Published online before print April 29, 2002, doi: 10.1161/01.CIR.0000018121.67607.CE
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:2712.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Obesity Accelerates the Progression of Coronary Atherosclerosis in Young Men
From the University of Texas Health Science Center at San Antonio (H.C.M., C.A.M.); the Southwest Foundation for Biomedical Research (H.C.M.), San Antonio, Tex; the Ohio State University (E.E.H.), Columbus, Ohio; and the Louisiana State University Health Sciences Center (A.W.Z., G.T.M., R.E.T., J.P.S.), New Orleans, La.
Correspondence to Henry C. McGill, Jr, MD, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549. E-mail hmcgill{at}icarus.sfbr.org Reprint requests to Jack P. Strong, MD, Department of Pathology, Louisiana State University Health Sciences Center, 1901 Perdido St, New Orleans, LA 70112-1393. E-mail jstron@lsumc.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— Obesity is a risk factor for adult coronary heart disease and is increasing in prevalence among youths as well as adults. Results regarding the association of obesity with atherosclerosis are conflicting, particularly when analyses account for other risk factors.
Methods and Results— The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study collected arteries, blood, and other tissue from 
3000 persons aged 15 to 34 years dying of external causes and autopsied in forensic laboratories. We measured gross atherosclerotic lesions in the right coronary artery (RCA), American Heart Association (AHA) lesion grade in the left anterior descending coronary artery (LAD), serum lipid concentrations, serum thiocyanate (for smoking), intimal thickness of renal arteries (for hypertension), glycohemoglobin (for hyperglycemia), and adiposity by body mass index (BMI) and thickness of the panniculus adiposus. BMI in young men was associated with both fatty streaks and raised lesions in the RCA and with AHA grade and stenosis in the LAD. The effect of obesity (BMI>30 kg/m2) on RCA raised lesions was greater in young men with a thick panniculus adiposus. Obesity was associated with non-HDL and HDL (inversely) cholesterol concentrations, smoking (inversely), hypertension, and glycohemoglobin concentration, and these variables accounted for 15% of the effect of obesity on coronary atherosclerosis in young men. BMI was not associated with coronary atherosclerosis in young women although there was trend among those with a thick panniculus adiposus.
Conclusions— Obesity is associated with accelerated coronary atherosclerosis in adolescent and young adult men. These observations support the current emphasis on controlling obesity to prevent adult coronary heart disease.
Key Words: coronary heart disease • atherosclerosis • obesity • risk factors • youth
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
For many years, there were inconsistent results regarding the association of obesity with atherosclerosis and coronary heart disease (CHD), despite overwhelming evidence of its association with CHD risk factors (reviewed by Alexander1). The relationship became clearer as long-term follow-up studies found obesity to be associated with CHD independently of other risk factors.2 The increasing prevalence of obesity among adults3 and youths,4 and recognition of the role of central adiposity,5 have directed renewed attention to the relation of obesity to atherosclerosis and CHD.
See p 2696
The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study was organized in 1985 to examine the effects of risk factors for adult CHD on atherosclerosis in autopsied persons aged 15 to 34 years dying of external causes.6 Previous reports have described the association of dyslipidemia, smoking, hypertension, hyperglycemia, and obesity with atherosclerosis in the coronary arteries and aorta.7–10 A previous analysis7 indicated little association of obesity with aortic atherosclerosis and a strong association with coronary atherosclerosis in men. The present report focuses on the effects of obesity on coronary atherosclerosis, consolidates previously reported results, adds 1300 cases (including over 300 women) to the analyses, examines the effects of fat distribution, and presents topographic maps of lesion prevalence in the right coronary artery. The results strongly support control of obesity in youth as important in the long-range primary prevention of atherosclerosis and its sequelae.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Study Design
Fifteen cooperating centers followed standardized procedures to collect specimens and information and to submit them to central laboratories for analysis. A statistical center received all data.
Study subjects were persons aged 15 through 34 years who died of external causes (accident, homicide, or suicide) within 72 hours after injury and were autopsied within 48 hours after death in a forensic laboratory.8 The analyses in this report are based on 2133 men and 688 women accessioned between June 1, 1987 and August 31, 1994. The Institutional Review Board of each participating center approved this study.
Preparation of Arteries
The PDAY team dissected the right coronary artery (RCA) from the heart, opened it longitudinally, and fixed it in 10% neutral buffered formalin. The team perfused the left main coronary artery and the left anterior descending coronary artery (LAD) with formalin at a pressure of 100 mm Hg. A central laboratory stained the fixed RCAs with Sudan IV. Another central laboratory excised a block from the LAD just distal to the origin of the circumflex artery. Paraffin sections from half of this block were stained with Gomori’s trichrome acid fuchsin (GTAF), and frozen sections from the other half were stained with Oil Red O.10 RCAs were available for 2736 cases, and LAD sections for 760 cases.
