Next Article in Journal
Short-Term Treatment with Empagliflozin Resulted in Dehydration and Cardiac Arrest in an Elderly Patient with Specific Complications: A Case Report and Literature Review
Previous Article in Journal
Botulinum Toxin Use for Modulating Neuroimmune Cutaneous Activity in Psoriasis
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Value of the Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Predicting CPET Performance in Patients with Stable CAD and Recent Elective PCI

by
Andrei Drugescu
1,
Mihai Roca
1,*,
Ioana Mădălina Zota
1,*,
Alexandru-Dan Costache
1,
Oana Irina Gavril
1,
Radu Sebastian Gavril
1,
Teodor Flaviu Vasilcu
1,
Ovidiu Mitu
1,
Irina Mihaela Esanu
1,
Iulia-Cristina Roca
2,
Cristina Mihaela Ghiciuc
3 and
Florin Mitu
1
1
Medical I Department, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
2
Surgery II Department, Faculty of Medicine, ”Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
3
Morpho-Functional Sciences II Department, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
*
Authors to whom correspondence should be addressed.
Medicina 2022, 58(6), 814; https://doi.org/10.3390/medicina58060814
Submission received: 23 April 2022 / Revised: 5 June 2022 / Accepted: 14 June 2022 / Published: 16 June 2022
(This article belongs to the Section Cardiology)

Abstract

:
Background and Objectives: Functional capacity (FC) assessed via cardiopulmonary exercise testing (CPET) is a novel, independent prognostic marker for patients with coronary artery disease (CAD). Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are two readily available predictors of systemic inflammation and cardiovascular event risk, which could be used as cost-effective predictors of poor FC. The purpose of this study was to evaluate the utility of NLR and PLR in predicting poor FC in patients with CAD and recent elective percutaneous coronary intervention (PCI). Materials and Methods: Our cross-sectional retrospective analysis included 80 patients with stable CAD and recent elective PCI (mean age 55.51 ± 11.83 years, 71.3% male) who were referred to a cardiovascular rehabilitation center from January 2020 to June 2021. All patients underwent clinical examination, cardiopulmonary exercise testing on a cycle ergometer, transthoracic echocardiography and standard blood analysis. Results: Patients were classified according to percent predicted oxygen uptake (% VO2 max) in two groups—poor FC (≤70%, n = 35) and preserved FC (>70%, n = 45). There was no significant difference between groups regarding age, gender ratio, presence of associated comorbidities, left ventricular ejection fraction and NLR. PLR was higher in patients with poor FC (169.8 ± 59.3 vs. 137.4 ± 35.9, p = 0.003). A PLR cut-off point of 139 had 74% sensitivity and 60% specificity in predicting poor FC. After multivariate analysis, PLR remained a significant predictor of poor functional status. Conclusions: Although CPET is the gold standard test for assessing FC prior to cardiovascular rehabilitation, its availability remains limited. PLR, a cheap and simple test, could predict poor FC in patients with stable CAD and recent elective PCI and help prioritize referral for cardiovascular rehabilitation in high-risk patients.

1. Introduction

Coronary artery disease (CAD) is a significant public health problem, with a substantial contribution to global morbidity and mortality, especially in low- and middle-income countries [1,2]. Current guidelines firmly recommend enrollment in a comprehensive cardiovascular rehabilitation (CR) program after CAD diagnosis or revascularization, with proven beneficial effects on cardiovascular and all-cause mortality and individual quality of life (QoL) [3,4,5,6]. CAD is associated with a significant impact on the individual’s exercise capacity, which can rapidly deteriorate after a major cardiovascular event [7]. Compared to post-acute coronary syndromes (ACS), CR addressability is lower in patients with stable CAD and following elective percutaneous coronary intervention (PCI) [8], as well as in women, elderly and socio-economically deprived patients [9].
Functional capacity (FC) is a strong, independent prognostic factor in heart failure (HF) [10] and CAD [11]. The prognostic value of FC is independent and additive to other well established mortality predictors such as left ventricular ejection fraction (LVEF), smoking, hypertension (HTN), dyslipidemia and diabetes [12,13,14]. Peak oxygen uptake (VO2 max) assessed via cardiopulmonary exercise testing (CPET) is an objective measure of FC, and an independent predictor of cardiovascular morbidity and mortality in patients with CAD [12,13,15,16]. However, CPET availability remains limited, especially in developing countries.
Systemic inflammation plays a major role in CAD etiopathogenesis [17] and routine inflammatory biomarkers (complete blood count, C-reactive protein) have proven their role for both acute and long-term cardiovascular risk assessment [18,19,20]. Physical activity decreases systemic markers of inflammation, thrombosis and endothelial dysfunction, and has a key role in preventing CAD [21,22,23]. The platelet to lymphocyte ratio (PLR) is an integrated reflection of two important opposite inflammatory pathways that can be easily calculated from a complete blood count. PLR initially served as a prognostic biomarker in neoplastic diseases [24,25], but has recently been studied in HF [26,27,28], ACS [29,30,31,32,33], atrial fibrillation [34,35], deep venous thrombosis [36], PCI [37,38,39] and infective endocarditis [40]. The neutrophil to lymphocyte ratio (NLR) is another readily available biomarker of inflammation in cardiac and non-cardiovascular disorders [41,42,43]. In previous reports, the NLR appeared to be a predictor of cardiovascular events and mortality in patients with stable CAD and was associated with coronary atherosclerosis severity [44,45]. NLR was also used as a predictor for functional capacity in patients undergoing CR [46] and a predictor of lipid-lowering effectiveness in patients with familial hypercholesterolemia and atherosclerotic cardiovascular disease [47]. However, the current literature offers limited data regarding the role of these readily available inflammatory biomarkers in predicting exercise performance in CAD patients. We therefore hypothesized that impaired cardiovascular performance (as defined by CPET) could be predicted by NLR and PLR in individuals with stable CAD and recent elective PCI. The aim of this study was to evaluate the utility of two readily available inflammatory biomarkers (NLR and PLR) in predicting poor FC in patients with CAD and recent elective PCI.

