C-reactive protein to albumin ratio provides important long-term prognostic information in patients undergoing endovascular abdominal aortic repair

Abstract

Background

The prognostic value of C-reactive protein/albumin ratio (CAR) is of import in cardiovascular diseases. Our aim was to evaluate the impact of the CAR in patients with asymptomatic abdominal aortic aneurysm (AAA) undergoing endovascular aneurysm repair (EVAR).

Material and Method

We retrospectively evaluated 127 consecutive patients who underwent technically successful elective EVAR procedure between December 2014 and September 2020. The optimal CAR cut-off value was determined by using receiver operating characteristic (ROC) curve analysis. Based on the cut-off value, we investigated the association of CAR with long-term all-cause mortality.

Results

32 (25.1%) of the patients experienced all-cause mortality during a mean 32.7 ± 21.7 months’ follow-up. In the group with mortality, CAR was significantly higher than in the survivor group (4.63 (2.60–11.88) versus 1.63 (0.72–3.24), p < 0.001). Kaplan–Meier curves showed a higher incidence of all-cause mortality in patients with high CAR compared to patients with low CAR (log-rank test, p < 0.001). Multivariable Cox regression analysis revealed that glucose ≥ 110 mg/dL (HR: 2.740; 95% CI: 1.354–5.542; p = 0.005), creatinine ≥ 0.99 mg/dL (HR: 2.957, 95% CI: 1.282–6.819, p = 0.011) and CAR > 2.05 (HR: 8.190, 95% CI: 1.899–35.320, p = 0.005) were the independent predictors of mortality.

Conclusion

CAR was associated with a significant increase in postoperative long-term mortality in patients who underwent EVAR. Preoperatively calculated CAR can be used as an important prognostic factor.

Keywords

Abdominal aortic aneurysm endovascular aneurysm repair CAR

Introduction

Abdominal aortic aneurysm (AAA) is defined as a localized enlargement of the abdominal aortic diameter exceeding 3 cm or 1.5 times the normal diameter¹ Since its frequency increases with age, it also includes many morbidity factors.^2,3 These aneurysms have been reported in 12% of men and 5.2% of women between the ages of 74–84³ In terms of intervention, the treatment of AAA consists of two main approaches: open surgical repair (OSR) and endovascular aneurysm repair (EVAR).

With the technological developments and increasing experience in recent years, EVAR is the preferred method in anatomically suitable patients due to less blood transfusion requirement, lower early mortality rates, shorter hospital stay, and better patient comfort when compared to conventional surgery.⁴ However, long-term survival in randomized trials trends slightly in favor of OSR relative to EVAR.⁵ This situation increases the importance of determining prognostic factors that will predict short- and long-term results in patients undergoing EVAR.

Highly sensitive C-reactive protein (CRP) is one of the most specific biomarkers of systemic inflammation. Because of the pathogenic role of inflammation on AAA, serum CRP levels have been shown to predict the progression and severity of AAA.⁶ In contrast to CRP, albumin decreases in the chronic inflammatory process as a negative acute phase reactant.⁷

Accordingly, the CRP/albumin ratio (CAR) is more sensitive than either CRP or albumin alone in predicting inflammation, due to its opposite direction (increased CRP and decreased albumin). While inflammatory markers were evaluated in terms of AAA severity and prognosis, we aimed to evaluate the prognostic value of CAR on mortality in patients with AAA who underwent EVAR.

Methods

Study population

In this retrospective cohort, 147 consecutive patients who underwent EVAR due to infrarenal AAA in our clinic between December 2014 and September 2020 were evaluated. Thirteen patients were excluded due to ruptured AAA, five patients because of infectious AAA, and seven patients due to missing demographic data. After excluding these patients, a total of 127 technical success achieved patients (116 males and 11 females; mean age (69.3 ± 8.0)) were accepted as the study population. All patients were evaluated by the heart team before the procedure. A consensus was reached for the treatment strategy according to the European Society of Cardiology guidelines.⁸ Before the procedure, patients had computed tomography (CT) angiography, and after determining whether they were anatomically suitable for endovascular repair, the necessary measurements were made and the appropriate size stent-graft was selected. The procedures were performed under appropriate sterilization conditions and general anesthesia in the interventional cardiology department by a team of two experienced invasive cardiologists, a cardiovascular surgeon, and an anesthesiologist. The technical success was defined as no intraoperative mortality or switch to open procedure, absence of type I and type III leaks, patency of the renal and hypogastric arteries, absence of iliac stenosis or impaired lower limb circulation. All patients were observed in the intensive care unit after the procedure. The study was approved by the local ethics committee and was conducted in accordance with the requirements of the Declaration of Helsinki.

