2023 Volume 30 Issue 5 Pages 491-501
Aim: The Achilles tendon (AT) thickening may be affected by several factors (e.g., lipid disorders or age). This study aims to determine the prevalence rate of AT thickening in patients with coronary artery disease (CAD) and investigate the correlation between AT thickening and the incidence of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI).
Methods: The clinical records of 887 patients who had undergone successful PCI and measured Achilles tendon thickness (ATT) using soft X-ray radiographs were retrospectively examined. Subjects were divided into two groups depending on the presence or absence of AT thickening. AT thickening was defined as having ATT of ＞8.0 and ＞7.5 mm in men and women, respectively. Among the two groups, the incidence of MACE was measured for a maximum of 5 years after PCI. MACE was defined as cardiovascular mortality, nonfatal myocardial infarction, or revascularization due to restenosis or the increase of stenosis in other lesions.
Results: This study found that 241 (27.2%) patients have AT thickening. Patients with AT thickening had higher low-density lipoprotein cholesterol (LDL-C) levels. In addition, the Kaplan–Meier curve with a log-rank test demonstrated that patients with AT thickening had a significantly higher incidence of MACE. Furthermore, the multivariate analysis indicated that the presence of AT thickening was independently correlated with the incidence of MACE after PCI.
Conclusion: A high percentage of patients with CAD were found to have AT thickening. In addition, the presence of AT thickening was significantly associated with a higher incidence of MACE, independent of LDL-C levels.
See editorial vol. 30: 440-442
Cardiovascular diseases, including coronary artery disease (CAD), are known to be the leading causes of morbidity and mortality worldwide; therefore, preventing cardiovascular disease is of utmost importance for extending healthy life expectancy. The relationship between lipid disorders and arteriosclerotic heart disease has been established, and many clinical studies have demonstrated that low-density lipoprotein cholesterol (LDL-C)-lowering therapy is one of the most effective strategies for reducing adverse cardiovascular events1-5). In Japan, the guidelines for secondary prevention of CAD include controlling the level of LDL-C to ＜100 mg/dL for standard patients or ＜70 mg/dL for patients with particular risk factors (e.g., acute coronary syndrome, diabetes, or familial hypercholesterolemia)6). However, residual cardiovascular risk factors can remain even in patients who meet target LDL-C levels or who have been treated sufficiently with statins7-9).
Familial hypercholesterolemia (FH) is one of the most common genetic disorders and is characterized by severely elevated LDL-C levels. According to the Japanese guidelines for the diagnosis of FH published in 2017, FH can be identified by two of the following three major indicators: (1) pretreatment serum LDL-C levels of more than 180 mg/dL, (2) family history of FH or premature CAD, or (3) tendon or skin xanthomas10). Achilles tendon xanthoma (ATX) is defined as having an Achilles tendon thickness (ATT) of ＞9 mm following soft X-ray radiography10). Furthermore, another study has demonstrated that hypercholesterolemia can cause the formation of ATX due to the deposition of cholesterol-rich materials11).
Therefore, the presence of AT thickening can be a bad sign for cardiovascular systems. A genetic study in Japan has indicated that the cutoff values of LDL-C (164 mg/dL) and ATT (8.0 mm) had the highest sensitivity and specificity in identifying patients with FH12). Another study has also demonstrated that the cutoff value of ATT is ＜9.0 mm13). In this study, AT thickening was defined as having ATT of ＞8.0 and ＞7.5 mm in men and women, respectively. The presence of AT thickening is believed to be related to the progress of arteriosclerosis and AT thickening may be one of the risk factors for CAD. Thus, this study aims to determine the prevalence rate of AT thickening in patients with CAD and to investigate the correlation between AT thickening and the incidence of cardiovascular events after percutaneous coronary intervention (PCI).
