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Objectives: To determine the levels and time trends of blood pressure and body size in a healthy population of youth., Study Design: Minneapolis, Minnesota, fifth through eighth grade public school children (aged 10 to 14 years) were surveyed in 1986 and 1996. Blood pressure, height, and weight were measured by technicians trained to the same rigorous protocol at each time period, and comparisons were made between the 2 groups (1986 and 1996)., Results: In 1986 and 1996, 8222 and 10,241 children, respectively, were measured with participation rates of over 93%. African American, Hispanic, Native American, Asian, and non-Hispanic white groups were all represented. Systolic blood pressure was significantly higher and diastolic blood pressure lower in 1996 than in 1986 in all ethnic and gender groups. Weight and body mass index (wt/ht2) were significantly higher in all groups in 1996. Adjustment for body size largely eliminated the systolic blood pressure differences but had no effect on measured diastolic blood pressure., Conclusions: Body size and systolic blood pressure are rising among school children. Weight and body mass index show substantial increases over 10 years (1986-1996). Diastolic blood pressure fell for unclear reasons. These changes may have future health implications for cardiovascular disease, as these youth move into adulthood.

Background: Weight gain is of concern during early development because adult obesity and its cardiovascular consequences appear to have their origins during childhood. Insulin resistance is known to be related to obesity. Thus, weight gain beginning in childhood may influence the development of insulin-induced cardiovascular risk during adulthood., Methods and Results: We monitored 679 individuals from 7.7+/-0.1 years of age with repeated measures of height, weight, and systolic blood pressure (SBP) until 23.6+/-0.2 years of age, when blood samples were obtained for measurements of insulin and lipids. Initial childhood weight, body mass index (BMI), and height were significantly correlated with young adult weight, BMI, and height and with fasting insulin, lipids, and SBP. The increases in weight and BMI but not height during childhood were significantly related to the young adult levels of insulin, lipids, and SBP., Conclusions: These data suggest that weight gain in excess of normal growth during childhood is a determinant of adult cardiovascular risk. The finding in multiple linear regression analysis that weight gain during childhood rather than the childhood weight at 7.7 years of age is significantly related to young adult risk factors suggests that a reduction in weight gain could reduce subsequent levels of cardiovascular risk.

Purpose: To examine the correlates of plasma leptin, including fasting insulin, adiposity, and several health habits and behaviors among a nondiabetic multiethnic population., Methods: A cross-sectional study was conducted among 25-44 year old African-Americans (n = 126), Cuban-Americans (n = 107), and non-Hispanic whites (n = 189) randomly selected from Dade County Florida. Fasting leptin levels were correlated with fasting insulin, percent body fat, smoking, alcohol use, and physical activity within each sex. Multiple linear regression and analysis of covariance were used to estimate the independent determinants of plasma leptin concentration separately among men and women., Results: Stepwise linear regression analyses revealed statistically significant associations of leptin with percent body fat, fasting insulin, cigarette smoking, and physical activity (both inversely) among men (p < 0.05 for each). Among women, percent body fat, fasting insulin (both positively), cigarette smoking, and alcohol use (inversely) were independent predictors of leptin levels explaining over 70% of the variance. Analyses of covariance revealed that women had higher adjusted mean leptin levels than men (13.1 ng/ml vs. 5.9 ng/ml; p < 0.001), whereas no separate effect of ethnicity was noted., Conclusions: Although adiposity was the strongest correlate of leptin levels, fasting insulin and several health habits and behaviors were independently associated with leptin. After adjustment for these factors, women had significantly higher mean leptin levels than men. The independent association among leptin and insulin levels is intriguing and suggests additional avenues for epidemiologic research.

It is apparent from the results of the 1995 and 1998 surveys reported by Kimm et al in this issue of Pediatrics that pediatricians are interested in blood pressure and lipids but uncertain about the management of these coronary heart disease (CHD) risk factors. Data from longitudinal epidemiologic studies initiated in pediatric cohorts support the important role for pediatricians in the detection of children at risk for CHD, and detection should be followed by effective intervention/treatment programs. However, the latter may be difficult in most office practices, because of the intensive effort by specialized personnel required to successfully reduce CHD risk.

Purpose: A survey to establish both the need and subject areas for a possible new set of ethics guidelines for epidemiologists was conducted among a random sample of 300 North American (Canada, Mexico, and United States) members of three major United States-based professional epidemiology organizations., Methods: An 88% response rate revealed wide agreement on topics to be included in any new set of guidelines, but uncertainty prevailed about the need for new guidelines; 41% agreed that there was a need to develop a new set, 43% had no opinion, and 16% disagreed., Results: There was almost no difference in preferences between men and women for topics to be included in a new set of guidelines, or between those aware or unaware of extant ethics guidelines in epidemiology. Fifty-four percent were aware of such guidelines and only 29% of these said they could describe the content of the guidelines., Conclusion: More needs to be done to evaluate the utility of ethics codes in epidemiology.

Purpose: The aim of this study was to examine the associations among fasting insulin, adiposity, waist girth, and blood pressure among a nondiabetic multiethnic population., Methods: A cross-sectional study was performed among 25-44-year-old African-Americans (n = 159), Cuban-Americans (n = 128), and non-Hispanic whites (n = 207) selected from Dade County, Florida. Fasting insulin levels were correlated with resting blood pressure level within each ethnic group. The separate effects of percentage body fat and waist girth on the association between blood pressure and insulin were analyzed in multiple linear regression and analysis of covariance., Results: Fasting insulin was positively associated with systolic (r = 0.26-0.39; P < 0.01) and diastolic blood pressure (r = 0.19-0.30; P = 0.10 to P < 0.001) among women of all ethnic groups and among non-Hispanic white men (r = 0.27; P < 0.05). Stepwise linear regression analyses revealed statistically significant associations between systolic and diastolic blood pressure and fasting insulin level in non-Hispanic whites independent of other covariates, including sex and percentage body fat (P < 0.001). Fasting insulin was also independently and significantly related to systolic blood pressure among African-Americans (P = 0.02). Among Cuban-Americans, sex and percentage body fat were the main correlates of blood pressure level. Analysis of covariance revealed a relationship between insulin and blood pressure that was independent of waist girth among men and women., Conclusions: Fasting insulin level and blood pressure were positively associated among African-Americans and non-Hispanic whites. This association was not entirely due to the common association with percentage body fat or waist girth.

This study was intended to clarify the relation between fasting insulin, lipids, and blood pressure in adolescents before the onset of hypertension and to examine the association of these data with similar data obtained in their parents. The participants in this study were 183 adolescents 14 to 18 years old (96 girls) completing a 4-year intervention trial and their parents (164 mothers, 122 fathers). Blood pressure was measured twice on the right arm in a seated position using a random-zero sphygmomanometer. Fasting blood samples were obtained for lipid and insulin analyses. Fasting insulin was significantly correlated with systolic blood pressure in the adolescents and also in the parents before and after adjustment for body mass index. Fasting insulin was correlated significantly with levels of cholesterol, triglycerides, and HDL and LDL cholesterol in the adolescents. It was correlated only with triglycerides and HDL-cholesterol in mothers and fathers. After adjustment for body mass index, the correlations between fasting insulin and lipids in the children were not significant. A significant relation was shown between children's systolic blood pressure and mothers' fasting insulin and systolic blood pressure. Significant correlations were found between the children's and fathers' triglycerides and HDL-cholesterol, whereas significant correlations were found for fasting insulin and all lipids between mothers and children, and these remained significant after adjustment for body mass index. These results show (1) a significant relation between fasting insulin and both lipids and systolic blood pressure in adolescents and (2) a significant relation for these factors between adolescents and their parents. Although weight appears to play an important role in this relation during adolescence, genetic and environmental factors other than those mediated via weight may control insulin metabolism within families. The data support a role for studies during early biological development to address these issues.

