A blood-based biomarker score for monitoring secondary prevention in coronary artery disease

Background Continuous risk monitoring of patients with coronary artery disease (CAD) may provide insight into patients’ adherence to medical therapy and heart-healthy lifestyle. Traditional risk scores have limited capacity to reflect lifestyle-dependent risk changes and may not be sensitive enough for early identification of disease worsening. Purpose To evaluate if a blood-based biomarker score can be used to monitor changes in cardiovascular risk in patients with CAD. Methods A longitudinal study of n=528 patients (20% women, 56.1±7 years) with a history of CAD following STEMI/NSTEMI and/or angioplasty and/or percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) was performed. Patients participated in a controlled, guideline-based phase II cardiac rehabilitation program for 3-4 weeks. Blood sampling and cardiopulmonary exercise testing (CPET) was conducted at three time points: at admission (T0), discharge (T1), and at six months after discharge (T2). The cardiac rehabilitation biomarker score (CRBS) was calculated at each time point, incorporating hsTNI, NT-proBNP, HbA1c, cystatin C, and hsCRP to calculate the individual cardiovascular risk expressed as 10-year mortality risk. Kaplan-Meier curves were generated for high and low risk groups (n=384, follow-up = 523±298 days). The Reynolds and Framingham score were used for comparison. Results With CR, the predicted 10-year mortality risk declined from 19.12±15.14% (T0) to 15.9±13.89% (T1, p<0.0001). Men and women showed a comparable reduction, despite men presenting with a higher initial risk (20.29% vs. 14.41%, p<0.0001). The CRBS detected higher risks in patients with prior MI, those treated with CABG, and multi-vessel CAD, with significant risk reduction post-CR in each group. Risk reduction occurred across all age groups, with slightly attenuated effects in the youngest (<40 years) group (p≤0.0852) group. After CR, slower but continuous risk reduction was observed predominantly in high-risk patients (weekly reduction of 0.19±0.11%). Post-CR (T1) CRBS risk predicted MACCE (p=0.039) while results for the Framingham and Reynolds score were not significant (p=0.059, p=0.29). Of note, the CRBS depended on physical fitness (%reference VO2max), as reduced risk was seen for patients with higher baseline fitness as well as those improving fitness during CR (p≤0.0162). The effect of baseline fitness on risk remained significant even after adjusting for event (MI), intervention (CABG), and disease severity (multi vessel CAD) (p=0.007). Conclusion We provide evidence that a blood-based biomarker score can be used to monitor the risk of CAD patients and the effectiveness of secondary prevention programs including CR and exercise-based lifestyle intervention programs. The score may further be used for stratifying patients according to individual risk profiles and MACCE prediction.