Pathophysiology of cardiovascular disease in hemodialysis patients
2000; Elsevier BV; Volume: 58; Linguagem: Inglês
10.1046/j.1523-1755.2000.07618.x
ISSN1523-1755
AutoresFrédérique Meeus, O Kourilsky, Alain P. Guérin, Catherine Gaudry, Sylvain J. Marchais, Gérard M. London,
Tópico(s)Chronic Kidney Disease and Diabetes
ResumoPathophysiology of cardiovascular disease in hemodialysis patients. Cardiovascular disease is the principal cause of morbidity and mortality in dialysis patients. The principal alterations responsible are left ventricular hypertrophy and arterial disease characterized by an enlargement and hypertrophy of arteries and the high prevalence of atheromatous plaques. Left ventricular hypertrophy is the consequence of combined effects of chronic hemodynamic overload and nonhemodynamic biochemical and neurohumoral factors characteristic of uremia. The hemodynamic overload is due to flow and pressure overload. The flow overload is tightly related to hyperkinetic circulation caused by anemia, arteriovenous fistula, or overhydration and is characterized by an enlargement of the left ventricular cavity. The pressure overload in these patients is more tightly related to abnormal geometry and function of large conduit arteries, principally the stiffening of arterial tree. The flow overload is also in large part responsible for remodeling of arterial tree, and as the heart and vessels are a coupled interactive physiological system, cardiac and vascular alterations occur in parallel, being induced to a great extent by the same hemodynamic abnormalities. The principal clinical consequences of left ventricular hypertrophy and arterial alterations are heart failure, ischemic heart disease, and peripheral artery disease. Cardiovascular alterations are only partly reversible, and efforts should be directed toward early prevention. Pathophysiology of cardiovascular disease in hemodialysis patients. Cardiovascular disease is the principal cause of morbidity and mortality in dialysis patients. The principal alterations responsible are left ventricular hypertrophy and arterial disease characterized by an enlargement and hypertrophy of arteries and the high prevalence of atheromatous plaques. Left ventricular hypertrophy is the consequence of combined effects of chronic hemodynamic overload and nonhemodynamic biochemical and neurohumoral factors characteristic of uremia. The hemodynamic overload is due to flow and pressure overload. The flow overload is tightly related to hyperkinetic circulation caused by anemia, arteriovenous fistula, or overhydration and is characterized by an enlargement of the left ventricular cavity. The pressure overload in these patients is more tightly related to abnormal geometry and function of large conduit arteries, principally the stiffening of arterial tree. The flow overload is also in large part responsible for remodeling of arterial tree, and as the heart and vessels are a coupled interactive physiological system, cardiac and vascular alterations occur in parallel, being induced to a great extent by the same hemodynamic abnormalities. The principal clinical consequences of left ventricular hypertrophy and arterial alterations are heart failure, ischemic heart disease, and peripheral artery disease. Cardiovascular alterations are only partly reversible, and efforts should be directed toward early prevention. Cardiovascular disease is the leading cause of mortality among patients with end-stage renal disease (ESRD), with cardiac disease alone accounting for 40% of deaths[1.U.S. Renal Data System USRDA 1991 Annual Report. Bethesda, The National Institute of Diabetes and Digestive and Kidney Diseases, 1991Google Scholar], [2.Raine A.E.G. Margreiter R. Brunner F.P. Ehrich J.H.H. Geelings W. Landais P. Loirat C. Mallick N.P. Selwood N.H. Tufveson G. Valderrabano F. Report on management of renal failure in Europe, XXII, 1991.Nephrol Dial Transplant. 