BRIEF TEXT
Background and Objective
… [1] Coronary artery disease (CAD) is a leading cause of death worldwide, and inflammation plays a key role in its pathogenesis [2]. … [3]. Atherosclerosis is a multifactorial disease and the main cause of cardiovascular disease, which is the leading cause of death worldwide [4]. … [5]… [6]… [7]. Recent studies have focused on simple, inexpensive, and promising complete blood count (CBC) parameters [8]. Among these parameters, the neutrophil-to-lymphocyte ratio (NLR) is an indicator of systemic inflammation [9]. Previous studies have demonstrated that NLR is a reliable inflammatory biomarker in the atherosclerotic process and a predictor of clinical outcomes in individuals with various cardiovascular diseases [10]. Additionally, other proposed inflammatory factors, such as high-sensitivity C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), have also been extensively studied in patients with CAD [11, 12]. This study aimed to investigate the association between CBC-derived inflammatory indices and the angiographic severity of CAD.
Materials and Methods
In this retrospective cross-sectional study, the records of 236 patients (189 men, 47 women) with a mean age of 47.9 ± 5.4 years who underwent elective coronary angiography were reviewed. The severity of CAD was determined using the SYNTAX score. Demographic data, CBC.diff parameters (including NLR and platelet-to-lymphocyte ratio [PLR]), and ESR and CRP levels were collected and analyzed using SPSS (version 16) and appropriate statistical tests.
Results
In the overall analysis, levels of white blood cell (WBC) (P = 0.046), neutrophil (P = 0.002), NLR (P = 0.012), PLR (P = 0.032), hematocrit (P = 0.020), ESR (P < 0.001), and CRP (P = 0.004) were all significantly associated with the severity of CAD. These associations were particularly stronger in men and individuals aged > 45 years. In contrast, none of the parameters showed a significant association in the female population, and lymphocyte count, platelet count, and hemoglobin also showed no significant association in the total sample (Tables 1, 2, and 3).
Discussion
In this retrospective cross-sectional study, the association between inflammatory factors and CBC. diff parameters with the severity of CAD in 236 patients (80.1% male) with a mean age of 47.9 years were investigated. The main findings revealed significant associations between WBC, neutrophil, NLR, PLR, hematocrit, ESR, and CRP levels with the severity of coronary artery involvement. These associations were notably robust in men and individuals aged > 45 years. Conversely, none of the parameters were significantly associated with the female population. Our discovery of an association between WBC and CAD severity aligns with prior studies [9,13]. As a readily available inflammatory marker, WBC may be as effective as CRP in identifying individuals at risk for cardiovascular disease (CVD) [11,14]. … [15]. Our findings indicate that neutrophils were a strong predictor of CAD severity. In contrast, lymphocytes alone did not show a significant association, a result consistent with a meta-analysis linking neutrophils to CVD [14]. The NLR was also notable in our study as a composite inflammatory marker, consistent with the findings of Bhat [16] and Lee [17]. PLR was associated with CAD severity in our study. This result aligns with the research of Shahabirabori [18] and Yayla [19], who identified PLR as a valuable prognostic marker in cardiovascular patients. While the association based on gender was not statistically significant in our study, Moosazadeh's research showed higher PLR levels in women [20]. The platelet count alone did not show a significant association with CAD severity in our current study, contradicting the findings of a study by Haybar et al. [21], which reported a positive relationship. The observation that hematocrit was significantly associated with CAD severity is consistent with the Ghandehari study [22]. Elevated hematocrit levels can lead to increased blood viscosity and reduced tissue perfusion, particularly in individuals with atherosclerosis [23]. In this study, ESR emerged as the strongest predictor of CAD severity. This finding aligns with Ceasovschih's study [24]. Despite ESR being an indirect and nonspecific marker of inflammation, its consistent association with disease severity across all age and gender subgroups of men indicates its high utility. Additionally, the significant association of CRP with CAD severity was another finding consistent with several studies [25], [26], [27]. CRP serves not only as a marker of inflammation but also as an active player in the pathogenesis of atherosclerosis, impacting endothelial function, LDL oxidation, and the innate immune response [28].
The lack of a significant association between hemoglobin and CAD severity in our study aligns with DeLuca's findings [29]. While theoretically, hemoglobin levels could influence myocardial oxygenation, the results across various studies have been inconsistent [30].
Conclusion
Simple and cost-effective CBC-derived inflammatory indices, especially ESR, neutrophil count, NLR, and CRP, were significantly correlated with the severity of CAD. They can be used as useful preliminary screening tools to identify high-risk patients and assist in prioritizing coronary angiography.
