Identifying Risk Factors for Native Coronary Atherosclerosis Progression After Percutaneous Coronary Intervention

Abstract

Objective: This study was aimed at investigating factors influencing the progression of native coronary atherosclerosis after percutaneous coronary intervention (PCI).

Methods: A cohort of 462 patients was classified into progressive (n = 73) or non-progressive (n = 389) groups according to the presence of native coronary atherosclerosis progression on coronary angiography. Clinical data and angiography results were compared during follow-up, and the time to progression of native coronary atherosclerosis was recorded. Subsequently, multivariate Cox regression analysis was conducted.

Results: In comparison to the non-progressive group, the progressive group had higher levels of glycosylated hemoglobin (HbA1c) and triglycerides (TG), and higher scores on the Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) scale, but lower levels of high-density lipoprotein cholesterol. Moreover, the rates of hyperuricemia and acute coronary syndrome (ACS) were higher in the progressive group than the non-progressive group. Multivariate analysis identified ACS, HbA1c level ≥6.5%, TG level ≥5.6 mmol/L, and SYNTAX score ≥23 as risk factors for the progression of native coronary atherosclerosis.

Conclusion: ACS, elevated HbA1c and TG levels, and higher SYNTAX scores may be associated with the progression of native coronary atherosclerosis after PCI.

Main article text

Introduction

Percutaneous coronary intervention (PCI) is used in the treatment of coronary atherosclerotic disease. In 2017, 753,142 PCI procedures were performed in China, with an associated mortality rate of 0.23% [1]. However, a substantial number of patients require repeat interventions, because of progression of native coronary atherosclerosis, thus resulting in a 2-year revascularization rate of 15% [2, 3]. The risk of significant cardiovascular complications 3 years post-PCI is associated with the progression of native coronary atherosclerosis [4], which may require hospitalization and invasive procedures [5]. Herein, our objective was to identify the risk factors influencing the progression of native coronary atherosclerosis after PCI.

Methods

Patient Enrollment and Ethical Considerations

This retrospective cohort study enrolled individuals diagnosed with coronary artery disease who underwent initial PCI at Three Gorges Hospital of Chongqing University between January 2017 and December 2019. After PCI, patients were monitored for 2 years within the cardiology unit. During that period, at least one follow-up coronary angiography (CAG) was conducted, either as part of routine postoperative assessment at the 1-year mark or prompted by emergent angina symptoms. This research was approved by the Ethics Committee of Three Gorges Hospital at Chongqing University. An exemption from the requirement for informed consent was granted by the committee, because of the minimal risk associated with the retrospective examination of medical records.

Clinical Characteristics

We collected data on variables including sex; age; smoking history; presence or absence of hypertension (persistently high blood pressure over time) and type 2 diabetes mellitus (a metabolic disorder characterized by elevated blood glucose concentrations, insulin resistance, and inadequate insulin production); body mass index (BMI); presence or absence of an initial diagnosis of acute coronary syndrome (ACS) at admission; intraoperative coronary Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) score; follow-up time (in months); and prompt review of CAG to verify the presence or absence of in-stent restenosis.

Selection Criteria

The inclusion criteria were as follows: (1) presence of clinical manifestations indicating myocardial ischemia, confirmed by a coronary heart disease diagnosis through diagnostic CAG and subsequent successful PCI; (2) receipt of a drug-eluting stent; (3) consistent administration of a secondary preventive pharmacotherapy for coronary atherosclerosis, including initiation of bipartite platelet inhibition therapy for a minimum duration of 1 year post-PCI and lifelong statin therapy; and (4) recommendation for follow-up CAG within 6–18 months post-PCI or having at least one hospital admission for CAG surveillance within 2 years, including admissions prompted by symptoms such as ischemic chest pain and angina. Comprehensive clinical and demographic data were collected both before and after admission, to ensure thorough monitoring and care.

The exclusion criteria were as follows: (1) prior or subsequent cardiac surgery, except PCI; (2) known contraindications to antiplatelet agents or statins; (3) presence of hypertension and diabetes with discontinued use of antihypertensive or antidiabetic medications against medical advice; (4) multiple hospital admissions due to terminal events or severe heart failure; and (5) presence of severe hemorrhagic disorders, hepatic insufficiency, renal failure, or malignancies.

