Rationale and Objectives
The purpose of this study was to investigate whether high-risk plaque (HRP) and calcium assessed by coronary computed tomography (CT) could predict future cardiovascular events after second-generation drug-eluting stent (DES) placement.
Materials and Methods
We analyzed 317 patients from December 2012 to April 2015 who underwent coronary CT followed by DES placement. HRP was defined as a plaque with positive remodeling and low attenuation or a plaque with a napkin-ring sign. Coronary calcium was assessed by Agatston score (AS). Patients were divided into three groups: low risk, HRP negative and AS <400; intermediate risk, HRP positive and AS ≥400; high risk, HRP positive and AS ≥400. The primary end point was a composite of all-cause mortality, myocardial infarction, fatal arrhythmia, or repeated revascularization. Kaplan-Meier analysis was used to estimate the distribution of time to events.
Results
A total of 74 events (23%) occurred during a median follow-up of 25.8 months. Patients with primary end points had HRP more frequently (70% vs 51%, P = 0.003) and were more calcified (AS, 471 [interquartile range, 143–1614] vs 289 [interquartile range, 63–787]; P = 0.01) than patients without primary end points. The frequency of primary end point increased significantly in the intermediate- and high-risk patients ( P = 0.0011). Multivariate analysis showed that the hazard ratio of the intermediate- and high-risk groups was 1.91 (95% confidence interval, 1.04–3.77; P = 0.037) and 2.66 (95% confidence interval, 1.27–5.73; P = 0.009), respectively.
Conclusion
Plaque and calcification analysis by coronary CT could predict future cardiovascular events after second-generation DES placement.
Introduction
Percutaneous coronary intervention (PCI) is a widely used method to treat coronary artery stenosis . The frequency of in-stent restenosis (ISR) and target-vessel failure (TVF) was initially high with bare-metal stents but decreased after the introduction of drug-eluting stents (DESs) . Increased stent thrombosis using first-generation DES remained a problem, but the second-generation DES reduced its frequency . However, repeated revascularization because of ISR, TVF, or de novo lesions remains a concern.
Recent advances in computed tomography (CT) allowed clear depiction of coronary plaques . Several plaque characteristics such as low attenuation , positive remodeling , and napkin-ring sign (NRS) have been associated with high-risk plaques (HRPs). Previous studies have shown that patients with these plaques, as well as coronary calcium detected by CT, are at risk of future cardiovascular events . We hypothesized that these characteristics would be a predictor for future events in patients who underwent PCI. Thus, the objective of the present study was to investigate whether CT-detected HRP and coronary calcium could predict future cardiovascular events after second-generation DES placement.
Materials and Methods
Patients
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CT Data Acquisition
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Image Analysis of Coronary CT Angiography
Calcium Scoring
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Plaque Analysis
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PCI Procedure
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Follow-up and End Points
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Statistical Analysis
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Results
Study Population and Clinical Characteristics
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TABLE 1
Patient Characteristics
All Patients Event (+) Event (−)P Number of patients 317 74 243 Male 189 (60) 51 (69) 138 (57) 0.78 Age (y) 70.7 ± 9.5 71.0 ± 9.9 70.6 ± 9.4 0.79 Body mass index (kg/m 2 ) 23.6 ± 3.0 23.8 ± 2.7 23.5 ± 3.0 0.43 Initial status 0.25 Stable angina 289 (91) 65 (88) 224 (92) Unstable angina 28 (9) 9 (12) 19 (8) Coronary risk factors Diabetes mellitus 124 (39) 29 (39) 95 (39) 1.00 Hypertension 260 (82) 63 (85) 197 (81) 0.49 Dyslipidemia 239 (75) 59 (80) 180 (74) 0.36 Smoking (current/ex) 51 (16)/119 (38) 14 (19)/28 (38) 37 (15)/91 (37) 0.71 Family history 66 (21) 13 (18) 53 (22) 0.51 Pretest risk score 12.7 ± 3.2 13.0 ± 3.1 12.6 ± 3.2 0.43 Laboratory data Baseline Hemoglobin A1c (%) 6.4 ± 1.0 6.3 ± 1.0 6.4 ± 1.0 0.65 Triglyceride (mg/dL) 158 ± 104 158 ± 92 158 ± 107 0.99 LDL (mg/dL) 120 ± 37 118 ± 29 121 ± 40 0.61 HDL (mg/dL) 52 ± 14 52 ± 14 53 ± 14 0.69 Follow-up Hemoglobin A1c (%) 6.3 ± 0.8 6.3 ± 0.8 6.3 ± 0.8 0.98 Triglyceride (mg/dL) 132 ± 88 135 ± 89 131 ± 88 0.76 LDL (mg/dL) 88 ± 25 84 ± 22 89 ± 26 0.14 HDL (mg/dL) 54 ± 15 53 ± 14 55 ± 15 0.34 Medication Baseline ACEI and ARB 106 (33) 23 (31) 83 (34) 0.67 Statin 109 (34) 26 (35) 83 (34) 0.89 Follow-up ACEI and ARB 113 (36) 25 (34) 88 (36) 0.78 Statin 254 (80) 59 (80) 195 (80) 1.00
ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin II receptor blockers; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Numbers are reported as average ± standard deviation or n (%).
