- Email: [email protected]
Effect of weight loss on coronary circulation and adiponectin levels in obese women
414
Letters to the Editor
In conclusion, accurate ECG prediction of left- or rightsided location of inferoseptal pathways is challenging. The most useful markers are the QRS and delta wave polarity in the inferior leads and V1. Acknowledgments This study was supported by the Dr. Peter Osypka foundation. Lars Eckardt holds the Peter Osypka professorship of experimental and clinical electrophysiology.
References [1] Katsouras CS, Greakas GF, Goudevenos JA, et al. Localization of accessory pathways by the electrocardiogram: which is the degree of accordance of three algorithms in use? Pacing Clin Electrophysiol 2004;27:189–93. [2] Cosio FG, Anderson RH, Kuck KH, et al. Living anatomy of the atrioventricular junctions. A guide to electrophysiologic mapping. Circulation 1999;100:e31–7. [3] Arruda MS, McClelland JH, Wang X, et al. Development and validation of an ECG algorithm for identifying accessory pathway ablation site in Wolff–Parkinson–White syndrome. J Cardiovasc Electrophysiol 1998; 9:2–12.
0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.12.083
Effect of weight loss on coronary circulation and adiponectin levels in obese women Antonino Coppolaa,⁎, Raffaele Marfellab , Ludovico Coppolab , Ercole Tagliamontea , Dario Fontanaa , Erminio Liguoria , Teresa Cirilloa , Maria Cafieroa , Silvana Natalea , Costantino Astaritaa a
b
Operative Unit of Cardiology, Ospedale S. Maria della Misericordia, Sorrento, Italy Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy
Received 28 September 2007; received in revised form 28 December 2007; accepted 29 December 2007 Available online 2 April 2008
Abstract Background: Obesity is independently associated with coronary endothelial dysfunction. Adiponectin, a protein whose circulating levels are decreased in obesity, has direct effects on vascular function. The aim of this study was to investigate in obese women the effect of sustained weight loss on coronary circulation and circulating adiponectin levels. Methods: Coronary flow velocity reserve (CFVR), assessed by transthoracic Doppler echocardiography (TTDE), blood pressure, lipid, glucose and insulin, HOMA scores, CRP-protein (CRP), and adiponectin parameters were investigated in forty obese pre-menopausal women and 40 healthy matched normal weight women at baseline and after sustained weight loss. Results: At baseline, the obese group had significantly higher fasting glucose (P b 0.05), insulin concentrations (P b 0.01), HOMA scores (P b 0.001), C-reactive protein (CRP) levels (P b 0.001) and lower plasma adiponectin levels (P b 0.001) than the controls. CFVR was significantly lower in obese group than in the normal weight group (P b 0.05). After 12 months of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. Fasting glucose (b0.001) and insulin concentrations (P b 0.001), HOMA scores (P b 0.001), CRP levels (P b 0.01) were significant reduced, whereas adiponectin levels (P b 0.001) and HDL cholesterol (P b 0.05) showed a significant increment. CFVR value significantly improved in obese subjects (P b 0.001). There was a significant correlation between changes in CFVR and changes in adiponectin levels (r = 0.47, P b 0.05). Multivariate analysis showed that adiponectin was the only independent predictor of change in CFVR (r = 0.38, P b 0.05). Conclusions: In obese women the weight loss improves coronary circulation and increases adiponectin levels. The improvement in coronary circulation is associated with adiponectin levels. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Coronary circulation; Adiponectin; Obesity
⁎ Corresponding author. Via A. Balsamo n.83, 80065 Sant'Agnello, Naples, Italy. Tel./fax: +39 081441499. E-mail address: [email protected] (A. Coppola).
