Simvastatin reduces sympathetic activity in men with hypertension and hypercholesterolemia

Abstract

Beyond their hypolipidemic effect, statins reduce cardiovascular risk in hypertensive subjects via various mechanisms; one suggested mechanism is that they reduce sympathetic activity. We investigated the hypothesis that simvastatin decreased muscle sympathetic nerve activity (MSNA) in 31 hypertensive subjects with hypercholesterolemia (aged 38.7±10 years). In this randomized, placebocontrolled, double-blinded study, patients were treated with simvastatin (40 mg day À1 ; n¼15) or placebo (n¼16) for 8 weeks. Before and after treatment, we measured MSNA, blood pressure and heart rate. Baroreceptor control of the heart rate, or baroreceptor sensitivity (BRS), was computed by the sequence method, a cross-analysis of systolic blood pressure and the electrocardiogram R-R interval. Blood samples were tested for plasma levels of catecholamines, neuropeptide Y, aldosterone, endothelin and renin activity. Simvastatin significantly reduced MSNA (from 36.5 ± 5 to 27.8 ± 6 bursts per min, P¼0.001), heart rate (from 77 ± 6.7 to 71 ± 6.1 beats per min, P¼0.01) and both total and low-density lipoprotein cholesterol (from 249±30.6 to 184±28.3 mg dl À1 , P¼0.001 and from 169±30.6 to 117±31.2 mg dl À1 , P¼0.01, respectively). Simvastatin also improved BRS (from 10.3 ± 4.1 to 17.1 ± 4.3 ms per mm Hg, P¼0.04). No changes were observed in systolic or diastolic blood pressures, or in plasma levels of catecholamines, neuropeptide Y, endothelin, aldosterone and renin activity. After simvastatin therapy, MSNA and BRS were inversely related (r¼À0.94, Po0.05). In conclusion, we found that, in patients with hypertension and hypercholesterolemia, simvastatin reduced MSNA, and this was related to increased baroreceptor sensitivity.

Statins and the autonomic nervous system

“…Siński et al [91] studied ten hypercholesterolaemic essential hypertensive men and found that, compared with an untreated control group, 8 weeks of atorvastatin (20 mg/day) reduced MSNA burst incidence and frequency by 17 % (46.5 + − 6.2 to 38.4 + − 5.5 bursts/100 heart beats; 36.0 + − 6.6 to 28.6 + − 4.8 bursts/min), without altering BP or heart rate. Subsequently this group conducted a larger randomized double-blind placebocontrolled study of simvastatin (40 mg/day for 8 weeks) in 31 hypercholesterolaemic hypertensive men [92]. Those receiving simvastatin (n = 15) exhibited significant reductions in MSNA burst None of these variables changed significantly in the placebo group.…”

“…Those receiving simvastatin (n = 15) exhibited significant reductions in MSNA burst None of these variables changed significantly in the placebo group. In both studies the statin treatment was reported to increase arterial baroreflex sensitivity of HR, a marker of reflex cardiac vagal modulation [91,92]. Using a more stringent randomized double-blind placebocontrolled cross-over study design, Gomes et al [93] reported significant mean 10 % and 11 % reductions in MSNA burst incidence (64.7 + − 3.0 to 58.5 + − 2.0 bursts/100 heart beats) and burst frequency (39.2 + − 1.5 to 35.0 + − 2.0 bursts/min) following 3 weeks of atorvastatin (80 mg/day) in 13 primary hypertensive patients.…”

Do antilipidemic agents reduce blood pressure?

“…However, the inhibitory effect of simvastatin on SNA was not observed with ezetimibe 17) . In a study in wherein ezetimibe was combined with simvastatin, BP was further decreased by 6 mmHg in the ezetimibe combination group compared with simvastatin alone 73) .…”

“…Because statins may interact with the RAAS, statins may lower arterial BP when administered alone or together with antihypertensive drugs acting via the RAAS 29) . Moreover, lipophilic statins have been shown to reduce muscle SNA by 12%-30% in patients with HT 30,31) . Because SNA is usually higher during daytime, statins may affect daytime BP more than nighttime BP.…”

“…In fact, several reports show that statins suppress sympathetic nerve activity (SNA) [16][17][18][19] . Because this effect was not observed with ezetimibe 17) , it is considered one of the multifaceted effects of statins, regardless of the extent of lipid reduction. Suppressing SNA obviously suppresses the increase in BP.…”