Related Definitions

Native coronary atherosclerosis progression is defined as the deterioration or progression of atherosclerotic plaques within untreated coronary arteries, manifesting as increased lesion severity, development of new lesions, or transformation of plaque characteristics. This definition encompasses both clinically symptomatic and asymptomatic atherosclerotic processes within the coronary vasculature [2, 4, 6, 7].

In-stent restenosis is characterized by a pathological decrease in the diameter of the lumen within the stent, quantitatively determined as a decrease in diameter exceeding 50%, not only inside the stent but also in the area extending 5 mm beyond the stent’s periphery. CAG images were analyzed by two independent interventional cardiologists, and disagreements were resolved through discussions and consensus among three or more physicians.

Progression of native coronary atherosclerosis is characterized as the fulfillment of any one of the following specified conditions during subsequent CAG evaluations: (1) ≥10% increase in existing ≥50% stenosis; (2) ≥30% increase in an existing <50% stenosis; (3) new formation of ≥30% stenosis in previously normal vessels; and (4) progression of stenosis to complete coronary artery occlusion [4, 6].

Biochemical Parameters

During the follow-up before the second hospital visit or readmission, fasting blood lipids, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipoprotein (LPa), and triglycerides (TG); glycosylated hemoglobin (HbA1c); high-sensitivity C-reactive protein (HSC-RP); blood uric acid; and serum creatinine levels were measured after a fasting period of at least 8 hours.

Statistical Evaluation

Statistical analyses were conducted using the IBM SPSS software (version 25.0, IBM Corp., Armonk, NY, USA) statistical package program. Continuous variables are presented as mean ± standard deviation for normally distributed data or as median and interquartile range (IQR, 25^th–75^th percentiles) for non-normally distributed data. Group comparisons for continuous variables were conducted with either an independent-samples t-test or the Mann–Whitney U test, depending on the data distribution. Categorical variables were compared with the chi-square test. To explore risk factors contributing to the advancement of native coronary atherosclerosis, we performed multivariate Cox regression analysis. The models included age; BMI; prior chronic conditions (hypertension and diabetes); hyperuricemia; levels of TG, HDL-C, LDL-C, LPa, and HbA1c; SYNTAX scores; and initial diagnosis of ACS at admission. P-values < 0.05 were considered statistically significant.

Results

Comparison of Baseline Features Between Groups

Among patients who received their first PCI at our institution, 462 met the inclusion criteria. The median follow-up period was 21.37 (IQR: 20–24) months. During that period, we observed progression of in-stent or native coronary artery disease in 73 patients (15.8%). Among them, 22 patients were asymptomatic and did not undergo immediate reoperation, whereas 31 of the 51 symptomatic patients opted for reoperation, and the remaining 20 patients managed their symptoms through medical therapy, including increased oral nitrate intake, without requiring additional PCI. Furthermore, we evaluated the characteristics of patients with coronary lesion progression (Figure 1).

Figure 1

Flowchart of the Research Design.

On the basis of the results of CAG re-examination, we categorized the patients into two groups: progressive (n = 73) and non-progressive (n = 389). The progressive group had higher levels of ACS, serum uric acid, HbA1c, and TG, and higher SYNTAX scores, than the non-progressive group. The HDL-C levels in the non-progression group were significantly higher than those in the progression group. Moreover, we observed significantly lower HDL-C levels in the progressive group than the non-progressive group (P < 0.05, Table 1). High serum uric acid, HbA1c, and TG levels, as well as increased SYNTAX scores, were identified as risk factors for native coronary artery atherosclerosis. In contrast, a high HDL-C level was considered a protective factor.

Table 1

Baseline Data Comparison Between the Progressive and Non-Progressive Groups.