Background: Whether subjects identified as being at increased risk of coronary heart disease (CHD) death by heart rate adjustment of exercise-induced ST-segment depression will benefit from therapy aimed at reducing risk factors has not been examined., Methods and Results: Exercise ECGs were performed in 11,880 men from the Usual Care (UC) and Special Intervention (SI) groups of the Multiple Risk Factor Intervention Trial. UC men were referred to customary sources of care in the community; SI men received counseling on smoking cessation and dietary reduction of cholesterol, and stepped-care therapy for hypertension. An abnormal ST-segment response to exercise was defined according to standard criteria as > or = 100 microV of additional horizontal or downsloping ST-segment depression and by an ST-segment/heart rate (ST/HR) index >1.60 microV/bpm. After 7 years of follow-up, CHD mortality was significantly lower in SI than UC men with an abnormal ST/HR index (2.4%, 19/786 versus 5.3%, 39/729, P=.005) but was comparable in SI and UC men with a normal ST/HR index (1.6%, 84/5154 versus 1.3%, 70/5211, P=NS). Risk reduction in SI men with an abnormal ST/HR index was independent of age and other cardiac risk factors. In contrast, there was no significant difference in CHD death rate between the smaller groups of SI and UC men with an abnormal test by standard criteria (3.6%, 7/192 versus 2.7%, 5/186, P=NS)., Conclusions: An abnormal ST/HR index identifies men in whom therapy aimed at reducing CHD risk factors reduces the risk of CHD death by 61%. These findings support the application of heart rate adjustment of ST depression for screening of asymptomatic subjects at increased risk of CHD to identify those who will benefit most from risk factor-reduction programs.

A number of coronary heart disease risk factors have been identified that often cluster together to increase the risk of macrovascular disease. This cluster is referred to as the insulin resistance syndrome, and the risk factors commonly include dyslipidemia, elevated blood pressure, an android pattern of body fat distribution, and glucose intolerance. Whether hyperinsulinemia or insulin resistance per se provides a common pathway for these metabolic abnormalities is unclear. The authors studied 50 nondiabetic persons who had completed a euglycemic hyperinsulinemic clamp protocol in addition to a 75-g oral glucose tolerance test and other measures of the coronary risk profile. Using principal-component analysis, we reduced nine coronary risk factors to two uncorrelated factors that explained 54.5% of the variance. Factor 1 consisted of positive loadings for uric acid, systolic and diastolic blood pressure, triglyceride concentration, and waist girth and negative loadings for HDL cholesterol and the rate of insulin-mediated glucose disposal (M, in milligrams per kilogram of body weight per minute). M also loaded on factor 2, along with fasting insulin and glucose concentrations, diastolic blood pressure, and waist girth. The observation that M loaded on both factors suggests that a resistance to insulin action may provide the mechanism uniting the features of the insulin resistance syndrome. Hyperinsulinemia with concomitant insulin resistance may be necessary to produce this metabolic derangement, as well as the increased risk of macrovascular complications.

A central requirement for epidemiologic studies and clinical trials is a bias-free, objective determination of cardiac incidence rates between comparison groups. Epidemiologic studies and clinical trials frequently use changes in the Minnesota Code to document incident ischemic events. An electrocardiographic (ECG) classification system was developed to document significant ECG pattern change using objective comparison rules for side-by-side annual ECG comparison. Previously, we showed that major evolving Q waves were strongly and independently associated with total and coronary disease mortality. Using baseline-to-annual ECG comparisons in the Multiple Risk Factor Intervention Trial, we evaluated major evolving Q waves, minor evolving Q waves combined with major evolving ST-T waves and major evolving ST-T waves alone for their prognostic associations with coronary, cardiovascular, and total mortality during 16 years of follow-up. The 16-year coronary mortality rate in men with evolving minor Q waves plus evolving ST-T waves had an average adjusted relative risk of 4, equivalent to that of a major evolving Q wave. These risk ratios held whether a clinical infarction had occurred. Silent evolving ST-T waves without Q-wave change had an average adjusted relative coronary mortality risk of 1.6. Serial comparison methodology documents additional incident ischemic ECG events beyond the traditional major Minnesota Q-code change used in older epidemiologic studies. The procedure is standardized, quantitative, and repeatable. It is applicable for any study, present or past, that used Minnesota coding. The method is also well suited for incorporation in computer analysis programs.

Among 35,192 postmenopausal, predominantly white women in Iowa age 55-69 years and free of cancer, we collected baseline history, dietary information, and anthropometric data by mail in 1986. We ascertained the 8-year incidence (62 new cases) of renal cell carcinoma using the Iowa Surveillance, Epidemiology, and End Results (SEER) register, the National Death Index, and mail follow-up. Risk factors for renal cell carcinoma included increasing age, increasing weight (either current, maximum adult weight, or weight at ages 18, 30, or 50 years), greater waist-to-hip ratio, and a history of blood transfusion. Total dietary calcium was associated independently with a reduced risk of renal cell carcinoma. No other dietary micro- or macronutrients or food groups were predictive of the development of renal cell carcinoma. Other previously identified risk factors were not confirmed: most notably, there was no increased risk from a history of hypertension, after adjustment for diuretic use. History of ever-use of diuretics was associated with a twofold increased risk of renal cancer, although the strength of association was markedly reduced after adjustment for age, weight, waist-to-hip ratio, and calcium intake.

Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication.

An association between blood pressure and insulin sensitivity among normotensive African-Americans has not been demonstrated consistently in epidemiologic studies. Part of the discrepancy may be due to studying persons with profound obesity-an insulin-resistant state itself. The association between insulin-mediated glucose uptake (i.e., insulin sensitivity) and blood pressure was examined among 25 nondiabetic African-American and 28 white non-Hispanic persons aged 25-44 years who ranged from normal weight to obese, using the hyperinsulinemic euglycemic clamp technique. In bivariate analyses, insulin sensitivity was inversely related to systolic (p < 0.01) and diastolic blood pressure (p = 0.08) among African-American persons and to diastolic blood pressure among white non-Hispanic subjects (p < 0.05). Covariate adjustment for age and sex had only a marginal effect on these results. When the data were pooled and further adjusted for ethnicity, insulin sensitivity remained significantly associated with both systolic and diastolic blood pressure (p < 0.01 for each). To consider the effect of obesity, body mass index (BMI) was divided at the sample median (26.5 kg/m2) and the analyses were repeated within each stratum. Among those whose BMI was below the median value, each increment in insulin sensitivity was associated with a 2-mmHg decrease in systolic blood pressure (p = 0.02). These results suggest that ethnicity was not a strong effect modifier in this sample and indicated that insulin sensitivity was inversely related to blood pressure level in these normotensive African-American and white, non-Hispanic participants.

