Abstract
Background:
Peripheral arterial disease shares common pathophysiological mechanisms with coronary artery disease (CAD), including inflammation and atherosclerosis. Carbohydrate antigen 125 (CA-125), previously known as a tumor marker, has been suggested to be elevated in patients with heart failure and CAD.
Aim:
The aim of this study was to assess the correlation of serum tumor marker carbohydrate antigen 125 with ankle–brachial index (ABI) in patients with CAD.
Materials and Methods:
A prospective study was conducted on 60 CAD patients. Based on ABI, they were grouped into low ABI (≤0.9) and normal ABI (1–1.4). Serum CA-125 and high-sensitivity C-reactive protein (hs-CRP) were measured, and transthoracic echocardiographic parameters were evaluated.
Results:
CA-125 was significantly higher in patients with low ABI compared to those with normal ABI (13.17 ± 4.48 vs. 10.03 ± 3.18 U/ml, P = 0.003). CA-125 was negatively correlated with ABI (r = −0.887, P < 0.001) and positively with hs-CRP (r = 0.696, P < 0.001).
Conclusion:
Serum CA-125 is a readily available biomarker that may have utility as a supplementary indicator of atherosclerotic burden and vascular risk in patients with CAD.
Keywords: Ankle–brachial index, carbohydrate antigen 125, coronary artery disease, peripheral arterial disease
INTRODUCTION
The ankle–brachial index (ABI) is a simple, low-cost, and noninvasive test used to diagnose peripheral artery disease (PAD). The ABI is the ratio of the patient’s systolic blood pressure at the ankle to the systolic blood pressure in the arm.[1]
CA-125, expressed on multiple epithelia, hydrates and lubricates surfaces, protecting against mechanical stress.[2]
PAD and coronary artery disease (CAD) share pathophysiologic mechanisms and risk factors. Evaluating CA-125 levels in PAD patients may provide additional clinical insight.[3]
The work aimed to assess the correlation of serum tumor marker carbohydrate antigen 125 with ABI in patients with CAD.
MATERIALS AND METHODS
This is a prospective study that included 60 patients with CAD and was performed in the Cardiovascular Disease Center in Menoufia University Hospital in the period from January 2024 to September 2024. This is a prospective study that included 60 patients, aged > 40 years old, both sexes, with CAD were diagnosed by invasive coronary angiography, performed in Cardiovascular Disease Center in Menoufia University Hospital in the period from January 2024 to September 2024.
The cases were divided into two groups according to ABI: Group I, which included 30 patients with PAD (low ABI ≤0.9) and Group II, which included 30 patients without PAD (normal ABI 1–1.40).
The cases with the following criteria were excluded: heart failure with reduced left ventricular ejection fraction (LVEF <40%), acute coronary syndrome, liver dysfunction, chronic obstructive pulmonary disease, acute renal failure, aortic dissection, malignant tumor, acute and chronic infection, pregnancy, and ascites.
The study was conducted in accordance with the Helsinki Standards as revised in 2013.[4] The study was conducted after obtaining approval from the local ethics committee, Faculty of Medicine, Menoufia University (IRB Number: 4/2022 CARDIO).
Study tools
A complete history was obtained from the included cases, with stress on comorbid conditions and associated risk factors. General examination and local cardiac examination was performed to detect and cardiac changes.
Laboratory analysis included the measurement of serum carbohydrate antigen 125 (CA-125). Blood samples were collected using standard sampling tubes, with serum separated and analyzed within 2 hours. Samples remain stable for up to 5 days when stored at 2–8 °C. Serum CA-125 levels were determined using an electrochemiluminescence immunoassay, and the analyzer automatically calculated the concentration in U/mL. The normal reference range was up to 35 U/mL.[5]
High-sensitivity C-reactive protein (hs-CRP) was measured by an automatic immune analyzer; the American Heart Association and Centers for Disease Control and Prevention guidelines recommended the following cut points for risk determination as low risk <1 mg/l, intermediate risk = 1–3 mg/l, and high risk >3 mg/l.[6]
Lipid profile (triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol level) was tested by an automatic biochemistry analyzer.