2. Materials and Methods

We conducted a retrospective cross-sectional study of all patients with stable CAD and recent elective PCI, referred for phase II CR in the Cardiovascular Unit of the Clinical Rehabilitation Hospital in Iași over a period of 18 months (January 2020–June 2021). The Cardiovascular Unit of the Clinical Rehabilitation Hospital in Iași is a nationally ranked dedicated rehabilitation center specializing in phases II and III of cardiovascular rehabilitation [4,48]. Inclusion criteria were as follows: elective PCI performed for stable CAD during the previous 3 months and CPET performed upon admission (Figure 1). Patients with ACSduring the previous 12 months, anemia (hemoglobin <12 g/dL in females and <13 g/dL in males), atrial fibrillation, moderate or severe valvular heart disease, decompensated congestive heart failure, any congenital heart disease or any other severe chronic disease except CAD were excluded from this analysis. All patients had a negative COVID-19 PCR upon admission. Socio-demographic, clinical, biological, CPET and echocardiographic data were extracted from hospital medical records.
All patients were under optimal CAD treatment, according to current guidelines [49]. Obesity was defined as a body mass index (BMI) ≥30 kg/m2. High blood pressure (HBP) was defined as current BP lowering treatment, prior diagnosis of HBP, resting systolic blood pressure (SBP) greater than 140 or resting diastolic blood pressure (DBP) greater than 90 mmHg [50]. Diabetes was defined as current antidiabetic treatment, previous diabetes diagnosis, fasting glucose ≥126 mg/dL on two separate occasions or a value for glycosylated hemoglobin ≥6.5% [51,52,53].
According to hospital protocol, blood samples were collected a jeun, in the morning upon admission, by qualified medical professionals. All blood samples were processed in the hospital’s laboratory. Complete blood count was processed using the Pentra DF Nexus Hematology System® (Horiba Healthcare, Kyoto, Japan). Biochemistry was processed using the Transasia XL 1000 Fully Automated Biochemistry Analyzer (Transasia Bio-Medicals Ltd., Mumbai, India). We recorded the following parameters: platelet count, neutrophil count, lymphocyte count, C-reactive protein (CRP), low-density lipoprotein (LDL) and glycated hemoglobin (HbA1c). NLR was calculated using the absolute neutrophil (N) and lymphocyte (L) values from the complete blood count, using the formula: NLR = N/L. PLR was calculated using the absolute platelets (P) and lymphocyte (L) values from the complete blood count, using the formula: PLR = P/L.
Standardized transthoracic echocardiography (2D, Doppler) was performed by experienced sonographists according to current EACVI guidelines [54] (Toshiba Aplio 500 Series, Toshiba Medical Systems Corporation, Ōtawara, Tochigi, Japan) prior to CPET evaluation. LVEF was calculated using Simpson biplane method.
CPET was performed by a certified pulmonologist on the Piston PRE-201 ergospirometer (Piston Ltd., Budapest, Hungary). According to hospital protocol, CPET was performed in the morning of the second day of hospitalization, in order to establish functional capacity and target heart rate for exercise rehabilitation. Each patient signed a written informed consent before the test. The test consisted of a 2 min resting period followed by 3 min warm up at 0 W followed by standard incremental exercise protocol of 15 W/min. The CPET was performed under continuous heart rate (HR), 12-lead ECG (electrocardiographic) and pulse oximetry (SpO2) monitoring. Blood pressure was recorded every 2 min. Indications for exercise termination included exhaustion, myocardial ischemia, complex ventricular arrythmia, grade 2 or 3 atrio-ventricular block, a sudden drop in BP levels > 20 mmHg, extreme BP elevation (SBP > 220 mmHg, DBP > 120 mmHg), SpO2 < 80%, confusion or severe dizziness. We recorded the following parameters: resting SBP and DBP (measured with a manual sphygmomanometer immediately prior to the CPET), resting HR (recorded on the resting ECG performed immediately prior to the CPET), % peak HR (maximum heart rate relative to predicted normal for age (220—age in years)), % peak WR (maximum workload relative to predicted normal according to age and sex, automatically calculated by the ergospirometer software) and % VO2 max (maximum oxygen uptake (highest value, mean of 20 s) relative to predicted normal according to age and sex, automatically calculated by the ergospirometer software). Functional capacity was assessed according % VO2 max, using a convention proposed by Cooper et al., as follows: >80%—normal, 71–80%—mildly reduced, 51–70%—moderately reduced and ≤50%—severely reduced [55]. Due to a relatively small number of enrolled patients, we divided our study group as follows: poor FC (% VO2 max ≤70) and preserved FC (% VO2 max >70).

2.1. Statistical Analysis

Data analysis was performed using SPSS 20.0 (Statistical Package for the Social Sciences, Chicago, IL, USA). For continuous data, the normality of distribution was assessed by Shapiro–Wilk test. Data are presented as mean ± standard deviation (SD) for continuous variables with normal distribution, or as median with interquartile range for non-normally distributed continuous variables. Categorical variables are presented as number of cases with percent frequency. An independent samples T-test was used to compare continuous variables with normal distribution. A non-parametric Mann–Whitney’s U test was applied to compare the variables not satisfying the assumption of normality. Categorical comparisons were performed using Chi-square test or Fisher’s exact test (when the expected number of values in any of the cells of a contingency table was ≤5). Variables with p < 0.05 in the univariate analysis were included in the multivariate logistic regression model, to assess the independent predictors of poor FC (% VO2 max ≤ 70). The results are presented as odds ratio (OR) with 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curve analysis was done to determine the optimum cut-off value of PLR in predicting poor FC of CAD patients and recent PCI. Correlation analyses, calculating Pearson correlation coefficients, were assessed considering normally distributed and linearly related variables. A two-sided p value < 0.05 was considered significant for all analyses.

2.2. Ethics Statement

The study was approved by the Review Board/Ethics Committee of the Clinical Rehabilitation Hospital Iași (number 28567/21.12.2020) and complied with the Declaration of Helsinki. The Clinical Rehabilitation Hospital Iasi Review Board/Ethics Committee considered informed consent unnecessary owing to the characteristics of this study (retrospective database analysis).

3. Results

Table 1 illustrates clinical and demographic features, laboratory findings and exercise measurements of the 80 analyzed patients (age range: 34–79 years old) and a univariate analysis of the two subgroups according to the values of % VO2 max. Age and the presence of cardiometabolic comorbidities (obesity, diabetes, HTN, LDL level) were similar among the two subgroups.
Our analysis included 35 patients with % VO2 ≤70 and 45 patients with % VO2 >70. Among the hematological parameters, the PLR was higher in the group of % VO2 max ≤70 than in the group of % VO2 max >70 (p = 0.003, Figure 2). NLR values were higher in patients with poor FC, but the difference did not reach statistical significance. Patients with preserved FC had higher LVEF values (p = 0.003) and reached a higher peak HR during exercise (p = 0.006). CRP, platelet, neutrophil and lymphocyte count, as well as resting HR and blood pressure values, were similar between the two subgroups.
PLR were positively correlated with % VO2 max (p < 0.05; Table 2). NLR was associated with PLR, but not with the analyzed CPET parameters.
In a logistic multivariate model, the PLR remained significant predictor of poor FC (Table 3). NLR was not a significant predictor of poor FC in univariate analysis; thus, it was not included in the multivariable regression model.
ROC curves explored the relationship between the PLR and FC. Using a cut-off point of 139, the PLR predicted poor FC with a sensitivity of 74% and specificity of 60% (ROC area under curve: 0.681, 95% CI: 0.563–0.799, p = 0.006; Figure 3).

