Author + information
- Received April 2, 2009
- Revision received July 8, 2009
- Accepted July 12, 2009
- Published online December 15, 2009.
- Lisa de las Fuentes, MD*,
- Alan D. Waggoner, MHS*,
- B. Selma Mohammed, MD, PhD†,
- Richard I. Stein, PhD†,
- Bernard V. Miller III, MD†,
- Gary D. Foster, PhD‡,
- Holly R. Wyatt, MD§,
- Samuel Klein, MD† and
- Victor G. Davila-Roman, MD*,* ()
- ↵*Reprint requests and correspondence:
Dr. Victor G. Davila-Roman, Cardiovascular Division, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110
Objectives The objective of this prospective, single-site, 2-year dietary intervention study was to evaluate the effects of moderate weight reduction and subsequent partial weight regain on cardiovascular structure and function.
Background Obesity is associated with adverse cardiac and vascular structural and functional alterations.
Methods Sixty obese subjects (age 46 ± 10 years, body mass index 37 ± 3 kg/m2) were evaluated during their participation in a weight loss study. Cardiac and vascular ultrasound studies were performed at baseline and at 3, 6, 12, and 24 months after start of intervention.
Results Forty-seven subjects (78%) completed the entire 2-year follow-up. Average weight loss was 7.3 ± 4.0%, 9.2 ± 5.6%, 7.8 ± 6.6%, and 3.8 ± 7.9% at 3, 6, 12, and 24 months, respectively. Age- and sex-adjusted mixed linear models revealed that the follow-up time was significantly associated with decreases in weight (p < 0.0001), left ventricular (LV) mass (p = 0.001), and carotid intima-media thickness (p < 0.0001); there was also significant improvement in LV diastolic (p ≤ 0.0001) and systolic (p = 0.001) function. Partial weight regain diminished the maximal observed beneficial effects of weight loss, however cardiovascular parameters measured at 2 years still showed a net benefit compared with baseline.
Conclusions Diet-induced moderate weight loss in obese subjects is associated with beneficial changes in cardiovascular structure and function. Subsequent weight regain is associated with partial loss of these beneficial effects. (The Safety and Effectiveness of Low and High Carbohydrate Diets; NCT00079547)
Obesity is associated with a 2-fold increase in the risk of developing heart failure (1). Abnormalities in cardiovascular structure and function that have been documented in obesity include left ventricular hypertrophy (LVH), left ventricular (LV) enlargement, and LV systolic and diastolic dysfunction, all of which are independent risk factors for heart failure (2–4). Weight reduction in obese subjects is associated with regression of these abnormalities (2,5–8). However, most studies have been confined to class III obese subjects (body mass index [BMI] ≥40 kg/m2) who have experienced considerable weight loss (i.e., >20% total body weight) after bariatric surgery.
Most obese persons have class I (BMI 30 to 34.9 kg/m2) and class II (BMI 35 to 39.9 kg/m2) obesity (9,10). The primary therapeutic approach in these patients is to decrease caloric intake and increase caloric expenditure by altering lifestyle behaviors. However, diet-induced weight loss is difficult to sustain, and many patients who lose weight by dieting regain their lost weight over time. The cardiovascular effects of weight regain in patients with class I and II obesity are not well-known. The purpose of this study was to prospectively evaluate the effects of moderate diet-induced weight loss (5% to 10% of body weight) and subsequent weight regain on cardiovascular structure and function as assessed by cardiac and vascular ultrasound in patients with class I (BMI 30 to 34.9 kg/m2) and class II (BMI 35 to 39.9 kg/m2) obesity over a 2-year period.
The study population consisted of 60 obese adults prospectively enrolled in a weight-loss study at Washington University School of Medicine. All subjects underwent a medical history, physical examination, and cardiovascular ultrasound. Exclusion criteria were: type 2 diabetes mellitus, taking weight-loss and/or lipid-lowering medications, pregnant, or lactating. The study was approved by the Human Research Protection Office at Washington University School of Medicine; written informed consent was obtained from all study participants.
