Reduced Risk of MASLD and Cardiometabolic Disease Following Renal Denervation Therapy in Patients With Resistant Hypertension.

INTRODUCTION: Autonomic dysfunction increases the risk of cardio-kidney-metabolic (CKM) syndrome including metabolic dysfunction-associated steatotic liver disease (MASLD), type 2 diabetes (T2D), cardiovascular disease (CVD) and chronic kidney disease (CKD). Renal denervation reduces renal sympathetic nerve activity and lowers blood pressure independent of long-term pharmacotherapy, with potential downstream effects on metabolic and hepatic pathways. We aimed to evaluate the impact of renal denervation, compared with intensive antihypertensive therapy, on cardiometabolic disease risk.

METHODS: We conducted a target trial emulation using the TriNetX global federated health research network. Eligible participants were adults with hypertension (ICD-10 code I10) who were treated with either renal denervation therapy and pharmacological treatment (identified via ICD-10 or Current Procedural Terminology codes), acting as the treatment group, or an intensive pharmacological antihypertensive regime (four of a beta blocker, calcium channel blocker, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, alpha blocker or diuretic), acting as the control group. Propensity score matching (1:1) balanced the treatment and control groups, accounting for confounding variables. The primary outcome was of MASLD/metabolic dysfunction-associated steatohepatitis (MASH), while secondary outcomes included T2D, CKD and a composite of major adverse cardiovascular events (MACE): sudden cardiac death, ischaemic heart disease (IHD), cerebrovascular accident (CVA), peripheral vascular disease (PVD) and heart failure (HF). Cox regression generated hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: After matching, 1735 patients remained in each group, with well-balanced baseline characteristics (mean age 42 vs. 41 years; standardised mean difference [SMD] 0.05; 52.6% vs. 54.3% male; SMD 0.03). After PSM, renal denervation was associated with a lower risk of MASLD (HR 0.38 [0.29, 0.51]), T2D (HR 0.21 [0.13, 0.33]), CKD (HR 0.26 [0.20, 0.35]), MACE (HR 0.46 [0.34, 0.62]), IHD (HR 0.56 [0.39, 0.80]), CVA (HR 0.33 [0.20, 0.52]) and HF (HR 0.39 [0.25, 0.62]).

CONCLUSION: Control of the sympathetic nervous system with renal denervation therapy in patients with resistant hypertension is associated with a lower risk of incident CKM syndrome including MASLD, T2D, CVD and CKD, supporting the role of autonomic dysfunction in the progression of cardiometabolic disease.