Neurohormonal and inflammatory markers in valvular heart disease

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dc.contributor.advisorStewart Ralphen_ZA
dc.contributor.advisorSack, Michael Nen_ZA
dc.contributor.authorGerber, Ivor Leslieen_ZA
dc.date.accessioned2014-10-20T07:16:42Z
dc.date.available2014-10-20T07:16:42Z
dc.date.issued2004en_ZA
dc.descriptionIncludes bibliographical references (leaves 147-180).en_ZA
dc.description.abstractChronic valvular heart disease is characterised by compensatory mechanisms that result in a long asymptomatic phase associated with variable disease progression. After the development of symptoms or left ventricular dysfunction, mortality is high without surgical intervention. Currently there is no known medical therapy that influences disease progression or clinical outcome. While the development of symptoms or left ventricular dysfunction are the cardinal indications for valve surgery, routine echocardiography may not detect early left ventricular dysfunction and the development of early symptoms may not be appreciated. Numerous studies demonstrate that increased natriuretic peptide plasma levels, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and amino-terminal BNP (N-BNP) reflect left ventricular dysfunction, correlate with symptoms of cardiac failure and are independent prognostic markers for clinical outcomes in diverse cardiac conditions, but very few studies address natriuretic peptides in patients with valvular heart disease. The aims of this thesis are firstly, to determine the clinical utility of measuring natriuretic peptide plasma levels in patients with valvular heart disease, and secondly, to provide supportive biochemical evidence to established histological evidence that aortic stenosis is an inflammatory disease. One hundred and sixty three patients with chronic valvular heart disease, including aortic stenosis (n=74), aortic regurgitation (n=40) and mitral regurgitation (n=49) underwent independent assessment of symptoms, transthoracic echocardiography and measurement of plasma levels of ANP, BNP and N-BNP. Natriuretic peptide levels were significantly higher in symptomatic compared with asymptomatic patients after adjustment for echocardiographic measures of disease severity and left ventricular function. Of 29 asymptomatic patients with aortic stenosis followed for a mean of 18 months, patients with an N-BNF level above the normal range or with a greater increase in N-BNP/year were at increased risk of symptomatic deterioration. In 33 patients with aortic stenosis who underwent aortic valve replacement, N-BNP levels decreased and symptoms consistently improved by 6 months postoperatively in patients with a preoperative N-BNP level above the normal range, but N-BNP levels did not decrease and symptoms less reliably improved in patients with a preoperative N-BNP level within normal limits. In contrast to the established theory that aortic stenosis is a degenerative process not amenable to medical therapy, recent histological studies suggest that aortic stenosis may be an inflammatory disease with similarities to coronary atherosclerosis. To further address this issue, high sensitivity C-reactive protein (CRP) was measured in 20 patients with non-rheumatic aortic stenosis, 19 patients with non-rheumatic aortic regurgitation and 31 healthy controls, as well as 6 months after valve replacement in aortic stenosis. CRP was significantly increased in aortic stenosis, but not aortic regurgitation compared with controls and decreased after valve replacement in aortic stenosis. These observations are consistent with histological evidence that the aortic valve is the site of active inflammation. In conclusion, measurement of plasma natriuretic peptide levels complement clinical and echocardiographic evaluation of patients with valvular heart disease and may assist with the timing of valve surgery. Novel evidence that aortic stenosis may be an inflammatory disease is presented and suggests further studies are required to determine whether agents with anti-inflammatory actions may have a role in delaying disease progression. Following on the studies presented in this thesis, a large multicentre study has commenced in New Zealand to confirm these findings that has the potential to change clinical practice.en_ZA
dc.identifier.apacitationGerber, I. L. (2004). <i>Neurohormonal and inflammatory markers in valvular heart disease</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Cardiology. Retrieved from http://hdl.handle.net/11427/8624en_ZA
dc.identifier.chicagocitationGerber, Ivor Leslie. <i>"Neurohormonal and inflammatory markers in valvular heart disease."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Cardiology, 2004. http://hdl.handle.net/11427/8624en_ZA