Group	Progressive group (n)	Non-progressive group (n)	Chi-squared/Z	P-value
Number of cases	73	389
Male sex [n, %]	48 (65.8)	277 (71.2)	0.877	0.349
Age (years)*	64 (54.5–72)	64 (54–72)	0.13	0.896
Smoking [n, %]	7 (9.6)	21 (5.4)	1.896	0.169
Hypertension [n, %]	41 (56.1)	189 (48.6)	1.412	0.235
Type 2 diabetes [n, %]	20 (27.4)	77 (19.8)	2.142	0.143
BMI ≥28 kg/m2 [n, %]	10 (13.7)	32 (8.2)	2.205	0.138
ACS [n, %]	53 (72.6)	202 (51.9)	10.624	0.001
SYNTAX score*	18 (13–22)	14 (9–18.5)	3.87	<0.001
Hyperuricemia [n, %]	7 (9.6)	15 (3.9)	4.455	0.035
Elevated HSC-RP [n, %]	6 (8.2)	31 (8)	0.005	0.942
Elevated serum creatinine [n, %]	9 (12.3)	44 (11.3)	0.063	0.802
ISR [n, %]	13 (17.8)	44 (11.3)	2.399	0.121
HbA1c (%)*	6.2 (5.72–6.95)	5.9 (5.5–6.28)	3.832	<0.001
TG (mmol/L)*	1.46 (0.935–2.125)	1.13 (0.83–1.74)	2.954	0.003
LDL-C (mmol/L)*	1.89 (1.355–2.445)	1.66 (1.34–2.18)	1.849	0.064
HDL-C (mmol/L)*	1.1 (0.87–1.27)	1.18 (0.95–1.4)	2.361	0.018
LPa (mg/dL)*	35.2 (10.7–97.95)	24.7 (9.95–68)	1.162	0.245

*Indicates non-normal distributions obtained with the Shapiro–Wilk normality test.

Abbreviations: ACS, acute coronary syndrome; BMI, body mass index; HbA1c, glycosylated hemoglobin; HDL-C, high-density lipoprotein cholesterol; HSC-RP, hypersensitive C-reactive protein; ISR, in-stent restenosis; LDL-C, low-density lipoprotein cholesterol; LPa, lipoprotein A; SYNTAX, Synergy Between PCI with Taxus and Cardiac Surgery; TG, triglycerides.

Factors known to influence the progression of native coronary atherosclerosis, including advanced age, dyslipidemia, hypertension, diabetes, obesity, smoking, and hyperuricemia (which are determinants of atherosclerotic cardiovascular disease [ASCVD] risk), were assessed. According to the revised edition of the 2016 Guidelines on the Management and Prevention of Dyslipidemia in Adults within the Chinese Population [8], we classified patients with high TG and low HDL-C levels into risk groups. Notably, patients clinically diagnosed with ASCVD were categorized into the extremely high-risk group. In accordance with the 2019 guidelines for dyslipidemia management issued by the European Society of Cardiology and European Society of Atherosclerosis, the recommended LDL-C level was below 1.8 mmol/L [9]. We successfully achieved this target in patients undergoing PCI for ACS, in whom LDL-C levels were effectively lowered to below 1.4 mmol/L, thus indicating successful achievement lipid-lowering goals in this patient population. In addition, individuals with a very high genetically determined level of LPa exceeding 180 mg/dL may have a lifelong risk of ASCVD equivalent to the lifelong risk of heterozygous familial hypercholesterolemia. According to American Diabetes Association guidelines [10], a diagnosis of diabetes was established when the HbA1c level was ≥6.5%, whereas an HbA1c level of 5.7–6.4% indicated the presence of prediabetes. Patients were divided into three groups with HbA1c levels of <5.7%, 5.7–6.4%, or ≥6.5%. Similarly, SYNTAX scores were classified into low (≤22 points), moderate (23–32 points), or high (≥33 points), with the three-digit grouping method [11].

Multivariate Cox Regression Analysis

Initial analyses revealed that ACS, hyperuricemia, high HbA1c levels, low HDL-C levels, high TG levels, and high SYNTAX scores were likely to be influential factors associated with the progression of native coronary arteriosclerosis. Adjustments were made for confounding variables such as age, BMI, chronic medical conditions (e.g., hypertension, diabetes), LDL-C levels, and LPa levels. Subsequently, we conducted multivariate Cox regression analysis to determine the timeframe between the recurrence of ischemic symptoms after initial PCI and the progression of native coronary atherosclerosis, as confirmed by CAG. Our findings demonstrated that ACS (hazard ratio [HR] = 2.324, 95% confidence interval [CI]: 1.323–4.083, P = 0.003), HbA1c levels ≥6.5% (HR = 3.658, 95% CI: 1.652–8.097, P = 0.001), TG levels ≥5.6 mmol/L (HR = 4.656, 95% CI: 1.728–12.548, P = 0.002), and moderate (23–32) (HR = 1.809, 95% CI: 1.051–3.116, P = 0.032) or high (≥33) (HR = 6.112, 95% CI: 1.326–28.165, P = 0.020) SYNTAX scores were independent factors associated with the progression of native coronary atherosclerosis (Table 2 and Figure 2).

