Editorial
A Novel Risk Stratification Marker in Patients with Coronary Artery Disease
2024 年 31 巻 4 号 p. 345-346
詳細
2024 年 31 巻 4 号 p. 345-346
See article vol. 31: 355-367
Cardiovascular disease (CVD) is a leading cause of death worldwide with high rates of recurrent cardiovascular events, including myocardial infarction, stroke, heart failure, and cardiovascular death1). Despite established medical therapy such as aspirin, statin, and other medications combined with lifestyle interventions, subsequent cardiovascular events still occur in patients with CVD2), which makes it essential to detect residual risks of recurrent cardiovascular events. Previous studies have suggested a mutual relationship between inflammation and coronary artery disease (CAD), revealing that inflammatory biomarkers were associated with prognosis of CAD or anti-inflammatory agents reduced cardiovascular events in patients with established CAD3-5).
In this issue of the Journal, Miyazaki et al. investigated the association between soluble programmed death ligand 1 (sPD-L1) and cardiovascular events in patients with atherosclerotic CVD admitted to Kumamoto University Hospital between December 2017 and January 2020 6). The primary outcome was a composite of death from noncardiovascular causes and cardiovascular causes, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, hospitalization for heart failure, and ischemic stroke. A total of 592 patients were divided into 2 groups according to the median value of sPD-L1 and analyzed with the median follow-up of 522 days.
The observed number of the primary outcomes was 124 (death from noncardiovascular causes, 15; cardiovascular death, 9; nonfatal myocardial infarction, 6; unstable angina pectoris, 12; coronary revascularization, 43; ischemic stroke, 7; and hospitalization for heart failure, 32). The rates of the primary outcome were higher in the high sPD-L1 group than in the low sPD-L1 group (25.0% vs. 16.9%; p=0.028, log-rank test), which were driven by the higher rates of hospitalization for heart failure in the high sPD-L1 group than in the low sPD-L1 group (11.7% vs 3.0%; p=0.015, log-rank test). No differences were observed for the other components of the primary outcome between the two groups. A multivariate Cox proportional hazards analysis showed that log sPD-L1 (hazard ratio [HR]: 1.364, 95% confidence interval [CI]: 1.018–1.828, p=0.038) and log brain natriuretic peptide (HR: 1.449, 95% CI: 1.207–1.741, p＜0.001) were significantly associated with the events after adjusting for high-sensitive C-reactive protein, estimated glomerular filtration rate ＜60 mL/min/1.73 m2, and left ventricular ejection fraction. A few limitations were noted other than the study design with a limited sample size and relatively high rates of lost to follow-up. One of the concern is the time of blood sample collection for assessment of sPD-L1. sPD-L1 values may vary depending on the disease status (i.e., acute phase of acute coronary syndrome or at discharge of hospitalization for acute coronary syndrome, before or after elective coronary artery intervention, and so on). In the study, no differences were observed between the high and low sPD-L1 groups for all the components of the primary outcome except for the hospitalization for heart failure. Although several covariates were adjusted in the multivariate analyses, the use of sodium–glucose cotransporter 2 inhibitors, which are established agents to prevent heart failure-related events, were not included in the model, raising other concerns of potential biases. Considering that the association between sPD-L1 and exacerbation of heart failure is true, mechanisms linking them should be examined in the future.
As secondary prevention is a key to reduce morbidity and mortality in patients with CAD, overarching programs that encompass a variety of interventions including pharmacological and nonpharmacological approaches that comprise healthy diet, physical activity, sleep hygiene, healthy body weight, and others are needed7). Anti-inflammatory medicine is a potential pharmacological therapy for CAD, with a variety of inflammatory markers including sPD-L1 reported to be markers or therapeutic targets of CAD. However, the anti-inflammatory approach is not simple, with multiple inflammatory pathways working both independently and interactively, and we do not know the attributable fraction of each pathway to the development of CAD. Future studies are needed to determine associations between inflammation and CAD and develop new medicine based on the research.
R.N. is affiliated with a department endowed by Philips, ResMed, and Fukuda Denshi.
