Ambulatory Blood Pressure Changes After Renal Sympathetic Denervation in Patients With Resistant Hypertension

Mahfoud, Felix; Ukena, Christian; Schmieder, Roland E.; Cremers, Bodo; Rump, Lars Christian; Vonend, Oliver; Weil, Joachim; Schmidt, Martin; Hoppe, Uta C.; Zeller, Thomas; Bauer, Axel; Ott, Christian; Blessing, Erwin; Sobotka, Paul; Krum, Henry; Schlaich, Markus P.; Esler, Murray; Böhm, Michael

doi:10.1161/circulationaha.112.000949

Cited by 238 publications

(182 citation statements)

References 41 publications

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“…22,23 Recently published data showed that the only parameter for prediction of RSD-related BP reduction was elevated systolic BP values at baseline. 33 No further predictive parameters have yet been identified. 33 To date, little is known about predicting RSDrelated success, in particular in identifying nonresponders or pseudoresistant patients with hypertension.…”

Section: Discussionmentioning

confidence: 99%

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Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation

et al. 2014

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A rterial hypertension (HT) represents a major risk factor for cardiovascular morbidity and mortality.1 HT is associated with endothelial dysfunction that aggravates progressive vascular damage and atherosclerosis.2-4 Endothelial dysfunction can be indicated by elevated serum concentrations of endothelial adhesion molecules, including intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). 5,6 These adhesion molecules play important roles in accelerating atherosclerosis by attaching inflammatory cells to the vascular endothelial wall and promoting their subsequent migration through the endothelium.The vascular endothelial growth factor and its soluble receptor fms-like tyrosine kinase-1 (sFLT-1) are also associated with endothelial dysfunction, vascular remodeling, and endothelial repair and regeneration mechanisms.7-11 Hypoxia and endothelial shear stress in HT are known to be major stimuli for sFLT-1 expression and release.12-16 Furthermore, sFLT-1 is stimulated by the vascular sympathetic nervous system and has been reported to be elevated in patients with HT. The persistence of hypertensive blood pressure (BP) in patients with resistant hypertension is partially regulated by the renal sympathetic nerve system. 17-21 Renal sympathetic denervation (RSD) is an interventional treatment option for patients who have resistant hypertension, despite optimal medical treatment. 22,23 However, RSD is not effective in ≈8% to 12% of treated patients. 22,23 Predictive parameters regarding the response or nonresponse to RSD have not yet been described.We postulated a relationship among successful RSD-related BP reduction, endothelial dysfunction, and activated endothelial cells as indicated by ICAM-1, VCAM-1, and sFLT-1, specific markers for endothelial cell activity and hypertension-related endothelial sheer stress. Therefore, the primary aim of the present study was to examine the predictive value of sFlt-1, ICAM-1, and See Editorial Commentary, pp 907-908Abstract-Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as...

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Section: Discussionmentioning

confidence: 99%

“…33 No further predictive parameters have yet been identified. 33 To date, little is known about predicting RSDrelated success, in particular in identifying nonresponders or pseudoresistant patients with hypertension. Data from a recent meta-analysis provide additional information on high variability in individual response to RSD.…”

Section: Discussionmentioning

confidence: 99%

Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation

et al. 2014

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“…34 Other derived indices of ABPM were not reported. Mahfoud et al 35 performed a retrospective multicenter meta-analysis of changes in 24-hour BP after RDN. In the subset of 303 patients with true treatmentresistant hypertension (ie, excluding white coat hypertension), significant decreases in daytime, nighttime, 24-hour, maximal, and minimal daily systolic BP were observed.…”

Section: P=0004mentioning

confidence: 99%

Effect of Catheter-Based Renal Denervation on Morning and Nocturnal Blood Pressure

