Platelet-to-Lymphocyte Ratio May Predict the Severity of Calcific Aortic Stenosis

Background

The prevalence of calcific aortic stenosis (AS) increases with age, and the prevalence in individuals over 75 years of age is 5% [1,2]. Calcific AS is the most common form of valve disease and the most common indication for surgical valve replacement in developed nations. Therefore, detecting a biomarker to predict the prognosis of calcific AS may be beneficial.

Previous studies have demonstrated that platelet activation occurs in patients with AS [3]. Additionally, platelet count decrease has been reported after percutaneous coronary intervention and surgical aortic valve replacement [4]. However, it has also been demonstrated that even though polycythemia vera is reported as a possible cause of aortic valve stenosis, platelet count does not significantly differ between polycythemic stenotic patients compared to non-stenotic ones, but it does not distinguish between patients with mild-to-moderate and severe AS [5].

Increased platelet and decreased lymphocyte counts in the circulation have been associated with increased cardiovascular morbidity and mortality [6,7]. Recent reports have demonstrated that there is a relationship between PLR and the severity and complexity of coronary artery disease in patients with acute coronary syndromes and have also shown that increased PLR is an independent predictor of higher SX-score in patients with acute coronary syndromes [8].

Therefore, we aimed to investigate the relationship between PLR and the severity of calcific AS.

Material and Methods

STUDY POPULATION:

The retrospective study included 86 patients diagnosed with calcific AS between May 2012 and January 2015. Patients with calcific AS were divided into two groups as mild-to-moderate AS and severe AS according to the transaortic mean pressure gradient.

Exclusion criteria included indications of atherosclerosis diagnosed by coronary angiography or scintigraphy, AS of congenital or rheumatic origin, severe mitral valve regurgitation, other forms of stenotic valve diseases, active and chronic infection, left ventricular systolic dysfunction, hemodynamically significant cardiac arrhythmias, renal or hepatic impairment, and comorbidities. An age- and gender-matched control group was formed including 42 healthy volunteers (24 females and 18 males with a mean age of 64.6±11.7 years). All the participants in the study and control groups were evaluated using echocardiography. No cardiac abnormalities were observed in the control group. Age, gender, hypertension, status of smoking, hyperlipidemia, diabetes mellitus, and family history were recorded. In addition, blood glucose, heart rate, blood pressure, hematological parameters, lipid profile, and serum creatinine were evaluated for each patient. The trial protocol was approved by the local ethics committee and the study conforms to the ethical principles contained in the Declaration of Helsinki.

ECHOCARDIOGRAPHY:

Each patient was evaluated using transthoracic two-dimensional echocardiography at rest under standard procedures. With the patient in the left lateral decubitus position, the examination was performed using a commercial echocardiographic device (Vivid 3, General Electric, Chicago, IL, USA) with a 3.0-MHz transducer. The examinations were conducted by two experienced cardiologists who were blinded to study. The measurement of left atrial and ventricular dimensions and left ventricular ejection fraction was achieved by M-mode echocardiography in the parasternal long-axis view. Aortic valve peak velocity, peak gradient, and mean gradient were measured by Doppler. Aortic and valve regurgitation were assessed using color flow Doppler.

BIOCHEMICAL MEASUREMENTS:

Blood sampling was achieved through the antecubital vein using a 21-g sterile syringe without stasis between 08.00 and 10.00 AM, following a 12-hour fasting period. To assess complete blood count (CBC), a Coulter LH 780 Hematology Analyzer (Architect plus ci16200 Abbott Illinois, USA) was used for measuring the hematological parameters including white blood cells, hemoglobin level, lymphocyte counts, mean platelet volume (MPV), and platelet counts. Platelet count, lymphocyte count and MPV were measured in a blood sample collected in dipotassium EDTA tubes and measured within 30 minutes after sampling to prevent EDTA-induced platelet swelling

STATISTICAL ANALYSIS:

Data analysis was achieved using SPSS 17.0 for Windows (SPSS Inc., USA). Continuous data were presented as mean±standard deviation and the categorical data were presented as percentage. The Pearson or the Spearman correlation coefficient was used for the analysis of the correlation between the variables, as needed. One-Way ANOVA was used for statistical comparisons, followed by Scheffé’s test. The p values less than 0.05 were accepted as statistically significant.

Results

A total of 128 patients (86 patients with AS and 42 control subjects) were included in the present study. Baseline demographic, clinical, echocardiographic, and laboratory characteristics of the study groups were presented in Tables 1 and 2. PLR, platelet count, and MPV were highest in severe AS group (151±31.2, p<0.001, 261±56.6 μ/L, p<0.001, 8.8±1.3 fL, p<0.001, respectively). In addition, PLR (138±28.8 vs. 126±26.5, p=0.008), platelet count (249±48.3 vs. 237±40.6 μ/L, p=0.046) and MPV (8.3±1.2 vs. 7.9±0.9 fL p=0.062) were higher in mild-to-moderate AS group compared to the control group. However, absolute lymphocyte count was lowest in the severe AS group (1.78±0.5 μ/L, p<0.001) and lower in mild-to-moderate AS group (1.85±0.6 μ/L, p=0.046) than in the control group.

Expectedly, transaortic mean pressure gradient, peak pressure gradient and aortic peak velocity were found to be significantly higher in the AS group compared to the control group (p<0.001 for all the parameters). Moreover, left ventricular end-diastolic diameter (p<0.005), left ventricular end-systolic diameter (p=0.008), interventricular septum (p=0.011), and posterior wall thickness (p=0.023) were significantly higher in the severe AS group compared to the control group. No difference was found between the two groups in terms of other baseline characteristics.

In patients with AS, PLR established a significant positive correlation with transaortic mean pressure gradient (odds ratio [OR] 1.021, 95% confidence interval [CI] 1.016 to 1.026, r=0.421, p<0.001) (Figure 1). In the subgroup analysis of AS patients, PLR, platelet count, and MPV were found to be higher in the severe AS group compared to mild-to-moderate group (p<0.001, p=0.032, and p=0.027, respectively), whereas the absolute lymphocyte count was found to be decreased in the severe AS group compared to the mild-to-moderate group (p=0.048).

Discussion

LIMITATION:

The main limitations of this study include the relatively small sample size due to numerous exclusion criteria. Moreover, we did not evaluate other cytokines or inflammatory markers such as, fibrinogen, nitric oxide, myeloperoxidase, and interleukin-6 and did not compare them with PLR. However, such inflammatory biomarkers are expensive and are not immediately available in everyday practice. Despite these limitations, we present the first study that focused on the predictive value of PLR in patients with calcific AS.

Conclusions

Our study results demonstrated that a high PLR was independently associated with the severity of calcific AS. These findings suggest that besides its already known effect on prothrombotic status, a higher PLR level may exhibit proinflammatory effect on calcific AS. Thus, PLR may be used in clinic practice for the prediction of calcific AS. Further studies are needed to explain the mechanisms and effects of the relationship between PLR and calcific AS.