Data collection

The follow-up files of the patients were analyzed retrospectively, and the age, gender, height, weight, laboratory results before the procedure, smoking status, comorbidities, echocardiographic parameters, aneurysm diameter, procedure date, procedure duration, graft type, intensive care unit, and in-hospital mortality and the length of stay were investigated. The comorbidities were defined as follows: hypertension (HT) as use of antihypertensive drugs; systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; diabetes mellitus (DM) as use of insulin or antidiabetic drugs; fasting blood glucose value ≥ 126 mg/dL and/or HbA1c value ≥ 6.5%; hyperlipidemia (HL) as use of cholesterol-lowering drugs and/or low-density lipoprotein cholesterol (LDL-C) value ≥ 140 mg/dL; chronic obstructive pulmonary disease (COPD) as chronic bronchitis or emphysema; congestive heart failure (CHF) as ejection fraction < 50% in preoperative echocardiography; coronary artery disease (CAD) as history of angina pectoris, myocardial infarction, or coronary revascularization; peripheral artery disease (PAD) as previous peripheral artery revascularization; arterial disease detected with Doppler ultrasound; presence of lower limb claudication; cerebrovascular accident (CVA) as stroke or history of transient ischemic attack; and chronic renal failure (CRF) as an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min.

Biochemical analysis

All biochemical analyses were measured before the EVAR procedure. Fasting blood glucose, creatinine and complete blood count, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were measured after a fasting between six to 8 hours. Blood samples were taken from the brachial veins. Laboratory parameters including serum CRP and albumin levels were measured using a Roche Diagnostics Cobas 8000 c502 analyzer (Roche Diagnostics). CAR was calculated as the ratio of CRP (mg/dL) to albumin level (mg/dL).

Endpoints and follow-up

Patients were followed from the date of EVAR procedures until September 2020 and were censored at the time of death or the last known follow-up. The mean follow-up duration was 32.7 ± 21.7 months. The endpoint of the study was the long-term all-cause mortality. Survival data of the patients were obtained from the electronic hospital system or the National Population Registry. The patients were divided into two groups, group 1 survivor patients and group 2 patients with mortality.

Statistics

Data was analyzed using the Statistical Package for the Social Sciences, version 24.0 (SPSS Inc., Chicago, Illinois, USA). Whether the variables show normal distribution, visual (histograms and probability curves) and analytical methods (KolmogorovSimirnov and ShapiroWilk) were evaluated. Numerical variables showing normal distribution were expressed as mean ± standard deviation (SD), numerical variables not showing normal distribution were expressed as median (interquartile range) and categorical variables as percentage (%). Numerical variables such as CAR were evaluated using Student t-tests and the MannWhitney U-test between the two groups. Chi-square or Fisher’s exact test were used to compare categorical variables. Receiver operating characteristic (ROC) curves were generated to investigate the prognostic accuracy of CAR for all-cause mortality. Event-free survival curves were constructed using the Kaplan–Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI) for clinical endpoints. Throughout the present study, a p value of < 0.05 was considered significant.

Results

The main characteristics of 127 patients were summarized in Table 1. The mean age of the patients was 69.3 ± 8.0 and 116 (91.3%) of the patients were male and 11 (8.7%) were female. In the tomographic examination performed before the EVAR procedure, the mean maximum AAA diameter was 66.3 ± 11.5 mm. We divided the patients who were followed up for a mean 48.0 ± 30.3 months after the technically successful EVAR procedure into two groups as those with all-cause mortality and survivors. At the end of the follow-up, 32 (25.1%) patients died. There was no difference between the two groups in terms of age, gender, diabetes mellitus, hypertension, coronary artery disease, congestive heart failure, hyperlipidemia, cerebrovascular disease, atrial fibrillation, chronic obstructive pulmonary disease, chronic renal failure, and AAA diameter. LV ejection fraction was lower in the mortality group (57.3 ± 7.8 vs 51.9 ± 11.0, p < 0.003). In the group with mortality, CAR was significantly higher than the survivor group (4.63 (2.60–11.88) versus 1.63 (0.72–3.24), p < 0.001) (Figure 1).

Table 1.

Characteristics of all-cause mortality and survivor patients undergoing EVAR.