4. Discussion

The results of the present study suggest that significant prognostic information can be obtained from routine blood test results in CAD patients undergoing CR. Walzik et al. recently published reference values for NLR and PLR, encouraging a more frequent use in clinical practice [56]. NLR and PLR were significantly higher among our patients (especially in the subgroup with poor functional capacity) compared to the average NLR and PLR values recently reported in a healthy population-based cohort: 1.76 (0.83–3.92) and 120 (61–239), respectively [57].
Functional capacity is an independent prognostic factor in CAD patients [4,15,58,59,60]. Our data show that impaired FC assessed with CPET is associated with changes in leukocyte subsets and platelets. Inflammation plays a role in the onset, progression and destabilization of atherosclerotic plaque. Systemic inflammation is known to be associated with parietal vascular inflammation [61]. Activation of lymphocytes and monocytes is essential in the early stages of atherosclerosis, while neutrophils are implicated in plaque destabilization and thrombosis [62]. NLR is an easily available biomarker of vascular parietal inflammation [63] with documented prognostic implications in various cardiovascular diseases [64]. Elevated NLR has been associated with an increased risk of atrial [65,66,67] and ventricular arrythmias [68] and with worse outcomes in acute decompensated heart failure [69] and acute coronary syndromes [70]. Besides CAD, NLR offers prognostic information in patients with abdominal aortic aneurysm [71], chronic threatening limb ischemia [72] and other cardiovascular emergencies [73,74,75,76,77]. NLR is also a biomarker of interest in severe mitral and aortic valvular heart disease [78,79] and is a predictor of poor FC in patients with HF (OR 3.085, 95% CI 1.52–6.26, p = 0.002) [80]. Indeed, immune dysregulation is known as an important characteristic of poor aerobic capacity. Increased NLR could be associated with poorer physical performance in CAD patients and with lower LVEF in patients with HF [80]. In a previous study, Yıldız et al. showed that a threshold level of 2.26 for NLR predicts a poor FC (sensitivity of 83% and specificity of 69%) in patients with idiopathic dilated cardiomyopathy [81]. In another study of 94 patients with compensated HF, NLR was correlated with exercise performance, and a cut-off point of 2.74 was established for predicting poor FC [80]. FC was expressed as maximal exercise intensity (METs) during treadmill test in both previous studies, a less specific marker for FC compared to % VO2 max. In the present analysis, although NLR values were higher in patients with poor FC, the difference did not reach statistical significance.
Elevated blood and plasma viscosity have been associated with an increased risk of CAD. CAD patients have increased platelet and monocyte aggregates in their bloodstream, which are associated with plaque instability, worse in-hospital outcomes and an increased risk of future cardiac events [82,83]. Exercise training improves blood rheology, which may contribute to the increased FC observed after CR [84]. PLR reflects the balance between thrombotic and inflammatory pathways, being influenced by blood viscosity and inflammation [63,82]. Ayca et al. showed that patients with high PLR had higher Syntax Score (SXS) and a PLR > 137 had a specificity of 52% and a sensitivity of 61% for predicting SXS > 22, marking PLR as a prognostic marker in primary PCI [39]. Azab et al. examined the prognostic value of PLR in non-STEMI [31]. At the 4-year follow up, patients with PLR > 176 had a 42% all-cause mortality, whereas patients with PLR < 118.4 had an all-cause mortality rate of 17%. In another study of patients with STEMI, Ugur et al. found that patients with PLR > 174.9 had higher all-cause mortality at 6 months compared with patients with PLR < 174.9 [32]. Moreover, previous studies also showed that high PLR is associated with increased risks of new-onset atrial fibrillation [38], contrast-induced acute kidney injury [85], more advanced HF [29] and no reflow after PCI in STEMI patients.
Our analysis shows that PLR is higher in patients with % VO2 max ≤70 than in patients with %VO2 max >70 (p = 0.003, Figure 2). PLR was positively correlated with % VO2 max (p < 0.05; Table 2) and remained significant predictor of poor FC (OR, 1.015; 95% CI, 1.004–1.027; p = 0.009) after multivariate analysis. Using a cut-off point of 139, the PLR predicted poor FC with a sensitivity of 74% and specificity of 60% (ROC area under curve: 0.681, 95% CI: 0.563–0.799, p = 0.006; Figure 3).
Other studies have assessed the relationship between CRP and FC in various non-cardiovascular conditions [86,87,88]. Our results do not support a significant association between CRP and FC in CAD patients with recent PCI.
The results of the present study suggest that significant prognostic information can be obtained from routine blood test results in CAD patients with recent PCI. Because the PLR is a ratio, it is less prone to bias/variations than individual blood parameters that can be altered by several variables (e.g., dehydration, over-hydration and blood specimen handling). To our knowledge, this is the first study that evaluated whether PLR can predict FC assessed by CPET in stable CAD with recent PCI.
This study has several limitations. Most importantly, this single-center retrospective analysis included a relatively small number of patients and did not include measurement of other important cardiac biomarkers such as troponin and natriuretic peptides. Furthermore, although all patients had a negative COVID-19 PCR upon admission, we were not able to accurately exclude prior COVID-19 infection (we did not perform antibody testing and we did not take into consideration vaccination status). Previous COVID-19 infection can negatively impact functional capacity and could influence our results. The retrospective structure of our study and the small number of cases, our multiple regression was limited to only a few covariates. Residual covariates and additional risk factors (for example smoking status) could significantly impact our results. Considering these limitations, our conclusions need to be validated in larger cohort analyses. Furthermore, larger prospective studies are needed to evaluate whether PLR can also predict FC improvement after cardiovascular rehabilitation programs.

5. Conclusions

PLR is higher in patients with recent PCI for stable CAD and poor FC compared to those with preserved FC. FC is an independent predictor of long-term prognosis in CAD. Although CPET is the gold standard test for assessing FC prior to cardiovascular rehabilitation, its availability remains limited. PLR, a cheap and simple test, could predict poor functional capacity in patients with stable CAD and recent elective PCI and help prioritize referral for cardiovascular rehabilitation in high-risk patients.

Author Contributions

Conceptualization, A.D., I.M.Z. and R.S.G.; methodology, F.M. and C.M.G.; software, M.R.; validation, O.M., T.F.V. and I.M.Z.; formal analysis, A.-D.C.; investigation, A.D.; resources, O.M. and F.M.; data curation, I.-C.R. and O.I.G.; writing—original draft preparation, A.D.; writing—review and editing, A.D. and I.M.Z.; visualization, I.M.E.; supervision, C.M.G. and F.M.; project administration, O.M. and F.M.; funding acquisition, I.M.E. and F.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Clinical Rehabilitation Hospital Iași (number 28567/21.12.2020).

Informed Consent Statement

Patient consent was waived because the Clinical Rehabilitation Hospital Iasi Review Board/Ethics Committee considered it unnecessary (retrospective database analysis).

