Cardiac and Systemic Hemodynamic Characteristics of Hypertension and Prehypertension in Adolescents and Young Adults The Strong Heart Study

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1 Cardiac and Systemic Hemodynamic Characteristics of Hypertension and Prehypertension in Adolescents and Young Adults The Strong Heart Study Jennifer S. Drukteinis, MD; Mary J. Roman, MD; Richard R. Fabsitz, PhD; Elisa T. Lee, PhD; Lyle G. Best, MD; Marie Russell, MD; Richard B. Devereux, MD Background The epidemic of overweight is increasing the prevalence of both prehypertension and early-onset hypertension, but few population-based data exist on their impact on cardiac structure and function in adolescents and young adults. Methods and Results We analyzed clinical characteristics, hemodynamic parameters, and left ventricular structure and function in 1940 participants, 14 to 39 years of age, in the Strong Heart Study. Hypertension occurred in 294 participants (15%), who were more often men (70% versus 30%), older (age, 31 7 versus 25 8 years), and more commonly diabetic (23% versus 4.5%; all P 0.001) than their normotensive counterparts. Prehypertension occurred in 675 (35%) of participants with similar trends in gender, age, and diabetes status. After adjustment for covariates, both hypertensive and prehypertensive participants had higher left ventricular wall thickness (0.83 and 0.78 versus 0.72 cm), left ventricular mass (182 and 161 versus 137 g), and relative wall thickness (0.30 and 0.29 versus 0.28 cm) and 3- and 2-fold-higher prevalences of left ventricular hypertrophy than their normotensive counterparts (all P 0.001). Hypertension and prehypertension also were associated with higher mean pulse pressure/stroke volume index (1.24 and 1.15 versus 1.02 mm Hg/mL m 2 ) and total peripheral resistance index (3027 and 2805 versus 2566 dynes s cm 5 m 2 ; all P 0.001). Conclusions In a population with high prevalences of obesity and diabetes, hypertension and prehypertension are associated with increases in both cardiac output and peripheral resistance index. Despite the young age of participants with hypertension and prehypertension, they had prognostically adverse preclinical cardiovascular disease, including left ventricular hypertrophy and evidence of increased arterial stiffness. (Circulation. 2007;115: ) Key Words: echocardiography hemodynamics hypertension hypertrophy prehypertension In the United States and other industrialized countries, physical inactivity and high-calorie diets are leading to increasing prevalences of obesity and diabetes. 1 Concordantly, hypertension also has become increasingly prevalent. 2 Obesity and higher blood pressure have been shown to track from childhood and adolescence to adulthood and to predict adult cardiovascular risk. 3,4 According to the Seventh Report of the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), 5 a new category based on blood pressure (BP) level, called prehypertension, requires attention and healthpromoting lifestyle modifications at an even earlier stage to prevent the progressive rise in BP and cardiovascular disease. Approximately 60% of American adults have prehypertension or hypertension, with hypertension increasing by 10% in the past decade. 6 Recent studies in population-based samples with mean ages from 45 to 55 years at baseline have shown increased cardiovascular event rates in adults with high-normal BP (130 to 139/85 to 89 mm Hg) 7 or prehypertension (BP, 120 to 139/80 to 89 mm Hg without antihypertensive medication). 8 Although the increased prevalence of hypertension and the common occurrence of prehypertension are affecting cardiovascular mortality in middle and older age, their earlier impact on cardiac structure and function in adolescents and young adults has not been extensively characterized in large, population-based samples. Continuing medical education (CME) credit is available for this article. Go to to take the quiz. Received February 24, 2006; accepted October 11, From the Weill Medical College of Cornell University, New York, NY (J.S.D., M.J.R., R.B.D.); National Heart, Lung, and Blood Institute, Bethesda, Md (R.R.F.); University of Oklahoma Health Sciences Center, Oklahoma City (E.T.L.); Missouri Breaks Industries Research, Inc, Timber Lake, SD (L.G.B.); and MedStar Research Institute, Washington, DC (M.R.). This manuscript presents the views of the authors and not necessarily those of the Indian Health Service. Correspondence to Richard B. Devereux, MD, Division of Cardiology, Box 222, New York Presbyterian Hospital, 525 E 68th St, New York, NY rbdevere@med.cornell.edu 2007 American Heart Association, Inc. Circulation is available at DOI: /CIRCULATIONAHA

