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Mediation Effect of Neutrophil Lymphocyte Ratio on Cardiometabolic Risk Factors and Cardiovascular Events.

ABSTRACT: Neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, is associated with cardiovascular events (CVEs), but its causal pathway is unknown. We aimed to explore the extent to which NLR is directly associated with CVEs or mediated through diabetes mellitus (DM), hypertension (HT) and creatinine (Cr). The study used data on 2,501 subjects from the Electricity Generating Authority of Thailand cohort 2002-2012. Two causal pathways A: NLR→(DM→Cr→HT)→CVEs and B: NLR→(DM → HT→Cr)→CVEs were constructed. A generalized structural equation model and 1,000-replication bootstrapping were applied. The incidence rate of CVE was 8.8/1000/year. Prevalence rates of HT, DM, and chronic kidney disease were 45.1%, 23.6%, and 16.5%, respectively. The total effect of NLR on CVEs was explained partly (44%) by a direct effect and partly (56%) by an indirect effect through DM, HT and Cr. For pathway A, the direct OR of NLR on CVE was 1.25 (95% CI: 1.13, 1.39); the ORs for the indirect effects of NLR on CVEs mediated through DM, Cr, and poor-controlled HT were 1.06 (95% CI: 1.01, 1.11), 1.01 (95% CI: 1.00, 1.02), and 1.07 (95% CI: 1.01, 1.14) respectively. Results were similar for pathway B. Our findings demonstrate that roughly half of the relationship between NLR and CVEs may be mediated through DM, HT and Cr.

SUBMITTER: Angkananard T

PROVIDER: S-EPMC6384908 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Mediation Effect of Neutrophil Lymphocyte Ratio on Cardiometabolic Risk Factors and Cardiovascular Events.

Angkananard Teeranan T Anothaisintawee Thunyarat T Ingsathit Atiporn A McEvoy Mark M Silapat Kongpop K Attia John J Sritara Piyamitr P Thakkinstian Ammarin A

Scientific reports 20190222 1

Neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, is associated with cardiovascular events (CVEs), but its causal pathway is unknown. We aimed to explore the extent to which NLR is directly associated with CVEs or mediated through diabetes mellitus (DM), hypertension (HT) and creatinine (Cr). The study used data on 2,501 subjects from the Electricity Generating Authority of Thailand cohort 2002-2012. Two causal pathways A: NLR→(DM→Cr→HT)→CVEs and B: NLR→(DM → HT→Cr)→CVEs were cons ...[more]

PMID: 30796249

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Project description:BACKGROUND:Preoperative risk prediction in patients at elevated cardiovascular risk shows limited accuracy. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) indicate systemic inflammation. Both have been investigated for outcome prediction in the field of oncology and cardiovascular medicine, as well as risk prediction of adverse cardiovascular events in non-surgical patients at increased cardiovascular risk. METHODS:For this post-hoc analysis, we included all 38 coronary heart disease patients from the Leukocytes and Cardiovascular Perioperative Events cohort-1 study scheduled for elective non-cardiac surgery. We evaluated preoperative differential blood counts for association with major adverse cardiovascular and cerebrovascular events (MACCE) defined as the composite endpoint of death, myocardial ischemia, myocardial infarction, myocardial injury after non-cardiac surgery, or embolic or thrombotic stroke within 30 days after surgery. We used Youden's index to calculate cut-off values for PLR and NLR. Additive risk-predictive values were assessed using receiver operating characteristic curve and net reclassification (NRI) improvement analyses. RESULTS:Patients with the composite endpoint MACCE had higher PLR and NLR (309 [206; 380] vs. 160 [132; 203], p = 0.001; 4.9 [3.5; 8.1] vs. 2.6 [2.2; 3.4]), p = 0.001). Calculated cut-offs for PLR > 204.4 and NLR > 3.1 were associated with increased risk of 30-day MACCE (OR 7, 95% CI [1.2; 44.7], p = 0.034; OR 36, 95% CI [1.8; 686.6], p = 0.001). Furthermore, NLR improved risk prediction in coronary heart disease patients undergoing non-cardiac surgery when combined with hs-cTnT or NT-proBNP (NRI total = 0.23, p = 0.008, NRI total = 0.26, p = 0.005). CONCLUSIONS:Both PLR and NLR were associated with perioperative cardiovascular adverse events in coronary heart disease patients. NLR proved to be of additional value for preoperative risk stratification. Both PLR and NLR could be used as inexpensive and broadly available tools for perioperative risk assessment. TRIAL REGISTRATION:NCT02874508, August 22, 2016.

Project description:Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.Data from the University of Malaya Medical Centre Breast Cancer Registry was used. Of 2059 consecutive patients diagnosed from 2000 to 2008, we included 1435 patients with an available pre-treatment differential blood count (∼70%). Patients were stratified into quintiles of the NLR/PLR. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR/PLR.Compared with the first quintile of the NLR, women in quintile 5 were younger, had bigger tumours, nodal involvement, distant metastases and higher tumour grades. Higher NLR quintiles were significantly associated with poorer survival with a 5-year relative survival ratio (RSR) of 76.4% (95% CI: 69.6-82.1%) in quintile 1, 79.4% (95% CI: 74.4-83.7%) in quintile 2, 72.1% (95% CI: 66.3-77.3%) in quintile 3, 65.6% (95% CI: 59.8-70.8%) in quintile 4 and 51.1% (95% CI: 43.3-58.5%) in quintile 5. Following adjustment for demography, tumour characteristics, treatment and the PLR, the adjusted hazard ratio (HR) for quintile 5 vs quintile 1 was 1.50 (95% CI: 1.08-1.63); Ptrend=0.004. Results were unchanged when the NLR was analysed as a dichotomous variable using different cutoff points. Although patients in PLR quintile 5 had lower survival than in quintile 1 (5-year RSR: 53.2% (95% CI: 46.9-59.2%) vs 77.0% (95% CI: 70.9-82.2%)), this association was not significant after multivariable adjustment. However, a PLR >185 was significantly associated with poorer survival; adjusted HR: 1.25 (95% CI: 1.04-1.52).Both the NLR and PLR are independently associated with an increased risk of mortality in breast cancer. Their added value in the prognostication of breast cancer in clinical practice warrants investigation.

Dataset Information

Mediation Effect of Neutrophil Lymphocyte Ratio on Cardiometabolic Risk Factors and Cardiovascular Events.

Publications

Mediation Effect of Neutrophil Lymphocyte Ratio on Cardiometabolic Risk Factors and Cardiovascular Events.

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