This study retrospectively examined the clinical records of 887 patients ＜75 years old who had undergone successful PCI for acute coronary syndrome (ACS) or stable angina (SA) between January 2011 and December 2019, and who had ATT measured after PCI. This study included 413 ACS cases who underwent emergent PCI for acute myocardial infarction or unstable angina and 474 cases who underwent elective PCI for SA. However, patients with the following health conditions or histories, which may independently affect their outcomes, were excluded from this study in advance: residual stenosis in major coronary artery branches (seven cases), residual heart failure of New York Heart Association class 2–4 (two cases), histories of coronary bypass surgery (seven cases), malignant tumors (two cases), renal failure needing dialysis treatment (16 cases), or hepatic damage with Child–Pugh score of more than 5 (one case). Furthermore, those who had experienced cardiovascular events within 3 months after PCI were likewise excluded to avoid the influence of the PCI procedure or subacute thrombosis (one case). This study was approved by the ethics committee of KKR Takamatsu Hospital (approval no. E194) and was performed in conformity with the Declaration of Helsinki.
ATT MeasurementThe ATT was measured using soft X-ray radiography in all patients. ATT was defined as a thickness at the widest part of the Achilles tendon on both legs. AT thickening was defined as having an ATT of ≥ 8.0 and ≥ 7.5 in men and women, respectively. However, measured data of the affected limb was excluded if patients had histories of AT injury. The measurement of soft X-ray radiography was performed by one skilled radiological technician to minimize measurement errors.
Study DesignThis study was conducted as a retrospective cohort study. Patients were starting exercise-based cardiac rehabilitation as well as receiving general lifestyle guidance and drug-taking instructions just after PCI. In addition, patients were carefully monitored with interviews and clinical examinations every 1–3 months. Furthermore, optimal medicine was prescribed by acquiring necessary information from blood tests as soon as possible. Blood samples and body weight were usually obtained in a nonfasting state. Each biomarker (e.g., blood pressure) was also checked in a visitor consultation room in the hospital of the current study. In addition, routine coronary angiography (CAG) was performed 6–8 months after PCI. In addition, treadmill exercise tests (TET) or cardiopulmonary exercise tests (CPX) were performed every 6 months. During the follow-up, CAG was conducted accordingly if relapses of some symptoms or a positive result on an exercise stress test were detected. Regarding medical treatment after PCI, lipid-lowering agents (e.g., statins or antiplatelet agents) were prescribed either before or just after PCI and continued following the judgment of the attending physicians.
Subjects were divided into two groups depending on the presence or absence of AT thickening. The baseline evaluation was performed 3 months after PCI. Demographic data including age, sex, and body mass index (BMI); the prevalence rate of hypertension, current smoking rates, and the value of LDL-C levels as directly measured using a unique surfactant of the Hitachi Chemical Diagnostics Systems Co. Ltd., (Tokyo, Japan); HDL-C, TG, and hemoglobin A1c (HbA1c) levels; the prevalence rate of diabetes, uric acid (UA) levels, and estimated glomerular filtration rate (eGFR) as calculated using the Schwartz formula; and the usage of statins, ezetimibe, or PCSK-9 inhibitor were retrospectively collected from the database. In addition, the ACS proportion was investigated. Patients were classified as having hypertension if they were prescribed oral antihypertensive drugs or had a blood pressure of ＞140/90 mmHg at an outpatient visit. Diabetes was defined as being prescribed oral antidiabetic drugs or having an HbA1c level of ≥ 6.5%.
Furthermore, the cumulative incidence of major adverse cardiac events (MACE) was investigated for a maximum of 5 years after PCI among the two groups using the Kaplan–Meier curve and a log-rank test. MACE was defined as cardiovascular mortality, nonfatal myocardial infarction, or revascularization due to restenosis or the increase of stenosis in other lesions. Cardiac death was documented as death-related myocardial infarction, congestive heart failure, or arrhythmia. Myocardial infarction was diagnosed from symptoms of myocardial ischemia, ECG changes that indicate new myocardial ischemia or necrosis, imaging evidence (e.g., new loss or abnormality of myocardial wall motion), or the increase of markers related to myocardial necrosis. Coronary stenosis was defined as ≥ 50% narrowing detected by quantitative coronary angiography. Restenosis was defined as stenosis within 5 mm of both sides of the PCI site including side branches covered by a stent (in-stent jail). In principle, PCI was performed for patients who had coronary stenosis with proven myocardial ischemia based on TET/CPX. During follow-up periods, patients who died of causes other than cardiovascular events or who enrolled in another clinical course due to other diseases were processed as censored data. Patients that could not be observed because of address removal were likewise processed as censored cases. However, patients with unscheduled CAGs without stenotic lesions continued to be observed. The MACE detail in both groups was also investigated.