2 222 Circulation January 16, 2007 Previous studies have examined cardiac structure and function in white, black, or Hispanic populations with modest prevalences of obesity and diabetes. 9,10 Accordingly, the present study was undertaken to evaluate the associations of hypertension and prehypertension with clinical characteristics, systemic hemodynamics, and cardiac structure and function in adolescent and young adult American Indian participants (age, 14 to 39 years) in the Strong Heart Study (SHS), a population in which obesity, diabetes, and hypertension are highly prevalent. Methods The SHS is a population-based survey of cardiovascular risk factors and cardiovascular disease in American Indian communities in Arizona, Oklahoma, and South and North Dakota. As previously described, 12 members of 13 communities in Arizona, Oklahoma, and South and North Dakota (45 to 74 years of age) were recruited from reservations or (in Oklahoma) in defined geographic areas (overall participation rate, 62%) for an initial examination in 1989 to Two additional examinations of the initial SHS cohort to assess change over time were performed during 1993 to 1995 and during 1997 to The fourth SHS examination in July 2001 to September 2003 included 520 SHS cohort members and 3138 of their relatives in 95 large 3-generation families (Strong Heart Family Study [SHFS]). 14 Standardized measurements of seated brachial BP and aspects of body habitus, including body mass index, waist-to-hip ratio, body composition by bioelectric impedance, fasting glucose, insulin and lipid concentrations, and 2-hour glucose tolerance test and glycosylated hemoglobin levels, were obtained. Brachial artery BP (first and fifth Korotkoff sounds) was measured 3 consecutive times on seated participants after they had rested 5 minutes with the use of a mercury sphygmomanometer (W.A. Baum Co, Copiague, NY). An appropriately sized cuff was placed on the right arm; pulse occlusion pressure was determined; and the cuff was inflated to 20 mm Hg above that pressure. The mean of the last 2 of these measurements was used to estimate BP. Hypertension was defined by systolic BP 140 mm Hg, diastolic pressure 90 mm Hg, or use of antihypertensive medications. 15 Participants were asked to bring their medications to the clinic and to recall (with assistance from an adult for minors) additional medications. Prehypertension was defined by systolic BP of 120 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg 5 in the absence of antihypertensive treatment. Fat-free mass and adipose mass were estimated with an RJL impedance meter (model B14101, RJL Equipment Co, Detroit, Mich) and equations based on total body water 12 that have been validated in the American Indian population. 16,17 Obesity was defined by a body mass index 30 kg/m 2 and central adiposity by waist circumference 102 cm for men and 88 cm for women. 18 Diabetes was diagnosed by 1997 American Diabetes Association diagnostic criteria. 19 Participants (or their parent or guardian in the case of minors) gave written informed consent under protocols approved by institutional review boards of the clinical centers. Echocardiographic Methods Imaging and Doppler echocardiograms, performed as previously described, 14,20,21 were recorded on videotape using phased-array echocardiographs with fundamental and harmonic M-mode and 2-dimensional imaging, as well as pulsed, continuous-wave, and color-flow Doppler capabilities (Sequoia, Siemens Inc, Mountain View, Calif). Participants were examined in a partial decubitus position with the head of table tilted at 30. Echocardiographic Measurements Correct orientation of planes for imaging and Doppler recordings was verified as previously described. 21,22 Measurements were made with a computerized review station equipped with digitizing tablet and monitor screen overlay for calibration and measurement performance. Interventricular and posterior wall thicknesses and left ventricular (LV) internal dimensions were measured at end diastole and end systole by American Society of Echocardiography recommendations. 22,23 Aortic annular diameter was measured as previously described. 24 Doppler transaortic flow was assessed by identifying the apical view in which peak flow velocity was maximal and, after calibration, tracing the black-white interface outlining the Doppler flow envelope. 25 Heart rate was measured simultaneously. Prolonged isovolumic relaxation time was recognized as 92.4 ms in this population, representing the 97.5th percentile of values in 497 nondiabetic, nonobese, nonhypertensive participants in the fourth SHS examination. Calculation of Derived Variables End-diastolic LV dimensions were used to calculate LV mass by an anatomically validated formula. 26 Concentric LV geometry was identified by taking into account age effects on LV relative wall thickness according to the method of de Simone et al. 27 Systolic fractional shortening of the LV internal dimension and end-systolic stress were calculated by standard methods. 21 Aortic annular crosssectional area was calculated as follows: (diameter/2). 2 Doppler stroke volume was calculated as annular cross-sectional area times the time-velocity integral. 26 Arterial stiffness was estimated by the ratio of pulse pressure to stroke volume index. 28 Measures of Myocardial Performance The primary approach to assess myocardial contractile efficiency was to examine LV midwall shortening in relation to circumferential end-systolic stress measured at the level of the LV midwall using previously described methods Midwall shortening calculated from echocardiographic measurements was expressed as a percentage of the value predicted from circumferential end-systolic stress using equations derived from previously studied healthy subjects 30 ; this variable is called stress-corrected midwall shortening. 