Body Mass Index
The body was weighed to the nearest 0.5 kg or 1 lb before tissue or fluids were removed from the body. Cadaver length, from the vertex of the cranium to the base of the heel, was measured to the nearest 1 cm or 0.5 in. We computed the body mass index (BMI) as weight (kilograms) divided by height (meters) squared. Cases were grouped into categories of BMI<25, 25
BMI
30, and BMI>30 kg/m2.
Panniculus Adiposus
The PDAY team measured subcutaneous abdominal fat, including the subcutaneous tissue from the inner edge of the rectus sheath, at a point halfway between the xiphoid process and the umbilicus, to the nearest 1 millimeter. Cases were classified as or > the median value for their sex and BMI classification (men: 12, 20, and 30 mm; women: 20, 28, and 37 mm for BMI<25, 25BMI30, BMI>30, respectively) in order to reflect fat distribution rather than overall fat and to offset the known sex difference.
Other Risk Factors
Methods for postmortem assessment of the other risk factors are described in previous publications.7–9 Briefly, we measured total serum cholesterol and HDL cholesterol (after precipitation of other lipoproteins) by a cholesterol oxidase method and calculated non-HDL cholesterol by subtraction. Because some trauma victims receive large quantities of fluids, we excluded all serum data if the serum cholesterol concentration was <100 mg/dL. Smokers were identified by serum thiocyanate concentration 90 µmol/L. Hypertension was identified when the intimal thickness of small renal arteries indicated a mean blood pressure 110 mm Hg. Chronic hyperglycemia was indicated by a red blood cell glycohemoglobin concentration 8%.
Gross RCA Lesions
Three pathologists independently estimated the percentage of intimal surface involved by fatty streaks (flat intimal lesions stained by Sudan IV) and by raised lesions (fibrous plaques and other complicated lesions).8 The mean of the 3 grades was used in the statistical analyses.
Microscopic LAD Lesions
As described in a previous publication,10 2 pathologists reached a consensus grade according to the American Heart Association (AHA) system.11,12 In GTAF sections, the morphometry laboratory measured the intimal area and the potential lumen area as the maximum area that could occur within the measured length of the internal elastic lamina. We defined an intimal area 40% of the potential lumen area combined with an AHA grade 3 as atherosclerotic stenosis 40%.
Topographic RCA Maps
The morphometry laboratory digitized the image of each Sudan IV–stained RCA and an outline of raised lesions on a black-and-white print and converted the images to a standard template.13 Composite images were assembled to indicate prevalence of each type of lesion at each location in the image of the artery.
Statistical Analysis
The associations of intimal surface involved by atherosclerosis, lipid risk factors, and glycohemoglobin with adiposity were analyzed by multiple regression analysis. A logit transformation, with a small constant added to avoid the logarithm of zero, was applied to the extent of surface area involved. We analyzed the prevalence of AHA grades using polytomous logistic regression.14 The associations of obesity with stenosis 40%, hypertension, and smoking were analyzed by binary logistic regression.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Adiposity
Table 1 shows the mean BMI and panniculus thickness by sex, race, and age. Among whites, men had a greater BMI than women (P=0.0001); among blacks, men had a slightly lower BMI than women (P=0.1733). White men had a greater BMI than black men (P=0.0080), whereas black women had a greater BMI than white women (P= 0.0062). In whites, BMI increased linearly with age (P=0.0001). In blacks, BMI increased from age 15 to 19 to 20 to 24 (P= 0.0004) and did not change in subsequent ages (P>0.2446).
|
Women of both races had a thicker panniculus than men (P0.0003). White men had a thicker panniculus than black men (P=0.0001), whereas white and black women were not significantly different (P=0.5456). The panniculus increased linearly with age in whites (P= 0.0001) and blacks (P=0.0008) although the rate of increase was greater in whites (P=0.0079).
The partial correlation coefficient between BMI and panniculus, adjusted for sex, race, and age, was 0.52 (P=0.0001).
Relation of Adiposity to Other Risk Factors
Table 2 shows that non-HDL cholesterol concentration was directly associated with both BMI (P=0.0001) and panniculus thickness (P=0.0444). HDL cholesterol concentration was inversely associated with BMI (P=0.0577), but not with panniculus thickness (P=0.2462). Glycohemoglobin was directly associated with BMI (P=0.0001), but not with panniculus thickness (P=0.1458). Smoking prevalence decreased with increasing BMI (P=0.0001), but not with panniculus thickness (P=0.6116), and smokers had a lower BMI than nonsmokers (nonsmokers, 25.5±0.2; smokers, 24.2±0.2 kg/m2; P=0.0001). Prevalence of hypertension did not differ between BMI<25 and 25BMI30 (P=0.3318), but was greater with BMI>30 than with BMI30 (P=0.0408). Prevalence of hypertension was not associated with panniculus thickness (P=0.5384).