	All patients (N = 127)	Mortality (−) (n = 95)	Mortality (+) (n = 32)	p value
Age, years	69.3 ± 8.0	69.4 ± 8.0	69.1 ± 8.1	0.863
Male, n (%)	116 (91.3)	86 (90.5)	30 (93.8)	0.729
Weight, kg	75.5 ± 9.3	75.3 ± 9.5	76.1 ± 8.7	0.671
Height, cm	171.3 ± 4.6	171.3 ± 4.8	171.2 ± 3.6	0.962
Body mass index, kg/m²	25.8 ± 3.2	25.7 ± 3.2	26.0 ± 3.2	0.641
Current smoking, n (%)	42 (33.1)	31 (32.6)	11 (34.4)	0.856
Comorbidities
Diabetes mellitus, n (%)	30 (23.6)	21 (22.1)	9 (28.1)	0.488
Hypertension, n (%)	79 (62.2)	59 (62.1)	22 (62.5)	0.968
Coronary artery disease, n (%)	57 (44.9)	41 (43.2)	16 (50.0)	0.501
PCI, n (%)	21 (16.5)	18 (18.9)	3 (9.4)	0.207
CABG, n (%)	28 (22.0)	22 (23.2)	6 (18.8)	0.603
Congestive heart failure, n (%)	16 (12.6)	9 (9.5)	7 (21.9)	0.119
Hyperlipidemia, n (%)	39 (30.7)	30 (31.6)	9 (28.1)	0.714
Cerebrovascular disease, n (%)	6 (4.7)	6 (6.3)	0 (0.0)	0.336
Atrial fibrillation, n (%)	13 (10.2)	12 (12.6)	1 (3.1)	0.182
Peripheral artery disease, n (%)	11 (8.7)	7 (7.4)	4 (12.5)	0.467
Chronic obstructive pulmonary disease, n (%)	20 (15.7)	12 (12.6)	8 (25.0)	0.097
Chronic kidney disease, n (%)	19 (15.0)	13 (13.7)	6 (18.8)	0.568
LV ejection fraction, %	56.0 ± 9.0	57.3 ± 7.8	51.9 ± 11.0	0.003
Laboratory data
Hemoglobin, g/dL	12.76 ± 1.84	12.86 ± 1.84	12.45 ± 1.83	0.273
White blood cells, 10^³/uL	8.07 ± 2.30	8.11 ± 2.22	7.92 ± 2.58	0.690
Platelet, 10^3/uL	228 ± 82	231 ± 85	221 ± 73	0.545
Albumin, g/dL	3.86 ± 0.50	3.99 ± 0.40	3.48 ± 0.56	< 0.001
Glucose, mg/dL	101 (90–112)	100 (90–108)	106 (92–123)	0.045
Creatinine, mg/dL	1.00 (0.81–1.16)	1.00 (0.80–1.10)	1.05 (0.93–1.40)	0.033
C-reactive protein, mg/dL	9 (4–17)	7 (3–13)	16 (10–44)	< 0.001
LDL-C, mg/dL	108 ± 38	106 ± 38	116 ± 38	0.221
HDL-C, mg/dL	42 ± 12	43 ± 11	40 ± 11	0.202
Triglyceride, mg/dL	124 (85–170)	127 (90–162)	120 (78–187)	0.981
Total cholesterol, mg/dL	177 ± 37	176 ± 37	181 ± 39	0.575
CAR	2.50 (0.90–4.69)	1.63 (0.72–3.24)	4.63 (2.60–11.88)	< 0.001
AAA Diameter, mm	66.3 ± 11.5	65.2 ± 11.2	69.4 ± 12.0	0.075
Procedure-related data
Type of endograft
Medtronic Endurant, n (%)	97 (76.4)	74 (77.9)	23 (71.9)	0.282
TriVascular ovation, n (%)	11 (8.7)	7 (7.4)	4 (12.5)
Cook Zenith, n (%)	7 (5.5)	7 (7.4)	0 (0.0)
Medtronic Talent, n (%)	8 (6.3)	4 (4.2)	4 (12.5)
Vascutec Anaconda, n (%)	3 (2.4)	2 (2.1)	1 (3.1)
Gore Exluder, n (%)	1 (0.8)	1 (1.1)	0 (0.0)
Operation time, min	149 (108–180)	140 (98–172)	160 (133–182)	0.027
Fluoroscopy time, min	28 (20–34)	25 (18–34)	30 (27–35)	0.025
ICU stay, days	2 (1–3)	1 (1–2)	2 (2–3)	< 0.001
Hospital stay, days	5 (4–7)	5 (4–7)	5 (4–8)	0.955

Data are presented as percentage, mean ± standard deviation, or median (interquartile range).

PCI: percutaneous coronary intervention; CABG: coronary artery bypass graft; LV: left ventricular; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; CAR: C-reactive protein to albumin ratio; AAA: abdominal aortic aneurysm; ICU: intensive care unit.

Figure 1.

CRP-to-albumin ratios of patients with and without mortality.