Objectives: We sought to assess the effect of heart rate adjustment of ST segment depression on risk stratification for the prediction of death from coronary artery disease., Background: Standard analysis of the ST segment response to exercise based on a fixed magnitude of horizontal or downsloping ST segment depression has demonstrated only limited diagnostic sensitivity for the detection of coronary artery disease and has variable test performance in predicting coronary artery disease mortality. Heart rate adjustment of the magnitude of ST segment depression has been proposed as an alternative approach to increase the diagnostic and prognostic accuracy of the exercise electrocardiogram (ECG)., Methods: Exercise ECGs were performed in 5,940 men from the Usual Care Group of the Multiple Risk Factor Intervention Trial at entry into the study. An abnormal ST segment response to exercise was defined according to standard criteria as > or = 100 micro V of additional horizontal or downsloping ST segment depression at peak exercise. The ST segment/heart rate index was calculated by dividing the change in ST segment depression from rest to peak exercise by the exercise-induced change in heart rate. An abnormal ST segment/heart rate index was defined as >1.60 micro V/beats per min., Results: After a mean follow-up of 7 years there were 109 coronary artery disease deaths. Using a Cox proportional hazards model, a positive exercise ECG by standard criteria was not predictive of coronary mortality (age-adjusted relative risk [RR] 1.5, 95% confidence interval [CI] 0.6 to 3.6, p = 0.39). In contrast, an abnormal ST segment/heart rate index significantly increased the risk of death from coronary artery disease (age-adjusted RR 4.1, 95% CI 2.7 to 6.0, p < 0.0001). Excess risk of death was confined to the highest quintile of ST segment/heart rate index values, and within this quintile, risk was directly related to the magnitude of test abnormality. After multivariate adjustment for age, diastolic blood pressure, serum cholesterol and cigarettes smoked per day, the ST segment/heart rate index remained a significant independent predictor of coronary death (RR 3.6, 95% CI 2.4 to 5.4, p < 0.001)., Conclusions: Simple heart rate adjustment of the magnitude of ST segment depression improves the prediction of death from coronary artery disease in relatively high risk, asymptomatic men. These findings strongly support the use of heart rate-adjusted indexes of ST segment depression to improve the predictive value of the exercise ECG.

The Minnesota code (MC) is a classification system for electrocardiograms (ECGs) that is used for ECG coding in epidemiologic studies. As the MC measurement procedures and rules are complex, visual coding is time-consuming and error-prone. Automation should reduce measurement and coding errors. The authors developed an MC program, closely adhering to the MC regulations. To validate the program, a test set of 300 ECGs containing a wide variety of codable patterns was collected. The ECGs were coded independently by the program and by an experienced human reader. A reference code ("truth") was established by resolving disagreements through a consensus procedure. If the computer and human agreed, they were considered to be correct. Sensitivity and specificity were computed for each of the nine main code categories of the MC, both for the computer and for visual coding. The results show that the program is as good as or better than the human reader for sensitivity and specificity of all MC categories. Particularly noteworthy is the good program performance for arrhythmia coding. Most coding differences between the program and truth arise from small, borderline measurement differences in combination with the all-or-none character of the coding criteria. In conclusion, computerized Minnesota coding is a valuable alternative or supplement to visual coding.

The association of the Type A behavior pattern with change in blood pressure was examined in a multiethnic sample of schoolchildren. Blood pressure was assessed in 1978 (mean age = 8 years) and approximately biannually thereafter through 1987-1990, when a post-high school screening was completed. The Matthews Youth Test for Health (MYTH) was completed by the teachers of a sample of participants in 1982 (n = 502). The Jenkins Activity Survey (JAS) was completed by all adolescents who participated in the post-high school screening (n = 816). Males were more likely to be classified as Type A than were females by the JAS and the MYTH. Type A status was not associated cross-sectionally with elevated blood pressure. JAS-assessed Type B males had significantly higher mean post-high school fourth- and fifth-phase diastolic blood pressures than did Type A males (70.2 mmHg vs. 68.2 mmHg, p < 0.05; 68.1 mmHg vs. 65.2 mmHg, p < 0.01). JAS-assessed Type A/B status was not associated with 10-year change in blood pressure. MYTH-determined Type B females tended to have higher diastolic blood pressures than MYTH-determined Type A females throughout the 10-year study period. Results from this study did not confirm the hypothesis that Type A participants would have significantly higher blood pressures than Type B participants at the time of Type A assessment; nor did they confirm the hypothesis that Type A participants would exhibit greater increases in blood pressure than Type B participants over a 10-year period.

Objective: To determine the extent to which gender differences in the rate of insulin-mediated glucose disposal are influenced by differences in body fatness., Design: A cross-sectional study of a biracial sample of men and women drawn from a population-based study., Subjects: Twenty-five 25-44 year old residents of Dade County, FL. Twenty-five African-Americans (14 men and 11 women) and 28 white, nonHispanics (15 men and 13 women). All participants were free of diabetes mellitus (WHO Criteria)., Measurements: All persons volunteered to undergo a hyperinsulinemic euglycemic clamp procedure to determine the rate of insulin-mediated glucose disposal (insulin sensitivity, M). Several measures of body fatness were quantified and the percentage body fat determined according to published equations., Results: Men and women had similar unadjusted M values. Within each gender and ethnic group M was inversely related to percentage body fat (r = -0.55 to -0.84; p < 0.05). After adjustment for percentage body fat, women were more insulin sensitive than men (10.1 vs 5.1 mg/kg/min among African-Americans and 10.1 vs 6.9 mg/kg/min among white, nonHispanics; p < 0.05 for each). When M was expressed per unit of fat free mass, women were still significantly more insulin sensitive than men (p < 0.05 for each ethnic group). In multivariate analyses, gender and percentage body fat were independently related to M in both ethnic groups accounting for 70% of the variance among African-American participants and 34% of the variance among white nonHispanic participants., Conclusion: The similar M values between men and women despite the higher percent body fat among women indicate that women are more insulin sensitive in muscle tissue than men. This was substantiated when M was normalized for fat free mass. This 'insulin advantage' may be related to the lower risk of coronary disease experienced by women and the loss of this advantage may in part underlie the stronger deleterious effects of diabetes that women suffer.

The South Florida Program on Aging and Health was initiated in 1992 with the aim to assess physical and mental health of the elderly in Dade County and provide a basis for public health policy. This report describes the methodology applied in the study and preliminary screening results in a probability sample of 2,400 African American, Cuban American and white non-Hispanic American elderly men and women. Of 2,013 participants screened by May 1995, 11.5% had cognitive impairment. An increase in prevalence from 4-7% to 25-36% with advancing age was found among men and women of each group, from the youngest (65-74) to the oldest (85+ years). Male and female prevalences were similar but vary by ethnic group and age.

