Assessment of the Relation between Mean Platelet Volume, Non-Dipping Blood Pressure Pattern, and Left Ventricular Mass Index in Sustained Hypertension

Background

Arterial blood pressure (BP) exhibits a diurnal rhythm that is higher at daytime than at night time [1–3]. A nocturnal decline in BP of less than 10% of the daytime value has been termed as “non-dippers” [4]. Continuous 24-h ambulatory blood pressure (ABP) monitoring has been used to show the diurnal rhythm of arterial BP. The mechanisms responsible for abnormal diurnal BP variation remain unclear, but it may be associated with a deterioration of autonomic balance [5]. Erdem et al. reported a possible cardiac autonomic dysfunction in pre-hypertensive subjects with non-dipper pattern [6]. Verdecchia et al. demonstrated that lack of nocturnal BP fall in patients with essential hypertension was a good predictor of cardiovascular prognosis [7]. Furthermore, lack of nocturnal BP fall is a predictor of target organ damage, including stroke, renal failure, and adverse cardiovascular events [8–10]. Kang et al. reported that patients with CAD often had nocturnal non-dipping pattern, which might increase the risk of future coronary events, including acute coronary syndromes [11]. Zain El et al. reported that non-dipping morning blood pressure was an independent predictor of hypertensive target organ damage in elderly patients with isolated systolic hypertension [12]. Cha et al. [13] reported that masked and sustained hypertension, as well as non-dipping or reverse dipping pattern, were more common in the settings of severe renal failure and proteinuria. Karakas et al. demonstrated the relation of non-dipping blood pressure pattern with impaired left ventricular dyssynchrony in dipper and non-dipper hypertensives [14].

Previous studies have reported that increased platelet activity is associated with cardiovascular morbidity and mortality [15,16]. Mean platelet volume (MPV) is a very general and indirect marker of platelet activation that is altered in many situations, such as cigarette smoking, vascular abnormalities, hematological diseases, and atherosclerosis [17]. Elevated MPV value may reflect presence of active large platelets – which contain more dense granules that are metabolically and enzymatically more active than small ones – lead to high thrombus burden lesions that result in fatal or non-fatal cardiovascular events [17, 18]. Furthermore, increased MPV level was found to be related with cardiovascular mortality following acute myocardial infarction and restenosis [19,20].

The relation of raised MPV level with left ventricular hypertrophy has also been reported in patients with essential hypertension [21,22]. Since high MPV level, non-dipping blood pressure pattern, and left ventricular hypertrophy are known as independent risk factors for adverse cardiovascular events, we aimed to investigate the relations between MPV, non-dipping blood pressure pattern, and left ventricular mass index in patients with sustained hypertension.

Material and Methods

STUDY DESIGN:

This study had a retrospective case-control design.

STUDY POPULATION:

A total of 2500 patients (range, 18–80 years of age) in a large-volume tertiary hospital, whose ambulatory blood pressure (ABP) records had been evaluated retrospectively between January 2010 and December 2012, were screened. Past medical history, including cardiovascular risk factors, medications, and results of physical examination and laboratory analyses (including whole blood counts and standard biochemical parameters), were recorded from patient files. Any deficiencies in the information or missing or unavailable data about admission blood counts resulted in exclusion of the patient. By the end of the recruitment process, 840 patients remained and were included in the study.

The exclusion criteria were: secondary hypertension, masking hypertension, white-coat hypertension, active or former smoking, heart failure, recent MI, history of coronary artery bypass surgery, stroke, peripheral vascular disease, diabetes mellitus, valvular diseases, hemodynamically significant arrhythmias, history of stable and unstable angina pectoris, chronic renal failure (serum creatinine >1.5 mg/dl, blood urea nitrogen >30 mg/dl), chronic liver diseases, thromboembolic disorders, and hematological abnormalities. Patients who were already on antiplatelet therapy (acetylsalicylic acid or clopidogrel) were also excluded.

The study complies with the Declaration of Helsinki and the trial protocol was approved by the local Ethics Committee. The written informed consent was obtained from all participants.

STUDY PROTOCOL:

Patients were divided into 3 groups according to their ambulatory BP values: non-dipper hypertensives (n=289), dipper hypertensives (n=255), and normotensives (n=306). Body mass index was calculated by dividing the weight (kg) by height squared (m2). All patients underwent trans-thoracic echocardiographic examination (General Electric Vivid 7 GE Vingmend Ultrasound AS, Horten, Norway). The value of left interventricular septal diameter in diastole (LVSd), left ventricular end-diastolic diameter (LVEDd), and left ventricular posterior wall diameter in diastole (LVPWd) were recorded from echocardiographic examination reports. The left ventricular mass index (LVMI) was calculated with the following formula:

AMBULATORY BLOOD PRESSURE MONITORING:

The 24-h ABP measurement was performed using a portable compact digital recorder (Tonoport V, Milwaukee, GE Healthcare) and an analyser using customized analytical software programmed to measure blood pressures at 15-min intervals, from 07:00 until 23:00, and at 30-min intervals from 23:00 until 07:00. Daytime was defined as the time interval between the hours of 07:00 and 23:00, and night-time was defined as the time interval between the hours of 23:00 and 07:00. The patients were instructed to perform their usual daily activities, but to stay inactive during the measurements. Recordings were accepted if more than 80% of the raw data were valid.

BLOOD SAMPLING:

Blood samples were drawn from the antecubital vein after overnight fasting into standardized tubes containing dipotassium ethylenedinitrotetraacetic acid (EDTA) to be stored at room temperature. An automatic blood counter (Beckman Coulter, Miami, FL) was used for whole blood counts. The levels of MPV and other hematologic parameters were measured after 120 min from venipuncture. The expected values for MPV in our laboratory ranged from 6.8 to 10.8 fL. Other biochemical analyses were determined by standard methods.

