spirapril and Hypertrophy--Left-Ventricular

Left ventricular hypertrophy (LVH) is a recognized complication of, rather than a physiological response to, hypertension, being a powerful independent indicator of cardiovascular disease risk. In addition, it is reasonable to assume that the reversal of LVH is a desirable therapeutic goal in the treatment of hypertension. Furthermore, the renin-angiotensin system plays an important role in LVH and, in particular, in the development of cardiac interstitial fibrosis. Therefore, the effect of angiotensin-converting enzyme (ACE) inhibition on LVH is of particular interest. In both experimental and human studies, ACE inhibitors appear to perform better than other antihypertensive agents in reversing cardiac structural changes. A recent meta-analysis showed ACE inhibitors to be more efficacious than other first-line antihypertensives in reducing left ventricular mass. A controlled long-term study of previously untreated men showed that enalapril reversed LVH significantly better than did hydrochlorothiazide and that the regression of LVH was independently related to blockade of the renin-angiotensin system. Indeed, there have been studies showing that ACE inhibitors can affect LVH without lowering blood pressure. Moreover, ACE inhibitors have shown cardioprotective and cardioreparative properties in experimental models of hypertensive LVH. In conclusion, ACE inhibitors are effective in reversing LVH as well as interstitial fibrosis. The prognostic implications of this remain to be seen. So far, the experience with spirapril on LVH is limited, but the accumulated data are promising.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Echocardiography; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Middle Aged; Time Factors

This study was designed to evaluate in 45 hypertensive patients with left ventricular hypertrophy (LVH) the effects of a 6-month course with one of three different antihypertensive regimens (the calcium channel blocker isradipine, the angiotensin converting enzyme inhibitor spirapril in monotherapy, or a combination of the two drugs, n = 15 per group) on blood pressure, LVH regression, and various functional correlates of LVH. All three treatment modalities decreased significantly LV mass index by an average of 10%, although the combination had the greatest blood pressure-lowering effect and spirapril had the least, as assessed by office resting pressures, ambulatory monitoring, and isometric grip testing. There was no correlation between magnitude of blood pressure lowering and degree of LVH regression. The effects of treatment on pressor hormone profiles differed among groups, as spirapril tended to suppress angiotensin II and norepinephrine, whereas isradipine had opposite effects. Exercise tolerance was prolonged by all three regimens, but significantly more by the combination. All three regimens decreased significantly the double product by 10% to 15%. Indices of electrophysiologic stability calculated from analysis of ambulatory electrocardiogram exhibited significant improvement in several parameters such as QRS duration, presence of late potentials, and measures of heart rate variability, resulting in fewer episodes of simple or complex ventricular arrhythmia. We conclude that all three regimens produce significant LVH regression associated with improved functional capacity and electrical stability. These results reflect the sum of the differential hemodynamic and hormonal effects exerted by each treatment modality.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Isradipine; Male

Left ventricular hypertrophy is a common clinical feature in hypertensive patients and may be associated with structural changes in vessel morphology. In an open prospective trial, we evaluated 14 patients with previously untreated hypertension (163 +/- 2/104 +/- 2 mm Hg) and an echocardiographically determined left ventricular mass index of 141.6 +/- 5.2 g/m2, indicating left ventricular hypertrophy. We obtained a gluteal skin biopsy sample before starting treatment to investigate subcutaneous small-artery (approximately 200 to 400 microns diameter) morphology and function. Patients then received antihypertensive treatment with a combination of spirapril (3 or 6 mg) and isradipine (2.5 or 5 mg). Echocardiographic recordings were made after 6 months and 1 year, and a final biopsy was taken after 1 year. After 1 year, blood pressure was significantly reduced to 142 +/- 3/ 90 +/- 1 mm Hg (P < .001), and left ventricular mass index decreased significantly to 105.3 +/- 5.8 g/m2 (P < .001). Baseline media-lumen ratio (7.64 +/- 0.48%) was not markedly reduced (7.21 +/- 0.55%), although a decrease occurred in 7 of 12 evaluable patients. Norepinephrine-induced vasoconstriction was markedly reduced after 1 year. In conclusion, a significant regression of left ventricular hypertrophy was obtained after 1 year of treatment with spirapril and isradipine, whereas a similar reduction in medial thickness relative to lumen diameter of subcutaneous small arteries could not be observed in all patients. Reversal of structural changes in resistance vessels may require a longer treatment period in patients with proven left ventricular hypertrophy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arteries; Blood Pressure; Drug Combinations; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Isradipine; Male; Prospective Studies; Vascular Resistance

