Hypercholesterolemia and Myocardial function evaluated via Tissue Doppler Imaging

Cardiovascular Ultrasound - Tập 7 - Trang 1-7 - 2009
Jack Rubinstein1, Augusta Pelosi2, Ameeth Vedre3, Pavan Kotaru4, George S Abela3
1University of Cincinnati, Department of Internal Medicine, Division of Cardiovascular Diseases, Cincinnati, USA
2College of Veterinary Medicine, Small Animal Clinical Sciences, Michigan State University, East Lansing, USA
3Department of Medicine, Division of Cardiology, Michigan State University, East Lansing, USA
4Department of Medicine, Division of General Internal Medicine, Michigan State University, East Lansing, USA

Tóm tắt

To establish a link between hypercholesterolemia and myocardial dysfunction. Heart failure is a complex disease involving changes in systolic and diastolic function. Newer echocardiographic imaging modalities may be able to detect discreet changes in myocardial function associated with hypercholesterolemia. Therefore we sought to establish a link between hypercholesterolemia and myocardial dysfunction with tissue Doppler imaging (TDI). Twenty-seven rabbits were studied: 7 were fed normal chow (group 1) and 20 a high cholesterol diet (10 with ezetimibe, 1 mg/kg/day; group 2 and 10 without, group 3). Echocardiographic images were obtained under general anesthesia. Serum cholesterol levels were obtained at baseline, 3 and 6 months and myocardial cholesterol levels measured following euthanasia. Doppler measurements, including E/A, E'/A' and S' were significantly lower in group 3 compared to both groups 1 and 2 but no significant differences were noted in chamber sizes or ejection fraction among the groups. Average serum cholesterol was higher in group 3 compared to groups 1 and 2 respectively (495 ± 305 mg/dl vs. 114 ± 95 mg/dl and 87 ± 37 mg/dl; p < 0.01). Myocardial cholesterol content was also higher in group 3 compared to group 2 (0.10 ± 0.04 vs. 0.06 mg/dl ± 0.02; p = 0.05). There was significant correlation between S', E'/A', E/E' and serum cholesterol (r2 = 0.17 p = 0.04, r2 = 0.37 p = 0.001 and r2 = 0.24 p = 0.01). Cholesterol load in the serum and myocardium was significantly associated with decreased systolic and diastolic function by TDI. Moreover, lipid lowering was protective.