31 Statistical Analysis Data, expressed as mean SD for continuous variables and proportions for categorical variables, were analyzed by SPSS 12.0 software (SPSS, Chicago, Ill). Differences between 2 groups for continuous variables were assessed by t tests, with log transformation when needed to satisfy the assumption of normality, and the 2 statistic was used to determine differences of categorical variables. Relations between clinical and echocardiographic variables were assessed with consideration of appropriate covariates. Independence of differences from effects of covariates (age, gender, diabetes, and center location) was assessed by ANCOVA in the general linear model with the Sidak post hoc test or by logistic regression analysis for categorical variables. Two-tailed values of P 0.05 indicated statistical significance. The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written. Results Characteristics Of the 3658 participants in the fourth SHS examination, 1940 relatives of members of the original SHS cohort were 40 years of age. Most participants (57.5%) were women; the mean age was years; 294 (15%) and 675 (35%) met JNC-7 criteria for hypertension and prehypertension, respectively. Among hypertensive participants, 45 (15%) had systolic hypertension, defined as BP 140 mm Hg; 138 (47%) had diastolic hypertension, defined as BP 90 mm Hg; 57 (19%) had both diastolic and systolic hypertension; and 54 (18%) had normal BP on antihypertensive medication. Hypertension was more prevalent in men than women and increased with age in both genders (the Figure), rising from 1.7% in women and 9.3% in men at 14 to 19 years of age

3 Drukteinis et al Hypertension and Prehypertension in Young Adults 223 Prevalence of hypertension (vertical axis) is greater in male (solid bars) than female (striped bars) adolescent and young adult SHS participants and increases with age (horizontal axis) in both genders. (P 0.001) to 6.2% of women and 16.5% of men at 20 to 24 years of age (P 0.007), 5.1% of women and 16.4% of men at 25 to 29 years of age (P 0.001), 4.5% of women and 21.0% of men at 30 to 34 years of age (P 0.001), and 18.0% of women and 41.6% of men at 35 to 39 years of age (P 0.001). Compared with the nonhypertensive group, hypertensive and prehypertensive participants were more likely to be men (70% and 52% versus 38%, respectively), to be obese (75% and 65% versus 53%, respectively), and to have diabetes (23% and 9% versus 6%, respectively) and impaired fasting glucose (10% and 6% versus 3%, respectively; all intergroup differences, P 0.05). Hypertension was more prevalent in Oklahoma or Arizona than in North and South Dakota (18% and 19% versus 11%, respectively; P 0.001). Hypertensive and prehypertensive participants were also older ( and versus years; both P 0.001). In analyses that adjusted for age, gender, diabetes, and center, hypertension and prehypertension were associated with higher weight, body mass index, percent body fat, body surface area, waist circumference, and adipose mass (Table 1). However, no difference was seen in ankle/brachial index between groups. According to National Institutes of Health guidelines, 19 79% and 69% of hypertensive and prehypertensive participants, respectively, had central adiposity by waist circumference criteria compared with 55% in the nonhypertensive group (P 0.001). The hypertensive participants had higher mean urine albumin-to-creatinine ratio and higher hemoglobin A 1c levels, whereas prehypertensive participants did not differ statistically from their normotensive counterparts. Both the hypertensive and prehypertensive groups had higher total cholesterol, insulin, and low-density lipoprotein cholesterol than their normotensive counterparts, with no difference between groups in plasma creatinine, triglycerides, or high-density lipoprotein cholesterol after adjustment for covariates. Systemic Hemodynamics Heart rate and cardiac output were higher in both hypertensive and prehypertensive participants than in normotensive participants in absolute terms and after adjustment for age, gender, diabetes, and center location (Table 2). Total peripheral resistance was higher in both the hypertensive and prehypertensive groups; however, after adjustment for covariates, the difference remained significant in only the hypertensive group. Peripheral resistance index and pulse pressure/ TABLE 1. Clinical Characteristics of Normotensive, Prehypertensive, and Hypertensive Adolescent and Young Adult SHS Participants NT (N 971) PH (N 675) HT (N 294) HT vs PH PH vs HT NT vs HT Systolic BP, mm Hg Diastolic BP, mm Hg Body mass index, kg/m Weight, kg Body surface area, m Body fat, % Adipose mass, kg Waist circumference, cm Ankle/arm index Plasma creatinine, mg/dl Log urinary albumin/creatinine Total cholesterol, mg/dl HDL cholesterol, mg/dl LDL cholesterol, mg/dl Triglycerides, mg/dl Insulin, U/mL Hemoglobin A 1C,% NT indicates normotensive; PH, prehypertensive; HT, hypertensive; HDL, high-density lipoprotein; and LDL, low-density lipoprotein. Values are mean SD unless otherwise indicated. *Adjusted for age, gender, diabetes, and center location.

