Sibylle Scheler

Mechanism of angina pectoris in patients with systemic hypertension and normal epicardial coronary arteries by arteriogram

Patients with arterial hypertension frequently have angina pectoris despite a normal coronary angiogram. This angina pectoris syndrome often goes along with an impaired coronary vasodilator reserve. The aim of the study was to find out whether an impaired coronary flow reserve is associated with electrographic signs of transient myocardial ischemia. Forty-three hypertensive patients not taking cardiovascular medication were studied with 24-hour Holter monitoring. Coronary blood flow and resistance were measured before and after intravenous administration of dipyridamole (0.5 mg/kg body weight). Coronary reserve was determined as the relation of coronary resistance before and after dipyridamole. For control purposes 9 normotensive subjects were studied with the same protocol. Hypertensive patients with ST-segment depressions (n = 31) had a significantly impaired coronary reserve (2.3 +/- 0.5) compared with normotensive subjects (4.9 +/- 1.0, p < 0.01). Coronary reserve in hypertensive patients without ST-segment depressions was only slightly impaired (4.0 +/- 1.8). Arterial pressure and left ventricular mass did not differ between hypertensive patients with and without ST-segment depressions. Left ventricular mass had no effect on coronary reserve. It is concluded that neither left ventricular hypertrophy nor arterial pressure were determinants for ST-segment depressions. Consequently primary functional and structural alterations on the level of the microcirculation appear to be responsible for the occurrence of transient ischemic episodes in the Holter electrocardiogram.

Transient myocardial ischemia in hypertensive heart disease

This study determined whether episodes of myocardial ischemia occur in hypertensive patients with normal coronary angiograms. ST-segment analysis during 24-hour Holter electrocardiography was determined in 48 patients (24 men and 24 women, mean age 54.6 +/- 10.4 years) with essential arterial hypertension (systolic/diastolic blood pressure 189.7 +/- 29/99.5 +/- 15 mm Hg). The thickness of left ventricular posterior wall and septum were measured with echocardiography. Stenosis of coronary vessels were excluded on angiography in all patients. In 24 of 48 patients, 12.8 +/- 13.8 episodes of transient myocardial ischemia (ST-segment depression greater than or equal to 1 mm, duration of the episode greater than or equal to 1 minute) were observed. The duration of the episodes was 48.1 +/- 69.93 minutes and the maximal ST-segment depression was 1.91 +/- 0.82 mm. In 95% of the episodes the patients did not experience any angina pectoris. The degree of left ventricular wall thickness did not differ in hypertensive patients with and without transient myocardial ischemia (septum thickness 11 +/- 2 mm). It is concluded that transient myocardial ischemia often occurs in hypertensive patients. Thus, left ventricular hypertrophy does not appear to play any important role. The underlying cause appears to be the impaired coronary dilation capacity, i.e., vascular alterations.

Coronary circulation in arterial hypertension

Arterial hypertension is the most common cause of congestive heart failure and an important risk factor in coronary artery disease (CAD). However, even in the absence of CAD, coronary reserve is frequently impaired in hypertensive patients. To study whether the reduced coronary reserve is due to the degree of left ventricular hypertrophy (LVH) or is a consequence of primary vascular alterations, coronary reserve was determined in 31 hypertensive patients (age of 56 +/- 10 years; systolic/diastolic blood pressure of 167 +/- 18/98 +/- 9 mm Hg) with angina pectoris and normal coronary angiogram. Coronary reserve was determined by measuring coronary resistance before and after dipyridamole (0.5 mg/kg of body weight i.v.). Coronary blood flow was measured quantitatively by the gas chromatographic argon method. LV muscle mass was measured by ventriculography. Twelve normotensive patients (age of 52 +/- 8 years) were studied for comparison. Coronary resistance was 20% higher in hypertensive than in normotensive patients, whereas coronary blood flow at rest was not significantly different. The maximal coronary blood flow after dipyridamole was 40% lower in hypertensive than in normotensive patients; accordingly, minimal coronary resistance was significantly increased by 112% in hypertensive patients (p less than 0.0005). Coronary reserve was reduced by 37% (p less than 0.001) in hypertensive patients compared with normotensive patients. Between the impairment in coronary reserve and left ventricular muscle mass, no significant correlation (r = 0.024, n.s.) was found. The impaired coronary vasodilator reserve is reflected by episodes of transient myocardial ischemia during ST-segment monitoring.

