Журнал «Здоровье ребенка» 2 (45) 2013

Arterial hypertension (AH) holds a leading position in incidence and remains a significant medical and social problem both in Ukraine and all over  the world, being the most frequent cause of complications, disability and mortality in working age individuals [2,3,5]. It has been estimated that mortality among the patients with increased arterial pressure is two times higher than in individuals with normal pressure [2,3,5]. According to statistical data, 11,9 million of patients with AH were registered in Ukraine at the beginning of 2009, which comprised about 31,5% of adult population [5]. There has been registered a trend toward youthification of arterial hypertension [2,3].

Contemporary researchers draw particular attention to the prevention of AH complications, namely target organ involvement (heart, blood vessels). Thus, a study of stroke causes has shown that the significant factors include not only increased blood pressure (BP) but also disorders in blood clotting system [10,11]. The above mentioned information stipulates the search for new crucial risk factors, the identification of which could influence the level of mortality from the previously mentioned diseases.

The fact that circulating in blood inflammation factors and procoagulants play an important role in pathogenesis of vascular disorders is practically assured nowadays [7-11]. It was not until fairly recently that hyperhomocysteinemia has been also included in the potential risk factors of cardiovascular complications [6,12].

In 1969 K. McCully when examining children with a high level of homocysteine in blood was the first to note that they soon develop severe forms of arterial disorders. The author made a suggestion that the high level of homocysteinemia is a risk factor of vascular damage development both of atherosclerotic and thrombogenic origin [11].

It was proved that homocysteine can promote oxidation of low-density lipoproteins, endothelial function disorder, vascular smooth muscles cells proliferation, thrombocytes and coagulation cascade activation. Due to this homocysteine metabolism and its affecting factors in adults have been thoroughly investigated over the last years [6, 12, 13].  

In norm homocysteine level in blood plasma in adults varies from 5 tо 15mcmol/l; according to data provided by O. P. Shevchenko (2002), mean values of this factor in children comprise 5mcmol/l [6].

Based on the above stated information, hyperhomocysteinemia detection in adolescents with AH can be an early marker of hypertension progression and development of alterations in cardio-vascular system. At the same time the studies concerned with the research of homocysteine level in blood of children and adolescents with AH are singular in the available literature [6].

The purpose of the present study is to improve the methods of prevention of arterial hypertension and cardiovascular complications development in adolescents with arterial hypertension by investigating homocysteine level in blood serum.

Subject and methods.

To complete present objectives 116 adolescences were examined at Kharkov Regional Children Cardiologic Center (79,4±1,3% boys and 20,6±1,3% girls) at the age from 14 to 17 (average age 15,8±0,66 years). All the patients were admitted due to the history of presenting increased blood pressure episodes.

The investigation included the study of history and clinical data, estimation of physical development along with determination of body mass index (BMI), estimation of lipid profile and sympathoadrenal system (SAS) mediators indices.

24-hour monitoring of blood pressure (24-MBP) using MDplus unit (Novosibirsk, Russia) was performed to verify BP alterations and specify diagnosis. Arterial hypertension diagnosis was established in accordance with ICD 10 (code I-10 and I-15.2).

The state of cardiovascular system was investigated by routine Doppler echocardiography using PARTNER-3 unit, ESAOT, by the procedure, recommended by the Association of Specialists in Echocardiography [1]; electrocardiographic investigation was performed.

Homocysteine level determination was carried out by immunoenzyme analysis.

Results and discussion.

After clinical instrumental investigation, which included 24-hour monitoring of blood pressure, the patients’ diagnoses were determined as follows: primary arterial hypertension (PAH) was determined in 14 adolescents (12,1%), symptomatic (secondary) arterial hypertension in the structure of Biemond syndrome of puberty was determined in 45 children (38,8±4,5%), neurocirculatory dystonia (NCD) of hypertension type was determined in 17 individuals (14,7±3,3%). Secondary cardiomyopathy (SCMP) was established in 28 children (24,1±3,7%) with hypothalamic syndrome of puberty, in whom 24-MBP did not reveal signs of arterial hypertension (time index of increased systolic or diastolic blood pressure did not exceed 25%). Control group consisted of 12 healthy adolescents (10,3±3,1%) with normal values of blood pressure.

The investigation of homocysteine level in blood serum of 116 patients with further cluster analysis allowed to obtain four cluster disjoint distribution (fig.1).