Alanine aminotransferase, aspartate aminotransferase, and creatinine were tested by an automatic biochemistry analyzer. Complete blood count was measured by an automatic hematology analyzer.
The ABI was measured, and the results were reported as follows: normal (ABI of 1–1.40) and low ABI ≤0.9.[7]
For measuring the ABI, the following equipment was used: a handheld continuous-wave Doppler probe, ultrasonic gel, and a sphygmomanometer with a blood pressure cuff, with the bladder width corresponding to 40% of the limb circumference. Examinations were performed with the patient in the supine position and in a warm environment to enhance comfort and ensure accuracy.[1]
The blood pressure cuff was placed on the patient’s arm, palpating their brachial pulse. Gel was applied to the pulse site, and a Doppler signal was obtained. The cuff was inflated to 20 mmHg above the cessation of brachial–artery flow and then deflated to note the systolic value. The procedure was repeated in the other arm and then placed above the ankle on the right or left leg. The dorsalis pedis artery was measured, and a Doppler probe was placed on the palpable dorsalis pedis pulse or the site producing the best arterial Doppler signal. The procedure was repeated for the posterior tibial artery and the contralateral leg. The ABI was calculated by dividing the systolic blood pressure in the ankle by the systolic blood pressure in the arm; the higher brachial systolic pressure was usually chosen for calculation. The higher of the systolic pressures from the dorsalis pedis or posterior tibial artery was used to determine the ABI.[1]
Transthoracic echocardiography was performed on all patients using Philips HD11 XE ultrasound equipped with 4 MHz transducer. Images were obtained while the patient was in left decubitus position, and an electrocardiogram (ECG) was connected to define the timing of cardiac cycle events. All patients were subjected to assessment of wall motion abnormality, detailed conventional 2D, M-mode, and Doppler echocardiographic examinations using standard parasternal and apical views following the recommendations of the American Society of Echocardiography (ASE); all measurements were taken on three consecutive beats, and the mean values were used.[8]
Statistical analysis
The data collected were coded, processed, and analyzed with the Statistical Package for the Social Sciences (SPSS) version 26 for Windows® (IBM, SPSS Inc., Chicago, IL, USA). Qualitative data were shown as number (frequency) and percentages. The Chi-square test (Monte Carlo test or Fisher’s exact test as a correction) made the comparison between the groups. The Kolmogorov–Smirnov test tested quantitative data for normality. Parametric data were shown as mean ± standard deviation (SD). To compare the two groups with normally distributed quantitative variables, an independent samples t-test was used, and a Mann–Whitney U-test was used if the data were abnormally distributed. Pearson’s correlation coefficient was used to assess the correlation between two parametric quantitative variables. Linear regression analysis was used to assess the equation for prediction between one dependent quantitative variable and one or more quantitative predictors. Univariate and multivariate logistic regression analyses were used to test dependent and independent risk predictors of a binary categorical outcome, respectively. For all tests, P < 0.05 was considered statistically significant.
RESULTS
The study was conducted on 60 patients with CAD in the period from January 2024 to September 2024. The study was performed in the Cardiovascular Disease Center of Menoufia University Hospital which was divided into two groups: Group I – 30 patients with low ABI ≤ 0.9. Group II – 30 patients with normal ABI 1–1.40.
The mean age in Group I was 58.37 ± 3.59 years, while in Group II, the mean age was 56.20 ± 4.27 years. Male gender represented 60% in Group I, while it represented 56.7% in Group II. The mean body mass index (BMI) in Group I was 28.71 ± 2.46 versus 27.49 ± 2.66 in Group II, so by comparing the two groups regarding age, gender, and BMI. There was a statistically significant difference between the two groups regarding age (P < 0.05), and there was no significant difference regarding sex and BMI.
Regarding risk factors, we compared the two groups and found that there was no significant difference regarding smoking and dyslipidemia, but there was a statistically significant difference regarding diabetes mellitus (DM) and hypertension as DM represented 63.3% in Group I versus 36.7% in Group II (P < 0.05), and hypertension represented 70.0% in Group I versus 43.3% in Group II (P < 0.05) [Table 1].
Table 1.