Table 2

Results of the Multivariate Regression Analysis.

Group	B	Standard deviation	Wald	Degree of freedom	P	HR	HR 95% CI
							Lower limit	Ceiling
Age, years	0.005	0.012	0.183	1	0.669	1.005	0.982	1.029
BMI ≥28 kg/m2
Is	0.362	0.359	1.014	1	0.314	1.436	0.710	2.905
No	0					1
Hypertension
Is	0.269	0.247	1.192	1	0.275	1.309	0.807	2.124
No	0					1
Diabetes
Is	0.454	0.346	1.724	1	0.189	0.635	0.323	1.250
No	0					1
Hyperuricemia
Is	0.635	0.419	2.298	1	0.130	1.888	0.830	4.293
No	0					1
TG (tendency/L)
1.7–5.5	0.109	0.295	0.137	1	0.711	1.115	0.626	1.988
≥5.6	1.538	0.506	9.248	1	0.002	4.656	1.728	12.548
<1.7	0					1
LDL-C (tendency/L)
1.4–1.7	0.147	0.362	0.166	1	0.684	0.863	0.425	1.754
≥1.8	0.080	0.302	0.070	1	0.792	1.083	0.599	1.956
<1.4	0					1
HDL-C (tendency/L)
<1	0.065	0.275	0.057	1	0.812	1.068	0.623	1.831
≥1
LPa (mg/dL)
>180	0.782	0.479	2.661	1	0.103	2.186	0.854	5.592
≤180	0					1
HbA1c (%)
5.7–6.4	0.283	0.339	0.696	1	0.404	1.327	0.683	2.577
≥6.5	1.297	0.405	10.232	1	0.001	3.658	1.652	8.097
<5.7	0					1
ACS
Is	0.843	0.287	8.608	1	0.003	2.324	1.323	4.083
No	0					1
SYNTAX score
23–32	0.593	0.277	4.573	1	0.032	1.809	1.051	3.116
≥33	1.810	0.780	5.392	1	0.020	6.112	1.326	28.165
≤22	0					1

Abbreviations: ACS, acute coronary syndrome; BMI, body mass index; HbA1c, glycosylated hemoglobin; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LPa, lipoprotein A; TG, triglycerides.

Figure 2

Forest Plot of Risk Factors for the Progression of Native Coronary Atherosclerosis.

Abbreviations: CI, confidence interval; HbA1c, glycosylated hemoglobin; HR, hazard ratio; SYNTAX, Synergy Between PCI with Taxus and Cardiac Surgery; TG, triglyceride.

Discussion

This study indicated that patients with disease progression after their initial PCI typically exhibit distinct characteristics. Notably, these patients often have low levels of HDL-C. In addition, significant contributors to the progression of native coronary atherosclerosis after PCI included ACS, high HbA1c (≥6.5%) and TG (≥5.6 mmol/L) levels, and high SYNTAX scores (≥23). These findings may aid in effectively managing and attenuating the progression of native coronary atherosclerosis, thus potentially leading to improved prognosis. The development and progression of atherosclerotic lesions are influenced by various risk factors, including systemic arterial hypertension, diabetes mellitus, tobacco use, dyslipidemia, and adiposity. Collectively, these factors increase the likelihood of development of ischemic heart disease [12]. Most patients undergoing PCI modify their lifestyle habits, such as through adherence to a low-sodium and low-fat diet, smoking cessation, weight management, and regular physical activity. Despite these changes, they continue to use antihypertensive and antidiabetic medications, and adhere to long-term oral antiplatelet and statin treatments for the management of recurrent coronary arteriosclerosis events. Nonetheless, some patients experience progression of native coronary arteriosclerosis. This retrospective study identified and categorized the risk factors for native atherosclerosis progression after PCI. Through multivariate Cox regression, the analysis further delineated the timeframe associated with disease progression. Our findings may aid in preventing recurrence of coronary heart disease after PCI.