Clinical recognition of hypertensive cardiac involvement depends primarily on use of noninvasive methods. The performance of 8 electrocardiographic (ECG) criteria sets were compared with an echocardiographic standard in the treatment of Mild Hypertension Study. Electrocardiograms were computer processed to define the following ECG criteria sets: (1) Casale/Devereux, (2) Cornell product, (3) Cornell voltage, (4) 12-lead voltage product, (5) sum of 12-lead voltage, (6) Rautaharju, (7) Sokolow-Lyon, and (8) Romhilt-Estes. Echocardiographic left ventricular (LV) mass index was calculated by using the Penn convention on a biracial population of 834 men and women. Correlations between ECG and echocardiographic LV mass index were modest (<0.40). ECG-LV hypertrophy sensitivity at 95% specificity was < 34%. The Casale/Devereux ECG criteria showed the highest average sensitivity (17%) at 95% specificity for all race-sex groups. Whites had significantly higher correlation values than blacks. ECG correlations with LV mass index were consistently improved by including systolic blood pressure and body mass index. ECG criteria sets appear to be optimized for white men. The study findings confirm the poor ECG sensitivity and correlation with echocardiographic LV mass and suggest: (1) further refinement of ECG criteria alone in white men is unlikely to improve its relationship with LV mass; and (2) combining the electrocardiogram with other non-ECG variables or noninvasive measurements offers the best strategy for improving ECG sensitivity and its prognostic value.

Background: Increased left ventricular mass (LVM) by echocardiography is associated with increased risk of cardiovascular disease. Thus, it is of interest to compare the effects of both pharmacological and nonpharmacological approaches to the treatment of hypertension on reduction of LVM., Methods and Results: Changes in LV structure were assessed by M-mode echocardiograms in a double-blind, placebo-controlled clinical trial of 844 mild hypertensive participants randomized to nutritional-hygienic (NH) intervention plus placebo or NH plus one of five classes of antihypertensive agents: (1) diuretic (chlorthalidone), (2) beta-blocker (acebutolol), (3) alpha-antagonist (doxazosin mesylate), (4) calcium antagonist (amlodipine maleate), or (5) angiotensin-converting enzyme inhibitor (enalapril maleate). Echocardiograms were performed at baseline, at 3 months, and annually for 4 years. Changes in blood pressure averaged 16/12 mm Hg in the active treatment groups and 9/9 mm Hg in the NH only group. All groups showed significant decreases (10% to 15%) in LVM from baseline that appeared at 3 months and continued for 48 months. The chlorthalidone group experienced the greatest decrease at each follow-up visit (average decrease, 34 g), although the differences from other groups were modest (average decrease among 5 other groups, 24 to 27 g). Participants randomized to NH intervention only had mean changes in LVM similar to those in the participants randomized to NH intervention plus pharmacological treatment. The greatest difference between groups was seen at 12 months, with mean decreases ranging from 35 g (chlorthalidone group) to 17 g (acebutolol group) (P = .001 comparing all groups). Within-group analysis showed that changes in weight, urinary sodium excretion, and systolic BP were moderately correlated with changes in LVM, being statistically significant in most analyses., Conclusions: NH intervention with emphasis on weight loss and reduction of dietary sodium is as effective as NH intervention plus pharmacological treatment in reducing echocardiographically determined LVM, despite a smaller decrease in blood pressure in the NH intervention only group. A possible exception is that the addition of diuretic (chlorthalidone) may have a modest additional effect on reducing LVM.

The objective of this study was to compare serum calcium levels, dietary calcium intake, and urinary calcium excretion between junior high students with high-normal and low-normal blood pressure. The study was conducted in 11- to 14-year-old children recruited after blood pressure screening of 5th to 8th grade Minneapolis and St. Paul Public School students. Comparisons were made between a group of 243 children selected from the upper 15 percentiles of the blood pressure distribution (high-normal group) and 40 children randomly selected from the lowest 10% of the blood pressure distribution (low-normal group). Blood samples were obtained from the participants at clinic visits conducted after school. Calcium measurements were based on the principle that serum calcium is found in three forms: 1) an ionized fraction; 2) a fraction complexed with organic anions such as citrate, phosphate, and lactate; and 3) a protein-bound fraction. Dietary calcium intake was determined from food diaries, and urinary electrolytes were determined in 24-h urine collections. Serum total calcium levels were not significantly different between groups. However, serum ultrafilterable, true ionized, ionized normalized for pH, and complexed calcium levels were significantly greater in the low-normal group. There was no significant difference in 24-h intake of calcium or other nutrients between the groups. The low-normal group excreted significantly more calcium than the high-normal group, but there were no significant differences in sodium, potassium, or chloride excretion. This report of the relation between calcium and blood pressure represents the first study in children or adolescents to include serum, dietary, and urine data.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography is becoming commonplace in clinical trials relating to hypertension for assessing changes in left ventricular mass (LVM). Factors affecting variability need to be considered in the design and management of such studies. These include (1) standardization of recordings and readings, (2) quality of recordings, (3) choice of sonographer vs. cardiologist readers, and (4) reader and temporal variability in measurements. The Treatment of Mild Hypertension Study (TOMHS) provides data and experience concerning these issues. TOMHS was a randomized trial of 902 participants, men and women, conducted in four clinical centers comparing six treatments for mild hypertension. M-mode echocardiograms were recorded at baseline and follow-up by centrally trained sonographers for assessment of LVM. Initial study design specified that each tracing be read by two sonographers with a study cardiologist adjudicating major differences in measurements. Poor agreement between sonographer readings prompted a change in design requiring one of two study cardiologists to read all tracings, with the same cardiologist reading all serial studies for a participant. Common tracings were read to assess interreader variability. The percentage of unreadable tracings varied by center (0.4-14.2%) and increased over follow-up. Reader agreement between the two cardiologists for LVM was greater (r = 0.83) than between sonographers (r = 0.68) or between sonographers and cardiologists (r = 0.64). The agreement between sonographer and cardiologist readings varied by center (range of r = 0.54-0.81), the highest correlations being in the two centers with physician echocardiographers. The intraclass correlation across visits for LVM was 0.66, being similar for all visit pairs. The standard deviation of the difference between baseline and follow-up LVM was 46 g using cardiologist readings, 51 g for readings made by the same sonographer, and 68 g for readings made by different sonographers, a difference that is large enough to appreciably affect sample size and power for studies. High-quality echocardiographic data can be obtained in multicenter trials, but this requires the continued training of sonographers and readers and ongoing monitoring of quality of tracings and measurements.