Disorders of coronary microcirculation and arrhythmias in systemic arterial hypertension.

Arterial hypertension is associated with an increased cardiovascular mortality and an increased risk of sudden cardiac death. Therefore, the prevalence of ventricular arrhythmias, identified on 24-hour ambulatory electrocardiographic monitoring, was analyzed in 54 patients (aged 56 +/- 10 years) with arterial hypertension and normal coronary angiograms with respect to left ventricular muscle mass, mass-to-volume ratio, systolic wall stress and coronary microangiopathy. Ventricular ectopic beats (VEBs) were assessed according to a score (modified Lown classification: 1 = no VEB, 2 = less than 30 VEB/hour, 3 = greater than 30 VEB/hour, 4 = polymorphic VEB, 5 = bigeminys, 6 = couplets, 7 = nonsustained ventricular tachycardia). Coronary blood flow was measured by the gas chromatographic argon method. Coronary reserve was determined by measuring coronary resistance before (Rcor) and after (Rmin) administration of intravenous dipyridamole (0.5 mg/kg body weight) (Cor Res = Rcor/Rmin). The frequency (p less than 0.05) and severity (p less than 0.025) of VEBs was higher in normotensive than in hypertensive patients. Although the score of VEBs did not correlate with left ventricular muscle mass (r = 0.20, difference not significant), a slight correlation with mass-to-volume ratio (r = 0.32; p less than 0.05) and systolic wall stress (r = 0.30; p less than 0.05) was found. Hypertensives with a severely reduced Cor Res (less than 2.0) had a significantly higher score of VEBs than those with a nearly normal Cor Res (greater than 3.0) (5.0 +/- 1.5 vs 3.5 +/- 1.7; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Medical repair of hypertensive left ventricular remodeling

Hypertensive left ventricular (LV) hypertrophy leads to myocytic hypertrophy, interstitial fibrosis, and structural alterations of the coronary microcirculation. This structural remodeling of the myocardium results in an impairment of diastolic function of the left ventricle and of coronary flow reserve despite normal epicardial arteries. Consequently, an antihypertensive treatment should aim at (a) reversing myocytic hypertrophy, (b) regression of myocardial fibrosis, and (c) improvement of coronary flow reserve apart from blood pressure lowering. In recent years many clinical studies have shown that regression of hypertensive hypertrophy can be induced by long-term treatment with angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, beta-receptor blockers, and antisympathonic drugs. However, vasodilators and diuretics, which stimulate adrenoceptor activity and increase angiotensin II levels, were found to be less effective in reversing LV hypertrophy. The trophic influence of catecholamines and angiotensin II on the myocardium counteracts the effect of systolic wall stress reduction due to blood pressure lowering. In respect of reversal of interstitial fibrosis, ACE inhibitors seem to be effective because the growth of fibroblasts was found to be stimulated by angiotensin II. Recently, clinical studies have confirmed previous experimental data that an improvement of the impaired coronary vasodilator reserve can be realized by long-term antihypertensive therapy. An antihypertensive treatment strategy which fully restores myocardial structure and completely repairs coronary microcirculation has to be considered as a causative treatment of hypertensive heart disease.

Regression of Cardiac Hypertrophy with Pharmacotherapeutic Regimen

Left ventricular hypertrophy represents the general structural mechanism of adaptation of the heart in response to a chronic pressure load of the left ventricle. This mechanism of adaptation enables the left ventricle to eject a normal stroke volume into the periphery in spite of an excessively elevated systolic pressure in the left ventricle. From this point of view, left ventricular hypertrophy should be considered as a desirable and favorable mechanism of adaptation of the heart to cope with an increased ventricular pressure burden [12, 16, 27, 44, 45].