Elevated LDL-C is widely acknowledged as a significant risk factor for the development of native coronary atherosclerosis, whereas lowering LDL-C levels is associated with a decreased risk of both initial and recurrent native coronary atherosclerosis [9]. In this study, multivariate analysis verified that LDL-C levels were not an independent risk factor for the progression of native coronary atherosclerosis after intensive statin therapy, thereby affirming the role of statins in preventing native coronary atherosclerosis. The progressive group had higher LDL-C levels (median: 1.89, IQR: 1.355–2.445 mmol/L) than the non-progressive group (median: 1.66, IQR: 1.34–2.18 mmol/L), thus suggesting potential benefits from more intensive LDL-C lowering. Previous research has shown that combining statins with ezetimibe synergistically decreases LDL-C levels and leads to superior improvements in cardiovascular health outcomes [13].

Mounting evidence supports the correlation between elevated TG levels and the development of native coronary atherosclerosis [14–16]. Observational studies, Mendelian randomization analyses, and pharmacological trials have robustly demonstrated the association of high TG concentrations with the occurrence and progression of coronary atherosclerosis. This evidence partially explains the residual risk of coronary atherosclerosis even after target LDL-C levels are achieved. Elevated TG levels contribute to atherosclerosis progression by promoting vascular endothelial dysfunction, accelerating foam cell development, and initiating inflammatory responses [9, 14, 16, 17]. In our study, a TG level of ≥5.6 mmol/L was determined to independently predict the progression of native coronary atherosclerosis (HR = 4.656, 95% CI: 1.728–12.548, P = 0.002). Therefore, actively controlling TG levels after PCI is clinically important for preventing native coronary atherosclerosis progression. Lowering lipid levels via health and lifestyle management, including diet, exercise, weight control, smoking cessation, and limiting alcohol intake, is crucial for primary cardiovascular disease prevention in China. When lifestyle management does not achieve lipid level management standards, drug treatment should be considered. Strategies for lowering elevated TG levels involve prescribing medications such as icosapent ethyl and fenofibrate [12]. According to the 2021 Guidelines for Combined Lipid Regulation for Patients with High Risk and Extremely High Risk published by the European Atherosclerosis Society, patients with ASCVD or diabetes undergoing statin therapy whose TG levels range from 2.3 to 5.6 mmol/L may be prescribed bempedoic acid. Moreover, for some patients, high doses of icosapent ethyl may be used [18].

Type 2 diabetes mellitus significantly elevates the risk of coronary artery atherosclerosis. The risk of individuals diagnosed with type 2 diabetes developing this condition is twice that of individuals without diabetes [19]. Patients with native coronary atherosclerosis complicated by diabetes typically present with multiple severe coronary artery lesions, a substantial plaque burden, and relatively poor prognosis. Moreover, patients with diabetes are more prone than those without diabetes to exhibit plaque progression in segments not treated with stents [20, 21]. HbA1c levels are a reliable indicator of blood glucose levels over a span of 2–3 months, and are unaffected by short-term dietary changes or stress, thus providing an invaluable biomarker for assessing diabetes treatment outcomes [22]. In our study, patients with diabetes exhibited a native coronary atherosclerosis progression rate of 20.62%, a rate similar to the 14.52% observed in patients without diabetes. In the progression group, the mean HbA1c level was 6.2%, which was significantly higher than the 5.9% observed in the non-progressive cohort. Multivariate analysis indicated that neither a history of diabetes nor post-PCI antidiabetic treatment predicted atherosclerosis progression. However, persistently poor glycemic control (HbA1c ≥6.5%) emerged as a distinct independent risk factor (HR = 3.658, 95% CI: 1.652–8.097, P = 0.001). Findings from a cohort study by Wang et al. [23] have suggested that, in patients with coronary heart disease without a history of diabetes undergoing PCI, the admission HbA1c concentration serves as an autonomous prognostic marker for the emergence of significant cardiac complications within a 2-year period. Therefore, patients should maintain HbA1c levels <6.5% after PCI, regardless of their diabetes status.

ACS is a critical ischemic event resulting from the rupture or erosion of unstable atherosclerotic plaques in the coronary arteries, which in turn triggers downstream thrombus formation [24, 25]. Through intravascular ultrasound examination of non-target lesions in patients with ACS with native coronary atherosclerosis, Stone et al. [4] have identified hallmark features of plaque instability, including attenuated fibrous caps and substantial lipid cores reminiscent of those observed in stented target lesions. Their study confirmed that the ACS group had a significantly higher likelihood of native lesion progression approximately 2.32 times that in the non-ACS group. Therefore, proactive monitoring and effective management of cardiovascular risk factors are imperative to halt the progression of native coronary atherosclerosis in patients with ACS.

