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Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic
Yuichi Chikata1, Hiroshi Iwata2, Katsutoshi Miyosawa3
1Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, Japan.
Insights
Elevated inactive stromal cell derived factor-1α (SDF-1α) predicts poor outcomes in diabetic patients after percutaneous coronary intervention (PCI). This finding offers a new biomarker for risk stratification in this high-risk population.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Biomarker Discovery
Background:
- Diabetes mellitus (DM) significantly increases cardiovascular risks in patients with coronary artery disease (CAD).
- Risk stratification is crucial for diabetic patients undergoing percutaneous coronary intervention (PCI), yet specific biomarkers are lacking.
- Stromal cell derived factor-1α (SDF-1α) has shown cardioprotective roles, but its prognostic impact and isoform-specific functions in diabetic CAD patients post-PCI require clarification.
Purpose of the Study:
- To evaluate the prognostic significance of total, active, and inactive isoforms of SDF-1α.
- To assess the predictive value of these SDF-1α forms for adverse outcomes in diabetic patients following PCI.
Main Methods:
- Retrospective analysis of 849 diabetic patients who underwent their first PCI between 2008 and 2018.
- Measurement of plasma total and active SDF-1α levels using ELISA; inactive SDF-1α calculated by subtraction.
- Primary endpoint: all-cause death; secondary endpoint: composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE).
Main Results:
- Elevated inactive SDF-1α levels were associated with increased risks of all-cause death and 3P-MACE.
- Multivariate analysis confirmed inactive SDF-1α as a significant predictor for both all-cause death (HR: 2.64) and 3P-MACE (HR: 2.51).
- Inactive SDF-1α demonstrated superior predictive performance compared to total SDF-1α for both outcomes.
Conclusions:
- Plasma inactive SDF-1α is a potential novel biomarker for predicting adverse long-term outcomes in diabetic patients post-PCI.
- This finding may aid in refining risk assessment and guiding clinical management strategies for this vulnerable patient group.
Background:
Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI.
Methods:
This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α.
Results:
Unadjusted Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28-5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12-5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively).
Conclusion:
The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI.
Trial Registration:
This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry, UMIN-CTR 000035587).
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