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Eur Heart J. 2018 Oct 21;39(40):3641-3653. doi: 10.1093/eurheartj/ehy533.

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.

Author information

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, UK.
Department of Biostatistics, University of Alabama at Birmingham School of Public Health, 1665 University Boulevard, Birmingham, AL, USA.
The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 600 N. Wolfe St, Carnegie 565-G, Baltimore, MD, USA.
Preventive Cardiology, CGH Medical Center, 01 East Miller Road, Sterling, IL, USA.
Department of Epidemiology, University of Alabama at Birmingham, 700 University Boulevard, Suite LHL 450, Birmingham, AL, USA.
Department of Medicine, Weill Cornell Medicine, 1320 York Avenue, HT-621 New York, NY, USA.
Department of Biology and Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, Kemigarden 4, SE-412 96 Gothenburg, Sweden.
Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Via Balzaretti 9, Milan, Italy.
Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Zeromskiego 113, Lodz, Poland.
Polish Mother's Memorial Hospital Research Institute, Rzgowska 281/288; Lodz, Poland.
Cardiovascular Research Centre, University of Zielona Gora, Zyty 28; Zielona Gora, Poland.



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 (hs-CRP), and clinical outcomes in a free-living US population.

Methods and results:

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 with ≥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). 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 hs-CRP (≥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).


In this high-risk population, we found that low hs-CRP (<2 mg/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.

[Available on 2019-10-21]

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