Peripheral endothelial and coronary microvascular responses to lipophilic versus hydrophilic ACE inhibitors in newly diagnosed hypertension

BACKGROUND: The clinical relevance of tissue-selectivity among angiotensin-converting enzyme (ACE) inhibitors is debated. This study aimed to compare the effects of a lipophilic (quinapril) and a hydrophilic (lisinopril) ACE inhibitor on peripheral endothelial function and coronary microvascular function in patients with de novo hypertension. METHODS: In a controlled crossover trial, 33 hypertensive patients received eight weeks of quinapril (10 mg/day) and lisinopril (10 mg/day), separated by a washout period. Brachial artery flow-mediated dilation (FMD) and coronary flow reserve (CFR) were assessed via transthoracic Doppler echocardiography at baseline and after each treatment. Treatment effects were analyzed using linear mixed-effects models accounting for repeated measures. RESULTS: At baseline, hypertensive patients exhibited significantly impaired FMD and CFR compared to healthy controls. Both treatments effectively lowered blood pressure and improved FMD and CFR from baseline (P < 0.05). Mixed-effects analyses demonstrated a significant time effect for both parameters, whereas no significant treatment-by-time interaction was observed, indicating no differential treatment effect between quinapril and lisinopril. Exploratory comparisons suggested numerically greater improvements in FMD with quinapril. Improvements in CFR were comparable between treatments. CONCLUSION: In patients with newly diagnosed hypertension, both lipophilic and hydrophilic ACE inhibitors improve peripheral endothelial and coronary microvascular function. The absence of a significant differential effect, particularly for CFR, supports a predominant class effect. While quinapril showed numerically greater improvements in FMD, this did not reach statistical significance, highlighting heterogeneity across vascular beds and warranting caution in interpreting surrogate markers.