A clinician's perspective of the role of renal sympathetic nerves in hypertension

Renal sympathetic hyperactivity is associated with hypertension and its progression, chronic kidney disease, and heart failure. We did a proof-of-principle trial of therapeutic renal sympathetic denervation in patients with resistant hypertension (ie, systolic blood pressure >/=160 mm Hg on three or more antihypertensive medications, including a diuretic) to assess safety and blood-pressure reduction effectiveness. We enrolled 50 patients at five Australian and European centres; 5 patients were excluded for anatomical reasons (mainly on the basis of dual renal artery systems). Patients received percutaneous radiofrequency catheter-based treatment between June, 2007, and November, 2008, with subsequent follow-up to 1 year. We assessed the effectiveness of renal sympathetic denervation with renal noradrenaline spillover in a subgroup of patients. Primary endpoints were office blood pressure and safety data before and at 1, 3, 6, 9, and 12 months after procedure. Renal angiography was done before, immediately after, and 14-30 days after procedure, and magnetic resonance angiogram 6 months after procedure. We assessed blood-pressure lowering effectiveness by repeated measures ANOVA. This study is registered in Australia and Europe with ClinicalTrials.gov, numbers NCT 00483808 and NCT 00664638. In treated patients, baseline mean office blood pressure was 177/101 mm Hg (SD 20/15), (mean 4.7 antihypertensive medications); estimated glomerular filtration rate was 81 mL/min/1.73m(2) (SD 23); and mean reduction in renal noradrenaline spillover was 47% (95% CI 28-65%). Office blood pressures after procedure were reduced by -14/-10, -21/-10, -22/-11, -24/-11, and -27/-17 mm Hg at 1, 3, 6, 9, and 12 months, respectively. In the five non-treated patients, mean rise in office blood pressure was +3/-2, +2/+3, +14/+9, and +26/+17 mm Hg at 1, 3, 6, and 9 months, respectively. One intraprocedural renal artery dissection occurred before radiofrequency energy delivery, without further sequelae. There were no other renovascular complications. Catheter-based renal denervation causes substantial and sustained blood-pressure reduction, without serious adverse events, in patients with resistant hypertension. Prospective randomised clinical trials are needed to investigate the usefulness of this procedure in the management of this condition.

Despite progress, many hypertensive patients remain uncontrolled. Defining characteristics of uncontrolled hypertensives may facilitate efforts to improve blood pressure control. Subjects included 13,375 hypertensive adults from National Health and Nutrition Examination Surveys (NHANESs) subdivided into 1988 to 1994, 1999 to 2004, and 2005 to 2008. Uncontrolled hypertension was defined as blood pressure ≥140/≥90 mm Hg and apparent treatment-resistant hypertension (aTRH) when subjects reported taking ≥3 antihypertensive medications. Framingham 10-year coronary risk was calculated. Multivariable logistic regression was used to identify clinical characteristics associated with untreated, treated uncontrolled on 1 to 2 blood pressure medications, and aTRH across all 3 survey periods. More than half of uncontrolled hypertensives were untreated across surveys, including 52.2% in 2005 to 2008. Clinical factors linked with untreated hypertension included male sex, infrequent healthcare visits (0 to 1 per year), body mass index 20% (P<0.01). Untreated, undertreated, and aTRH patients have consistent characteristics that could inform strategies to improve blood pressure control by decreasing untreated hypertension, reducing therapeutic inertia in undertreated patients, and enhancing therapeutic efficiency in aTRH.