References
- Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33(13):1635-701. PMID: 22555213 DOI: 10.1093/eurheartj/ehs092
- Little WC, Constantinescu M, Applegate R, Kutcher M, Burrows M, Kahl F, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988;78(5):1157-66. PMID: 3180375 DOI: 10.1161/01.cir.78.5.1157
- Shao C, Wang J, Tian J, Tang Y. Coronary artery disease: from mechanism to clinical practice. Adv Exp Med Biol. 2020;1177:1-36. PMID: 32246442 DOI: 10.1007/978-981-15-2517-9_1
- Mustafa Serkan K, Necmettin K, Veysel T, Refik Emre A, Fatih K, Sinan Cemgil O, et al. Red cell distribution width and neutrophil-to-lymphocyte ratio predict left ventricular dysfunction in acute anterior ST-segment elevation myocardial infarction. J Saudi Heart Assoc. 2016;28(3):152-8. PMID: 27358532 DOI: 10.1016/j.jsha.2015.07.001
- Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135-43. PMID: 11877368 DOI: 10.1161/hc0902.104353
- Yuksel A, Velioglu Y, Cayir MC, Kumtepe G, Gurbuz O. Current status of arterial revascularization for the treatment of critical limb ischemia in infrainguinal atherosclerotic disease. Int J Angiol. 2018;27(3):132-7. PMID: 30154631 DOI: 10.1055/s-0037-1620242
- Wilhelmsen L, Wedel H, Tibblin G. Multivariate analysis of risk factors for coronary heart disease. Circulation. 1973;48(5):950-8. PMID: 4751960 DOI: 10.1161/01.cir.48.5.950
- Cho KI, Ann SH, Singh GB, Her AY, Shin ES. Combined usefulness of the platelet-to-lymphocyte ratio and the neutrophil-to-lymphocyte ratio in predicting long-term adverse events in patients who have undergone percutaneous coronary intervention with a drug-eluting stent. PLoS One. 2015;10(7):e0133934. PMID: 26207383 DOI: 10.1371/journal.pone.0133934
- Ergelen M, Uyarel H, Altay S, Kul S, Ayhan E, Isik T, et al. Predictive value of elevated neutrophil-to-lymphocyte ratio in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction. Clin Appl Thromb Hemost. 2014;20(4):427-32. PMID: 23314674 DOI: 10.1177/1076029612473516
- Lee MJ, Park SD, Kwon SW, Woo SI, Lee MD, Shin SH, et al. Relation between neutrophil-to-lymphocyte ratio and index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Am J Cardiol. 2016;118(9):1323-8. PMID: 27600462 DOI: 10.1016/j.amjcard.2016.07.072
- Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA. 1998;279(18):1477-82. PMID: 9600484 DOI: 10.1001/jama.279.18.1477
- Rasouli M, Kiasari AM, Bagheri B. Total and differential leukocyte counts, but not hsCRP, ESR, and five fractioned serum proteins, have significant potency to predict stable coronary artery disease. Clin Chim Acta. 2007;377(1-2):127-32. PMID: 17067564 DOI: 10.1016/j.cca.2006.09.009
- Akpek M, Kaya MG, Lam YY, Sahin O, Elcik D, Celik T, et al. Relation of neutrophil-to-lymphocyte ratio to coronary flow and in-hospital major adverse cardiac events in patients with ST-segment elevation myocardial infarction undergoing primary coronary intervention. Am J Cardiol. 2012;110(5):621-7. PMID: 22608360 DOI: 10.1016/j.amjcard.2012.04.041
- Lassale C, Curtis A, Abete I, van der Schouw YT, Verschuren WM, Lu Y, et al. Elements of the complete blood count associated with cardiovascular disease incidence: findings from the EPIC-NL cohort study. Sci Rep. 2018;8(1):3290. PMID: 29459661 DOI: 10.1038/s41598-018-21661-x
- Vakili H, Khaheshi I, Sharifi A, Nickdoost N, Namazi MH, Safi M, et al. Assessment of admission time complete blood count parameters in predicting post-primary percutaneous coronary intervention TIMI frame count in patients with ST-segment elevation myocardial infarction. Cardiovasc Hematol Disord Drug Targets. 2020;20(3):191-7. PMID: 32026789 DOI: 10.2174/1871529x20666200206123118
- Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther. 2013;11(1):55-9. PMID: 23259445 DOI: 10.1586/erc.12.159
- Lee CD, Folsom AR, Nieto FJ, Chambless LE, Shahar E, Wolfe DA. White blood cell count and incidence of coronary heart disease and ischemic stroke, and mortality from cardiovascular disease. Am J Epidemiol. 2001;154(8):758-64. PMID: 11590089 DOI: 10.1093/aje/154.8.758
- Shahabirabori V, Shahabirabori R, Hatami Y, Hajizadeh R, Rahimi B. Relationship of peripheral blood platelet-to-lymphocyte ratio with severity of coronary disease in patients with acute coronary syndrome. J Ilam Univ Med Sci. 2021;29(1):30-8. DOI: 10.52547/sjimu.29.1.4