1992; 7: S7-S35PubMed Google Scholar]. Cardiomyopathy and ischemic heart disease are the most frequent causes of cardiac death[3.Rostand R.G. Kirk K.A. Rutsky E.A. Dialysis ischemic heart disease: Insight from coronary angiography.Kidney Int. 1984; 25: 653-659Abstract Full Text PDF PubMed Scopus (220) Google Scholar, 4.Harnett J.D. Foley R.N. Kent G.M. Barre P.E. Murray D. Parfrey P.S. Congestive heart failure in dialysis patients: Prevalence, incidence, prognosis and risk factors.Kidney Int. 1995; 47: 884-890Abstract Full Text PDF PubMed Scopus (547) Google Scholar, 5.Parfrey P.S. Foley R.N. Harnett J.D. Kent M.G. Murray D.C. Barre P.E. Outcome and risk factors of ischemic heart disease in chronic uremia.Kidney Int. 1996; 49: 1428-1434Abstract Full Text PDF PubMed Scopus (276) Google Scholar]. At all ages, dialysis patients are at a 10- to 20-fold increased risk of death from a cardiovascular cause, with the relative risk being higher in younger patients and declining with age[2.Raine A.E.G. Margreiter R. Brunner F.P. Ehrich J.H.H. Geelings W. Landais P. Loirat C. Mallick N.P. Selwood N.H. Tufveson G. Valderrabano F. Report on management of renal failure in Europe, XXII, 1991.Nephrol Dial Transplant. 1992; 7: S7-S35PubMed Google Scholar]. Left ventricular hypertrophy (LVH) is the most frequent cardiac alteration in ESRD and is an independent risk factor for survival in these patients[6.London G.M. Marchais S.J. Guérin A.P. Fabiani F. Métivier F. Cardiovascular function in hemodialysis patients.Advances in Nephrology. edited by Grünfeld JP, Bach JF, Funck-Brentano JL, Maxwell MH. St. Louis, Mosby Year Book Publishers, 1991: 249-273Google Scholar, 7.Harnett J.D. Kent G.M. Barre P.E. Taylor R. Parfrey P.S. Risk factors for the development of left ventricular hypertrophy in a prospective followed cohort of dialysis patients.J Am Soc Nephrol. 1994; 4: 1486-1490PubMed Google Scholar, 8.London G.M. Parfrey P.S. Cardiac disease in chronic uremia: Pathogenesis.Adv Ren Replace Ther. 1997; 4: 194-211PubMed Google Scholar, 9.Silberberg J. Barre P.E. Prichard S.S. Sniderman A.D. Impact of left ventricular hypertrophy on survival in end-stage renal disease.Kidney Int. 1989; 36: 286-290Abstract Full Text PDF PubMed Scopus (723) Google Scholar]. Epidemiological and clinical studies have shown that damage of large arteries is a major contributory factor to the high mortality of ESRD patients. Macrovascular disease develops rapidly in uremic patients and is responsible for the high incidence of ischemic heart disease[1.U.S. Renal Data System USRDA 1991 Annual Report. Bethesda, The National Institute of Diabetes and Digestive and Kidney Diseases, 1991Google Scholar], [2.Raine A.E.G. Margreiter R. Brunner F.P. Ehrich J.H.H. Geelings W. Landais P. Loirat C. Mallick N.P. Selwood N.H. Tufveson G. Valderrabano F. Report on management of renal failure in Europe, XXII, 1991.Nephrol Dial Transplant. 1992; 7: S7-S35PubMed Google Scholar]. Although the majority of these accidents may be due to atherosclerotic obstructive lesions, in 25 to 30% of these patients its origin is nonatherosclerotic, being associated with microvascular disease or fibroelastic thickening of the aorta and reduced arterial compliance3.Rostand R.G. Kirk K.A. Rutsky E.A. Dialysis ischemic heart disease: Insight from coronary angiography.Kidney Int. 1984; 25: 653-659Abstract Full Text PDF PubMed Scopus (220) Google Scholar, 10.Roig E. Betriu A. Castaner A. Magrina J. Sanz G. Navarra-Lopez F. Disabling angina pectoris with normal coronary arteries in patients