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Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia

BACKGROUND: HMG-CoA reductase inhibitors (statins) have pleiotropic effects that are independent of cholesterol-lowering, including a dose-dependent effect on angiogenesis. Angiogenesis plays a critical role both in vascularization of the chronically ischemic myocardium and in stabilization of ather...

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Autores principales: Camnitz, Will, Burdick, Marie D, Strieter, Robert M, Mehrad, Borna, Keeley, Ellen C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560987/
https://www.ncbi.nlm.nih.gov/pubmed/23369699
http://dx.doi.org/10.1186/2001-1326-1-23
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author Camnitz, Will
Burdick, Marie D
Strieter, Robert M
Mehrad, Borna
Keeley, Ellen C
author_facet Camnitz, Will
Burdick, Marie D
Strieter, Robert M
Mehrad, Borna
Keeley, Ellen C
author_sort Camnitz, Will
collection PubMed
description BACKGROUND: HMG-CoA reductase inhibitors (statins) have pleiotropic effects that are independent of cholesterol-lowering, including a dose-dependent effect on angiogenesis. Angiogenesis plays a critical role both in vascularization of the chronically ischemic myocardium and in stabilization of atherosclerotic plaques. Chemokines, a family of structurally-related cytokine molecules, exert diverse biological functions including control of angiogenesis. The effect of statin therapy on angiogenic and angiostatic chemokines has not been evaluated extensively. We sought to test the hypothesis that, in subjects with hyperlipidemia, statin therapy influences plasma levels of angiogenic and angiostatic chemokines in a dose-dependent manner. METHODS: We prospectively collected demographic, angiographic and laboratory data from subjects with a history of hyperlipidemia who were either untreated or on statin therapy. A peripheral blood sample was obtained for measurement of plasma angiogenic and angiostatic chemokines. Multivariable analysis using logistic regression was performed adjusting for the following variables: age, gender, prior myocardial infarction, and chronic administration of aspirin, clopidogrel, insulin, oral hypoglycemic agents, beta-blockers and calcium channel blockers. RESULTS: 168 patients on statin therapy (48 on low-dose, defined as <10mg atorvastatin-equivalent, and 120 on high-dose, defined as ≥10mg atorvastatin-equivalent dose) and 11 subjects from the same database who had a history of hyperlipidemia but who were not on statins were enrolled. There were no significant differences in baseline demographics, co-morbidities, lipid panels, other medications, or angiographic data between the groups. The angiogenic chemokines CXCL1 and CXCL12 levels were significantly different across the groups. Median levels of CXCL1 were highest in subjects not on statin therapy. Compared to subjects either not on statin therapy or on low-dose statins, those taking high-dose statins had lower median values of CXCL12 (2316 [2255–11071], vs 2362 [2016–10622], vs 2189 [1968–2705] pg/mL, p=0.042). On multivariate analysis, CXCL12 remained the only factor that was strongly and inversely associated with statin dose at the 95% level (p=0.011). CONCLUSIONS: Compared to no therapy or low-dose statin therapy, treatment with high-doses of HMG-CoA reductase inhibitors is associated with decreased circulating CXCL12 levels in subjects with hyperlipidemia, and CXCL12 is strongly and inversely associated with statin dose. Additional studies are needed to confirm this finding in other cohorts and to determine if high-dose statins affect angiogenesis in patients.
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spelling pubmed-35609872013-02-04 Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia Camnitz, Will Burdick, Marie D Strieter, Robert M Mehrad, Borna Keeley, Ellen C Clin Transl Med Research BACKGROUND: HMG-CoA reductase inhibitors (statins) have pleiotropic effects that are independent of cholesterol-lowering, including a dose-dependent effect on angiogenesis. Angiogenesis plays a critical role both in vascularization of the chronically ischemic myocardium and in stabilization of atherosclerotic plaques. Chemokines, a family of structurally-related cytokine molecules, exert diverse biological functions including control of angiogenesis. The effect of statin therapy on angiogenic and angiostatic chemokines has not been evaluated extensively. We sought to test the hypothesis that, in subjects with hyperlipidemia, statin therapy influences plasma levels of angiogenic and angiostatic chemokines in a dose-dependent manner. METHODS: We prospectively collected demographic, angiographic and laboratory data from subjects with a history of hyperlipidemia who were either untreated or on statin therapy. A peripheral blood sample was obtained for measurement of plasma angiogenic and angiostatic chemokines. Multivariable analysis using logistic regression was performed adjusting for the following variables: age, gender, prior myocardial infarction, and chronic administration of aspirin, clopidogrel, insulin, oral hypoglycemic agents, beta-blockers and calcium channel blockers. RESULTS: 168 patients on statin therapy (48 on low-dose, defined as <10mg atorvastatin-equivalent, and 120 on high-dose, defined as ≥10mg atorvastatin-equivalent dose) and 11 subjects from the same database who had a history of hyperlipidemia but who were not on statins were enrolled. There were no significant differences in baseline demographics, co-morbidities, lipid panels, other medications, or angiographic data between the groups. The angiogenic chemokines CXCL1 and CXCL12 levels were significantly different across the groups. Median levels of CXCL1 were highest in subjects not on statin therapy. Compared to subjects either not on statin therapy or on low-dose statins, those taking high-dose statins had lower median values of CXCL12 (2316 [2255–11071], vs 2362 [2016–10622], vs 2189 [1968–2705] pg/mL, p=0.042). On multivariate analysis, CXCL12 remained the only factor that was strongly and inversely associated with statin dose at the 95% level (p=0.011). CONCLUSIONS: Compared to no therapy or low-dose statin therapy, treatment with high-doses of HMG-CoA reductase inhibitors is associated with decreased circulating CXCL12 levels in subjects with hyperlipidemia, and CXCL12 is strongly and inversely associated with statin dose. Additional studies are needed to confirm this finding in other cohorts and to determine if high-dose statins affect angiogenesis in patients. Springer 2012-10-06 /pmc/articles/PMC3560987/ /pubmed/23369699 http://dx.doi.org/10.1186/2001-1326-1-23 Text en Copyright ©2012 Camnitz et al.; licensee Springer. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Camnitz, Will
Burdick, Marie D
Strieter, Robert M
Mehrad, Borna
Keeley, Ellen C
Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia
title Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia
title_full Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia
title_fullStr Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia
title_full_unstemmed Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia
title_short Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia
title_sort dose-dependent effect of statin therapy on circulating cxcl12 levels in patients with hyperlipidemia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560987/
https://www.ncbi.nlm.nih.gov/pubmed/23369699
http://dx.doi.org/10.1186/2001-1326-1-23
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