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Abstract

Objectives:

To compare the mean platelet volume (MPV; a general marker of platelet activation) in groups of patients with and without hypertension and to analyse its relationship with left ventricular mass index (LVMI).

Methods:

This cross-sectional, observational study enrolled newly diagnosed patients with untreated stage I–II hypertension and healthy control subjects without hypertension. MPV was measured using a haematology analyser. Echocardiography was performed on all of the study participants.

Results:

A total of 50 newly diagnosed patients with hypertension and 50 healthy control subjects were enrolled in the study. The majority of the demographic characteristics and laboratory findings were not significantly different between the two groups. The mean ± SD MPV was significantly higher in the hypertensive group compared with the control group (10.3 ± 1.4 fl versus 9.2 ± 1.8 fl, respectively). The mean ± SD LVMI was significantly higher in the hypertensive group compared with the control group (115.9 ± 23.0 g/m² versus 95.7 ± 23.4 g/m², respectively). There was no significant correlation between MPV and LVMI.

Conclusion:

In patients with untreated hypertension, despite elevated MPV levels there was no correlation between LVMI and MPV.

Keywords

Hypertension mean platelet volume left ventricular mass index

Introduction

Large platelets are more active metabolically and enzymatically, and they have increased thrombotic potential, compared with small platelets.¹ Mean platelet volume (MPV) has been shown to be a marker of platelet activation, which plays an important role in the pathophysiology of atherosclerosis.^1–3 Elevated MPV levels are thought to be closely associated with cardiovascular diseases (especially acute coronary syndromes) as well as hypertension, diabetes mellitus and hyperlipidaemia.^2–5 Subclinical target-organ damage caused by hypertension is a well-known major risk factor for cardiovascular disease.⁶ The main pathophysiological mechanisms of elevated MPV in hypertension are not clearly understood.

In order to investigate the existence of platelet activation in patients with hypertension, this study compared the MPV in patients with hypertension and healthy control subjects without hypertension. In addition, the study analysed the relationship between MPV and left ventricular mass index (LVMI).

Patients and methods

Study population

This cross-sectional, observational study included consecutive, newly diagnosed patients with stage I–II hypertension according to the Seventh Report of the Joint National Committee (JNC-7) criteria,⁷ who were not being treated with antihypertensive medication, attending the Department of Cardiology, School of Medicine, Firat University, Elazig, Turkey between January 2012 and January 2013. Healthy age- and sex-matched control subjects without hypertension were recruited from among the clinic staff of the Department of Cardiology, School of Medicine, Firat University. Patients with ischaemic heart disease, heart failure, valvular heart disease, severe kidney disease, elevated urea or creatinine levels, chronic obstructive pulmonary disease, diabetes mellitus, atrial fibrillation, severe anaemia, hypo- or hyperthyroidism, oncologic or any rheumatic disease were excluded from the study. The exclusion criteria also included known previous myocardial infarction, unstable angina pectoris, congenital heart disease, left ventricular systolic dysfunction on echocardiography (ejection fraction < 50%), chronic renal failure, known inflammatory disease, haematological disease, autoimmune disease, acute infectious hyperthyroidism, pregnancy, anticoagulant agent use, white blood cell count > 12 000 cells/µl or < 4000 cells/µl, and a high body temperature > 38℃.

Written informed consent was obtained from each study participant. This study was approved by the Local Ethics Committee of the School of Medicine, Firat University.

Blood pressure measurements

All of the study participants were seated on a chair with a backrest. Their feet were placed on the ground and their right arm was supported. They were allowed to rest in this position for ≥ 10 min before their blood pressure measurements were taken with a sphygmomanometer (Erka; Majac Medical Products, Geebung, Australia). Systolic and diastolic blood pressure levels were determined and recorded by using the Korotkoff sounds. Study participants did not consume cigarettes, tea or coffee for ≥ 30 min before the blood pressure measurements were taken. Consecutive measurements were performed at least twice per day in the morning for 3 days; only patients with measurements ≥ 140/90 mmHg were included in the study.

Measurement of blood cells and biochemical parameters

In all study participants, antecubital venous blood samples for laboratory analyses were drawn on admission to the hospital and added to ethylenediaminetetra-acetic acid (EDTA)-containing anticoagulation tubes (Sarstedt, Essen, Belgium). Using plasma samples, routine blood parameters including a complete blood count were measured using a Sysmex K-1000 haematology autoanalyser (Sysmex Corporation, Kobe, Japan).

Venous blood samples were also used to routinely prepare serum. Serum levels of blood glucose, creatinine, blood urea nitrogen, and the lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides) were determined using an Olympus AU-600 autoanalyser (Olympus Optical, Tokyo, Japan) according to the manufacturer’s instructions. Blood samples that were not used immediately were stored at −20℃.

The MPV was evaluated using a Sysmex SE 9000 haematology analyser (Roche Diagnostics, Mannheim, Germany) using a 3-ml sample of venous blood collected in EDTA-containing anticoagulation tubes that had been left at room temperature for 3 h.