Later on the patients were distributed over four groups depending on 1, 2, 3 or 4 clusters, i.e. according to homocysteine content level in blood serum (table 1).

The first cluster included 11 adolescents with the lowest level of blood homocysteine (2,43±0,31 mcmol/l). The second cluster (n=48) amounted for the patients with homocysteine levels, which corresponded to normal indices (6,65±1,94 mcmol/l). 

The third cluster included 39 examined individuals with an increased level of homocysteine in blood serum (13,68±2,45 mcmol/l). The fourth cluster comprised 18 children with a high level of blood homocysteine (29,56±8,42 mcmol/l).

The investigation of the patients’ complaints in different clusters revealed their non-specific character and absence of statistically significant differences in the frequency of certain complaints.  

Estimation of physical development showed the prevalence of abdominal obesity in the patients of the 4^th cluster, which predominantly included children with SAH (61%) and SCMP (28%) in the structure of Biemond syndrome of puberty.

 24-MBP analysis is summarized in Table  2.

Thus, it has been shown that there are statistically significant differences between patients groups with low homocysteine level (cluster 1) and increased homocysteine level (cluster 3) in the following criteria: mean SBP and mean DBP during a day; mean SBP and mean DBP at night; time index of increased SBP and DBP during a day and index of increased DBP at night time. There has also been found a statistically significant difference in the level of mean SBP during a day in patients with normal and increased homocysteine level (clusters 1 and 3, p=0,04). Patients with low and high values of blood serum homocysteine have shown a statistically significant difference in DBP level at night time (clusters 1 and 3, p=0,04).

The study of diagnoses structure in the groups of the examined individuals with different levels of blood homocysteine detected that the 1^st cluster (low level of blood homocysteine) mainly consists of patients with SCMP (45±4,2%), NCD pf hypertension type (27±3,2%); less than one third is made up of patients with SAH (27±3,2%). The 2^nd cluster (with normal value of blood homocysteine level) included all the control group patients (25±3,1%), and also adolescents with NCD of hypertension type (13±2,9%), SAH (29±3,2%), SCMP (27±3,2%).  Among the patients, who belonged to the 3^rd cluster (with an increased level of blood homocysteine) 72±4,7% of adolescents had PAH (28±3,2%) and symptomatic arterial hypertension (SAH) in the structure of Biemond syndrome of puberty (44±3,9%). Hyperhomocysteinemia was seen much less frequently in adolescents with NCD of hypertension type (15±2,9%%) and in patients with secondary cardiomyopathy (13±2,9%). The 4^th  cluster (with high level of blood serum homocysteine) mainly included adolescents with SAH in the structure of Biemond syndrome of puberty (61±4,9%). Adolescents who belonged to this cluster with NCD of hypertension type (11±2,8%) and SCMP (28±3,2%) were overweight (BMI=32,2±1,6 kg/m², which exceeds 95 percentile). Thus, there has been detected a trend toward an increase in the number of patients with PAH and SAH with an increase in the level of homocysteine in blood serum.

The study of homocysteine level in patients with different nosologic forms has shown that there are highly reliable differences in homocysteine content in blood serum between the examined control group individuals and patients with PAH and SAH; homocysteine level in aptients with secondary cardiomyopathy did not show statistically significant difference from control group indices (Table 3). 

The study of the present research results allows to draw the following conclusion:

1.  It has been found that there is a statistically significant increase in the level of homocysteine in blood serum in children with primary arterial hypertension (р<0,01) and symptomatic (secondary) arterial hypertension in the structure of Biemond syndrome of puberty (р<0,01) as compared to control group indices.

2. The highest level of blood serum homocysteine has been detected in adolescents with symptomatic arterial hypertension in the structure of Biemond syndrome of puberty Ме = 13,1 (LQ = 6,9;UQ = 19,3) mcmol/l.

3. There have been determined statistically significant differences in 24-hour blood pressure monitoring indices (mean systolic and diastolic blood pressure during a day and night; increased systolic blood pressure index during a day and night, increased diastolic blood pressure index at night) between the patients with low and increased level of homocysteine in blood serum.

We consider it expedient to continue the research in order to specify the influence of hyperhomocysteinemia on the progression of arterial hypertension in adolescents, among them the ones who are overweight.