et al. 2015

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U ncontrolled hypertension is associated with an increasing incidence of stroke, cardiovascular events such as myocardial infarction, peripheral artery disease, and end-stage renal disease across all ages, and ethnicities. [1][2][3][4][5] Detailed studies of blood pressure (BP) variability over 24 hours have further described an increased risk of cardiovascular events and stroke with elevated BP during the nighttime 6,7 and early morning hours. 8,9The sympathetic nervous system plays an active role in the modulation of BP, and its overactivation can lead to hypertension.10,11 Percutaneous catheter-based renal denervation (RDN) by radiofrequency ablation of the renal artery nerves has been shown to reduce central sympathetic activity 12,13 and BP in patients with uncontrolled hypertension. Although recently reported results from the Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN-3) 14 and SYMPLICITY HTN-Japan (HTN-Japan) 15 clinical trials did not demonstrate superiority of RDN over pharmacological management of hypertension based on superiority analyses of office BP or 24-hour ambulatory BP measurements (ABPM), 14,15 further evaluation of the SYMPLICITY HTN-3 trial identified several potential confounding factors that may have impacted the overall results, including insufficient ablation attempts, insufficient 4-quadrant ablations, and antihypertensive medication changes. 16In contrast to the results of SYMPLICITY HTN-3, the recently reported prospective Renal Denervation for Hypertension (DENER HTN) 17 trial reported small but statistically significant reductions in ambulatory BP (though not office or home BP) in denervated patients compared with a nonblinded, randomized control group of patients with resistant hypertension treated with a stepped-care pharmacological strategy. These reductions included greater decreases in both daytime and nighttime ambulatory systolic BP in the denervated group.Abstract-High nighttime and early morning blood pressure (BP) have been associated with greater risk for cardiovascular events than high clinic or daytime BP. BP is typically highest in the rising hours, when morning activities typically begin. We examined the effect of renal denervation on morning (6:00-8:59 AM), daytime (9:00 AM-8:59 PM), and nighttime ( P=0.28), but the classes prescribed and changes in prescription varied by study. Among patients treated with renal denervation, although the number of ablation treatments were similar in both studies (11.2±2.8 versus 11.5±1.9, P=0.55), patients in SYMPLICITY HTN-3 were less likely to receive at least 1 four-quadrant ablation treatment (25% versus 82%, P<0.001). In SYMPLICITY HTN-3, compared with controls (n=159), patients treated with renal denervation (n=325) experienced a significantly greater change in morning (−7.3±19.8 mm Hg, P<0.001) and nighttime (−6.1±18.2 versus −1.6±19.7 mm Hg, P=0.02) but not daytime systolic BP (−7.2±16.2 versus −6.4±18.6 mm Hg, P=0.67). This same trend was observed in the pooled analysis with HTN-Japan. Re...

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“…Recent meta-analysis of 7 randomised-control studies demonstrated a 16.5-mm Hg decrease of office and 9.2-mm Hg of 24-h SBP [10]. By contrast, Mahfoud et al [11] demonstrated excellent office SBP reduction by 23.7 and 27.3 mm Hg after 6 and 12 months in 303 patients with true-resistant hypertension. However, in that study the 24-h SBP changes were also less pronounced (-10 and -11.7 mm Hg, respectively).…”

Section: Discussionmentioning

confidence: 99%

Effects of renal sympathetic denervation on blood pressure and glycaemic control in patients with true resistant hypertension: results of Polish Renal Denervation Registry (RDN-POL Registry)

et al. 2016

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A b s t r a c t Background and aim:The assessment of percutaneous renal sympathetic denervation (RDN) efficacy in patients with true-resistant hypertension (true-RH) in a newly established net of Polish centres (RDN-POL Registry). Methods and results:Forty-four patients with true-RH (23 men, mean age 52.3 years) with daytime systolic blood pressure (SBP) in ambulatory blood pressure monitoring (ABPM) ≥ 135 mm Hg, on ≥ three antihypertensive agents, including diuretic, underwent RDN and completed 12-month follow-up. Mean reductions of office SBP/diastolic blood pressure were -23.8/-10.0, -12.5/-4.6, and -12.6/-6.1 mm Hg at 3, 6, and 12 months, respectively (all significant except diastolic at 6 months). Diabetes was the only predictor of office SBP reduction at 6 months (OR 9.6, 95% CI 1.4-66.5, p < 0.05). Mean 24-h SBP change was -8.3 mm Hg at 6 months and -4.6 mm Hg at 12 months. Increased 2 h-glucose in oral glucose tolerance test was the only predictor of 24-h SBP reduction at 6 months (OR 1.24 for 10 mg/dL glucose increase, 95% CI 1.04-1.48, p < 0.05). At 12 months, 24-h SBP change predictors were: baseline office SBP (OR 4.93 for 10 mm Hg SBP increment, 95% CI 1.01-24.1, p < 0.05) and 2 h-glucose (OR 1.47, 95% CI 1.08-2.00, p < 0.05). In ABPM responders, significant reduction of 2 h glucose was found as compared to the non-responders (-45.8 vs. -7.7 mg/dL, p < 0.005). Conclusions:The RDN-POL Registry demonstrated moderate blood pressure decrease after RDN. The predictors of blood pressure reduction were diabetes, 2 h-glucose, and baseline office SBP. Analysis of ABPM responders indicates a probable positive impact of RDN on glycaemic control.

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Ambulatory Blood Pressure Changes After Renal Sympathetic Denervation in Patients With Resistant Hypertension

Abstract: RDN reduced office BP and improved relevant aspects of ambulatory BP monitoring, commonly linked to high cardiovascular risk, in patients with true-treatment resistant hypertension, whereas it only affected office BP in pseudoresistant hypertension.

Cited by 238 publications

References 41 publications

Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation

Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation

Effect of Catheter-Based Renal Denervation on Morning and Nocturnal Blood Pressure

Effects of renal sympathetic denervation on blood pressure and glycaemic control in patients with true resistant hypertension: results of Polish Renal Denervation Registry (RDN-POL Registry)

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