Letters to the Editor
415
1. Introduction Obesity is independently associated with coronary endothelial dysfunction, which is considered a key process in the development and progression of coronary atherosclerosis [1]. Adiponectin is an adipocyte-derived protein that exhibits antiinflammatory, anti-atherogenic properties and direct effects on vascular function [2,3]. Circulating adiponectin levels are decreased in obese subjects, diabetic subjects and in subjects with coronary artery disease [4–8]. The aim of this study was to evaluate in obese women the effect of sustained weight loss (at least of 10% of the initial body weight) on coronary circulation and circulating adiponectin levels. 2. Materials and methods Forty obese pre-menopausal women (age 35.2 ± 4.1) and 40 healthy matched normal weight women were enrolled for this study. The protocol was approved by the local ethic committee, and all subjects gave informed written consent. Study protocol and methods have been previously described [9]. Briefly, obese women were treated with a multidisciplinary approach consisting of diet, exercise, and behavioural and nutrition counselling for 12 months. Laboratory parameters and coronary flow velocity reserve (CFVR) were determined in all participants at baseline and at 12 months. The CFVR was determined by transthoracic Doppler echocardiography (TTDE) as previously described [10]. Insulin sensitivity in the fasting state was assessed with homeostasis model assessment (HOMA) and calculated with the formula: fasting plasma glucose (millimoles per liter) × fasting serum insulin (microunits per milliliter) divided by 25, as described by Matthews et al. [11]. Plasma adiponectin was measured by radioimmunoassay (Linco Research, St. Charles, MO, USA). Data are presented as means ± SD. Data were analyzed by ANOVA; individual means were compared using paired or unpaired Student's test, as appropriate. Pearson's correlations and multivariate regression analyses were used as appropriate. All analyses were conducted using SPSS version 9.0 (SPSS, Chicago, IL). 3. Results At baseline, the obese group had significantly higher BMI (34.4 ± 2.3 vs. 24.1 ± 1.8 kg/m2, P b 0.001), waist-to-hipratio (WHR) (0.85 ± 0.06 vs. 0.71 ± 0.04, P b 0.001), fasting glucose (5.2 ± 0.3 vs. 4.8 ± 0.4 mmol/l, P b 0.05), insulin concentrations (15.7 ± 2.8 vs. 8.0 ± 2.1 µU/ml, P b 0.01), HOMA scores (3.2 ± 0.3 vs. 1.6 ± 0.2, P b 0.001), C-reactive protein (CRP) levels (3.5 ± 0.7 vs. 1.3 ± 0.2 mg/l, P b 0.001) and lower plasma adiponectin levels (5.1 ± 1.3 vs. 9.1 ± 2.5 µg/ml, P b 0.001) than the controls. There was no statistical difference between the two groups with regard to serum lipid and blood pressure levels. The basal coronary flow velocity was similar in the obese group (25.3 ± 3.4 cm/s)
Fig. 1. Correlation between changes in adiponectin levels and changes in CFVR.
and in the control subjects (24.1 ± 4.1 cm/s). By contrast, coronary flow velocity in response to dypiridamole was significantly lower in obese patients than in control subjects (67.4 ± 13.5 vs. 88.5 ± 18.9 cm/s, P b 0.05). As a consequence, CFVR was significantly lower in obese group (2.7 ± 0.5 vs. 3.7 ± 0.8, P b 0.05). After 12 months, obese women had a significant decrease in BMI (from 34.4 ± 2.3 to 30.1 ± 1.4 kg/m2, P b 0.001), WHR (from 0.85 ± 0.06 to 0.77 ± 0.05, P b 0.001), fasting glucose (from 5.2 ± 0.3 to 4.7 ± 0.3 mmol/ l, P b 0.001) and insulin concentrations (from 15.7 ± 2.8 to 10.1 ± 5.6 µU/ml, P b 0.001), HOMA scores (from 3.2 ± 0.3 to 1.9 ± 0.8, P b 0.001), CRP levels (from 3.5 ± 0.7 to 2.1 ± 0.4 mg/l, P b 0.01), and increase in adiponectin levels (from 5.1 ± 1.3 vs. 8.1 ± 2.6 µg/ml, P b 0.001) and HDL cholesterol (from 1.1 ± 0.2 vs. 1.3 ± 0.1 mmol/l, P b 0.05). Serum total cholesterol, LDL cholesterol, triglycerides and blood pressure values were almost unaltered after the same period. CFVR value significantly improved in obese subjects (from 2.7 ± 0.5 to 3.3 ± 0.2, P b 0.001). There was a significant positive relationship between changes in CFVR and changes in adiponectin levels (r = 0.47, P b 0.05) (Fig. 1). No significant correlation was found between BMI, WHR or insulin levels and CFVR before and after weight loss, but there was a trend for an inverse relationship among these parameters. In multivariate analysis performed with other variables (BMI, WHR, glucose, insulin, HDL, CRP), adiponectin was the only independent predictor of change in CFVR (r = 0.38, P b 0.05). In control group, anthropometric, metabolic and coronary circulation parameters were not significantly different from baseline after 12 months. 4. Discussion The main findings of this study are that a multidisciplinary approach aimed to reducing body weight by 10% or more significantly improves coronary flow velocity reserve and increases adiponectin plasma levels in obese premenopausal women. Another important finding is that the amelioration in coronary circulation is closely linked to increased adiponectin levels. This result was associated with a significant reduction in fasting glucose, insulin levels, HOMA scores and CRP levels reflecting an improvement in insulin sensitivity and