Univariable Cox regression analysis was performed to determine independent predictors of all-cause mortality in patients who underwent EVAR (Table 2). As a result of the analysis, it was determined that COPD, LVEF, glucose, creatinine, CAR, and AAA diameter were associated with mortality. Numerical variables among these variables were categorized by using ROC curves and Youden index (max (sensitivity + selectivity − 1)) determining the cut-off values, before entering the multivariable analysis. The cut-off value for CAR was 2.05 (AUC: 0.799; 95% CI: 0.716–0.883; p < 0.001). For this cut-off value, CAR could detect the mortality with 93.8% sensitivity and 57.9% specificity (Figure 2).

Table 2.

Univariable COX regression analysis to determine independent predictors of mortality in patients undergoing EVAR.

	Univariable analysis
	HR	95% CI	p value
Age	1.019	0.972–1.069	0.433
Male	1.403	0.333–5.906	0.644
Body mass index	0.982	0.885–1.089	0.729
Current smoking	1.209	0.578–2.529	0.613
Diabetes mellitus	1.842	0.834–4.073	0.131
Hypertension	1.236	0.602–2.535	0.564
Coronary artery disease	0.909	0.445–1.857	0.793
Congestive heart failure	2.196	0.944–5.110	0.068
Hyperlipidemia	0.711	0.356–1.672	0.511
Atrial fibrillation	0.552	0.074–4.110	0.561
Peripheral artery disease	1.815	0.631–5.222	0.269
Chronic obstructive pulmonary disease	2.377	1.057–5.347	0.036
Chronic kidney disease	1.629	0.665–3.992	0.286
LV ejection fraction	0.958	0.930–0.987	0.005
Hemoglobin	0.886	0.732–1.072	0.212
White blood cells	0.967	0.825–1.133	0.679
Platelet	0.998	0.992–1.003	0.401
Glucose	1.014	1.004–1.024	0.006
Creatinine	1.665	0.979–2.831	0.060
LDL-C	1.001	0.991–1.011	0.838
HDL-C	0.983	0.953–1.014	0.292
Triglyceride	1.002	0.999–1.006	0.223
Total cholesterol	0.998	0.989–1.008	0.750
CAR	1.076	1.048–1.104	< 0.001
AAA diameter	1.028	0.999–1.058	0.055

HR: hazard ratio; CI: confidence interval; LV: left ventricular; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; CAR: C-reactive protein to albumin ratio; AAA: abdominal aortic aneurysm.

Figure 2.

ROC curve for CAR for detecting all-cause mortality in patients undergoing EVAR.

In Table 3, multivariable Cox regression analysis was performed with parameters that were significant in univariable analysis. While COPD (p = 0.309), LVEF ≤ 55% (p = 0.071), and AAA diameter ≥ 69 mm (p = 0.403) were not found to be significant, glucose ≥ 110 mg/dL (HR: 2.740, 95% CI: 1.354–5.542, p = 0.005), creatinine ≥ 0.99 mg/dL (HR: 2.957, 95% CI: 1.282–6.819, p = 0.011), and CAR > 2.05 (HR: 8.190, 95% CI: 1.899–35.320, p = 0.005) were identified as independent predictors of mortality.

Table 3.

Multivariable Cox proportional hazard model of all-cause mortality.

	Multivariable analysis
	HR	95% CI	p value
COPD	1.540	0.671–3.539	0.309
LVEF ≤ 55%	1.989	0.943–4.196	0.071
Glucose ≥ 110 mg/dL	2.740	1.354–5.542	0.005
Creatinine ≥ 0.99 mg/dL	2.957	1.282–6.819	0.011
CAR > 2.05	8.190	1.899–35.320	0.005
AAA diameter ≥ 69 mm	1.353	0.666–2.749	0.403

HR: hazard ratio; CI: confidence interval. COPD: chronic obstructive pulmonary disease; LVEF: left ventricular ejection fraction; CAR: C-reactive protein to albumin ratio; AAA: abdominal aortic aneurysm.

In Table 4, procedural and post-procedural data were compared in the patient groups divided into two groups according to the CAR cut-off value. Although the operation and total hospital stay durations of both groups were similar, the duration of ICU stay was significantly longer in the high CAR group (p < 0.001). Moreover, total mortality was significantly higher in the high CAR group (p < 0.001).

Table 4.

Comparison of procedural and post-procedural characteristics of patient groups divided according to CAR cut-off value.

	CRP/Albumin ≤ 2.05 (n = 57)	CRP/Albumin > 2.05 (n = 70)	p value
Operation time, min	149 (99–176)	148 (120–181)	0.540
Fluoroscopy time, min	27 (19–34)	29 (20–35)	0.523
ICU stay, days	1 (1–2)	2 (1–3)	< 0.001
Hospital stay, days	5 (4–6)	6 (4–8)	0.028
30-Day mortality, n (%)	0 (0.0)	5 (7.1)	0.064
Total mortality, n (%)	2 (3.5)	30 (42.9)	< 0.001

Data are presented as percentage, mean ± standard deviation, or median (interquartile range).