Echocardiography

Transthoracic echocardiography was performed by two independent echocardiography cardiologists (M.F.Y. and E.K.) using a Vivid 5 instrument (GE Medical Systems, Milwaukee, WI, USA), with a 2.5 MHz transducer and harmonic imaging according to the recommendations of the American Society of Echocardiography.⁸ Left ventricular systolic and diastolic diameters were measured by M-mode echocardiography. The left ventricular ejection fraction was assessed using the Teichholz method.⁸ The left ventricular mass (LVM) was calculated according to published methodology:⁹ LVM (g) = 1.04 [(IVST + LVEDD + PWT)³−(LVEDD)³]−13.6; where IVST is interventricular septum thickness, LVEDD is left ventricular end-diastolic diameter, and PWT is posterior wall thickness. LVMI (g/m²) was calculated as follows: LVMI = left ventricular mass/body surface area.⁹

Statistical analyses

All statistical analyses were performed using the SPSS® statistical package, version 17.0 (SPSS Inc., Chicago, IL, USA) for Windows®. All results are expressed as mean ± SD for continuous variables and as n (%) for categorical variables. All data were tested for normal distribution using the Kolmogorov–Smirnov test. Categorical data were compared between the two groups using χ²-test or Fisher’s exact test. Parametric continuous data were compared between the two groups using unpaired Student’s t-test. Nonparametric data were compared using the Mann–Whitney U-test. Pearson’s correlation coefficient analysis was used to examine possible relationships between parameters. A two-tailed P-value < 0.05 was considered statistically significant.

Results

A total of 50 newly diagnosed untreated patients with stage I–II hypertension and 50 healthy age- and sex-matched control subjects were enrolled in the study. Clinical and demographic data are presented in Table 1. There were no significant differences between the two groups in terms of age, height, weight and sex distribution. Body mass index, diastolic and systolic blood pressure, left ventricular ejection fraction, left atrial diameter, LVM and LVMI were significantly higher in patients with hypertension compared with control subjects (P < 0.05 for all comparisons; Table 1).

Table 1.

Clinical and demographic characteristics of patients with newly diagnosed hypertension (n = 50) and healthy control subjects (n = 50).

Parameter	Hypertensive group n = 50	Control group n = 50	Statistical significance^a
Age, years	57.5 ± 11.1	56.3 ± 9.1	NS
Height, m	1.61 ± 0.07	1.64 ± 0.08	NS
Weight, kg	78.4 ± 10.4	74.6 ± 9.2	NS
Sex, female	41	34	NS
Body mass index, kg/m²	30.1 ± 4.3	27.6 ± 3.0	P = 0.006
Current smoker	0	0	–
Diabetes mellitus	0	0	–
Systolic BP, mmHg	147 ± 21	114 ± 14	P < 0.0001
Diastolic BP, mmHg	84 ± 1 2	70 ± 10	P < 0.0001
LV ejection fraction, %	61.1 ± 2.9	59.7 ± 2.8	P = 0.01
Left atrial diameter, mm	37.2 ± 3.9	32.6 ± 3.2	P < 0.0001
LVM, g	212.3 ± 41.5	172.0 ± 42.1	P < 0.0001
LVMI, g/m²	115.9 ± 23.0	95.7 ± 23.4	P < 0.0001

Data presented as mean ± SD or n of study participants.

^aCategorical data were compared between the two groups using χ²-test or Fisher’s exact test. Parametric continuous data were compared between the two groups using unpaired Student’s t-test. Nonparametric data were compared using the Mann–Whitney U-test.

BP, blood pressure; LV, left ventricular; LVM, left ventricular mass; LVMI, left ventricular mass index; NS, not statistically significant (P ≥ 0.05).

Results of routine biochemical analyses including MPV are presented in Table 2. Glucose, and total and low-density lipoprotein cholesterol levels were significantly higher in patients with hypertension compared with control subjects (P < 0.05 for all comparisons). The mean MPV was significantly higher in patients with hypertension compared with control subjects (P = 0.001). There was no significant correlation between MPV and LVMI (r = 0.125; Pearson’s correlation coefficient analysis).

Table 2.

Routine biochemical data for patients with newly diagnosed hypertension (n = 50) and healthy control subjects (n = 50).

Parameter	Hypertensive group n = 50	Control group n = 50	Statistical significance^a
MPV, fl	10.3 ± 1.4	9.2 ± 1.8	P = 0.001
White blood cell count, cells/µl	7932 ± 2226	7506 ± 1682	NS
Haematocrit, %	42.2 ± 4.1	41.8 ± 4.2	NS
Haemoglobin, g/dl	14.1 ± 1.5	14.4 ± 1.6	NS
Platelet counts, ×10⁹/l	271 ± 76	279 ± 60	NS
Total cholesterol, mg/dl	214 ± 34	197 ± 35	P = 0.02
LDL cholesterol, mg/dl	144 ± 32	119 ± 35	P = 0.001
Triglycerides, mg/dl	173 ± 92	160 ± 113	NS
Glucose, mg/dl	111 ± 7	93 ± 10	P = 0.04
Sodium, mmol/l	139 ± 3	134 ± 29	NS
Potassium, meq/l	4.3 ± 0.4	4.3 ± 0.3	NS
Urea, mg/dl	29.8 ± 8.1	30.1 ± 15.6	NS
Creatinine, mg/dl	0.79 ± 0.19	0.77 ± 0.38	NS

Data presented as mean ± SD.

