Sympathetic Overactivation in the Resistant Hypertensive Phenotype: A Meta-Analysis of Published Studies

Indirect and direct approaches to assess sympathetic cardiovascular drive have shown that patients with essential hypertension responsive to the blood pressure-lowering effects of antihypertensive drugs are characterized by a pronounced adrenergic overactivity. Whether an emerging clinical hypertensive phenotype such as drug-resistant hypertension (RHT) is also characterized by sympathetic activation and whether its magnitude and underlying pathophysiological mechanisms differ from those of non-RHT is undefined.

Among the 54 studies identified providing information in RHT on muscle sympathetic nerve traffic (MSNA), 12 were eligible (508 patients) and meta-analyzed, grouping them based on clinically relevant questions: (1) Is MSNA increased in RHT? (2) Does the magnitude of the sympathetic activation differ from that observed in non-RHT? (3) Are heart rate and plasma norepinephrine valuable surrogate markers of MSNA in RHT? and (4) Is baroreflex-MSNA control impaired?

MSNA was significantly greater in patients with RHT than in normotensive patients (73.2±6.6 versus 46.1±11.1 bursts/100 heartbeats, means±SD; P<0.0001) and this was the case also when data were compared with patients with non-RHT (59.8±8.4 bursts/100 heartbeats; P<0.001), despite the greater number of antihypertensive drugs. At variance from non-RHT, in RHT, elevated MSNA was unrelated to heart rate and plasma venous norepinephrine. Similar to non-RHT, MSNA in RHT was inversely related to the baroreflex function.

RHT is characterized by a sustained sympathetic overdrive, significantly greater in magnitude than the 1 detected in non-RHT. Neither heart rate nor norepinephrine are capable of reflecting the marked adrenergic overdrive seen in this condition via MSNA recordings.