Data Availability Statement

Data are available from the corresponding author upon request.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Nowbar, A.N.; Howard, J.P.; Finegold, J.A.; Asaria, P.; Francis, D.P. 2014 Global Geographic Analysis of Mortality from Ischaemic Heart Disease by Country, Age and Income: Statistics from World Health Organisation and United Nations. Int. J. Cardiol. 2014, 174, 293–298. [Google Scholar] [CrossRef] [Green Version]
  2. Ralapanawa, U.; Sivakanesan, R. Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: A Narrative Review. J. Epidemiol. Glob. Health 2021, 11, 169–177. [Google Scholar] [CrossRef]
  3. Goel, K.; Lennon, R.J.; Tilbury, R.T.; Squires, R.W.; Thomas, R.J. Impact of Cardiac Rehabilitation on Mortality and Cardiovascular Events after Percutaneous Coronary Intervention in the Community. Circulation 2011, 123, 2344–2352. [Google Scholar] [CrossRef] [Green Version]
  4. Ambrosetti, M.; Abreu, A.; Corrà, U.; Davos, C.H.; Hansen, D.; Frederix, I.; Iliou, M.C.; Pedretti, R.F.; Schmid, J.-P.; Vigorito, C.; et al. Secondary Prevention through Comprehensive Cardiovascular Rehabilitation: From Knowledge to Implementation. 2020 Update. A Position Paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur. J. Prev. Cardiol. 2020, 28, 460–495. [Google Scholar] [CrossRef] [Green Version]
  5. Price, K.J.; Gordon, B.A.; Bird, S.R.; Benson, A.C. A Review of Guidelines for Cardiac Rehabilitation Exercise Programmes: Is There an International Consensus? Eur. J. Prev. Cardiol. 2016, 23, 1715–1733. [Google Scholar] [CrossRef]
  6. Thomas, R.J.; Beatty, A.L.; Beckie, T.M.; Brewer, L.C.; Brown, T.M.; Forman, D.E.; Franklin, B.A.; Keteyian, S.J.; Kitzman, D.W.; Regensteiner, J.G.; et al. Home-Based Cardiac Rehabilitation: A Scientific Statement from the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology. Circulation 2019, 140, e69–e89. [Google Scholar] [CrossRef]
  7. Libby, P.; Ridker, P.M.; Hansson, G.K. Leducq Transatlantic Network on Atherothrombosis Inflammation in Atherosclerosis: From Pathophysiology to Practice. J. Am. Coll. Cardiol. 2009, 54, 2129–2138. [Google Scholar] [CrossRef] [Green Version]
  8. Olsen, S.J.; Schirmer, H.; Bønaa, K.H.; Hanssen, T.A. Cardiac Rehabilitation after Percutaneous Coronary Intervention: Results from a Nationwide Survey. Eur. J. Cardiovasc. Nurs. 2018, 17, 273–279. [Google Scholar] [CrossRef]
  9. Long, L.; Anderson, L.; He, J.; Gandhi, M.; Dewhirst, A.; Bridges, C.; Taylor, R. Exercise-Based Cardiac Rehabilitation for Stable Angina: Systematic Review and Meta-Analysis. Open Heart 2019, 6, e000989. [Google Scholar] [CrossRef]
  10. Lala, A.; Shah, K.B.; Lanfear, D.E.; Thibodeau, J.T.; Palardy, M.; Ambardekar, A.V.; McNamara, D.M.; Taddei-Peters, W.C.; Baldwin, J.T.; Jeffries, N.; et al. Predictive Value of Cardiopulmonary Exercise Testing Parameters in Ambulatory Advanced Heart Failure. JACC Heart Fail. 2021, 9, 226–236. [Google Scholar] [CrossRef]
  11. Keteyian, S.J.; Brawner, C.A.; Savage, P.D.; Ehrman, J.K.; Schairer, J.; Divine, G.; Aldred, H.; Ophaug, K.; Ades, P.A. Peak Aerobic Capacity Predicts Prognosis in Patients with Coronary Heart Disease. Am. Heart J. 2008, 156, 292–300. [Google Scholar] [CrossRef] [PubMed]
  12. Mezzani, A.; Hamm, L.F.; Jones, A.M.; McBride, P.E.; Moholdt, T.; Stone, J.A.; Urhausen, A.; Williams, M.A.; European Association for Cardiovascular Prevention and Rehabilitation; American Association of Cardiovascular and Pulmonary Rehabilitation; et al. Aerobic Exercise Intensity Assessment and Prescription in Cardiac Rehabilitation: A Joint Position Statement of the European Association for Cardiovascular Prevention and Rehabilitation, the American Association of Cardiovascular and Pulmonary Rehabilitation and the Canadian Association of Cardiac Rehabilitation. Eur. J. Prev. Cardiol. 2013, 20, 442–467. [Google Scholar] [CrossRef] [PubMed]
  13. Guazzi, M.; Adams, V.; Conraads, V.; Halle, M.; Mezzani, A.; Vanhees, L.; Arena, R.; Fletcher, G.F.; Forman, D.E.; Kitzman, D.W.; et al. Clinical Recommendations for Cardiopulmonary Exercise Testing Data Assessment in Specific Patient Populations. Circulation 2012, 126, 2261–2274. [Google Scholar] [CrossRef] [PubMed]
  14. Forman, D.E.; Arena, R.; Boxer, R.; Dolansky, M.A.; Eng, J.J.; Fleg, J.L.; Haykowsky, M.; Jahangir, A.; Kaminsky, L.A.; Kitzman, D.W.; et al. Prioritizing Functional Capacity as a Principal End Point for Therapies Oriented to Older Adults with Cardiovascular Disease: A Scientific Statement for Healthcare Professionals from the American Heart Association. Circulation 2017, 135, e894–e918. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. Hung, R.K.; Al-Mallah, M.H.; McEvoy, J.W.; Whelton, S.P.; Blumenthal, R.S.; Nasir, K.; Schairer, J.R.; Brawner, C.; Alam, M.; Keteyian, S.J.; et al. Prognostic Value of Exercise Capacity in Patients with Coronary Artery Disease: The FIT (Henry Ford Exercise Testing) Project. Mayo Clin. Proc. 2014, 89, 1644–1654. [Google Scholar] [CrossRef] [PubMed]
  16. Mikkelsen, N.; Cadarso-Suárez, C.; Lado-Baleato, O.; Díaz-Louzao, C.; Gil, C.P.; Reeh, J.; Rasmusen, H.; Prescott, E. Improvement in VO2peak Predicts Readmissions for Cardiovascular Disease and Mortality in Patients Undergoing Cardiac Rehabilitation. Eur. J. Prev. Cardiol. 2020, 27, 811–819. [Google Scholar] [CrossRef]
  17. Yoshikane, H.; Yamamoto, T.; Ozaki, M.; Matsuzaki, M. Clinical significance of high-sensitivity C-reactive protein in lifestyle-related disease and metabolic syndrome. J. Cardiol. 2007, 50, 175–182. [Google Scholar]
  18. Erikssen, G.; Liestøl, K.; Bjørnholt, J.V.; Stormorken, H.; Thaulow, E.; Erikssen, J. Erythrocyte Sedimentation Rate: A Possible Marker of Atherosclerosis and a Strong Predictor of Coronary Heart Disease Mortality. Eur. Heart J. 2000, 21, 1614–1620. [Google Scholar] [CrossRef]
  19. Andresdottir, M.B.; Sigfusson, N.; Sigvaldason, H.; Gudnason, V. Erythrocyte Sedimentation Rate, an Independent Predictor of Coronary Heart Disease in Men and Women: The Reykjavik Study. Am. J. Epidemiol. 2003, 158, 844–851. [Google Scholar] [CrossRef]
