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Reviews in Cardiovascular Medicine  2021, Vol. 22 Issue (3): 1053-1062     DOI: 10.31083/j.rcm2203115
Special Issue: New Frontiers in Cardiac Surgery: Biomarkers and Treatment
Original Research Previous articles | Next articles
Predictive potential of biomarkers and risk scores for major adverse cardiac events in elderly patients undergoing major elective vascular surgery
Velimir S. Perić1, *(), Mladjan D. Golubović1, 2, Milan V. Lazarević1, 2, Tomislav L. Kostić2, 3, Dragana S. Stokanović2, Miodrag N. Đorđević2, 4, Vesna G. Marjanović2, 5, Marija D. Stošić5, Dragan J. Milić1, 2
1Clinic of Cardiovascular Surgery, Clinical Center Nis, 18000 Nis, Serbia
2Medical School of Nis, University of Nis, 18000 Nis, Serbia
3Clinic for Cardiology, Clinical Center Nis, 18000 Nis, Serbia
4Clinic for Endocrine Surgery, Clinical Center Nis, 18000 Nis, Serbia
5Clinic for Anesthesiology and Intensive Therapy, Clinical Center Nis, 18000 Nis, Serbia
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Abstract:

Elderly patients scheduled for major elective vascular surgery are at high risk for a major adverse cardiac events (MACE). The objectives of the study were: (1) To determine the individual discriminatory ability of four risk prediction models and four biomarkers in predicting MACEs in elderly patients undergoing major elective vascular surgery; (2) to find a prognostic model with the best characteristics; (3) to examine the significance of all preoperative parameters; and (4) to determine optimal cut-off values for biomarkers with best predictor capabilities. We enrolled 144 geriatric patients, aged 69.97 ± 3.73 years, with a 2:1 male to female ratio. Essential inclusion criteria were open major vascular surgery and age >65 years. The primary outcome was the appearance of MACEs within 6 months. These were noted in 33 (22.9%) patients. The most frequent cardiac event was decompensated heart failure, which occurred in 22 patients (15.3%). New onset atrial fibrillation was registered in 13 patients (9%), and both myocardial infarction and ventricular arrhythmias occurred in eight patients each (5.5%). Excellent discriminatory ability (AUC >0.8) was observed for all biomarker combinations that included the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP). The most predictive two-variable combination was the Geriatric-Sensitive Cardiac Risk Index (GSCRI) + NT-proBNP (AUC of 0.830 with a 95% confidence interval). Female gender, previous coronary artery disease, and NT-proBNP were three independent predictors in a multivariate model of binary logistic regression. The Cox regression multivariate model identified high-sensitivity C-reactive protein and NT-proBNP as the only two independent predictors.

Key words:  Biomarker      Risk score      Elderly      Vascular surgery      MACE     
Submitted:  14 July 2021      Revised:  05 August 2021      Accepted:  27 August 2021      Published:  24 September 2021     
*Corresponding Author(s):  Velimir S. Perić     E-mail:  velperic@gmail.com

Cite this article: 

Velimir S. Perić, Mladjan D. Golubović, Milan V. Lazarević, Tomislav L. Kostić, Dragana S. Stokanović, Miodrag N. Đorđević, Vesna G. Marjanović, Marija D. Stošić, Dragan J. Milić. Predictive potential of biomarkers and risk scores for major adverse cardiac events in elderly patients undergoing major elective vascular surgery. Reviews in Cardiovascular Medicine, 2021, 22(3): 1053-1062.

URL: 

https://rcm.imrpress.com/EN/10.31083/j.rcm2203115     OR     https://rcm.imrpress.com/EN/Y2021/V22/I3/1053

Fig. 1.  Individual discriminative ability of risk scores and biomarkers. The receiver operating characteristic (ROC) curve illustrates the discriminative ability of four biomarkers and four risk scores. Abbreviations: ROC, receiver operating characteristic; RCRI, Revised Cardiac Risk Index; MICA, myocardial infarction and cardiac arrest; GSCRI, Geriatric-Sensitive Cardiac Risk Index; ASA, American Society of Anesthesiologist; CK, creatine kinase - MB isoenzyme; NT-proBNP, N-terminal fragment of pro-B-type natriuretic peptide; Hs-TnI, High-sensitivity troponin I; Hs-CRP, high-sensitivity C-reactive protein.

