Background: There are many studies on high-sensitivity C-reactive protein (hs-CRP) association with cardiovascular disease (CVD); however, just a few studies investigated whether the low-density lipoprotein cholesterol (LDL-C) could participate in hs-CRP prognostic strength. This study aimed to determine the alliance of hs-CRP and LDL-C in different concentrations in occurrence cardiovascular events in the Isfahan Cohort Study (ICS).

Methods: 3277 participants aged 35 and above were included in the current analysis. We evaluated the association of elevated hs-CRP levels (≥ 3 mg/dL) and CVD events including myocardial infarction, ischemic heart disease, stroke, CVD, CVD mortality, and all-cause mortality in those with LDL-C ≥ or < 130 mg/dL Cox frailty models was used to determine possible interactions. Results: In both crude and fully adjusted models, there was no significant interaction between LDL-C and hs-CRP levels with the incidence of MI, stroke, CVD mortality, and all-cause death. Neither elevated LDL-C alone nor elevated CRP alone were associated with the risk of all cardiovascular events and all-cause death. However, participants with elevated concentrations of both hs-CRP and LDL-C had a greater risk of ischemic heart disease (IHD) (hazards ratio (HR) 1.44; 95% CI 1.03-2.02) and CVD (HR 1.36; 95% CI 1.01-1.83) than those with low LDL-C and hs-CRP.

Conclusion: These results indicate that despite a null association between elevated levels of CRP or LDL-C alone and CVD events, concurrent rise in LDL-C and hs-CRP levels is associated with higher risk of IHD and CVD.

Keywords: Cardiovascular disease; High-sensitivity C-reactive protein; Low-density lipoprotein cholesterol.