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Lesion Characteristics and Stent Procedure
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TABLE 2
Lesion Characteristics
All Patients Event (+) Event (−)P Lesion severity <0.0001 \* 1VD 160 (50) 23 (31) 137 (56) 2VD 84 (26) 20 (27) 64 (26) 0.003 \* 3VD or LM 73 (23) 31 (42) 42 (17) 0.01 \* High-risk plaque 175 (55) 52 (70) 123 (51) Agatston score † 314 (76–866) 471 (143–1614) 289 (63–787) PCI procedure Number of stents 2.2 ± 1.5 2.9 ± 1.9 2.0 ± 1.3 <0.0001 \* Total stent length (mm) 55.1 ± 43.3 73.2 ± 52.5 49.5 ± 38.6 <0.0001 \* Minimum diameter (mm) 2.76 ± 0.43 2.60 ± 0.39 2.80 ± 0.44 0.0006 \* SYNTAX score 12.7 ± 9.3 15.6 ± 9.8 11.8 ± 8.9 0.002 \* EuroSCORE 1.20 ± 0.65 1.25 ± 0.77 1.19 ± 0.61 0.47
LM, left main; PCI, percutaneous coronary intervention; VD, vessel disease.
Numbers are reported as average ± standard deviation or n (%).
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Predictors of Primary End Point
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TABLE 3
Cox Proportional Hazards Regression Model to Identify Predictors of Events
Variables Univariate Hazard Ratio_P_ Multivariate Hazard Ratio_P_ Age 1.01 (0.98–1.03) 0.63 Male 1.55 (0.96–2.59) 0.07 Body mass index 1.03 (0.95–1.11) 0.52 Diabetes mellitus 1.01 (0.63–1.61) 0.96 Hypertension 1.29 (0.71–2.59) 0.42 Dyslipidemia 1.29 (0.75–2.36) 0.37 Smoking status Never Reference 0.96 Ex-smoker 1.01 (0.61–1.68) 0.68 Current smoker 1.14 (0.59–2.10) Family history 0.77 (0.41–1.36) 0.38 Agatston score ≥400 2.01 (1.11–3.72) 0.02 \* High-risk plaque 2.06 (1.27–3.47) 0.003 \* Risk group Low risk † Reference 0.009 \* Reference 0.037 \* Intermediate risk † 2.17 (1.20–4.21) 0.0004 \* 1.91 (1.04–3.77) 0.009 \* High risk † 3.65 (1.80–7.61) 2.66 (1.27–5.73) Total stent length 1.01 (1.00–1.01) 0.0003 \* 1.00 (0.99–1.01) 0.31 Minimum diameter 0.34 (0.18–0.62) 0.0003 \* 0.48 (0.23–0.96) 0.037 \* SYNTAX score 1.03 (1.01–1.05) 0.007 \* 0.99 (0.16–4.64) 0.92
Data in parentheses represent 95% confidence interval.
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Secondary End Points in Different Risk Groups
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Discussion
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Conclusion
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