Participants were randomly assigned to 1 of 2 reduced-calorie diets for 2 years: low-fat vs. low-carbohydrate diet. Low-carbohydrate diet subjects were instructed to limit carbohydrate intake and to eat foods rich in fat and protein. Low-fat diet subjects were instructed to limit fat intake to approximately 30% of total calories and reduce energy intake (women: 1,200 to 1,500 kcal/day; men: 1,500 to 1,800 kcal/day). All participants received: 1) daily multivitamin supplement; 2) comprehensive group behavioral treatment (weekly for 20 weeks, every other week for 20 weeks, and every other month for the remainder of the 2-year study) (11,12); and 3) instructions for physical activity (principally walking), beginning at week 4 (4 sessions of 20 min each), progressing by week 19 to 4 sessions of 50 min each.
Body weight was measured at each treatment visit on calibrated scales while participants wore light clothing and no shoes. Height was measured by a stadiometer at baseline.
Cardiovascular assessments were performed at baseline and at 3, 6, 12, and 24 months after starting a hypocaloric diet therapy program. Fasting serum lipoproteins and glucose were collected after a 12-h fast at baseline and at each follow-up visit; fasting insulin was drawn at baseline. Heart rate and blood pressure were assessed with automated instruments (Dinamap, GE Healthcare, United Kingdom) after 5 min of quiet sitting, with the average of 2 readings taken 1 min apart reported. Metabolic syndrome was diagnosed according to the amended National Cholesterol Education Program (NCEP) Adult Treatment Panel III guidelines, except a BMI ≥30 kg/m2satisfied the criteria for increased waist circumference (13).
Complete 2-dimensional, M-mode, and Doppler echocardiograms as well as carotid artery ultrasound were performed by use of commercially available ultrasound equipment (Sequoia-C256, Acuson-Siemens, Mountain View, California). Two-dimensional echocardiographic measurements included the LV ejection fraction calculated with the biplane method of discs (modified Simpson's method). The LV mass was measured by the M-mode–derived cubed method and indexed to height2.7(LVM/Ht2.7) (14). The LV geometric patterns were determined as previously described (15). Tissue Doppler imaging (TDI)-derived myocardial systolic (S') and early diastolic (E') tissue velocities were obtained from the apical 4-chamber view (septal and lateral velocities averaged and reported as a global measurement) (16–18). All measurements were performed in accordance with published guidelines and represent the average of 3 consecutive cardiac cycles obtained by a single observer blinded to all clinical parameters (19).
Carotid artery intima-media thickness (CIMT) was measured by a single vascular sonographer from B-mode images of both carotid arteries expressed as the average of the far walls of the right and left common carotid arteries; each site represents the average of 3 separate measurements (20). The intraclass correlation coefficient for repeated measures of the CIMT is 0.91 and for echocardiographic measurements ranges from 0.85 to 0.90 at our laboratory.
The SAS software (version 9.2, SAS Institute, Cary, North Carolina) was used for all statistical analyses. Chi-square analysis and Student ttests were performed to compare baseline values. Mixed linear models with repeated measures and pairwise contrasts were performed with a covariance structure including the fixed-effect parameters of the duration of dietary intervention (i.e., follow-up time interval) for all models. All regression models included age, sex, and dietary group as potential covariates. Continuous variables are presented as the mean ± 1 SD, except in graphics where the SEM is shown. A p value <0.05 after adjustment for multiple testing by the false discovery rate was considered statistically significant.
The study population consisted of 60 obese subjects; all subjects had normal LV systolic function (i.e., LV ejection fraction >50%). There were no differences between subjects who consumed a low-carbohydrate versus a low-fat diet in terms of baseline characteristics (age, sex, racial composition, systolic and diastolic blood pressures, serum lipids and triglycerides, glucose, insulin, homeostasis model assessment insulin resistance, or percent with metabolic syndrome). Mean age was 46 ± 10 years, 43 (72%) were women, 15 (25%) were African American, BMI was 37 ± 3 kg/m2, insulin was 13.7 ± 9.9 μU/ml, and the homeostasis model assessment insulin resistance was 3.1 ± 2.5. Additional baseline characteristics of the combined group are shown in Table 1.
