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Clinical and Biochemistry Determinants for Bnp and Renin-Angiotensin-Aldosterone Activation in Patients With Heart Failure
Abstracts
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significant increases in an established prognostic biomarker in HF, brain natriuretic peptide (BNP), for HFpEF (meanSEM, 18834 pg/mL; p<0.001) and HFrEF (30335 pg/mL; p<0.001) with respect to control (212 pg/mL). In the combined HF cohort, males had significantly higher ACE2 activity (48.23.0 vs. 35.33.6 pmol/hr/mL; p¼0.009), and while there was no significant difference in plasma ACE2 activity in response to obesity, hypertension or diabetes, BNP was significantly higher in non-obese compared to obese individuals (meanSEM, 22235 pg/mL vs. 14323 pg/mL; p¼0.011). ACE2 increased from mild to severe HF as per New York Heart Association (NYHA) class (I & II, 40.32.5 pmol/hr/mL vs. III & IV, 51.85.7 pmol/hr/mL; p¼0.037). CONCLUSION: Plasma ACE2 activity is increased in both types of HF and is similar within risk factor subgroups; this is in contrast to BNP, which varies in response to obesity. Males have higher plasma ACE2 activity than females, which reflects generally poorer outcomes for males. ACE2 is elevated in severe HF as compared to mild HF. These data suggest a potential utility of ACE2 as a prognostic biomarker in HF, particularly in patient subpopulations, such as obese persons, where traditional biomarkers, such as BNP, might have reduced efficacy. CIHR
renin activity (PRA), and aldosterone. Other parameters of interest included glucose, insulin and microalbuminuria. RESULTS: Mean BNP was 221286 ng/L and NT-proBNP was 12281556 pg/mL. There was a significant increase in all biomarkers compared with reference values. The correlation between BNP and NT-proBNP was 0.81. The relationships between selected neurohormones and clinical parameters were analysed by multi-variate linear regression model. Both BNP and NT-proBNP were inversely correlated with creatinine clearance (r¼-0.6 and -0.65 respectively; p<0.01). NT-proBNP was significantly associated with the presence of atrial fibrillation (r¼0.48; p<0.01). There was a significant relationship between PRA with furosemide use (0.69; p¼0.02), spironolactone (0.89; p<0.01), beta blocker (-0.90; p<0.01) and statin use (r¼0.51; p¼0.03), as well as the presence of hypertension (r¼-0.42; p¼0.03). Aldosterone levels correlated with the administration of spironolactone and GFR (both p<0.01). CONCLUSION: Renal function, furosemide and aldactone utilisations exert a significant impact on BNP as well as on the parameters of RAAS activation in patients with symptomatic HF. In addition, the presence of hypertension, atrial fibrillation and statins utilisation appears associated with the markers of LV wall stress and systemic RAAS activation in these patients. AstraZeneca Canada
Featured Research 063 CLINICAL AND BIOCHEMISTRY DETERMINANTS FOR BNP AND RENIN-ANGIOTENSIN-ALDOSTERONE ACTIVATION IN PATIENTS WITH HEART FAILURE M White, A Mansour, M Guertin, J Lavoie, S Lepage, R Sheppard, S Kouz, M Leblanc, M Dubé, E O'Meara, N Racine, A Ducharme, J Tardif, J Rouleau, S de Denus Montréal, Québec BACKGROUND:
Patients with heart failure (HF) present a variable state of neurohumoral activation. The clinical and biochemistry determinants for neurohumoral activation have been incompletely studied. The objective of this investigation was to assess the relationship between some selected clinical and biochemistry parameters with activation of brain natriuretic peptide (BNP) and renin-angiotensin-aldosterone system (RAAS) in patients with symptomatic HF. METHODS: Two hundred ninety-nine patients were enrolled in a prospective multi-centers (15 sites) open study to investigate the impact of selected candidate genes on the clinical, hemodynamic and biochemical effects of candesartan in patients with HF treated with an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker. Eighty percent of patients presented with class II symptoms and the mean ejection fraction was 29.97% (meanSD). The etiology was ischemic in 71.6% of subjects. Ninety-nine percent of patients were chronically treated with an ACE inhibitor while 90.3% were treated with a beta-blocker. The mean dose of ACE inhibitor in enalapril equivalent was 18.110.1 mg/day. Selected neurohormones included BNP, NT-proBNP, renin mass and plasma
Canadian Cardiovascular Society (CCS) Poster GENETIC AND METABOLIC CELLULAR INJURY Thursday, October 17, 2013 066 WHOLE-GENOME EXPRESSION PROFILE OF CALCIFIED BICUSPID AND TRICUSPID AORTIC VALVES S Guauque-Olarte, N Gaudreault, P Pibarot, P Mathieu, Y Bossé Québec, Québec BACKGROUND: Calcific aortic valve stenosis (AS) is a fatal disease with no medical treatment other than surgery. Bicuspid aortic valve (BAV) is present in 1-2% of the population. Patients with BAV have increased risk of AS and develop symptoms of AS 10-15 years younger than patients with a tricuspid valve (TAV). The objective of this study was to identify genes differentially expressed between BAV and TAV with and without calcification. METHODS: Calcified aortic valves (12 BAV and 12 TAV) were explanted from 24 white male patients who underwent aortic valve replacement surgery. All valves had the same degree of fibro-calcific remodeling. Twelve nonstenotic TAV (controls) were taken from white males who underwent heart transplantation. The gene expression profile of each valve was measure with the Illumina HumanHT-12 v4 Expression BeadChip. Normalization and quality controls were performed with the lumi package in R. Gene expression levels were compared between the