undergoing hemodialysis.Am J Med. 1981; 71: 437-444Abstract Full Text PDF Scopus (41) Google Scholar, 11.London G.M. Guérin A.P. Marchais S.J. Pannier B. Safar M.E. Day M. Metivier F. Cardiac and arterial interactions in end-stage renal disease.Kidney Int. 1996; 50: 600-608Abstract Full Text PDF PubMed Scopus (444) Google Scholar associated with nonatherosclerotic arterial remodeling[11.London G.M. Guérin A.P. Marchais S.J. Pannier B. Safar M.E. Day M. Metivier F. Cardiac and arterial interactions in end-stage renal disease.Kidney Int. 1996; 50: 600-608Abstract Full Text PDF PubMed Scopus (444) Google Scholar, 12.Barenbrock M. Spieker C. Laske V. Rahn K.-H. Studies of the vessel wall properties in hemodialysis patients.Kidney Int. 1994; 45: 1397-1400Abstract Full Text PDF PubMed Scopus (150) Google Scholar, 13.Kawagishi T. Nishizawa Y. Konishi T. Kawasaki K. Emoto M. Shoji T. Tabata T. Inoue T. Morii H. High-resolution B-mode ultrasonography in evaluation of atherosclerosis in uremia.Kidney Int. 1995; 48: 820-826Abstract Full Text PDF PubMed Scopus (290) Google Scholar, 14.London G.M. Drüeke T.B. Atherosclerosis and arteriosclerosis in chronic renal failure.Kidney Int. 1995; 51: 1678-1695Abstract Full Text PDF Scopus (348) Google Scholar]. The cardiac and vascular abnormalities share several common pathophysiological mechanisms and are frequently interrelated[11.London G.M. Guérin A.P. Marchais S.J. Pannier B. Safar M.E. Day M. Metivier F. Cardiac and arterial interactions in end-stage renal disease.Kidney Int. 1996; 50: 600-608Abstract Full Text PDF PubMed Scopus (444) Google Scholar]. The purpose of the present article is to summarize the pathophysiological mechanisms of cardiac and arterial alterations in ESRD patients undergoing replacement therapy. Left ventricular hypertrophy is an adaptive response to increased cardiac work Figure 1. The initiating signal includes myocardial stretch increasing the LV tensile stress[15.Grossman W. Cardiac hypertrophy: Useful adaptation or pathological process?.Am J Med. 1980; 69: 576-584Abstract Full Text PDF PubMed Scopus (399) Google Scholar], [16.Katz A.M. Cardiomyopathy of overload: a major determinant of prognosis in congestive heart failure.N Engl J Med. 1990; 322: 100-110Crossref PubMed Scopus (481) Google Scholar]. Increased cardiac work is frequently associated with increased release of neurotransmitters and vasoactive substances that may have a permissive or direct effect on cardiomyocyte growth[17.Morgan H.E. Baker K.M. Cardiac hypertrophy: Mechanical, neural, and endocrine dependence.Circulation. 1991; 83: 13-25Crossref PubMed Scopus (605) Google Scholar], [18.Dzau V.J. The role of mechanical and humoral factors in growth regulation of vascular smooth muscle and cardiac myocytes.Curr Opin Nephrol Hypertens. 1993; 2: 27-32Crossref PubMed Scopus (102) Google Scholar]. LVH is both beneficial and detrimental. The benefit is linked to an increased number of sarcomeres, enhancing the working capacity while keeping the parietal tensile stress stable, thus sparing energy[17.Morgan H.E. Baker K.M. Cardiac hypertrophy: Mechanical, neural, and endocrine dependence.Circulation. 1991; 83: 13-25Crossref PubMed Scopus (605) Google Scholar], [18.Dzau V.J. The role of mechanical and humoral factors in growth regulation of vascular smooth muscle and cardiac myocytes.Curr Opin Nephrol Hypertens. 