4 224 Circulation January 16, 2007 TABLE 2. Systemic Hemodynamics of Normotensive and Hypertensive Adolescent and Young Adult SHS Participants Heart rate, bpm Cardiac output, ml/min Cardiac output/body surface area, ml min m Total peripheral resistance, dyne cm s Pulse pressure/stroke index, mm Hg/mL m Peripheral resistance body surface area, dyne cm s 5 m Abbreviations as in Table 1. Values are mean SD unless otherwise indicated. *Adjusted for age, gender, diabetes status, and center location. stroke index were higher in both the hypertensive and prehypertensive groups. LV Systolic Function LV endocardial fractional shortening and ejection fraction from linear LV dimension or 2-dimensional wall motion scores were not statistically different among groups (Table 3). Hypertensive and prehypertensive participants had lower midwall shortening than the nonhypertensive group. Stresscorrected midwall shortening was not statistically different among groups. Circumferential end-systolic stress was significantly elevated in both the hypertensive and prehypertensive groups. The circumferential end-systolic stress/end-systolic volume index, a load-adjusted measure of chamber contractility, did not differ among groups after adjustment for age, gender, diabetes, and center. LV Diastolic Filling Isovolumic relaxation time was longer and the mean E velocity was slightly lower in hypertensive and prehypertensive participants, but the differences were not significant after adjustment for covariates (Table 4). More participants had prolonged isovolumic relaxation time in both the hypertensive and prehypertensive groups; however, after adjustment for covariates, the difference remained significant only in the hypertensive group. Mean mitral A velocity and atrial filling fraction were higher and the mean mitral E/A ratio was lower in both hypertensive and prehypertensive participants, even after covariate adjustment. Mitral deceleration time was slightly higher in hypertensive and prehypertensive participants, although this difference did not remain significant after covariate adjustment. LV Geometry Hypertensive and prehypertensive patients had, on average, thicker interventricular septal and LV posterior walls than normotensive participants (Table 5). Both LV chamber diameter and relative wall thickness were increased in the hypertensive and prehypertensive groups. As a result, LV mass in absolute terms or indexed for body surface area and height to its allometric power was higher in both the hypertensive and prehypertensive groups. The prevalence of LV hypertrophy was 3-fold higher in hypertensive and 2-fold higher in prehypertensive participants than in their normotensive counterparts. Classification of LV geometry, using age-adjusted relative wall thickness 27 and LV mass/height 2.7 partition values of 46.9 g/m 2.7 in women and 49.2 g/m 2.7 in men, shows minimally higher prevalence of concentric remodeling and 3-fold- and 2-fold-higher prevalences of eccentric LV hypertrophy in the hypertensive and prehypertensive groups, respectively. Concentric LV hypertrophy was rare (n 6, 0.4%) in the present study population. Discussion The present study documents high prevalences of hypertension (15%) and prehypertension (35%) in a large population- TABLE 3. Left Ventricular Systolic Function of Normotensive and Hypertensive Adolescent and Young Adult SHFS Participants Ejection fraction, % Dimensional ejection fraction, % Endocardial fractional shortening, % Midwall shortening, % Stress-corrected midwall shortening, % Circumferential end-systolic stress, kdyne/cm Circumferential end-systolic stress/end-systolic volume index, 10 kdynes cm 2 m Abbreviations as in Table 1. Values are mean SD unless otherwise indicated. *Adjusted for age, gender, diabetes status, and center location.