Comparison between the two studied groups according to demographic data and risk factors
| Group I (ABI ≤0.9) (n=30) | Group I (ABI 1–1.40) (n=30) | P | |
|---|---|---|---|
| Age (years) | 58.37±3.59 | 56.20±4.27 | 0.038* |
| Sex | |||
| Male | 18 (60.0) | 17 (56.7) | 0.793 |
| Female | 12 (40.0) | 13 (43.3) | |
| BMI (kg/m2) | 28.71±2.46 | 27.49±2.66 | 0.069 |
| Risk factors | |||
| HTN | 21 (70.0) | 13 (43.3) | 0.037* |
| DM | 19 (63.3) | 11 (36.7) | 0.039* |
| Smoker | 10 (33.3) | 15 (50.0) | 0.190 |
| Dyslipidemia | 14 (46.7) | 13 (43.3) | 0.795 |
*Significant P<0.05. Data are presented as mean±SD or frequency (%). BMI=Body mass index, HTN=Hypertension, DM=Diabetes mellitus, SD=Standard deviation, ABI=Ankle–brachial index
Regarding laboratory data, there was no significant difference between the two groups regarding creatinine, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, and triglycerides, but there was a significant difference regarding hs-CRP and CA-125 levels between the two groups (P < 0.05).
Regarding echocardiographic data, there was no significant difference between the two groups regarding left ventricular internal dimension in diastole (LVIDd), left ventricular internal dimension in systole (LVIDs), interventricular septum end-diastole thickness (IVSd), posterior wall thickness at end-diastole (PWd), and left atrium (LA) diameter, but showed that the mean LVEF in Group I was 60.03 ± 3.93 versus 63.23 ± 3.11 in Group II, so there was a significant difference between the two groups regarding LVEF (P = 0.001) [Table 2].
Table 2.
Comparison between the two studied groups according to laboratory data and echocardiographic parameters
| Group I (ABI ≤0.9) (n=30) | Group I (ABI 1–1.40) (n=30) | P | |
|---|---|---|---|
| LDL | 148.5±27.87 | 139.2±25.97 | 0.183 |
| HDL | 40.40±3.49 | 39.10±2.90 | 0.122 |
| Total cholesterol | 216.2±34.43 | 200.9±29.47 | 0.068 |
| Triglycerides | 124.7±23.60 | 120.1±17.66 | 0.396 |
| Creatinine | 1.13±0.18 | 1.03±0.22 | 0.074 |
| Hs-CRP | 1.59±0.57 | 1.27±0.50 | 0.021* |
| CA-125 | 13.17±4.48 | 10.03±3.18 | 0.003* |
| LVIDd | 48.70±4.65 | 50.53±4.58 | 0.129 |
| LVIDs | 31.77±3.95 | 32.43±3.68 | 0.501 |
| IVSd | 8.10±0.99 | 8.0±1.08 | 0.711 |
| PWd | 8.10±0.99 | 8.0±1.08 | 0.711 |
| LA diameter | 34.43±2.40 | 34.47±2.39 | 0.957 |
| LVEF% | 60.03±3.93 | 63.23±3.11 | 0.001* |
*Significant P<0.05. Data are presented as mean±SD or frequency (%). LDL=Low-density lipoprotein, HDL=High-density lipoprotein, Hs-CRP=High-sensitivity C-reactive protein, CA-125=Carbohydrate antigen 125, LVIDd=Left ventricular internal dimension diastole, LVIDs=Left ventricular internal dimension systole, IVSd=Interventricular septum end-diastole thickness, PWd=Posterior wall thickness at end-diastole, LA=Left atrium, LVEF=Left ventricular ejection fraction, SD=Standard deviation, ABI=Ankle–brachial index
Correlation analysis in Group 1 [Table 3] demonstrated that CA-125 was negatively correlated with ABI (r = −0.887, P < 0.001), indicating that lower ABI values were associated with higher CA-125 levels. In contrast, CA-125 showed a positive correlation with hs-CRP (r = 0.696, P < 0.001), such that increases in hs-CRP were accompanied by increases in CA-125 [Figure 1].
Table 3.
