Determinants of echocardiographic aortic root size. The Framingham Heart Study

BACKGROUND: Previous studies that evaluated the determinants of aortic root size have not yielded uniform results. We examined the relations of age, height, weight, body surface area, sex, and blood pressure to echocardiographically determined aortic root size in a population-based cohort. METHODS AND RESULTS: The study sample consisted of 1849 men and 2152 women in the Framingham Heart Study and Framingham Offspring Study who were free of clinically apparent cardiac disease when echocardiography was performed. Aortic root measurements were made by M-mode echocardiography using a leading-edge-to-leading-edge technique. The relations of age, height, weight, body surface area, and blood pressure variables (contemporary and those obtained 8 years before) to aortic root dimension were examined by use of sex-specific correlations and linear regression analyses. Age, height, weight, and sex emerged as the principal determinants of aortic root dimensions in adults (cumulative R2 = .2085 in men and .2327 in women). The additional effect of contemporary or previous blood pressure measures was small and revealed direct associations of aortic root dimension with mean arterial and diastolic blood pressures and inverse associations with pulse and systolic blood pressures. Previous blood pressure measurements did not contribute significantly to prediction of aortic root size once contemporary blood pressure variable entered the models. Results of regression analyses using a sex-pooled data set showed that on average, the aortic root measurement in women was 2.4 mm smaller than that of men of comparable age, height, and weight. Logistic regression was used to assess the likelihood of aortic root enlargement according to blood pressure levels. After adjustment for age, height, and weight, the odds ratio of aortic dilation for a 1-SD increment in systolic pressure was 0.70 (95% CI, 0.52 to 0.95) in men and 0.79 (95% CI, 0.60 to 1.04) in women; the odds ratio for a 1-SD increment in diastolic pressure was 1.22 (95% CI, 0.91 to 1.63) in men and 1.33 (95% CI, 1.01 to 1.73) in women. CONCLUSIONS: Age, height, weight, and sex emerged as the principal determinants of aortic root dimensions. The additional influences of blood pressure measurements were small; direct associations of aortic root dimensions with mean arterial and diastolic blood pressures and inverse associations with pulse and systolic blood pressures were observed. Additional prospective studies are needed to confirm these observations and to assess the impact of aortic root dimensions on the incidence of hypertension.     

Dimensions of the proximal thoracic aorta from childhood to adult age: reference values for two-dimensional echocardiography. Ligurian Group of SIEC (Italian Society of Echocardiography)

BACKGROUND: Two-dimensional echocardiography (2-DE) represents the main tool for detecting and monitoring abnormalities of proximal thoracic aorta. However, previous studies performed to assess the reference values of aortic diameters using this technique are few and, often, involve a small number of subjects. Furthermore, such a study has not been performed on an Italian population. METHODS: To assess the reference values and the growth curves of the dimensions of the proximal thoracic aorta in an Italian population, we measured aortic diameters at the level of the anulus, of the sinuses of Valsalva and of the supraaortic ridge, by using 2-DE, in 134 healthy volunteers (78 males, 56 females), aged 35 +/- 16 years (range 5-76). Sex, age, weight, height, body surface area (BSA), heart rate, systolic and diastolic blood pressure were analyzed as determinants of proximal thoracic aorta diameters. In addition, to compare the specificity of the reference values, we have obtained with those provided by literature, we studied another independent group of 23 healthy volunteers, aged 32 +/- 15 years (range 11-65). RESULTS: In our study population, mean values and range of aortic 2-DE diameters were 2.1 +/- 0.3 cm (range 1.3-2.9) at the level of the anulus, 2.6 +/- 0.4 cm (range 1.7-3.7) at the level of the sinuses of Valsalva and 2.4 +/- 0.4 cm (range 1.5-3.4) at the level of the supraaortic ridge. At multivariate regression analysis, sex and age emerged as the only independent determinants of the aortic root diameters (r2 = 0.35, 0.43, and 0.52 for aortic diameter at the level of anulus, sinuses of Valsalva, and supraaortic ridge, respectively). On average, aortic root dimensions at the level of the anulus, of the sinuses of Valsalva and of the supraaortic ridge in females were 1.5 mm, 2.8 mm, and 1 mm, respectively, smaller than those of males of comparable age, height and weight. The growth curves showed that proximal thoracic aorta increases in size in the first 30 years of life; thereafter, it remains relatively constant in size up to 55 years, after which the proximal thoracic aorta tends to enlarge gradually. The ratios of sinuses of Valsalva to annular diameter and of supraaortic ridge to annular diameter (1.27 +/- 0.17 and 1.17 +/- 0.16, respectively) were found to be indexes of aortic root dimension independent of sex and age. No correlation was found between aortic root dimensions and systolic blood pressure. M-mode echocardiography systematically overestimated 2-DE aortic diameters at the level of the anulus, as well as at the level of the sinuses of Valsalva and of the supraaortic ridge (+0.8 +/- 0.04 cm, +0.2 +/- 0.04 cm, and +0.4 +/- 0.04 cm, respectively, p < 0.0001 for all). In the control population, our reference values demonstrated a specificity significantly higher than that of the main reference values reported in literature (97 +/- 2% versus 62 +/- 4%, p < 0.0001). CONCLUSIONS: Our study provides a prospectic, systematic and detailed analysis of 2-DE proximal thoracic aorta diameters in a wide group of healthy Italian subjects. Our data show that: 1) 2-DE aortic root dimensions are influenced by sex and age but not by body size or blood pressure; 2) the ratios of sinuses of Valsalva to annular diameter and of supraaortic ridge to annular diameter are indexes of aortic root dimension which are independent of age and sex; 3) M-mode diameter systematically overestimates 2-DE diameters of the aortic root; and 4) Italian population based reference values showed higher specificity than values provided by literature.     

