Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus
ObjectivesPremature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE...
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| Published in | Annals of the rheumatic diseases Vol. 81; no. 11; pp. 1576 - 1584 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
BMJ Publishing Group Ltd and European League Against Rheumatism
01.11.2022
Elsevier Limited BMJ Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0003-4967 1468-2060 1468-2060 |
| DOI | 10.1136/ard-2022-222658 |
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| Abstract | ObjectivesPremature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE.MethodsEighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed.ResultsSeventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose.ConclusionPGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE.Trial registration number NCT02338999. |
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| AbstractList | ObjectivesPremature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE.MethodsEighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed.ResultsSeventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose.ConclusionPGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE.Trial registration numberNCT02338999. Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE. Eighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed. Seventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose. PGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE. NCT02338999. ObjectivesPremature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE.MethodsEighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed.ResultsSeventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose.ConclusionPGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE.Trial registration number NCT02338999. Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE.OBJECTIVESPremature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE.Eighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed.METHODSEighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed.Seventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose.RESULTSSeventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose.PGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE.CONCLUSIONPGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE.NCT02338999.TRIAL REGISTRATION NUMBERNCT02338999. |
| Author | Claybaugh, Dillon Cheung, Foo Chu, Jun Hasni, Sarfaraz Lu, Shajia Mehta, Nehal N Koroleva, Galina Apps, Richard Chen, Jinguo Gadina, Massimo Ochoa-Navas, Isabel Shi, Yinghui Heller, Theo Playford, Martin P Carlucci, Philip Thomas, Donald E Poncio, Elaine Gupta, Sarthak Belkaid, Yasmine Davis, Michael Oliveira, Christopher Han, Kyu Lee Dey, Amit Naqi, Mohammad Li, Xiaobai Tsang, John S Wang, Xinghao Kaplan, Mariana J Temesgen-Oyelakin, Yenealem Purmalek, Monica Mukherjee, Amrita Manna, Zerai G |
| AuthorAffiliation | 4 Translational Immunology Section, NIH , National Institute of Arthritis and Musculoskeletal and Skin Diseases , Bethesda , Maryland , USA 9 NIH Center for Human Immunology , National Institutes of Health , Bethesda , Maryland , USA 5 Office of the Clinical Director, NIH , National Institute of Arthritis and Musculoskeletal and Skin Diseases , Bethesda , Maryland , USA 6 National Institutes of Health , Bethesda , Maryland , USA 7 Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases , National Institutes of Health , Bethesda , Maryland , USA 1 Lupus Clinical Trials Unit, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases , National Institutes of Health , Bethesda , Maryland , USA 10 Arthritis and Pain Associates of PG County , Greenbelt , Maryland , USA 2 Systemic Autoimmunity Branch/NIAMS , National Institutes of Health , Bethesda , Maryland , USA 11 NIDDK , National Instit |
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| Author_xml | – sequence: 1 givenname: Sarfaraz orcidid: 0000-0002-4164-8837 surname: Hasni fullname: Hasni, Sarfaraz email: sarfaraz.hasni@nih.gov organization: Lupus Clinical Trials Unit, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA – sequence: 2 givenname: Yenealem surname: Temesgen-Oyelakin fullname: Temesgen-Oyelakin, Yenealem organization: Lupus Clinical Trials Unit, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA – sequence: 3 givenname: Michael surname: Davis fullname: Davis, Michael organization: Lupus Clinical Trials Unit, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA – sequence: 4 givenname: Jun surname: Chu fullname: Chu, Jun organization: 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Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA – sequence: 24 givenname: John S orcidid: 0000-0003-3186-3047 surname: Tsang fullname: Tsang, John S organization: NIH Center for Human Immunology, National Institutes of Health, Bethesda, Maryland, USA – sequence: 25 givenname: Richard surname: Apps fullname: Apps, Richard organization: National Institutes of Health, Bethesda, Maryland, USA – sequence: 26 givenname: Donald E surname: Thomas fullname: Thomas, Donald E organization: Arthritis and Pain Associates of PG County, Greenbelt, Maryland, USA – sequence: 27 givenname: Theo surname: Heller fullname: Heller, Theo organization: NIDDK, National Institutes of Health, Bethesda, Maryland, USA – sequence: 28 givenname: Massimo orcidid: 0000-0001-9084-6736 surname: Gadina fullname: Gadina, Massimo organization: NIAMS, National Institutes of Health, Bethesda, Maryland, USA – sequence: 29 givenname: Martin P orcidid: 0000-0002-5571-7266 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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35914929$$D View this record in MEDLINE/PubMed |
