Metabolic effects two years after renal denervation in insulin resistant hypertensive patients. The Re-Shape CV-risk study.

BACKGROUND & AIMS: Denervation of renal sympathetic nerves (RDN) is an invasive endovascular procedure introduced as an antihypertensive treatment with a potential beneficial effect on insulin resistance (IR). We have previously demonstrated a reduction in blood pressure (BP) six months after RDN, but severe hepatic and peripheral IR, assessed by glucose tracer and two step hyperinsulinemic-euglycemic clamp (HEC), did not improve. The aim of the current study was to evaluate IR and adipokines profiles in relation to BP and arterial stiffness changes two years after RDN. METHODS: In 20 non-diabetic patients with true treatment-resistant hypertension, ambulatory and office BP were measured after witnessed intake of medications prior to, six and 24 months after RDN. Arterial stiffness index (AASI) was calculated from ambulatory BP. Insulin sensitivity (IS) was assessed using an oral glucose tolerance test (OGTT), the Homeostasis Model Assessment (HOMA-IR), HOMA-Adiponectin Model Assessment (HOMA-AD), the Quantitative Insulin Sensitivity Check Index (QUICKI), the Triglyceride and Glucose Index (TyG) and the Leptin-to-Adiponectin Ratio (LAR). These surrogate indices of IS were compared with tracer/HEC measurements to identify which best correlated in this group of patients. RESULTS: All measured metabolic variables and IS surrogate indices remained essentially unchanged two years after RDN apart from a significant increase in HOMA-AD. OGTT peak at 30 min correlated best with reduction in endogenous glucose release (EGR) during low insulin HEC (r = -0.6, p = 0.01), whereas HOMA-IR correlated best with whole-body glucose disposal (WGD) (r = -0.6, p = 0.01) and glucose infusion rate (r = -0.6, p = 0.01) during high insulin HEC. BP response was unrelated to IS prior to RDN. Nocturnal systolic BP and arterial stiffness before RDN correlated positively with a progression in hepatic IR at six-month follow-up. CONCLUSION: IR, adiponectin and leptin did not improve two years after RDN. There was no correlation between baseline IS and BP response. Our study does not support the notion of a beneficial metabolic effect of RDN in patients with treatment resistant hypertension.

Renal sympathetic denervation: effect on ambulatory blood pressure and blood pressure variability in patients with treatment-resistant hypertension. The ReShape CV-risk study.

Renal sympathetic denervation (RDN) represents a potential treatment option for highly selected patients with resistant arterial hypertension. In this open label study, we aimed to investigate the response of blood pressure (BP) and short-term BP variability (BPV) to RDN 6 months after procedure. We defined treatment-resistant hypertension as office systolic BP>140 mm Hg, despite maximum tolerated doses of ⩾4 antihypertensive drugs, including a diuretic. In addition, daytime systolic ambulatory blood pressure (ABPM) >135 mm Hg was required after witnessed intake of antihypertensive drugs. Bilateral RDN was performed with the Symplicity Catheter System (n=23). The mean systolic office BP and ABPM fell from 162±20 mm Hg to 139±19 mm Hg (P<0.001) and from 154±20 mm Hg to 144±16 mm Hg (P<0.038), respectively. In addition, we observed a significant reduction in diastolic office BP and ABPM. The current study also demonstrated a significant decrease of both systolic and diastolic average real variability, weighted standard deviation (s.d.) as well as conventional s.d. of mean and daytime BP, but not of s.d. of nighttime BP. RDN after witnessed intake of ⩾4 antihypertensive drugs reduced both office BP and ABPM at 6 months in patients with truly resistant hypertension. Also BPV improved, possibly reflecting an additional effect from intervening on the sympathetic nerve system.