Improvement of Coronary Flow Reserve After Long-term Therapy With Enalapril

Abstract

Abstract To date, no clinical study shows an improvement in coronary flow reserve due to long-term antihypertensive therapy. In view of the contribution of the renin-angiotensin system to the process of hypertensive remodeling of the heart and coronary circulation, angiotensin-converting enzyme (ACE) inhibitors might act as cardioreparative drugs in arterial hypertension. Accordingly, our objective in this investigation was to examine under clinical conditions to what extent long-term antihypertensive treatment with an angiotensin-converting enzyme inhibitor improved the diminished coronary flow reserve in hypertensive patients with microvascular angina pectoris. For the purpose of comparison, we also treated a normotensive control group of 6 patients with hypertrophic nonobstructive cardiomyopathy. Fifteen hypertensive individuals (10 men, 5 women; age, 58±6 years) were treated with enalapril (10 to 20 mg/d; mean, 16.7±4.9 mg/d) for 11 to 13 months. At the end of the treatment period, systolic pressure decreased from 178±14 to 137±12 mm Hg and diastolic pressure from 102±11 to 86±4 mm Hg under ambulatory conditions. Left ventricular muscle mass index decreased by 8%, from 149±32 to 137±28 g/m 2 ( P <.05). Maximal coronary blood flow after dipyridamole was increased by 43%, from 181±69 to 258±116 mL/min per 100 g ( P <.001), and minimal coronary vascular resistance was diminished by 29%, from 0.66±0.23 to 0.47±0.24 mm Hg·min·100 g·mL −1 ( P <.001) after enalapril treatment. Consequently, the calculated coronary reserve increased from 2.2±0.6 to 3.3±1.2 ( P <.001). After enalapril therapy, the functional class of angina pectoris according to the Canadian classification system had changed from 2.5±0.6 to 1.5±0.6 ( P <.01). The maximal working capacity had increased from 23.775±3.970 to 26.255±4.598 J (mean±SE, P <.05). The maximal ST-segment depression at maximal workload was reduced from 0.18±0.02 to 0.06±0.02 mV (mean±SE, P <.01). In summary, long-term therapy with the angiotensin-converting enzyme inhibitor enalapril must be considered a cardioreparative treatment with respect to the coronary microcirculation in hypertensive heart disease.