Correlation between carbohydrate antigen 125 and different parameters in Group 1 (n=30)
| CA-125 |
||
|---|---|---|
| R | P | |
| Age (years) | 0.161 | 0.396 |
| BMI (kg/m2) | 0.063 | 0.742 |
| Creatinine | 0.212 | 0.260 |
| Hs-CRP | 0.696 | <0.001** |
| LDL | 0.090 | 0.638 |
| HDL | −0.278 | 0.137 |
| Total cholesterol | 0.026 | 0.890 |
| Triglycerides | 0.224 | 0.235 |
| ABI | −0.887 | <0.001** |
| LVEF% | −0.315 | 0.090 |
| LVIDd | −0.100 | 0.598 |
| LVIDs | −0.217 | 0.250 |
| IVSd | −0.197 | 0.296 |
| PWd | −0.197 | 0.296 |
| LA | −0.288 | 0.123 |
**Significant P value <0.001. R=Pearson coefficients. BMI=Body mass index, ABI=Ankle–brachial index, Hs-CRP=High-sensitivity C-reactive protein, LVEF=Left ventricular ejection fraction, LDL=Low-density lipoprotein, HDL=High-density lipoprotein, LVIDd=Left ventricular internal dimension diastole, LVIDs=Left ventricular internal dimension systole, IVSd=Interventricular septum end-diastole thickness, PWd=Posterior wall thickness at end-diastole, LA=Left atrium, CA-125=Carbohydrate antigen 125
Figure 1.
Correlation between carbohydrate antigen 125 and (a) ankle–brachial index and (b) high-sensitivity C-reactive protein in Group I. Hs-CRP = High-sensitivity C-reactive protein, CA-125 = Carbohydrate antigen 125, ABI = Ankle–brachial index
Univariate regression analysis of parameters affecting serum CA-125 revealed that hs-CRP was significantly positively associated with CA-125, whereas ABI was significantly negatively associated with CA-125 (P < 0.05). In multivariable regression analysis, it was found that both Hs-CRP and ABI are significantly independent factors affecting CA-125 (P < 0.05) [Table 4].
Table 4.
Univariate and multivariate linear regression analysis for the parameters affecting carbohydrate antigen 125 in Group I (n=30)
| Univariate |
Multivariate# |
|||
|---|---|---|---|---|
| P | B (LL – UL 95% CI) | P | B (LL – UL 95% CI) | |
| Age (years) | 0.396 | 0.201 (−0.277–0.678) | ||
| BMI (kg/m2) | 0.742 | 0.114 (−0.590–0.819) | ||
| HTN | 0.292 | −1.911 (−5.560–1.738) | ||
| DM | 0.178 | 2.360 (−1.142–5.862) | ||
| Creatinine | 0.260 | 5.434 (−4.250–15.123) | ||
| Hs-CRP | <0.001* | 5.459 (3.276–7.642) | 0.005* | 2.217 (0.717–3.717) |
| LDL | 0.137 | −0.357 (−0.834–0.121) | ||
| HDL | 0.638 | 0.014 (−0.048–0.076) | ||
| Total cholesterol | 0.890 | 0.003 (−0.047–0.054) | ||
| Triglycerides | 0.235 | 0.042 (−0.029–0.114) | ||
| ABI | <0.001* | −33.422 (−40.145–−26.698) | <0.001* | −27.376 (−34.574–−20.177) |
| EF% | 0.090 | −0.359 (−0.779–0.060) | ||
| LVIDd | −0.097 | 0.598 (−0.467–0.274) | ||
| LVIDs | 0.250 | −0.246 (−0.676–0.183) | ||
| IVSd | 0.296 | −0.889 (−2.599–0.821) | ||
| PWd | 0.296 | −0.889 (−2.599–0.821) | ||
| LA | 0.123 | −0.537 (−1.229–0.154) | ||
#All variables with P<0.05 was included in the multivariate. *Significant P<0.05. BMI=Body mass index, ABI=Ankle–brachial index, Hs-CRP=High-sensitivity C-reactive protein, LDL=Low-density lipoprotein, HDL=High-density lipoprotein, LVIDd=Left ventricular internal dimension diastole, LVIDs=Left ventricular internal dimension systole, IVSd=Interventricular septum end-diastole thickness, PWd=Posterior wall thickness at end-diastole, LA=Left atrium, HTN=Hypertension, DM=Diabetes mellitus, CI: Confidence interval, LL=Lower limit, UL=Upper limit, EF=Ejection fraction
DISCUSSION
The prospective study was conducted on 60 patients with CAD in the period from January 2024 to September 2024. The study was performed in the Cardiovascular Disease Center of Menoufia University Hospital, which was divided into two groups: Group I: 30 patients with low ABI ≤0.9. Group II: 30 patients with normal ABI 1–1.40. This is a prospective study that included 60 patients, aged > 40 years old, both sexes, with CAD were diagnosed by invasive coronary angiography, performed in Cardiovascular Disease Center in Menoufia University Hospital in the period from January 2024 to September 2024.
