doi: 10.1161/01.CIR.0000012604.07640.10
(Circulation. 2002;105:e82.)
© 2002 American Heart Association, Inc.
Correspondence |
A Pill for Every Ill
Cardiology, National Heart and Lung Institute,, Royal Brompton Hospital,, London, UK, lornaswan@yahoo.com
To the Editor:
Dr Lip1 and The HOPE investigators2 again sing the praises of ACE inhibitors ("the pill for every ill")—this time in the regression and prevention of ECG-LVH. The numerous "non–blood pressure" properties of ACE inhibition are elegantly described in Dr Lip’s editorial, as the benefits noted were not simply explained by blood pressure reduction. However, the blood pressure story may not be quite dead yet.
ACE inhibitors have a more favorable effect on central aortic pressure and pulsatile hemodynamics than other antihypertensive agents.3 End-organ damage is known to correlate with parameters of pulse wave morphology. The regression of carotid intima media thickness, for example, is closely correlated with regional reductions in pulse pressure.4 Pulse pressure, a marker of conduit vessel compliance, was a significant predictor of adverse cardiovascular events in both the SAVE (Survival And Ventricular Enlargement study) and SOLVD (Studies Of Left Ventricular Dysfunction) cohorts.5
ACE inhibitors decrease wave reflection and pulse wave velocity and to focus solely on the effects these agents have on systolic and diastolic blood pressures fails to appreciate these important components. Loss of arterial wall compliance per se is a stimulus to the development of atheroma—yet another manifestation of end-organ damage. It may well be that the "additional" benefits of ACE inhibitors are due to these beneficial changes in central aortic pulsatility. Examination of pulse pressure, or carotid pressure by tonometry, opens up yet another area of interest in these impressive drugs.
References
1.
Lip GY. Regression of left ventricular hypertrophy and improved prognosis. Circulation. 2001; 104: 1582–1584.
2.
Mathew J, Sleight P, Lonn E, et al. Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril. Circulation. 2001; 104: 1615–1621.
3. O’Rourke M. Systolic blood pressure: arterial compliance and early wave reflection, and their modification by antihypertensive therapy. J Hum Hypertens. 1989; 3: 47–52.
4.
Boutouyrie P, Bussy C, Hayoz D, et al. Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment. Circulation. 2000; 101: 2601–2606.
5.
Domanski MJ, Mitchell GF, Norman JE, et al. Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction. J Am Coll Cardiol. 1999; 33: 951–958.
Response
Galesburg Cottage Hospital, Galesburg, Ill
We agree with Dr Swan that ACE inhibitors have a favorable effect on arterial compliance and central pulse pressure. We also agree that this hemodynamic effect might be associated with clinical benefit. At the same time, we again emphasize our view that ACE inhibitors by virtue of their autocrine/paracrine effect might cause regression of left ventricular hypertrophy independent of their hemodynamic properties, based on the following points.
(1) Improvement of arterial compliance and reduction of pulse pressure by antihypertensive agents is not a unique property of ACE inhibitors. Properly controlled studies, for example, have shown that the ACE inhibitor enalapril and the ß-blocker celiprolol have similar effects in this regard, 1 as do nitrates.2 (2) Angiotensin II is a direct growth promoter to the myocardium at doses too low to affect blood pressure. (3) In addition to its circulating form, angiotensin II is also locally produced in the heart; all components of the renin-angiotensin system have been demonstrated in the heart muscle both at mRNA levels and at protein levels. (4) ACE inhibitors can block the hypertrophic effect of angiotensin II on the myocardium without affecting blood pressure. (5) In our study, the beneficial effect of ramipril on left ventricular hypertrophy was consistent in patients with or without hypertension by history, and in patients with various blood pressure levels; it was also independent of blood pressure reduction during the study.3 Therefore, in our study a direct antihypertrophic effect of the ACE inhibitor (over and above its effect through hemodynamic mechanisms) seems probable.
References
1. Boutouyrie P, Bussy C, Hayoz D, et al. Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment. Circulation. 2000; 101: 2601–2606.
2. O’Rourke M. Systolic blood pressure: arterial compliance and early wave reflection, and their modification by antihypertensive therapy. J Hum Hypertens. 1989; 3: 47–52.
3. Mathew J, Sleight P, Lonn E, et al. Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor, ramipril. Circulation. 2001; 104: 1615–1621.
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