Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation

Benjamin C. Storey, Natalie Staplin, Richard Haynes, Christina Reith, Jonathan Emberson, William Herrington, David C. Wheeler, Robert Walker, Bengt Fellström, Christoph Wanner, Martin J. Landray, Colin Baigent, The SHARP Collaborative Group, Alan Cass, Jonathan Craig, Bruce Neal

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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.

Original languageEnglish
Pages (from-to)1000-1007
Number of pages8
JournalKidney International
Volume93
Issue number4
DOIs
Publication statusPublished - Apr 2018

Bibliographical note

Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Copyright © 2017, International Society of Nephrology.

Keywords

  • C-reactive protein
  • inflammation
  • LDL cholesterol
  • randomized trials
  • vascular disease

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  • Cite this

    Storey, B. C., Staplin, N., Haynes, R., Reith, C., Emberson, J., Herrington, W., Wheeler, D. C., Walker, R., Fellström, B., Wanner, C., Landray, M. J., Baigent, C., The SHARP Collaborative Group, Cass, A., Craig, J., & Neal, B. (2018). Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation. Kidney International, 93(4), 1000-1007. https://doi.org/10.1016/j.kint.2017.09.011