The SYNTAX score, an evaluative index assessing the quantity, functional consequences, spatial arrangement, and complexity of lesions in coronary vessels, serves as a quantitative metric for determining the severity of coronary artery pathology. A higher score reflects greater complexity in coronary artery anomalies [26, 27]. For patients treated with PCI, the SYNTAX score has been identified as an independent prognostic factor for predicting outcomes at 1-year follow-up [28]. Similarly, a higher SYNTAX score indicates more complex coronary lesions and greater likelihood of native coronary atherosclerosis progression [3, 29]. We further determined that both moderate and elevated SYNTAX scores independently predicted the advancement of native coronary atherosclerosis, in agreement with findings from earlier studies.

Nevertheless, this study has several limitations. First, intravascular imaging could have enabled more detailed characterization of the native atherosclerotic changes contributing to coronary atherosclerosis progression. Moreover, because of the retrospective design of this investigation, the reliability of hypertension control measures could not be verified. This limitation might explain the absence of correlation observed between elevated arterial tension and progression risk in the current analysis.

In conclusion, prioritizing individuals with risk indicators such as ACS, HbA1c levels ≥6.5%, TG levels ≥5.6 mmol/L, and SYNTAX scores ≥23 is crucial for preventing and managing the progression of native coronary artery disease (Figure 3). These factors have been identified as significant contributors to the advancement of native coronary atherosclerosis. By proactively addressing these indicators, healthcare professionals can better tailor interventions and treatments to mitigate the risk of disease progression and improve patient outcomes.

Figure 3

The Area Indicated by the Arrow Depicts a Lesion of a Native Coronary Atherosclerotic Plaque.

The degree of stenosis was assessed with quantitative coronary angiography (QCA) with both automatic and manual calibrations on a Japanese Shimadzu Bransist Alexa C12 Digital Subtraction Angiography (DSA) system.

Data Availability Statement

All data produced or examined during this investigation are encompassed within this publication. For additional information, please contact the corresponding author.

Ethics Statement

The Ethics Committee of the Three Gorges Hospital at Chongqing University granted approval for this investigation. Because of the negligible associated risk, the requirement for informed consent was waived for this retrospective analysis of patient records.

Author Contributions

Jianbing Wang and Zhiyu Ling designed the study. Jianbing Wang collected clinical data and drafted the manuscript. Zhiyu Ling revised the article.

Grant Information

This study was not supported by any sponsor or funder.

Conflict of Interest

Zhiyu Ling is the editorial board member of Cardiovascular Innovations and Applications. Zhiyu Ling was not involved in the peer review or decision-making process of the manuscript. The other author have no conflict of interest to declare.

Citation Information

Download Citation.

References

1. SS Hu, RL Gao, LS Liu, ML Zhu, W Wang, YJ Wang, et al. Summary of the 2018 report on cardiovascular diseases in China. Chin Circ J 2019;34:209–20.

2. GG Stefanini, F Alfonso, E Barbato, RA Byrne, D Capodanno, R Colleran, et al. Management of myocardial revascularisation failure: an expert consensus document of the EAPCI. EuroIntervention 2020;16:e875–90.

3. M Taniwaki, GG Stefanini, S Silber, G Richardt, P Vranckx, PW Serruys, et al. 4-year clinical outcomes and predictors of repeat revascularization in patients treated with new-generation drug-eluting stents: a report from the RESOLUTE All-Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention). J Am Coll Cardiol 2014;63:1617–25.

4. GW Stone, A Maehara, AJ Lansky, B de Bruyne, E Cristea, GS Mintz, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med 2011;364:226–35.

5. CA Parasca, SJ Head, M Milojevic, MJ Mack, PW Serruys, MC Morice, et al. Incidence, characteristics, predictors, and outcomes of repeat revascularization after percutaneous coronary intervention and coronary artery bypass grafting: the SYNTAX trial at 5 years. JACC Cardiovasc Interv 2016;9:2493–507.

6. L Fu, J Yang, Q Xue, L Rao, J Hu, Q Zhang, et al. Clinical characteristics and risk factors of rapid progression of nontarget vascular plaques in elderly patients with coronary heart disease and diabetes mellitus. Chin J Diabetes Mellitus 2020;28:587–93.

7. J Li, Y Han, J Jing, S Tu, W Chen, JH Reiber, et al. Non-culprit coronary lesions in young patients have higher rates of atherosclerotic progression. Int J Cardiovasc Imaging 2015;31:889–97.