Electrocardiographic abnormalities of 200 asymptomatic, chronic cocaine abusers (aged < or = 45 years, 69% black) admitted for rehabilitation (group 1) were compared with 38 cocaine abusers treated in the emergency room (group 2), 21 cocaine abusers who died suddenly (group 3), and 425 control subjects from the general population. In group 1, 39% of electrocardiograms were abnormal: Increased QRS voltage was noted in 27%, ST elevation in 22%, ST-T changes in 17%, and prior myocardial infarction in 3%. Increased QRS voltage (35% vs 10%, p = 0.00007) and ST elevation (26% vs 13%, p = 0.0278) were more prevalent in blacks than in whites. With use of Minnesota coding, electrocardiograms in group 1 were compared with those of 141 black and 284 white men (aged < 40 years) from the general population. ST elevation was more prevalent in both black (22% vs 8%, p = 0.00073) and white (15% vs 1%, p < 0.00001) cocaine abusers than in the general population. Compared with group 1, group 2 had higher prevalence of sinus tachycardia (16% vs 1%, p = 0.0002), supraventricular tachycardia (5% vs 0%, p = 0.024), ST-T changes (34% vs 17%, p = 0.0164), and QTc > 440 ms (26% vs 4%, p = 0.00003); mean QTc was also greater among group 2 subjects (427 +/- 38 vs 404 +/- 19 ms, p < 0.0001). In group 3, QTc was > 440 ms in 6 of 8 subjects (75%) with 12-lead electrocardiograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To determine whether elevated blood pressure tracks to a greater degree in overweight than in lean children., Design: Prospective cohort study., Methods: We examined 758 adolescents (mean age 13.4 years) who participated in a longitudinal study of blood pressure. The degree of tracking was examined by cross-classification of sex-specific tertiles of systolic blood pressure (SBP) and body mass index determined at baseline and 5 years later. Those children that were in the highest tertile of SBP and body mass index were considered to be 'overweight with elevated blood pressure'. Those that were in the highest tertile of SBP but lowest tertile of body mean index were considered to be 'lean with elevated blood pressure'., Results: Of those boys that were initially classified as lean with elevated blood pressure, 38% remained so classified compared with 54.6% of those that were initially classified as overweight with elevated blood pressure. Among the girls the respective proportions were 48 and 44.2%. The subjects of each sex who were lean with elevated blood pressure were significantly shorter at baseline than their overweight counterparts, and over the follow-up period experienced a greater mean increase in SBP than their overweight peers. This difference was almost totally explained for the boys once the difference in height change was taken into account. For the girls a difference of 5.9 mmHg remained after covariate adjustment for the change in height., Conclusion: These results fail to support the hypothesis that blood pressure tracks differently in obese and in lean adolescents, particularly once differences in sexual maturation are considered.

Because height is a more appropriate index of maturation than weight for use with normative blood pressure (BP) data, we developed normative BP levels for children, by sex, while accounting for age and height simultaneously. Eight U.S. studies used in the Report of the Second Task Force on Blood Pressure Control in Children and one additional study of BP in U.S. children were reanalyzed to develop age-sex-height-specific values for normative BP values among 56,108 children, aged 1 to 17 years, seen at 76,018 visits. Height percentiles were computed on the basis of standard National Center for Health Statistics growth charts. When height is taken into account, more short children (10th age-sex-specific height percentile) and fewer tall children (90th age-sex-specific height percentile) are likely to be classified as hypertensive than when the current age-sex-specific percentiles of BP alone are used. Tables are provided for boys and girls separately, by single year of age (1 to 17 years) and by the 90th and 95th percentiles of systolic blood pressure and diastolic blood pressure (fifth phase of Korotkoff sounds) for selected age-sex-specific height percentiles based on standard U.S. growth charts.

Objective: To compare six antihypertensive interventions for the treatment of mild hypertension., Design: Randomized, double-blind, placebo-controlled clinical trial., Setting: Four hypertension screening and treatment centers in the United States., Participants: Hypertensive men and women, aged 45 to 69 years, with diastolic blood pressure less than 100 mm Hg., Intervention: Sustained nutritional-hygienic advice to all participants to reduce weight, dietary sodium intake, and alcohol intake, and increase physical activity. Participants were randomly allocated to take (1) placebo (n = 234); (2) chlorthalidone (n = 136); (3) acebutolol (n = 132); (4) doxazosin mesylate (n = 134); (5) amlodipine maleate (n = 131); or (6) enalapril maleate (n = 135)., Main Outcome Measures: Blood pressure, quality of life, side effects, blood lipid levels and analysis of other serum components, echocardiographic and electrocardiographic changes, and incidence of cardiovascular events over an average of 4.4 years of follow-up., Results: Blood pressure reductions were sizable in all six groups, and were significantly greater for participants assigned to drug treatment than placebo (-15.9 vs -9.1 mm Hg for systolic blood pressure and -12.3 vs -8.6 mm Hg for diastolic blood pressure; P < .0001). After 4 years, 59% of participants assigned to placebo and 72% of participants given drug treatment continued on their initial medication as monotherapy. A smaller percentage of participants assigned to the drug-treatment groups died or experienced a major nonfatal cardiovascular event than those assigned to the placebo group (5.1% vs 7.3%; P = .21). After including other clinical events, the percentage of participants affected was 11.1% for those in the drug-treatment groups and 16.2% for those in the placebo group (P = .03). Incidence rates of most resting electrocardiographic abnormalities were lower and quality of life was improved more for those assigned to drug-treatment groups rather than the placebo group. Differences among the five drug treatments did not consistently favor one group in terms of regression of left ventricular mass, blood lipid levels, and other outcome measures., Conclusions: As an initial regimen, drug treatment in combination with nutritional-hygienic intervention was more effective in preventing cardiovascular and other clinical events than was nutritional-hygienic treatment alone. Drug-treatment group differences were minimal. Pending results from large-scale clinical trials to evaluate drug treatments for their effect on cardiovascular clinical events, these findings support the recommendations of the new fifth Joint National Committee report regarding treatment choices for people with stage 1 ("mild") hypertension.

Objective: To test the hypothesis that history of blood transfusion is associated with an increased incidence of cancer in older women., Design: Prospective cohort study., Setting: General community in the state of Iowa., Participants: Random sample of 37,337 cancer-free Iowa women ages 55 to 69 years., Measurements: Transfusion history was assessed with a mailed questionnaire completed in January 1986. Cancer incidence in 5 years was ascertained by a population-based cancer registry., Results: Women who had ever received a blood transfusion were at an increased risk for non-Hodgkin lymphoma (relative risk (RR) = 2.20; 95% CI, 1.35 to 3.58) and kidney cancer (RR = 2.53; CI, 1.34 to 4.78). The relative risks for these cancers were greater with decreasing time from first transfusion. No increased risk occurred for cancers of the breast, lung, uterine corpus, ovary, pancreas, colon, rectum, skin (melanoma), or for all cancers considered together., Conclusion: These findings suggest that previous blood transfusion may be a risk factor for non-Hodgkin lymphoma and kidney cancer but is not associated with the most common neoplasms.

