HORMONAL AND BIOCHEMICAL CHARACTERISTICS OF PATIENTS WITH ISCHEMIC HEART DISEASE AND GROWTH HORMONE DEFICIENCY IN ADULTS"

Urmanova Yu.M

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UDK: 616.12-005.4:612.44:577.17+576.32/36

HORMONAL AND BIOCHEMICAL CHARACTERISTICS OF PATIENTS WITH ISCHEMIC HEART DISEASE AND GROWTH HORMONE

DEFICIENCY IN ADULTS"

Urmanova Yu.M.

Alfraganus University.

Department of Clinical Disciplines

Аннотация

В данной статье автор анализирует результаты обследования 21 взрослого пациента с ишемической болезнью сердца и МС на фоне ДВСР. Выявлено снижение средних значений ГР, ЛГ у мужчин и ФСГ у женщин в 1-й группе пациентов и в во 2-й группе снижение средних значений ГР, ИФР-1, ЛГ у мужчин и ФСГ у женщин свидетельствует о гипопитуитаризме в обеих группах пациентов, а также о склонности к развитию вторичного гипогонадизма у мужчин. наблюдалось достоверное увеличение уровней ОХ, ЛПОНП и коэффициента атерогенности (Р < 0,005), при этом наиболее значимо увеличивались средние значения триглицеридов (Р < 0,0001), при этом наиболее выраженные нарушения липидного и углеводного обмена выявлены у пациентов 2-й группы.

Annotation

In this article the authors analyzed the results of investigation of 21 adults withischemic heart disease and growth hormone deficiency. The decreasing of mean levels of STH, LH in men and FSH in women in first group of patients, and decreasing of mean levels of STH, IGF-1, LH in men and FSH in women in second group of patients showed the hypopituitarism in both groups of patients, besides that to the development of secondary hypogonadism in men. In patients of 1 and 2 groups we found increasing of the levels of cholesterin, lipoproteins of low density, coefficient of atherogenesis (P < 0.005), at this time mean levels of tryglycerids had been increased (P < 0.0001). We found more deep disorders of lipids and

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carbohydrates in patients of second group.

Keywords:Growth hormone deficiency (GHD) in adults, coronary heart disease, obesity

Annotaciya

Ushbu makolada muallif 21 nafar YIK va MSda KOGT holatini tekshirib tahlil kildilar. 1-gurux,dagi mizhozlarda YG, erkaklarda yz navbatida LGning, ayollarda esa FSG miqdorining yrtacha kyrsatkichlari kamaiganligi aniklandi. Shu bilan bir qatorda 2 - gurux,dagi mizhozlarda YG, IYF-1ning, erkaklarda LGning, ayollarda esa FSGning kamayishi aniklandi. Yukloridagilarning barchasi ikkita gurukhda hypopituitarismni erkaklarda ikkilamchi hypogonadismni takidlandi.

Ikkita gurukh bemorlarida ham UH, LPUKZ kyrsatkichlariorganini, atherogen coefficients (P < 0.005), organini takidlanadi. Shu bilan bir qatorda triglyceridlarning umumiy kyrsatkichlari sezilarli darazhad ortgandir (P < 0.0001), ya'ni bundan tashkari ikkita gurukh bemorlarda ham yoF va carbohydrate almashinuvida uzgarishlar kuzatilgandir.

Relevance.The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis regulates cardiac growth, stimulates myocardial contractility, and influences the vasculature. The GH/IGF-1 axis controls intrinsic cardiac contractility by increasing intracellular calcium availability and regulating contractile protein expression; stimulates cardiac growth by increasing protein synthesis; modifies systemic vascular resistance by activating the nitric oxide system and regulating non-endothelial-dependent actions. The relationship between the GH/IGF-1 axis and the cardiovascular system has been widely demonstrated in numerous experimental studies and is supported by cardiac disorders secondary to both GH excess and deficiency. [1,2].