Tài liệu tham khảo

Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y: Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2007, 115: e69-171. Jessup M, Brozena S: Heart Failure. N Engl J Med 2003, 348: 2007-18. Castelli WP, Anderson K, Wilson PW, Levy D: Lipids and risk of coronary heart disease. The Framingham Study. Annals of Epidemiology 2: 23-8. Stokes KY, Cooper D, Tailor A, Granger DN: Hypercholesterolemia promotes inflammation and microvascular dysfunction: Role of nitric oxide and superoxide. Free Radical Biology & Medicine 2002, 33: 1026-1036. Simes J, Furberg CD, Braunwald E, Davis BR, Ford I, Tonkin A, Shepherd J: Effects of pravastatin on mortality in patients with and without coronary heart disease across a broad range of cholesterol levels. The Prospective Pravastatin Pooling project. Eur Heart J 2002, 23: 207-15. Kalantar-Zadeh K, Block G, Horwich T, Fonarow GC: Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. J Am Coll Cardiol 2004, 43: 1439-44. GISSI-HF investigators: Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008, 372: 1231-9. Lavie CJ, Mehra MR, Milani RV: Obesity and heart failure prognosis: paradox or reverse epidemiology? Eur Heart J 2005, 26: 5-7. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW: ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 2005, 112: e154-235. Yu C-M, Sanderson JE, Marwick TH, Oh JK: Tissue Doppler imaging a new prognosticator for cardiovascular diseases. J Am Coll Cardiol 2007, 49: 1903-14. Dokainish H, Zoghbi WA, Lakkis NM, Ambriz E, Patel R, Quinones MA, Nagueh SF: Incremental predictive power of B-type natriuretic peptide and tissue Doppler echocardiography in the prognosis of patients with congestive heart failure. J Am Coll Cardiol 2005, 45: 1223-6. Wang M, Yip GWK, Yu CM, Zhang Y, Zhang Q, Tse MK, Kong SL, Sanderson JE: Independent and incremental prognostic value of early mitral annulus velocity in patients with impaired left ventricular systolic function. J Am Coll Cardiol 2005, 45: 272-7. Sanderson JE: Heart failure with a normal ejection fraction. Heart 2007, 93: 155-8. Abela GS, Picon PD, Friedl SE, Gebara OC, Miyamoto A, Federman M, Tofler GH, Muller JE: Triggering of Plaque Disruption and Arterial Thrombosis in an Atherosclerotic Rabbit Model. Circulation 1995, 91: 776-84. Yanni AE: The laboratory rabbit: an animal model of atherosclerosis research. Laboratory animals 2004, 38: 246-56. Nagueh SF, Kopelen HA, Lim DS, Zoghbi WA, Quinones MA, Roberts R, Marian AJ: Tissue Doppler Imaging Consistently Detects Myocardial Contraction and Relaxation Abnormalities, Irrespective of Cardiac Hypertrophy, in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy. Circulation 2000, 102: 1346-50. Fontes-Sousa APN, Bras-Silva C, Moura C, Areias JC, Leite-Moreira AF: M-mode and Doppler echocardiographic reference values for male New Zealand white rabbits. Am J Vet Res 2006, 67: 1725-9. Vuille C, Weyman AE: Left ventricle I: general considerations, assessment of chamber size and function. In Principles and Practice of Echocardiography. 2nd edition. Edited by: Vuille C, Weyman AE. Philadelphia, PA, USA: Lea & Febiger; 1994:575-611. Huang Y, Walker KE, Hanley F, Narula J, Houser SR, Tulenko TN: Cardiac Systolic and Diastolic Dysfunction After a Cholesterol-Rich Diet. Circulation 2004, 109: 97-102. Chiu HC, Kovacs A, Blanton RM, Han X, Courtois M, Weinheimer CJ, Yamada KA, Brunet S, Xu H, Nerbonne JM, Welch MJ, Fettig NM, Sharp TL, Sambandam N, Olson KM, Ory DS, Schaffer JE: Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res 2005, 96: 225-33. McGavock JM, Lingvay I, Zib I, Tillery T, Salas N, Unger R, Levine BD, Raskin P, Victor RG, Szczepaniak LS: Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation 2007, 116: 1170-5. Zaca V, Rastogi S, Imai M, Wang M, Sharov VG, Jiang A, Goldstein S, Sabbah HN: Chronic monotherapy with rosuvastatin prevents progressive left ventricular dysfunction and remodeling in dogs with heart failure. J Am Coll Cardiol 2007, 50: 551-7. Wu J-H, Hagaman J, Kim S, Reddick RL, Maeda N: Aortic constriction exacerbates atherosclerosis and induces cardiac dysfunction in mice lacking apolipoprotein E. Arterioscler Thromb Vasc Biol 2002, 22: 469-75. Ruberg FL: Myocardial lipid accumulation in the diabetic heart. Circulation 2007, 116: 1110-2. Kjekshus J, Apetrei E, Barrios V, Böhm M, Cleland JGF, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Jánosi A, Kamensk G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJV, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J, for the CORONA Group: Rosuvastatin in Older Patients with Systolic Heart Failure. N Engl J Med 2007, 357: 2248-61. Kjekshus J, Pedersen TR, Olsson AG, Faergeman O, Pyörälä K: The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail 1997, 3: 249-54. de Lorgeril M, Salen P, Bontemps L, Belichard P, Geyssant A, Itti R: Effects of lipid-lowering drugs on left ventricular function and exercise tolerance in dyslipidemic coronary patients. J Cardiovasc Pharmacol 1999, 33: 473-8. Dickinson MG, Ip JH, Olshansky B, Hellkamp AS, Anderson J, Poole JE, Mark DB, Lee KL, Bardy GH: Statin use was associated with reduced mortality in both ischemic and nonischemic cardiomyopathy and in patients with implantable defibrillators: mortality data and mechanistic insights from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Am Heart J 2007, 153: 573-8. Van Heek M, France CF, Compton DS, Mcleod RL, Yumibe NP, Alton KB, Sybertz EJ, Davis HR Jr: In vivo metabolism-based discovery of a potent cholesterol absorption inhibitor, SCH5 in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J Pharmacol Exp Ther 8235, 283: 157-63. Masoudi FA, Inzucchi SE: Diabetes mellitus and heart failure: epidemiology, mechanisms, and pharmacotherapy. Am J Cardiol 2007, 99: 113B-132B. Dabestani A, Child JS, Peloff JK, Figueroa WG, Schelbert HR, Engel TR: Cardiac abnormalities in primary hemochromatosis. Ann N Y Acad Sci 1988, 526: 234-44. Ashrafian H, Frenneaux MP, Opie LH: Metabolic Mechanisms in Heart Failure. Circulation 2007, 116: 434-48. O'Keefe JH, Gheewala NM, O'Keefe JO: Dietary Strategies for Improving Post-Prandial Glucose, Lipids, Inflammation, and Cardiovascular Health. J Am Coll Cardiol 2008, 51: 249-55. Poornima IG, Parikh P, Shannon RP: Diabetic cardiomyopathy: the search for a unifying hypothesis. Circ Res 2006, 98: 596-605. Sharma S, Adrogue JV, Golfman L, Uray I, Lemm J, Youker K, Noon GP, Frazier OH, Taegtmeyer H: Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J 2004, 18: 1692-1700.