The major findings from the present analysis are as follows: (1) patients with longer DM duration, especially more than 10 years, showed poorer clinical outcomes in terms of TVF and RR than non-diabetic patients or those with shorter DM duration even after revascularization; (2) a long DM duration did not affect the procedural details, in-hospital and procedural outcomes except for CIN during PCI using RA.
This is the first study to examine the associations between DM duration and clinical outcomes in a Korean population with CAD. Our registry is the largest, all-comer, multi-center registry, including CAD patients with advanced atherosclerosis in Korea. All patients received PCI with drug-eluting stents (DESs), especially 2nd generation DES, except for one patient with 1st generation DES, which reflect the current revascularization strategy for significant CAD (17, 18).
Also, all patients underwent RA during PCI, which meant that majority of patients in this study population might have significant CAD lesions with severe calcification. Using this registry, our study showed the novel results which demonstrated the clinical impact of DM duration on clinical outcomes in advanced CAD after revascularization. Indeed, there have been several studies demonstrating poor clinical outcome of DM duration in CAD patients (8, 19). However, those studies were designed as cohort or epidemiological studies with relatively healthy patients, while the majority of patients in this study received treatment at tertiary or specialized cardiology centers, and may have more severe disease compared with community-treated patients. Therefore, this study has strengths over prior studies that have examined the relation between DM duration and clinical outcomes in revascularized CAD patients with advanced atherosclerosis and calcification.
It is well-known that DM is an independent predictor of adverse clinical outcome in CAD patients after revascularization (5, 6). Our study also showed that patients with a longer duration (≥ 10 years) of DM showed poorer clinical outcomes regarding TVF and RR than non-DM and shorter duration DM (< 10 years) groups. The risk of TVF and any revascularization was 1.863 times and 2.395 times higher in L-DM than in non-DM, respectively. The plausible mechanisms are as follows: (1) CAD severity and the extent atherosclerosis is getting worse during prolonged diabetes (2, 3). (2) DM duration had a strong correlation with the nature of unfavorable coronary artery lesions. Vulnerable plaque including lipid-rich plaque and thin cap fibroatheroma and plaque rupture were frequently observed in long DM duration (10 ≥ year) group compared to shorter duration DM or non-DM group (20, 21). (3) CAC can be promoted by multifocal factors of the hormonal and physiological abnormalities associated with DM, including oxidative stress, endothelial dysfunction, and increased inflammatory cytokine production (22, 23). These changes were enhanced by prolonged DM with poor glycemic control (24), leading to adverse procedural complications and long-term clinical outcomes (25–27).
However, the incidence rate of clinical outcome in shorter DM duration group was numerically higher but did not achieve statistically significance compared to non-DM group in this study. In our registry, duration of S-DM group was relatively short (median 5 [IQR 0.17–7.33] years), including 20 (30.8%) patients were diagnosed as DM within 1 year. Therefore, S-DM group may include diabetic patients without complications. Even though the presence of DM itself is associated with poor clinical outcomes as mentioned above (5, 6), adverse clinical events are usually prevented by revascularization with optimization, which is already known for an important protective predictor (28). Several previous studies have shown in line with this result in patients with CAD (29, 30).
Our study showed a similar results regarding to the procedural details, in-hospital and procedural outcomes except for CIN. CIN occurred more frequently in the longer DM duration group. Prolonged DM is associated with microvascular complication including microalbuminuria (19, 31, 32). In this context, we could understand that CKD was frequently observed in the L-DM group. This would be a plausible explanation of difference in CIN occurrence after procedure.
Operators are usually more careful for patients with diffuse narrowing CAD during RA and worry about distal embolization, leading to flow compromising and peri-procedure MI. Because DM may affect the coronary vessel more diffusely narrowing including capillaries (33) and longer DM duration reduces myocardial blood flow in remote myocardium (34), diabetic patients would have more chance to suffer peri-procedure MI. However, the incidence rates of peri-procedure MI were similar among the three groups in our study. According to the results, one of our message is that, we may not be hesitate RA even in longer duration of diabetic patients in terms of slow or no reflow.
In subgroup analysis, the present study was in agreement with several previous studies that showed that the relative risk of vascular disease associated with DM was substantially higher in women than men (35, 36). Although the mechanisms were not fully identified, it may be associated with hormonal and storage patterns of adipose tissue differences (37, 38).
Study limitation. This study was based on a nonrandomized registry with inherent methodological limitations. Thus there is a possibility of selection bias. Second, the number of study participants and events was relatively small, limiting the statistical power of our multivariate analysis. Third, the proportion of S-DM group was relatively small (14%). Therefore, caution is necessary when interpretating our results.