Validations of time-resolved fluoroimmunoassays for urinary estrone 3-glucuronide and pregnanediol 3-glucuronide

OBJECTIVE: In this study, we determined the effect of age, sex, and body size on left ventricular mass. DESIGN: Two-dimensional-guided M-mode echocardiography was used in an assessment of 111 healthy, normal adults. MATERIAL AND METHODS: Left ventricular mass was calculated with the cube function formula corrected by a regression equation to agree with autopsy estimates of left ventricular mass. Calculated left ventricular mass, indexed by body surface area and by height, was analyzed on the basis of sex and age of the study participants. Age was analyzed as a dichotomous, trichotomous, and continuous variable. The effects of age, sex, and obesity, as well as interactions, were tested within a multiple linear regression model framework. RESULTS: Left ventricular mass, when indexed for either body surface area or height, was greater in men than in women. For women, but not men, we found a small but significant increase in left ventricular mass with advancing age. Body mass index, an indicator of obesity, increased with aging in women but not in men and affected left ventricular mass. No significant changes were noted in left ventricular cavity size with advancing age, and the increase in left ventricular mass in women was due to increased ventricular wall thickness. CONCLUSION: The findings in this study suggest that left ventricular mass, as assessed by two-dimensional-guided M-mode echocardiography, is affected not only by sex and body size but also by age in women. This phenomenon may be related to an increase in body mass index with advancing age in women. In clinical studies that use echocardiographic left ventricular mass to diagnose left ventricular hypertrophy, these observations should be considered.     

The influence of cigarette smoking on the association between body weight and mortality. The Framingham Heart Study revisited

PURPOSE: To calculate for two measures of obesity, the Metropolitan Relative Weight (MRW) and body mass index (BMI), the value at which minimum mortality occurs. This was done to retest the hypothesis, in the Framingham Heart Study data, that the association between obesity and mortality can be obscured by an interaction between the measure of obesity and smoking. In the original analysis of the Framingham data it was suggested that there was a U- or J-shaped relationship between MRW and death in smokers but a linear relationship in nonsmokers. The design and setting were those of the NHLBI Framingham Heart Study. METHODS: The 5209 members of the Framingham Heart Study underwent a baseline examination in 1948-1952 (Exam 1) and they were reexamined at approximately two-year intervals over a 30-year period. The study included both men (n = 2336) and women (n = 2873) in the age range of 28 to 62 years. After excluding persons with missing baseline data, the analytic sample size was 5163. Additional analyses were conducted by deleting persons with cardiovascular disease (CVD) at baseline (n = 135), the sample used by the original paper by Garrison and colleagues, and persons who died within the first four years of follow-up (n = 62). The main outcome measures consisted of thirty-year survival through Exam 16, approximately in 1980, as influenced by MRW or BMI, age, and smoking status at baseline (Exam 1). RESULTS: We were able to show that the sample sizes of male nonsmokers were too small to test the hypothesis within age groups < 40 and 40-49 years. In men ages 50-62 there was a significant age-adjusted quadratic relationship between BMI or MRW, and risk of death. The estimated BMI at the minimum risk of death for smokers (24.5) and nonsmokers (23.8) were not statistically different. Identical results were found for MRW (minimum: smokers = 112.5, nonsmokers = 111.4). In men and women ages 28-62 there appeared to be a u- or j-shaped relationship between the 30-year crude mortality rate and MRW. After excluding persons with missing data, CVD at baseline, and persons who died within the first four years of follow-up, the age adjusted estimated BMI value at the minimum risk of death was nearly identical for men and women and for smokers and nonsmokers (Men: smokers = 22.8, nonsmokers = 22.8; Women: smokers = 22.9, nonsmokers = 23.3). Additionally, the estimates of the minimum were always below the mean. Identical results were found without deleting persons with CVD at baseline and deaths in the first four years of follow-up. Identical results were found for MRW. CONCLUSIONS: Reanalysis of the Framingham Heart Study data does not support the hypothesis that there is an interaction between smoking and measures of obesity. Moreover, the estimated BMI or MRW at the minimum risk of death was similar for men and women smokers and nonsmokers alike even after deleting prevalent cases of CVD and deaths within the first four years of follow-up.     