  20. Strang, F.; Schunkert, H. C-Reactive Protein and Coronary Heart Disease: All Said—Is Not It? Mediat. Inflamm. 2014, 2014, 757123. [Google Scholar] [CrossRef] [Green Version]
  21. Colbert, L.H.; Visser, M.; Simonsick, E.M.; Tracy, R.P.; Newman, A.B.; Kritchevsky, S.B.; Pahor, M.; Taaffe, D.R.; Brach, J.; Rubin, S.; et al. Physical Activity, Exercise, and Inflammatory Markers in Older Adults: Findings from the Health, Aging and Body Composition Study. J. Am. Geriatr. Soc. 2004, 52, 1098–1104. [Google Scholar] [CrossRef] [PubMed]
  22. Koenig, W.; Ernst, E. Exercise and Thrombosis. Coron. Artery Dis. 2000, 11, 123–127. [Google Scholar] [CrossRef] [PubMed]
  23. Linke, A.; Schoene, N.; Gielen, S.; Hofer, J.; Erbs, S.; Schuler, G.; Hambrecht, R. Endothelial Dysfunction in Patients with Chronic Heart Failure: Systemic Effects of Lower-Limb Exercise Training. J. Am. Coll. Cardiol. 2001, 37, 392–397. [Google Scholar] [CrossRef] [Green Version]
  24. Krenn-Pilko, S.; Langsenlehner, U.; Thurner, E.-M.; Stojakovic, T.; Pichler, M.; Gerger, A.; Kapp, K.S.; Langsenlehner, T. The Elevated Preoperative Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis in Breast Cancer Patients. Br. J. Cancer 2014, 110, 2524–2530. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  25. You, J.; Zhu, G.-Q.; Xie, L.; Liu, W.-Y.; Shi, L.; Wang, O.-C.; Huang, Z.-H.; Braddock, M.; Guo, G.-L.; Zheng, M.-H. Preoperative Platelet to Lymphocyte Ratio Is a Valuable Prognostic Biomarker in Patients with Colorectal Cancer. Oncotarget 2016, 7, 25516–25527. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  26. Durmus, E.; Kivrak, T.; Gerin, F.; Sunbul, M.; Sari, I.; Erdogan, O. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Are Predictors of Heart Failure. Arq. Bras. De Cardiol. 2015, 105, 606–613. [Google Scholar] [CrossRef]
  27. Heidarpour, M.; Bashiri, S.; Vakhshoori, M.; Heshmat-Ghahdarijani, K.; Khanizadeh, F.; Ferdowsian, S.; Shafie, D. The Association between Platelet-to-Lymphocyte Ratio with Mortality among Patients Suffering from Acute Decompensated Heart Failure. BMC Cardiovasc. Disord. 2021, 21, 454. [Google Scholar] [CrossRef]
  28. Ye, G.; Chen, Q.; Chen, X.; Liu, Y.; Yin, T.; Meng, Q.; Liu, Y.; Wei, H.; Zhou, Q. The Prognostic Role of Platelet-to-Lymphocyte Ratio in Patients with Acute Heart Failure: A Cohort Study. Sci. Rep. 2019, 9, 10639. [Google Scholar] [CrossRef] [Green Version]
  29. Sun, X.-P.; Li, J.; Zhu, W.-W.; Li, D.-B.; Chen, H.; Li, H.-W.; Chen, W.-M.; Hua, Q. Impact of Platelet-to-Lymphocyte Ratio on Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction. Angiology 2017, 68, 346–353. [Google Scholar] [CrossRef]
  30. Dong, G.; Huang, A.; Liu, L. Platelet-to-lymphocyte Ratio and Prognosis in STEMI: A Meta-analysis. Eur. J. Clin. Investig. 2021, 51, e13386. [Google Scholar] [CrossRef]
  31. Azab, B.; Shah, N.; Akerman, M.; McGinn, J.T. Value of Platelet/Lymphocyte Ratio as a Predictor of All-Cause Mortality after Non-ST-Elevation Myocardial Infarction. J. Thromb. Thrombolysis 2012, 34, 326–334. [Google Scholar] [CrossRef] [PubMed]
  32. Ugur, M.; Gul, M.; Bozbay, M.; Cicek, G.; Uyarel, H.; Koroglu, B.; Uluganyan, M.; Aslan, S.; Tusun, E.; Surgit, O.; et al. The Relationship between Platelet to Lymphocyte Ratio and the Clinical Outcomes in ST Elevation Myocardial Infarction Underwent Primary Coronary Intervention. Blood Coagul. Fibrinolysis 2014, 25, 806–811. [Google Scholar] [CrossRef] [PubMed]
  33. Willim, H.A.; Harianto, J.C.; Cipta, H. Platelet-to-Lymphocyte Ratio at Admission as a Predictor of In-Hospital and Long-Term Outcomes in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis. Cardiol. Res. 2021, 12, 109–116. [Google Scholar] [CrossRef] [PubMed]
  34. Zuo, K.; Yang, X. Decreased Platelet-to-Lymphocyte Ratio as Predictor of Thrombogenesis in Nonvalvular Atrial Fibrillation. Herz 2020, 45, 684–688. [Google Scholar] [CrossRef]
  35. Dereli, S.; Bayramoğlu, A.; Yontar, O.C. Usefulness of Platelet to Lymphocyte Ratio for Predicting Recurrence of Atrial Fibrillation after Direct Current Cardioversion. Ann. Noninvasive Electrocardiol. 2019, 24, e12616. [Google Scholar] [CrossRef] [Green Version]
  36. Velioğlu, Y.; Yüksel, A. Utility of Platelet-to-Lymphocyte Ratio to Support the Diagnosis of Acute Deep Vein Thrombosis. Turk. Gogus Kalp Damar Cerrahisi Derg. 2019, 27, 493–498. [Google Scholar] [CrossRef] [Green Version]
  37. Zhen, Y.; Chang, Z.; Liu, Z.; Zheng, J. Platelet to Lymphocyte Ratio Predicting 6-Month Primary Patency of Drug-Coated Balloon for Femoropopliteal Disease. BMC Cardiovasc. Disord. 2020, 20, 9. [Google Scholar] [CrossRef]
  38. Karataş, M.B.; Çanga, Y.; İpek, G.; Özcan, K.S.; Güngör, B.; Durmuş, G.; Onuk, T.; Öz, A.; Şimşek, B.; Bolca, O. Association of Admission Serum Laboratory Parameters with New-Onset Atrial Fibrillation after a Primary Percutaneous Coronary Intervention. Coron Artery Dis. 2016, 27, 128–134. [Google Scholar] [CrossRef]
  39. Ayça, B.; Akin, F.; Çelik, Ö.; Yüksel, Y.; Öztürk, D.; Tekiner, F.; Çetin, Ş.; Okuyan, E.; Dinçkal, M.H. Platelet to Lymphocyte Ratio as a Prognostic Marker in Primary Percutaneous Coronary Intervention. Platelets 2015, 26, 638–644. [Google Scholar] [CrossRef]
  40. Meshaal, M.S.; Nagi, A.; Eldamaty, A.; Elnaggar, W.; Gaber, M.; Rizk, H. Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) as Independent Predictors of Outcome in Infective Endocarditis (IE). Egypt Heart J. 2019, 71, 13. [Google Scholar] [CrossRef]
  41. Tamhane, U.U.; Aneja, S.; Montgomery, D.; Rogers, E.-K.; Eagle, K.A.; Gurm, H.S. Association between Admission Neutrophil to Lymphocyte Ratio and Outcomes in Patients with Acute Coronary Syndrome. Am. J. Cardiol. 2008, 102, 653–657. [Google Scholar] [CrossRef] [PubMed]
  42. Park, J.J.; Jang, H.-J.; Oh, I.-Y.; Yoon, C.-H.; Suh, J.-W.; Cho, Y.-S.; Youn, T.-J.; Cho, G.-Y.; Chae, I.-H.; Choi, D.-J. Prognostic Value of Neutrophil to Lymphocyte Ratio in Patients Presenting with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Am. J. Cardiol. 2013, 111, 636–642. [Google Scholar] [CrossRef] [PubMed]