The study compared the two groups based on demographic data, revealing a statistically significant difference in age, with Group I exhibiting a higher mean age. No significant differences were observed between the groups in terms of gender distribution or BMI.
Our results were supported by Fung et al.[9], who reported that increasing age was strongly associated with PAD, whereas no significant associations were found with gender or BMI. Savji et al.[10] demonstrated the striking association between increasing age and prevalence of PAD.
On comparison of risk factors between the two groups, no statistically significant differences were observed in the prevalence of smoking or dyslipidemia. In contrast, DM and hypertension were significantly more prevalent in Group I, indicating a higher burden of these comorbidities in this group, which was in concordance with Jude et al.[11] who aimed to quantify the distribution of peripheral arterial disease in the diabetic and nondiabetic population attending for angiography and to compare severity and outcome between both the groups of patients. The authors showed that diabetic patients have worse peripheral arterial disease and a poorer outcome than nondiabetic patients. Soyoye et al.[12] demonstrated that DM remains a major risk factor for PAD, with patients with DM having more than a two-fold higher prevalence of PAD compared with the general population.
According the guidelines, hypertension and DM are major risk factors for PAD.[2,13]
Our echocardiographic evaluation demonstrated no statistically significant differences between the two groups in terms of left ventricular internal dimension in diastole and systole (LVIDd, LVIDs), IVSd, PWd, or LA diameter. However, a statistically significant difference was observed in LVEF, which was notably lower in Group I. This finding is consistent with the results of Rizvi et al.[14] reported a strong positive correlation between mean LVEF and ABI values.
Laboratory investigations revealed no statistically significant differences between the two groups in terms of serum creatinine, LDL, HDL, total cholesterol, or triglyceride levels. However, hs-CRP levels were significantly elevated in Group I that was in concordance with McDermott et al.[15] reported an association between elevated serum hs-CRP and low ABI <0.9. Ibaram.[16] systematically reviewed 17 studies investigating the role of CRP and hs-CRP as biomarkers in PAD. These studies demonstrated a strong association between elevated hs-CRP levels and PAD.
Our study demonstrated a significant elevation in serum CA-125 levels in Group I compared to Group II, which is consistent with the findings of Sang et al.[17], who analyzed 518 patients with CAD to evaluate the association between serum CA-125 and carotid intima-media thickness (cIMT). This study showed that CA-125 concentrations were significantly higher in CAD patients with early carotid atherosclerosis than in those without. These findings support a positive correlation between serum CA-125 levels and cIMT, suggesting a potential link between CA-125 and subclinical atherosclerosis in CAD patients.
Correlation analysis in Group 1 showed that CA-125 was negatively correlated with ABI, indicating that lower ABI values were associated with higher CA-125 levels. In contrast, CA-125 was positively correlated with hs-CRP, such that increases in hs-CRP were accompanied by increases in CA-125.
By assessing univariate regression analysis for parameters affecting serum CA-125, it was found that hs-CRP is significantly positively associated with CA-125, while ABI is significantly negatively associated with CA-125.
By assessing multivariable regression analysis, it was found that both hs-CRP and ABI are significantly independent factors affecting CA-125.
Our findings align with the study conducted by Sang et al.[17] showed that serum CA-125 concentrations were increased in patients with early carotid atherosclerosis compared with patients without early carotid atherosclerosis in CAD patients, so there was a positive correlation between serum CA-125 and carotid atherosclerosis in CAD patients and also showed a positive correlation between serum CA-125 and hs-CRP. Bulska-Będkowska et al.[18] reported that the level of CA-125 correlated positively with the hs-CRP. This study was the first one to analyze a large group of Caucasian women.