Muscle mass and fat mass in relation to bone mineral density in very old men and women: the Framingham Heart Study

Aim of the study was investigate the cross-sectional relationship between body composition and bone mineral density (BMD) in very old men and women. The study sample consisted of 504 women and 285 men, aged 72-93 yr, participating in examination 22 (1992-1993) of the Framingham Heart Study. Total body BMD, regional BMD, and soft-tissue body composition was measured by dual-energy X-ray absorptiometry. Both muscle mass and percentage body fat were positively associated with total body BMD in women. After adjustment for age, physical activity, smoking status, estrogen use, and thiazide use, BMD increased with increasing tertile of muscle mass (p = 0.007) and with increasing tertile of percentage body fat (p = 0.0001) in women. In men muscle mass, not percentage body fat, was positively associated with BMD. After adjustment for potential confounders, BMD remained associated with muscle mass only (p = 0.02). These results were similar for leg BMD and arm BMD. The study suggests that the influence of muscle and fat mass on bone mineral density is different between very old men and women.     

Lipoproteins, apolipoproteins, and low-density lipoprotein size among diabetics in the Framingham offspring study

Diabetes mellitus has been shown to be associated with lipid abnormalities. Prior studies have indicated that women with diabetes have a risk of coronary heart disease similar to that of men. We compared lipid parameters in diabetic and nondiabetic participants in cycle 3 of the Framingham Offspring Study. Values for plasma total cholesterol (TC), triglyceride, lipoprotein, cholesterol, apolipoprotein (apo) A1, B, apo and lipoprotein(a) [Lp(a)] and low-density lipoprotein (LDL) particle size were analyzed in 174 diabetic and 3,757 nondiabetic subjects. Data from a total of 2,025 men and 2,042 women participating in the third examination (1983 to 1987) of the Framingham Offspring Study were subjected to statistical analysis. Male and female diabetics showed lower high-density lipoprotein (HDL) cholesterol, higher triglycerides, higher very-low-density lipoprotein (VLDL) cholesterol, lower apo A1, and higher LDL particle scores, indicating smaller size, than nondiabetics. Female diabetics also showed significantly higher TC and apo B values than nondiabetics. The results remained statistically significant after controlling for obesity and menopausal status. The presence of small dense LDL particles (pattern B) was highly associated with diabetes and hypertriglyceridemia in both sexes, and the relative odds for pattern B remained significant in women but not in men after adjustment for age and hypertriglyceridemia. No differences in apo E isoform distribution were found for diabetics and nondiabetics. Diabetes was not associated with elevated LDL cholesterol levels. In conclusion, diabetics have lower HDL cholesterol and higher triglyceride levels and are more likely to have small dense LDL particles. Diabetes is not a secondary cause of elevated LDL cholesterol. Lipid screening of diabetics should include full quantification of lipids for proper assessment of potential atherosclerotic risk.     