1993; 2: 27-32Crossref PubMed Scopus (102) Google Scholar]. This beneficial effect maintains normal systolic function during the initial phase of compensated “adaptive” LVH. The sustained overload leads progressively to “maladaptive” hypertrophic response[16.Katz A.M. Cardiomyopathy of overload: a major determinant of prognosis in congestive heart failure.N Engl J Med. 1990; 322: 100-110Crossref PubMed Scopus (481) Google Scholar]. In the maladaptive phase of LVH, the active myocardial cells have an imbalance between energy expenditure and production, resulting in a chronic energy deficit and accelerated death of myocytes[15.Grossman W. Cardiac hypertrophy: Useful adaptation or pathological process?.Am J Med. 1980; 69: 576-584Abstract Full Text PDF PubMed Scopus (399) Google Scholar], [16.Katz A.M. Cardiomyopathy of overload: a major determinant of prognosis in congestive heart failure.N Engl J Med. 1990; 322: 100-110Crossref PubMed Scopus (481) Google Scholar]. The increase in extracellular matrix and collagen content permits maintenance of the mechanical efficiency of the contracting heart at the expense of impaired diastolic filling. LVH usually develops in a pattern specific to the initiating mechanical stress[15.Grossman W. Cardiac hypertrophy: Useful adaptation or pathological process?.Am J Med. 1980; 69: 576-584Abstract Full Text PDF PubMed Scopus (399) Google Scholar], [16.Katz A.M. Cardiomyopathy of overload: a major determinant of prognosis in congestive heart failure.N Engl J Med. 1990; 322: 100-110Crossref PubMed Scopus (481) Google Scholar]. Pressure overload results in a parallel addition of new sarcomeres with a disproportionate increase of the LV wall thickness and normal chamber radius (concentric hypertrophy). Volume overload results primarily in the addition of new sarcomeres in series and secondarily in the addition of sarcomeres in parallel, resulting in an enlargement of the LV chamber with an increased wall thickness sufficient to counterbalance the increased radius (eccentric hypertrophy)[15.Grossman W. Cardiac hypertrophy: Useful adaptation or pathological process?.Am J Med. 1980; 69: 576-584Abstract Full Text PDF PubMed Scopus (399) Google Scholar]. The development and characteristics of LVH are influenced by several other factors, such as age, gender, race, and coexistent diseases like diabetes, systemic diseases, or renal failure. The prevalence of LVH is high among ESRD patients. The structural alterations occur early in the course of renal failure. In a prospective study in patients starting renal replacement therapy, 74% of the patients had LVH, and high LV mass index was an independent predictor of death after two years of treatment[19.Foley R.N. Parfrey P.S. Harnett J.D. Kent G.M. Martin C.J. Murray D.C. Barre P.E. Clinical and echocardiographic disease in patients starting ESRD therapy.Kidney Int. 1995; 47: 186-192Abstract Full Text PDF PubMed Scopus (1072) Google Scholar]. In dialysis patients, as many as 80% of patients have an increased LV mass[6.London G.M. Marchais S.J. Guérin A.P. Fabiani F. Métivier F. Cardiovascular function in hemodialysis patients.Advances in Nephrology. edited by Grünfeld JP, Bach JF, Funck-Brentano JL, Maxwell MH. St. Louis, Mosby Year Book Publishers, 1991: 249-273Google Scholar, 7.Harnett J.D. Kent G.M. Barre P.E. Taylor R. Parfrey P.S. Risk factors for the development of left ventricular hypertrophy in a prospective followed cohort of dialysis patients.J Am Soc Nephrol. 1994; 4: 1486-1490PubMed Google Scholar, 8.London G.M. Parfrey P.S. Cardiac disease in chronic uremia: Pathogenesis.Adv Ren Replace Ther. 1997; 4: 194-211PubMed Google Scholar, 9.Silberberg J. Barre P.E. Prichard S.S. Sniderman A.D. Impact of left ventricular hypertrophy on survival in end-stage renal disease.Kidney Int. 1989; 36: 286-290Abstract Full Text PDF PubMed Scopus (723) Google Scholar, 10.Roig E. Betriu A. Castaner A. Magrina J. Sanz G. Navarra-Lopez F. Disabling angina pectoris with normal coronary arteries in patients undergoing hemodialysis.Am J Med. 1981; 71: 437-444Abstract Full Text PDF Scopus (41) Google Scholar, 11.London G.M. Guérin A.P. Marchais S.J. Pannier B. Safar M.E. Day M. Metivier F. Cardiac and arterial interactions in end-stage renal disease.Kidney Int. 1996; 50: 600-608Abstract Full Text PDF PubMed Scopus (444) Google Scholar, 12.Barenbrock M. Spieker C. Laske V. Rahn K.