Failure of Antihypertensive Treatment to Restore Normal Sympathetic Activity

Abstract

Background: Sympathetic deactivation represents a major goal of antihypertensive drug treatment. However, whether treatment normalizes the hypertension-related sympathetic cardiovascular overdrive remains uncertain.

Methods: In 219 middle-aged essential hypertensives, we analyzed, along with office systolic and diastolic blood pressure (BP) and heart rate, muscle sympathetic nerve traffic (MSNA, microneurography) before and after 3-month treatment, either as monotherapy or as combination. Controls were represented by 100 age-matched normotensives.

Results: Treatment caused, along with a small heart rate decrease, a clear BP reduction (from 160.5/95.5 to 142.3/85.0 mm Hg, P<0.01) and a significant MSNA inhibition (from 70.7±11.5 to 65.0±10.2 bursts/100 heartbeats, mean±SD, P<0.01). A similar pattern was detected in patients under monotherapy (n=81) or combination drug treatment (n=138). MSNA was significantly related to systolic BP before and during treatment but unrelated to heart rate. In treated patients achieving the lower BP (135.1/84.5 mm Hg, n=90), the MSNA reduction was greater than that detected in patients with the higher on-treatment BP (146.7/87.4 mm Hg, n=129). However, even in patients achieving a BP target <140/90 mm Hg, MSNA remained markedly higher (on average +66.4%) compared with controls. This was the case even when treated BP was <130/80 mm Hg. Data were similar for different antihypertensive drug classes.

Conclusions: Thus, antihypertensive treatment, even when effective in achieving BP control, fails to restore the level of normotension-related MSNA, with a persistence of the pattern of heightened sympathetic influences typical of untreated patients with hypertension. Failure of normalization may contribute to the development of the residual cardiovascular risk reported in treated hypertensives.

Keywords: antihypertensive agents; blood pressure; goal; heart rate; risk factors.