Plasma lipoprotein and apolipoprotein levels in Taipei and Framingham

We compared the plasma lipoprotein cholesterol, triglyceride, apolipoprotein (apo) A-I, apoB, and lipoprotein(a) [Lp(a)] concentrations in a low coronary heart disease (CHD) risk population (n = 440) in Taipei with a high CHD risk population (n = 428) in Framingham matched for age, sex, and menopausal status. Taipei men had significantly lower low-density lipoprotein cholesterol (LDL-C) (-20 mg/dL, -14%, P < .01) and apoB (-7 mg/dL, -6%, P < .05) levels and significantly higher high-density lipoprotein cholesterol (HDL-C) levels (6 mg/dL, 13%, P < .01) than Framingham men. Taipei women had significantly lower LDL-C (-18 mg/dL, -15%, P < .01) and higher HDL-C (4 mg/dL, 7%, P < .01) levels than Framingham women. Median concentrations and distributions of Lp(a) by sex were similar in Taipei and Framingham. After adjusting for body mass index and smoking status, only differences in total cholesterol and LDL-C levels remained significantly different for both sexes between the two populations (P < .01). Gender differences for lipids within populations were similar. After adjusting for age, body mass index, and smoking status, women in both Taipei and Framingham had significantly lower mean triglyceride, LDL-C, and apoB levels and significantly higher HDL-C and apoA-I levels than men. Postmenopausal women in Taipei had significantly higher mean total cholesterol, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) levels than premenopausal women (P < .05), whereas in Framingham postmenopausal women had significantly higher total cholesterol, triglyceride, LDL-C, and apoB levels than premenopausal women (P < .05). Our data are consistent with the concept that plasma lipoprotein cholesterol levels (especially LDL-C) but not apolipoprotein values explain some of the twofold difference in age-adjusted CHD mortality between these two populations.     

Impact of atrial fibrillation on the risk of death: the Framingham Heart Study

BACKGROUND: Atrial fibrillation (AF) causes substantial morbidity. It is uncertain whether AF is associated with excess mortality independent of associated cardiac conditions and risk factors. METHODS AND RESULTS: We examined the mortality of subjects 55 to 94 years of age who developed AF during 40 years of follow-up of the original Framingham Heart Study cohort. Of the original 5209 subjects, 296 men and 325 women (mean ages, 74 and 76 years, respectively) developed AF and met eligibility criteria. By pooled logistic regression, after adjustment for age, hypertension, smoking, diabetes, left ventricular hypertrophy, myocardial infarction, congestive heart failure, valvular heart disease, and stroke or transient ischemic attack, AF was associated with an OR for death of 1.5 (95% CI, 1.2 to 1.8) in men and 1.9 (95% CI, 1.5 to 2.2) in women. The risk of mortality conferred by AF did not significantly vary by age. However, there was a significant AF-sex interaction: AF diminished the female advantage in survival. In secondary multivariate analyses, in subjects free of valvular heart disease and preexisting cardiovascular disease, AF remained significantly associated with excess mortality, with about a doubling of mortality in both sexes. CONCLUSIONS: In subjects from the original cohort of the Framingham Heart Study, AF was associated with a 1.5- to 1.9-fold mortality risk after adjustment for the preexisting cardiovascular conditions with which AF was related. The decreased survival seen with AF was present in men and women and across a wide range of ages.     

The effects of milrinone and its mechanism in the fatigued diaphragm in dogs

The development of the left ventricle parallels body growth. During infancy, the relation between body size and left ventricular (LV) mass is very close. With advancing age, variability of LV mass in relation to body size markedly increases. To test the hypothesis that the age-related increase in variability of LV mass is due to the progressive impact of hemodynamic stimuli on LV growth, quantitative M-mode echocardiograms were obtained in 766 normal-weight, normotensive individuals over a range of ages from 1 day to 85 years (330 female subjects, 373 subjects younger than 18 years). LV mass was linearly related to height2.7 (r2=.69). Prediction of values of LV mass by body size was more accurate at birth and progressively less precise with increasing age. Stroke work (stroke volume times systolic pressure) was closely related to LV mass (r2=.74). The explained variance of LV mass increased from 69% in the univariate regression with height2.7 to 82% in a multivariate model including height2.7, stroke work, and gender. In children and adolescents (younger than 18 years), height2.7 was the main determinant of LV mass, whereas during adulthood stroke work and gender were more important predictors of LV mass than height2.7. Thus (1) the influence of body growth on development of LV mass decreases after early infancy because of both the variability of hemodynamic load and the increasing effect of gender; (2) after adolescence, during adulthood, in normotensive, normal-weight individuals, the impact of hemodynamic load and male gender on LV mass is greater than the one of body size; and (3) an appreciable proportion of variability of LV mass remains unexplained with the studied models. This might be due to genotypic variations and/or measurement error.     