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significant increases in an established prognostic biomarker in HF, brain natriuretic peptide (BNP), for HFpEF (meanSEM, 18834 pg/mL; p<0.001) and HFrEF (30335 pg/mL; p<0.001) with respect to control (212 pg/mL). In the combined HF cohort, males had significantly higher ACE2 activity (48.23.0 vs. 35.33.6 pmol/hr/mL; p¼0.009), and while there was no significant difference in plasma ACE2 activity in response to obesity, hypertension or diabetes, BNP was significantly higher in non-obese compared to obese individuals (meanSEM, 22235 pg/mL vs. 14323 pg/mL; p¼0.011). ACE2 increased from mild to severe HF as per New York Heart Association (NYHA) class (I & II, 40.32.5 pmol/hr/mL vs. III & IV, 51.85.7 pmol/hr/mL; p¼0.037). CONCLUSION: Plasma ACE2 activity is increased in both types of HF and is similar within risk factor subgroups; this is in contrast to BNP, which varies in response to obesity. Males have higher plasma ACE2 activity than females, which reflects generally poorer outcomes for males. ACE2 is elevated in severe HF as compared to mild HF. These data suggest a potential utility of ACE2 as a prognostic biomarker in HF, particularly in patient subpopulations, such as obese persons, where traditional biomarkers, such as BNP, might have reduced efficacy. CIHR
renin activity (PRA), and aldosterone. Other parameters of interest included glucose, insulin and microalbuminuria. RESULTS: Mean BNP was 221286 ng/L and NT-proBNP was 12281556 pg/mL. There was a significant increase in all biomarkers compared with reference values. The correlation between BNP and NT-proBNP was 0.81. The relationships between selected neurohormones and clinical parameters were analysed by multi-variate linear regression model. Both BNP and NT-proBNP were inversely correlated with creatinine clearance (r¼-0.6 and -0.65 respectively; p<0.01). NT-proBNP was significantly associated with the presence of atrial fibrillation (r¼0.48; p<0.01). There was a significant relationship between PRA with furosemide use (0.69; p¼0.02), spironolactone (0.89; p<0.01), beta blocker (-0.90; p<0.01) and statin use (r¼0.51; p¼0.03), as well as the presence of hypertension (r¼-0.42; p¼0.03). Aldosterone levels correlated with the administration of spironolactone and GFR (both p<0.01). CONCLUSION: Renal function, furosemide and aldactone utilisations exert a significant impact on BNP as well as on the parameters of RAAS activation in patients with symptomatic HF. In addition, the presence of hypertension, atrial fibrillation and statins utilisation appears associated with the markers of LV wall stress and systemic RAAS activation in these patients. AstraZeneca Canada
Featured Research 063 CLINICAL AND BIOCHEMISTRY DETERMINANTS FOR BNP AND RENIN-ANGIOTENSIN-ALDOSTERONE ACTIVATION IN PATIENTS WITH HEART FAILURE M White, A Mansour, M Guertin, J Lavoie, S Lepage, R Sheppard, S Kouz, M Leblanc, M Dubé, E O'Meara, N Racine, A Ducharme, J Tardif, J Rouleau, S de Denus Montréal, Québec BACKGROUND:
Patients with heart failure (HF) present a variable state of neurohumoral activation. The clinical and biochemistry determinants for neurohumoral activation have been incompletely studied. The objective of this investigation was to assess the relationship between some selected clinical and biochemistry parameters with activation of brain natriuretic peptide (BNP) and renin-angiotensin-aldosterone system (RAAS) in patients with symptomatic HF. METHODS: Two hundred ninety-nine patients were enrolled in a prospective multi-centers (15 sites) open study to investigate the impact of selected candidate genes on the clinical, hemodynamic and biochemical effects of candesartan in patients with HF treated with an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker. Eighty percent of patients presented with class II symptoms and the mean ejection fraction was 29.97% (meanSD). The etiology was ischemic in 71.6% of subjects. Ninety-nine percent of patients were chronically treated with an ACE inhibitor while 90.3% were treated with a beta-blocker. The mean dose of ACE inhibitor in enalapril equivalent was 18.110.1 mg/day. Selected neurohormones included BNP, NT-proBNP, renin mass and plasma
Canadian Cardiovascular Society (CCS) Poster GENETIC AND METABOLIC CELLULAR INJURY Thursday, October 17, 2013 066 WHOLE-GENOME EXPRESSION PROFILE OF CALCIFIED BICUSPID AND TRICUSPID AORTIC VALVES S Guauque-Olarte, N Gaudreault, P Pibarot, P Mathieu, Y Bossé Québec, Québec BACKGROUND: Calcific aortic valve stenosis (AS) is a fatal disease with no medical treatment other than surgery. Bicuspid aortic valve (BAV) is present in 1-2% of the population. Patients with BAV have increased risk of AS and develop symptoms of AS 10-15 years younger than patients with a tricuspid valve (TAV). The objective of this study was to identify genes differentially expressed between BAV and TAV with and without calcification. METHODS: Calcified aortic valves (12 BAV and 12 TAV) were explanted from 24 white male patients who underwent aortic valve replacement surgery. All valves had the same degree of fibro-calcific remodeling. Twelve nonstenotic TAV (controls) were taken from white males who underwent heart transplantation. The gene expression profile of each valve was measure with the Illumina HumanHT-12 v4 Expression BeadChip. Normalization and quality controls were performed with the lumi package in R. Gene expression levels were compared between the