Body weight response to diet intervention
The entire 24-month follow-up was completed by 47 subjects (78%). There were no differences between the 2 diet groups in terms of weight loss or any of the primary end points, namely diet-induced changes in cardiac structure/function and CIMT; therefore, the data for the 2 groups were combined (Table 1, Fig. 1).For the entire group, average weight loss was 7.8 ± 4.9 kg, 9.9 ± 6.9 kg, 8.4 ± 7.6 kg, and 4.1 ± 8.8 kg at 3, 6, 12 and 24 months, respectively, representing a 7.3 ± 4.0%, 9.2 ± 5.6%, 7.8 ± 6.6%, and 3.8 ± 7.9% decrease, respectively, from baseline body weight. Maximal weight loss occurred at 6 months. Although weight regain occurred at 12 and 24 months, mean body weight remained lower than baseline values. Both dietary intervention groups exhibited significant differences between baseline and some follow-up intervals in weight, heart rate, systolic blood pressure, diastolic blood pressure, and lipid levels. Where dietary group assignment resulted in group differences, the low-carbohydrate diet showed differences in triglyceride and high-density lipoprotein cholesterol levels, whereas only high-density lipoprotein cholesterol was significantly different in the high-carbohydrate group. Neither group demonstrated significant changes in blood glucose or in the percentage of subjects with metabolic syndrome during the follow-up interval (Table 1).
Cardiovascular structure-function response to weight loss
Compared with baseline measures, there was a significant increase (improvement) in the E' (an index of LV diastolic relaxation) at 6, 12, and 24 months; a significant decrease (improvement) in LVM/Ht2.7at 3, 6, and 12 months; and a significant decrease (improvement) in CIMT at 6, 12, and 24 months (Fig. 1). Age- and sex-adjusted mixed linear models revealed that follow-up time was significantly associated with decreases in weight (F= 42.51, p < 0.0001), E' (F= 8.71, p ≤ 0.0001), LV mass (F= 5.27, p = 0.004), and CIMT (F= 10.18, p < 0.0001). There was a modest increase (improvement) in S' (an index of LV contractile performance) at 24 months (F= 5.21, p = 0.001). Further post-hoc analyses divided the cohort into 2 equal groups by the median of S' at baseline. In the baseline S' <8.0-cm/s group, a significant improvement in S' was noted at 3, 6, 12, and 24 months compared with baseline (F= 16.75, p ≤ 0.0001); there were no significant differences over time in the baseline S' ≥8.0-cm/s group.
Changes in LV geometric patterns
At baseline, a majority (52%) exhibited normal geometry (Table 2),whereas at 3 months, the proportions with normal geometry and eccentric LVH both increased, and the proportion with concentric remodeling and concentric LVH decreased. Further analyses show that the changes in LV geometry are related to the percentage of subjects with increased relative wall thickness (adjusted p value = 0.03); these findings are consistent with decreased LVM/Ht2.7at 3, 6, and 12 months.
The results of this 2-year study demonstrate that weight loss intervention was associated with beneficial changes in cardiovascular structure and function, manifested by decreased LV mass, improved diastolic and systolic function, and decreased vascular hypertrophy. Whereas maximal weight loss occurred at 6 months, the maximal cardiovascular benefits “lagged” behind the maximal weight loss by 3 to 12 months for all measured variables. Subsequent weight regain, which occurred by 6 to 12 months, was paralleled by worsening of LV mass, diastolic function, and vascular hypertrophy.
Abnormalities in cardiovascular structure-function in obesity have been well-characterized and include increased blood pressures, increased LV volumes, LV hypertrophy, increased wall stress, and systolic and/or diastolic dysfunction (2–8). Data from previous studies have shown that obese subjects undergoing a combined exercise-hypocaloric weight management program experience modest weight loss that is associated with lower blood pressure and with beneficial changes in cardiac structure (i.e., decreased relative wall thickness and LVH) at 6 and 12 months (6,7). However, the current study extends these finding by showing that changes in LV structure and function are not only sustained at 24 months after the start of the intervention but also associated with improvement in LV diastolic function and CIMT. It is reasonable to assume that improvement of these adverse cardiovascular imaging biomarkers with weight loss intervention would result in a risk reduction compared with those who remain obese (21,22). Studies conducted in morbidly obese individuals have shown that profound weight reduction after bariatric surgery (i.e., >20% loss from initial body weight) results in regression of LV hypertrophy and improved systolic function (2,4,22–24).