Oxygen consumption in infants and children during heart catheterization

Oxygen consumption was measured in infants, children, and adolescents during diagnostic heart catheterizations. A total of 825 measurements of oxygen consumption (VO2) was performed in 504 subjects using a semiopen hood system and a paramagnetic oxygen analyzer. In 256 subjects under 3 years of age, body dimensions and heart rate were found to be significant factors for oxygen consumption. The regression equation for both sexes was: VO2/BSA (ml/min.m2) = 3.42.height (cm) - 7.83.weight (kg) + 0.38.HR - 54.1 (r2 = 0.39, SD = 38.7), where BSA is body surface area and HR is heart rate. VO2/BSA was significantly lower in infants less than 3 months of age (133 +/- 33 ml/min.m2) compared with infants of 3-12 months (171 +/- 37 ml/ min.m2; p < 0.01). In 272 children aged 3 years and older and adolescents, gender was a significant factor in oxygen consumption together with BSA and HR. The regression line equation for males was VO2/BSA (ml/ min.m2) = 0.79.HR - 7.4.BSA(m2) + 108.1 (r2 = 0.45, SD = 34.2). The regression line equation for females is VO2/BSA (ml/min.m2) = 0.77.HR - 5.2.BSA(m2) + 106.8 (r2 = 0.43, SD = 34.4). Hematocrit, systemic oxygen saturation, and blood pressure were not significant factors. The predictive value of nomograms for oxygen consumption is limited because of the large interindividual variations not explained by differences in gender, body size, or simple hemodynamic variables. Preferably, oxygen consumption is measured; but if nomograms for oxygen consumption are used for hemodynamic assessment, the wide confidence intervals should be considered.     

Physical activity and risk of breast cancer in the Framingham Heart Study

The authors analyzed data from the Framingham Heart Study to evaluate the association between physical activity and breast cancer risk. Physical activity was ascertained by a physician-administered questionnaire from 2,321 women at the fourth biennial examination conducted in 1954-1956. Breast cancers were identified by self-report, surveillance of admissions to Framingham Union Hospital, and review of death records; all but one were histologically confirmed. During 28 years of follow-up, 117 breast cancer cases were diagnosed among the 2,307 women with data on physical activity and reproductive history (a potential confounder). Analysis was performed using Cox proportional hazards models with age as the underlying time variable. Models were adjusted for age at physical activity assessment, menopausal status, age at first pregnancy, parity, education, occupation, and alcohol ingestion. We observed a gradient of increasing risk of breast cancer with increasing physical activity (trend p = 0.06). The relative risk for women in the highest versus lowest activity quartile was 1.6 (95% confidence interval 0.9-3.0; p = 0.13). Although both moderate-to-heavy leisure and occupational activities were associated with an increased risk, the association was marginally significant only for leisure activity (p = 0.06). Our findings do not support a protective effect of physical activity during adulthood for breast cancer, but suggest an increased risk among more active women.     

Evidence for cAMP-independent mechanisms mediating the effects of adrenomedullin, a new inotropic peptide

OBJECTIVE: To determine the relation of skeletal body build and obesity to blood pressure and the prevalence of hypertension. DESIGN: Cross-sectional data obtained from the baseline recruitment of the EPIC-Potsdam Study, which is part of the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: A total of 10,303 subjects (4387 men, aged 40-65 y and 5916 women, aged 35-65 y) were recruited between January 1995 and July 1996. MEASUREMENTS: Anthropometric measures included body mass index (BMI), waist-hip ratio (WHR) and metrik index (MIX) as a measure of body build that is derived from the relation of chest depth and breadth to body height. Systolic and diastolic blood pressure was obtained using automatic oscillometric devices. Hypertension was defined as blood pressure > or = 160/95 mmHg or current use of antihypertensive medication. Information on lifestyle factors were obtained by personal interview. STATISTICAL ANALYSIS: Logistic regression was used to define the association of categories of BMI, WHR, and MIX and the prevalence of hypertension. Odds ratios (ORs) of being hypertensive were estimated comparing the highest to the lowest quintile, adjusting for age, smoking status, alcohol intake level, educational attainment, physical activity categories, and each of the anthropometric variables. RESULTS: The simultaneously adjusted OR of being hypertensive, comparing the highest vs the lowest category, was for BMI 2.3 (95% confidence interval (CI) = 1.6-3.2) in men and 1.8 (95% CI = 1.4-2.5) in women, for WHR 1.8 (95% CI = 1.4-2.4) in men and 1.5 (95% CI = 1.2-2.0) in women, and for MIX (largest chest size vs lowest chest size relative to body height) 2.0 (95% CI = 1.4-2.8) in men and 2.2 (95% CI = 1.6-3.1) in women. CONCLUSION: In addition to measures of overall obesity (BMI) as well as central obesity (WHR), skeletal body build (MIX) was independently associated with the prevalence of hypertension. The biological mechanism relating MIX to hypertension, however, is still unclear and needs further exploration.     

Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study

Plasma low density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B, the major protein constituent of LDL, were measured in 1,533 men (mean age 49 +/- 10 years) and 1,597 women (mean age 49 +/- 10 years) participating in the 3rd examination cycle of the Framingham Offspring Study. Mean plasma levels of LDL cholesterol and apoB were higher in men than in women (136 versus 132 mg/dl, P < 0.0001; and 109 versus 95 mg/dl, P < 0.0001, respectively). Increased age was associated with higher plasma LDL cholesterol and apoB levels, especially in women. After adjustment for age and body mass index, LDL cholesterol and apoB levels were still significantly higher in postmenopausal than in premenopausal women, indicating a hormonal effect on LDL metabolism. The associations between coronary heart disease (CHD) and LDL cholesterol, non-HDL cholesterol, apoB, and other plasma lipid and lipoprotein parameters were examined by dividing participants in four groups, based on approximate quartiles for these parameters. Elevated LDL cholesterol levels were not significantly associated with CHD in men, but were in women. This result, at variance with that of several longitudinal studies, is likely due to the cross-sectional design of our analysis. Elevated non-HDL cholesterol and apoB levels were significantly associated with the presence of CHD, in both males and females. A plasma apoB value > or = 125 mg/dl may be associated with an increased risk for CHD. Low plasma levels of HDL cholesterol were also significantly associated with CHD. Plasma triglyceride levels, age and body mass index were strong determinants of LDL cholesterol, non-HDL cholesterol, and apoB levels in men and women. In women, postmenopausal status and elevated blood pressure were also significantly associated with elevated levels of these parameters.     

Body weight change and carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study

The impact of weight change in adulthood on cardiovascular disease is controversial. This study examined the association of change in body weight, from young adulthood to middle age, with average carotid artery intimal-medial wall thickness by B-mode ultrasound measured in middle age. Participants were 13,282 men and women aged 45-64 years from the baseline examination of the Atherosclerosis Risk in Communities (ARIC) Study (1987-1989). Weight change was calculated as the difference between weight at the baseline examination and self-reported weight at age 25. White men gained a mean of 9.7 kg; black men, 10.1 kg; white women, 12.0 kg; and black women, 20.8 kg. Weight change was positively, albeit modestly, associated with intimal-medial thickness in black men and white men and in white women, but not in black women. Adjusted for age, examination center, smoking, education, sports activity level, height, and body mass index at age 25, the differences in intimal-medial thickness associated with a 10-kg increment in weight change were 0.016 (95% confidence interval 0.010 to 0.022) mm in white men, 0.008 (95% confidence interval 0.001 to 0.015) mm in black men, 0.013 (95% confidence interval 0.009 to 0.017) mm in white women, and 0.002 (95% confidence interval -0.002 to 0.006) mm in black women. These findings support the hypothesis that weight gain in adulthood promotes atherosclerotic changes in white men and women and in black men.     

Indomethacin inhibits responses to all vasoconstrictors in the rat mesenteric vascular bed: restoration of responses by prostaglandin E2

Saliva half-life of antipyrine was studied in 49 healthy Gambians between 20 and 60 yr of age of whom 27 were male (mean age, 44.5) and 22 female (mean age, 39.1). Body wieght, height, ponderal index, albumin, and hemoglobin were moderately reduced compared to accepted normal values. Antipyrine half-life was 13.6 +/- 0.58 (SEM) hr. Multiple regression analysis showed that sex, cola nut consumption, hemoglobin in women, and height in men were statiscally significant independent predictors of antipyrine half-life. Half-life was shorter in women, decreased with an increase in height in men, and was prolonged by cola nut consumption. Half-life in women increased with hemoglobin. These factors explained 36% of the variation and suggest that geographic differences in the environment could be important in drug metabolism in man.     