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| Copyright | Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. 2022 Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. 2022 |
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| Issue | 11 |
| Keywords | lipids systemic lupus erythematosus cardiovascular diseases |
| Language | English |
| License | This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/. Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. |
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| PublicationTitle | Annals of the rheumatic diseases |
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start-page: 340 year: 2009 ident: 10.1136/ard-2022-222658_bib19 article-title: The peroxisome proliferator-activated receptor gamma agonist rosiglitazone ameliorates murine lupus by induction of adiponectin publication-title: J Immunol doi: 10.4049/jimmunol.182.1.340 – volume: 2 year: 2013 ident: 10.1136/ard-2022-222658_bib22 article-title: The peroxisome proliferator activated receptor-γ pioglitazone improves vascular function and decreases disease activity in patients with rheumatoid arthritis publication-title: J Am Heart Assoc doi: 10.1161/JAHA.113.000441 – volume: 64 start-page: 2975 year: 2012 ident: 10.1136/ard-2022-222658_bib7 article-title: Type I interferons modulate vascular function, repair, thrombosis, and plaque progression in murine models of lupus and atherosclerosis publication-title: Arthritis Rheum doi: 10.1002/art.34504 – volume: 6 year: 2019 ident: 10.1136/ard-2022-222658_bib9 article-title: Association of lipoprotein subfractions and glycoprotein acetylation with coronary plaque burden in SLE publication-title: Lupus Sci Med doi: 10.1136/lupus-2019-000332 – volume: 183 start-page: 2729 year: 2009 ident: 10.1136/ard-2022-222658_bib20 article-title: The peroxisome proliferator-activated receptor gamma agonist pioglitazone improves cardiometabolic risk and renal inflammation in murine lupus publication-title: J Immunol doi: 10.4049/jimmunol.0804341 – volume: 33 start-page: 50 year: 2006 ident: 10.1136/ard-2022-222658_bib33 article-title: Hyperinsulinemia, insulin resistance, and circulating oxidized low density lipoprotein in women with systemic lupus erythematosus publication-title: J Rheumatol – volume: 131 year: 2021 ident: 10.1136/ard-2022-222658_bib8 article-title: Bite of the wolf: innate immune responses propagate autoimmunity in lupus publication-title: J Clin Invest doi: 10.1172/JCI144918 – volume: 70 start-page: 54 year: 2011 ident: 10.1136/ard-2022-222658_bib27 article-title: An assessment of disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and the flare version of SELENA publication-title: Ann Rheum Dis doi: 10.1136/ard.2010.132068 – volume: 15 start-page: 519 year: 2003 ident: 10.1136/ard-2022-222658_bib4 article-title: Update on vascular disease in systemic lupus erythematosus publication-title: Curr Opin Rheumatol doi: 10.1097/00002281-200309000-00001 – volume: 65 start-page: 772 year: 2005 ident: 10.1136/ard-2022-222658_bib18 article-title: Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock publication-title: Cardiovasc Res doi: 10.1016/j.cardiores.2004.12.008 – volume: 44 start-page: 1492 year: 2005 ident: 10.1136/ard-2022-222658_bib5 article-title: ‘Not only…but also’: factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus publication-title: Rheumatology doi: 10.1093/rheumatology/kei142 – volume: 40 year: 1997 ident: 10.1136/ard-2022-222658_bib24 article-title: Updating the American College of rheumatology revised criteria for the classification of systemic lupus erythematosus publication-title: Arthritis Rheum doi: 10.1002/art.1780400928 – volume: 23 start-page: 155 year: 2016 ident: 10.1136/ard-2022-222658_bib29 article-title: The role of a novel arterial stiffness parameter, Cardio-Ankle vascular index (CAVI), as a surrogate marker for cardiovascular diseases publication-title: J Atheroscler Thromb doi: 10.5551/jat.32797 – volume: 36 start-page: 389 year: 2018 ident: 10.1136/ard-2022-222658_bib12 article-title: Effect of the metabolic syndrome on organ damage and mortality in patients with systemic lupus erythematosus: a longitudinal analysis publication-title: Clin Exp Rheumatol – volume: 29 start-page: 288 year: 2002 ident: 10.1136/ard-2022-222658_bib26 article-title: Systemic lupus erythematosus disease activity index 2000 publication-title: J Rheumatol – volume: 296 start-page: R1282 year: 2009 ident: 10.1136/ard-2022-222658_bib21 article-title: Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus publication-title: Am J Physiol Regul Integr Comp Physiol doi: 10.1152/ajpregu.90992.2008 – volume: 305 start-page: 645 year: 1992 ident: 10.1136/ard-2022-222658_bib25 article-title: Validating the SF-36 publication-title: BMJ doi: 10.1136/bmj.305.6854.645-c – volume: 63 start-page: 167 year: 2015 ident: 10.1136/ard-2022-222658_bib28 article-title: A pilot study to determine the optimal timing of the physician global assessment (PGA) in patients with systemic lupus erythematosus publication-title: Immunol Res doi: 10.1007/s12026-015-8712-7 – volume: 35 start-page: 2238 year: 2017 ident: 10.1136/ard-2022-222658_bib31 article-title: Reference values of