-H. Studies of the vessel wall properties in hemodialysis patients.Kidney Int. 1994; 45: 1397-1400Abstract Full Text PDF PubMed Scopus (150) Google Scholar, 13.Kawagishi T. Nishizawa Y. Konishi T. Kawasaki K. Emoto M. Shoji T. Tabata T. Inoue T. Morii H. High-resolution B-mode ultrasonography in evaluation of atherosclerosis in uremia.Kidney Int. 1995; 48: 820-826Abstract Full Text PDF PubMed Scopus (290) Google Scholar, 14.London G.M. Drüeke T.B. Atherosclerosis and arteriosclerosis in chronic renal failure.Kidney Int. 1995; 51: 1678-1695Abstract Full Text PDF Scopus (348) Google Scholar, 15.Grossman W. Cardiac hypertrophy: Useful adaptation or pathological process?.Am J Med. 1980; 69: 576-584Abstract Full Text PDF PubMed Scopus (399) Google Scholar, 16.Katz A.M. Cardiomyopathy of overload: a major determinant of prognosis in congestive heart failure.N Engl J Med. 1990; 322: 100-110Crossref PubMed Scopus (481) Google Scholar, 17.Morgan H.E. Baker K.M. Cardiac hypertrophy: Mechanical, neural, and endocrine dependence.Circulation. 1991; 83: 13-25Crossref PubMed Scopus (605) Google Scholar, 18.Dzau V.J. The role of mechanical and humoral factors in growth regulation of vascular smooth muscle and cardiac myocytes.Curr Opin Nephrol Hypertens. 1993; 2: 27-32Crossref PubMed Scopus (102) Google Scholar, 19.Foley R.N. Parfrey P.S. Harnett J.D. Kent G.M. Martin C.J. Murray D.C. Barre P.E. Clinical and echocardiographic disease in patients starting ESRD therapy.Kidney Int. 1995; 47: 186-192Abstract Full Text PDF PubMed Scopus (1072) Google Scholar]. The increase in the LV mass in ESRD patients can be due to an increase in either LV end-diastolic diameter or LV wall thickness and combines the features of both eccentric and concentric hypertrophy4.Harnett J.D. Foley R.N. Kent G.M. Barre P.E. Murray D. Parfrey P.S. Congestive heart failure in dialysis patients: Prevalence, incidence, prognosis and risk factors.Kidney Int. 1995; 47: 884-890Abstract Full Text PDF PubMed Scopus (547) Google Scholar, 6.London G.M. Marchais S.J. Guérin A.P. Fabiani F. Métivier F. Cardiovascular function in hemodialysis patients.Advances in Nephrology. edited by Grünfeld JP, Bach JF, Funck-Brentano JL, Maxwell MH. St. Louis, Mosby Year Book Publishers, 1991: 249-273Google Scholar, 8.London G.M. Parfrey P.S. Cardiac disease in chronic uremia: Pathogenesis.Adv Ren Replace Ther. 1997; 4: 194-211PubMed Google Scholar. The precise classification of LVH as an eccentric or concentric type is sometimes difficult in hemodialysis patients because of cyclic variations in extracellular fluid volume and humoral balance. The internal dimensions of the LV are influenced by volume status, and the contraction of blood volume during the dialysis session decreases the LV diameter, thus inducing “acute” changes in the relative wall thickness of the LV[6.London G.M. Marchais S.J. Guérin A.P. Fabiani F. Métivier F. Cardiovascular function in hemodialysis patients.Advances in Nephrology. edited by Grünfeld JP, Bach JF, Funck-Brentano JL, Maxwell MH. St. Louis, Mosby Year Book Publishers, 1991: 249-273Google Scholar]. In stable patients with compensated hypertrophy, the systolic function remains in the normal range, while the diastolic filling is frequently altered[6.London G.M. Marchais S.J. Guérin A.P. Fabiani F. Métivier F. Cardiovascular function in hemodialysis patients.Advances in Nephrology. edited by Grünfeld JP, Bach JF, Funck-Brentano JL, Maxwell MH. St. Louis, Mosby Year Book Publishers, 1991: 249-273Google Scholar, 7.Harnett J.D. Kent G.M. Barre P.E. Taylor R. Parfrey P.S. Risk factors for the development of left ventricular hypertrophy in a prospective followed cohort of dialysis patients.J Am Soc Nephrol. 