Moreover, the correlation between the incidence of MACE and various risk factors including AT thickening was evaluated using the univariate and multivariate Cox proportional hazards regression model. In addition, the investigation of the cumulative incidence of MACE among the two groups was likewise conducted exclusively among patients with an LDL-C level of ＜100 mg/dL to minimize the impact of the LDL-C level. Furthermore, patients with AT thickening were divided into two groups based on LDL-C levels as follows: groups 1 (with LDL-C levels of ＜70 mg/dL) and 2 (with LDL-C levels of ≥ 70 mg/dL). The cumulative incidence of MACE for a maximum of 5 years was investigated after PCI among the above-described two groups.
Statistical AnalysisContinuous variables were expressed as the mean±standard deviation, and a p value of ＜0.05 was considered statistically significant. The two-sample t-tests and chi-square tests were used to compare the baseline characteristics of patients classified by ATT. The cumulative incidence of MACE was analyzed using the Kaplan–Meier curve and the log-rank test. In addition, the univariate and multivariate Cox proportional hazards regression analysis was performed to investigate the correlation between the incidence of MACE and coronary risk. The data was analyzed using StatMate V (Nihon 3B Scientific Inc.) and R version 4.0.2 (The R Foundation).
The average ATT in male and female patients was 7.50 mm (median ATT, 7.1 mm) and 6.86 mm (median ATT, 6.53; Fig.1A). Moreover, 241 (27.2%) had AT thickening (Fig.1B). According to sex, 212 (27.1%) and 29 (27.4%) male and female patients had AT thickening, respectively. Of these, eight female patients had ATT from 7.5 to 8.0 mm in one of their legs. In addition, eight patients had had bilateral differences of ATT due to Achilles tendon injury from AT thickening.
ATX: Achilles tendon xanthoma.
The subjects’ baseline clinical characteristics are shown in Table 1. No significant differences in age and the percentage of male patients were observed among the two groups. The BMI in the group with AT thickening was higher than the group without AT thickening. In addition, no significant differences were noted in the prevalence rate of hypertension, current smoking rate, or the percentage of patients with ACS. Furthermore, LDL-C and HbA1c levels in the group with AT thickening were higher than in the group without AT thickening. However, no significant differences in HDL-C, TG, UA, and eGFR were noted among the two groups. No differences were also observed in the usage of statin, ezetimibe, or PCSK9 inhibitor (Table 1).
| Group with AT thickening (n = 241) | Group without AT thickening (n = 646) | P Value | |
|---|---|---|---|
| Mean age (years) | 60.4±8.8 | 61.6±8.3 | 0.057 |
| Male | 212 (88.0%) | 569 (88.8%) | 0.907 |
| BMI (Kg/mm2) | 25.9±3.8 | 25.0±3.2 | ＜0.001 |
| Hypertension | 164 (68.0%) | 390 (66.4%) | 0.043 |
| Smoking | 56 (23.2%) | 154 (23.8%) | 0.656 |
| LDL-C (mg/dl) | 100.6±27.1 | 93.6±27.5 | ＜0.001 |
| HDL-C (mg/dl) | 51.4±14.8 | 51.4±13.2 | 0.984 |
| TG (mg/dl) | 166.3±92.0 | 154.5±96.4 | 0.102 |
|
HbA1c (%) (Diabetes) |
6.54±1.04 (106 (41.1%)) |
6.34±0.99 (236 (36.5%)) |
0.009 (0.244) |
| UA (mg/dl) | 5.71±1.37 | 5.83±1.27 | 0.207 |
| eGFR | 70.3±16.7 | 69.1±15.5 | 0.324 |
| Statin | 194 (80.5%) | 534 (82.7%) | 0.491 |
| Ezetimibe | 16 (6.7%) | 53 (8.2%) | 0.481 |
| PCSK9 inhibitor | 1 | 3 | 0.573 |
| ACS | 99 (41.1%) | 314 (48.6%) | 0.049 |
AT: Achilles Tendon, Data are expressed as mean＋standard deviation or number (in percentage).
