The relationship between platelet to lymphocyte ratio and the diurnal variation of hypertension

Aim: Platelet to lymphocyte ratio (PLR) predicts worse outcome in cardiovascular disease. However data is limitted about the role of PLR in the diurnal variation of hypertension. In this study we evaluated the relationship between the diurnal variation of hypertension and PLR. Material and Methods: The study included a total of 247 essential hypertensive patients. All patients underwent 24hour ambulatory blood monitoring. Thereafter hypertensive patients were divided into two groups: 64 dipper patients (30 female, mean age 53.8±12.9 years) and 38 non-dipper patients (18 female, mean age 52.6±12.5years). Complete blood count and biochemistry were measured by standard methods. PLR was measured by dividing platelet count to lymphocyte count. Results: Non-dipper hypertensives had signifi cantly higher PLR levels than dippers (127.9±32.16 vs 103.4±10.67, p<0.001). There was a negatif correlation between percentage of sistolic and diastolic blood pressure fall and PLR. Conclusion: We demonstrated that PLR, an inexpensive and easily accessible biomarker, is significantly higher in nondipper hypertensives than the dipper hypertensives.


Introduction
Hypertension is considered as an important risk factor for cardiovascular mortality and morbidity. Hypertension shows diurnal variation. A decrease in systolic and diastolic blood pressure of more than 10% in night time compared to daytime is considered as dipper pattern and the absence of this decrease is considered as non-dipper pattern. Current literature shows that non-dipper pattern increases the risk of cardiovascular events and end-organ damage due to hypertension compared to dipper pattern [1][2][3]. Even though the underlying reason for this situation has not been fully enlightenede, it is known that inflammatory and thrombotic processes are more common in non-dipper patients [4][5].
Both lymphocytes and platelets are important mediators of inflammatory and thrombotic processes. It has been shown that the platelet/lymphocyte ratio (PLR) obtained by dividing the platelet count by lymphocyte count can be used as a predictor for cardiovascular events [6][7]. Increased PLR has been associated with unfavorable coronary events and coronary artery disease [8].
A number of studies have shown that the levels of inflammatory markers are elevated in non-dipper patients. However, data on PLR, a thrombotic marker in inflammatory and thrombotic processes, is limited in hypertensive patients. In this study, our aim was to investigate the relationship between PLR in hypertensive patients and diurnal pattern in hypertension.

Study Population
A total of 150 patients were screened fort his retrospective cross-sectional study. Fourty eight patients were excluded according to exclusion criterias. The remaining 102 patients (48 women, 54 men) with a history of chronic hypertension and receiving appropriate antihypertensive medications for at least 3 months prior to enrolment were enrolled. Hypertension was defi ned as systolic BP (SBP) 140 mmHg or a diastolic BP (DBP) 90 mmHg and/or use of the anti-hypertensive drug therapy [9]. After diagnosis of hypertension, ambulatory blood pressure monitoring (ABPM) was performed. Exclusion criteria included the presence of the following: Patients with diabetes mellitus, hematopoietic system disorders, histories of malignancy and/or chemotherapy treatment, signs of accompanying infectious diseases, leukocyte disorders (such as an acute infection or chronic inflammatory status), histories of secondary hypertension, known coronary artery or cerebrovascular disease, chronic renal failure, chronic liver disorders, moderate, or severe valvular disease, congenital heart disease, left ventricular systolic and/or diastolic dysfunction on echocardiography and those who had used glucocorticoid therapy within the last 3 months.
Each of the patients signed an informed consent form, and the study protocol was approved by the local ethics committee.
The patients 'clinical and demographic characteristics such as age, sex, smoking habits and antihypertensive drugs were noted. In addition, serum levels of hsCRP, fasting blood glucose level, creatinine level and fasting serum lipid status including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels were also recorded.
Body mass index (BMI) was calculated as weight (kg) divided by height squared (m 2). Each patient was assessed using 12-lead electrocardiography and transthoracic echocardiography.

Laboratory analysis
All laboratory data were obtained from venous blood samples after 12 h of fasting. Haematologic parameters were measured using an automated haematologyanalyser(XE-2100;Sysmex Corporation, Kobe, Japan). The biochemical measurements were determined using a molecular analyser

Statistical Analysis
Statistical analysis was performed using SPSS 22.0 statistical software. (SPSS Inc., Chicago, IL, USA). Continuous variables are described as the means±SD, whereas discrete variables are reported as frequencies and percentages. The equality of the data to the normal distribution was assessed with Shapiro-Wilk test. Normal distributed variables were given as mean SD and non-normally distributed variables were given as medians with interquartile ranges. The chi-square test was used for categorical variables. Mean values of the groups were compared with Student's t-test and Mann -Whitney U test where appropriate. Similarly, Pearson and Spearman correlation coeffi cients were used to test univariate correlations. Statistical significance was set at p 0.05.

Figure 1-2:
The negative correlation between platelet to lymphocyte ratio (PLR) and nocturnal blood pressure fall. SBP, systolic blood pressure; DBP, diastolic blood pressure.

Discussion
In this study we have found that PLR is significantly higher in the non-dipper HT groups compared with those of the dipper HT group.
It is known that the diurnal rhythm of hypertension is associated with hypertension-related end organ damage and unfavorable cardiovascular outcomes [11][12][13].
It has been shown that non-dipper hypertension which is defined as a decrease in blood pressure of less than 10 mmHg during the night hours causes more undesirable cardiovascular events in non-hypertensive patients and in dipper hypertensive patients whose blood pressure decreases 10 mmHg or more [14][15]. This situation in non-  [7,21]. In our study, we demonstrated that diurnal rhythm of hypertension is associated with PLR. Therefore, increased PLR, an inflammatory and thrombotic marker, may be associated with an increased incidence of adverse events in non-dipper hypertensive patients. Large-scale randomized studies are necessary to clarify this subject.

Conclusion
We can state a close relationship between increased cardiovascular risk and non-dipper status in hypertensive patients. Data in literature suggests that this condition is related to increased inflammation and platelet aggregation in non-dipper status. In addition, it is known that increased platelet count promotes inflammation. Therefore, the results of our study supports the hypothesis that the increased risk of cardiovascular events in non-dipper status is associated with abnormalities in inflammation and thrombogenesis.