1994; 4: 1486-1490PubMed Google Scholar, 8.London G.M. Parfrey P.S. Cardiac disease in chronic uremia: Pathogenesis.Adv Ren Replace Ther. 1997; 4: 194-211PubMed Google Scholar]. Left ventricular hypertrophy in ESRD patients is principally due to an increase in LV minute work resulting from volume and pressure overload[8.London G.M. Parfrey P.S. Cardiac disease in chronic uremia: Pathogenesis.Adv Ren Replace Ther. 1997; 4: 194-211PubMed Google Scholar], [20.London G.M. Guérin A.P. Marchais S.J. Pressure-overload cardiomyopathy in end-stage renal disease.Curr Opin Nephrol Hypertens. 1999; 8: 179-186Crossref Scopus (20) Google Scholar]. Nevertheless, experimental and clinical studies demonstrated that the cardiovascular structural changes in ESRD are in part independent from hemodynamic factors[21.Amann K. Wiest G. Klaus G. Ritz E. Mall G. The role of parathyroid hormone in the genesis of interstitial cell activation in uremia.J Am Soc Nephrol. 1994; 4: 1814-1819PubMed Google Scholar, 22.Amann K. Kronenberg G. Gehlen F. Wessels S. Orth S. Münter K. Ehmke H. Mall G. Ritz E. Cardiac remodelling in experimental renal failure—An immunohistochemical study.Nephrol Dial Transplant. 1998; 13: 1958-1966Crossref PubMed Scopus (101) Google Scholar, 23.London G.M. Pannier B. Guérin A.P. Marchais S.J. Safar M.E. Cuche J.L. Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease: Comparative effects of ACE inhibition and calcium channel blockade.Circulation. 1994; 90: 2786-2796Crossref PubMed Google Scholar, 24.Vlahakos D.V. Hahalis G. Vassilakos P. Marathias K.P. Geroulanos S. Relationship between left ventricular hypertrophy and plasma renin activity in chronic hemodialysis patients.J Am Soc Nephrol. 1997; 8: 1764-1770PubMed Google Scholar, 25.Demuth K. Blacher J. Guérin A.P. Benoit M.-O. Moatti N. Safar M.E. London G.M. Endothelin and cardiovascular remodelling in end-stage renal disease.Nephrol Dial Transplant. 1998; 13: 375-383Crossref PubMed Scopus (86) Google Scholar]. In experimental renal failure, increased cardiac mass with interstitial fibrosis[26.Mall G. Huther W. Schneider J. Lundin P. Ritz E. Diffuse intramyocardial fibrosis in uraemic patients.Nephrol Dial Transplant. 1990; 5: 39-44Crossref PubMed Scopus (227) Google Scholar], reduced capillary density, and increased intramyocardial arteriolar wall thickness has been demonstrated[27.Amann K. Törnig J. Flechtenmacher Ch Nabokov A. Mall G. Ritz E. Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uremia: Evidence for a permissive action of PTH.Nephrol Dial Transplant. 1995; 10: 2043-2048PubMed Google Scholar], [28.Amann K. Breitbach M. Ritz E. Mall G. Myocyte/capillary mismatch in the heart of uremic patients.J Am Soc Nephrol. 1998; 9: 1018-1022PubMed Google Scholar]. Experimental studies have shown that parathyroid hormone could have a permissive role in the cardiac fibrogenesis and the activation of cardiac fibroblasts[21.Amann K. Wiest G. Klaus G. Ritz E. Mall G. The role of parathyroid hormone in the genesis of interstitial cell activation in uremia.J Am Soc Nephrol. 1994; 4: 1814-1819PubMed Google Scholar]. Cardiac remodeling in experimental uremia is characterized by activation of postmitotic cardiomyocytes[22.Amann K. Kronenberg G. Gehlen F. Wessels S. Orth S. Münter K. Ehmke H. Mall G. Ritz E. Cardiac remodelling in experimental renal failure—An immunohistochemical study.Nephrol Dial Transplant. 