Severe degenerative aortic stenosis with preserved ejection fraction does not change adipokines serum levels
Abstract
Background: The role of the adipokines in the pathogenesis of aortic stenosis (AS) is not well established. The aim was to evaluate the relationship between adipokines and clinical characteristics as well as echocardiographic indices and noninvasive markers of vascular remodeling in patients with severe AS with preserved ejection fraction (EF).
Methods: Sixty-five patients (F/M: 38/27; age: 68.3 ± 9.0 years; body mass index [BMI]: 29.6 ± 4.3 kg/m2) with severe AS with preserved EF: 33 patients with paradoxical low-flow low-gradient AS (PLFLG AS) and 32 patients with normal flow high-gradient AS (NFHG AS) were prospectively enrolled into the study. Twenty-four subjects (F/M: 14/10; age: 65.4 ± 8.7 years; BMI: 29.6 ± 4.3 kg/m2) who matched as to age, sex, BMI and coronary artery disease (CAD) constituted the control group (CG). Clinical data and markers of vascular remodeling were related to the serum adipokines.
Results: There were no differences in the adipokines concentrations in the AS/CG. Patients with AS and coexisting CAD were characterized by decreased serum adiponectin (9.9 ± 5.5 vs. 12.7 ± 5.8 μg/mL, p = 0.040) and leptin (8.3 ± 7.8 vs. 21.6 ± 17.1 ng/mL, p < 0.001) levels compared to subjects without CAD. There were no differences in the serum adipokines concentrations between patients with PLFLG AS and NFHG AS. Systemic hypertension, diabetes, hyperlipidemia or markers of vascular remodeling did not discriminate adipokines concentrations. Multivariate regression analysis indicated that age (F = 3.02; p = 0.015) and E/E’ index (F = 0.87, p = 0.032) were independent predictors of the adiponectin level in the AS group.
Conclusions: The presence of AS with preserved EF did not change the adipokine serum profile. Adipokines levels were modified by coexisting atherosclerosis but not the typical cardiovascular risk factors or the hemodynamic type of AS.
Keywords: echocardiographyaortic stenosisatherosclerosisadipokinesvascular remodeling
References
- 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(6): 1595–1599.
- Lam KSL, Xu A. Adiponectin: protection of the endothelium. Curr Diab Rep. 2005; 5(4): 254–259.
- Chen H, Montagnani M, Funahashi T, et al. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem. 2003; 278(45): 45021–45026.
- Wang M, Wang D, Zhang Y, et al. Adiponectin increases macrophages cholesterol efflux and suppresses foam cell formation in patients with type 2 diabetes mellitus. Atherosclerosis. 2013; 229(1): 62–70.
- Folco EJ, Rocha VZ, López-Ilasaca M, et al. Adiponectin inhibits pro-inflammatory signaling in human macrophages independent of interleukin-10. J Biol Chem. 2009; 284(38): 25569–25575.
- Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes. 2001; 50(5): 1126–1133.
- Peri-Okonny PA, Ayers C, Maalouf N, et al. Adiponectin protects against incident hypertension independent of body fat distribution: observations from the Dallas Heart Study. Diabetes Metab Res Rev. 2017; 33(2).
- Pratesi A, Di Serio C, Orso F, et al. Prognostic value of adiponectin in coronary artery disease: Role of diabetes and left ventricular systolic dysfunction. Diabetes Res Clin Pract. 2016; 118: 58–66.
- Sharma S, Colangelo LA, Lloyd-Jones D, et al. Longitudinal associations between adiponectin and cardiac structure differ by hypertensive status: Coronary Artery Risk Development in Young Adults. Cardiovasc Endocrinol. 2016; 5(2): 57–63.
- Paolisso G, Tagliamonte MR, Galderisi M, et al. Plasma leptin concentration, insulin sensitivity, and 24-hour ambulatory blood pressure and left ventricular geometry. Am J Hypertens. 2001; 14(2): 114–120.
- Puurunen VP, Lepojärvi ES, Piira OP, et al. High plasma leptin levels are associated with impaired diastolic function in patients with coronary artery disease. Peptides. 2016; 84: 17–21.
- Schulze PC, Kratzsch J, Linke A, et al. Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure. Eur J Heart Fail. 2003; 5(1): 33–40.
- Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature. 2001; 409(6818): 307–312.