Table 1.  Demographic and clinical characteristics and occurrence of MACEs during the 6-months of follow-up.
Variable With MACE Without MACE p-value
Age (years) 69.76 ± 4.88 69.65 ± 3.34 0.109*
aGender (male) 5 (15.2%) 45 (40.5%) 0.007
Dyspnea (NYHA class) 2.58 ± 0.61 2.04 ± 0.62 <0.001*
Atrial fibrillation 3 (9.1%) 4 (3.6%) 0.197
Previous CVI 5 (15.2%) 37 (32.5%) 0.051
Previous CAD 14 (42.4%) 17 (15.3%) 0.002
Previous cardiomyopathy 6 (18.2%) 12 (10.8%) 0.367
Prior PCI 2 (6.1%) 3 (2.7%) 0.323
Previous MI 9 (27.3%) 16 (14.4%) 0.115
Prior CABG 1 (3.0%) 1 (0.9%) 0.407
Previous hypertension 30 (90.9%) 92 (82.9%) 0.408
Previous DM 14 (42.4%) 39 (35.1%) 0.538
Insulin-dependent DM 11 (33.3%) 22 (19.8%) 0.155
Insulin-independent DM 3 (9.1%) 17 (15.3%) 0.567
Previous hyperlipidaemia 10 (30.3%) 23 (20.7%) 0.361
Smoking 16 (48.5%) 41 (36.9%) 0.311
Family history 18 (54.5%) 38 (34.2%) 0.043
Beta-blocker 27 (81.8%) 77 (69.4%) 0.189
ACE inhibitor 28 (84.8%) 78 (70.3%) 0.117
Calcium channel antagonist 16 (48.5%) 23 (20.7%) 0.003
Antiplatelet therapy 27 (81.8%) 55 (49.5%) 0.001
Statins 17 (51.5%) 51 (45.9%) 0.692
Diuretics 3 (9.1%) 21 (18.9%) 0.286
Nitrates 3 (9.1%) 7 (6.3%) 0.696
Intervention type 0.006
AAAR 13 (39.4%) 18 (16.2%)
CE 14 (42.4%) 66 (59.5%)
AFBP 2 (6.1%) 1 (0.9%)
FPBP 4 (12.1%) 26 (23.4%)
ASA score 3.0 (2.5–3.0) 2.0 (2.0–3.0) 0.002#
Haemoglobin (g/dL) 13.4 (12.0–14.3) 13.6 (12.5–14.4) 0.479#
Creatinine (μmol/L) 92.0 (80.2–125.6) 88.4 (79.0–106.6) 0.166#
WBC count (109/L) 7.3 (6.4–8.6) 7.0 (5.8–8.1) 0.161#
Platelet count (109/L) 213.0 (148.0–251.0) 228.0 (191.0–274.0) 0.073#
Urea (mmol/L) 6.0 (5.2–8.6) 5.6 (5.0–6.9) 0.176#
CRP (mg/L) 2.8 (2.0–4.9) 3.4 (2.1–6.5) 0.403#
LDL (mmol/L) 2.84 ± 0.83 2.79 ± 0.99 0.783*
HDL (mmol/L) 1.2 (0.9–1.3) 1.2 (1.0–1.4) 0.263#
CK-MB (U/L) 104.0 (47.5–132.0) 74.0 (56.0–108.0) 0.130#
EF (%) 50.06 ± 6.69 55.76 ± 7.17 <0.001*
BMI (kg/m2) 25.76 ± 1.84 25.65 ± 2.76 0.844*
ICU (days) 3.0 (2.0–4.0) 1.0 (1.0–1.0) <0.001#
RCRI 2.06 ± 1.22 1.18 ± 1.15 <0.001*
RCRI (%) 10.18 ± 4.01 7.27 ± 3.73 <0.001*
Gupta MICA 0.7 (0.2–1.5) 0.4 (0.2–0.7) 0.001#
GSCRI 4.5 (1.9–11.1) 1.7 (0.3–7.2) <0.001#
NT-proBNP (pg/mL) 234.0 (89.2–429.5) 95.0 (74.0–114.0) <0.001#
Hs-TnI (ng/mL) 0.003 (0.001–0.008) 0.004 (0.002–0.010) 0.559#
Hs-CRP (mg/L) 0.9 (0.4–3.2) 0.4 (0.3–0.9) 0.040#
Legend: *, t-test; , Chi-squared test; #, Z-test.