Several years ago, an open-label clinical trial showed that seven patients with idiopathic dilated cardiomyopathy and chronic heart failure (CHF) had significant improvements in cardiac function and structure after three months of treatment with recombinant GH plus standard heart failure therapy. More recent studies, including a small, double-blind, placebo-controlled trial of the effects of GH on exercise capacity and cardiac and pulmonary function, have shown that GH is beneficial in patients with CHF secondary to ischemic and idiopathic dilated cardiomyopathy.[3.4].

In addition to its growth-promoting and metabolic effects, the GH/IGF-1 axis regulates cardiac growth, stimulates myocardial contractility, and influences the

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vascular system.[5.6]. The myocardium and endothelium not only express receptors for both GH and IGF-1, but also locally produce IGF-1. Thus, there is a direct action of GH via an endocrine mechanism and/or an indirect action via autocrine/paracrine mechanisms of IGF-1 [ 7-10].

The link between the GH/IGF-1 axis and the cardiovascular system has been well demonstrated in numerous experimental studies and confirmed by abnormalities in cardiac structure and function reported in patients with both GH excess (acromegaly) and GH deficiency (GHD).

All this indicates the relevance of the chosen topic and served as the reason for conducting this study.

The aim of the study isto study the hormonal and biochemical characteristics of patients with coronary heart disease (CHD) with DHRV

Material and research methods. We examined 21 adult patients with coronary heart disease and MS. Of these, 13 were men (61.9%) and 8 were women (38%). The average age was 58.0 years for men and 58.2 years for women. The duration of the disease ranged from 2 months to 25 years.

The study methods included: 1) general clinical (examination of endocrine, neurological and ophthalmological status, anthropometry - height, weight, WC, HC, BMI, assessment of Conflicting results were obtained in a randomized, double-blind, placebo-controlled study of rhGH treatment, which showed that in fifty patients with CHF, an increase in LV mass associated with serum IGF-1 levels, but no change in LV wall stress, blood pressure, ejection fraction, clinical status or 6-minute walk distance, 2) instrumental (fundus, visual acuity, ECG, echo-ECG, hM-ECG, ultrasound of the liver, kidneys, ultrasound of the carotid arteries, etc.), 3) hormonal blood tests (STH, IGF-1, LH, FSH, PRL, TSH, ACTH, prolactin, testosterone, estradiol, progesterone, cortisol, T3, T4), which were performed by the immunochemiluminescent method, 4) general clinical and biochemical blood tests (ALT, AST, LDL, HDL, cholesterol, triglycerides, calcium, coagulogram, blood glucose, total bilirubin, urea and creatinine, CRP, etc.). and urine.

Lipid metabolism study: total cholesterol and TG were determined using Randox tests on a Centrifichem-600 autoanalyzer, HDL-C — on a Technicon AAP autoanalyzer (USA) after precipitation of LDL and VLDL from plasma with phosphotungstic acid. The level of LDL-C and VLDL-C was calculated using W. Friedwald formulas.

The diagnosis of coronary heart disease and stable angina was established on the basis of typical pain syndrome provoked by physical exertion, anamnesis

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data, typical ECG changes and a positive bicycle ergometric test. The functional class (FC) of angina according to NYHO was determined in accordance with the classification of angina by the Canadian Heart Association (1976.). It was found that patients with coronary heart disease and patients with clinical signs of obesity had signs of stage NC0 or stage NC1.

All patient data were entered into the computer database we created, "Volumetric formations of the hypothalamic -pituitary system with growth hormone deficiency," for further statistical processing (Intellectual Property Agency of the Republic of Uzbekistan, Certificate of Registration BGU 00263 dated 25.03. 2011 Tashkent, Shakirova M.Yu., Urmanova Yu.M.)

The obtained data were processed using the computer programs Microsoft Excel and STATISTICA_6. Differences between groups were considered statistically significant at P<0.005. The mean values (M), standard deviations of the means (m) were calculated.

Reliability of differences in level between ggroups was assessed by the size of the confidence interval and the Student's criterion (p).

Comparison of anthropometric indicators was performed in comparison with literature data (3).

Research results and their discussion. Table 1 shows the distribution of patients by gender and age.