  43. Akpek, M.; Kaya, M.G.; Lam, Y.Y.; Sahin, O.; Elcik, D.; Celik, T.; Ergin, A.; Gibson, C.M. Relation of Neutrophil/Lymphocyte Ratio to Coronary Flow to in-Hospital Major Adverse Cardiac Events in Patients with ST-Elevated Myocardial Infarction Undergoing Primary Coronary Intervention. Am. J. Cardiol. 2012, 110, 621–627. [Google Scholar] [CrossRef] [PubMed]
  44. Papa, A.; Emdin, M.; Passino, C.; Michelassi, C.; Battaglia, D.; Cocci, F. Predictive Value of Elevated Neutrophil-Lymphocyte Ratio on Cardiac Mortality in Patients with Stable Coronary Artery Disease. Clin. Chim. Acta 2008, 395, 27–31. [Google Scholar] [CrossRef]
  45. Kaya, H.; Ertaş, F.; İslamoğlu, Y.; Kaya, Z.; Atılgan, Z.A.; Çil, H.; Çalışkan, A.; Aydın, M.; Oylumlu, M.; Soydinç, M.S. Association between Neutrophil to Lymphocyte Ratio and Severity of Coronary Artery Disease. Clin. Appl. Thromb. Hemost. 2014, 20, 50–54. [Google Scholar] [CrossRef] [Green Version]
  46. Okan, S. The Relationship between Exercise Capacity and Neutrophil//Lymphocyte Ratio in Patients Taken to Cardiopulmonary Rehabilitation Program. Bratisl. Lek Listy 2020, 121, 206–210. [Google Scholar] [CrossRef]
  47. Scicali, R.; Mandraffino, G.; Di Pino, A.; Scuruchi, M.; Ferrara, V.; Squadrito, G.; Purrello, F.; Piro, S. Impact of High Neutrophil-to-Lymphocyte Ratio on the Cardiovascular Benefit of PCSK9 Inhibitors in Familial Hypercholesterolemia Subjects with Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid Units. Nutr. Metab. Cardiovasc. Dis. 2021, 31, 3401–3406. [Google Scholar] [CrossRef]
  48. Mitu, M.; Suceveanu, M.; Mitu, F. Cardiovascular Rehabilitation in Romania. Rom. J. Cardiol. 2020, 30, 1–6. [Google Scholar] [CrossRef]
  49. Knuuti, J.; Wijns, W.; Saraste, A.; Capodanno, D.; Barbato, E.; Funck-Brentano, C.; Prescott, E.; Storey, R.F.; Deaton, C.; Cuisset, T.; et al. 2019 ESC Guidelines for the Diagnosis and Management of Chronic Coronary Syndromes. Eur. Heart J. 2020, 41, 407–477. [Google Scholar] [CrossRef] [Green Version]
  50. Williams, B.; Mancia, G.; Spiering, W.; Agabiti Rosei, E.; Azizi, M.; Burnier, M.; Clement, D.L.; Coca, A.; de Simone, G.; Dominiczak, A.; et al. 2018 ESC/ESH Guidelines for the Management of Arterial Hypertension. Eur. Heart J. 2018, 39, 3021–3104. [Google Scholar] [CrossRef]
  51. American Diabetes Association 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019, 42, S13–S28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  52. World Health Organization; International Diabetes Federation. Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia: Report of a WHO/IDF Consultation; WHO: Geneva, Switzerland, 2006; ISBN 978-92-4-159493-6. [Google Scholar]
  53. World Health Organization. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation; WHO Guidelines Approved by the Guidelines Review Committee; World Health Organization: Geneva, Switzerland, 2011. [Google Scholar]
  54. Lancellotti, P.; Zamorano, J.L.; Habib, G.; Badano, L. The EACVI Textbook of Echocardiography; Oxford University Press: Oxford, UK, 2017; ISBN 978-0-19-103889-1. [Google Scholar]
  55. Cooper, C.B.; Storer, T.W. Exercise Testing and Interpretation: A Practical Approach; Cambridge University Press: Cambridge, UK; New York, NY, USA, 2001; ISBN 978-0-521-64842-4. [Google Scholar]
  56. Walzik, D.; Joisten, N.; Zacher, J.; Zimmer, P. Transferring Clinically Established Immune Inflammation Markers into Exercise Physiology: Focus on Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Systemic Immune-Inflammation Index. Eur. J. Appl. Physiol. 2021, 121, 1803–1814. [Google Scholar] [CrossRef] [PubMed]
  57. Fest, J.; Ruiter, R.; Ikram, M.A.; Voortman, T.; van Eijck, C.H.J.; Stricker, B.H. Reference Values for White Blood-Cell-Based Inflammatory Markers in the Rotterdam Study: A Population-Based Prospective Cohort Study. Sci. Rep. 2018, 8, 10566. [Google Scholar] [CrossRef] [PubMed]
  58. Arena, R.; Myers, J.; Williams, M.A.; Gulati, M.; Kligfield, P.; Balady, G.J.; Collins, E.; Fletcher, G. American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Nursing Assessment of Functional Capacity in Clinical and Research Settings: A Scientific Statement from the American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing. Circulation 2007, 116, 329–343. [Google Scholar] [CrossRef]
  59. Vanhees, L.; Fagard, R.; Thijs, L.; Staessen, J.; Amery, A. Prognostic Significance of Peak Exercise Capacity in Patients with Coronary Artery Disease. J. Am. Coll. Cardiol. 1994, 23, 358–363. [Google Scholar] [CrossRef] [Green Version]
  60. Coeckelberghs, E.; Buys, R.; Goetschalckx, K.; Cornelissen, V.A.; Vanhees, L. Prognostic Value of the Oxygen Uptake Efficiency Slope and Other Exercise Variables in Patients with Coronary Artery Disease. Eur. J. Prev. Cardiol. 2016, 23, 237–244. [Google Scholar] [CrossRef]
  61. Libby, P. Inflammation in Atherosclerosis. Arter. Thromb. Vasc. Biol. 2012, 32, 2045–2051. [Google Scholar] [CrossRef] [Green Version]
  62. Yayan, J. Emerging Families of Biomarkers for Coronary Artery Disease: Inflammatory Mediators. Vasc. Health Risk. Manag. 2013, 9, 435–456. [Google Scholar] [CrossRef] [Green Version]
  63. Gary, T.; Pichler, M.; Belaj, K.; Hafner, F.; Gerger, A.; Froehlich, H.; Eller, P.; Rief, P.; Hackl, G.; Pilger, E.; et al. Platelet-to-Lymphocyte Ratio: A Novel Marker for Critical Limb Ischemia in Peripheral Arterial Occlusive Disease Patients. PLoS ONE 2013, 8, e67688. [Google Scholar] [CrossRef] [Green Version]
  64. Afari, M.E.; Bhat, T. Neutrophil to Lymphocyte Ratio (NLR) and Cardiovascular Diseases: An Update. Expert Rev. Cardiovasc. 2016, 14, 573–577. [Google Scholar] [CrossRef]
  65. Canpolat, U.; Aytemir, K.; Yorgun, H.; Şahiner, L.; Kaya, E.B.; Kabakçı, G.; Tokgözoğlu, L.; Oto, A. Role of Preablation Neutrophil/Lymphocyte Ratio on Outcomes of Cryoballoon-Based Atrial Fibrillation Ablation. Am. J. Cardiol. 2013, 112, 513–519. [Google Scholar] [CrossRef] [PubMed]