The roots of essential hypertension extend back into the first two decades of life, suggesting that effective intervention during those years may lead to a reduction in the incidence of adult hypertension. Decreasing the dietary sodium/potassium ratio offers a potentially effective approach to blood pressure reduction. This study tested the feasibility of 3-year sodium reduction or potassium supplementation in adolescents and the effect of these interventions on the rate of rise of blood pressure during adolescence. After 19,452 5th to 8th grade students were screened, 210 from the upper 15 percentiles of blood pressure distribution (105 boys, 105 girls) were randomly assigned to one of three groups: low sodium diet (70 mmol sodium intake per day), potassium chloride supplementation (normal diet plus 1 mmol/kg potassium chloride per day), or placebo (normal diet plus placebo capsule). Capsules for the potassium chloride and placebo groups were administered in a double blind protocol. Blood pressure was measured every 3 months for 3 years. The effect of the intervention was determined by comparing the rate of rise (slope) of blood pressure among the groups using a random-coefficient growth curve model. The boys groups and the girls placebo group had similar positive blood pressure slopes that were significantly different from zero. The girls low sodium group had a slightly negative slope (significantly lower than the slope of the girls placebo group), and the girls potassium group had a slightly positive slope. Both of these slopes were not significantly different from zero and were significantly lower than the slopes of the respective boys groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To test the hypothesis that both body mass index (expressed as the ratio of weight in kilograms per height in meters squared) and the ratio of waist circumference to hip circumference are positively associated with mortality risk in older women., Design: Prospective cohort study with a 5-year follow-up period., Setting: General community., Participants: Random sample of 41,837 Iowa women aged 55 to 69 years., Main Outcome Measure: Total mortality (1504 deaths)., Main Results: Body mass index, an index of relative weight, was associated with mortality in a J-shaped fashion: rates were elevated in the leanest as well as in the most obese women. In contrast, waist/hip circumference ratio was strongly and positively associated with mortality in a dose-response manner. Adjusted for age, body mass index, smoking, education level, marital status, estrogen use, and alcohol use, a 0.15-unit increase in waist/hip circumference ratio (eg, a 15-cm [6-in] increase in waist measurement in a woman with 100-cm [40-in] hips) was associated with a 60% greater relative risk of death. The observed associations were not explained to any great degree by bias from weight loss prior to baseline or higher early deaths among lean participants., Conclusions: Waist/hip circumference ratio is a better marker than body mass index of risk of death in older women. Waist/hip circumference ratio should be measured as part of routine surveillance and risk monitoring in medical practice.

The relation between central adiposity, measured by the waist/hip circumference ratio (WHR), and 4-year risk of fatal coronary artery disease was examined in a large cohort (n = 32,898) of women aged 55 to 69 years. The age-adjusted relative risk of death from coronary artery disease (115 deaths) was 3.3 for women in the highest tertile of WHR compared to the lowest tertile (95% confidence interval: 2.0, 5.6). After adjustment for age, body mass, smoking, physical activity, estrogen use, marital status, and alcohol intake, the relative risk of coronary death for women in the middle and highest tertiles versus those in the lowest tertile of WHR were 1.3 and 2.8, respectively (P for linear trend < 0.001). Further adjustment for hypertension and diabetes mellitus reduced the estimates slightly to 1.2 and 2.0, but the trend in relative risk remained statistically significant (P = 0.03). In contrast, body mass index showed no independent association with coronary death. Hypertension, diabetes mellitus, cigarette smoking, estrogen nonuse, and being unmarried were significant predictors of greater risk of coronary death in the multivariate model. These results indicate that central adiposity, reflected by an increased WHR, is an important risk factor for death from coronary artery disease in women, most of whom were postmenopausal. The association of central adiposity with risk of coronary death is independent, for the most part, of its association with hypertension and diabetes.

Objective: To estimate the independent contribution of the blood pressure cuff bladder width: mid-upper arm circumference (CW:AC) ratio to the variability in systolic blood pressure (SBP), diastolic blood pressure phase 4 (DBP4) and diastolic blood pressure phase 5 (DBP5) in children and adolescents, and its impact upon the estimate of prevalence of high blood pressure derived at screening., Design: Use of cuffs with a CW:AC ratio below 40% causes overestimation of the true blood pressure level. With higher CW:AC ratios the level is underestimated. National recommendations for adults state that the CW:AC ratio is optimal at approximately 40%, but no consistent recommendations exist for children., Methods: We measured SBP and diastolic blood pressure phases 4 and 5 in 811 boys and 771 girls aged 10-17 years (93% participation rate). In each subject the blood pressure was measured with a cuff conforming to the 40% rule (recommended cuff), with one smaller (mean decrease in the CW:AC ratio:7.4%), and with one larger (mean increase in the CW:AC ratio:10.2%). Cuffs were used in random order., Results: Smaller cuffs gave significantly higher blood pressure readings. With the larger cuff there were significant mean decreases. The differences were independent of the blood pressure level obtained with the recommended cuff. The impact upon the estimate of the prevalence of high blood pressure was substantial., Conclusions: Selection of the proper cuff size is important for children and adolescents, in order to avoid both over- and underdiagnosis of hypertension.

Although many reports have shown that obesity (as defined by weight for height indices) tends to run in families, considerably fewer data are available concerning the familial resemblance of body fat distribution as defined by the waist to hip ratio (WHR), which is a risk factor for coronary heart disease. This question was examined among 712 participants of the Minneapolis Children's Blood Pressure Study. For each family member separately (son, daughter, father and mother) the distribution of the WHR was divided into quintiles. Quintiles of WHR were cross-classified between child and parent to examine the proportion of subjects clustering in each quintile. A significantly higher than expected proportion of parent-child WHRs clustered in the top quintile. For example, 42.5% of sones were placed in the top quintile of their father's WHR (P less than 0.001) and 36.7% of daughters were placed in the top quintile of their mother's WHR (P less than 0.001). Multiple linear regression analyses revealed that these findings were independent of parent and child body mass indices and other covariates. These results indicate significant familial aggregation of body fat distribution and may aid in suggesting specific primary preventive strategies targetted at appropriate families to reduce the risk of cardiovascular disease.

Blood pressure variability is an important consideration in hypertension trials for determining required sample size and consequently making accurate outcome statements. The Hypertension Prevention Trial was a randomized controlled trial carried out in 1983-1986 in four US clinics on men and women with high normal diastolic blood pressure. This trial provided an opportunity to assess conditions affecting blood pressure measurement variability. Trained blood pressure observers measured systolic and diastolic blood pressures twice, 30 seconds apart, using a random-zero sphygmomanometer. The quality of blood pressure measurements was assessed by computing the variability of the two readings per participant-visit for each blood pressure observer at each study clinic. Other sources of variability investigated included observer digit preference, time of day, and ambient temperature. On the basis of data from this population, it is estimated that the standard deviation of blood pressure values can be reduced by 5% by taking two measurements per participant-visit. An additional reduction of variability can be effected by having the duplicate blood pressure measurements made by different blood pressure observers. In special instances where the range of blood pressure values is very restricted, use of the random-zero sphygmomanometer can increase or decrease the among-participant variability in blood pressure values, depending upon where the distribution of blood pressure values is centered.

Sudden death in sleep occurs in substantial numbers among young men in South-East Asia. The frequencies of electrocardiographic abnormalities were measured in groups with varying risks of such sudden death. The mean heart-rate-corrected QT interval (QTc) was significantly (p less than 0.05) greater among 123 Laotian refugees in Thailand at high risk (405 [95% confidence interval 397-413] ms) than in 77 Laotian refugees in the United States at lower risk (364 [359-369] ms) and 199 non-Asian US residents at negligible risk (358 [354-362] ms). Among refugees in Thailand, prolonged QTc interval was associated with poor thiamine status and a history of seizure-like episodes in sleep. Thiamine deficiency may be a cause of prolonged QT interval and sudden death in this region.

