Circulation. 2009;119:2471-2479
Insights From the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) Study
Background— Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction.
Methods and Results— In a substudy of the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), which evaluated the effects of the selective aldosterone receptor antagonist eplerenone versus placebo, serum levels of collagen biomarkers were measured in 476 patients with congestive heart failure after acute myocardial infarction complicated with left ventricular systolic dysfunction. The combination of the type I collagen telopeptide and brain natriuretic peptide levels above median at baseline was associated with all-cause mortality and the composite end point of cardiovascular death or heart failure hospitalization, with hazard ratios of 2.49 (P=0.039) and 3.03 (P=0.002), respectively. During follow-up, levels of aminoterminal propeptide of type I and type III procollagen were found to be consistently lower in the eplerenone group and significantly lower beginning at 6 months.
Conclusions— Changes in biomarkers of collagen synthesis and degradation suggest that extracellular matrix remodeling is an active process in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. High type I collagen telopeptide and high brain natriuretic peptide serum levels are associated with the highest event rate. Eplerenone suppresses post–acute myocardial infarction collagen turnover changes.
Wafae Iraqi, PharmD; Patrick Rossignol, MD, PhD; Michael Angioi, MD; Renaud Fay, PharmD; Josette Nuée, PhD; Jean Marie Ketelslegers, MD, PhD; John Vincent, MD; Bertram Pitt, MD; Faiez Zannad, MD, PhD
Tuesday
RENIN AND HEART FAILURE
THE RENIN SYSTEM AND ATRIAL NATRIURETIC HORMONE IN CONGESTIVE HEART FAILURE
Abstract. The renin angiotensin system is activated in the majority of patients with chronic congestive heart failure of moderate to severe symptomology. Renin release may result from one of several different stimuli: renal tubular sodium delivery and sensing by the macula densa, sympathetic nervous system activity, and baroreceptor to changes in renal blood flow. Difficulties arise with an analysis of renin angiotensin system activity due to the necessity for diuretic therapy in the majority of these patients. Despite the presence of diuretic therapy, however, there is a wide range of renin angiotensin system activity. In evaluating this activity the administration of a converting enzyme inhibitor will block the contribution of angiotensin mediated vasoconstriction, thereby confirming the importance of the renin angiotensin system activity as a mediator of the long-term consequences of heart failure In situations of low plasma renin activity, vasoconstriction is mediated by an alternate mechanism. The mechanisms of this non-renin mediated vasoconstriction are less apparent, but may include calcium mediated vasoconstriction, and the effects of increased cytosolic content.
This low renin group of patients appear to be very sensitive to reversal of vasoconstriction by calcium channel antagonists, especially when converting enzyme inhibitors are ineffective. In an analysis of the factors that may result in renin release, tubular delivery of sodium to the macula densa may emerge as the most important regulator of renin release.
In milder forms of heart failure, or in the absence of diuretic therapy, the renin angiotensin system does not show the degree of activation that occurs in the more severe form of heart failure when diuretics are given. From a theroretical standpoint, endogenous atrial natriuretic factor may emerge as an important regular of sodium and water excretion, acting either independently, or as a regulator of the renin angiotensin system, It will therefore be necessary to evaluate the impact of atrial natriuretic factor in patients with congestive heart failure particularly in relation to the renin angiotensin system.
John H. Laragh M.D., Robert J. Cody M.D., Andrew B. Covit M.D. and Steven A. Atlas M.D.Cardiovascular Center, The New York Hospital-Cornell University Medical Center, New York, N.Y.
Abstract. The renin angiotensin system is activated in the majority of patients with chronic congestive heart failure of moderate to severe symptomology. Renin release may result from one of several different stimuli: renal tubular sodium delivery and sensing by the macula densa, sympathetic nervous system activity, and baroreceptor to changes in renal blood flow. Difficulties arise with an analysis of renin angiotensin system activity due to the necessity for diuretic therapy in the majority of these patients. Despite the presence of diuretic therapy, however, there is a wide range of renin angiotensin system activity. In evaluating this activity the administration of a converting enzyme inhibitor will block the contribution of angiotensin mediated vasoconstriction, thereby confirming the importance of the renin angiotensin system activity as a mediator of the long-term consequences of heart failure In situations of low plasma renin activity, vasoconstriction is mediated by an alternate mechanism. The mechanisms of this non-renin mediated vasoconstriction are less apparent, but may include calcium mediated vasoconstriction, and the effects of increased cytosolic content.
This low renin group of patients appear to be very sensitive to reversal of vasoconstriction by calcium channel antagonists, especially when converting enzyme inhibitors are ineffective. In an analysis of the factors that may result in renin release, tubular delivery of sodium to the macula densa may emerge as the most important regulator of renin release.
In milder forms of heart failure, or in the absence of diuretic therapy, the renin angiotensin system does not show the degree of activation that occurs in the more severe form of heart failure when diuretics are given. From a theroretical standpoint, endogenous atrial natriuretic factor may emerge as an important regular of sodium and water excretion, acting either independently, or as a regulator of the renin angiotensin system, It will therefore be necessary to evaluate the impact of atrial natriuretic factor in patients with congestive heart failure particularly in relation to the renin angiotensin system.
John H. Laragh M.D., Robert J. Cody M.D., Andrew B. Covit M.D. and Steven A. Atlas M.D.Cardiovascular Center, The New York Hospital-Cornell University Medical Center, New York, N.Y.
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