The present study investigated the clinical predictors of the rapid progression and revascularization of coronary non-target lesions. Our results showed that 19.0% patients had rapid progression in a mean interval of 14.8 months and 42.7% of them underwent revascularization. In multivariate analysis, hypertension, STEMI, HbA1c and lesion classification were significant factors associated with rapid progression. In addition, triglyceride and lesion classification were significant factors associated with lesion revascularization.
It has been reported that coronary lesions would go through rapid progression in a short period of time and induce adverse cardiac events7,12. In our study, in a mean interval of 14.4 months between two serial CAGs, nearly one of five patients had lesion progression and 42.7% of them underwent revascularization. Patients with rapid progression also had higher prevalence of myocardial infarction. These results were in accordance with previous works and suggested that rapid progression was quite common and deserve more cautions. Previous studies showed that most acute coronary events result from the progression of mildly stenotic plaques, based on angiographic information available from many months to years before the event. Stone et al. 13 in the PROSPECT study found that among 106 non-culprit lesions in 697 patients resulting in subsequent acute coronary syndrome during median 3.4 years follow-up and the mean angiographic diameter stenosis of these progressed lesion was 32% ± 21% at first CAG. In our study, the progressed lesions had a mean percent diameter stenosis of 37.8% at the first CAG which was also in line with previous studies. These results suggested that screening clinical risk factors associated with rapid progression is of potential ability to improve clinical outcomes.
Traditional risk factors for lesion progression are cigarette use and high cholesterol level. The impacts of smoking cessation on the cardiovascular outcomes is still controversial14. Our previous work also revealed that smoking cessation was not associated with reduced frequency of rapid progression15. Several imaging studies using different modalities have uniformly demonstrated that intensive treatment with statins reduces total plaque burden and is able to halt progression16. In our study, the cholesterol level was not different between patients with and without progression at first CAG and the proportion of statin use was also comparable. These results indicate that other factors might contribute to rapid progression.
In this study, multivariate analysis showed that hypertension, the presentation of STEMI, HbA1c and lesion classification (B2/C versus A/B1) were independent risk factors for rapid progression. The coefficients of these factors are all positive, except that hypertension was negatively associated with rapid progression. Studies from De Luca et al. and Yan et al. found that patients with CHD and hypertension were more likely to have future cardiovascular events17,18. In this case, the negative association between hypertension and rapid progression in our study might be results of relatively short CAG interval or just statistical significance but with limited clinical value. It has been showed earlier the presentation of STEMI accelerates non-culprit coronary lesion atherosclerosis19. Goldstein et al. reported that additional angiographic lesions are present in 39.5% of patients with AMI, and this subgroup of patients has an increased incidence of recurrent ischemia20. In our study, STEMI was independently associated with rapid progression which were consistent with previous studies. Therefore, more attention should be paid in patients with the presentation of STEMI and additional coronary lesions to prevent future cardiovascular events. We also found that the level of HbA1c was risk factor for rapid progression. Inaba et al. found that accelerated plaque progression was blunted in diabetic patients with HbA1c < 6.5%21. In addition, results from Ahmed et al. showed greater reductions in minimum luminal diameter in coronary lesions from diabetic patients with a baseline HbA1c ≥ 6.5%22. Meanwhile, our results showed that diabetes mellitus was not risk factor for rapid progression. These results indicated that the level of glycemic control was more important than the diagnosis of diabetes mellitus to the prevention of lesion progression.
Besides demographic features, our work also found that an angiographic feature, AHA/ACC lesion classification, was also risk factor for rapid progression. In our study, patients with B2/C type lesions were more likely to have rapid lesion progression. Theuerle et al. also showed that patients with more complex lesion classification such as B2 or C type had more major adverse cardiac events at one year follow-up23. In addition, Qiu et al. found that type C lesion was interpedently associated with worse prognosis24. Furthermore, we showed that lesion classification was not only risk factor for rapid progression but also independently associated with future revascularization. We postulated that clinicians also take the morphology characters into consideration when performing revascularization. Meanwhile, Pinilla-Echeverri et al. demonstrated that lesion angiographic morphology was closed related to lesion vulnerability as assessed by optical coherence tomography 25. These results indicate that lesion morphology could predict clinical outcomes and enough attention should be paid in these patients during routine clinical management. Another risk factor we found for lesion revascularization was the level of triglyceride. High triglyceride as a component of cardiovascular metabolic abnormalities was shown to be associated with the risk of CHD26 and poor clinical outcomes in patients with acute myocardial infarction27. In our study, the level of triglyceride was also significantly elevated in progression compared with non-progression group. These results suggested that abnormal lipid and glycemic metabolism together contribute to lesion progression and eventually revascularization.
This study had several limitations. First, the generalizability of our findings was limited by the retrospective nature and single center as well as the selection bias in study populations. Second, intravascular ultrasound and optic coherence tomography should be applied to evaluate lesion progression in the future studies. Third, we did not include target lesion-related events in our clinical outcomes because these events, such as in-stent restenosis or stent thrombosis, have different mechanisms compared with the progression of de novo coronary lesions. Fourth, the results needed to be confirmed in large, prospective studies.
In conclusion, our study showed that coronary non-target lesions rapid progressed and underwent revascularization in a short period of time. Risk factors including hypertension, STEMI, HbA1c and AHA/ACC lesion classification were useful to identify patients at high risk for rapid progression. Strictly medication and more attentions should be paid in these patients to prevent future cardiovascular events.