Serum CA-125 concentrations were related to inflammatory cytokines, such as interleukin-6 (IL-6), IL-1, and tumor necrosis factor-α, as demonstrated by Turgut et al.[19] and Huang et al.[20] Increased CA-125 levels may be due to the activation of inflammatory cytokines in the early stages of atherosclerosis that corroborated by Tousoulis et al.[21] Showed that inflammatory cytokines were associated with atherosclerosis, which is consistent with the findings of Rong et al.[22] and Li et al.[23], who reported increased serum CA-125 concentrations in patients with CAD.
Serum CA-125 may be a marker for subclinical atherosclerosis in patients with CAD. However, the mechanism underlying the correlation between serum CA-125 levels and ABI remains unclear, although atherosclerosis and inflammation may contribute to this relationship.
Therefore, we found that serum CA-125 may be used as a supplementary indicator of atherosclerotic burden and vascular risk in patients with CAD.
Further studies are needed to confirm our results, as there were some limitations to our study, including a limited number of patients and a lack of prognostic value.
CONCLUSION
Serum CA-125 is a readily available biomarker that may have utility as a supplementary indicator of atherosclerotic burden and vascular risk in patients with CAD.
Ethical statement
The study was reviewed by Institutional Review Board of Menoufia University (IRB Number: 4/2022 CARDIO).
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
REFERENCES
- 1.Aboyans V, Criqui MH, Abraham P, Allison MA, Creager MA, Diehm C, et al. Measurement and interpretation of the ankle-brachial index: A scientific statement from the American Heart Association. Circulation. 2012;126:2890–909. doi: 10.1161/CIR.0b013e318276fbcb. [DOI] [PubMed] [Google Scholar]
- 2.Bates KJ, Moore MM, Cibotti-Sun M. 2024 lower extremity peripheral artery disease guideline-at-a-glance. J Am Coll Cardiol. 2024;83:2605–9. doi: 10.1016/j.jacc.2024.04.003. [DOI] [PubMed] [Google Scholar]
- 3.D’Aloia A, Faggiano P, Aurigemma G, Bontempi L, Ruggeri G, Metra M, et al. Serum levels of carbohydrate antigen 125 in patients with chronic heart failure: Relation to clinical severity, hemodynamic and Doppler echocardiographic abnormalities, and short-term prognosis. J Am Coll Cardiol. 2003;41:1805–11. doi: 10.1016/s0735-1097(03)00311-5. [DOI] [PubMed] [Google Scholar]
- 4.World Medical Association. World Medical Association declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–4. doi: 10.1001/jama.2013.281053. [DOI] [PubMed] [Google Scholar]
- 5.Yoo SM, Jeon YM, Heo SY. Electrochemiluminescence systems for the detection of biomarkers: Strategical and technological advances. Biosensors (Basel) 2022;12:738. doi: 10.3390/bios12090738. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: Application to clinical and public health practice: A statement for healthcare professionals from the centers for disease control and prevention and the American Heart Association. Circulation. 2003;107:499–511. doi: 10.1161/01.cir.0000052939.59093.45. [DOI] [PubMed] [Google Scholar]
- 7.Chaudru S, de Müllenheim PY, Le Faucheur A, Kaladji A, Jaquinandi V, Mahé G. Training to perform ankle-brachial index: Systematic review and perspectives to improve teaching and learning. Eur J Vasc Endovasc Surg. 2016;51:240–7. doi: 10.1016/j.ejvs.2015.09.005. [DOI] [PubMed] [Google Scholar]
- 8.Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1–39.e14. doi: 10.1016/j.echo.2014.10.003. [DOI] [PubMed] [Google Scholar]