|
Relation of Adiposity to Lesions of the RCA
The mean extent of lesions by BMI, panniculus thickness, and sex, adjusted for race and 5-year age group, is shown in Figure 1. In men, extent of fatty streaks increased with increasing BMI (P=0.0001) but was not affected by panniculus thickness (P=0.1734). There was a nonsignificant trend for extent of fatty streaks to increase with increasing BMI in women with a thick panniculus (P=0.1449), whereas there was no association in women with a thin panniculus (P=0.3454). Over all categories of BMI, women with a thick panniculus had an increased extent of fatty streaks (P=0.0225).
|
Extent of raised lesions increased with increasing BMI in men regardless of panniculus thickness (P=0.0001). In men, there was no effect of panniculus thickness for BMI30, whereas for BMI>30, those with a thick panniculus had more extensive raised lesions (P=0.0244). Neither BMI nor panniculus thickness was associated with extent of raised lesions in women.
There were no significant interactions of age with obesity (P>0.6981) or race with obesity (P>0.4617) for fatty streaks or raised lesions.
Topographic maps of lesion prevalence in the RCA of men (Figure 2) and women (Figure 3) show that adiposity did not change the pattern of lesion distribution. Adiposity increased the prevalence of both fatty streaks and raised lesions in men although it had little effect on prevalence of lesions in women. These relationships were similar to that shown by analyses of extent of intimal surface (Figure 1). Lesion prevalence was greatest in the first 2 to 3 cm of the RCA,13 and in men, the effects of adiposity on raised lesions in this region were evident even before age 25.
|
|
Adiposity and RCA Lesions After Adjusting for Other Risk Factors
We compared the effects of adiposity with and without adjusting for the other risk factors in 1080 men having measurements for all risk factors. The mean extent of lesions in these men with and without adjusting for other risk factors is shown in Figure 4. Adjusting for the other risk factors diminished but did not eliminate the effects of adiposity (fatty streaks, P=0.0001; raised lesions, P=0.0642) and did not change the observed associations. The effects of adiposity on lesions, expressed as the ratio of mean extent of lesions relative to the mean extent in the category of BMI<25 kg/m2 and panniculus thicknessmedian, were reduced an average of 15% for fatty streaks and 12% for raised lesions due to adjustment for other risk factors.
|
Adiposity and LAD Lesions
Preliminary analyses indicated no difference in prevalence of AHA grades or stenosis 40% between BMI 25 to 30 and BMI<25, but there were differences between BMI30 and BMI>30. Table 3 shows odds ratios before and after adjusting for other risk factors. Men with BMI>30 had a greater prevalence of AHA grades 2 to 3, AHA grades 4 to 5, and stenosis 40% than those with BMI30. There was no association of BMI with AHA grade or stenosis in women. Panniculus thickness was not associated with AHA grade or stenosis in men or women. Other risk factors did not account for the association of BMI with AHA grade or stenosis in men. 0
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Summary of Results
Obesity in young men, as defined by BMI, is associated with both fatty streaks and raised lesions in the RCA and with the microscopic grade of atherosclerosis and stenosis in the LAD. The effect of BMI on RCA raised lesions is greater among men with a thick panniculus adiposus, that is, men with a central pattern of adiposity. There is little association of adiposity with coronary atherosclerosis in young women, although there is a slight but nonsignificant trend for an association of BMI with fatty streaks in women who have a thick panniculus adiposus. Obesity is associated with non-HDL and HDL cholesterol concentration, hypertension, smoking, and glycohemoglobin concentration, but these risk factors account for only about 15% of its effects on atherosclerosis.
Comparison With Other Studies
Alexander1 reviewed the predominantly negative results regarding the relationship of obesity to atherosclerosis in both autopsy and angiographic studies. Positive findings may be more frequent among the more recent studies, possibly because the increasing prevalence of obesity makes the association easier to detect. The association of obesity with other cardiovascular risk factors in youth is consistent with the results of many other studies.15,16
Mechanism of Effects of Obesity on Atherosclerosis and CHD
Obesity may affect atherosclerosis through unrecognized intervening variables.1 Emerging risk factors for CHD also associated with obesity are C-reactive protein in adults17 and children,18,19 insulin resistance,20–22 and fibrinogen.23 As other physiological variables related to obesity are identified, they may explain a larger proportion of the association of obesity with atherosclerosis through plausible physiological mechanisms.
Lack of Association of Obesity With Atherosclerosis in Young Women
The association of obesity with clinical CHD in middle-aged and older women is firmly established, but the relative risks for women are slightly lower than those for men.24 However, we find only a weak and nonsignificant trend of an association of BMI with fatty streaks in the RCA of young women who also had a thick panniculus (Figure 1). Serum lipids, smoking, blood pressure, or elevated glycohemoglobin did not account for the differences in the effects of obesity in men compared with women.