The blood pressures and body sizes of children aged 10-15 years in the Minneapolis and St. Paul, Minnesota, public schools were measured during 1986 and 1987. The sample consisted of 1,680 Southeast Asian refugees--including 219 Cambodians, 1,086 Hmong, 149 Lao, and 226 Vietnamese--and 3,424 blacks and 11,336 whites. Mean systolic blood pressure in Hmong boys was higher than that in black boys and white boys. Mean systolic blood pressures of Hmong, Lao, and Vietnamese girls were lower than those of black girls and white girls. The mean diastolic blood pressures of Hmong boys and of Cambodian and Hmong girls were greater than those of blacks and whites of the same sexes. Southeast Asian children were shorter and weighed less than black children and white children. Body size may confound associations between ethnic groups and blood pressures and may obscure the problem of hypertension among the smaller Southeast Asian children. Southeast Asian boys had greater mean systolic blood pressures than did black and white boys across all weight strata; a similar contrast among girls did not reveal this difference. The risk of hypertension, defined by US National Heart, Lung, and Blood Institute guidelines, was assessed in multiple logistic regression analyses that controlled for differences in weight, height, age, and pulse rate. The odds ratios for hypertension, relative to blacks and whites of the same sexes, were 2.69 (95% confidence interval (CI) 1.85-3.65) in Hmong boys, 2.89 (95% CI 1.35-6.21) in Lao boys, 2.10 (95% CI 1.03-4.28) in Cambodian girls, and 1.49 (95% CI 1.00-2.20) in Hmong girls. Hypertension and subsequent cardiovascular disease may emerge as a significant problem among Southeast Asian refugees in the United States.

The Sosium-Potassium Blood Pressure Trial in Children (NaKS), is a clinical trial in a healthy, free living population of children and adolescents. It is designed to test the hypotheses that a reduction in dietary sodium and/or an increase in potassium intake will decrease the rate of rise in blood pressure during normal maturation in children and adolescents with high normal blood pressure. Screening was conducted in 19,452 students in grades 5-8 in Minneapolis and St. Paul between January 1986 and May 1987. After screening, 3,223 students were found to have blood pressures that fulfilled the initial eligibility criteria for the study, and of these, 643 (20.0%) attended the orientation meeting, i.e., the first clinic visit. A total of four clinic visits, designed to test the willingness and capability of the potential participants to comply with the study protocol were conducted prior to randomization. At the conclusion of the four prerandomization visits, 243 children (7.5% of the initially eligible children) agreed to be randomized to one of four trial groups: low-sodium diet; potassium supplement administration; placebo-treated control group; and a no-treatment control group (to test the effect of acclimatization on blood pressure measurements) that will not be seen after randomization until the 4-year termination of the study. The first participant was randomized into the study on June 17, 1986, and the last on December 29, 1987. The potassium and placebo capsules are administered double-masked. Participants will be examined and receive intervention instruction four times yearly for 4 years counted from the date of their randomization. All groups were comparable with regard to distribution of school district, sex, and race and with respect to baseline physical characteristics. Results from this study will provide information about the feasibility and effect of dietary intervention during childhood and adolescence on the prevention of essential hypertension.

We measured blood pressure differences by cuff size in 181 adults aged 25 to 74 years, allocated to a random sequence that involved the measurement of blood pressure using a small cuff, a large cuff, and an appropriate cuff as determined by standardized arm circumference measurement. Systolic and diastolic blood pressure were underestimated by 3-5 mm Hg in men and 1-3 mm Hg in women when the cuff was one size larger than appropriate. Systolic and diastolic blood pressure were overestimated by 2-6 mm Hg in men and 3-4 mm Hg in women when the cuff was one size smaller than appropriate. In addition, 30-40% of subjects were "misclassified" when blood pressure cutpoints were used to define hypertension.

There is a need for caution in measuring blood pressure in the obese. Problems related to adequate cuff-bladder size and shape are apparent from a review of the literature. Imperfections in experiments comparing intra-arterial/indirect blood pressure measurements remain. Cuff characteristics, as well as cuff-bladder width and length, can bias measurement of blood pressure in the obese. Authoritative committee recommendations and the differing needs of blood pressure measurement in obese adults and children still need to be rationalized. Manufacturing faults of cuff bladder and cuff availability continue to be a problem for blood pressure measurement in the obese. Measurement of blood pressure in large obese and large muscular arms may require different adjustments for cuff width and arm circumference. Nomograms for adjusting blood pressure recording in the obese are inadequate. The most important adjustment for measuring blood pressure in the obese derives from choosing the correct cuff width-arm circumference (CW/AC) ratio. Such action reduces the intersubject variability of blood pressure measurement in clinical and epidemiologic studies. Past studies probably overestimated blood pressure level in the obese and so underestimated the risk of elevated blood pressure in the obese.

The associations of body mass and body fat distribution, as measured by waist-to-hip circumference ratio, with serum concentrations of sex hormones and sex hormone binding globulin were examined in 88 postmenopausal women. Body mass index (BMI) was significantly and negatively associated with sex hormone binding globulin (SHBG) (r = -0.41), luteinizing hormone (LH) (r = -0.40) and follicle stimulating hormone (FSH) (r = -0.38) and was also significantly positively associated with both total and free oestradiol (r = 0.40 and 0.45, respectively). Waist-to-hip circumference ratio was significantly negatively correlated with SHBG (r = -0.53), LH (r = -0.35), and FSH (r = -0.35). After adjustment for BMI and other related factors, waist-to-hip circumference ratio was significantly and negatively associated with SHBG, LH, and FSH, and demonstrated a significant curvilinear relationship with free testosterone. These results suggest that in postmenopausal women, abdominal adiposity is associated with a relatively more androgenic sex hormone profile.

Studies that examine the effect of altered body weight or dietary sodium on blood pressure level are reviewed. Emphasis is placed on studies that compare the effects of weight reduction or sodium restriction in separate comparison groups or analyze the independent effect of the two intervention modalities in multiple regression analysis. Additional analyses of the Hypertension Prevention Trial data are presented. Most studies, where comparison can be made, suggest a greater effect for weight reduction than for the achieved, moderate, or short-term reduction in sodium intake on subsequent lowering of blood pressure; the lowering effect on blood pressure of weight reduction is independent of the effect of dietary sodium restriction. However, long-term (over a year) substantial reductions (up to 70 meq/day) of dietary sodium have not been achieved in comparative trials, nor are the effects of combined weight and sodium reduction in the prevention and treatment of hypertension quantified. Future studies and potential problems are discussed.

The relationship between body fat distribution, measured by the ratio of waist-to-hip circumferences (WHR), and the 2 year incidence of diabetes mellitus was examined in a cohort of 41,837 women aged 55-69 years. The 399 women who reported the new onset of diabetes had a significantly greater mean body mass index (kg/m2) and WHR than non-cases. After adjustment for body mass index (BMI), age and education level using multivariate logistic regression, WHR was a significant independent predictor of diabetes in a dose-response fashion. Cases were 4.6 times (95% CI = 3.8, 5.6) more likely than non-cases to be in the upper tertile of WHR and 2.2 times (95% CI = 1.8, 2.7) more likely to be in the middle tertile. Women in the highest tertiles of both WHR and BMI had a 14.4-fold (95% CI = 9.5, 21.9) higher risk of diabetes than women in the lowest tertiles. These results demonstrate that increased abdominal adiposity is a significant independent risk factor for the development of diabetes mellitus in older women.

