1. Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation
- Author
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Benjamin C. Storey, Natalie Staplin, Richard Haynes, Christina Reith, Jonathan Emberson, William G. Herrington, David C. Wheeler, Robert Walker, Bengt Fellström, Christoph Wanner, Martin J. Landray, Colin Baigent, Will G. Herrington, Charles Tomson, Vera Krane, Alan Cass, Jonathan Craig, Bruce Neal, Lixin Jiang, Lai Seong Hooi, Adeera Levin, Lawrence Agodoa, Mike Gaziano, Bertram Kasiske, Ziad A. Massy, Bo Feldt-Rasmussen, Udom Krairittichai, Vuddidhej Ophascharoensuk, Hallvard Holdaas, Vladimir Tesar, Andrzej Wiecek, Diederick Grobbee, Dick de Zeeuw, Carola Grönhagen-Riska, Tanaji Dasgupta, David Lewis, William Herrington, Marion Mafham, William Majoni, Karl Wallendszus, Richard Grimm, Terje Pedersen, Jonathan Tobert, Jane Armitage, Alex Baxter, Christopher Bray, Yiping Chen, Zhengming Chen, Michael Hill, Carol Knott, Sarah Parish, David Simpson, Peter Sleight, Alan Young, and Rory Collins
- Subjects
Male ,Simvastatin ,Medicin och hälsovetenskap ,Time Factors ,Ezetimibe, Simvastatin Drug Combination ,randomized trials ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Medical and Health Sciences ,0302 clinical medicine ,Risk Factors ,Medicine ,030212 general & internal medicine ,Myocardial infarction ,Randomized Controlled Trials as Topic ,biology ,Anticholesteremic Agents ,Absolute risk reduction ,vascular disease ,Middle Aged ,Lipids ,Treatment Outcome ,Cardiovascular Diseases ,Nephrology ,LDL cholesterol ,Cardiology ,Female ,Drug Therapy, Combination ,lipids (amino acids, peptides, and proteins) ,Inflammation Mediators ,medicine.drug ,medicine.medical_specialty ,Statin ,medicine.drug_class ,Down-Regulation ,Article ,C-reactive protein ,03 medical and health sciences ,Ezetimibe ,Internal medicine ,Humans ,Renal Insufficiency, Chronic ,Aged ,Dyslipidemias ,Inflammation ,business.industry ,Vascular disease ,Cholesterol, LDL ,medicine.disease ,Endocrinology ,inflammation ,biology.protein ,Azetidines ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Biomarkers ,Kidney disease - Abstract
Markers of inflammation, including plasma C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease, and it has been suggested that this association is causal. However, the relationship between inflammation and cardiovascular disease has not been extensively studied in patients with chronic kidney disease. To evaluate this, we used data from the Study of Heart and Renal Protection (SHARP) to assess associations between circulating CRP and LDL cholesterol levels and the risk of vascular and non-vascular outcomes. Major vascular events were defined as nonfatal myocardial infarction, cardiac death, stroke or arterial revascularization, with an expanded outcome of vascular events of any type. Higher baseline CRP was associated with an increased risk of major vascular events (hazard ratio per 3x increase 1.28; 95% confidence interval 1.19-1.38). Higher baseline LDL cholesterol was also associated with an increased risk of major vascular events (hazard ratio per 0.6 mmol/L higher LDL cholesterol; 1.14, 1.06-1.22). Higher baseline CRP was associated with an increased risk of a range of non-vascular events (1.16, 1.12-1.21), but there was a weak inverse association between baseline LDL cholesterol and non-vascular events (0.96, 0.92-0.99). The efficacy of lowering LDL cholesterol with simvastatin/ezetimibe on major vascular events, in the randomized comparison, was similar irrespective of CRP concentration at baseline. Thus, decisions to offer statin-based therapy to patients with chronic kidney disease should continue to be guided by their absolute risk of atherosclerotic events. Estimation of such risk may include plasma biomarkers of inflammation, but there is no evidence that the relative beneficial effects of reducing LDL cholesterol depends on plasma CRP concentration.
- Published
- 2018
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