To assess the long-term course of regression of left ventricular hypertrophy (LVH) and haemodynamic changes during spirapril treatment, 11 male hypertensive patients with a left ventricular mass (LVM) > 240 g and a mean age of 48 (range 41-60) years were followed-up with echo-Doppler examinations for 36 months. The initial spirapril dose was 6 or 12 mg once daily, which was titrated to a minimum of 3 mg and a maximum of 24 mg to keep diastolic blood pressure (DBP) < or = to 95 mmHg. Patient compliance based on tablet counts was 98% (range 95-100%). The mean spirapril dose was 9 +/- 6 mg at 3 months, 9 +/- 6 mg at 12 months, and 15 +/- 9 mg at 36 months. Blood pressure was reduced from 161 +/- 20/107 +/- 6 mmHg at baseline to 137 +/- 11/89 +/- 6 mmHg at 3 months (p < 0.001), 141 +/- 20/89 +/- 4 mmHg at 12 months and 135 +/- 11/87 +/- 6 mmHg at 36 months. The respective values for LVM at baseline and at 3, 12 and 36 months were 340 +/- 71 g, 305 +/- 61 g (p < 0.05 vs baseline), 303 +/- 88 g and 298 +/- 94 g. Cardiac output did not change whereas systemic arteriolar resistance (SAR) was significantly reduced after 3 and 36 months (p < 0.01). Thus, the regression of LVH with spirapril was 10% of LVM at 3 months, 11% at 12 months, and 12% at 36 months. These changes were mainly related to a reduction of LV posterior wall thickness and SAR.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Echocardiography, Doppler; Enalapril; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Time Factors

Topics: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Single-Blind Method

In view of the prevalence of left ventricular hypertrophy (LVH) in patients with essential hypertension, (15-30%), with an increased risk (2-4 x) of developing myocardial infarction, heart failure or malignant arrhythmia, possibly even leading to sudden cardiac death, effective reversal of LVH is a major aim of treatment. For this purpose, angiotensin-converting enzyme (ACE) inhibitors have proved to be most suitable.. In an open bicentric study involving 37 hypertensive patients with LVH confirmed by echocardiography, the effect of spirapril in reversing the left ventricular mass index (LVMI) and diastolic left ventricular wall thickness was investigated after 3 and 6 months.. The LVMI decreased by 14.7% after 3, and by 27.3% after 6 months, irrespective of whether spirapril was given alone or in addition to other antihypertensive pre-medication. The results may be due to the proven 24-hour effect of spirapril in conjunction with the very long half-life.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Echocardiography; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Time Factors

To test whether angiotensin-converting enzyme (ACE) inhibition may prevent myocardial damage and may affect coronary microvasculature in spontaneously hypertensive rats (SHR), young 5-week-old SHR were treated for 3 months with spirapril and changes in blood pressure (BP) were monitored. Untreated SHR were used as controls. The rats were killed; left ventricular (LV) shape, weight, and wall thickness were examined and the ventricular myocardium was analyzed morphometrically to determine the effect of the drug on the relative amount, number per unit area of myocardium, and average dimension of foci of myocardial scarring. Moreover, volume fraction, surface, numerical density, and diffusion distance for oxygen of the coronary capillaries were analyzed. BP remained 20-30% lower in treated SHR with respect to controls, and LV weight and thickness decreased 20 and 21%, respectively. The number and dimension of the foci of fibrosis were reduced, resulting in an overall 68% decrement in the amount of myocardial damage. Finally, a 28% increment in numerical density of capillary profiles associated with a 13% reduction in their cross-sectional area decreased the diffusion distance for oxygen from the capillary wall to the myocytes by 14% in treated SHR. Spirapril decreases BP and LV weight and thickness in the SHR model of hypertension and substantially improves coronary capillary microvasculature, decreasing hypertensive myocardial damage. These results may be attributed to inhibition of the systemic effects of angiotensin II (AII) as well as to a local protective action of the drug against possible intramyocardial AII production.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Weight; Capillaries; Coronary Vessels; Enalapril; Fibrosis; Heart Rate; Hypertension; Hypertrophy, Left Ventricular; Male; Myocardium; Rats; Rats, Inbred SHR