EFFECTS OF BETA-ADRENOCEPTOR BLOCKERS ON THE PLATELET AND CARDIOMETABOLIC INDICES IN UNCONTROLLED HYPERTENSION

EFFECTS OF BETA-ADRENOCEPTOR BLOCKERS ON THE PLATELET AND CARDIOMETABOLIC INDICES IN UNCONTROLLED HYPERTENSION

Zahraa A. G. Mohammed Ali

Department of Clinical Pharmacy, College of Pharmacy, Al-Mustansiriyah University, Baghdad, Iraq.

ABSTRACT: Background: Metabolic derangement in term of glucose dysregulation, dyslipidemia, and electrolyte disturbances are the adverse reactions of beta-adrenoceptor blockers that limit their use. Aims: To investigate the effect of BARBs on the cardio-metabolic risk factors and platelet indices that play a role in accelerating the atherogenicity. Materials and methods: This observational clinical study was done in the Department of Clinical Pharmacy, College of Pharmacy, Al-Mustansiriya University in Baghdad, Iraq from 1^st August 2016 to 31^st December 2016.  A total number of 54 uncontrolled hypertensive patients were enrolled in this study. They grouped into Group I (n=25): hypertensive patients treated with angiotensin receptor blockers (ARBs) or angiotensin converting enzyme inhibitors (ACEIs), and Group II (n=29): hypertensive patients treated with beta-adrenoceptor agents in addition to the ARBs or ACEIs. The anthropometric, blood pressure, fasting serum glucose and lipid profile, and the platelet indices were determined. Results: Group II patients have significant low fasting serum glucose and non-significant high serum levels of triglycerides and cholesterol. Significant negative correlation between fasting serum triglycerides and plateletcrit (r=0.444, df=23, p=0.0250 observed in Group I patients. Conclusion: BARBs carried a metabolic derangement in term of alterations in the fasting serum glucose, triglycerides and cholesterol, but they offered a favorable effect on the platelet function and thereby reduced the risk of coronary artery disease.

Beta-adrenoceptor blockers, Hypertension, Platelet indices, Metabolic derangement

INTRODUCTION: There are many classes of antihypertensive agents act via different mechanisms are used in management of hyper -tension and none of them is free from adverse reactions. Metabolic derangement in term of hyper- glycemia or hypoglycemia, dyslipidemia, and electrolyte disturbances are the adverse reactions that limit the use of these drugs in hypertension comorbidities e.g. diabetes mellitus ^{1 - 4}.

Angiotensin converting enzyme inhibitors (ACEIs) are commonly used in management of hypertension and their main adverse reactions included dry cough, hyperkalemia, proteinuria and hyper- sensitivity reactions ^{5, 6}. There is no evidence that ACEIs exerts a beneficial or harmful effect on the lipid profile or the blood glucose levels even in experimental studies ^{7, 8}.

There is evidence that angiotensin receptor blockers (ARBs) can improve the dyslipidemia that occurred in diabetic patients with nephropathy complications ⁹ and they also attenuate the harmful effects of hyperglycemia ^{10, 11}. Beta-adrenoceptor blocking agents (BADRBs) induced many adverse reactions that depended on their cardio selectivity and intrinsic sympathetic activity.

BADRBs interfere with glucose regulation leading to cause hyperglycemia as an adverse reaction, in addition to their inhibitory effects on the hepatic gluconeogenesis   ¹². Dyslipidemia in term of increase plasma levels of triglycerides occurred with using the BARBs even those with cardio selective effect e.g. atenolol ¹³. BARBs are known compounds that inhibit the aggregation of the blood platelet and there is evidence that propranolol is more effective than atenolol in this concern ¹⁴. On the other hands, platelet indices and hypertension are interrelated, and these indices used as a diagnostic or prognostic markers ¹⁵.

The rationale of this study that the metabolic derangement and changes in the platelet indices that induced by BADRBs may be influenced by using other antihypertensive drugs. The aims of this study were to explore the effect of BARBs on the cardio-metabolic risk and platelet indices that play a role in accelerating the atherogenicity.

