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Ace inhibition in coronary artery disease
AJH-APRIL 199~VOL. 9, NO.4, PART 2
206A ASH XI ABSTRAcrS
Saturday, May 18, West Ballroom, 6:30 am Sunrise Seminar Series: The Effect of ACE Inhibition on Vascular Biology
Saturday, May 18, West Ballroom, 6:30 am Sunrise Seminar Series: The Effect of ACE Inhibition on Vascular Biology
Angiotensin Converting Enzyme Inhibition, with Quinapril, Improves Endothelial Vasomotor Dysfunction in Patients with Coronary Artery Disease: the TREND Study (Trial on REversing ENdothelial Dysfunction) GB 10hn Mancini, University of British Columbia, Vancouver, Canada on behalf ofthe TREND Investigators.
ACE INHIBITION IN CORONARY ARTERY DISEASE CARL J. PEPINE, MD, UNIVERSITY OF FLORIDA
Quinapril (Q) is a potent antagonist of tissue ACE that prevents local synthesis of angiotensin II and degradation of bradykinin \Wich elicits arterial vasodilation by stimulation of endothelial nitric oxide production. Acute infusions of Q in the human forearm is known to decrease forearm vascular resistance and increase blood flow. To determine if Q can improve endothelial dysfunction, an early marker of atherosclerosis, in the coronaries ofpatients (pts) with CAD we studied the effects of Q on the vasomotor tone of coronary arteries with ~40% stenoses (mean 22.S%) adjacent to arteries undergoing PTCA Pts (N=129) exhibiting vasoconstriction or lack of dilation to acetylcholine (ACH), an endothelial-dependent vasodilator, as analysed by QCA were randomized to Q or placebo (P) 40 mg once daily for 6 months. The primary endpoint was the mean % change in the ACH-induced constriction of the target segment (mean diameter). The Q group showed significant improvement in ACH response (P=O.014) at six months. The improvement could not be attn"buted to any changes in blood pressure or lipid fractions.
Key Words: qui napri 1, endothe 1i urn, acetyl echel i ne
Saturday, May 18, Murray Hill Suite, 4:00 pm Hypertension and the Heart-Left Ventricular Hypertrophy and Heart Failure: New Approaches to Therapy MechanismsofProgressionto VentricularHypertrophyand Failurein Hypertension RobertJ.Cody, M.D. CardiologyDivision,The Ohio Stale UniversityMedicalCenter
The myocardium undergoes structural changes in response to cardiovascular disease states. As cardiac myocytes are terminally differentiated, they cannot replicate in response to injury. The response to injUry is limited primarily to myocyte hypertrophy. with functional and structural changes of the interst~ial tissue matrix, culminating in a change of geometry. w~h subsequent akeration of ventricular function. Cellular signalling for these changes is accomplished by the mechanical stimulus of increased afterload. activated growth factors. and autonomic and hormonal mediators. Studies of the adaptation of the ventricle following acute damage (myocardial infarction) or long term akeration (hypertension) have popularized the concept of 'remodeling' to describe the dynamic myocardial changes that can occur in response to cardiovascular disease. The time progression from normal ventricular function to hypertrophy depends upon the time course and sever~y of hypertension. These factors generally cannot be tracked over the course of several decades in man, so that insights for disease progression are generally determined from animal models.lmportant co-morbid factors. such as coronary artery disease, diabetes, and obesity may accelerate this process. Coronary disease may induce long term cellular changes, or abrupt changes in ventricular function, in the setting of myocardial infarction. Hypertensive 'heart failure", and "cardiomyopathy" are clinical descriptors which erroneously cover a diversity of clinical conditions of ventricular performance. Differentiating the type of ventricular dysfunction in hypertension is important, in order to better identify treatment strategies. which can be applied for long term management. l<,yWords:
" HypertensIOn. ventncular function heart failure. autonomic functIOn. hormonal factors •
Purpose: To review the evidence on the effects of angiotensin converting enzyme (ACE) inhibitors in coronary artery disease. Experimentalsludies: In experimental studies ACE inhibitors show potent sntiatherogenic effects. ACE inhibitors have also modulated slteratlOns in endothelial-mediated dilation. Clinicalsludies: The renin-angiotensin syslem and ACE genotype DO have been linked with increased risk for myocardial infarction. Cardiac ischemic events have been prevented by ACE inhibition in patients with coronary artery disease and left ventricular dysfunction resulting from prior myocardial infarction in a number of studies. Additionally. several mega trials have shown that ACE inhibition early (within hours) after an acute myocardial infarction saves lives and reduces heart failure in unselected patients. Other ongoing studies are assessing ACE inhibitor effects in patients with coronary artery disease and normal left ventricular function who have not had an acute myocardial infarction. Conclusions: ACE inhibitors prevent the development of atherosclerosis in animal models. In some animal models they also prevent the myointimal proliferative response to injury and reverse or prevent endothelial dysfunction. They can reduce the number of cardiac ischemic events in selected patients with coronary artery disease and left ventricular dysfunction related to remote infarction. as well as unselected patients with evolving myocardial infarction. Their effects in patients with coronary artery disease and without either myocardial infarction or left ventricular dysfunction are now being assessed in several large trials. KeyWords'
ACE inhibitors, coronary artery disease. atherosclerosis, myocardial infarction, endothelial dysfunction
206A ASH XI ABSTRAcrS
Saturday, May 18, West Ballroom, 6:30 am Sunrise Seminar Series: The Effect of ACE Inhibition on Vascular Biology
Saturday, May 18, West Ballroom, 6:30 am Sunrise Seminar Series: The Effect of ACE Inhibition on Vascular Biology
Angiotensin Converting Enzyme Inhibition, with Quinapril, Improves Endothelial Vasomotor Dysfunction in Patients with Coronary Artery Disease: the TREND Study (Trial on REversing ENdothelial Dysfunction) GB 10hn Mancini, University of British Columbia, Vancouver, Canada on behalf ofthe TREND Investigators.