- Ohmori R, Momiyama Y, Kato R, et al. Associations between serum resistin levels and insulin resistance, inflammation, and coronary artery disease. J Am Coll Cardiol. 2005; 46(2): 379–380.
- Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science. 2005; 307(5708): 426–430.
- Lin YT, Jian DY, Kwok CF, et al. Visfatin promotes foam cell formation by dysregulating CD36, SRA, ABCA1, and ABCG1 expression in RA264.7 macrophages. Shock. 2016; 45(4): 460–468.
- Xiao J, Xiao ZJ, Liu ZG, et al. Involvement of dimethylarginine dimethylaminohydrolase-2 in visfatin-enhanced angiogenic function of endothelial cells. Diabetes Metab Res Rev. 2009; 25(3): 242–249.
- Mazaherioun M, Hosseinzadeh-Attar MJ, Janani L, et al. Elevated serum visfatin levels in patients with acute myocardial infarction. Arch Iran Med. 2012; 15(11): 688–692.
- Eleid MF, Sorajja P, Michelena HI, et al. Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival. Circulation. 2013; 128(16): 1781–1789.
- Hachicha Z, Dumesnil JG, Bogaty P, et al. Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation. 2007; 115(22): 2856–2864.
- Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr. 2009; 10(1): 1–25.
- Dieplinger B, Poelz W, Haltmayer M, et al. Hypoadiponectinemia is associated with symptomatic atherosclerotic peripheral arterial disease. Clin Chem Lab Med. 2006; 44(7): 830–833.
- Matsuura F, Oku H, Koseki M, et al. Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver. Biochem Biophys Res Commun. 2007; 358(4): 1091–1095.
- Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999; 100(25): 2473–2476.
- Otsuka F, Sugiyama S, Kojima S, et al. Plasma adiponectin levels are associated with coronary lesion complexity in men with coronary artery disease. J Am Coll Cardiol. 2006; 48(6): 1155–1162.
- Kawano J, Arora R. The role of adiponectin in obesity, diabetes, and cardiovascular disease. J Cardiometab Syndr. 2009; 4(1): 44–49.
- Gucuk Ipek E, Guray U, Guray Y, et al. Relationship between serum adiponectin levels and calcific aortic valve disease. Kardiol Pol. 2013; 71(3): 241–246.
- Kolasa-Trela R, Miszalski-Jamka T, Grudzień G, et al. Adiponectin, leptin, and resistin in patients with aortic stenosis without concomitant atherosclerotic vascular disease. Pol Arch Med Wewn. 2011; 121(10): 352–359.
- Mohty D, Pibarot P, Després JP, et al. Age-related differences in the pathogenesis of calcific aortic stenosis: the potential role of resistin. Int J Cardiol. 2010; 142(2): 126–132.
- Mohty D, Pibarot P, Côté N, et al. Hypoadiponectinemia is associated with valvular inflammation and faster disease progression in patients with aortic stenosis. Cardiology. 2011; 118(2): 140–146.
- Stojanović S, Ilić MD, Ilić S, et al. The significance of adiponectin as a biomarker in metabolic syndrome and/or coronary artery disease. Vojnosanit Pregl. 2015; 72(9): 779–784.
- Chiara TDi, Argano C, Scaglione A, et al. Circulating adiponectin: a cardiometabolic marker associated with global cardiovascular risk. Acta Cardiol. 2015; 70(1): 33–40.
- Kitaoka H, Kubo T, Okawa M, et al. Plasma adiponectin levels and left ventricular remodeling in hypertrophic cardiomyopathy. Int Heart J. 2010; 51(1): 51–55.
- Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007; 8(1): 21–34.
- Simiti LA, Todor I, Stoia MA, et al. Better prognosis in overweight/obese coronary heart disease patients with high plasma levels of leptin. Clujul Med. 2016; 89(1): 65–71.
- Kahn B, Flier J. Obesity and insulin resistance. J Clin Invest. 2000; 106(4): 473–481.
- Karmazyn M, Gan XT, Rajapurohitam V. The potential contribution of circulating and locally produced leptin to cardiac hypertrophy and failure. Can J Physiol Pharmacol. 2013; 91(11): 883–888.
- Schautz B, Later W, Heller M, et al. Impact of age on leptin and adiponectin independent of adiposity. Br J Nutr. 2012; 108(2): 363–370.