At an equivalent BMI, women at all ages, even as children, have a larger percentage of body fat than men.25 However, men are more likely to have a central (visceral) distribution of fat than women,26 and most reports indicate that the adverse consequences of obesity are more strongly associated with central obesity27–29 than non-central obesity.
Another possible explanation is the slower progression of atherosclerosis with age in young women compared with that in young men. Coronary raised lesions in young women lag behind those in young men by about 10 years independently of risk factor status, and obesity may accelerate the process in women only after 35 years of age. In older women, obesity may affect susceptibility to plaque rupture and thrombosis rather than affecting atherosclerosis.1
Fat Distribution
The potential importance of central obesity compared with peripheral obesity was not appreciated when this study began in 1985, and we do not have any of the usual measurements of this variable. Subcutaneous abdominal fat is associated with visceral fat (r 0.6),30 and therefore, the thickness of the panniculus may also provide information on visceral fat. Despite the numerous reports similar to those cited regarding the contribution of visceral obesity to CHD, 2 studies report that subcutaneous abdominal fat is more closely associated with insulin resistance than visceral fat;21,22 and 2 others find that BMI is a stronger predictor of other major risk factors than waist-hip ratio.31,32 Apparently, excess adipose tissue in any depot adversely affects health-related variables.
Implications
Our results show that obesity in adolescent and young adult men is associated with extent and severity of early atherosclerotic lesions. This conclusion is consistent with results of long-term follow-up studies, which show that obesity in youth not only predicts obesity in adulthood,20,33 but also predicts CHD morbidity and mortality.34,35 These results indicate that obesity in adolescents and young adults, through mechanisms yet to be identified, accelerates the progression of atherosclerosis decades before clinical manifestations appear. Obesity is an important modifiable contributor to coronary atherosclerosis, particularly in young adult men, and efforts to control childhood obesity are justified for the long-range prevention of CHD as well as other chronic diseases. The increasing prevalence of obesity among young persons4 emphasizes the need for obesity control efforts.
|
Acknowledgments |
|---|
The following is a list of institutions cooperating in the PDAY study and supporting grants from the NHLBI and other sources: University of Alabama, HL-33733, HL-33728; Albany Medical College, HL-33765; Baylor College of Medicine, HL-33750; University of Chicago, HL-33740, HL-45715; The University of Illinois, HL-33758; Louisiana State University Health Science Center, HL-33746, HL-45720; University of Maryland, HL-33752, HL-45693; Medical College of Georgia, HL-33772; University of Nebraska Medical Center, HL-33778; The Ohio State University, HL-33760, HL-45694; Southwest Foundation for Biomedical Research, HL-39913; gift of Peter and Beth Dahlberg; University of Texas Health Science Center at San Antonio, HL-33749, HL-45719; Vanderbilt University, HL-33770, HL-45718; and West Virginia University Health Sciences Center, HL-33748.
Received December 27, 2001; revision received March 29, 2002; accepted March 29, 2002.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Alexander JK. Obesity and coronary heart disease. Am J Med Sci. 2001; 321: 215–224.[CrossRef][Medline] [Order article via Infotrieve]
2.
Jousilahti P, Tuomilehto J, Vartiainen E, et al. Body weight, cardiovascular risk factors, and coronary mortality: 15-year follow-up of middle-aged men and women in eastern Finland. Circulation. 1996; 93: 1372–1379.
3.
Kuczmarski RJ, Flegal KM, Campbell SM, et al Increasing prevalence of overweight among US adults: the National Health and Nutrition Examination Surveys, 1960 to 1991. JAMA. 1994; 272: 205–211.
4.
Troiano RP, Flegal KM, Kuczmarski RJ, et al. Overweight prevalence and trends for children and adolescents: the National Health and Nutrition Examination Surveys, 1963 to 1991. Arch Pediatr Adolesc Med. 1995; 149: 1085–1091.
5.
Stern MP, Haffner SM. Body fat distribution and hyperinsulinemia as risk factors for diabetes and cardiovascular disease. Arteriosclerosis. 1986; 6: 123–130.
6. Wissler RW. U S A multicenter study of the pathobiology of atherosclerosis in youth. Ann N Y Acad Sci. 1991; 623: 26–39.[Medline] [Order article via Infotrieve]
7.
McGill HC Jr, McMahan CA, Malcom GT, et al. Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Arterioscler Thromb Vasc Biol. 1995; 15: 431–440.
8.
McGill HC Jr, McMahan CA, Malcom GT, et al. Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. Arterioscler Thromb Vasc Biol. 1997; 17: 95–106.
9.
McGill HC Jr, McMahan CA, Tracy RE, et al. Relation of a postmortem renal index of hypertension to atherosclerosis and coronary artery size in young men and women. Arterioscler Thromb Vasc Biol. 1998; 18: 1108–1118.