ATX: Achilles Tendon Xanthoma, BMI: Body Mass Index, TG: Triglyceride, UA: Uric Acid, eGFR: estimated Glomerular Filtration Rate, ACS: Acute Coronary Syndrome
The median follow-up period was 60 months. During the follow-up period, the observation of 21 patients were discontinued for several reasons, including a change of residence (n=14), a change to another hospital due to new cancer (n=3), brain hemorrhage (n=1), or new renal failure (n=1). Two patients died of severe infection. In addition, 273 (30.8%) patients experienced MACE, including cardiac death (n=1), myocardial infarction (n=9), restenosis (n=120), and the increase of stenosis in other lesions (n=143; Table 2). The details of MACE among the two groups are also shown in Table 2. Based on this data, the cumulative incidence of MACE among the two groups was analyzed using the Kaplan–Meier method and the log-rank test. Consequently, this analysis showed that the incidence of MACE in the group with AT thickening was significantly higher than in the group without AT thickening (P＜0.001; Fig.2).
| With AT thickening (n = 241) | Without AT thickening (n = 646) | |
|---|---|---|
| Cardiac death | 1 (0.4%) | 0 (0%) |
| Myocardial infarction | 3 (1.2%) | 6 (1.3%) |
| Increase of stenosis in other coronary arteries | 57 (23.7%) | 86 (13.3%) |
| Restenosis | 46 (19.1%) | 74 (11.5%) |
| Total MACE | 107 (44.4%) | 166 (25.7%) |
AT: Achilles tendon, MACE: Major Adverse Cardiac Events, Data are expressed as number (%).
ATX: Achilles Tendon Xanthoma, MACE: Major Adverse Cardiac Events
According to the univariate and multivariate analysis in all patients using the Cox proportional hazard regression model, the occurrence of AT thickening was independently associated with the incidence of MACE after PCI (hazard ratio=1.887; 95% confidence interval, 1.511–2.434; P＜0.001; Table 3). In addition, an analysis of patients with LDL-C levels ＜100 mg/dL demonstrated that patients with AT thickening also had a significantly higher incidence of MACE compared to patients without AT thickening (Fig.3). Furthermore, patients with AT thickening whose LDL-C levels are ＜70 mg/dL had a significantly lower incidence of MACE after PCI (Fig.4).
| Univariate Analysis | Multivariate Analsis | |||||
|---|---|---|---|---|---|---|
| Hazard ratio | 95%Cl | P value | Hazard ratio | 95%Cl | P value | |
| Age | 0.997 | 0.983-1.011 | 0.722 | 1.005 | 0.989-1.021 | 0.391 |
| BMI | 1.047 | 1.012-1.083 | 0.008 | 1.018 | 0.980-1.056 | 0.365 |
| Smoking | 1.194 | 0.915-1.561 | 0.198 | 1.029 | 0.777-1.362 | 0.841 |
| LDL-C | 1.010 | 1.007-1.013 | ＜0.001 | 1.009 | 1.005-1.013 | ＜0.001 |
| HDL-C | 0.976 | 0.966-0.985 | ＜0.001 | 0.984 | 0.974-0.994 | 0.002 |
| TG | 1.002 | 1.001-1.003 | ＜0.001 | 1.001 | 0.999-1.002 | 0.355 |
| HbA1c | 1.152 | 1.040-1.278 | 0.007 | 1.094 | 0.974-1.228 | 0.129 |
| UA | 1.123 | 1.025-1.230 | 0.013 | 1.064 | 0.962-1.177 | 0.226 |
| eGFR | 0.993 | 0.985-1.000 | 0.152 | 0.994 | 0.986-1.002 | 0.152 |
| AT thickening | 1.864 | 1.461-2.378 | ＜0.001 | 1.887 | 1.511 -2.434 | ＜0.001 |
| Stalin use | 0.644 | 0.490-0.848 | 0.002 | 0.969 | 0.707-1.327 | 0.844 |
| Ezelimibe use | 0.944 | 0.585-1.524 | 0.814 | 0.912 | 0.698-1.221 | 0.243 |
CI: confidence interval, BMI: body mass index, TG: triglyseride, UA: uric acid, eGFR: estimated glomerular filtration rate, ATX: Achilles Tendon Xanthoma, AT: Achilles Tendon
AT: Achilles tendon, MACE: Major Adverse Cardiac Events
MACE: Major Adverse Cardiac Events
The present study demonstrated that a high percentage of patients with CAD were found to have AT thickening and those patients with AT thickening had a higher incidence of MACE after PCI compared to patients without AT thickening. In addition, following multivariate analysis, the presence of AT thickening was independently associated with a higher incidence of MACE after PCI.