CRP: C-reactive protein; ICU: intensive care unit.

Kaplan–Meier cumulative survival curves for all-cause mortality in patients classified using the CAR cut-off values were presented in Figure 3. Kaplan–Meier curves showed a higher incidence of all-cause mortality in patients with high CAR compared to patients with low CAR (Log-rank test, p < 0.001).

Figure 3.

Kaplan–Meier curve for determining all-cause mortality.

Discussion

In this study, we investigated the prognostic effect of CAR on the all-cause mortality in patients who underwent EVAR with technical success. After a long-term follow-up, patients with all-cause mortality had significantly higher CAR. CAR > 2.05, glucose and creatinine levels were found to be independent predictors of mortality. It predicted mortality with 93.8% sensitivity and 57.9% specificity. The high group of CAR had longer ICU stays and hospital stays.

Abdominal aortic aneurysm (AAA) is a very common disease, especially in men older than 65 years old.⁹ In recent years, EVAR has become an effective treatment option in the treatment of AAA, especially in elderly patients with high surgical risk, and more than 70% of the patients are treated by the endovascular method.¹⁰ Previous studies have shown that long-term survival in patients who survive AAA repair was worse than in the age- and sex-matched population and that long-term mortality was predominantly attributable to the concomitant chronic diseases.^11,12 Our study population also had high comorbidity rates (62.2% HT, 44.9% CAD, 30.7% HL, 23.6% DM, 15.7% COPD, and 15% CRF) and a long-term mortality rate of 25.1%. Our mortality rate was similar to EVAR studies in the literature. In another study conducted by O'Driscoll et al., which evaluated the relationship between preop transthoracic echocardiographic data and mortality in EVAR patients, reported a 28.6% mortality rate after 3.2 ± 1.5 years of follow-up and showed the relationship between low left ventricular ejection fraction and long-term mortality.¹³ In our study, we found significantly lower ejection fraction values in patients with mortality when compared to other patients (51.0 ± 11.0 vs 57.3 ± 7.8, p = 0.003). In the study of Jeon-Slaughter et al., in which they investigated the effect of aneurysm diameter on long-term survival in patients who underwent EVAR, mortality rate was 41.2% in 325 EVAR patients followed for a mean of 45.5 ± 29.2 months. In the study, it was concluded that the aneurysm diameter was significantly associated mid-term survival after EVAR, but not an independent predictor of long-term mortality.¹⁴ In our study, although a higher mean aneurysm diameter was observed in the mortality group compared to the other group, this difference did not reach the limit of significance (65.2 ± 11.2 mm versus 69.4 ± 12 mm, p = 0.075).

Consensus guidelines recommend preoperative risk stratification of patients with AAA to optimize patient care and prevent complications, including mortality.^15,16 Risk prediction based on clinical risk factors alone have limitations and existing models for elective AAA repair fail to predict outcome with sufficient accuracy to be widely adopted into routine clinical practice.^17,18 Therefore, it is essential for researchers to find new markers to improve their risk estimation. In our study, we tested the utility of CAR in risk classification.

Inflammation is known as an important risk factor for cardiovascular diseases.¹⁹ The “degenerative” form of AAA is thought to be a chronic disease of the media artery layer.²⁰ Indeed, inflammatory processes play an important role in the formation of this type of aneurysm, sharing a possible etiopathogenic origin with other diseases of atherosclerosis. In this context, it has been reported that proinflammatory cytokines are overexpressed in aneurysmal tissues.²¹ Indeed, the plasma concentration of interleukin-8 has been associated with the diameter of the aneurysm, tumor necrosis factor with the symptoms of AAA, and interferon-γ with the expansion of AAA.^22,23 Many previous studies have attempted to verify that the CRP value can be an indicator of AAA progression and rate of expansion.^24,25 Tryfon et al. reported that CRP was primarily associated with aneurysmal size.²⁶ Joaquin et al. confirmed a statistical relationship between AAA diameter and CRP levels. The authors reported that the aortic diameter increased in relation to the CRP level and that the CRP level was the only factor associated with the initial diameter and the variation of enlargement.²⁵ These suggest that chronic systemic inflammatory mechanisms, similar to the formation of atherosclerotic plaques, may play a role in the formation of “degenerative” aneurysms.

