Combined Effects of Inflammatory Status and Carotid Atherosclerosis: A 12-Year Follow-Up Study

Mayer FJ, Binder CJ, Wagner OF, et al.
Stroke. 2016;47:2952-2958

Background

Inflammation plays a substantial role in atherogenesis, and elevated pro-inflammatory responses promote plaque progression and its vulnerability to rupture [1]. Several inflammatory biomarkers predictive of CV outcomes in patients with atherosclerotic diseases have been identified, but the only circulatory biomarker frequently used for CV risk assessment in current clinical practice is hsCRP (high-sensitivity C-reactive protein) [2,3]. Serum levels of hsCRP are associated with morphological features of carotid atherosclerosis, progression of carotid narrowing and short-term CV events, and represents an important risk factor for the development and progression of carotid atherosclerosis [4,5]. However, no study has investigated whether, or to what extent, hsCRP might be predictive of mortality in patients with carotid stenosis.
In this study, the prognostic value of hsCRP for cause-specific mortality was evaluated, in a large prospective cohort of patients with asymptomatic carotid atherosclerosis. It was further hypothesised that the degree of carotid narrowing and the levels of hsCRP jointly contribute to the CV risk in these patients.

Main results

• The overall survival rate for the median follow-up of 11.81 years (IR: 6.01–12.43 years) was 48.5%. Of 549 (51.5%) deaths overall, 362 (34.0%) were CV deaths, 142 (13.3%) due to malignant diseases, and 45 (4.2%) due to other causes.
• Elevated hsCRP levels were significantly associated with an increased risk of all-cause mortality (adjusted HR for an increase of 1 mg/dL of hsCRP levels: 1.46; 95% CI: 1.31–1.63; P<0.001).
• Compared with the lowest tertile, the adjusted HRs for the risk of death from all causes were 1.18 (95% CI: 0.95–1.47) for the second tertile and 1.57 (95% CI: 1.26–1.95; P<0.001) for the third tertile.
• Increased hsCRP levels were significantly associated with increased risk of CV death (adjusted HR for an increase of 1 mg/dL of hsCRP levels: 1.47; 95% CI: 1.29–1.68; P<0.001).
• Compared with the first tertile, adjusted HRs for increasing tertiles of hsCRP were 1.28 (95% CI: 0.97–1.68) and 1.75 (95% CI: 1.34–2.29; P<0.001) for CV death.
• The cumulative 12-year survival rates for all-cause death were 60% in patients with carotid narrowing of <50% and levels of hsCRP <0.29 mg/dL and 32% in patients with carotid stenosis >50% and hsCRP levels of >0.29 mg/dL (log-rank P<0.001).
• The adjusted HR for the risk of all-cause death was 1.75 (95% CI 1.37–2.50; P<0.001) for patients with carotid stenosis >50% and hsCRP levels of >0.29 mg/dL compared with patients with carotid narrowing of <50% and levels of hsCRP <0.29 mg/dL.
• The combined assessment of degree of carotid stenosis and continuous levels of hsCRP displayed a significant improvement in the discriminatory power for CV mortality (carotid narrowing >50%: 0.56 versus carotid narrowing and hsCRP: 0.60; P<0.001).
• An improvement in individual risk stratification with combined assessment of degree of carotid stenosis and levels of hsCRP was confirmed by a significant improvement in the continuous net reclassification improvement, with 15% for CV mortality (P=0.02) compared with the degree of carotid stenosis alone.

Conclusion

In a large prospective cohort of patients with asymptomatic carotid atherosclerosis, there was a significant association between hsCRP levels and long-term mortality. Moreover, the combination of the extent of carotid atherosclerosis and inflammatory status provides additional prognostic information for these patients.

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References

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