ACE INHIBITION IN CORONARY ARTERY DISEASE CARL J. PEPINE, MD, UNIVERSITY OF FLORIDA
Quinapril (Q) is a potent antagonist of tissue ACE that prevents local synthesis of angiotensin II and degradation of bradykinin \Wich elicits arterial vasodilation by stimulation of endothelial nitric oxide production. Acute infusions of Q in the human forearm is known to decrease forearm vascular resistance and increase blood flow. To determine if Q can improve endothelial dysfunction, an early marker of atherosclerosis, in the coronaries ofpatients (pts) with CAD we studied the effects of Q on the vasomotor tone of coronary arteries with ~40% stenoses (mean 22.S%) adjacent to arteries undergoing PTCA Pts (N=129) exhibiting vasoconstriction or lack of dilation to acetylcholine (ACH), an endothelial-dependent vasodilator, as analysed by QCA were randomized to Q or placebo (P) 40 mg once daily for 6 months. The primary endpoint was the mean % change in the ACH-induced constriction of the target segment (mean diameter). The Q group showed significant improvement in ACH response (P=O.014) at six months. The improvement could not be attn"buted to any changes in blood pressure or lipid fractions.
Key Words: qui napri 1, endothe 1i urn, acetyl echel i ne
Saturday, May 18, Murray Hill Suite, 4:00 pm Hypertension and the Heart-Left Ventricular Hypertrophy and Heart Failure: New Approaches to Therapy MechanismsofProgressionto VentricularHypertrophyand Failurein Hypertension RobertJ.Cody, M.D. CardiologyDivision,The Ohio Stale UniversityMedicalCenter
The myocardium undergoes structural changes in response to cardiovascular disease states. As cardiac myocytes are terminally differentiated, they cannot replicate in response to injury. The response to injUry is limited primarily to myocyte hypertrophy. with functional and structural changes of the interst~ial tissue matrix, culminating in a change of geometry. w~h subsequent akeration of ventricular function. Cellular signalling for these changes is accomplished by the mechanical stimulus of increased afterload. activated growth factors. and autonomic and hormonal mediators. Studies of the adaptation of the ventricle following acute damage (myocardial infarction) or long term akeration (hypertension) have popularized the concept of 'remodeling' to describe the dynamic myocardial changes that can occur in response to cardiovascular disease. The time progression from normal ventricular function to hypertrophy depends upon the time course and sever~y of hypertension. These factors generally cannot be tracked over the course of several decades in man, so that insights for disease progression are generally determined from animal models.lmportant co-morbid factors. such as coronary artery disease, diabetes, and obesity may accelerate this process. Coronary disease may induce long term cellular changes, or abrupt changes in ventricular function, in the setting of myocardial infarction. Hypertensive 'heart failure", and "cardiomyopathy" are clinical descriptors which erroneously cover a diversity of clinical conditions of ventricular performance. Differentiating the type of ventricular dysfunction in hypertension is important, in order to better identify treatment strategies. which can be applied for long term management. l<,yWords:
" HypertensIOn. ventncular function heart failure. autonomic functIOn. hormonal factors •
Purpose: To review the evidence on the effects of angiotensin converting enzyme (ACE) inhibitors in coronary artery disease. Experimentalsludies: In experimental studies ACE inhibitors show potent sntiatherogenic effects. ACE inhibitors have also modulated slteratlOns in endothelial-mediated dilation. Clinicalsludies: The renin-angiotensin syslem and ACE genotype DO have been linked with increased risk for myocardial infarction. Cardiac ischemic events have been prevented by ACE inhibition in patients with coronary artery disease and left ventricular dysfunction resulting from prior myocardial infarction in a number of studies. Additionally. several mega trials have shown that ACE inhibition early (within hours) after an acute myocardial infarction saves lives and reduces heart failure in unselected patients. Other ongoing studies are assessing ACE inhibitor effects in patients with coronary artery disease and normal left ventricular function who have not had an acute myocardial infarction. Conclusions: ACE inhibitors prevent the development of atherosclerosis in animal models. In some animal models they also prevent the myointimal proliferative response to injury and reverse or prevent endothelial dysfunction. They can reduce the number of cardiac ischemic events in selected patients with coronary artery disease and left ventricular dysfunction related to remote infarction. as well as unselected patients with evolving myocardial infarction. Their effects in patients with coronary artery disease and without either myocardial infarction or left ventricular dysfunction are now being assessed in several large trials. KeyWords'
ACE inhibitors, coronary artery disease. atherosclerosis, myocardial infarction, endothelial dysfunction