Albumin is produced in the liver and has antioxidant activity.²⁷ In contrast to CRP, albumin is reduced by inflammatory agents, including IL-6, as a negative acute phase response protein in the chronic inflammatory process.²⁸ A decrease in serum albumin level causes an increase in blood viscosity and deterioration in endothelial functions.²⁹ Inagaki et al. associated preoperative hypoalbuminemia with poor clinical outcomes after open and endovascular abdominal aortic aneurysm repair.³⁰ Max Wohlauer et al. found that hypoalbuminemia was associated with short- and long-term mortality after endovascular abdominal aortic aneurysm repair.³¹ Demir et al. found that malnutrition had a significant effect on postoperative long-term mortality in EVAR patients.³²

Acute-phase reactants are not responsive to each inflammatory condition to a similar degree. Therefore, different prognostic scores were determined to provide more stable regulation. CAR, as a single inflammatory index, is superior to CRP and albumin alone. In previous studies, CAR had a more valuable prognostic factor to reflect the inflammatory state in different inflammatory diseases. Fairclough et al. found that CAR had a favorable prognostic value in elderly patients in acute exacerbations of chronic disease.³³ Moreover, CAR has been shown to be a better parameter than CRP alone for predicting long-term mortality in patients in intensive care units.³⁴

CAR has also been studied in cardiovascular diseases, particularly atherosclerotic coronary artery disease. CAR has been independently associated with in-hospital and short-term MACEs in patients with acute coronary syndrome.³⁵ Additionally, in other studies, it was found that there was a relationship between pre-procedural CAR and the severity of the disease in patients with ACS and stent restenosis in patients with ST-segment elevation myocardial infarction.^36,37 Kahraman et al. revealed that CAR had a significant effect on prognosis in patients who underwent aortic valve replacement surgery.³⁸ It has been shown that CRP predicted mortality after transcatheter aortic valve implantation and the long-term results of percutaneous coronary intervention.³⁹

According to the previously reported data, the increased inflammation critically affects the vascular endothelium and triggers atherosclerosis. Thus, aneurysm damage can be seen more prominently, and its progression and prognosis may be worse. As expected, our study showed that higher inflammatory status was associated with poor prognosis. In previous studies, increased CRP was found to be associated with poor prognosis in AAA patients undergoing EVAR.⁴⁰ In our study, the prognostic value of CAR in mortality after EVAR was evaluated. To the best of our knowledge, our study is the first to show this subject in the literature, and the high inflammatory state affected mortality in AAA patients who underwent EVAR.

In our study, we found 30-day mortality in 6 (4.0%) patients, of which 4 (2.7%) were in-hospital. Two patients died due to heart failure, two patients due to pneumonia, one patient due to multi-organ failure, and one patient due to septic shock. Patients with high CAR had higher 30-day mortality rates than those with low levels (p = 0.003).

In the light of the data, CAR is an easy, cheap, and fast prognostic risk score to identify high-risk patients for EVAR. Tighter perioperative and long-term postoperative cardiological follow-up of patients with high CAR before the procedure and more aggressive medical treatment would be the right approach. However, large-scale studies are needed to evaluate the effect of CAR on clinical adverse events in patients with AAA after EVAR.

Study limitations

The main limitation of the study was relatively small sample size. The lack of data about the certain reasons of mortality was the other limitation due to the retrospective nature of the study. The CAR-related cardiovascular events other than mortality were not investigated as the other limitation.

Conclusion

CAR is a novel prognostic marker in patients undergoing EVAR. This is a rapid, easy, and cheap prognostic determinant in those patients. It is also an independent predictor of mortality in EVAR patients.

Footnotes

Authorship contributions

Concept—G.D. and A.R.D.Design—G.D. and A.R.D.Supervision—B.E., Ö.Ç., and M.E.Materials—U.B., Y.A., S.T.K., K.M.S., and T.A.Data—U.B., Y.A., S.T.K., K.M.S., and T.A.Analysis—G.D. and A.R.D.Literature search—G.D. and Ö.Ç.Writing—G.D.Critical revision—Ö.Ç. and M.E.

Conflict-of-interest

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics Committee Approval

Ethics committee approval was received for this study from the Ethics Committee of University of Health Sciences İstanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital.

ORCID iDs

Gökhan Demirci

Ali Riza Demir

Yalcin Avci

Kadriye Memiç Sancar

References

Yang

Kim

Choi

, et al. Comparison of clinical outcomes between surgical repair and endovascular stent for the treatment of abdominal aortic aneurysm. Vasc Spec Int 2017; 33(4): 140–145. DOI: 10.5758/vsi.2017.33.4.140.

Tayfur

Senel Bademci

Yazman

, et al. Endovascular approach in isolated abdominal aortic dissections. Vascular 2018; 26(5): 477–482. DOI: 10.1177/1708538118760941.

Keisler

Carter

. Abdominal aortic aneurysm. Am Fam Physician 2015; 91(8): 538–43.

Duarte

Maldjian

Laskowski

. Comparison of endovascular versus open repair of abdominal aortic aneurysms. Cardiol Rev 2009; 17(3): 112–114. DOI: 10.1097/CRD.0b013e31819d6124.

