Biomarkers of Inflammation: Platelet:Lymphocyte Ratio (PLR)

Optimal Takeaways

The platelet:lymphocyte ratio (PLR) indicates a pro-thrombotic inflammatory state and is a significant marker in evaluating systemic inflammation, cardiovascular risks, and the prognosis of various cancers.

An elevated PLR has been linked with an array of adverse health conditions, including severe coronary atherosclerosis, heart failure, and malignancy, signifying a higher inflammatory state and increased risks of adverse events in these conditions. Values above certain thresholds (varying in different studies) indicate higher risk and severity of disease. However, PLR is not a standalone diagnostic marker and should be considered alongside other inflammatory markers and associated conditions for a comprehensive evaluation.

A low PLR usually suggests the absence of a pro-inflammatory, pro-thrombotic state.

Low platelet:lymphocyte ratio may be seen with thrombocytopenia (Pagana 2022)-

High platelet:lymphocyte ratio is associated with inflammation, thrombosis, severe coronary atherosclerosis, myocardial infarction, major adverse cardiac events (MACE), including heart rupture, acute heart failure, total adverse events, and mortality (Wang 2023), heart failure (Tamaki 2023), arrhythmias, valvular disease, CVD, acute coronary syndrome, and acute and long-term mortality (Kurtul 2019).

A higher PLR is also associated with bipolar disorder (Mazza 2018), rheumatoid arthritis (Erre 2019), metastases and poor overall survival in breast cancer (Gong 2022), and poorer prognosis in heart failure (Ye 2019), peripheral arterial occlusive disease (Uzun 2017), acute ischemic stroke (Chen 2021), COVID-19 (Ravindra 2022, Sarkar 2022, Seyit 2021), ovarian, cervical (Jiang 2019), prostate (Huszno 2022, and advanced cancer in general (Li 2018).

Overview    

The platelet:lymphocyte ratio (PLR) is a prognostic inflammatory marker to evaluate systemic inflammation, cardiovascular risk, and cancer survival. Chronic low-grade inflammation is associated with dysfunction, including insulin resistance, type 2 diabetes, CVD, and cancer (Fest 2018).

Platelets are associated with the development and progression of coronary thrombosis (Wang 2023). They release pro-inflammatory compounds and growth factors involved in thrombosis and vascular inflammation. Activated platelets respond to plaque rupture or endothelial damage by promoting blood clot formation and contributing to monocyte recruitment and adverse cardiovascular events. However, lymphocytes decrease with physiological stress and inflammation, and lower levels are associated with increased cardiovascular risk and mortality. The ratio of platelets to lymphocytes predicts cardiac and chronic disease risk better than either marker alone. The PRL is calculated by dividing the total platelet count by the absolute lymphocyte count. A higher PRL suggests the presence of inflammation and increased risk of acute coronary syndrome, arrhythmias, valvular disease, heart failure, CVD, and acute and long-term mortality. A PLR above 137 was associated with adverse outcomes in a study of 440 STEMI patients undergoing PCI (Kurtul 2019).

A higher PLR is independently associated with a higher Gensini score, a score that reflects the severity and extent of atherosclerosis. In one study of 388 high-risk patients undergoing coronary angiography, PLR was independently associated with a higher Gensini score, WBC count, age, and a lower HDL-C. A PLR above 111 predicted higher Gensini scores and greater severity of atherosclerosis (Yuksel 2015).

A review of angiographic data in a cross-sectional retrospective study of 1,646 angina patients found that PLR was significantly higher in those with mild to moderate CAD/atherosclerosis. Those with no CAD and a Gensini score of zero had a mean PLR of 97.8, while those with moderate CAD and a Gensini score of 1-20 had a PLR of 120.3, and those with severe CAD and a Gensini score above 20 had a PLR of 146.9. Levels of CRP were significantly higher with mild and moderate CAD as well. Researchers note that the decrease in lymphocytes associated with myocardial infarction may be related to the increased cortisol associated with physiological stress (Akboga 2016).

A meta-analysis of 10 studies comprising 8,932 acute coronary syndrome (ACS) patients found that a higher PLR was associated with a worse prognosis, a 2.24-fold increased risk of adverse outcomes while in hospital, and a 2.32-fold increased risk of long-term adverse outcomes. The cut-offs ranged from 116 to 174.9 in 8 of the ten studies. Researchers also note that past studies confirm a higher PLR is associated with higher peak CK-MB, creatinine, glucose, anemia incidence, GRACE risk scores, and other inflammatory markers, including CRP and fibrinogen. These observations confirm the prognostic value of evaluating PLR (Li 2017).