1998; 13: 1958-1966Crossref PubMed Scopus (101) Google Scholar], possibly predisposing to apoptosis and “maladaptive” hypertrophy[29.Katz A.M. The cardiomyopathy of overload: An unnatural growth response in the hypertrophied heart.Ann Intern Med. 1994; 121: 363-371Crossref PubMed Scopus (184) Google Scholar]. The LV of ESRD patients is characterized by an expansion of the cardiac interstitium. The latter is more prominent than in patients with diabetes or primary essential hypertension with comparable LV mass[26.Mall G. Huther W. Schneider J. Lundin P. Ritz E. Diffuse intramyocardial fibrosis in uraemic patients.Nephrol Dial Transplant. 1990; 5: 39-44Crossref PubMed Scopus (227) Google Scholar]. Intramyocardial fibrosis in hemodialyzed patients with secondary hyperparathyroidism could account for the development of an inadequate hypertrophy with persistence of high LV systolic stress[30.London G.M. Fabiani F. Marchais S.J. de Vernejoul M-Ch Guérin A.P. Safar M.E. Metivier F. Llach F. Uremic cardiomyopathy: An inadequate left ventricular hypertrophy.Kidney Int. 1987; 31: 973-980Abstract Full Text PDF PubMed Scopus (207) Google Scholar]. Nevertheless, the role of hyperparathyroidism is controversial, and parathyroidectomy did not produce significant effects on cardiac structure and function[31.Gafter U. Battler A. Eldar M. Zevin D. Neufeld H.N. Levi J. Effect of hyperparathyroidism on cardiac function in patients with end-stage renal disease.Nephron. 1985; 41: 30-33Crossref PubMed Scopus (31) Google Scholar, 32.Zucchelli P. Santoro A. Zucchelli A. Spongano M. Ferrari G. Long-term effects of parathyroidectomy on cardiac and autonomic nervous system functions in haemodialysis patients.Nephrol Dial Transplant. 1988; 3: 45-50PubMed Google Scholar, 33.Fellner S.K. Lang R.M. Neumann A. Bushinsky D.A. Borow K.M. Parathyroid hormone and cardiac performance in dialysis patients.Am J Kidney Dis. 1991; 18: 320-325Abstract Full Text PDF PubMed Scopus (25) Google Scholar]. With some exception[24.Vlahakos D.V. Hahalis G. Vassilakos P. Marathias K.P. Geroulanos S. Relationship between left ventricular hypertrophy and plasma renin activity in chronic hemodialysis patients.J Am Soc Nephrol. 1997; 8: 1764-1770PubMed Google Scholar], an association of LVH and plasma renin-angiotensin activity was not demonstrated[23.London G.M. Pannier B. Guérin A.P. Marchais S.J. Safar M.E. Cuche J.L. Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease: Comparative effects of ACE inhibition and calcium channel blockade.Circulation. 1994; 90: 2786-2796Crossref PubMed Google Scholar]. Nevertheless, angiotensin I-converting enzyme (ACE) inhibitors are able to partially regress LVH independently of their antihypertensive effect, suggesting that the tissular and cardiac renin-angiotensin system could play a role in the pathogenesis of LVH in uremic patients[23.London G.M. Pannier B. Guérin A.P. Marchais S.J. Safar M.E. Cuche J.L. Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease: Comparative effects of ACE inhibition and calcium channel blockade.Circulation. 1994; 90: 2786-2796Crossref PubMed Google Scholar]. A recent study by Demuth et al showed that the increased plasma endothelin in ESRD patients was associated with LVH, suggesting that endothelin may be of pathophysiological significance in the process of cardiac remodeling[25.Demuth K. Blacher J. Guérin A.P. Benoit M.-O. Moatti N. Safar M.E. London G.M. Endothelin and cardiovascular remodelling in end-stage renal disease.Nephrol Dial Transplant. 1998; 13: 375-383Crossref PubMed Scopus (86) Google Scholar]. The influence of endothelin in the cardiac remodeling was also demonstrated experimentally in rats in which the endothelin receptor antagonists were able to attenuate the development of myocardial hypertrophy[34.Ehmke H. Faulhaber J. Münter K. Kirchengast M. Wiesner R.J. Chronic ETA receptor blockade attenuates cardiac hypertrophy independently of blood pressure effects in renovascular hypertensive rats.Hypertension. 