Patel

Sweeting

Powell

, et al. Endovascular versus open repair of abdominal aortic aneurysm in 15-years' follow-up of the UK endovascular aneurysm repair trial 1 (EVAR trial 1): a randomised controlled trial. Lancet 2016; 388(10058): 2366–2374. DOI: 10.1016/S0140-6736(16)31135-7.

Shangwei

Yingqi

Jiang

, et al. Serum high-sensitive C-reactive protein level and CRP genetic polymorphisms are associated with abdominal aortic aneurysm. Ann Vasc Surg 2017; 45: 186–192. DOI: 10.1016/j.avsg.2017.05.024.

Levitt

. Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements. Int J Gen Med 2016; 9: 229–255. DOI: 10.2147/IJGM.S102819.

Moll

Powell

Fraedrich

, et al. Management of abdominal aortic aneurysms clinical practice guidelines of the European Society for Vascular Surgery. Eur J Vasc Endovasc Surg 2011; 41(Suppl 1): S1–S58. DOI: 10.1016/j.ejvs.2010.09.011.

Jones

Phillips

Williams

MJA

, et al. Two C‐C family chemokines, eotaxin and RANTES, are novel independent plasma biomarkers for abdominal aortic aneurysm. J Am Heart Assoc 2016; 5(5): e002993. DOI: 10.1161/JAHA.115.002993.

10.

Powell

Forbes

, et al. Final 12-year follow-up of surgery versus surveillance in the UK small aneurysm trial. Br J Surg 2007; 94(6): 702–708. DOI: 10.1002/bjs.5778.

11.

Batt

Staccini

Pittaluga

, et al. Late survival after abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg 1999; 17(4): 338–342. DOI: 10.1053/ejvs.1998.0779.

12.

Karthikesalingam

Bahia

Patterson

, et al. The shortfall in long-term survival of patients with repaired thoracic or abdominal aortic aneurysms: retrospective case-control analysis of hospital episode statistics. Eur J Vasc Endovasc Surg 2013; 46(5): 533–541. DOI: 10.1016/j.ejvs.2013.09.008.

13.

O’Driscoll

Bahia

Gravina

, et al. Transthoracic echocardiography provides important long-term prognostic information in selected patients undergoing endovascular abdominal aortic repair. Circ Cardiovasc Imaging 2016; 9(2): e003557. DOI: 10.1161/CIRCIMAGING.115.003557.

14.

Jeon-Slaughter

Krishnamoorthi

Timaran

, et al. Effects of abdominal aortic aneurysm size on mid- and long-term mortality after endovascular aneurysm repair. J Endovasc Ther 2019; 26(2): 231–237. DOI: 10.1177/1526602819829901.

15.

Fleischmann

Beckman

, et al. 2009 ACCF/AHA focused update on perioperative beta blockade. Circulation 2009; 120(21): 2123–2151. DOI: 10.1161/CIRCULATIONAHA.109.192689.

16.

Moll

Powell

Fraedrich

, et al. Management of abdominal aortic aneurysms clinical practice guidelines of the European society for vascular surgery. Eur J Vasc Endovasc Surg 2011; 41(Suppl 1): S1–S58. DOI: 10.1016/j.ejvs.2010.09.011.

17.

Ford

Beattie

Wijeysundera

. Systematic review: prediction of perioperative cardiac complications and mortality by the revised cardiac risk index. Ann Intern Med 2010; 152(1): 26–35. DOI: 10.7326/0003-4819-152-1-201001050-00007.

18.

Patterson

Holt

PJE

Hinchliffe

, et al. Predicting risk in elective abdominal aortic aneurysm repair: a systematic review of current evidence. Eur J Vasc Endovasc Surg 2008; 36(6): 637–645. DOI: 10.1016/j.ejvs.2008.08.016.

19.

Agmon

Khandheria

Jamil Tajik

, et al. Inflammation, infection, and aortic valve sclerosis. Atherosclerosis 2004; 174(2): 337–342. DOI: 10.1016/j.atherosclerosis.2004.01.028.

20.

Zarins

Glagov

. Aneurysmal and occlusive atherosclerosis of the human abdominal aorta. J Vasc Surg 2001; 33(1): 91–96. DOI: 10.1067/mva.2001.109744.

21.

Jones

Brull

Brown

, et al. Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation 2001; 103(18): 2260–2265. DOI: 10.1161/01.cir.103.18.2260.

22.

Třeška

Topolčan

Pecen

. Cytokines as plasma markers of abdominal aortic aneurysm. Clin Chem Lab Med 2000; 38(11): 1161–4. DOI: 10.1515/CCLM.2000.178.

23.

