Low hs-CRP associated with lower risk of adverse outcomes in primary prevention cohort

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

Literature - Penson PE, Leann Long D, Howard G, et al. - Eur Heart J 2018; published online ahead of print

Introduction and methods

Reduction in plasma LDL-c has repeatedly been associated with improved cardiovascular (CV) morbidity and mortality in primary and secondary prevention. However, CV risk is often not entirely eliminated, even when LDL-c target values are met [1]. It is hypothesized that the residual CV risk may be due to inflammation [2].

In this analysis of the REasons for Geographical And Racial Differences in Stroke (REGARDS) study [3], the relationship between high sensitivity C-reactive protein (hs-CRP), LDL-c and clinical outcomes was investigated, in patients with similar LDL-c levels and a high baseline 10 year risk (Framingham-CHD ≥10% or ASCVD ≥7.5%). REGARDS is a longitudinal cohort study that recruited 30,239 non-hispanic black or white participants, aged ≥45 years between 2003 and 2007. Outcome measures included all-cause mortality, incident coronary heart disease (CHD), and incident stroke.

Main results

  • Out of 6,136 eligible participants, 5% had low LDL-c levels (<70 mg/dL), the rest had LDL-c ≥70 mg/dL. There was a significant non-linear relationship between LDL-c levels and all-cause mortality.
  • In individuals with a 10-year Framingham score ≥10%, compared with the referent group (LDL-c ≥70 mg/dL and hs-CRP ≥2 mg/L), patients with LDL-c ≥70 mg/dL and hs-CRP <2 mg/L, had the following outcomes: HR for all-cause mortality: 0.86 (95%CI: 0.71-1.03), HR for incident stroke: 0.69 (95%CI: 0.47-0.99), HR for incident CHD: 0.71 (95%CI: 0.53-0.95) and HR for CHD death: 0.70 (0.50-0.99).
  • Individuals with LDL-c <70 mg/dL and hs-CRP ≥2 mg/L had the greatest risk of all-cause mortality compared with the referent group (HR: 1.37, 95%CI: 1.07-1.74) and of CHD mortality (HR: 1.35, 95%C(: 0.97-1.88).
  • Participants with LDL-c ≥70 mg/dL and hs-CRP <2 mg/L were at lowest risk of all-cause death (HR: 0.75, 95%CI: 0.67-0.85) and CHD mortality (HR: 0.67, 95%CI: 0.54-0.85).
  • Similar results were observed in the group of participants with an ASCVD score ≥7.5.
  • Various statistical analyses did not reveal a significant association between lower LDL-c levels and incident CHD or incident stroke.


In a primary prevention cohort, the combination of LDL-c ≥70 mg and low hs-CRP (<2 mg/L) was associated with a reduced risk of stroke, CHD, and CHD-death, compared with patients in the same LDL-c category and high hs-CRP levels. LDL-c levels below 70 mg/dL were not associated with protective effects, in several analyses. These data support the important role of inflammatory processes in the pathogenesis of CVD.


1. Sampson UK, Fazio S, Linton MF. Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges. Curr Atheroscler Rep 2012;14:1–10.

2. Ridker PM, Everett BM, Thuren T, et al; CANTOS Trail Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119–1131.

3. Lakoski SG, Le AH, Muntner P, Judd SE, et al. Adiposity, inflammation, and risk for death in black and white men and women in the United States: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. J Clin Endocrinol Metab 2011;96:1805–1814

Find this article online at Eur Heart J

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