cardio-ankle vascular index in a random sample of a white population publication-title: J Hypertens doi: 10.1097/HJH.0000000000001437 – volume: 20 start-page: 1260 year: 2011 ident: 10.1136/ard-2022-222658_bib17 article-title: Implications of immunosuppressive agents in cardiovascular risks and carotid intima media thickness among lupus nephritis patients publication-title: Lupus doi: 10.1177/0961203311411347 – volume: 3 year: 2018 ident: 10.1136/ard-2022-222658_bib6 article-title: Neutrophil subsets and their gene signature associate with vascular inflammation and coronary atherosclerosis in lupus publication-title: JCI Insight doi: 10.1172/jci.insight.99276 – volume: 12 year: 2021 ident: 10.1136/ard-2022-222658_bib13 article-title: Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus publication-title: Nat Commun doi: 10.1038/s41467-021-23361-z – volume: 105 start-page: 1670 year: 2020 ident: 10.1136/ard-2022-222658_bib32 article-title: Pioglitazone for the primary and secondary prevention of cardiovascular and renal outcomes in patients with or at high risk of type 2 diabetes mellitus: a meta-analysis publication-title: J Clin Endocrinol Metab doi: 10.1210/clinem/dgz252 – volume: 2 year: 2017 ident: 10.1136/ard-2022-222658_bib10 article-title: Type I interferon responses drive intrahepatic T cells to promote metabolic syndrome publication-title: Sci Immunol doi: 10.1126/sciimmunol.aai7616 – volume: 167 start-page: 301 year: 2013 ident: 10.1136/ard-2022-222658_bib14 article-title: Efficacy and safety of statins in the prevention of atherosclerosis in patients with systemic lupus erythematosus–a meta-analysis of randomized controlled trials publication-title: Int J Cardiol doi: 10.1016/j.ijcard.2012.09.190 – volume: 15 start-page: R110 year: 2013 ident: 10.1136/ard-2022-222658_bib23 article-title: Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial publication-title: Arthritis Res Ther doi: 10.1186/ar4290 – volume: 349 start-page: 2399 year: 2003 ident: 10.1136/ard-2022-222658_bib1 article-title: Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus publication-title: N Engl J Med doi: 10.1056/NEJMoa035471 – volume: 56 start-page: 3412 year: 2007 ident: 10.1136/ard-2022-222658_bib3 article-title: Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus publication-title: Arthritis Rheum doi: 10.1002/art.22924 – volume: 30 start-page: 1026 year: 2013 ident: 10.1136/ard-2022-222658_bib36 article-title: Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies publication-title: Diabet Med doi: 10.1111/dme.12144 – volume: 25 start-page: 3590 year: 2019 ident: 10.1136/ard-2022-222658_bib37 article-title: Pioglitazone therapy decreases bone mass density and increases fat mass: a meta-analysis publication-title: Curr Pharm Des doi: 10.2174/1381612825666190920123129 – volume: 73 start-page: 459 year: 2021 ident: 10.1136/ard-2022-222658_bib11 article-title: Modulation of cardiometabolic disease markers by type I interferon inhibition in systemic lupus erythematosus publication-title: Arthritis Rheumatol doi: 10.1002/art.41518 – volume: 12 year: 2021 ident: 10.1136/ard-2022-222658_bib35 article-title: Pioglitazone for NAFLD patients with prediabetes or type 2 diabetes mellitus: a meta-analysis publication-title: Front Endocrinol doi: 10.3389/fendo.2021.615409 – volume: 8 start-page: 15 year: 2009 ident: 10.1136/ard-2022-222658_bib38 article-title: Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes publication-title: Cardiovasc Diabetol doi: 10.1186/1475-2840-8-15 – volume: 21 start-page: 27 year: 2012 ident: 10.1136/ard-2022-222658_bib34 article-title: Pioglitazone improves the cardiovascular profile in patients with uncomplicated systemic lupus erythematosus: a double-blind randomized clinical trial publication-title: Lupus doi: 10.1177/0961203311422096 – volume: 145 start-page: 408 year: 1997 ident: 10.1136/ard-2022-222658_bib2 article-title: Age-Specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study publication-title: Am J Epidemiol doi: 10.1093/oxfordjournals.aje.a009122 – volume: 21 start-page: 1617 year: 2020 ident: 10.1136/ard-2022-222658_bib16 article-title: Management of cardiovascular disease in patients with systemic lupus erythematosus publication-title: Expert Opin Pharmacother doi: 10.1080/14656566.2020.1770227 – volume: 70 start-page: 760 year: 2011 ident: 10.1136/ard-2022-222658_bib15 article-title: Lupus atherosclerosis prevention study (LAPS) publication-title: Ann Rheum Dis doi: 10.1136/ard.2010.136762 – volume: 385 start-page: 35 year: 2007 ident: 10.1136/ard-2022-222658_bib30 article-title: Atherosclerosis is accelerated in patients with long-term well-controlled systemic lupus erythematosus (SLE) publication-title: Clin Chim Acta doi: 10.1016/j.cca.2007.04.023 |
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| Snippet | ObjectivesPremature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies... Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described... |
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| StartPage | 1576 |
| SubjectTerms | Agonists Ankle Cardiovascular diseases Disease Gene expression Inflammatory diseases Insulin Insulin resistance Leukocytes (neutrophilic) lipids Lupus Metabolism Morbidity Neutrophils Pioglitazone Placebos Systemic Lupus Erythematosus Vascular diseases |
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| Title | Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus |
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