Singh

Bønaa

Jacobsen

, et al. Prevalence of and risk factors for abdominal aortic aneurysms in a population-based study: the tromso study. Am J Epidemiol 2001; 154(3): 236–244. DOI: 10.1093/aje/154.3.236.

24.

Saratzis

Abbas

Kiskinis

, et al. Abdominal aortic aneurysm: a review of the genetic basis. Angiology 2011; 62(1): 18–32. DOI: 10.1177/0003319710373092.

25.

De Haro

Acin

Bleda

, et al. Prediction of asymptomatic abdominal aortic aneurysm expansion by means of rate of variation of C-reactive protein plasma levels. J Vasc Surg 2012; 56(1): 45–52. DOI: 10.1016/j.jvs.2012.01.003.

26.

Vainas

Lubbers

Stassen

FRM

, et al. Serum C-reactive protein level is associated with abdominal aortic aneurysm size and may be produced by aneurysmal tissue. Circulation 2003; 107(8): 1103–1105. DOI: 10.1161/01.cir.0000059938.95404.92.

27.

Roche

Rondeau

Singh

, et al. The antioxidant properties of serum albumin. FEBS Lett 2008; 582(13): 1783–1787. DOI: 10.1016/j.febslet.2008.04.057.

28.

Levitt

29.

Tan

Dainty

, et al. Hypoalbuminaemia, systemic albumin leak and endothelial dysfunction in peritoneal dialysis patients. Nephrol Dial Transplant 2012; 27(12): 4437–4445. DOI: 10.1093/ndt/gfs075.

30.

Inagaki

Farber

Eslami

, et al. Preoperative hypoalbuminemia is associated with poor clinical outcomes after open and endovascular abdominal aortic aneurysm repair. J Vasc Surg 2017; 66(1): 53–63. DOI: 10.1016/j.jvs.2016.10.110.

31.

Wohlauer

Brier

Kuramochi

, et al. Preoperative hypoalbuminemia is a risk factor for early and late mortality in patients undergoing endovascular juxtarenal and thoracoabdominal aortic aneurysm repair. Ann Vasc Surg 2017; 42: 198–204. DOI: 10.1016/j.avsg.2017.03.058.

32.

Demir

Celik

Uygur

, et al. Malnutrition provides important long-term prognostic information in patients undergoing endovascular abdominal aortic aneurysm repair. Vascular 2020; 29: 330–339. DOI: 10.1177/1708538120960859.

33.

Fairclough

Cairns

Hamilton

, et al. Evaluation of a modified early warning system for acute medical admissions and comparison with C-reactive protein/albumin ratio as a predictor of patient outcome. Clin Med 2009; 9(1): 30–33. DOI: 10.7861/clinmedicine.9-1-30.

34.

Ranzani

Zampieri

Forte

, et al. C-reactive protein/albumin ratio predicts 90-day mortality of septic patients. PLoS One 2013; 8(3): e59321. DOI: 10.1371/journal.pone.0059321.

35.

Wang

Ren

Wang

, et al. Prognostic efficacy of high-sensitivity C-reactive protein to albumin ratio in patients with acute coronary syndrome. Biomark Med 2019; 13(10): 811–820. DOI: 10.2217/bmm-2018-0346.

36.

Çağdaş

Rencüzoğullari

Karakoyun

, et al. Assessment of relationship between C-reactive protein to albumin ratio and coronary artery disease severity in patients with acute coronary syndrome. Angiology 2019; 70(4): 361–368. DOI: 10.1177/0003319717743325.

37.

Rencuzogullari

Karabağ

Çağdaş

, et al. Assessment of the relationship between preprocedural C-reactive protein/albumin ratio and stent restenosis in patients with ST-segment elevation myocardial infarction. Rev Port Cardiol 2019; 38(4): 269–277, English, Portuguese. DOI: 10.1016/j.repc.2018.08.008.

38.

Kahraman

Can Dogan

Demirci

, et al. The prognostic value of C-reactive protein to albumin ratio in patients with isolated degenerative aortic valve stenosis undergoing surgical aortic valve replacement. Braz J Cardiovasc Surg 2020; 35(3): 299–306. DOI: 10.21470/1678-9741-2019-0114.

39.

Hioki

Watanabe

Kozuma

, et al. Effect of serum C-reactive protein level on admission to predict mortality after transcatheter aortic valve implantation. Am J Cardiol 2018; 122(2): 294–301. DOI: 10.1016/j.amjcard.2018.04.005.

40.

Nagai

Kudo

Inoue

, et al. Preoperative predictors of long-term mortality after elective endovascular aneurysm repair for abdominal aortic aneurysm. Ann Vasc Dis 2016; 9(1): 42–47. DOI: 10.3400/avd.oa.15-00129.