10.
McGill HC Jr, McMahan CA, Zieske AW, et al. Association of coronary heart disease risk factors with microscopic qualities of coronary atherosclerosis in youth. Circulation. 2000; 102: 374–379.
11.
Stary HC, Chandler AB, Glagov S, et al. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1994; 89: 2462–2478.
12.
Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb Vasc Biol. 1995; 15: 1512–1531.
13.
McGill HC Jr, McMahan CA, Herderick EE, et al. Effects of coronary heart disease risk factors on atherosclerosis of selected regions of the aorta and right coronary artery. Arterioscler Thromb Vasc Biol. 2000; 20: 836–845.
14. Hosmer DW Jr, Lemeshow S. Applied Logistic Regression. New York, NY: John Wiley and Sons; 1989.
15. Gillum RF. Distribution of waist-to-hip ratio, other indices of body fat distribution and obesity and associations with HDL cholesterol in children and young adults aged 4–19 years: the Third National Health and Nutrition Examination Survey. Int J Obes. 1999; 23: 556–563.[CrossRef]
16.
Daniels SR, Morrison JA, Sprecher DL, et al. Association of body fat distribution and cardiovascular risk factors in children and adolescents. Circulation. 1999; 99: 541–545.
17.
Visser M, Bouter LM, McQuillan GM, et al. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999; 282: 2131–2135.
18. Cook DG, Mendall MA, Whincup PH, et al. C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis. 2000; 149: 139–150.[CrossRef][Medline] [Order article via Infotrieve]
19. Ford ES, Galuska DA, Gillespie C, et al. C-reactive protein and body mass index in children: findings from the Third National Health and Nutrition Examination Survey, 1988–1994. J Pediatr. 2001; 138: 486–492.[CrossRef][Medline] [Order article via Infotrieve]
20. Steinberger J, Moran A, Hong CP, et al. Adiposity in childhood predicts obesity and insulin resistance in young adulthood. J Pediatr. 2001; 138: 469–473.[CrossRef][Medline] [Order article via Infotrieve]
21. Abate N, Garg A, Peshock RM, et al. Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest. 1995; 96: 88–98.
22. Goodpaster BH, Thaete FL, Simoneau J-A, et al. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes. 1997; 46: 1579–1585.[Abstract]
23.
Cook DG, Whincup PH, Miller G, et al. Fibrinogen and factor VII levels are related to adiposity but not to fetal growth or social class in children aged 10–11 years. Am J Epidemiol. 1999; 150: 727–736.
24.
Calle EE, Thun MJ, Petrelli JM, et al. Body-mass index and mortality in a prospective cohort of U.S. adults. N Eng J Med. 1999; 341: 1097–1105.
25.
Gallagher D, Visser M, Sepulveda D, et al. How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups? Am J Epidemiol. 1996; 143: 228–239.
26.
Lemieux S, Prud’homme D, Bouchard C, et al. Sex differences in the relation of visceral adipose tissue accumulation to total body fatness. Am J Clin Nutr. 1993; 58: 463–467.
27.
Folsom AR, Kaye SA, Sellers TA, et al. Body fat distribution and 5-year risk of death in older women. JAMA. 1993; 269: 483–487.
28. Lemieux S, Despres JP, Moorjani S, et al. Are gender differences in cardiovascular disease risk factors explained by the level of visceral adipose tissue? Diabetologia. 1994; 37: 757–764.[Medline] [Order article via Infotrieve]
29. Duncan BB, Chambless LE, Schmidt MI, et al. Correlates of body fat distribution: variation across categories of race, sex, and body mass in the Atherosclerosis Risk in Communities Study. Ann Epidemiol. 1995; 5: 192–200.[CrossRef][Medline] [Order article via Infotrieve]
30.
Enzi G, Gasparo M, Biondetti PR, et al. Subcutaneous and visceral fat distribution according to sex, age, and overweight, evaluated by computed tomography. Am J Clin Nutr. 1986; 44: 739–746.
31.
Young TK, Gelskey DE. Is noncentral obesity metabolically benign? Implications for prevention from a population survey. JAMA. 1995; 274: 1939–1941.
32. Rexrode KM, Buring JE, Manson JE. Abdominal and total adiposity and risk of coronary heart disease in men. Int J Obes. 2001; 25: 1047–1056.[CrossRef][Medline] [Order article via Infotrieve]
33.
Whitaker RC, Wright JA, Pepe MS, et al. Predicting obesity in young adulthood from childhood and parental obesity. N Eng J Med. 1997; 337: 869–873.