416
Letters to the Editor
inflammatory factors. To our knowledge, this is the first study that investigated the effects of a program of changes in lifestyle designed to obtain a reduction of body weight on coronary circulation and adiponectin levels. Several mechanisms underlying the improvement of coronary circulation may be hypothesized. Recent data show a significant association between decreased circulating adiponectin levels and angiographic coronary disease progression in patients with angina pectoris, suggesting that this effect could be via a direct anti-atherosclerotic action of adiponectin [12]. On the other hand, various studies have demonstrated a direct effect of adiponectin on endothelial function at several levels [3,13,14]. In general, enhanced NO bioavailability is thought to be a key mechanism. Finally, an indirect action of adiponectin, by modifying defining characteristics of the metabolic syndrome, also is a likely mechanism [15]. At this regard, adiponectin exhibits insulin-sensitizing effects in glucose and lipid metabolism by multiple mechanisms [2,3]. Accordingly, although it's difficult to identify the exact mechanism underlying the improvement of coronary circulation after weight loss, our data from the current study show a significant reduction in fasting glucose, insulin levels and HOMA scores, reflecting an improved metabolic status. It is likely that the improvement of coronary circulation after weight loss could be mediated by multiple mechanisms, staying difficult to fully clarify the exact role of these factors because each one may affect the other reciprocally [6,16,17]. On the other hand, our results put forward for adiponectin a central role to link insulin resistance and coronary dysfunction in obese subjects. In fact, consistent with this early hypothesis, in multivariate regression analysis adiponectin was the only independent predictor of CFVR. 5. Conclusion In conclusion the present study shows that in obese women the weight loss improves coronary circulation and increases adiponectin levels, and that the improvement in coronary circulation is associated with adiponectin levels. References [1] Suwaidi JA, Higano ST, Holmes DR, Lennon R, Lerman A. Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries. J Am Coll Cardiol 2001;37:1523–8.
0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.12.087
[2] Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005;96:939–49. [3] Goldestein BJ, Scalia R. Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 2004;89: 2563–8. [4] Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adiposespecific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999;257:79–83. [5] Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000;20:1595–9. [6] Tan KCB, Xu A, Chow WS, et al. Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. J Clin Endocrinol Metab 2004;89:765–9. [7] Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 2003;23:85–9. [8] Wolk R, Berger P, Lennon RJ, Brilakis ES, Davison DE, Somers VK. Association between plasma adiponectin levels and unstable coronary syndromes. Eur Heart J 2007;28:292–8. [9] Marfella R, Esposito K, Siniscalchi M, et al. Effect of weight loss on cardiac synchronization and proinflammatory cytokines in premenopausal obese women. Diabetes Care 2004;27:47–52. [10] Coppola A, Astarita C, Oliviero M, et al. Impairment of coronary circulation by acute hyperhomocysteinemia in type 2 diabetic patients. Diabetes Care 2004;27:2055–6. [11] Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting glucose and insulin concentrations in man. Diabetologia 1985;28:412–9. [12] Liang KW, Sheu WH, Lee WL, et al. Decreased circulating protective adiponectin level is associated with angiographic coronary disease progression in patients with angina pectoris. Int J Cardiol Jul 23 2007 [Electronic publication ahead of print] PMID: 17651832. [13] Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem 2003;45:45021–6. [14] Okui H, Hamasaki S, Ishida S, et al. Adiponectin is a better predictor of endothelial function of the coronary artery than HOMA-R, body mass index, immunoreactive insulin, or triglycerides. Int J Cardiol 2008;126:53–61. [15] Matsushita K, Tamakoshi K, Yatsuya H, et al. Further inflammatory information on metabolic syndrome by adiponectin evaluation. Int J Cardiol 2008;124:339–44. [16] Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001;86:1930–5. [17] Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationship between insulin resistance and endothelial dysfunction. Circulation 2006;113:1888–904.