The present study shows that obese subjects exhibit mild alterations in cardiovascular structure and function. There are major implications of the present study. First, the modest observed weight loss (i.e., approximately 10% of initial body weight) represents a realistic and attainable goal for most obese individuals. Second, improvement in cardiovascular structure-function parameters occur relatively early (i.e., at 3 to 12 months) during modest weight loss and most persist for the entire 24-month follow-up period, thus implying that obesity-related cardiovascular structural-functional abnormalities are reversible. Third, partial weight regain diminished the maximal observed beneficial effects of weight loss in the cardiovascular system. Further studies are necessary to better define the mechanisms responsible for the improvement in cardiac and vascular structure and function observed in this study. Possible mechanisms include an improvement in blood pressure, reduction of insulin resistance, alterations in myocardial substrate metabolism, and/or reduction in inflammatory cytokines (18,25–31). The results of the present study are interpreted in the context of a recent, large, 2-year trial that found that the magnitude of weight loss was related to overall caloric intake, independent of the different diet macronutrient composition (32). Thus, taken together, the findings of these 2 studies suggest that the beneficial effects on the cardiovascular system are related to the weight loss independent of the macronutrient composition of the diet.
Although subjects were encouraged to increase their physical activity, a structured, monitored exercise program was not part of the study; thus, it is possible that increased physical activity contributed to the beneficial effects observed.
Moderate weight loss leads to early improvement of cardiovascular structural-functional abnormalities. Although partial weight regain diminished the maximal observed beneficial effects of weight loss, cardiovascular parameters measured at 2 years still showed a net benefit compared with baseline. Whether the salutary effects of weight loss on cardiovascular structure-function observed in this study translate into improved clinical outcomes requires further investigation.
The authors thank Joann L. Reagan, RN, RVT; Sharon L. Heuerman, RN; and Karen E. Spence, MS, for their assistance in the performance of this study.
This study was supported in part by National Institutes of Health Grants K12RR023249, KL2RR024994, and UL1RR024992 (Dr. de las Fuentes), AT 1103 (Dr. Klein), Robert Wood Johnson Foundation (Princeton, New Jersey) Grant 048875 (Dr. de las Fuentes); and a grant from the Barnes-Jewish Hospital Foundation (St. Louis, Missouri). Mr. Waggoner is a consultant for St. Jude Medical and Boston Scientific; however, such relationships present no conflicts related to the present work. Dr. Foster is on the scientific advisory board for ConAgra Foods and serves on the scientific advisory board and has received research grants from NutriSystem. Dr. Wyatt serves on scientific advisory boards for Arena, Wellspring, and Pfizer. Dr. Klein receives speaker honoraria or consulting fees from Amylin, Dannon/Yakult, Ethicon Endosurgery, Johnson & Johnson, Merck, and Takeda Pharmaceuticals; is a stockholder of Aspirations Medical Technologies; and has received research grants from the Atkins Foundation Charitable Trust and Kilo Foundation. Dr. Davila-Roman is a consultant for St. Jude Medical, AGA Medical, Arbor Surgical Technologies, Inc., Boston Scientific, CoreValve Inc., Medtronic, and AtriCure, Inc.; however, such relationships present no conflicts related to the present work.
- Abbreviations and Acronyms
- body mass index
- carotid intima-media thickness
- early diastolic myocardial velocity
- left ventricular
- left ventricular hypertrophy
- left ventricular mass indexed to height2.7
- systolic myocardial velocity
- systolic blood pressure
- tissue Doppler imaging
- Received April 2, 2009.
- Revision received July 8, 2009.
- Accepted July 12, 2009.
- American College of Cardiology Foundation
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