34. Must A, Jacques PF, Dallal GE, et al. Long-term morbidity and mortality of overweight adolescents: a follow-up of the Harvard Growth Study of 1922–1935. N Eng J Med. 1992; 327: 1350–1355.[Abstract]
35. Gunnell DJ, Frankel SJ, Nanchahal K, et al. Childhood obesity and adult cardiovascular mortality: a 57-y follow-up study based on the Boyd Orr cohort. Am J Clin Nutr. 1998; 67: 1111–1118.[Abstract]
This article has been cited by other articles:
 |
|
 |
|
  M. R. Meyer and M. Barton ER{alpha}, ER{beta}, and gpER: novel aspects of oestrogen receptor signalling in atherosclerosis Cardiovasc Res, September 1, 2009; 83(4): 605 - 610. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Steinberger, S. R. Daniels, R. H. Eckel, L. Hayman, R. H. Lustig, B. McCrindle, and M. L. Mietus-Snyder Progress and Challenges in Metabolic Syndrome in Children and Adolescents: A Scientific Statement From the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism Circulation, February 3, 2009; 119(4): 628 - 647. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rosengren, J. Perk, and J. Dallongeville CHAPTER 12 Prevention of Cardiovascular Disease ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Abel, S. E. Litwin, and G. Sweeney Cardiac Remodeling in Obesity Physiol Rev, April 1, 2008; 88(2): 389 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. McGill Jr, C. A. McMahan, and S. S. Gidding Preventing Heart Disease in the 21st Century: Implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study Circulation, March 4, 2008; 117(9): 1216 - 1227. [Full Text] [PDF]
|
|
|
|
 |
|
 F. W. Kiefer, M. Zeyda, J. Todoric, J. Huber, R. Geyeregger, T. Weichhart, O. Aszmann, B. Ludvik, G. R. Silberhumer, G. Prager, et al. Osteopontin Expression in Human and Murine Obesity: Extensive Local Up-Regulation in Adipose Tissue but Minimal Systemic Alterations Endocrinology, March 1, 2008; 149(3): 1350 - 1357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Surmi, R. D. Atkinson, M. L. Gruen, K. R. Coenen, and A. H. Hasty The role of macrophage leptin receptor in aortic root lesion formation Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E488 - E495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Nesto and K. Mackie Endocannabinoid system and its implications for obesity and cardiometabolic risk Eur. Heart J. Suppl., March 1, 2008; 10(suppl_B): B34 - B41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Mutungi, J. Ratliff, M. Puglisi, M. Torres-Gonzalez, U. Vaishnav, J. O. Leite, E. Quann, J. S. Volek, and M. L. Fernandez Dietary Cholesterol from Eggs Increases Plasma HDL Cholesterol in Overweight Men Consuming a Carbohydrate-Restricted Diet J. Nutr., February 1, 2008; 138(2): 272 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Atkinson, K. R. Coenen, M. R. Plummer, M. L. Gruen, and A. H. Hasty Macrophage-derived apolipoprotein E ameliorates dyslipidemia and atherosclerosis in obese apolipoprotein E-deficient mice Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E284 - E290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D De Ferranti and S. K Osganian Epidemiology of paediatric metabolic syndrome and type 2 diabetes mellitus Diabetes and Vascular Disease Research, December 1, 2007; 4(4): 285 - 296. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Barton and M. J. Husmann Effects of obesity on mortality in patients with unstable angina or non-ST-elevation myocardial infarction Eur. Heart J., December 1, 2007; 28(23): 2950 - 2950. [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Getz and C. A. Reardon Nutrition and Cardiovascular Disease Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2499 - 2506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Barton, R. Minotti, and E. Haas Inflammation and Atherosclerosis Circ. Res., October 12, 2007; 101(8): 750 - 751. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gomez-Ambrosi, V. Catalan, B. Ramirez, A. Rodriguez, I. Colina, C. Silva, F. Rotellar, C. Mugueta, M. J. Gil, J. A. Cienfuegos, et al. Plasma Osteopontin Levels and Expression in Adipose Tissue Are Increased in Obesity J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3719 - 3727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Lear, K. H. Humphries, S. Kohli, J. J. Frohlich, C. L. Birmingham, and G. B. J. Mancini Visceral Adipose Tissue, a Potential Risk Factor for Carotid Atherosclerosis: Results of the Multicultural Community Health Assessment Trial (M-CHAT) Stroke, September 1, 2007; 38(9): 2422 - 2429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Coenen and A. H. Hasty Obesity potentiates development of fatty liver and insulin resistance, but not atherosclerosis, in high-fat diet-fed agouti LDLR-deficient mice Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E492 - E499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ninomiya, M. Kubo, Y. Doi, K. Yonemoto, Y. Tanizaki, M. Rahman, H. Arima, K. Tsuryuya, M. Iida, and Y. Kiyohara Impact of Metabolic Syndrome on