MATERIALS AND METHODS: This observational clinical study was done in the Department of Clinical Pharmacy, College of Pharmacy, Al-Mustansiriya University in Baghdad, Iraq from 1^st August 2016 to 31^st December 2016.  The protocol of the approved by the Institutional Scientific Committee. The study in­cluded hypertensive patients who attended the private clinics for follow-up of essential hypertension. All patients provided informed consent to participate in the study. The criteria of inclusion were essential hypertension treated with antihypertensive drugs (not more than two drugs related to different classes, one of them related to the beta-adrenoceptor blocking agents). The criteria of exclusion included secondary hypertension, diabetes mellitus, pregnancy, renal and hepatic failure.

Each patient asked to answer specific questions related to the demographic characteristics and his/her illness history and then the patients subjected to the following measurements, blood pressure, anthropometric indices, fasting serum lipid profile, complete blood count and the related hematological indices. The blood pressure was measured in sitting position and the mean of three readings was taken.

The anthropometric measurements included height, weight and waist circumference. Body mass index (BMI) was calculated by applying the Quetlete's equation:

Body mass index (kg/m²) = weight (kg) /height ² (m)

Peripheral venous blood drew immediately after admission into a plane and EDTA-tubes Plane tubes that contained blood were centrifuging at 2500 RPM for 10 min, and the sera were separated for determination of lipid profile. The determinants of lipid profile included fasting serum total cholesterol (TC), triglycerides (TG), and high-density lipoprotein-cholesterol (HDL-c).  Low-density lipoprotein-cholesterol (LDL-c) was calculated by using the following equation:

LDL-c (mg/dl) = TC- (HDL-c+[0.2ÍTG])

The EDTA tubes were used for determination of blood platelet indices using hematology analyzer. The platelet indices included platelet count, plateletcrit (PCT), mean platelet volume (MPV), and platelet width distribution (PWD).

A total number of 54 hypertensive patients were enrolled in this study. They grouped into:

Group I (n=25):  hypertensive patients treated with one medication related to the angiotensin receptor blockers (ARBs) (candesartan, losartan, valsartan) or one of angiotensin converting enzyme inhibitors (ACEIs) ( capropril, enalopril, lisinopril).

Group II (n=29): hypertensive patients treated with one medication related to the beta-adrenoceptor agents (atenolol, bisprolol, metoprolol) and one medication either related to the angiotensin receptor blockers (ARBs) (candesartan, losartan, valsartan) or one of angiotensin converting enzyme inhibitors (ACEIs) (capropril, enalopril, lisinopril).

Statistical Analysis: The statistical analysis was performed by using SPSS v.20.0 for Windows (IBM Corp., Armonk, NY, USA).

The results are expressed as a number, percentage and mean ± SD. Difference between percentages test was used to compare categorical variables. The differences in means were analyzed by using the two- tailed unpaired t-test and a simple correlation test was used to determine the relationship between platelet indices and the variables related to the metabolic derangement determinants. The level of statistical significance was set at p ≤ 0.05.

RESULTS: Table 1 shows the characteristics of the study. There was non-significant differences between Group I and II regarding the age, duration of hypertension, smoking or past history of ischemic heart disease. There was non-significant differences between Group I and II in respect to the using the antihypertensive agents of ACEIs and/or ARBs.

TABLE 1: CHARACTERISTICS OF THE PATIENTS ENROLLED IN THE STUDY

The results are expressed as number (%) and mean ± SD. Group I: patients not treated with beta-adrenoceptor blocking agents; Group II: patients treated with beta-adrenoceptor blocking agents. ARBs; angiotensin receptor blockers, ACEIs; angiotensin converting enzyme inhibitors, BARB; beta-adrenorecetor blockers.

Table 2 shows the determinants of the cardio-metabolic risk factors. There was non-significant differences in the levels of blood pressure or the anthropometric measurements presented with BMI and waist circumference.

TABLE 2: MEASUREMENTS OF THE CARDIO-METABOLIC RISK FACTORS 

The results are expressed as mean ± SD. Group I: patients not treated with beta-adrenoceptor blocking agents; Group II: patients treated with beta-adrenoceptor blocking agents.

Despite there is no significant difference between waist to height ratio between Group I and Group II, the value of this ratio exceeded the cut off value of 0.5, which indicated that the patients of both groups were at risk of cardiovascular events. The mean levels of fasting serum glucose were within normal range in both groups but Group I patient had a significant high level compared with Group II. The fasting lipid profile levels did not show significant difference between Group I and Group II but the patients of Group II had a mean level of serum triglycerides that exceeded the cut off value of 150mg/dl, which indicated the evidence of metabolic syndrome.