- 9.Fung ET, Wilson AM, Zhang F, Harris N, Edwards KA, Olin JW, et al. A biomarker panel for peripheral arterial disease. Vasc Med. 2008;13:217–24. doi: 10.1177/1358863X08089276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Savji N, Rockman CB, Skolnick AH, Guo Y, Adelman MA, Riles T, et al. Association between advanced age and vascular disease in different arterial territories: A population database of over 3.6 million subjects. J Am Coll Cardiol. 2013;61:1736–43. doi: 10.1016/j.jacc.2013.01.054. [DOI] [PubMed] [Google Scholar]
- 11.Jude EB, Oyibo SO, Chalmers N, Boulton AJ. Peripheral arterial disease in diabetic and nondiabetic patients: A comparison of severity and outcome. Diabetes Care. 2001;24:1433–7. doi: 10.2337/diacare.24.8.1433. [DOI] [PubMed] [Google Scholar]
- 12.Soyoye DO, Abiodun OO, Ikem RT, Kolawole BA, Akintomide AO. Diabetes and peripheral artery disease: A review. World J Diabetes. 2021;12:827–38. doi: 10.4239/wjd.v12.i6.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Mazzolai L, Teixido-Tura G, Lanzi S, Boc V, Bossone E, Brodmann M, et al. 2024 ESC guidelines for the management of peripheral arterial and aortic diseases. Eur Heart J. 2024;45:3538–700. doi: 10.1093/eurheartj/ehae179. [DOI] [PubMed] [Google Scholar]
- 14.Rizvi S, Kamran H, Salciccioli L, Saiful F, Lafferty J, Lazar JM. Relation of the ankle brachial index to left ventricular ejection fraction. Am J Cardiol. 2010;105:129–32. doi: 10.1016/j.amjcard.2009.08.664. [DOI] [PubMed] [Google Scholar]
- 15.McDermott MM, Green D, Greenland P, Liu K, Criqui MH, Chan C, et al. Relation of levels of hemostatic factors and inflammatory markers to the ankle brachial index. Am J Cardiol. 2003;92:194–9. doi: 10.1016/s0002-9149(03)00537-x. [DOI] [PubMed] [Google Scholar]
- 16.Ibaram RS. Role of C-reactive protein in peripheral arterial. IJIRMS. 2018;30:17–35. [Google Scholar]
- 17.Sang GY, Chen ZY, Meng CR, Tian T, Zhang ZX. Serum tumor marker carbohydrate antigen 125 levels and carotid atherosclerosis in patients with coronary artery disease. Open Med (Wars) 2018;13:534–8. doi: 10.1515/med-2018-0078. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Bulska-Będkowska W, Chełmecka E, Owczarek AJ, Mizia-Stec K, Witek A, Szybalska A, et al. CA125 as a marker of heart failure in the older women: Population-based analysis. J Clin Med. 2019;8:607. doi: 10.3390/jcm8050607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Turgut O, Tandogan I, Yilmaz MB, Gul I, Zorlu A. CA125 in heart failure: Implications for immunoinflammatory activity. Int J Cardiol. 2011;146:99–100. doi: 10.1016/j.ijcard.2010.05.077. [DOI] [PubMed] [Google Scholar]
- 20.Huang F, Chen J, Liu Y, Zhang K, Wang J, Huang H. New mechanism of elevated CA125 in heart failure: The mechanical stress and inflammatory stimuli initiate CA125 synthesis. Med Hypotheses. 2012;79:381–3. doi: 10.1016/j.mehy.2012.05.042. [DOI] [PubMed] [Google Scholar]
- 21.Tousoulis D, Oikonomou E, Economou EK, Crea F, Kaski JC. Inflammatory cytokines in atherosclerosis: Current therapeutic approaches. Eur Heart J. 2016;37:1723–32. doi: 10.1093/eurheartj/ehv759. [DOI] [PubMed] [Google Scholar]
- 22.Rong X, Yunke Z, Guoping L, Zhenyue C. Clinical and prognostic value of elevated CA125 levels in patients with coronary heart disease. Herz. 2015;40:690–4. doi: 10.1007/s00059-014-4109-y. [DOI] [PubMed] [Google Scholar]
- 23.Li X, He M, Zhu J, Yao P, Li X, Yuan J, et al. Higher carbohydrate antigen 125 levels are associated with increased risk of coronary heart disease in elderly Chinese: A population-based case-control study. PLoS One. 2013;8:e81328. doi: 10.1371/journal.pone.0081328. [DOI] [PMC free article] [PubMed] [Google Scholar]