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High-dose simvastat...
High-dose simvastatin exhibits enhanced lipid-lowering effects relative to simvastatin/ezetimibe combination therapy
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- Snowden, Stuart G. (författare)
- Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden
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- Grapov, Dmitry (författare)
- NIH West Coast Metabolomics Center, University of California, Davis, United States; Department of Nutrition, University of California, Davis, United States
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- Settergren, Magnus (författare)
- Karolinska Institutet
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- D'Alexandri, Fabio Luiz (författare)
- Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden
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- Haeggström, Jesper Z. (författare)
- Karolinska Institutet
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- Fiehn, Oliver (författare)
- NIH West Coast Metabolomics Center, University of California, Davis, United States
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- Hyötyläinen, Tuulia, 1971- (författare)
- Örebro universitet,Institutionen för naturvetenskap och teknik,Department of Bio- and Chemical Processes, VTT Technical Research Centre of Finland, Espoo, Finland; gSteno Diabetes Center A/S, Gentofte, Denmark
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- Pedersen, Theresa L (författare)
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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- Newman, John W. (författare)
- Department of Nutrition, University of California, Davis, United States; Obesity and Metabolism Research Unit, USDA-ARS Western Human Nutrition Research Center, Davis CA, United States
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- Oresic, Matej, 1967- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Department of Bio- and Chemical Processes, VTT Technical Research Centre of Finland, Espoo, Finland; gSteno Diabetes Center A/S, Gentofte, Denmark
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- Pernow, John (författare)
- Karolinska Institutet
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- Wheelock, Craig E. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- Lippincott Williams & Wilkins, 2014
- 2014
- Engelska.
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 1942-325X .- 1942-3268. ; 7:6, s. 955-964
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Statins are the frontline in cholesterol reduction therapies; however, their use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in low-density lipoprotein cholesterol. Thirty-nine patients were treated with either 80 mg simvastatin (n=20) or 10 mg simvastatin plus 10 mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable low-density lipoprotein cholesterol reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (eg, eicosanoids and endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. After statistical analysis and orthogonal projections to latent structures multivariate modeling, no changes were observed in lipid mediator levels, whereas global structural lipids were reduced in response to both monotherapy (R(2)Y=0.74; Q(2)=0.66; cross-validated ANOVA P=7.0×10(-8)) and combination therapy (R(2)Y=0.67; Q(2)=0.54; cross-validated ANOVA P=2.6×10(-5)). Orthogonal projections to latent structures modeling identified a subset of 12 lipids that classified the 2 treatment groups after 6 weeks (R(2)Y=0.65; Q(2)=0.61; cross-validated ANOVA P=5.4×10(-8)). Decreases in the lipid species phosphatidylcholine (15:0/18:2) and hexosyl-ceramide (d18:1/24:0) were the strongest discriminators of low-density lipoprotein cholesterol reductions for both treatment groups (q<0.00005), whereas phosphatidylethanolamine (36:3e) contributed most to distinguishing treatment groups (q=0.017). Shifts in lipid composition were similar for high-dose simvastatin and simvastatin/ezetimibe combination therapy, but the magnitude of the reduction was linked to simvastatin dosage. Simvastatin therapy did not affect circulating levels of lipid mediators, suggesting that pleiotropic effects are not associated with eicosanoid production. Only high-dose simvastatin reduced the relative proportion of sphingomyelin and ceramide to phosphatidylcholine (q=0.008), suggesting a pleiotropic effect previously associated with a reduced risk of cardiovascular disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- eicosanoids
- ezetimibe
- hydroxymethylglutaryl-CoA reductase inhibitors
- lipids
- mass spectrometry
- simvastatin
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Snowden, Stuart ...
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Grapov, Dmitry
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Settergren, Magn ...
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D'Alexandri, Fab ...
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Haeggström, Jesp ...
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Fiehn, Oliver
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Hyötyläinen, Tuu ...
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Pedersen, Theres ...
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Newman, John W.
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Oresic, Matej, 1 ...
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Pernow, John
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Wheelock, Craig ...
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