Comparison of Effects of Rosuvastatin (10 mg) Versus Atorvastatin (40 mg) on Rho Kinase Activity in Caucasian Men With a Previous Atherosclerotic Event

Ron Rawlings, Anju Nohria, Ping-Yen Liu, Jason Donnelly, Mark A. Creager, Peter Ganz, Andrew Selwyn, James K. Liao

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

In addition to inhibiting cholesterol biosynthesis, statins also inhibit the formation of isoprenoid intermediates, which are required for the activation of the Rho/Rho kinase (ROCK) pathway. Increased ROCK activity has been implicated in causing endothelial dysfunction and atherosclerosis. However, it is not known whether statins, at doses used to lower cholesterol levels, inhibit ROCK activity in humans with atherosclerosis. Furthermore, it is not known whether lipophilic and hydrophilic statins differ in their ability to inhibit ROCK activity. Accordingly, we enrolled 30 men with stable atherosclerosis (low-density lipoprotein [LDL] ≥100 mg/dL) in a randomized, double-blind study comparing equivalent LDL-lowering doses of a hydrophilic statin (rosuvastatin 10 mg once a day) with a lipophilic statin (atorvastatin 40 mg once a day) for 28 days. We assessed the change in lipids, ROCK activity, and flow-mediated dilation (FMD) of the brachial artery before and after statin therapy. Both treatment groups exhibited comparable 30% to 32% and 42% to 45% reductions in total and LDL cholesterol, respectively. Only atorvastatin reduced triglycerides, and neither statin altered high-density lipoprotein cholesterol. Whereas both statins inhibited ROCK activity (p <0.0001), the extent of inhibition was greater with rosuvastatin (18 ± 2% vs 8 ± 2%, p = 0.0006). Statins also improved FMD from 7.4 ± 0.6 to 9.3 ± 0.4 (p = 0.003) with rosuvastatin being slightly better than atorvastatin. The inhibition of ROCK activity by statins did not correlate with reductions in LDL (p = 0.57) but was associated with improvement in FMD. In conclusion, these findings provide direct clinical evidence that statins, at clinically relevant doses, could differentially inhibit ROCK activity and improve endothelial function by cholesterol-independent mechanism.

Original languageEnglish
Pages (from-to)437-441
Number of pages5
JournalAmerican Journal of Cardiology
Volume103
Issue number4
DOIs
Publication statusPublished - 2009 Feb 15

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
rho-Associated Kinases
LDL Lipoproteins
Dilatation
Atherosclerosis
Cholesterol
Atorvastatin Calcium
Rosuvastatin Calcium
Brachial Artery
Terpenes
Double-Blind Method
Human Activities
LDL Cholesterol
HDL Cholesterol
Triglycerides

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Rawlings, Ron ; Nohria, Anju ; Liu, Ping-Yen ; Donnelly, Jason ; Creager, Mark A. ; Ganz, Peter ; Selwyn, Andrew ; Liao, James K. / Comparison of Effects of Rosuvastatin (10 mg) Versus Atorvastatin (40 mg) on Rho Kinase Activity in Caucasian Men With a Previous Atherosclerotic Event. In: American Journal of Cardiology. 2009 ; Vol. 103, No. 4. pp. 437-441.
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abstract = "In addition to inhibiting cholesterol biosynthesis, statins also inhibit the formation of isoprenoid intermediates, which are required for the activation of the Rho/Rho kinase (ROCK) pathway. Increased ROCK activity has been implicated in causing endothelial dysfunction and atherosclerosis. However, it is not known whether statins, at doses used to lower cholesterol levels, inhibit ROCK activity in humans with atherosclerosis. Furthermore, it is not known whether lipophilic and hydrophilic statins differ in their ability to inhibit ROCK activity. Accordingly, we enrolled 30 men with stable atherosclerosis (low-density lipoprotein [LDL] ≥100 mg/dL) in a randomized, double-blind study comparing equivalent LDL-lowering doses of a hydrophilic statin (rosuvastatin 10 mg once a day) with a lipophilic statin (atorvastatin 40 mg once a day) for 28 days. We assessed the change in lipids, ROCK activity, and flow-mediated dilation (FMD) of the brachial artery before and after statin therapy. Both treatment groups exhibited comparable 30{\%} to 32{\%} and 42{\%} to 45{\%} reductions in total and LDL cholesterol, respectively. Only atorvastatin reduced triglycerides, and neither statin altered high-density lipoprotein cholesterol. Whereas both statins inhibited ROCK activity (p <0.0001), the extent of inhibition was greater with rosuvastatin (18 ± 2{\%} vs 8 ± 2{\%}, p = 0.0006). Statins also improved FMD from 7.4 ± 0.6 to 9.3 ± 0.4 (p = 0.003) with rosuvastatin being slightly better than atorvastatin. The inhibition of ROCK activity by statins did not correlate with reductions in LDL (p = 0.57) but was associated with improvement in FMD. In conclusion, these findings provide direct clinical evidence that statins, at clinically relevant doses, could differentially inhibit ROCK activity and improve endothelial function by cholesterol-independent mechanism.",
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Comparison of Effects of Rosuvastatin (10 mg) Versus Atorvastatin (40 mg) on Rho Kinase Activity in Caucasian Men With a Previous Atherosclerotic Event. / Rawlings, Ron; Nohria, Anju; Liu, Ping-Yen; Donnelly, Jason; Creager, Mark A.; Ganz, Peter; Selwyn, Andrew; Liao, James K.

In: American Journal of Cardiology, Vol. 103, No. 4, 15.02.2009, p. 437-441.

Research output: Contribution to journalArticle

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T1 - Comparison of Effects of Rosuvastatin (10 mg) Versus Atorvastatin (40 mg) on Rho Kinase Activity in Caucasian Men With a Previous Atherosclerotic Event

AU - Rawlings, Ron

AU - Nohria, Anju

AU - Liu, Ping-Yen

AU - Donnelly, Jason

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