dc.identifier.citationGerber, I. 2004. Neurohormonal and inflammatory markers in valvular heart disease. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Gerber, Ivor Leslie AB - Chronic valvular heart disease is characterised by compensatory mechanisms that result in a long asymptomatic phase associated with variable disease progression. After the development of symptoms or left ventricular dysfunction, mortality is high without surgical intervention. Currently there is no known medical therapy that influences disease progression or clinical outcome. While the development of symptoms or left ventricular dysfunction are the cardinal indications for valve surgery, routine echocardiography may not detect early left ventricular dysfunction and the development of early symptoms may not be appreciated. Numerous studies demonstrate that increased natriuretic peptide plasma levels, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and amino-terminal BNP (N-BNP) reflect left ventricular dysfunction, correlate with symptoms of cardiac failure and are independent prognostic markers for clinical outcomes in diverse cardiac conditions, but very few studies address natriuretic peptides in patients with valvular heart disease. The aims of this thesis are firstly, to determine the clinical utility of measuring natriuretic peptide plasma levels in patients with valvular heart disease, and secondly, to provide supportive biochemical evidence to established histological evidence that aortic stenosis is an inflammatory disease. One hundred and sixty three patients with chronic valvular heart disease, including aortic stenosis (n=74), aortic regurgitation (n=40) and mitral regurgitation (n=49) underwent independent assessment of symptoms, transthoracic echocardiography and measurement of plasma levels of ANP, BNP and N-BNP. Natriuretic peptide levels were significantly higher in symptomatic compared with asymptomatic patients after adjustment for echocardiographic measures of disease severity and left ventricular function. Of 29 asymptomatic patients with aortic stenosis followed for a mean of 18 months, patients with an N-BNF level above the normal range or with a greater increase in N-BNP/year were at increased risk of symptomatic deterioration. In 33 patients with aortic stenosis who underwent aortic valve replacement, N-BNP levels decreased and symptoms consistently improved by 6 months postoperatively in patients with a preoperative N-BNP level above the normal range, but N-BNP levels did not decrease and symptoms less reliably improved in patients with a preoperative N-BNP level within normal limits. In contrast to the established theory that aortic stenosis is a degenerative process not amenable to medical therapy, recent histological studies suggest that aortic stenosis may be an inflammatory disease with similarities to coronary atherosclerosis. To further address this issue, high sensitivity C-reactive protein (CRP) was measured in 20 patients with non-rheumatic aortic stenosis, 19 patients with non-rheumatic aortic regurgitation and 31 healthy controls, as well as 6 months after valve replacement in aortic stenosis. CRP was significantly increased in aortic stenosis, but not aortic regurgitation compared with controls and decreased after valve replacement in aortic stenosis. These observations are consistent with histological evidence that the aortic valve is the site of active inflammation. In conclusion, measurement of plasma natriuretic peptide levels complement clinical and echocardiographic evaluation of patients with valvular heart disease and may assist with the timing of valve surgery. Novel evidence that aortic stenosis may be an inflammatory disease is presented and suggests further studies are required to determine whether agents with anti-inflammatory actions may have a role in delaying disease progression. Following on the studies presented in this thesis, a large multicentre study has commenced in New Zealand to confirm these findings that has the potential to change clinical practice. DA - 2004 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2004 T1 - Neurohormonal and inflammatory markers in valvular heart disease TI - Neurohormonal and inflammatory markers in valvular heart disease UR - http://hdl.handle.net/11427/8624 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/8624
dc.identifier.vancouvercitationGerber IL. Neurohormonal and inflammatory markers in valvular heart disease. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Cardiology, 2004 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/8624en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Cardiologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherCardiologyen_ZA
dc.titleNeurohormonal and inflammatory markers in valvular heart diseaseen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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