ATX, represented as ATT of ＞9 mm, is one of the most important diagnostic criteria for heterozygous FH as defined by the Japan Atherosclerosis Society10). ATX has been observed in 100% and 82% of homozygous and heterozygous FH cases, respectively14). In general, the prevalence of homozygous FH ranges from 1/160,000 to 1/1,000,000, and the frequency of heterozygous FH has been estimated to range from 1/200 to 1/50015-17). An early FH diagnosis is critical for providing appropriate treatments and preventing early cardiovascular events and mortality18-20). In addition, previous studies have shown that a high percentage of patients with CAD, including SA and ACS, were found to have ATX21, 22). The results of this study showed that 90 (10.1%) patients had ATT of ＞9 mm.
However, little evidence shows that the ATX, defined by the traditional definition of having ATT ＞9.0 mm, is appropriate. Tada et al. demonstrated that the cutoff value of ATT is ＜9.0 mm. According to their study, the receiver operating characteristics analysis indicated that the best cutoff values of ATT were 7.6 and 7.0 mm for male and female patients, respectively. In addition, they have indicated that the ATT thresholds of 8.0/7.5 and 7.5/7.0 mm for males and females, respectively, had high sensitivities and specificities13). Referring to this study, AT thickening was defined as having ATT of ＞8.0 and ＞7.5 mm in men and women, respectively. Consequently, the present study demonstrated that 27.2%of patients with CAD had AT thickening and that the presence of AT thickening was significantly associated with a higher incidence of MACE. Therefore, this study demonstrated that having thicker ATT can indicate the progression of cardiovascular disease or adverse outcomes, regardless of FH. In addition, the AT thickening defined as ATT of ＞8.0 and ＞7.5 mm in men and women, respectively, was an independent risk factor of LDL-C levels 3 months after PCI. Thus, AT thickening may indicate patients who have already had the accumulation of LDL-C or the exacerbation of arteriosclerosis. AT thickening may be one of the expression elements of arteriosclerosis. In addition, LDL-C levels for secondary prevention of CAD patients with AT thickening should be more strictly controlled.
This study has no information on family history of FH or premature CAD, and an accurate FH diagnosis could not be established. However, Kitahara et al. reported that approximately one in three patients with ATX were diagnosed with heterozygous FH22). Furthermore, a multicenter Japanese registry demonstrated that 5.7% of ACS patients were diagnosed with heterozygous FH23). Therefore, a high percentage of patients with CAD can have heterozygous FH. A clinical study has also shown that patients with heterozygous FH are 20 times more likely to develop CAD24). However, many patients with FH may be underdiagnosed or undertreated due to a lack of awareness of FH among clinicians24), and, ethically, doing genetic testing is difficult for all patients with CAD or lipid disorders. Collecting whole family histories is also difficult. Moreover, evaluating ATX using soft X-ray radiography is very simple. Michikura et al. have also indicated that the AT ultrasonography can be useful for detecting ATX25). Thus, evaluating ATT can lead to early detection of FH in patients with CAD.
