithium countertransport was related to sex and race, but not age. Body mass index had an independent relationship with lithium countertransport in some age groups. Lithium countertransport was lower in normotensive adults than in both younger and older hypertensive adults. Lithium countertransport did not differ significantly between subjects with hypertension treated with antihypertensive medications and those with untreated hypertension. Short-term dietary sodium restriction did not influence lithium countertransport in normotensive adolescents. Long-term dietary intervention was associated with low lithium countertransport in hypertensive adults able to maintain blood pressure control without medication. These findings indicate that lithium countertransport is related to blood pressure and hypertension among free-living individuals.

In 1975-1978, the Chicago Department of Health conducted a screening program that included measurements of blood pressure, heart rate, height, weight, triceps skinfold thickness, and arm circumference, and calculation of body mass index and muscle circumference for non-public school children. Based on data on 4,086 boys and girls aged 5-10 years from the program, this study examined the ethnic differences in blood pressure and heart rate among children of white, black, Latino, and Oriental ethnicity. Mean levels for both systolic and diastolic blood pressure were higher for Oriental and black children than for white and Latino children. These differences were independent of age, height, weight, and skinfold thickness. The black children had a much lower mean heart rate than the other children. A seasonal variation was observed for systolic blood pressure, i.e., with each sex group, the mean systolic blood pressure adjusted for age, skinfold thickness, and height tended to be higher in spring than in fall and winter. (Note-- no child was screened during the summer because of summer break.) With control for season, ethnic differences in systolic blood pressure disappeared, but not the ethnic differences in diastolic blood pressure and heart rate.

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.

The need to prevent and control high blood pressure (HBP), including so-called "mild" hypertension [diastolic blood pressure (DBP) 90-104 mm Hg in adults age 30+] stems from the extensive data on the increased risks due to these common blood pressure (BP) levels, including risk of catastrophic cardiovascular events (coronary, cerebrovascular, etc.), both nonfatal and fatal. Prospective population data from the national cooperative Pooling Project and the Chicago Heart Association Detection Project in Industry illustrate the extensively documented facts. They also show that only a small minority of middle-aged and older Americans have optimal low-normal BP levels, i.e., DBP less than 80 mm Hg (SBP less than 120). Thus, the problem of BP above optimal level for health over a long life span is a population-wide problem. The data also show that the great majority of excess catastrophic events attributable to elevated BP occur among people with DBP 90-104 and 80-89 mm Hg, levels very common in the population. Most people with such BP levels also have one or more other major risk factors (e.g., hypercholesterolemia, cigarette use, ECG abnormalities) and thus are at markedly increased risk, both relative and absolute. In addition to these excess risks for major illness, disability, and death, people with BP above optimal levels are more highly prone to other events, clinical and subclinical, that have adverse effects on long-term prognosis, including development of target organ damage and severe hypertension. These data lead to the following inferences about medical care and public health strategy: (a) A key task is, by safe nutritional-hygienic means, to shift the entire population distribution of BP downward, for both primary and secondary prevention of HBP. Such means include prevention and control of obesity, high sodium and alcohol intake, and sedentary habit, from early childhood on. (b) People with DBP 80-89 mm Hg need to be identified promptly, with institution of nutritional-hygienic measures to prevent development of frank hypertension and to correct other risk factors. (c) People with DBP 90-104 and higher need to be identified promptly, with institution of measures to normalize BP and control other major risk factors, by nutritional-hygienic means alone whenever possible or in combination with drug treatment for HBP when necessary to prevent organ system damage, serious illness, disability, and premature death.(ABSTRACT TRUNCATED AT 400 WORDS)

The Chicago study on the Primary Prevention of Hypertension (PPH) is a long-term, randomized controlled trial to test the ability of nutritional-hygienic non-pharmacological methods to prevent high blood pressure in hypertension-prone persons aged 30-44 years at entry. In order to assess the effects of this programme on cardiovascular responses to exercise, graded submaximal treadmill exercise tests were done serially at baseline and during the trial. Eighty-five participants (48 intervention, 37 control) successfully finished baseline and 2- or 3-year follow-up tests. The exercise maximal double product (DP) [systolic blood pressure (SBP) X heart rate/100] was significantly lower for both groups at 2-3 years compared with baseline, and this reduction was greater for the intervention than for the control group (-27.1 versus -15.5; P = 0.055). Similarly, improvement in maximal increase in DP (maximal DP minus standing DP) was greater for the intervention than the control group (-22.1 versus -9.9, respectively; P = 0.068). The lowest DP during the 6-min recovery period and the debt DP (lowest recovery DP minus standing DP) fell significantly at 2-3 years compared with baseline in the intervention but not in the control group (-12.7 versus -4.8; P = 0.017 for the first index, and -7.7 versus +0.9; P = 0.029 for the second). These interim data from this trial indicate that its intervention procedures favourably influenced cardiovascular responses to graded submaximal exercise.