^aParametric continuous data were compared between the two groups using unpaired Student’s t-test. Nonparametric data were compared using the Mann–Whitney U-test.

LDL, low-density lipoprotein; NS, not statistically significant (P ≥ 0.05).

Discussion

This current study demonstrated that MPV was significantly increased in patients with hypertension compared with healthy normotensive control subjects, but it was not correlated with LVMI.

The successful measurement of cell dimensions with electronic cell counters has enabled the assessment of MPV in both clinical and research settings.¹⁰ Circulating platelets are heterogeneous in terms of size, density and reactivity. Increased platelet reactivity leads to shortening of bleeding time and increased platelet volume.¹¹ Normally, platelets are heterogeneous when they are produced from megakaryocytes, but when they are newly produced they are not usually large and dense.^10–12 Large platelets are more active metabolically and enzymatically, and they have increased thrombotic potential.^1–3,5 However, if platelet production is stimulated then not only does the MPV increase, but also the platelet width increases.⁵ Megakaryocytes in bone marrow biopsies after acute myocardial infarction were found to have an increased cytoplasmic volume.⁵ The biological and prognostic value of increased MPV remains controversial and the precise reasons for the increase in the size of platelets have not been elucidated. In this present study, the reason for the MPV increase in the patients with hypertension could be due to the stimulation of platelet production in the bone marrow by hypertension-induced stress. Other studies have shown an association between hypertension and MPV.^4,13–15 However, the relationship between LVMI and MVP is unclear. MPV was found to be significantly higher in patients with hypertension than in normotensive control subjects, and within the hypertensive group larger platelets were associated with target-organ damage.⁴ A correlation between LVMI and MPV has been demonstrated, which was more pronounced in untreated patients with concentric hypertrophy.¹⁶ MPV in patients with gestational hypertension was significantly higher than MPV in normal pregnant women.¹⁷ MPV was shown to be positively correlated with diastolic ambulatory blood pressure in essential hypertension and white-coat hypertension groups.¹³ MPV in hypertensive or prehypertensive patients with metabolic syndrome was associated with coronary artery disease.¹⁴ Bulur et al.¹⁵ did not observe a correlation between MPV and LVMI in hypertensive patients with target-organ damage, which was compatible with the findings of the present study. The platelet half-life of ∼7–10 days may be the reason for the lack of correlation between MPV and LVMI in the present study. Although MPV can be affected by daily events, LVMI is affected by long-term events. Consequently, MPV can easily return to the normal range after the recovery from daily events, but LVMI requires a longer time-period to recover. Therefore, the lack of any correlation between these two parameters might be attributed to this situation.

This current study had a number of limitations. Firstly, the major limitations were that this was a single-centre study that included only a small number of patients. However, the study population contained homogeneous unselected patients with hypertension, which mirrored the real-world scenario. Secondly, the method used to measure MPV is associated with technical issues that can directly affect the MPV: this method involves allowing the blood sample containing EDTA to stand for a period of time at room temperature prior to analysis, which can induce known artifacts. In previous studies, blood samples containing EDTA were left to stand for ≥1 h (often between 1 and 4 h) in order to avoid the effects of any rapid changes during this time period.^4,10 In this study, the blood samples containing EDTA were evaluated after 3 h of standing at room temperature. Because MPV changes according to the method of measurement, it is difficult to determine a standard normal range. Therefore, each laboratory must determine its normal limits for the method that they use. Thirdly, MPV is only a general indicator of platelet function, therefore it might be appropriate to use more expensive but widely accepted parameters of platelet function in future studies, to provide more valid information about the relationship between MVP and LVMI than could be obtained using the methods that were available for this study. Fourthly, albuminuria levels and retinal examinations were not undertaken to detect the development of end-organ damage in patients with newly diagnosed hypertension who were enrolled in the study, therefore the relationship between these parameters and MPV could not be evaluated. Fifthly, this study did not stratify the patients with hypertension according to their MPV (low versus high MPV based on a cut-off MPV value from a receiver operating characteristic [ROC] analysis), which would have allowed an evaluation of LVMI and markers of end-organ damage between these two MPV groups. Finally, multivariate regression analyses were not undertaken to establish independent relationships between MPV and other parameters; neither was a ROC analysisundertaken to establish the relationship between MPV and hypertension.

In conclusion, in newly diagnosed patients with untreated stage I–II hypertension, the MPV level (which was used as a marker of increased thrombotic potential), was significantly elevated compared with the MPV level in healthy control subjects, but there was no correlation between LVMI and MPV.

Footnotes

Declaration of conflicting interest

The authors declare that there are no conflicts of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Relationship between mean platelet volume elevation and left ventricular mass index in hypertensive patients