In addition, a clinical study has demonstrated that hypercholesterolemia can cause ATX formation due to the deposition of cholesterol-rich materials11). Furthermore, AT thickness is also dependent on the exposure duration of high LDL-C levels and may be underestimated in younger patients26, 27). Kitahara et al. have also demonstrated that ATX is independently associated with CAD severity despite the presence of clinically diagnosed FH28). The prevalence rate of FH among patients with AT thickening defined by this study is unclear. However, the results of the present study have indicated that the presence of AT thickening was significantly associated with the incidence of MACE after PCI, exclusively in patients who had LDL-C levels of ＜100 mg/dL. Based on these facts, the presence of AT thickening can be an indicator of high-risk patients with cardiovascular diseases. In Japan, the guidelines for secondary prevention of CAD recommend controlling the level of LDL-C to ＜100 mg/dL for standard patients. Furthermore, the guidelines recommend the level of LDL-C to be ＜70 mg/dL for high-risk patients (e.g., patients with FH)6). Patients with AT thickening set in this study are currently not recognized as high-risk patients. However, from the results of the present study, an AT thickness of ＞8.0 and ＞7.5 mm in men and women, respectively, may be one of the risk factors for the occurrence of CAD in patients ≤ 75 years old.
Several possible mechanisms by which AT thickening impacts the development of cardiovascular diseases have been suggested. As may be expected, patients with FH have been exposed to long-term high LDL-C levels. Consequently, it may be concluded that vascular endothelial cells have already been damaged. Some studies have indicated that patients with FH had thicker ATT compared with healthy controls and that ATT was positively related to LDL-C levels29, 30). In addition, LDL-C-lowering treatments using statins seem likely to lead to ATX regression. From the results obtained in the present study, LDL-C levels in patients with AT thickening were significantly higher than LDL-C levels in patients without AT thickening despite taking lipid-lowering agents (e.g., statins or ezetimibe). However, following the results from multivariate analysis, AT thickening set in the current study was independently associated with the incidence of MACE after PCI. Furthermore, among patients with LDL-C levels of ＜100 mg/dL, the incidence of MACE in those with AT thickening was significantly higher than in those without AT thickening. Accordingly, the presence of AT thickening has been recognized to indicate a high-risk patient who needs stricter LDL-C level control.
From another point of view, patients with heterozygous FH may have unknown factors affecting the progress of arteriosclerosis. A clinical study indicated that patients with FH have higher lipoprotein(a) levels than the normal population31). Lipoprotein(a) may be a risk factor in FH patients, but little evidence was noted to indicate that lowering lipoprotein(a) can lead to preventing CAD in patients with FH. The results of the present study showed that, among patients who had AT thickening, those with LDL-C levels of ＜70 mg/dL had a significantly lower incidence of MACE after PCI compared to those with LDL-C levels of ≥ 70 mg/dL. The Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017 has also suggested maintaining LDL-C levels to ＜70 mg/dL in secondary prevention6). Accordingly, lowering LDL-C levels to ＜70 mg/dL is believed to be the most important strategy for preventing cardiovascular diseases in patients with ATX or FH.
Many clinical studies have demonstrated that LDL-C-lowering therapy is one of the most useful strategies for reducing adverse cardiovascular events1-5). The JAS guidelines for secondary prevention of CAD include controlling the level of LDL-C to ＜70 mg/dL for patients with particular risk factors (e.g., ACS, diabetes, or FH)6). However, in the present study, average LDL-C levels were 100.6 and 93.6 mg/dL with standard deviations of 27.1 and 27.5 in patients with and without AT thickening, respectively. In addition, the percentage of subjects who achieved the target LDL-C value in all patients was 59.4% when the target LDL-C value was ＜100 mg/dL regardless of the use of statin or ezetimibe. Furthermore, the percentage of subjects who achieved target LDL-C value in all patients was 15.1%, when the target LDL-C value was ＜70 mg/dL. A proprotein convertase subtilisin-kexin type-9 (PCSK-9) inhibitor is one option for lowering LDL-C levels in patients who did not achieve the guideline-recommended target LDL-C value. The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Patients with Elevated Risk (FOURIER) trial has shown that, when added to statin therapy, the PCSK-9 monoclonal antibody evolocumab lowered LDL-C by 59% and significantly reduced the risk of cardiovascular events in patients with stable atherosclerotic cardiovascular disease, the majority of whom had a history of myocardial infarction32). In addition, the subanalysis from the FOURIER trial has demonstrated that LDL-C-lowering therapy using evolocumab was useful in patients with recent myocardial infarction, multiple prior myocardial infarctions, or residual multivessel CAD33). Furthermore, the Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab trial demonstrated that the PCSK-9 inhibitor alirocumab can reduce cardiovascular and cerebrovascular events in patients with recent ACS34). As described above, PCSK9 inhibitors can be useful for patients with ATX as well as patients with FH. In the present study, very few patients were taking the PCSK-9 inhibitor, and the correlation between AT thickening and PCSK9 inhibitors could not be indicated. Further studies will be necessary to confirm the effect of the PCSK-9 inhibitors on patients with AT thickening.
