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Associations Between Very Low Concentrations of LDL-Cholesterol, hs-CRP and Health Outcomes in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study

Penson, P, Long, DL, Howard, G, Toth, PP, Muntner, P, Howard, VJ, Safford, MM, Jones, SR, Martin, SS, Mazidi, M, Catapano, AL and Banach, M (2018) Associations Between Very Low Concentrations of LDL-Cholesterol, hs-CRP and Health Outcomes in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study. European Heart Journal, 39 (40). pp. 3641-3653. ISSN 0195-668X

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Introduction: Recent findings have demonstrated the important contribution of inflammation to the risk of cardiovascular disease (CVD) in individuals with optimally managed low density lipoprotein cholesterol (LDL-C). We explored relationships between LDL-C, high sensitivity C-reactive protein (hsCRP) and clinical outcomes in a free-living US population.
Methods: We used data from the REasons for Geographical And Racial Differences in Stroke (REGARDS), and selected individuals at “high risk” for coronary events with a Framingham Coronary Risk Score of >10% or atherosclerotic cardiovascular disease (ASCVD) risk >7.5% in order to explore relationships between low LDL-C (<70 mg/dl [1.8 mmol/L] in comparison to >70 mg/dl [1.8 mmol/L]); hs-CRP <2 compared to ≥2 mg/L and clinical outcomes (all-cause mortality, incident coronary heart disease [CHD] and incident stroke). To assess the association between the LDL-C and hs-CRP categories and each outcome, a series of incremental Cox proportional hazards models were employed on complete cases. To account for missing observations, the most adjusted model was used to interrogate the data using multiple imputation with chained equations (MICE).
Results: In this analysis, 6136 REGARDS high risk participants were included. In the MICE analysis, participants with high LDL-C (>70 mg/dl) and low hs-CRP (<2 mg/L) had a lower risk of incident stroke (hazard ratio [HR] 0.69, 0.47-0.997) incident CHD (HR 0.71, 0.53- 0.95) and CHD death (HR 0.70, 0.50-0.99) than those in the same LDL-C category high hs- CRP (≥2 mg/L). In participants with high hsCRP (≥2 mg/dL), low LDL-C (<70 mg/dL [1.8 mmol/L]) was not associated with additional risk reduction of any investigated outcome, but with the significant increase of all-cause mortality (HR 1.37, 1.07-1.74).
Conclusions: In this high-risk population, we found that low hsCRP (<2mg/L) appeared to be associated with reduced risk of incident stroke, incident CHD and CHD death, whereas low LDL-C (<70 mg/dL) was not associated with protective effects. Thus, our results support other data with respect to the importance of inflammatory processes in the pathogenesis of CVD.

Item Type: Article
Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal following peer review. The version of record Peter E Penson, D Leann Long, George Howard, Peter P Toth, Paul Muntner, Virginia J Howard, Monica M Safford, Steven R Jones, Seth S Martin, Mohsen Mazidi, Alberico L Catapano, Maciej Banach, Associations between very low concentrations of low density lipoprotein cholesterol, high sensitivity C-reactive protein, and health outcomes in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study, European Heart Journal, Volume 39, Issue 40, 21 October 2018, Pages 3641–3653, is available online at: https://doi.org/10.1093/eurheartj/ehy533
Uncontrolled Keywords: 1102 Cardiovascular Medicine And Haematology
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Oxford University Press (OUP)
Date Deposited: 14 Aug 2018 09:50
Last Modified: 04 Sep 2021 10:14
DOI or ID number: 10.1093/eurheartj/ehy533
URI: https://researchonline.ljmu.ac.uk/id/eprint/9086
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