Low-degree inflammation is a mediator of target organ damage and a target for renal denervation in diabetic patients with resistant hypertension
Authors: Falkovskaya A , Mordovin V F , Pekarsky S E , Manukyan M A , Zyubanova I V , Lichikaki V A , Tsoi E I , Ryabova T R , Gusakova A M , Ryumshina N I , Sukhareva A E 
Published: October 2021

Abstract

Introduction
Sympathetic activity is involved in low-degree inflammation, which is seen as a new cardiovascular risk factor and a possible therapeutic target. Resistant hypertension (RH) and diabetes mellitus (DM) are associated with increased sympathetic and pro-inflammatory activity, and renal denervation (RDN) is sympatholytic procedures with anti-inflammatory potential.

Objective
To investigate the relationship of inflammatory markers with target organ damage in patients with RH and type 2 DM, as well as the relationship between changes in organ damage after renal denervation with the anti-inflammatory effect of the procedure.

Materials and methods
We studied 74 patients with RH and type 2 DM (28 men (38%), mean age 59.1±8.6 years, office blood pressure (BP) (systolic/diastolic) 168.5/90.4 mm Hg, HbA1c 7.0±1.3%), of which 58 patients were included in single-arm prospective interventional study and underwent RDN (registration numbers NCT01499810 and NCT02667912 at ClinicalTrial.gov). Office and ambulatory BP measurement, laboratory tests (hsCRP, TNF-α, IL-6, sICAM-1, GDF-15 (ELISA)), echocardiography, renal Doppler ultrasound, and 1.5 Tesla MRI (assessment of white matter hyperintensity (WMH) of the brain and the enhancement index (IE) of the wall of the renal arteries (RA) after contrast enhancement with gadodiamide) were performed. Twelve months follow up were completed by 45 patients. Patients were instructed not to change the regimen of antihypertensive and hypoglycemic therapies throughout the study.

Results
At baseline there was a direct relation of left ventricular mass (LVM) with the level of sICAM-1 (r=0.72, p=0.003) and GDF-15 (r=0.53, p=0.036); values of renal resistive indices (RI) and severity of WMH of the brain correlated with levels of TNF-α (r=0.33, p=0.03 and r=0.55, p=0.01, respectively) and hsCRP (r=0.64 p=0.045 and r=0.64, p=0.045 respectively). IE of the wall of RA had positive relationship with hsCRP (R=0.51, p=0.04) and IL-6 (R=0.57, p=0.003).
RDN significantly reduced BP (−12.4/−7.2 mm Hg, p=0.01), level of TNF-α (from 6.8±3.1 to 6.2±3.1 pg/mL, p=0.004) and hsCRP (from 4.6±3.8 to 3.1±2.3 mg/L, p=0.02) as well as values of IE of the wall of the RA from trunk to segmental branches (p&lt;0.05). The effect of RDN on severity of WMH, renal RI, and LVM was not significant; however, 51% patients had regression of LVM. The changes in LVM and IE of the wall of RA did not depend on the degree of BP reduction. At the same times, there were relationships between changes of IE of the wall of RA and the changes in inflammatory markers (r=0.62, p=0.03 for hsCRP and r=0.56, p=0.04 for TNF-α). Changes of LVM correlated with changes in TNF-α too (r=0.43, p=0.01).

Conclusion
The severity of target organ damage in diabetic patients with RH are closely associated with chronic low-intensity inflammation, the suppression of which may by one of the mechanisms of beneficial effects of RDN on cardiovascular organs.

Funding Acknowledgement
Type of funding sources: None.