  66. Im, S.I.; Shin, S.Y.; Na, J.O.; Kim, Y.H.; Choi, C.U.; Kim, S.H.; Kim, J.W.; Kim, E.J.; Han, S.W.; Rha, S.-W.; et al. Usefulness of Neutrophil/Lymphocyte Ratio in Predicting Early Recurrence after Radiofrequency Catheter Ablation in Patients with Atrial Fibrillation. Int. J. Cardiol. 2013, 168, 4398–4400. [Google Scholar] [CrossRef] [PubMed]
  67. Aribas, A.; Akilli, H.; Gul, E.E.; Kayrak, M.; Demir, K.; Duman, C.; Alibasic, H.; Yazici, M.; Ozdemir, K.; Gok, H. Can Neutrophil/Lymphocyte Ratio Predict Recurrence after Electrical Cardioversion in Non-Valvular Atrial Fibrillation? Anadolu Kardiyol. Derg. 2012, 13, 123–130. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  68. Chatterjee, S.; Chandra, P.; Guha, G.; Kalra, V.; Chakraborty, A.; Frankel, R.; Shani, J. Pre-Procedural Elevated White Blood Cell Count and Neutrophil-Lymphocyte (N/L) Ratio Are Predictors of Ventricular Arrhythmias During Percutaneous Coronary Intervention. Cardiovasc. Haematol. Disord.-Drug Targets 2011, 11, 58–60. [Google Scholar] [CrossRef]
  69. Uthamalingam, S.; Patvardhan, E.A.; Subramanian, S.; Ahmed, W.; Martin, W.; Daley, M.; Capodilupo, R. Utility of the Neutrophil to Lymphocyte Ratio in Predicting Long-Term Outcomes in Acute Decompensated Heart Failure. Am. J. Cardiol. 2011, 107, 433–438. [Google Scholar] [CrossRef]
  70. Guasti, L.; Dentali, F.; Castiglioni, L.; Maroni, L.; Marino, F.; Squizzato, A.; Ageno, W.; Gianni, M.; Gaudio, G.; Grandi, A.; et al. Neutrophils and Clinical Outcomes in Patients with Acute Coronary Syndromes and/or Cardiac Revascularisation: A Systematic Review on More than 34,000 Subjects. Thromb. Haemost. 2011, 106, 591–599. [Google Scholar] [CrossRef] [Green Version]
  71. Ntalouka, M.P.; Nana, P.; Kouvelos, G.N.; Stamoulis, K.; Spanos, K.; Giannoukas, A.; Matsagkas, M.; Arnaoutoglou, E. Association of Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratio with Adverse Events in Endovascular Repair for Abdominal Aortic Aneurysm. J. Clin. Med. 2021, 10, 1083. [Google Scholar] [CrossRef]
  72. Russu, E.; Mureșan, A.V.; Arbănași, E.M.; Kaller, R.; Hosu, I.; Voidăzan, S.; Arbănași, E.M.; Coșarcă, C.M. The Predictive Role of NLR and PLR in Outcome and Patency of Lower Limb Revascularization in Patients with Femoropopliteal Disease. J. Clin. Med. 2022, 11, 2620. [Google Scholar] [CrossRef]
  73. Garagoli, F.; Fiorini, N.; Pérez, M.N.; Rabellino, J.M.; Valle Raleigh, J.; Chas, J.G.; DI Caro, V.; Pizarro, R.; Bluro, I.M. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Predict in-Hospital Mortality in Symptomatic but Unruptured Abdominal Aortic Aneurysm Patients. Int. Angiol. 2022, 5, 149–156. [Google Scholar] [CrossRef]
  74. Arbănași, E.M.; Mureșan, A.V.; Coșarcă, C.M.; Kaller, R.; Bud, T.I.; Hosu, I.; Voidăzan, S.T.; Arbănași, E.M.; Russu, E. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Impact on Predicting Outcomes in Patients with Acute Limb Ischemia. Life 2022, 12, 822. [Google Scholar] [CrossRef]
  75. Pasqui, E.; de Donato, G.; Giannace, G.; Panzano, C.; Alba, G.; Cappelli, A.; Setacci, C.; Palasciano, G. The Relation between Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios with Mortality and Limb Amputation after Acute Limb Ischaemia. Vascular 2022, 30, 267–275. [Google Scholar] [CrossRef] [PubMed]
  76. Lee, S.; Hoberstorfer, T.; Wadowski, P.P.; Kopp, C.W.; Panzer, S.; Gremmel, T. Platelet-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratios Predict Target Vessel Restenosis after Infrainguinal Angioplasty with Stent Implantation. J. Clin. Med. 2020, 9, 1729. [Google Scholar] [CrossRef] [PubMed]
  77. Efros, O.; Beit Halevi, T.; Meisel, E.; Soffer, S.; Barda, N.; Cohen, O.; Kenet, G.; Lubetsky, A. The Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Patients Hospitalized with Acute Pulmonary Embolism. J. Clin. Med. 2021, 10, 4058. [Google Scholar] [CrossRef] [PubMed]
  78. Baysal, E.; Burak, C.; Cay, S.; Aksu, T.; Altintas, B.; Yaylak, B.; Sevük, U.; Bilge, Ö. The Neutrophil to Lymphocyte Ratio Is Associated with Severity of Rheumatic Mitral Valve Stenosis. J. Blood Med. 2015, 6, 151. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  79. Polat, N.; Yildiz, A.; Yuksel, M.; Bilik, M.Z.; Aydin, M.; Acet, H.; Akil, M.A.; Oylumlu, M.; Kaya, H.; Ertas, F.; et al. Association of Neutrophil–Lymphocyte Ratio with the Presence and Severity of Rheumatic Mitral Valve Stenosis. Clin. Appl. Thromb. Hemost. 2014, 20, 793–798. [Google Scholar] [CrossRef]
  80. Cakici, M. Neutrophil to Lymphocyte Ratio Predicts Poor Functional Capacity in Patients with Heart Failure. Arch. Turk. Soc. Cardiol. 2014, 42, 612–620. [Google Scholar] [CrossRef] [Green Version]
  81. Yıldız, A.; Yüksel, M.; Oylumlu, M.; Polat, N.; Akıl, M.A.; Acet, H. The Association between the Neutrophil/Lymphocyte Ratio and Functional Capacity in Patients with Idiopathic Dilated Cardiomyopathy. Anatol. J. Cardiol. 2015, 15, 13–17. [Google Scholar] [CrossRef]
  82. Furman, M.I.; Benoit, S.E.; Barnard, M.R.; Valeri, C.R.; Borbone, M.L.; Becker, R.C.; Hechtman, H.B.; Michelson, A.D. Increased Platelet Reactivity and Circulating Monocyte-Platelet Aggregates in Patients with Stable Coronary Artery Disease. J. Am. Coll. Cardiol. 1998, 31, 352–358. [Google Scholar] [CrossRef] [Green Version]
  83. Zhang, S.-Z.; Jin, Y.-P.; Qin, G.-M.; Wang, J.-H. Association of Platelet-Monocyte Aggregates with Platelet Activation, Systemic Inflammation, and Myocardial Injury in Patients with Non-St Elevation Acute Coronary Syndromes. Clin. Cardiol. 2007, 30, 26–31. [Google Scholar] [CrossRef]
  84. Church, T.S.; Lavie, C.J.; Milani, R.V.; Kirby, G.S. Improvements in Blood Rheology after Cardiac Rehabilitation and Exercise Training in Patients with Coronary Heart Disease. Am. Heart J. 2002, 143, 349–355. [Google Scholar] [CrossRef]
  85. Sun, X.-P.; Li, J.; Zhu, W.-W.; Li, D.-B.; Chen, H.; Li, H.-W.; Chen, W.-M.; Hua, Q. Platelet to Lymphocyte Ratio Predicts Contrast-Induced Nephropathy in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Angiology 2018, 69, 71–78. [Google Scholar] [CrossRef] [PubMed]