Prognostic significance of the pattern of aortic root dilation in the Marfan syndrome

OBJECTIVES: The present study examines the incidence of aortic complications (dissection, marked dilation requiring surgery or progressive moderate to severe aortic regurgitation) and their relation to clinical features and aortic root morphology in patients with the Marfan syndrome. BACKGROUND: Considerable phenotypic variability exists in the Marfan syndrome, and the prospective prediction of the risk for aortic complications in individual patients remains elusive. METHODS: One hundred thirteen patients with the Marfan syndrome underwent anthropometric and echocardiographic evaluation and were followed-up for 49 +/- 24 (mean +/- SD) months. Aortic root dilation was defined as localized when confined to the sinuses of Valsalva (based on two-dimensional echocardiographic confidence limits utilizing age and body size) and generalized if dilation additionally involved the supraaortic ridge and proximal ascending aorta. RESULTS: Aortic root dilation was present in 80% of patients and was localized in 28% and generalized in 51%. Aortic complications occurred during follow-up in none of 23 patients with normal initial aortic size, in 2 (6%) of 32 patients with initially localized dilation and in 19 (33%) of 58 patients with generalized dilation (p < 0.0005). Complications were associated with larger initial aortic size (p < 0.00005), higher systolic blood pressure (p < 0.005), height (p < 0.05), aortic growth rate (p < 0.05) and older age (p < 0.01). The only independent predictor of aortic complications was initial aortic root size (p < 0.005). However, when aortic size, one of the indications for surgical referral, was excluded from analyses, the only independent predictor of aortic complications was generalized aortic dilation (p < 0.005). CONCLUSIONS: The present study indicates that generalized aortic root dilation is a potent marker of an increased risk for subsequent aortic complications in Marfan syndrome.     

Effect of age on pentylenetetrazol-kindling and kindling-induced impairments of learning performance

PURPOSE: To assess the effects of age, gender, race, and body size on infrarenal aortic diameter (IAD) and to determine expected values for IAD on the basis of these factors. METHODS: Veterans aged 50 to 79 years at 15 Department of Veterans Affairs medical centers were invited to undergo ultrasound measurement of IAD and complete a pre-screening questionnaire. We report here on 69,905 subjects who had no previous history of abdominal aortic aneurysm (AAA) and no ultrasound evidence of AAA (defined as IAD > or = 3.0 cm). RESULTS: Although age, gender, black race, height, weight, body mass index, and body surface area were associated with IAD by multivariate linear regression (all p < 0.001), the effects were small. Female sex was associated with a 0.14 cm reduction in IAD and black race with a 0.01 cm increase in IAD. A 0.1 cm change in IAD was associated with large changes in the independent variables: 29 years in age, 19 cm or 40 cm in height, 35 kg in weight, 11 kg/m2 in body mass index, and 0.35 m2 in body surface area. Nearly all height-weight groups were within 0.1 cm of the gender means, and the unadjusted gender means differed by only 0.23 cm. The variation among medical centers had more influence on IAD than did the combination of age, gender, race, and body size. CONCLUSIONS: Age, gender, race, and body size have statistically significant but small effects on IAD. Use of these parameters to define AAA may not offer sufficient advantage over simpler definitions (such as an IAD > or = 3.0 cm) to be warranted.     

Effects of weight and body mass index on bone mineral density in men and women: the Framingham study

We evaluated the association of weight and bone mass in elderly male and female subjects of the Framingham osteoporosis study, a subset of the Framingham study cohort. By examining the differences in the correlations of weight with bone mass among men and women in weight-bearing and non-weight-bearing sites and weight change since early adulthood, we attempted to understand different ways in which weight or body mass index affects bone mass. During biennial examination 20 of the Framingham cohort (1988-1989), 693 women and 439 men (mean age 76 years) had proximal femur bone mineral density assessed by dualphoton absorptiometry (DPA) and radius bone mass assessed by single-photon absorptiometry. The majority of these subjects also had spine measurements by DPA. Subjects had been weighed repeatedly over 40 years. After adjusting for other factors affecting bone density, we found that both recent weight and body mass index explained a substantial proportion of the variance in bone mineral density for all sites in women (8.9-19.8% of total variance, all p < 0.01) and for only weight-bearing sites (femur and spine) in men (2.8-6.9% of total variance, all p < 0.01). For bone mineral density at the proximal radius, weight and body mass index accounted for < 1% of variance in men (p NS). Weight change since biennial examination 1 (1948-1951) was the strongest explanatory factor for bone mineral density among women at all sites, but weight change did not affect radius bone mineral density in men. The effect of weight and of weight change on bone mineral density was in general much less in men than in women. Our results suggest that the strong effect of weight on bone mineral density is due to load on weight-bearing bones sexes. The sex difference is unexplained but may be due to adipose tissue production of estrogen in women after menopause.     