Table 1. Distribution of patients by gender and age (according to WHO)

Age, years Number of men (%) Number of women (%)

16 - 29 - -

30-44 - 1 (12.5%)

45-59 9 (69.2%) 4 (50%)

60-74 4(30.7%) 3 (38%)

75 and Art. - -

Total: 21 13 (61.9%) 8 (38%)

The patients were divided into 2 main groups depending on the severity of the underlying disease: Group 1 - patients with coronary heart disease. Angina pectoris. FCII - 4 patients (19.0%), group 2 -patients with ischemic heart disease. Angina pectoris. FCIII - 17 (81.0%).

When studying the average hormone values among our patients, the following

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disorders were established (Table 2). In group 1 of patients, the average levels of pituitary tropic hormones in the blood plasma were significantly reduced -STG(P < 0.005), although the level of IGF-1 was within the normal range (P > 0.05) - closer to the lower limits of the norm, as well as the levels of LH in men(P < 0.005), FSH was decreased in women(P < 0.005), and peripheral: free testosterone and thyroxine were closer to the lower limits of the norm (P > 0.05). At the same time, hyperprolactinemia was observed in patients of this group (P < 0.005), and a decrease in the average values of estradiol in women (P < 0.005). Thus, a decrease in the average values of STH, LH in men and FSH in women in group 1 of patients indicates hypopituitarism in this group of patients, as well as a tendency to develop secondary hypogonadism in men.

AnalysisThe average values of hormones in patients of group 2 also revealed a number of disorders. First of all, these patients had significantly reduced levels of GH and IGF-1 in plasma (P < 0.005, respectively). As is known, IGF-1 deficiency is a marker of DHRH (1-5), so we primarily paid attention to this. In addition, average LH levels in men were significantly reduced(P < 0.005), and FSH was decreased in women(P < 0.005).

Table 2. Average values of various hormones in both groups of patients

Hormones Control Group I n=4 P, significanc e of differences with control II group n=17 P, significan ce of differenc es with control

STH 3.5 ± 0.3 1.1±0.2 P < 0.005 0.2± 0.01 P < 0.005

IGF-1 485 ± 9.8 156.3±13.2 P > 0.05 129.7±11. 2 P < 0.005

LH M 9.0 ± 0.3 IU/L F* 12.5 ±2.4 M 3.4± 0.4 AND13.2±3. 2 P < 0.005 P > 0.05 M 3.05± 0.6 W 17.4± 3.4 P < 0.005 P > 0.05

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FSH M6.5±0.8 ME/L F* 35.7±2.6 M 4.4± 0.2 AND16.3±3. 3 P > 0.05 P < 0.005 M 4.01± 0.8 W 22.3± 4.6 P > 0.05 P < 0.005

Prolactin 5.7±0.3ng/ ml 23.6±7.2 P < 0.0001 10.4±1.3 P < 0.05

TSH 2.5±0.2ME /L 2.4±0.3 P > 0.05 2.78±0.4 P > 0.05

T3 1.2-2.8 nmol/l 1.65±0.8 P > 0.05 1.93±0.7 P > 0.05

T4 60-160 nmol/l 75.3±5.2 P > 0.05 114.64±1 3.1 P > 0.05

Cortisol 596.5 ± 11.7 nmol/l 388.5±11.7 P > 0.05 408.2±13. 8 P > 0.05

Free testosterone M 32.6 ± 3.7 pg/ml M17.05±4.6 P > 0.05 M12.4±3. 3 P > 0.05

Estradiol F* 55.2 ± 1.9 W 47.9±9.8 P > 0.05 W 34.5±8.6 P < 0.005

ACTH 25 ± 8.9 pg/ml 25.2±3.5 P > 0.05 30.6±4.3 P > 0.05

W* - in this case for postmenopausal women, M - men, P - reliability of differences in comparison with the control.

A tendency towards a decrease in peripheral hormones was noted: free testosterone was closer to the lower limits of the norm (P> 0.05). At the same time, moderate hyperprolactinemia was observed in patients of this group (P< 0.005), and a decrease in the average values of estradiol in women (P< 0.005). A decrease in the average values of STH, IGF-1, LH in men and FSH in women in the 2nd group of patients indicates hypopituitarism in this group of patients, as well as a tendency towards the development of secondary hypogonadism in men.

