Risk stratification of coronary artery disease patients during rehabilitation using a blood-based biomarker score

Introduction: This study aimed to evaluate the effectiveness of a blood-based biomarker score in tracking cardiovascular risk reduction during and after phase II cardiac rehabilitation (CR) in patients with coronary artery disease (CAD). Specifically, we sought to determine if the score could identify patients at risk for major adverse cardiovascular and cerebrovascular events (MACCE) and monitor short- and long-term risk changes in patient subgroups.

Methods: This longitudinal study included 528 patients with CAD (20% women; mean age 56.1 ± 7 years) who participated in phase II CR at a rehabilitation center in Germany. Eligible participants were male and female patients with a confirmed history of CAD, specifically following myocardial infarction (STEMI/NSTEMI) and/or angioplasty and/or percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) surgery. Clinical assessments, including blood sampling and cardiopulmonary exercise testing (CPET), were conducted at three time points: at admission (T0), discharge (T1), and at six months (T2) post-discharge. The biomarker score was calculated at each time point, incorporating NT-proBNP, troponin I, cystatin C, and CRP reflecting cardiovascular risk. Statistical analyses included mixed-effects models and Kaplan-Meier analysis.

Results: The mean predicted 10-year mortality risk significantly declined from 19 ± 14.9% at T0 to 15.4 ± 13.4%  at T1 (p < 0.0001). Both men and women showed a comparable reduction, despite men presenting with a higher initial risk (20.2% vs. 14.3%, p < 0.0001). The risk was higher in patients with multi-vessel CAD, prior MI, or those treated with CABG, with each group experiencing a significant risk reduction post-CR. Risk reduction occurred across all age groups, with slightly attenuated effects in the youngest (<40 years) and oldest (>70 years, p ≤ 0.0379) groups. Key biomarkers NT-proBNP and hsCRP decreased significantly over CR (by 33.3%, and 31.4%, both p ≤ 0.0043), particularly in CABG and MI patients. During phase III maintenance, risk reduction continued, predominantly in high-risk patients (weekly reduction of 0.19 ± 0.11%). Kaplan-Meier analysis showed that post-CR risk scores predicted MACCE (p = 0.016). Physical fitness was found to significantly reduce the risk since patients with higher baseline fitness were at lower risk and those improving fitness during CR showed a greater risk reduction (p = 0.0002).

Conclusion: The biomarker score is a sensitive tool for capturing cardiovascular risk reductions during and after phase II CR. Key biomarkers such as NT-proBNP and CRP played a pivotal role in monitoring changes, likely reflecting improved cardiac function and reduced inflammation due to CR interventions. This score was effective in stratifying patients based on clinical characteristics and in predicting MACCE, enabling ongoing risk monitoring of cardioprotective lifestyle.