  86. Lopes, L.C.C.; Gonzalez, M.C.; Avesani, C.M.; Prado, C.M.; Peixoto, M.D.R.G.; Mota, J.F. Low Hand Grip Strength Is Associated with Worse Functional Capacity and Higher Inflammation in People Receiving Maintenance Hemodialysis. Nutrition 2022, 93, 111469. [Google Scholar] [CrossRef] [PubMed]
  87. Szortyka, M.F.V.; Cristiano, V.B.; Ceresér, K.M.; Francesconi, L.P.; Lobato, M.I.; Gama, C.; Belmonte-de-Abreu, P. Physical Functional Capacity and C-Reactive Protein in Schizophrenia. Front. Psychiatry 2016, 7, 131. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  88. Kerget, B.; Aksakal, A.; Kerget, F. Evaluation of the Relationship between Laboratory Parameters and Pulmonary Function Tests in COVID-19 Patients. Int. J. Clin. Pract. 2021, 75, e14237. [Google Scholar] [CrossRef]
Figure 1. Flow chart diagram of patients hospitalized in the Cardiovascular Rehabilitation Clinic Unit between January 2020 and June 2021. CAD—coronary artery disease, PCI—percutaneous coronary intervention, ACS—acute coronary syndrome, CPET—cardiopulmonary exercise test, % VO2 max—percentage of the predicted value of maximal oxygen uptake.
Figure 1. Flow chart diagram of patients hospitalized in the Cardiovascular Rehabilitation Clinic Unit between January 2020 and June 2021. CAD—coronary artery disease, PCI—percutaneous coronary intervention, ACS—acute coronary syndrome, CPET—cardiopulmonary exercise test, % VO2 max—percentage of the predicted value of maximal oxygen uptake.
Medicina 58 00814 g001
Figure 2. Platelet to lymphocyte ratio levels according to functional capacity groups.
Figure 2. Platelet to lymphocyte ratio levels according to functional capacity groups.
Medicina 58 00814 g002
Figure 3. Receiver operating characteristic curve of platelet to lymphocyte ratio for predicting poor functional capacity.
Figure 3. Receiver operating characteristic curve of platelet to lymphocyte ratio for predicting poor functional capacity.
Medicina 58 00814 g003
Table 1. Univariate analysis of the two groups according to the values of % VO2 max in all study participants.
Table 1. Univariate analysis of the two groups according to the values of % VO2 max in all study participants.
ParametersAll Patients
(n = 80)
% VO2 Max >70
(n = 45)
% VO2 Max ≤70
(n = 35)
p Value *
Age (years) ×55.51 ± 11.8357.02 ± 12.0853.57 ± 11.380.19
NLR ×1.97 ± 0.801.83 ± 0.652.15 ± 0.930.07
PLR ×155.6 ± 52.7137.4 ± 35.9169.8 ± 59.30.003
Platelet count, ×103/μL ×256 ± 60244.4 ± 56.1266.3 ± 56.10.11
Neutrophil count, ×103/μL ×3.32 ± 1.252.92 ± 0.903.83 ± 1.450.001
Lymphocyte count, ×103/μL 1.72 (1.44–1.99)1.45 (1.31–2.43)1.86 (1.65–1.88)0.06
CRP (mg/dl) 0.41 (0.24–1.04)0.28 (0.15–1.26)0.54 (0.26–0.89)0.82
LVEF ×51.31 ± 11.0455.67 ± 9.2648.71 ± 10.930.003
BMI (kg/m2) 28.7 (27.4–33)28.4 (27.4–32.4)30.15 (25.82–33.17)0.68
Hypertension 66 (82.5)38 (84.4)28 (80)0.76
Diabetes 22 (27.5)14 (31,1)8 (22.9)0.45
HbA1c (%) ×7.11 ± 1.476.58 ± 1.107.67 ± 1.660.05
LDL (mg/dl) 84 (69.8–108)73(69.8-104)100.8 (56.6–124)0.57
Resting HR ×81.9 ± 15.6984.00 ± 17.2577.57 ± 12.760.05
% peak HR × 77.98 ± 12.2582.38 ± 11.2172.31 ± 11.270.001
Resting SBP (mmHg) ×127.3 ± 12.65130 ± 13.39125.3 ± 11.790.1
Resting DBP (mmHg) ×81.5 ± 7.5280.78 ± 7.30582.43 ± 7.80.33
NLR—neutrophil to lymphocyte ratio, PLR—platelet to lymphocyte ratio, CRP—C-reactive protein, LVEF—left ventricular ejection fraction, BMI—body mass index, LDL—low-density lipoprotein, % HR—percentage of maximal predicted heart rate during test, SBP—systolic blood pressure, DBP—diastolic blood pressure, * Difference between % VO2 max ≤70 and % VO2 max >70. Data are presented as: × Mean ± SD;   n, %; Median (interquartile range).
Table 2. Pearson correlation between NLR, PLR and CPET parameters.
Table 2. Pearson correlation between NLR, PLR and CPET parameters.
ParametersNLRPLRResting HR% Peak HR % Peak WR% VO2 Max
NLR10.369 *−0.087−0.043−0.104−0.133
PLR0.369 *10.2070.1720.1050.249 *
Resting HR−0.0870.20710.594 *−0.0530.144
% peak HR −0.0430.1720.594 *1360 *0.448 *
% peak WR−0.1040.105−0.0530.360 *10.705 *
% VO2 max−0.1330.249 *0.1440.448 *0.705 *1
* p < 0.05, NLR—neutrophil to lymphocyte ratio, PLR—platelet to lymphocyte ratio, HR—heart rate, % HR—percentage of maximal predicted heart rate during test, % WR—percentage of the predicted value of maximal work rate, % VO2 max—percentage of the predicted value of maximal oxygen uptake.
Table 3. Multivariate regression analysis to predict poor functional capacity.
Table 3. Multivariate regression analysis to predict poor functional capacity.
VariablesOdds Ratio95% Confidence Intervalp
Neutrophil count, ×103/μL1.000.999–1.0020.523
PLR1.0151.004–1.0270.009
LVEF1.071.003–1.1410.042
% peak HR1.0881.029–1.1510.003
PLR—platelet to lymphocyte ratio, LVEF—left ventricular ejection fraction, % HR—percentage of maximal predicted heart rate during test.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Drugescu, A.; Roca, M.; Zota, I.M.; Costache, A.-D.; Gavril, O.I.; Gavril, R.S.; Vasilcu, T.F.; Mitu, O.; Esanu, I.M.; Roca, I.-C.; et al. Value of the Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Predicting CPET Performance in Patients with Stable CAD and Recent Elective PCI. Medicina 2022, 58, 814. https://doi.org/10.3390/medicina58060814

AMA Style

Drugescu A, Roca M, Zota IM, Costache A-D, Gavril OI, Gavril RS, Vasilcu TF, Mitu O, Esanu IM, Roca I-C, et al. Value of the Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Predicting CPET Performance in Patients with Stable CAD and Recent Elective PCI. Medicina. 2022; 58(6):814. https://doi.org/10.3390/medicina58060814

Chicago/Turabian Style

Drugescu, Andrei, Mihai Roca, Ioana Mădălina Zota, Alexandru-Dan Costache, Oana Irina Gavril, Radu Sebastian Gavril, Teodor Flaviu Vasilcu, Ovidiu Mitu, Irina Mihaela Esanu, Iulia-Cristina Roca, and et al. 2022. "Value of the Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Predicting CPET Performance in Patients with Stable CAD and Recent Elective PCI" Medicina 58, no. 6: 814. https://doi.org/10.3390/medicina58060814

Article Metrics

Back to TopTop