Carotid intima-media thickness, hs-CRP and TNF-α are independently associated with cardiovascular event risk in patients with atherosclerotic occlusive disease

Abstract

This prospective study aimed to determine whether carotid intima-media thickness (CIMT) and biomarkers can enhance the predictive value of classic atherosclerosis risk factors (RFs) for cardiovascular (CV) event risk in patients with confirmed atherosclerosis.

Methods: Baseline levels of hs-CRP, Tumor Necrosis Factor alpha (TNF-α), Transforming Growth Factor beta (TGF-β), Interleukin-6 (IL-6), Interleukin-10 (IL-10) and Nt-proBNP were measured in 304 subjects (189 men) aged 64.2±9.4 years, with confirmed atherosclerotic occlusive disease. Maximum CIMT values of common, bulb and internal carotid arteries were measured and expressed as mean CIMT value. The incidences of CV death, myocardial infarction (MI), ischemic stroke (IS) and symptomatic lesion progression were recorded.

Results: During 44.7±12.1 months of follow-up, CV events occurred in 61 (20.1%) patients. Age (odds ratio: OR=1.04; p=0.013), diabetes (OR=2.01; p=0.007), LDL-cholesterol>3.35mmol/L (OR=2.03; p=0.007), previous MI (OR=2.14; p=0.003) and previous IS (OR=3.35; p<0.001) were found independent CV event RFs. Adding biomarkers or CIMT to classic RFs revealed that levels of TNF-α>6pg/mL (OR=1.77; p=0.024), hs-CRP>6mg/L (OR=1.69; p=0.009) or CIMT>1.25mm (OR=5.11; p<0.001) were independently associated with CV event risk. While Nt-proBNP was found RF of CV death (OR=1.19; p=0.003) and MI (OR=1.19; p=0.002). In patients with RFs plus TNF-α>6pg/mL and hs-CRP>6mg/L, a 2- and 5-year event-free survival was 8% and 4%, respectively, as compared to 42% and 33% in those with RFs but lower TNF-α and hs-CRP levels. While, CIMT<1.25mm increased a 2- and 5-year CV event-free survival probability to 79% and 73%, respectively, despite classic RFs presence.

Conclusion: Additive value of TNF-α, hs-CRP and CIMT to classic RFs in CV risk stratification was found in patients with confirmed atherosclerosis. Nt-proBNP was found an independent risk factor of CV death and MI.