the Development of Cardiovascular Disease in a General Japanese Population: The Hisayama Study Stroke, July 1, 2007; 38(7): 2063 - 2069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Russo, P. Del Mese, G. Doronzo, A. De Salve, M. Secchi, M. Trovati, and G. Anfossi Platelet Resistance to the Antiaggregatory Cyclic Nucleotides in Central Obesity Involves Reduced Phosphorylation of Vasodilator-Stimulated Phosphoprotein Clin. Chem., June 1, 2007; 53(6): 1053 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Fantuzzi and T. Mazzone Adipose Tissue and Atherosclerosis: Exploring the Connection Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 996 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shimazaki, T. Saito, K. Yonemoto, Y. Kiyohara, M. Iida, and Y. Yamashita Relationship of Metabolic Syndrome to Periodontal Disease in Japanese Women: The Hisayama Study Journal of Dental Research, March 1, 2007; 86(3): 271 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Mundy, E. Haas, I. Bhattacharya, C. C. Widmer, M. Kretz, R. Hofmann-Lehmann, R. Minotti, and M. Barton Fat intake modifies vascular responsiveness and receptor expression of vasoconstrictors: Implications for diet-induced obesity Cardiovasc Res, January 15, 2007; 73(2): 368 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. De Lorenzo, V. Del Gobbo, M. G. Premrov, M. Bigioni, F. Galvano, and L. Di Renzo Normal-weight obese syndrome: early inflammation? Am. J. Clinical Nutrition, January 1, 2007; 85(1): 40 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Dick, P. S. Katz, M. Farias III, M. Morris, J. James, J. D. Knudson, and J. D. Tune Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2997 - H3002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Gidding, C. A. McMahan, H. C. McGill, L. A. Colangelo, P. J. Schreiner, O. D. Williams, and K. Liu Prediction of Coronary Artery Calcium in Young Adults Using the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score: The CARDIA Study Arch Intern Med, November 27, 2006; 166(21): 2341 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. McMahan, S. S. Gidding, G. T. Malcom, R. E. Tracy, J. P. Strong, H. C. McGill Jr, and for the Pathobiological Determinants of Atheroscle Pathobiological Determinants of Atherosclerosis in Youth Risk Scores Are Associated With Early and Advanced Atherosclerosis Pediatrics, October 1, 2006; 118(4): 1447 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W Anderson, S. M Schwartz, J. Hauptman, M. Boldrin, M. Rossi, V. Bansal, and C. A Hale Low-Dose Orlistat Effects on Body Weight of Mildly to Moderately Overweight Individuals: A 16 Week, Double-Blind, Placebo-Controlled Trial Ann. Pharmacother., October 1, 2006; 40(10): 1717 - 1723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zarich, C. Luciano, J. Hulford, and A. Abdullah Prevalence of metabolic syndrome in young patients with acute MI: does the Framingham Risk Score underestimate cardiovascular risk in this population? Diabetes and Vascular Disease Research, September 1, 2006; 3(2): 103 - 107. [Abstract] [PDF]
|
|
|
|
|
|
P. Poirier, T. D. Giles, G. A. Bray, Y. Hong, J. S. Stern, F. X. Pi-Sunyer, and R. H. Eckel Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 968 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Meyer, G. Kundt, M. Steiner, P. Schuff-Werner, and W. Kienast Impaired Flow-Mediated Vasodilation, Carotid Artery Intima-Media Thickening, and Elevated Endothelial Plasma Markers in Obese Children: The Impact of Cardiovascular Risk Factors Pediatrics, May 1, 2006; 117(5): 1560 - 1567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Poirier, T. D. Giles, G. A. Bray, Y. Hong, J. S. Stern, F. X. Pi-Sunyer, and R. H. Eckel Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss: An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism Circulation, February 14, 2006; 113(6): 898 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Chen, G. Yang, M. Zhou, M. Smith, A. Offer, J. Ma, L. Wang, H. Pan, G. Whitlock, R. Collins, et al. Body mass index and mortality from ischaemic heart disease in a lean population: 10 year prospective study of 220 000 adult men Int. J. Epidemiol., February 1, 2006; 35(1): 141 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Watson Commentary Clin Nurs Res, November 1, 2005; 14(4): 324 - 326. [PDF]
|
|
|
|
|
|
