Usefulness of high-sensitivity CRP increases during circadian rhythm for prediction of long-term cardiovascular events in patients with stable coronary artery disease

Objectives: We investigated the value of circadian variations in high sensitivity C-reactive protein (hs-CRP) levels in prediction of long-term cardiovascular events (CVE) in patients with stable coronary artery disease (CAD).
Study design: The study included 94 patients (70 men, 24 women; mean age 58±9 years) with stable CAD. High sensitivity CRP levels were measured at six-hour intervals, namely, morning (06: 00), midday (12: 00), evening (18: 00), and midnight (24: 00). Absolute change in hs-CRP (absolute ΔCRP) was calculated by subtracting the midday hs-CRP level from that of the morning. Relative change in hs-CRP (relative ΔCRP) was calculated by dividing absolute ΔCRP by the midday hs-CRP level. The patients were followed-up for a mean of 40.2±8.0 months for monitoring of CVE.
Results: During the follow-up period, CVE occurred in 24 patients (25.5%). Patients who developed CVE exhibited significantly higher serum creatinine, B-type natriuretic peptide, morning, evening, and midnight hs-CRP levels, absolute and relative ΔCRP, and left atrial end-diastolic diameter compared to patients without CVE (p<0.05). In logistic regression analysis, only left atrial end-diastolic diameter and absolute ΔCRP were independent predictors of CVE (OR=1.11, 95% CI 1.003-1.236, p=0.044 and OR=1.58, 95% CI 1.195-2.090, p=0.001, respectively). Every 1 mg/l increase in absolute ΔCRP represented a 58.1% increase in CVE risk. In receiver operating characteristics curve analysis, the cut-off value of 2 mg/l for absolute ΔCRP predicted CVE with 89.5% sensitivity and 84.2% specificity.
Conclusion: Our findings suggest that absolute circadian increases in hs-CRP levels may be helpful in predicting long-term CVEs in patients with stable CAD.

Keywords: Biological markers, C-reactive protein, circadian rhythm, coronary artery disease; prognosis