Letters to the Editor
In conclusion, accurate ECG prediction of left- or rightsided location of inferoseptal pathways is challenging. The most useful markers are the QRS and delta wave polarity in the inferior leads and V1. Acknowledgments This study was supported by the Dr. Peter Osypka foundation. Lars Eckardt holds the Peter Osypka professorship of experimental and clinical electrophysiology.
References [1] Katsouras CS, Greakas GF, Goudevenos JA, et al. Localization of accessory pathways by the electrocardiogram: which is the degree of accordance of three algorithms in use? Pacing Clin Electrophysiol 2004;27:189–93. [2] Cosio FG, Anderson RH, Kuck KH, et al. Living anatomy of the atrioventricular junctions. A guide to electrophysiologic mapping. Circulation 1999;100:e31–7. [3] Arruda MS, McClelland JH, Wang X, et al. Development and validation of an ECG algorithm for identifying accessory pathway ablation site in Wolff–Parkinson–White syndrome. J Cardiovasc Electrophysiol 1998; 9:2–12.
0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.12.083
Effect of weight loss on coronary circulation and adiponectin levels in obese women Antonino Coppolaa,⁎, Raffaele Marfellab , Ludovico Coppolab , Ercole Tagliamontea , Dario Fontanaa , Erminio Liguoria , Teresa Cirilloa , Maria Cafieroa , Silvana Natalea , Costantino Astaritaa a
b
Operative Unit of Cardiology, Ospedale S. Maria della Misericordia, Sorrento, Italy Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy
Received 28 September 2007; received in revised form 28 December 2007; accepted 29 December 2007 Available online 2 April 2008
Abstract Background: Obesity is independently associated with coronary endothelial dysfunction. Adiponectin, a protein whose circulating levels are decreased in obesity, has direct effects on vascular function. The aim of this study was to investigate in obese women the effect of sustained weight loss on coronary circulation and circulating adiponectin levels. Methods: Coronary flow velocity reserve (CFVR), assessed by transthoracic Doppler echocardiography (TTDE), blood pressure, lipid, glucose and insulin, HOMA scores, CRP-protein (CRP), and adiponectin parameters were investigated in forty obese pre-menopausal women and 40 healthy matched normal weight women at baseline and after sustained weight loss. Results: At baseline, the obese group had significantly higher fasting glucose (P b 0.05), insulin concentrations (P b 0.01), HOMA scores (P b 0.001), C-reactive protein (CRP) levels (P b 0.001) and lower plasma adiponectin levels (P b 0.001) than the controls. CFVR was significantly lower in obese group than in the normal weight group (P b 0.05). After 12 months of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. Fasting glucose (b0.001) and insulin concentrations (P b 0.001), HOMA scores (P b 0.001), CRP levels (P b 0.01) were significant reduced, whereas adiponectin levels (P b 0.001) and HDL cholesterol (P b 0.05) showed a significant increment. CFVR value significantly improved in obese subjects (P b 0.001). There was a significant correlation between changes in CFVR and changes in adiponectin levels (r = 0.47, P b 0.05). Multivariate analysis showed that adiponectin was the only independent predictor of change in CFVR (r = 0.38, P b 0.05). Conclusions: In obese women the weight loss improves coronary circulation and increases adiponectin levels. The improvement in coronary circulation is associated with adiponectin levels. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Coronary circulation; Adiponectin; Obesity
⁎ Corresponding author. Via A. Balsamo n.83, 80065 Sant'Agnello, Naples, Italy. Tel./fax: +39 081441499. E-mail address: [email protected] (A. Coppola).