STUDY VARIABLES:

The variables of the study were as follows: age, sex, weight, height, body mass index (BMI), fasting serum glucose, plasma lipids (triglyceride, HDL cholesterol, total cholesterol, and LDL cholesterol concentrations), creatinine, MPV, LVMI, platelet count, daytime systolic blood pressure (SBP), daytime diastolic blood pressure (DBP), night-time SBP, night-time DBP, 24-h SBP, and 24-h DBP.

DIAGNOSIS AND DEFINITIONS:

HT was defined as an office blood pressure (OBP) of ≥140/90 mm Hg, daytime ABP ≥135/85 mm Hg, or the active use of antihypertensive drugs. Sustained HT was defined as both an office blood pressure (OBP) of ≥140/90 mm Hg and a daytime ABP of ≥135/85 mm Hg. Normotension was defined as a consistent normal BP on OBP and daytime ABP measurements in patients not receiving antihypertensive treatment (OBP <140/<90 mm Hg and daytime ABP <135/<85 mm Hg) [23]. Non-dippers were defined as those with nocturnal decrease in systolic blood pressure (SBP) of less than 10% of daytime, and dippers were defined as those with a 10% or larger decline in systolic blood pressure during the nocturnal period of diurnal blood pressure [4].

STATISTICAL ANALYSIS:

All statistical analyses were performed using SPSS version 17 (SPSS for Windows, Version 17.0, SPSS Inc., Chicago, IL). The variables were investigated using visual (histograms, probability plots) and analytical methods (Kolmogorov-Smirnov and Shapiro-Wilks test) to determine whether the variables were normally distributed. Descriptive analyses are presented as the mean±standard deviation (SD), and categorical variables are expressed as percentages. Groups were compared with one-way analysis of variance (ANOVA; age, total cholesterol, low-density lipid [LDL] cholesterol, body mass index, and hematocrit), the Kruskal-Wallis test, and the chi-square test. The Mann-Whitney U test was performed to test the significance of pairwise differences using Bonferroni correction to adjust for multiple comparisons. A Spearman correlation analysis was performed to describe the association of MPV with 24-h SBP, 24-h DBP, and LVMI. A p value <0.05 was considered to be statistically significant.

Results

Baseline demographic, clinical, and laboratory characteristics of the study groups are presented in Table 1. There were no differences among 3 groups regarding age and male sex (p=0.690 and p=0.411, respectively). BMI was lower in the normotensive group than in non-dipper and dipper hypertensive groups, but the difference was not statistically significant (p=0.330). Moreover, the other baseline clinical and laboratory characteristics of the study groups were not significantly different between the 3 groups except for MPV levels, platelet count, and LVMI (all p values >0.05). The non-dipper and dipper hypertensive groups had significantly higher MPV levels than those of the normotensive subjects (8.4±1 fL, 8.3±1 fL, and 8.1±0.6 fL, p<0.001, respectively). However, there was no difference between the non-dipper and dipper groups in terms of MPV level (p=0.675) (Figure 1). Platelet counts were found to be significantly higher in the normotensive group than in dippers and non-dippers (275±65×106/mL, 266±722×106/mL, 54±65×106/mL, p<0.001). However, platelet counts were similar in the dippers and non-dippers groups (p=0.48). LVMI was significantly different between non-dippers, dippers, and normotensive groups (p=0.009). Also, it was found to be significantly higher in non-dippers as compared to normotensives (p=0.01).

The comparison of the ABP monitoring variables among the 3 groups are reported in Table 2. When the ABP values were compared among the 3 groups; daytime SBP, daytime DBP, nighttime DBP, 24-h SBP, and 24-h DBP were found to be significantly higher in non-dippers and dippers groups than in normotensives (all p values<0.001). Whereas night-time SBP and DBP in the non-dippers group were significantly higher than those of the dippers group (p<0.001), the daytime SBP and DBP were higher in dippers than in non-dippers, but the difference was not statistically significant. Twenty-four hour SBP and 24-h DBP were also found to be similar among non-dippers and dippers groups (p>0.017).

When the relation of MPV level with ABP variables was investigated, significant correlations were only found between MPV and 24-h DBP and 24-h SBP (r=0.076, p=0.027, and r=0.073, p=0.033, respectively). Furthermore, the association of MPV with left ventricular hypertrophy represented by LVMI was evaluated among hypertensive groups in this study. There was no correlation between MPV and LVMI in dipper and non-dipper hypertensive patients (r=−0.080, p=0.142, r: −0.086, p=0.158, respectively).

Discussion

STUDY LIMITATIONS:

The present study has some limitations. First, this study had a non-randomized retrospective design, and is from a single center. Second, we excluded patients with clinically overt cardiovascular disease (such as coronary artery disease, cerebrovascular disease, and renal failure); therefore, our results cannot be extrapolated to all hypertensive subjects. Thirdly, our study provides no information regarding long-term clinical outcomes in patients with sustained hypertension.

Conclusions

We demonstrated that MPV level, as an indirect indicator of platelet activation, was significantly higher in sustained hypertensive patients as compared to normotensives, but there was no significant difference between dippers and non-dippers subgroups. Also, we did not find any correlation between MPV and 24-h DBP, 24-h SBP, and LVMI among the 3 groups. MPV level was not found to be correlated with the non-dipping pattern of blood pressure and LVMI in patient with sustained hypertension. Elevated MPV level may be the possible mechanism behind the raised cardiovascular risk in sustained hypertension.