Measurement of diastolic blood pressure is complicated by the presence of two diastolic Korotkoff phases (fourth phase and fifth phase) in many children and adults. In the present study, diastolic fourth phase and diastolic fifth phase were evaluated in 1986-1987 in 19,274 Minneapolis-St. Paul school children aged 10-15 years. Approximately 50 percent of the children had no difference between fourth phase and fifth phase (i.e., fourth phase - fifth phase = 0) and 15 percent had a difference of only 1-4 mmHg. However, the fourth phase - fifth phase difference was 5-10 mmHg in 20 percent, 11-20 mmHg in 11 percent and greater than 21 mmHg in 3 percent of the children. Statistical analyses showed that the fourth phase - fifth phase difference tended to be greater in boys than girls and in older than younger children, was positively related to height, systolic blood pressure and fourth phase blood pressure, and negatively related to body mass index and fifth phase blood pressure. Using fifth phase instead of fourth phase in 10-12-year-old children and fourth phase instead of fifth phase in 13-15-year-old children to define diastolic blood pressures significantly changed the prevalence for significant diastolic hypertension by 2-3 percent.

The Treatment of Mild Hypertension Study (TOMHS) is a randomized, double-blind clinical trial currently being conducted to compare the effects of nonpharmacologic therapy alone with those of 1 of 5 active drug regimens combined with nonpharmacologic therapy, for long-term management of patients with mild hypertension. Six classes of drugs were studied: (1) acebutolol (beta blocker), (2) amlodipine (calcium antagonist), (3) chlorthalidone (diuretic), (4) doxazosin (alpha 1 antagonist), (5) enalapril (angiotensin-converting enzyme inhibitor) and (6) placebo. All participants received nutritional-hygienic advice to reduce weight and sodium and alcohol intakes and to increase physical activity. End points include blood pressure change, side effects and quality-of-life indices; incidence of electrocardiographic and echocardiographic abnormalities; and incidence of cardiovascular clinical events, including death, among participants receiving drugs as first-step treatment as well as nonpharmacologic treatment compared with incidence among those participants randomized to nonpharmacologic treatment only as the initial step.

We examined the cross-sectional association of fat distribution with a number of lifestyle and reproductive factors in a random sample of 40,980 postmenopausal women, aged 55 to 69 years. The relationship of weight history with current fat distribution was also explored. Body fat distribution, defined by the ratio of waist-to-hip circumferences (WHR), was most strongly related to body mass index (BMI). WHR was also significantly and negatively associated with physical activity, alcohol consumption, and education, and was significantly positively associated with age, cigarette smoking, and a number of reproductive factors, such as history of infertility, number of live births, age at first live birth, and replacement estrogen use. WHR was not related to past BMIs, after adjusting for current body mass. The best-fit final regression model included (beta +/- s.e.) age (0.003 +/- 0.0001), BMI (0.02 +/- 0.0005), a curvilinear term for BMI (-0.0002 +/- 0.00001), greater than high school education (-0.007 +/- 0.001), cigarette smoking (0.02 +/- 0.001), alcohol drinker (-0.005 +/- 0.001), and number of live births (0.001 +/- 0.0002). The model R2 was 0.21. BMI (R2 = 0.18) and age (R2 = 0.02) accounted for most of the variation in WHR. The association of these lifestyle and reproductive factors with WHR suggests that the deposition of fat in the abdominal versus the gluteal region may be influenced somewhat by factors other than overall adiposity and genetics.

Epidemiologic studies have established that increased body weight is associated with a greater incidence of breast cancer in postmenopausal women. The authors hypothesized that abdominal adiposity further increases risk of postmenopausal breast cancer. They therefore investigated the waist-to-hip circumference ratio in relation to breast cancer incidence in a nested case-control study of 41,837 postmenopausal Iowa women aged 55-69 years. Women were recruited through a mail survey in January 1986 and were asked to have someone measure their body circumferences using a paper tape measure and written instructions. Cancer incidence was ascertained using a statewide cancer registry. A total of 229 incident breast cancers occurred among at-risk women during the first 2 years of follow-up (1986-1987). Compared with randomly selected controls (n = 1,839), women with incident breast cancer had a higher age-adjusted mean waist-to-hip ratio (by 0.013 units, p = 0.030), as well as greater mean weight (by 1.7 kg, p = 0.07), body mass index (by 0.6 kg/m2, p = 0.08), and weight gain since age 18 (by 2.7 kg, p less than 0.01). In multiple logistic regression models, age and current body mass index were significant effect modifiers of the association between the waist-to-hip ratio and breast cancer. A two-standard deviation increase in the waist-to-hip ratio (0.168 units) was associated with no increase in the relative risk of breast cancer in younger and lighter postmenopausal women. However, in older, heavier postmenopausal women, the same increase in the waist-to-hip ratio carried greater than a twofold excess relative risk. Adjustment for other breast cancer risk factors did not materially alter this finding. Two plausible explanations for elevated breast cancer incidence in women with abdominal adiposity include 1) increased concentrations of non-protein-bound estrogens due to reduced sex hormone binding globulin, or 2) increased conversion of adrenal androgens to estrone with abdominal adiposity.

The relation between body fat distribution, as measured by the waist-to-hip circumference ratio, and the 2-year incidences of hypertension and stroke were examined in a cohort of 41,837 women aged 55-69 years. Women who developed hypertension were 2.1 (95% confidence interval 1.7-2.6) times more likely to be in the upper tertile of waist-to-hip ratio than those who did not. Adjustment for age, body mass index (kilograms per meter squared), cigarette smoking, physical activity, alcohol intake, and education level reduced this odds ratio to 1.6 (95% confidence interval 1.3-2.1). Women who developed a stroke were also 2.1 (95% confidence interval 1.5-2.9) times more likely to be in the upper tertile of waist-to-hip ratio than those who did not. Adjustment for the same covariates also lowered this odds ratio to 1.6 (95% confidence interval 1.1-2.4). Further adjustment for hypertension and diabetes mellitus reduced the estimated risk of stroke due to elevated waist-to-hip ratio to 1.3 (95% confidence interval 0.8-2.1). Hypertension, diabetes mellitus, and cigarette smoking remained significantly associated with stroke incidence in the multivariate model. These results indicate that abdominal adiposity, as measured by an increased waist-to-hip ratio, increases the risks of hypertension and stroke, even after accounting for overall body mass. The association of abdominal adiposity with risk of stroke is related, in part, to the association of abdominal adiposity with hypertension and diabetes.

Recommendations state that the optimum ratio of blood pressure cuff width/arm circumference (CW/AC) is about 0.4. In this study of middle-aged men (n = 940) and women (n = 1484), we analysed the effect of CW/AC on blood pressure measurement variability and its interaction with age, body mass index (BMI), pulse rate and room temperature. In univariate polynomial regression, the variability (R2) in blood pressure that was explained by CW/AC was greater for women (systolic 6.3% and diastolic 5.7%) than for men (2.0% and 0.5%). In multivariate analysis the maximum variability explained independently by CW/AC was 2.7% for male and 6.7% for female systolic blood pressure, and 1.1% and 6.0% for male and female diastolic blood pressure, respectively. For systolic blood pressure this represented 10.4% of the explained variability in men and 9.3% of that in women. CW/AC is an important independent contributor to inter-individual variation in blood pressure measurement. It should therefore be taken into consideration in epidemiological studies and when medical care is being planned.