Background—: Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. We investigated the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension. Methods and Results—: We enrolled 50 patients with therapy-resistant hypertension. Thirty-seven patients underwent bilateral catheter-based renal denervation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A _1c , calculated insulin sensitivity (homeostasis model assessment–insulin resistance), and glucose levels during oral glucose tolerance test were measured before and 1 and 3 months after treatment. Mean office blood pressure at baseline was 178/96±3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by −28/−10 mm Hg ( P <0.001) and −32/−12 mm Hg ( P <0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118±3.4 to 108±3.8 mg/dL ( P =0.039). Insulin levels were decreased from 20.8±3.0 to 9.3±2.5 μIU/mL ( P =0.006) and C-peptide levels from 5.3±0.6 to 3.0±0.9 ng/mL ( P =0.002). After 3 months, homeostasis model assessment–insulin resistance decreased from 6.0±0.9 to 2.4±0.8 ( P =0.001). Additionally, mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dL ( P =0.012). There were no significant changes in blood pressure or metabolic markers in the control group. Conclusions—: Renal denervation improves glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure. However, this improvement appeared to be unrelated to changes in drug treatment. This novel procedure may therefore provide protection in patients with resistant hypertension and metabolic disorders at high cardiovascular risk. Clinical Trial Registration—: URL: http://www.ClinicalTrials.gov . Unique identifiers: NCT00664638 and NCT00888433.

Increased renal resistive index and urinary albumin excretion are markers of hypertensive end-organ damage and renal vasoconstriction involving increased sympathetic activity. Catheter-based sympathetic renal denervation (RD) offers a new approach to reduce renal sympathetic activity and blood pressure in resistant hypertension. The influence of RD on renal hemodynamics, renal function, and urinary albumin excretion has not been studied. One hundred consecutive patients with resistant hypertension were included in the study; 88 underwent interventional RD and 12 served as controls. Systolic, diastolic, and pulse pressure, as well renal resistive index in interlobar arteries, renal function, and urinary albumin excretion, were measured before and at 3 and 6 months of follow-up. RD reduced systolic, diastolic, and pulse pressure at 3 and 6 months by 22.7/26.6 mm Hg, 7.7/9.7 mm Hg, and 15.1/17.5 mm Hg ( P for all <0.001), respectively, without significant changes in the control group. SBP reduction after 6 months correlated with SBP baseline values ( r =−0.46; P <0.001). There were no renal artery stenoses, dissections, or aneurysms during 6 months of follow-up. Renal resistive index decreased from 0.691±0.01 at baseline to 0.674±0.01 and 0.670±0.01 ( P =0.037/0.017) at 3- and 6-month follow-up. Mean cystatin C glomerular filtration rate and urinary albumin excretion remained unchanged after RD; however, the number of patients with microalbuminuria or macroalbuminuria decreased. RD reduced blood pressure, renal resistive index, and incidence of albuminuria without adversely affecting glomerular filtration rate or renal artery structure within 6 months and appears to be a safe and effective therapeutic approach to lower blood pressure in patients with resistant hypertension.

There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension.

Arterial hypertension is a leading cause of death globally. Due to ageing, the rising incidence of obesity, and socioeconomic and environmental changes, its incidence increases worldwide. Hypertension commonly coexists with Type 2 diabetes, obesity, dyslipidaemia, sedentary lifestyle, and smoking leading to risk amplification. Blood pressure lowering by lifestyle modifications and antihypertensive drugs reduce cardiovascular (CV) morbidity and mortality. Guidelines recommend dual- and triple-combination therapies using renin–angiotensin system blockers, calcium channel blockers, and/or a diuretic. Comorbidities often complicate management. New drugs such as angiotensin receptor-neprilysin inhibitors, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists improve CV and renal outcomes. Catheter-based renal denervation could offer an alternative treatment option in comorbid hypertension associated with increased sympathetic nerve activity. This review summarises the latest clinical evidence for managing hypertension with CV comorbidities.

Hypertension is highly prevalent and one of the most frequent chronic diseases worldwide.¹ It has been suggested that over the next two decades up to 50% of the adult population will be diagnosed with hypertension, according to the standard guideline definitions.¹ Despite the availability of many safe and effective antihypertensive drugs, control rates to target blood pressure remain low.² Approximately 5–10% of all patients with high blood pressure are resistant to drug treatment defined as blood pressure >140/90 mmHg, >130–139/80–85 mmHg in diabetes mellitus or >130/80 mmHg in chronic kidney disease in the presence of three or more antihypertensives of different classes, including a diuretic, at maximal or the highest tolerated dose.³ Resistant hypertension is associated with an increased risk of cardiovascular events.⁴ Current non-invasive therapeutic strategies are mainly based on lifestyle interventions and pharmacological treatment, including mineralocorticoid receptor antagonists.³ Up until recently treatment options for patients with resistant hypertension were limited. Nowadays catheter-based renal denervation offers a new approach targeting the renal sympathetic nerves. Indeed, the technique has been shown to reduce sympathetic nerve activity,⁵ norepinephrine spillover⁶ as well as blood pressure^7–9 in patients with resistant hypertension. Several national^10–13 and international¹⁴ consensus documents from different societies have recently been published, with different degrees of involvement of interventionalists. This expert consensus document summarizes the view of an expert panel of the European Society of Cardiology and the European Association of Percutaneous Cardiovascular Interventions to provide guidance regarding appropriate patient selection, efficacy, safety, limitations, and potential new indications of renal denervation for referring physicians, interventionalists, and healthcare providers.