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...