1999; 33: 954-960Crossref PubMed Scopus (67) Google Scholar]. Low serum albumin in ESRD was associated with the development of heart failure in progressive dilation of the LV[4.Harnett J.D. Foley R.N. Kent G.M. Barre P.E. Murray D. Parfrey P.S. Congestive heart failure in dialysis patients: Prevalence, incidence, prognosis and risk factors.Kidney Int. 1995; 47: 884-890Abstract Full Text PDF PubMed Scopus (547) Google Scholar], [7.Harnett J.D. Kent G.M. Barre P.E. Taylor R. Parfrey P.S. Risk factors for the development of left ventricular hypertrophy in a prospective followed cohort of dialysis patients.J Am Soc Nephrol. 1994; 4: 1486-1490PubMed Google Scholar]. The causal mechanisms of this association are not clear. Hypoalbuminemia could reflect the existence of an inflammatory state characterized by increased C-reactive protein, fibrinogen, and cytokines, which are considered as cardiovascular risk factors. In ESRD patients, hypoalbuminemia is also associated with the presence of atheromatous plaques[35.Savage T. Clarke A.L. Giles M. Tomson C.R.V. Raine A.E.G. Calcified plaque is common in the carotid and femoral arteries of dialysis patients without clinical vascular disease.Nephrol Dial Transplant. 1998; 13: 2004-2012Crossref PubMed Scopus (147) Google Scholar] and abnormal endothelial function[36.Pannier B. Guérin A.P. Marchais S.J. Métivier F. Safar M.E. London G.M. Postischemic vasodilation, endothelial activation and cardiovascular remodeling in end-stage renal disease.Kidney Int. 2000; 57: 1091-1099Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar]. Hypoalbuminemia may affect endothelial function and may inhibit nitric oxide (NO)-mediated vascular relaxation and LV/vascular coupling[37.Joles J.A. Willekes-Koolschijn N. Koomans H.A. Hypoalbuminemia causes high blood viscosity by increasing red cell lysophosphatidylcholine.Kidney Int. 1997; 52: 761-770Abstract Full Text PDF PubMed Scopus (82) Google Scholar], [38.Minamiyama Y. Takemura S. Inoue M. Albumin is an important vascular tonus regulator as a reservoir of nitric oxide.Biochem Biophys Res Commun. 1996; 225: 112-115Crossref PubMed Scopus (71) Google Scholar]. Three factors are involved: (1) an increased stroke volume and hyperkinetic high-output state (flow/volume overload), (2) an increased opposition to LV ejection (pressure overload), and (3) an increased heart rate[5.Parfrey P.S. Foley R.N. Harnett J.D. Kent M.G. Murray D.C. Barre P.E. Outcome and risk factors of ischemic heart disease in chronic uremia.Kidney Int. 1996; 49: 1428-1434Abstract Full Text PDF PubMed Scopus (276) Google Scholar, 6.London G.M. Marchais S.J. Guérin A.P. Fabiani F. Métivier F. Cardiovascular function in hemodialysis patients.Advances in Nephrology. edited by Grünfeld JP, Bach JF, Funck-Brentano JL, Maxwell MH. St. Louis, Mosby Year Book Publishers, 1991: 249-273Google Scholar, 7.Harnett J.D. Kent G.M. Barre P.E. Taylor R. Parfrey P.S. Risk factors for the development of left ventricular hypertrophy in a prospective followed cohort of dialysis patients.J Am Soc Nephrol. 1994; 4: 1486-1490PubMed Google Scholar, 8.London G.M. Parfrey P.S. Cardiac disease in chronic uremia: Pathogenesis.Adv Ren Replace Ther. 1997; 4: 194-211PubMed Google Scholar]. Volume/flow overload is characterized by an increased stroke volume and cardiac output in association with an increase in the LV end-diastolic diameter4.Harnett J.D. Foley R.N. Kent G.M. Barre P.E. Murray D. Parfrey P.S. Congestive heart failure in dialysis patients: Prevalence, in
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