In addition, clinical studies have demonstrated that comprehensive cardiac rehabilitation (CCR) can decrease LDL-C levels and improve outcomes in patients with high-risk cardiovascular diseases35, 36). CCR is also believed as essential for maintaining LDL-C levels to ＜70 mg/dL in secondary prevention, regardless of the use of PCSK-9 inhibitors. In the present study, the results obtained from the baseline data 3 months after PCI would likely be unsatisfactory for secondary prevention. However, the efficient execution of CCR may affect the incidence of MACE after PCI because all subjects were attending exercise-based cardiac rehabilitation programs and accepting lifestyle guidance as well as drug-taking instructions soon after PCI. Therefore, carrying on CCR and maintaining LDL-C levels of ＜70 mg/dL is important in preventing cardiovascular disease in patients with AT thickening.
The greatest limitation in this study was the insufficient number of patients, which resulted in unevenness in the number of patients and associated characteristics (e.g., BMI, LDL-C levels, and HbA1c) among the two groups. Advanced elderly patients (＞75 years old) were also excluded from this study in advance because early recognition of AT thickening is believed to be important for predicting the occurrence of cardiovascular diseases, especially among young patients. In addition, AT thickening, which is defined in the current study as having ATT of ＞8.0 and 7.5 mm in men and women, respectively, is not established as a global standard. However, following the results of the present study, the set AT thickening seems likely to be useful for predicting the occurrence of cardiovascular events after PCI. Moreover, the incidence of MACE was relatively high because stent jail stenosis or occlusion into restenosis was included, and the increase of stenosis in other lesions as MACE was defined. However, the present study has indicated that the presence of AT thickening may be associated with the occurrence of restenosis as well as the increase of stenosis in other lesions.
Furthermore, the present study is a retrospective analysis. The patients’ clinical courses before PCI or the change of clinical data during follow-up could not be evaluated. As expected, the lipid profiles (e.g., LDL-C levels) may be affected during follow-up by subsequent environmental changes (e.g., diet, exercise habits, and the addition or discontinuation of some medicines) which would affect lipid metabolism. However, the patients underwent sufficient CCR including medical treatment soon after PCI, and their lifestyle habits, medications, or serum lipid levels remained during follow-up. It is believed that the data 3 months after PCI may be more stable as baseline data and more suitable for evaluating the relationship between some indicators and the incidence of cardiovascular diseases. Thus, in the present study, the data of baseline clinical characteristics were evaluated 3 months after PCI.
The aforementioned factors can affect the outcome after PCI, but little doubt exists that evaluating the presence of AT thickening was one of the most important factors in the follow-up after PCI. Moving forward, further studies will be necessary to confirm these findings.
The present study demonstrated that a high percentage of patients with CAD were found to have AT thickening. In addition, the presence of AT thickening may be significantly associated with a higher incidence of MACE.
No conflict of interest and no financial support from any institute.
The ethical committee of KKR Takamatsu hospital (approval No.: E194)
The authors would like to thank all participant and medical staff at KKR Takamatsu Hospital.
The deidentified participant data will not be shared
