Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial

Abstract

Background: The DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped-care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months.

Methods and results: This post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline-adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was -10.1 mm Hg (P=0.0462) in the lowest tertile and -2.5 mm Hg (P=0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m²) but decreased in the control group (-8.0 mL/min per 1.73 m², P=0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups (P=0.2640).

Conclusions: RDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Keywords: antihypertensive therapy/sympathetic nervous system; aortic calcification; aortic disease; atherosclerosis; renal denervation; resistant hypertension.

Figure 1

Example of aortic calcification segmentation: frontal view of the abdominal aorta (A) and corresponding cross‐sectional reconstructions at 2 levels: level 1 (B and B′) and level 2 (C and C′). Native images (B and C) and segmented images (B′ and C′) are provided with an overlay for the calcifications. Three‐dimensional volume reconstruction for the abdominal aorta of patients, by tertile for abdominal aortic calcification, is shown (D through F), with the results for axial slices (G through I).

Figure 2

Flowchart of the study. No interpretable CT of the abdominal aorta indicates that the patients were evaluated at baseline by magnetic resonance imaging of the abdominal aorta, rather than CT angiogram. ABPM indicates ambulatory blood pressure monitoring; CT, computed tomography; eGFR, estimated glomerular filtration rate.

Figure 3

Individual changes in daytime ABPM, by tertile, for abdominal aortic calcification in the RDN group and in the control group, after 6 months of follow‐up (A: tertile 1; B: tertiles 2 and 3). AAC indicates abdominal aortic calcifications; ABPM, ambulatory blood pressure monitoring; RDN, renal denervation.

Figure 4

Baseline‐adjusted changes in daytime ambulatory systolic blood pressure (A and B), number of antihypertensive treatments prescribed (C and D) and percentage of fully adherent patients (E and F) in the renal denervation (red) and control (blue) groups by tertile (tertile 1 vs tertiles 2 and 3 for abdominal aortic calcification volume).

Figure 5

Relationship between the changes from baseline to 6 months in mean baseline‐adjusted eGFR and daytime ambulatory SBP in the 4 subgroups of patients. Red plot: patients of tertile 1 for AAC volume treated with RDN plus SSAHT; green plot: patients of tertiles 2 and 3 for AAC volume treated with RDN plus SSAHT; blue plot: patients of tertile 1 for AAC volume treated with SSAHT alone; orange plot: patients of tertiles 2 and 3 for AAC volume treated with SSAHT alone. The data shown are mean±SD. AAC indicates abdominal aortic calcifications; eGFR, estimated glomerular filtration rate; RDN, renal denervation; SBP, systolic blood pressure; SSAHT, standardized stepped‐care antihypertensive treatment.