Elevated PLR is associated with additional markers of inflammation. Evaluation of data from a cohort of 8,711 disease-free subjects from the prospective population-based Rotterdam Study looked at markers of inflammation, including PLR, neutrophil:lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). Mean values for these markers in the general population were 120, 1.76, and 459, respectively. Researchers note that these markers were significantly higher in those with more elevated CRP values of 129, 2.24, and 691, respectively (Fest 2018). However, a retrospective cohort study of 12,160 healthy South Koreans found a mean PLR of 132.40 across all ages and genders (Lee 2018). It is essential to consider other inflammatory markers and associated conditions when evaluating PLR, as it is not a standalone diagnostic marker.

A PLR above 178 indicated an increased risk of major adverse cardiac events (MACE) in a prospective longitudinal study of 799 individuals undergoing percutaneous coronary intervention (PCI) following acute MI. MACE events included heart rupture, acute heart failure, CVD mortality, and total adverse events, and were 2.3 times more prevalent with a PLR above 178. The elevated PLR was considered an independent predictor of adverse outcomes in this group and was also associated with significantly higher total WBCs and neutrophil:lymphocyte ratio. The mean PLR was 298.74 in the high PLR group and 126.22 in the low PLR group (Wang 2023). In another study, the PLR cut-off for identifying in-hospital complications was 151.28 for developing MACE and 139.31 for detecting a high Gensini score above 60 (Li 2020).

An elevated PLR is associated with rheumatoid arthritis as well. One meta-analysis of 8 studies comprising 685 subjects observed significantly higher PLR in patients versus controls. Those with rheumatoid arthritis presented with a mean/median PLR above 137, while controls presented with a mean/median PLR below 134 (Erre 2019).

References  

Akboga, Mehmet Kadri et al. “Association of Platelet to Lymphocyte Ratio With Inflammation and Severity of Coronary Atherosclerosis in Patients With Stable Coronary Artery Disease.” Angiology vol. 67,1 (2016): 89-95. doi:10.1177/0003319715583186

Chen, Cuiping et al. “Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Potential Predictors of Prognosis in Acute Ischemic Stroke.” Frontiers in neurology vol. 11 525621. 25 Jan. 2021, doi:10.3389/fneur.2020.525621

Erre, Gian Luca et al. “Meta-analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in rheumatoid arthritis.” European journal of clinical investigation vol. 49,1 (2019): e13037. doi:10.1111/eci.13037

Fest, Jesse et al. “Reference values for white blood-cell-based inflammatory markers in the Rotterdam Study: a population-based prospective cohort study.” Scientific reports vol. 8,1 10566. 12 Jul. 2018, doi:10.1038/s41598-018-28646-w

Gong, Zhixun et al. “Platelet-to-lymphocyte ratio associated with the clinicopathological features and prognostic value of breast cancer: A meta-analysis.” The International journal of biological markers vol. 37,4 (2022): 339-348. doi:10.1177/03936155221118098

Jiang, Shanshan et al. “Platelet-lymphocyte ratio as a potential prognostic factor in gynecologic cancers: a meta-analysis.” Archives of gynecology and obstetrics vol. 300,4 (2019): 829-839. doi:10.1007/s00404-019-05257-y

Kurtul, Alparslan, and Ender Ornek. “Platelet to Lymphocyte Ratio in Cardiovascular Diseases: A Systematic Review.” Angiology vol. 70,9 (2019): 802-818. doi:10.1177/0003319719845186

Lee, Jeong Soo et al. “Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea.” Medicine vol. 97,26 (2018): e11138. doi:10.1097/MD.0000000000011138

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Seyit, Murat et al. “Neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio and platelet to lymphocyte ratio to predict the severity of COVID-19.” The American journal of emergency medicine vol. 40 (2021): 110-114. doi:10.1016/j.ajem.2020.11.058

Tamaki, Shunsuke et al. “Combination of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as a Novel Predictor of Cardiac Death in Patients With Acute Decompensated Heart Failure With Preserved Left Ventricular Ejection Fraction: A Multicenter Study.” Journal of the American Heart Association vol. 12,1 (2023): e026326. doi:10.1161/JAHA.122.026326

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