Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics

Ronaldo Altenburg Gismondi, Ricardo Bedirian, Cesar Romaro Pozzobon, Márcia Cristina Ladeira, Wille Oigman, Mário Fritsch Neves, Ronaldo Altenburg Gismondi, Ricardo Bedirian, Cesar Romaro Pozzobon, Márcia Cristina Ladeira, Wille Oigman, Mário Fritsch Neves

Abstract

Background: Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness.

Objective: To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness.

Methods: Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring), endothelial function (brachial artery flow-mediated dilation), and vascular stiffness (pulse wave velocity) were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively).

Results: The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007), and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003) when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820). There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586).

Conclusion: Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

Trial registration: ClinicalTrials.gov NCT01603940.

Conflict of interest statement

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1
Flowchart of the participants throughout the study.
Figure 2
Figure 2
Comparison of office systolic and diastolic blood pressure values between the SU and NSU groups before and after association of antihypertensive treatment; SU: Statin users group; NSU: Non-statin users group; *p = 0.100, patients in the SU group before and after treatment; †p = 0.016, patients in the SU group before and after treatment.
Figure 3
Figure 3
Comparison of mean 24-hour systolic and diastolic blood pressures in the SU and NSU groups before and after association of antihypertensive treatment; SU: Statin users group; NSU: Non-statin users group; *p = 0.007, patients in the SU group before and after treatment.
Figure 4
Figure 4
Comparison of the values of brachial artery flow-mediated dilation between the SU and NSU groups before and after association of antihypertensive treatment; SU: Statin users group; FMD: Brachial artery flow-mediated dilation; NSU: Non-statin users group; *p = 0.003, patients in the SU group before and after treatment.

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