Angiotensin–converting enzyme (ACE) inhibitors are the primarily chosen drugs to treat various cardiovascular diseases, such as hypertension. Although the most recent guidelines do not differentiate among the various ACE inhibitory drugs, there are substantial pharmacological differences. Goal: Here, we tested if lipophilicity affects the efficacy of ACE inhibitory drugs when used as the first therapy in newly identified hypertensives in a prospective study. Methods: We tested the differences in the cardiovascular efficacy of the hydrophilic lisinopril (8.3 ± 3.0 mg/day) and the lipophilic enalapril (5.5 ± 2.3 mg/day) (n = 59 patients). The cardiovascular parameters were determined using sonography (flow-mediated dilation (FMD) in the brachial artery, intima-media thickness of the carotid artery), 24 h ambulatory blood pressure monitoring (peripheral arterial blood pressure), and arteriography (aortic blood pressure, augmentation index, and pulse wave velocity) before and after the initiation of ACE inhibitor therapy. Results: Both enalapril and lisinopril decreased blood pressure. However, lisinopril failed to improve arterial endothelial function (lack of effects on FMD) when compared to enalapril. Enalapril-mediated improved arterial endothelial function (FMD) positively correlated with its blood–pressure–lowering effect. In contrast, there was no correlation between the decrease in systolic blood pressure and FMD in the case of lisinopril treatment. Conclusion: The blood–pressure–lowering effects of ACE inhibitor drugs are independent of their lipophilicity. In contrast, the effects of ACE inhibition on arterial endothelial function are associated with lipophilicity: the hydrophilic lisinopril was unable to improve, while the lipophilic enalapril significantly improved endothelial function. Moreover, the effects on blood pressure and endothelial function did not correlate in lisinopril-treated patients, suggesting divergent mechanisms in the regulation of blood pressure and endothelial function upon ACE inhibitory treatment.

Both lisinopril and enalapril are angiotensin-converting enzyme (ACE) drugs and widely used in the treatment of hypertension. Enalapril does not cross the blood–brain barrier, but lisinopril is centrally active. Our goal was to find out if there was a link between the actual concentration of ACE inhibitors and cognition and if there was a detectable difference between the two types of ACE inhibitors. Asymptomatic, non-treated patients were diagnosed by screening and the hypertension was confirmed by ambulatory blood pressure monitoring (ABPM). A battery of cognitive tests was used to assess the impact of randomly assigning participants to receive either lisinopril or enalapril. All neurocognitive functions were measured, especially the most affected by conditions of compromised perfusion pressures, such as hypertension, which are attention and executive functions. The lisinopril concentration showed a significant inverse correlation with mosaic test (coeff. = −0.5779) and seemed to have a significant negative effect on perceptual motor skills (coeff. = −0.5779), complex attention (coeff. = −0.5104) and learning (coeff. = −0.5202). Compared with enalapril, lisinopril is less successful in improving the components of cognitive functions.

Background/Objectives: Controlling hypertension may reduce the risk of cognitive impairment. A marker for the identification of hypertensive patients who are more likely to suffer cognitive impairment would be of clinical benefit. In our research, 105 patients with newly diagnosed primary hypertension were assessed at the Department of Neurology, the University of Debrecen. Methods: The available data covered detailed medical history and data, the results of different tests, ambulatory blood pressure monitoring, the intima–media thickness, the flow-mediated dilatation, the augmentation index, the pulse wave velocity, and neuropsychological evaluation. Multiple linear regression models were created to evaluate the associations found in simple analyses (Spearman’s rank correlation and Pearson’s chi-squared test). Results: The flow-mediated dilatation showed significant correlations with working memory, attention, learning, and executive functions. The intima–media thickness showed significant correlations with attention and reaction time. The composite flow-mediated dilatation/IMT ratio showed a significant relationship with the overall index of cognitive functions. Based on our results, a flow-mediated dilatation/IMT ratio of 15 represents a cut-off value. The pulse wave velocity showed a significant correlation with working memory and attention. The augmentation index showed significant relationships with reaction time and executive functions. Conclusions: Based on our results, the intima–media thickness, flow-mediated dilatation, and their ratio are suitable for the identification of a particularly vulnerable subgroup of patients for whom a detailed cognitive examination is required for the early detection and treatment of functional disorders. The assessment of attention, executive functions, working memory, and reaction time is required in early hypertension.