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
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 . It is hypothesized that the residual CV risk may be due to inflammation .
In this analysis of the REasons for Geographical And Racial Differences in Stroke (REGARDS) study , 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.
- 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.