- Yayla C, Akboga MK, Canpolat U, Akyel A, Yayla KG, Dogan M, et al. Platelet-to-lymphocyte ratio can be a predictor of infarct-related artery patency in patients with ST-segment elevation myocardial infarction. Angiology. 2015;66(9):831-6. PMID: 25712290 DOI: 10.1177/0003319715573658
- Moosazadeh M, Maleki I, Alizadeh-Navaei R, Kheradmand M, Hedayatizadeh-Omran A, Shamshirian A, et al. Normal values of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio among Iranian population. Caspian J Intern Med. 2019;10(3):320-5. PMID: 31558995 DOI: 10.22088/cjim.10.3.320
- Haybar H, Pezeshki SMS, Saki N. Evaluation of complete blood count parameters in cardiovascular diseases: an early indicator of prognosis? Exp Mol Pathol. 2019;110:104267. PMID: 31194963 DOI: 10.1016/j.yexmp.2019.104267
- Ghandehari K, Kazemi T. Hematocrit level in patients with stroke or ischemic heart disease, Khorasan 2002–2003. J Hormozgan Univ Med Sci. 2004;8:77-80. Link
- Carr JH. Clinical Hematology Atlas. 6th ed. St. Louis (MO): Elsevier; 2021. Link
- Ceasovschih A, Sorodoc V, Onofrei V, Tesloianu D, Tuchilus C, Anisie E, et al. Biomarker utility for peripheral artery disease diagnosis in real clinical practice. Diagnostics. 2020;10(9):723. PMID: 32962217 DOI: 10.3390/diagnostics10090723
- Rahbari-Manesh A, Salamati P, Ghaforian S, Zekavat M. Relationship between ESR, CRP, platelet count and coronary artery disease in Kawasaki disease. Iran J Pediatr. 2005;15(2):139-44. Link
- Mohebbi H, Mehrvarz S, Khorrami M. Evaluation of serum CRP, procalcitonin and WBC in the diagnosis of acute appendicitis. Iran J Surg. 2011;19(1):41-6. Link
- Dahmardehei M, Vahab M, Sargazimoghadam M. Diagnostic value of leukocytosis, ESR and CRP in patients with suspected acute appendicitis. Zahedan J Res Med Sci. 2013;15(7):e92915. Link
- Shrivastava AK, Singh HV, Raizada A, Singh SK. C-reactive protein, inflammation and coronary heart disease. Egypt Heart J. 2015;67(2):89-97. DOI: 10.1016/j.ehj.2014.11.005
- De Luca G, Secco GG, Cassetti E, Verdoia M, Bellomo G, Marino P, et al. Haemoglobin levels do not correlate with the extent of coronary artery disease. Coron Artery Dis. 2014;25(6):463-8. PMID: 24614627 DOI: 10.1097/mca.0000000000000103
- Muzzarelli S, Pfisterer M; TIME Investigators. Anemia as independent predictor of major events in elderly patients with chronic angina. Am Heart J. 2006;152(5):991-6. PMID: 17070178 DOI: 10.1016/j.ahj.2006.06.014
Table 1. Frequency Distribution of Participants by Age and Gender Groups
| Variables | No. (%) | |
|---|---|---|
| Gende | Female | 47 (19.9) |
| Male | 189 (80.1) | |
| Age | ≤ 45 | 66 (28) |
| > 45 | 170 (72) | |
| Severity of the disease | Mild (< 22) | 196 (83) |
| (SYNTAX) | Medium (22-32) | 31 (13) |
| Severe (> 32) | 9 (4) |
Table 2. Statistical Correlation (P value) of the Studied Parameters with the Severity of Coronary Artery Disease
| Parameter | Total | Age ≤ 45 | Age > 45 | Males | Females |
|---|---|---|---|---|---|
| WBC | 0.046 | 0.020 | 0.366 | 0.137 | 0.548 |
| Neutrophil | 0.002 | 0.109 | 0.023 | 0.002 | 0.639 |
| Lymphocyte | 0.071 | 0.314 | 0.164 | 0.069 | 0.791 |
| NLR | 0.012 | 0.447 | 0.063 | 0.017 | 0.718 |
| Platelet count | 0.109 | 0.106 | 0.463 | 0.131 | 0.637 |
| PLR | 0.032 | 0.649 | 0.002 | 0.185 | 0.134 |
| Hematocrit | 0.020 | 0.049 | 0.157 | 0.006 | 0.674 |
| Hemoglobin | 0.308 | 0.691 | 0.489 | 0.285 | 0.697 |
| ESR | > 0.001 | 0.001 | > 0.001 | > 0.001 | 0.079 |
| CRP | 0.004 | 0.109 | 0.049 | 0.004 | 0.456 |
Abbreviations: NLR, neutrophil-to-lymphocyte ratio; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; PLR, platelet-to-lymphocyte ratio; WBC, white blood cell.
Table 3. Distribution of Coronary Artery Disease Severity Based on Erythrocyte Sedimentation Rate (ESR) Status
| Severity of the disease (SYNTAX) | Normal ESR, No. (%) | High ESR, No. (%) | Total, No. (%) |
|---|---|---|---|
| Mild (<22) | 143 (73) | 53 (27) | 196 (100) |
| Medium (22-32) | 19 (61) | 12 (39) | 31 (100) |
| Severe (>32) | 0 (0) | 9 (100) | 9 (100) |
| Total | 162 (69) | 74 (31) | 236 (100) |