Table 3 shows the non-significant differences in the platelets indices between Group I and II. The levels of fasting serum triglycerides were significantly correlated in an inverse pattern with the plateletcrit (r= -0.447, df =23, p=0.025) in Group I patients (Table 4).

TABLE 3: MEASUREMENTS OF THE PLATELETS INDICES

The results are expressed as number (%) and mean ± SD. Group I: patients not treated with beta-adrenoceptor blocking agents; Group II: patients treated with beta-adrenoceptor blocking agents.

TABLE 4: CORRELATIONS BETWEEN PLATELET INDICES WITH TRIGLYCERIDES AND HIGH DENSITY LIPOPROTEIN-CHOLESTEROL

The results are expressed as a correlation factor (r). Group I: patients not treated with beta-adrenoceptor blocking agents; Group II: patients treated with beta-adrenoceptor blocking agents. PCT; plateletcrit, MPV; mean platelet volume, PWD; platelet width distribution, TG; triglycerides, HDL-c; high-density lipoprotein-cholesterol.

DISCUSSION: The results showed that hypertensive patients treated with BARBs have a significant low serum glucose level and non-significant high serum triglycerides and cholesterol levels compared with those patients did not treat with BADRBs. This observation may relate to the BARBs in addition to the other factors for the following reasons:

First: the characteristic features of participants enrolled in the study did not show significant difference between Group I and II. The number of smokers in Group II was less than corresponding number of Group I  (p=0.056) and this finding is in agreement with other studies that show active smoking is a risk factor of diabetes. The fasting serum glucose among Group I patients who are non-diabetic was significantly higher than corresponding level of Group II patients ¹⁶.

Second: the number of Group II patients who used ARBs was non-significantly less corresponding number of Group I. This observation is in favor that low fasting serum glucose level among Group II patients is due to the using BARBs because ARBs reduced the serum glucose ¹⁷.

Third:  The anthropometric measurements and the levels of the blood pressure did not show significant difference. Therefore, these factors did not bias the results of low fasting serum glucose among group II patients. This finding is in agreement with other studies that using BARBs resulted in a significant correlation between reduction of the blood pressure and changes in the anthropometric measurements ¹⁸. In this study, the levels of blood pressure are still high as well as the anthropometric measurement.

Fourth:  Significant low fasting serum glucose and a non-significant high serum triglycerides and cholesterol levels highlight the guideline of using BARBs in diabetic patients. The use of BARBs increased the risk of dyslipidemia and atherogenic lipids as this study reports this observation ¹⁹. The significant low serum glucose level that observed in this study does not agree with other studies, which most probably due to the heterogenecity of the prescribed BARBs as DiNicolantonio et al 2015 mentioned ¹⁹. Therefore, one of the limitations of the study is the small number size that does not allow a significant analysis of the effect of each BARBs on the metabolic derangement.

Fifth: The result of this study do not show significant effect of using BARBs on the platelet indices but there is a non-significant correlation with fasting serum triglycerides whereas a significant negative correlation observed in Group I patients. This indicates that BARBs affect the plateletcrit indirectly irrespective of their effects on the serum triglycerides. There is evidence that there is a dysfunction of the blood platelet when there is metabolic derangement in term of hyperuricemia or dyslipidemia ²⁰. This observation is of great importance that indicates the patients of Group II are free from the risk for coronary artery disease as previous studies reported a significant alteration in the platelet indices in patients with diabetes ²¹.

In conclusion, BARBs carried a metabolic derangement in term of alterations in the fasting serum glucose, triglycerides and cholesterol, but they offered a favorable effect on the platelet function and thereby reduced the risk of coronary artery disease.  

ACKNOWLEDGEMENT: Author is highly thankful to Dr. Ismail I. Hussein, Assistant Professor of Physiology, College of Medicine, Al-Mustansiriyah University, for his effort and support for this study.

CONFLICT OF INTEREST: The author declares that there is no conflict of interest.

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    How to cite this article:

    Ali ZAGM: Effects of beta-adrenoceptor blockers on the platelet and cardiometabolic indices in uncontrolled hypertension. Int J Pharm Sci Res 2018; 9(2): 761-65.doi: 10.13040/IJPSR.0975-8232.9(2).761-65.

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