G. P. Van Guilder, G. L. Hoetzer, D. T. Smith, H. M. Irmiger, J. J. Greiner, B. L. Stauffer, and C. A. DeSouza Endothelial t-PA release is impaired in overweight and obese adults but can be improved with regular aerobic exercise Am J Physiol Endocrinol Metab, November 1, 2005; 289(5): E807 - E813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.H. Whincup, J.A. Gilg, A.E. Donald, M. Katterhorn, C. Oliver, D.G. Cook, and J.E. Deanfield Arterial Distensibility in Adolescents: The Influence of Adiposity, the Metabolic Syndrome, and Classic Risk Factors Circulation, September 20, 2005; 112(12): 1789 - 1797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. S. Hannon, G. Rao, and S. A. Arslanian Childhood Obesity and Type 2 Diabetes Mellitus Pediatrics, August 1, 2005; 116(2): 473 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. W. Lau, B. Dhillon, H. Yan, P. E. Szmitko, and S. Verma Adipokines: molecular links between obesity and atheroslcerosis Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2031 - H2041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. McMahan, S. S. Gidding, Z. A. Fayad, A. W. Zieske, G. T. Malcom, R. E. Tracy, J. P. Strong, H. C. McGill Jr, and for the Pathobiological Determinants of Atheroscle Risk Scores Predict Atherosclerotic Lesions in Young People Arch Intern Med, April 25, 2005; 165(8): 883 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mora, L. R. Yanek, T. F. Moy, M. D. Fallin, L. C. Becker, and D. M. Becker Interaction of Body Mass Index and Framingham Risk Score in Predicting Incident Coronary Disease in Families Circulation, April 19, 2005; 111(15): 1871 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Lawlor and D. A. Leon Association of Body Mass Index and Obesity Measured in Early Childhood With Risk of Coronary Heart Disease and Stroke in Middle Age: Findings From the Aberdeen Children of the 1950s Prospective Cohort Study Circulation, April 19, 2005; 111(15): 1891 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. de Simone, K. Wachtell, V. Palmieri, D. A. Hille, G. Beevers, B. Dahlof, U. de Faire, F. Fyhrquist, H. Ibsen, S. Julius, et al. Body Build and Risk of Cardiovascular Events in Hypertension and Left Ventricular Hypertrophy: The LIFE (Losartan Intervention For Endpoint reduction in hypertension) Study Circulation, April 19, 2005; 111(15): 1924 - 1931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P Friberg, A Allansdotter-Johnsson, A Ambring, R Ahl, H Arheden, J Framme, A Johansson, D Holmgren, H Wahlander, and S Marild Increased left ventricular mass in obese adolescents Eur. Heart J., June 1, 2004; 25(11): 987 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Marx, D. Walcher, C. Raichle, M. Aleksic, H. Bach, M. Grub, V. Hombach, P. Libby, A. Zieske, S. Homma, et al. C-Peptide Colocalizes with Macrophages in Early Arteriosclerotic Lesions of Diabetic Subjects and Induces Monocyte Chemotaxis In Vitro Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 540 - 545. [Abstract] [Full Text]
|
|
|
|
|
|
M. Gossl, N. M. Malyar, M. Rosol, P. E. Beighley, and E. L. Ritman Impact of coronary vasa vasorum functional structure on coronary vessel wall perfusion distribution Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2019 - H2026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B Tanko, Y. Z Bagger, P. Alexandersen, P. J Larsen, C. Christiansen, and for the PERF study group Central and peripheral fat mass have contrasting effect on the progression of aortic calcification in postmenopausal women Eur. Heart J., August 2, 2003; 24(16): 1531 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cook, M. Weitzman, P. Auinger, M. Nguyen, and W. H. Dietz Prevalence of a Metabolic Syndrome Phenotype in Adolescents: Findings From the Third National Health and Nutrition Examination Survey, 1988-1994 Arch Pediatr Adolesc Med, August 1, 2003; 157(8): 821 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Carr Summary of the Role of Statins in the Treatment of Dyslipidemia J Am Osteopath Assoc, July 1, 2003; 103(7_suppl_3): S1 - S3. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rehman, R. V. Considine, J. E. Bovenkerk, J. Li, C. A. Slavens, R. M. Jones, and K. L. March Obesity is associated with increased levels of circulating hepatocyte growth factor J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1408 - 1413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Goran, G. D. C. Ball, and M. L. Cruz Obesity and Risk of Type 2 Diabetes and Cardiovascular Disease in Children and Adolescents J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1417 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Tanko, Y. Z. Bagger, P. Alexandersen, P. J. Larsen, and C. Christiansen Peripheral Adiposity Exhibits an Independent Dominant Antiatherogenic Effect in Elderly Women Circulation, April 1, 2003; 107(12): 1626 - 1631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Keller and L. Lemberg Obesity and the Metabolic Syndrome Am. J. Crit. Care., March 1, 2003; 12(2): 167 - 170. [Full Text] [PDF]
|
|
|
|
|
|
P. Greenland, S. S Gidding, and R. P Tracy Commentary: Lifelong prevention of atherosclerosis: the critical importance of major risk factor exposures Int. J. Epidemiol., December 1, 2002; 31(6): 1129 - 1134. [Full Text]
|
|
|
|
 |
|
 Obesity Is Linked with Accelerated Atherosclerosis in Young Men Journal Watch (General), July 26, 2002; 2002(726): 4 - 4. [Full Text]
|
|
|
|
|
|
S. M. Grundy Obesity, Metabolic Syndrome, and Coronary Atherosclerosis Circulation, June 11, 2002; 105(23): 2696 - 2698. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||