NYHA, New York Heart Association; CVI, cerebrovascular insult; CAD, coronary artery disease; PCI, percutaneous coronary intervention; MI, myocardial infarction; CABG, coronary artery bypass graft; DM, diabetes mellitus; ACE, angiotensin converting enzyme; AAAR, repair of abdominal aortic aneurysm; CE, carotid endarterectomy; AFBP, aortobifemoral bypass; FPBP, femoropopliteal bypass; ASA, American Society of Anesthesiologist; WBC, white blood cells; CRP, C-reactive protein; LDL, low-density lipoprotein; HDL, high-density lipoprotein; CK-MB, MB isoenzyme of creatine kinase; EF, ejection fraction; BMI, body mass index; ICU, intensive care unit; RCRI, Revised Cardiac Risk Index; MICA, myocardial infarction and cardiac arrest; GSCRI, Geriatric-Sensitive Cardiac Risk Index; NT-proBNP, N-terminal fragment of pro-B-type natriuretic peptide; Hs-TnI, High-sensitivity troponin I; Hs-CRP, high-sensitivity C-reactive protein.
Table 2.  Individual discriminative ability of risk scores and biomarkers.
Variable Area (95% CI) p-value Cut-off Sensitivity (%) Specificity (%)
RCRI 0.707 (0.609–0.805) <0.001 2 66.7 68.5
RCRI (%) 0.706 (0.608–0.804) <0.001 10.1 66.7 68.5
Gupta MICA 0.682 (0.570–0.795) 0.001 0.8 48.5 86.5
GSCRI 0.731 (0.644–0.818) <0.001 1.5 90.9 45.9
ASA score 0.654 (0.551–0.757) 0.008 3 75.8 55
NT-proBNP (pg/mL) 0.713 (0.600–0.826) <0.001 208 60.6 84.7
Hs-TnI (ng/mL) 0.462 (0.347–0.578) 0.512 0.035 9.1 100
Hs-CRP (mg/L) 0.618 (0.501–0.735) 0.04 0.92 51.5 75.7
CK-MB (U/L) 0.587 (0.465–0.709) 0.13 94 63.6 66.7
Legend: RCRI, Revised Cardiac Risk Index; MICA, myocardial infarction and cardiac arrest; GSCRI, Geriatric-Sensitive Cardiac Risk Index; ASA, American Society of Anesthesiologist; NT-proBNP, N-terminal fragment of pro-B-type natriuretic peptide; Hs-TnI, High-sensitivity troponin I; Hs-CRP, high-sensitivity C-reactive protein; CK-MB, MB isoenzyme of creatine kinase.
Fig. 2.  Discriminative ability of NT-proBNP and different risk-score combinations. The receiver operating characteristic (ROC) curve illustrates the discriminative ability seven different NT-proBNP combinations of biomarkers and/or risk scores. Abbreviations: ROC, receiver operating characteristic; NT-proBNP, N-terminal fragment of pro-B-type natriuretic peptide; GSCRI, Geriatric-Sensitive Cardiac Risk Index; RCRI, Revised Cardiac Risk Index; MICA, myocardial infarction and cardiac arrest.