5 Drukteinis et al Hypertension and Prehypertension in Young Adults 225 TABLE 4. Diastolic Function of Normotensive and Hypertensive Adolescent and Young Adult SHFS Participants IVRT, ms IVRT 92 ms, n (%) 44 (4.6) 43 (6.5) 38 (13.3) Mitral E velocity, cm/s Mitral A velocity, cm/s Mitral E/A ratio Mitral deceleration time, ms Atrial filling fraction, % IVRT indicates isovolumic relaxation time. Other abbreviations as in Table 1. Values are mean SD unless otherwise indicated. *Adjusted for age, gender, diabetes status, and center location. based sample of adolescent and young adult American Indians (mean age, 29 years) who are particularly affected by the epidemic of obesity that is engulfing industrialized nations. Twice as many participants in this population and age range had diastolic hypertension than systolic hypertension. The higher prevalence of diastolic hypertension in this younger age group is consistent with previous data that arterial elasticity decreases with age, consequently increasing systolic hypertension, and is an independent risk factor for cardiovascular disease. 31,32 The presence of systolic hypertension in 102 participants and increased pulse pressure/ stroke index in the entire group of hypertensive participants identifies an early prevalence of increased arterial stiffness with multiple features related to insulin resistance, as suggested by the Bogalusa Heart Study. 33 In the present study population, hypertension was more prevalent in obese than nonobese participants (21% versus 9%), particularly those with central adiposity (19% versus 9%), and in those with TABLE 5. than without diabetes (24% versus 6%), consistent with evidence implicating these factors in precipitating hypertension in middle-aged to elderly adults. 34 Previous data in hypertensive adults indicated that lower stress-corrected midwall shortening predicts a higher rate of cardiovascular events. 35 Our population did not exhibit a difference in circumferential end-systolic stress/end-systolic volume index or stress-corrected midwall shortening between groups. The lack of difference in these contractility indexes between young normotensive and hypertensive SHS participants indicates that myocardial function has not yet been compromised despite LV geometric abnormalities at this early and relatively mild stage of hypertension. The percentage of patients with prolonged isovolumic relaxation time was higher in the hypertensive and prehypertensive groups, which also had higher peak mitral A velocity and atrial filling fractions. Hypertensive and prehypertensive participants had significantly lower mean mitral E/A ratios, suggesting LV Geometry of Normotensive and Hypertensive Adolescent and Young Adult SHFS Participants IVSd, cm LVIDd, cm PWTd, cm LVIDs, cm LV mass, g LV mass/bsa, g/m LV mass/height 2.7, g/m RWTd, cm LV hypertrophy, n (%) 62 (6.5) 76 (11.4) 56 (19.9) Normal LV geometry, n (%) 889 (92.8) 579 (87.2) 220 (78.3) Concentric remodeling, n (%) 7 (0.7) 9 (1.4) 5 (1.8) NS NS NS Concentric LV hypertrophy, n (%) 4 (0.4) 2 (0.3) 0 (0) NS NS NS Eccentric LV hypertrophy, n (%) 58 (6.1) 74 (11.1) 56 (19.9) IVSd indicates interventricular septal thickness in diastole; LVIDd, LV internal dimension diastole; LVIDs, LVID in systole; PWTd, posterior wall thickness in diastole; BSA, body surface area; and RWTd, relative wall thickness, diastole. Other abbreviations as in Table 1. Values are mean SD unless otherwise indicated. *Adjusted for age. Unadjusted for age.