A 5-year trial involving 201 men and women with high-normal blood pressure at baseline demonstrated the ability to reduce the incidence of hypertension in participants randomized to nutritional-hygienic intervention compared with a control group. The incidence of hypertension was 8.8% among 102 intervention group participants vs 19.2% among 99 control group members. The odds ratio for the incidence of hypertension in the control group was 2.4. Mean trial blood pressure also was lower in the intervention compared with the control group ( -1.2 and -1.9 mm Hg, respectively, for diastolic blood pressure at work-site and office visits and -1.3 and - 2.0 mm Hg, respectively, for systolic blood pressure at the two sites). Net weight loss in the intervention group averaged 2.7 kg during the trial; sodium intake was reduced by 25% and reported alcohol intake decreased by 30%. The majority of intervention participants also reported an increase in physical activity. Effect on blood pressure was related particularly to degree of weight loss. Results indicate that even a moderate reduction in risk factors for hypertension among hypertension-prone individuals contributes to the primary prevention of the disease. ( JAMA . 1989;262:1801-1807)

THE HYPERTENSION Detection and Follow-up Program (HDFP) was a national, multicenter, randomized, 5-year clinical trial of the effectiveness of antihypertensive therapy in reducing all-cause mortality in hypertensive participants screened from the general population. The study was funded under contract by the National Heart, Lung, and Blood Institute (NHLBI). Clinical centers in 14 US communities were selected by competitive contract review to participate in the study. Also selected were a Central Laboratory for standardized determinations of participant biochemical values, an ECG Center for standardized ECG interpretations, and a Coordinating Center for (1) data collection, (2) monitoring and analysis, (3) standardization, staff training, and regulation of study protocol, and (4) overall project coordination.

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.

INTERSALT found a significant association between 24-hour urine sodium excretion and systolic blood pressure in individuals. There was also a significant association between sodium and slope (increase) of blood pressure with age across population samples. The weight of evidence from animal-experimental, clinical, intervention, and epidemiological data favors a causal relation. INTERSALT data from 52 centers in 32 countries permit an estimate of effect on average population blood pressure of lower sodium intake. Based on the sodium-blood pressure association in individuals, it was estimated that a habitual population sodium intake that was lower by 100 mmol/day (e.g., 70 vs. 170 mmol/day) would correspond to an average population systolic pressure that was lower by at least 2.2 mm Hg. This size difference in systolic blood pressure in major US and UK population studies is associated with 4% lower risk of coronary death and 6% lower risk of stroke death in middle age. If habitual diet is both lower in sodium and higher in potassium with lower alcohol intake and less obesity, INTERSALT data estimate average population systolic pressure would be lower by 5 mm Hg. This was calculated to correspond to a 9% lower risk of coronary death and a 14% lower risk of stroke death. INTERSALT cross-population data also suggest that, with a 100 mmol/day lower sodium intake over the life span, the average increase in population systolic pressure from age 25 to 55 years would be less by 9 mm Hg, corresponding at age 55 to a 16% lower risk of subsequent coronary death and 23% lower risk of stroke death.(ABSTRACT TRUNCATED AT 250 WORDS)

2 years of experience in the first phase of a large cooperative national hypertension programme yielded data indicating that a good level of patient adherence can be achieved and that satisfactory blood-pressure control can be maintained long term. For 116 participants, all employed persons, dropout in the first year was 20% but only 3% dropped out in the second year. At the second annual examination, 82% of those still in the programme had diastolic pressures under 90 mm Hg, with an average reduction of 18 mm Hg. Thus, nearly two-thirds (64%) of all patients originally enrolled were both active and with normal levels of blood-pressure after two years. Only 18% of active programme-treated patients had diastolic pressure 90 mm Hg or higher at the second anniversary in contrast with 33% of patients referred to their own doctors. In programme-treated patients, standard medication was used; diuretics effectively lowered blood-pressure in a third of patients, and diuretics plus reserpine were effective for another 20%. Special features of the programme included assisance to physicians by health counsellor therapists. Methods for achieving a high adherence-rate and satisfactory blood-pressure control probably have wider applicability.

INTERSALT is an epidemiological study of electrolyte excretion and blood pressure in 10,079 men and women from 52 centres and 32 countries. The data were collected according to strict protocol with extensive quality control, and were analysed both in individuals and across centres. In the individual analysis, with adjustment for confounding variables, significant positive associations were observed between blood pressure and twenty-four hour sodium excretion, body mass index and alcohol intake, and significant negative associations between blood pressure and potassium excretion. For a number of reasons, it is likely that the size of these relationships was underestimated. Across centres, linear slope of blood pressure with age was positively related to median sodium excretion. These observations imply that a policy combining changes in sodium and potassium intake with reductions in obesity and alcohol consumption could bring important public health benefits.

This study used cross-sectional data for 19,704 white men and 13,895 white women from the Chicago Heart Association Detection Project in Industry (November 1967 to January 1973) to investigate whether weight explains the association between age and blood pressure, and in particular, whether age is associated with blood pressure and hypertension in the absence of overweight. The relations among age, relative weight, and blood pressure were examined through assessment of mean blood pressure levels and prevalence of hypertension in 25 subgroups stratified by age (18-24, 25-34, 35-44, 45-54, and 55-64 years) and by relative weight (less than 100%, 100-109%, 110-119%, 120-134%, and greater than or equal to 135%). For all five relative weight groups, for both men and women, mean diastolic blood pressure was higher at successive ages. This phenomenon was also seen for systolic blood pressure after ages 35-44 years for men, and after ages 25-34 years for women. On the other hand, the higher the relative weight was, the higher the blood pressure was. Regression analysis demonstrated that the observed relation between age and blood pressure was consistent for all five relative weight groups, including those at desirable weight. These data indicate that for US subjects, age and blood pressure are generally associated in the absence of overweight.

In a nationwide screening program, blood pressure measurements, family (parental) histories of hypertension, and self-evaluations of weight class were obtained for more than a half million people. Positive family history was associated with hypertension prevalence double that found in persons with negative history and was independent of weight. When overweight was also present, however, hypertension prevalence was three to four times as high. Hypertension was more likely to have been previously diagnosed in screenees if family history was positive. However, such screenees did not have a higher proportion receiving effective treatment than those with negative family history. When an index case of hypertension is found, other family members should be examined. For persons with positive family history, nutritional-hygienic recommendations to avoid overweight may be important in reducing the risk of becoming hypertensive. ( JAMA 241:43-46, 1979)