Letters to the Editor
415
1. Introduction Obesity is independently associated with coronary endothelial dysfunction, which is considered a key process in the development and progression of coronary atherosclerosis [1]. Adiponectin is an adipocyte-derived protein that exhibits antiinflammatory, anti-atherogenic properties and direct effects on vascular function [2,3]. Circulating adiponectin levels are decreased in obese subjects, diabetic subjects and in subjects with coronary artery disease [4–8]. The aim of this study was to evaluate in obese women the effect of sustained weight loss (at least of 10% of the initial body weight) on coronary circulation and circulating adiponectin levels. 2. Materials and methods Forty obese pre-menopausal women (age 35.2 ± 4.1) and 40 healthy matched normal weight women were enrolled for this study. The protocol was approved by the local ethic committee, and all subjects gave informed written consent. Study protocol and methods have been previously described [9]. Briefly, obese women were treated with a multidisciplinary approach consisting of diet, exercise, and behavioural and nutrition counselling for 12 months. Laboratory parameters and coronary flow velocity reserve (CFVR) were determined in all participants at baseline and at 12 months. The CFVR was determined by transthoracic Doppler echocardiography (TTDE) as previously described [10]. Insulin sensitivity in the fasting state was assessed with homeostasis model assessment (HOMA) and calculated with the formula: fasting plasma glucose (millimoles per liter) × fasting serum insulin (microunits per milliliter) divided by 25, as described by Matthews et al. [11]. Plasma adiponectin was measured by radioimmunoassay (Linco Research, St. Charles, MO, USA). Data are presented as means ± SD. Data were analyzed by ANOVA; individual means were compared using paired or unpaired Student's test, as appropriate. Pearson's correlations and multivariate regression analyses were used as appropriate. All analyses were conducted using SPSS version 9.0 (SPSS, Chicago, IL). 3. Results At baseline, the obese group had significantly higher BMI (34.4 ± 2.3 vs. 24.1 ± 1.8 kg/m2, P b 0.001), waist-to-hipratio (WHR) (0.85 ± 0.06 vs. 0.71 ± 0.04, P b 0.001), fasting glucose (5.2 ± 0.3 vs. 4.8 ± 0.4 mmol/l, P b 0.05), insulin concentrations (15.7 ± 2.8 vs. 8.0 ± 2.1 µU/ml, P b 0.01), HOMA scores (3.2 ± 0.3 vs. 1.6 ± 0.2, P b 0.001), C-reactive protein (CRP) levels (3.5 ± 0.7 vs. 1.3 ± 0.2 mg/l, P b 0.001) and lower plasma adiponectin levels (5.1 ± 1.3 vs. 9.1 ± 2.5 µg/ml, P b 0.001) than the controls. There was no statistical difference between the two groups with regard to serum lipid and blood pressure levels. The basal coronary flow velocity was similar in the obese group (25.3 ± 3.4 cm/s)
Fig. 1. Correlation between changes in adiponectin levels and changes in CFVR.
and in the control subjects (24.1 ± 4.1 cm/s). By contrast, coronary flow velocity in response to dypiridamole was significantly lower in obese patients than in control subjects (67.4 ± 13.5 vs. 88.5 ± 18.9 cm/s, P b 0.05). As a consequence, CFVR was significantly lower in obese group (2.7 ± 0.5 vs. 3.7 ± 0.8, P b 0.05). After 12 months, obese women had a significant decrease in BMI (from 34.4 ± 2.3 to 30.1 ± 1.4 kg/m2, P b 0.001), WHR (from 0.85 ± 0.06 to 0.77 ± 0.05, P b 0.001), fasting glucose (from 5.2 ± 0.3 to 4.7 ± 0.3 mmol/ l, P b 0.001) and insulin concentrations (from 15.7 ± 2.8 to 10.1 ± 5.6 µU/ml, P b 0.001), HOMA scores (from 3.2 ± 0.3 to 1.9 ± 0.8, P b 0.001), CRP levels (from 3.5 ± 0.7 to 2.1 ± 0.4 mg/l, P b 0.01), and increase in adiponectin levels (from 5.1 ± 1.3 vs. 8.1 ± 2.6 µg/ml, P b 0.001) and HDL cholesterol (from 1.1 ± 0.2 vs. 1.3 ± 0.1 mmol/l, P b 0.05). Serum total cholesterol, LDL cholesterol, triglycerides and blood pressure values were almost unaltered after the same period. CFVR value significantly improved in obese subjects (from 2.7 ± 0.5 to 3.3 ± 0.2, P b 0.001). There was a significant positive relationship between changes in CFVR and changes in adiponectin levels (r = 0.47, P b 0.05) (Fig. 1). No significant correlation was found between BMI, WHR or insulin levels and CFVR before and after weight loss, but there was a trend for an inverse relationship among these parameters. In multivariate analysis performed with other variables (BMI, WHR, glucose, insulin, HDL, CRP), adiponectin was the only independent predictor of change in CFVR (r = 0.38, P b 0.05). In control group, anthropometric, metabolic and coronary circulation parameters were not significantly different from baseline after 12 months. 4. Discussion The main findings of this study are that a multidisciplinary approach aimed to reducing body weight by 10% or more significantly improves coronary flow velocity reserve and increases adiponectin plasma levels in obese premenopausal women. Another important finding is that the amelioration in coronary circulation is closely linked to increased adiponectin levels. This result was associated with a significant reduction in fasting glucose, insulin levels, HOMA scores and CRP levels reflecting an improvement in insulin sensitivity and