6 226 Circulation January 16, 2007 slightly impaired LV relaxation that was offset by a greater atrial contribution to ventricular filling in a young, mildly hypertensive population. Our results are more marked than the marginal differences in LV diastolic function reported by Palatini et al 36 in the Hypertension and Ambulatory Recording Venetia Study (HARVEST) in young adults 18 to 45 years of age with mild, stage 1 hypertension, a difference that may be due to the greater prevalence and severity of obesity in our large, population-based sample of young participants. The importance of systemic hypertension in the pathogenesis of LV hypertrophy is well established, and previous population-based studies have shown strong associations between LV mass and BP within the normal to slightly elevated range Even after adjustment for age, both the hypertensive and prehypertensive groups exhibited cardiac structural features associated with increased cardiovascular risk, including increased interventricular septal, posterior wall, and relative wall thicknesses and higher LV mass, LV mass/body surface area, and LV mass/height. 2.7 In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 37,38 systolic BP was responsible for much of the increase in LV mass over a 10-year period in young, healthy black and white men and women with low prevalences of hypertension (1.6% to 3.8%). The present study differs from previous ones in population-based samples in grouping adolescents and young adults by the JNC-7 categories of normal BP, prehypertension, and hypertension and by documenting substantial prevalences of prognostically important measures of preclinical cardiovascular disease in prehypertensive and especially in hypertensive participants despite their young age. Future studies are needed to determine whether the abnormalities of LV structure that we have identified at this stage contribute to subsequent cardiovascular events. The prevalence of LV hypertrophy was elevated in hypertensive and prehypertensive SHFS participants and was similar to findings in hypertensive children and adolescents by Daniels et al. 41 Approximately 20% of hypertensive participants in the present study had eccentric LV hypertrophy, but few had either concentric LV hypertrophy or concentric LV remodeling. This is in contrast to 16% of hypertensive children having concentric hypertrophy in a study by Hanevold et al, 10 with especially higher prevalences among Hispanic or black subjects. The absence of concentric LVH in young SHS participants may reflect their generally mild hypertension, whereas the high prevalence of eccentric LVH may be related to the high prevalence of obesity in our population, with a larger volume of circulating plasma. 42 Our study is the first large population-based study to examine specifically the cardiac and systemic hemodynamic status of the new JNC-7 category of prehypertension. A recent study by Zhang et al 8 provides evidence for an increase in incident cardiovascular disease among prehypertensive adults 45 to 74 years of age at baseline and an even more striking incident among those with both prehypertension and diabetes in the SHS, suggesting a need for more vigilant monitoring of prehypertensive adults. A previous report by Toikka et al 43 used borderline hypertension as a model for prehypertension before the new JNC-7 criteria and found no difference in LV mass but differences in LV geometry between borderline hypertensive young adult men and normotensive control subjects. From our data, it appears that prehypertension represents an intermediate point between hypertension and normal BP. In ANCOVAs, prehypertensive participants differ similarly from hypertensive and the now more stringently defined normotensive participants with regard to changes in cardiac structure and function. The differences seen between prehypertensive and normotensive participants may be due in part to a supranormalization of normotensive control subjects. This suggests that new partition values for normal cardiac structural and functional measures are needed if prehypertension is documented to be a robust predictor of increased cardiovascular risk. Although our data suggest parallels between cardiovascular effects of prehypertension in adolescents and young adults and the well-known detrimental effects of hypertension, further data from longitudinal observational and therapeutic studies are needed before we can draw conclusions about the clinical implications of prehypertension. Study Limitations The present study assessed a population-based sample of American Indians with higher prevalences of overweight and diabetes than the general US population. Although this may limit the generalizability of the present results to some populations, our findings are relevant to the increasing proportion of young adults in developed countries who suffer from overweight and/or diabetes. In addition, despite extensive efforts to standardize measurements, with the use of the same echocardiographic method as in other clinical and population-based studies, subtle differences in performance technique among sites also could have influenced results. Conclusions Our results show that even small elevations in BP, as seen with prehypertension, can have detrimental effects on hemodynamics and cardiovascular structure and function in an adolescent and young adult American Indian population with many of the same risk factors plaguing the United States and industrialized countries around the world. Acknowledgments We thank the Indian Health Service, SHS participants, and participating tribal communities for their extraordinary cooperation and involvement that made this study possible; Betty Jarvis, RN, Tauqeer Ali, MD, and Marcia O Leary for their coordination of 3 study centers; Dawn Fishman, BA, for her data coordination and management of the database; Tauqeer Ali, MD, Rosina Briones, RDMS, Joanne Carter, RDMS, for their technical assistance; and Virginia M. Burns for her assistance in the preparation of this manuscript. Sources of Funding This work was supported in part by grants HL41642, HL41652, HL41654, HL65521, and M10RR (GCRC) from the National Institutes of Health, Bethesda, Md. None. Disclosures References 1. Mokdad AJ, Ford ES, Bowman BA, Dietz WH, Vinivor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, JAMA. 2003;289:76 79.

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