Table 3.  Binary logistic regression model of MACE occurrence during the 6-months after the procedure.
Variable Univariable analysis - OR (95% CI) p-value Multivariable analysis - OR (95% CI) p-value
Gender (female) 3.818 (1.371–10.633) 0.01 7.303 (1.084–49.208) 0.041
Previous CAD 4.074 (1.720–9.650) 0.001 10.380 (1.320–81.599) 0.026
Positive family history 2.305 (1.047–5.077) 0.038 0.436 (0.091–1.950) 0.277
Calcium channel antagonists 3.601 (1.582–8.198) 0.002 1.377 (0.266–7.131) 0.703
Antiplatelet drugs 4.582 (1.755–11.962) 0.002 2.911 (0.455–18.620) 0.259
Dyspnea (NYHA class) 4.443 (2.128–9.274) <0.001 1.444 (0.317–6.582) 0.635
ASA score 3.812 (1.582–9.188) 0.003 1.059 (0.089–12.577) 0.964
EF (%) 0.881 (0.823–0.942) <0.001 0.928 (0.834–1.033) 0.174
CK-MB (U/L) 1.006 (1.001–1.011) 0.017 1.010 (1.000–1.020) 0.058
CE vs. AAAR 0.294 (0.117–0.735) 0.009 0.491 (0.050–4.861) 0.543
AFBP vs. AAAR 2.769 (0.226–33.879) 0.425 31.339 (0.570–1722.649) 0.092
FPBP vs. AAAR 0.213 (0.060–0.760) 0.017 2.299 (0.133–37.361) 0.577
RCRI 1.788 (1.285–2.486) 0.001
RCRI (%) 1.194 (1.082–1.317) <0.001 0.935 (0.686–1.275) 0.673
RCRI (2 or 10.1%) 4.343 (1.899–9.931) 0.001
Gupta MICA 2.720 (1.465–5.049) 0.002
Gupta MICA (0.8) 6.024 (2.516–14.421) <0.001 2.486 (0.403–15.339) 0.327
GSCRI 1.135 (1.051–1.227) 0.001
GSCRI (1.5) 8.500 (2.450–29.495) 0.001 6.775 (0.830–55.268) 0.074
NT-proBNP (pg/mL) 1.006 (1.003–1.009) <0.001
NT-proBNP (208.0 pg/mL) 8.507 (3.569–20.276) <0.001 25.599 (4.869–134.574) 0
Hs-CRP (0.92 mg/L) 3.306 (1.472–7.421) 0.004 3.751 (0.761–18.487) 0.104
Legend: OR, odds ratio; CI, confidence interval; CAD, coronary artery disease; NYHA, New York Heart Association; ASA, American Society of Anesthesiologist; EF, ejection fraction; CK-MB, MB isoenzyme of creatine kinase; AAAR, repair of abdominal aortic aneurysm; CE, carotid endarterectomy; AFBP, aortobifemoral bypass; FPBP, femoropopliteal bypass; RCRI, Revised Cardiac Risk Index; MICA, myocardial infarction and cardiac arrest; GSCRI, Geriatric-Sensitive Cardiac Risk Index; NT-proBNP, N-terminal fragment of pro-B-type natriuretic peptide; Hs-CRP, high-sensitivity C-reactive protein.
Table 4.  Cox regression model of MACE occurrence during the 6-months after the procedure.
Variable Univariable analysis - HR (95% CI) p-value Multivariable analysis - HR (95% CI) p-value
Gender (female) 3.177 (1.226–8.231) 0.017 1.713 (0.543–5.407) 0.358
Previous CAD 2.998 (1.502–5.983) 0.002 1.818 (0.566–5.840) 0.315
Positive family history 2.003 (1.009–3.977) 0.047 1.491 (0.533–4.169) 0.447
Calcium channel antagonists 2.767 (1.396–5.482) 0.004 0.715 (0.212–2.415) 0.589
Antiplatelet drugs 3.811 (1.572–9.235) 0.003 2.566 (0.762–8.639) 0.128
Dyspnea (NYHA class) 3.600 (1.925–6.735) <0.001 1.752 (0.584–5.256) 0.317
ASA score 3.170 (1.429.7.033) 0.005 2.163 (0.388–12.056) 0.379
EF (%) 0.905 (0.860–0.953) <0.001 1.001 (0.934–1.073) 0.974
CK-MB (U/L) 1.004 (1.002–1.006) 0.001 1.002 (0.999–1.005) 0.115
CE vs. AAAR 0.386 (0.181–0.823) 0.014 0.261 (0.056–1.213) 0.087
AFBP vs. AAAR 2.069 (0.466–9.197) 0.339 6.537 (0.794–53.662) 0.08
FPBP vs. AAAR 0.290 (0.095–0.891) 0.031 0.789 (0.145–4.303) 0.784
RCRI 1.504 (1.185–1.908) 0.001
RCRI (%) 1.145 (1.059–1.239) 0.001 0.849 (0.690–1.094) 0.231
RCRI (2 or 10.1%) 3.495 (1.696–7.215) 0.001
Gupta MICA 1.907 (1.304–2.790) 0.001
Gupta MICA (0.8) 4.182 (2.105–8.312) <0.001 1.407 (0.451–4.391) 0.556
GSCRI 1.097 (1.038–1.160) 0.001 1.071 (0.987–1.161) 0.098
GSCRI (1.5) 7.050 (2.150–23.121) 0.001
NT-proBNP (pg/mL) 1.004 (1.003–1.006) <0.001 1.004 (1.001–1.006) 0.002
NT-proBNP (208.0 pg/mL) 5.928 (2.939–11.955) <0.001
Hs-TnI (ng/mL) 1889.529 (2.136–1671404.819) 0.029 1460.863 (0.216–9895313.278) 0.105
Hs-CRP (0.92 mg/L) 2.822 (1.424–5.590) 0.003 2.716 (1.107–6.665) 0.029
Legend: HR, hazard ratio; CI, confidence interval; CAD, coronary artery disease; NYHA, New York Heart Association; ASA, American Society of Anesthesiologist; EF, ejection fraction; CK-MB, MB isoenzyme of creatine kinase; AAAR, repair of abdominal aortic aneurysm; CE, carotid endarterectomy; AFBP, aortobifemoral bypass; FPBP, femoropopliteal bypass; RCRI, Revised Cardiac Risk Index; MICA, myocardial infarction and cardiac arrest; GSCRI, Geriatric-Sensitive Cardiac Risk Index; NT-proBNP, N-terminal fragment of pro-B-type natriuretic peptide; Hs-TnI, High-sensitivity troponin I; Hs-CRP, high-sensitivity C-reactive protein.
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