8. J Zhu. Supplementary notes to guidelines for prevention and treatment of dyslipidemia in Chinese adults (2016 revised Edition). Chin Circ J 2017;32:53.

9. F Mach, C Baigent, AL Catapano, KC Koskinas, M Casula, L Badimon, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111–88.

10. WK Chung, K Erion, JC Florez, AT Hattersley, MF Hivert, CG Lee, et al. Precision medicine in diabetes: a consensus report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020;43:1617–35.

11. A Kundu, P Sardar, K O’Day, S Chatterjee, T Owan, J Dawn Abbott. SYNTAX score and outcomes of coronary revascularization in diabetic patients. Curr Cardiol Rep 2018;20:28.

12. DK Arnett, RS Blumenthal, MA Albert, AB Buroker, ZD Goldberger, EJ Hahn, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines. Circulation 2019;140:e596–646.

13. CP Cannon, MA Blazing, RP Giugliano, A McCagg, JA White, P Theroux, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015;372:2387–97.

14. Y He, TH Lam, LS Li, LS Li, SF He, BQ Liang. Triglyceride and coronary heart disease mortality in a 24-year follow-up study in Xi’an, China. Ann Epidemiol 2004;14:1–7.

15. UK Sampson, S Fazio, MF Linton. Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges. Curr Atheroscler Rep 2012;14:1–10.

16. S Raposeiras-Roubin, X Rosselló, B Oliva, L Fernández-Friera, JM Mendiguren, V Andrés, et al. Triglycerides and residual atherosclerotic risk. J Am Coll Cardiol 2021;77:3031–41.

17. P He, X Ouyang, Y Tang, J Li, W Yin, C Tang. Research advances of relationship between triglyceride level and atherosclerotic cardiovascular disease. Chin J Arterioscler 2013;21:951–4.

18. M Averna, M Banach, E Bruckert, H Drexel, M Farnier, D Gaita, et al. Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: a statement from a European Atherosclerosis Society Task Force. Atherosclerosis 2021;325:99–109.

19. CS Fox, S Coady, PD Sorlie, D Levy, JB Meigs, RB D’Agostino Sr, et al. Trends in cardiovascular complications of diabetes. JAMA 2004;292:2495–99.

20. R Shi, K Shi, ZG Yang, YK Guo, KY Diao, Y Gao, et al. Serial coronary computed tomography angiography-verified coronary plaque progression: comparison of stented patients with or without diabetes. Cardiovasc Diabetol 2019;18:123.

21. MW Kennedy, E Fabris, H Suryapranata, E Kedhi. Is ischemia the only factor predicting cardiovascular outcomes in all diabetes mellitus patients? Cardiovasc Diabetol 2017;16:51.

22. W Jia, L Chen. Chinese guidelines for clinical application of blood glucose monitoring (2015 ed). Chin J Diabetes 2015;7:603–13.

23. H Wang, S Jia, Y Liu, J Xu, Z Gao, Y Song, et al. Impact of glycosylated hemoglobin levels at admission on long-term prognosis after percutaneous coronary intervention in patients without diabetes history. Chin Circ J 2020;35:142–48.

24. A Ahmadi, J Leipsic, R Blankstein, C Taylor, H Hecht, GW Stone, et al. Do plaques rapidly progress prior to myocardial infarction? The interplay between plaque vulnerability and progression. Circ Res 2015;117:99–104.

25. E Falk, M Nakano, JF Bentzon, AV Finn, R Virmani. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J 2013;34:719–28.

26. FW Mohr, MC Morice, AP Kappetein, TE Feldman, E Ståhle, A Colombo, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet 2013;381:629–38.

27. MM Vroegindewey, AS Schuurman, I Kardys, SS Anroedh, RM Oemrawsingh, J Ligthart, et al. SYNTAX score in relation to intravascular ultrasound and near-infrared spectroscopy for the assessment of atherosclerotic burden in patients with coronary artery disease. EuroIntervention 2019;14:1408–15.

28. PW Serruys, MC Morice, AP Kappetein, A Colombo, DR Holmes, MJ Mack, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360:961–72.

29. M Taniwaki, S Windecker, S Zaugg, GG Stefanini, S Baumgartner, T Zanchin, et al. The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study. Eur Heart J 2015;36:2167–76.