Osteoarthritis, bone density, postural stability, and osteoporotic fractures: a population based study

OBJECTIVE: Osteoarthritis (OA) is associated with an increase in bone density both locally and at distant sites. Prospective data are limited on the relationship between OA and fracture. We studied the possible relationship between self-reported OA, bone density, postural stability measures, and atraumatic fractures as part of a study of men and women over 60 years of age. METHODS: Subjects were part of the Dubbo Osteoporosis Epidemiology Study (a longitudinal population based study of fracture risk factors). Bone density was measured by dual energy x-ray absorptiometry. Postural stability was assessed by the validated measures of quadriceps strength and sway. Medication use and self-reported arthritis were assessed by a structured personal interview. Fractures were ascertained retrospectively by interview and prospectively by viewing radiographic reports for fracture. RESULTS: Among a study population of 1101 women and 720 men (mean age 69) there were 462 subjects (25%) who reported a diagnosis of OA. In both sexes, subjects with OA had higher bone density (adjusted for age and body mass index) at both the femoral neck (men, p = 0.026; women, p = 0.048) and lumbar spine (men, p = 0.0007; women, p = 0.0007). However, in both sexes, those with self-reported OA also had higher body sway and lower quadriceps strength. The combination of these observed differences in fracture risk factors led to no predicted change in fracture risk overall when using established nomograms for this population [men, OR = 1.11 (95% CI 0.83-1.45); women, OR = 1.08 (95% CI 0.83-1.39)]. This paralleled our observational finding that self-reported OA was not associated with a decrease in fracture incidence compared to those not reporting OA in both men (RR 0.64, 95% CI 0.29-1.39) and women (RR 1.00, 95% CI 0.66-1.51). CONCLUSION: Individuals with self-reported OA, despite higher bone density, are not protected against nonvertebral osteoporotic fracture, apparently due to worsened postural stability and thus an increased tendency to fall.     

Introduction. Early identification and assessment of emerging health technology

The association between obesity and risk of coronary artery disease is well established. The distribution of body fat was shown to be related to serum lipids and lipoproteins in a group of healthy men, but the association between body fat and haemostatic factors is less clear. The aim of the present study was to determine the association of overall adiposity (OVRAD, percent total fat mass contributing to body weight) and body mass index (BMI, weight/height2) with lipids and haemostatic factors in order to evaluate which of these was more associated with circulating procoagulant factors. The total fat mass was estimated by dual-energy X-ray absorptiometry (DEXA) and OVRAD computed for 28 male and 36 healthy female subjects, whose median age were 44.2 years and 48.4 years respectively. In addition, the BMI was computed for each of them from their weight and height measurements. Fasting samples were analysed for serum lipids (total, HDL- and LDL-cholesterol and triglyceride) and plasma fibrinogen, factor VII coagulant (FVII:C) activity, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities. The men and women had similar median BMI (23.9 kg/m2 and 23.1 kg/m2 respectively), but the median fat mass of women (19.6 kg) was higher than that of men (16.9 kg). Age, BMI and OVRAD exhibited statistically significant correlations with lipids and haemostatic factors in both men and women. However, when BMI was adjusted for age and OVRAD, the statistically significant associations were no longer apparent in men or women. In contrast, OVRAD adjusted for age and BMI still exhibited statistically significant associations with FVII:C activity (R = 0.38, p = 0.05), triglyceride (R = 0.51, p = 0.008), LDL-cholesterol (R = 0.45, p = 0.02) and HDL/Total cholesterol ratio (R = -0.63, p <0.001). It is concluded that OVRAD, a fat mass-based index, rather than BMI, a weight-height based index, is better associated with circulating coronary risk factors.