416
Letters to the Editor
inflammatory factors. To our knowledge, this is the first study that investigated the effects of a program of changes in lifestyle designed to obtain a reduction of body weight on coronary circulation and adiponectin levels. Several mechanisms underlying the improvement of coronary circulation may be hypothesized. Recent data show a significant association between decreased circulating adiponectin levels and angiographic coronary disease progression in patients with angina pectoris, suggesting that this effect could be via a direct anti-atherosclerotic action of adiponectin [12]. On the other hand, various studies have demonstrated a direct effect of adiponectin on endothelial function at several levels [3,13,14]. In general, enhanced NO bioavailability is thought to be a key mechanism. Finally, an indirect action of adiponectin, by modifying defining characteristics of the metabolic syndrome, also is a likely mechanism [15]. At this regard, adiponectin exhibits insulin-sensitizing effects in glucose and lipid metabolism by multiple mechanisms [2,3]. Accordingly, although it's difficult to identify the exact mechanism underlying the improvement of coronary circulation after weight loss, our data from the current study show a significant reduction in fasting glucose, insulin levels and HOMA scores, reflecting an improved metabolic status. It is likely that the improvement of coronary circulation after weight loss could be mediated by multiple mechanisms, staying difficult to fully clarify the exact role of these factors because each one may affect the other reciprocally [6,16,17]. On the other hand, our results put forward for adiponectin a central role to link insulin resistance and coronary dysfunction in obese subjects. In fact, consistent with this early hypothesis, in multivariate regression analysis adiponectin was the only independent predictor of CFVR. 5. Conclusion In conclusion the present study shows that in obese women the weight loss improves coronary circulation and increases adiponectin levels, and that the improvement in coronary circulation is associated with adiponectin levels. References [1] Suwaidi JA, Higano ST, Holmes DR, Lennon R, Lerman A. Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries. J Am Coll Cardiol 2001;37:1523–8.
0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.12.087
[2] Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005;96:939–49. [3] Goldestein BJ, Scalia R. Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 2004;89: 2563–8. [4] Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adiposespecific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999;257:79–83. [5] Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000;20:1595–9. [6] Tan KCB, Xu A, Chow WS, et al. Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. J Clin Endocrinol Metab 2004;89:765–9. [7] Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 2003;23:85–9. [8] Wolk R, Berger P, Lennon RJ, Brilakis ES, Davison DE, Somers VK. Association between plasma adiponectin levels and unstable coronary syndromes. Eur Heart J 2007;28:292–8. [9] Marfella R, Esposito K, Siniscalchi M, et al. Effect of weight loss on cardiac synchronization and proinflammatory cytokines in premenopausal obese women. Diabetes Care 2004;27:47–52. [10] Coppola A, Astarita C, Oliviero M, et al. Impairment of coronary circulation by acute hyperhomocysteinemia in type 2 diabetic patients. Diabetes Care 2004;27:2055–6. [11] Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting glucose and insulin concentrations in man. Diabetologia 1985;28:412–9. [12] Liang KW, Sheu WH, Lee WL, et al. Decreased circulating protective adiponectin level is associated with angiographic coronary disease progression in patients with angina pectoris. Int J Cardiol Jul 23 2007 [Electronic publication ahead of print] PMID: 17651832. [13] Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem 2003;45:45021–6. [14] Okui H, Hamasaki S, Ishida S, et al. Adiponectin is a better predictor of endothelial function of the coronary artery than HOMA-R, body mass index, immunoreactive insulin, or triglycerides. Int J Cardiol 2008;126:53–61. [15] Matsushita K, Tamakoshi K, Yatsuya H, et al. Further inflammatory information on metabolic syndrome by adiponectin evaluation. Int J Cardiol 2008;124:339–44. [16] Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001;86:1930–5. [17] Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationship between insulin resistance and endothelial dysfunction. Circulation 2006;113:1888–904.