Thus, the study of the hormonal background of patients with coronary heart disease.Angina pectoris. FCII and IIIshowed that the most pronounced disorders were observed in patients of the second group compared to the first. The study of hormonal status revealed significant disturbances in the concentration of somatotropic hormone (STH) and insulin-like growth factor-1 (IGF-1) in blood

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plasma. It was found that the frequency of DGR in the examined patients with coronary heart disease of both groups was 15 cases out of 21 (71.4%). At the same time, 8 (53.3%) patients with laboratory-established DGR showed a reliable decrease in the concentration of IGF-1 in blood plasma. It should be emphasized that STH levels fluctuated within the range from 0.15ng/mlup to 0.53ng/mlin 13 (86.6%) of 15 patients overall, indicating a predominance of low basal STH concentrations. And IGF-1 levels were within the range of 58ng/mlup to 120ng/ml in 10 (50%) of 20 patients.

All the above-mentioned hormonal disorders in both groups of patients aggravate the degree of metabolic disorders in these patients.

IN Table 3 shows the average values of the lipid spectrum and other biochemical blood parameters in patients in group 1.

As can be seen from the studies performed, presented in the table,In patients of group 1, there was a significant increase in the levels of TC, VLDL, and the atherogenicity coefficient (P < 0.05), while mean triglyceride values were increased most significantly (P < 0.0001). Also significantly increased were the average values of LDL, HDL, direct bilirubin, urea, blood creatinine, as well as fasting glucose. The levels of total protein, ALT, AST, PTI were within normal limits. All the above-mentioned violations of the lipid spectrum and other biochemical parameters indicate significant violations of lipid and carbohydrate metabolism.

Table 3. Average values of lipid spectrum and other biochemical blood parameters in patients of group 1 (n=4)

Indicators Average value P, reliability of differences with the norm Control

Total cholesterol 223,05 ± 4.8 P < 0.005 117 ± 8.9 mg/dL

(TC)

Triglycerides 280,1 ± 12.6 P < 0.0001 145 ± 6.3 mg/dL

HDL 50,2 ± 4.3 P < 0.005 40, 1 ± 3.5 mg/dl

VLDL 56,5 ± 3.2 P < 0.005 34.2 ± 4.7 mg/dl

LDL 114,12 ± 8.9 P < 0.005 65.3 ± 7.2 mg/dl

Atherogenicity 3.65± 0.4 P < 0.005 1.8 ± 0.3

coefficient

ALT 16,4 ± 2.7 P > 0.05 12.5 ± 0.7 U/L

AST 19,8 ± 1.6 P > 0.05 23, 2 ± 2.4 U/L

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Total protein 85,0 ± 6.5 P > 0.05 79, 8 ± 5.8 g/l

Total bilirubin 10.3± 2.9 P > 0.05 7.1±1.4 ^mol/l

Direct bilirubin 7.0± 0.5 P < 0.005 2.3±0.6 ^mol/l

Urea 7.3± 0.8 P < 0.0001 0.9 ± 0.02 mg/dL

Creatinine 112.7± 14.6 P < 0.0001 27.7±4.3 ^mol/l

PTI 91.05± 11.7 P > 0.05 95, 5± 6.7%

Fasting glucose 8.2± 3.9 P < 0.005 4.3± 0.5mmol/l

HbA1C-glycated 6.0± 0.2 P < 0.005 6.2± 0.3%

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hemoglobin

P - significant difference comparec to the normal group.

Table 4 shows the average values of the lipid spectrum and other biochemical blood parameters in patients in group 2.

As can be seen from the studies performed, presented in Table 5, patients in group 2, compared to group 1, showed a more reliable increase in the levels of TC, VLDL, and the atherogenicity coefficient (P < 0.0001), while mean triglyceride values were increased most significantly (P < 0.0001). Also, the average values of LDL, HDL, direct bilirubin, urea, blood creatinine, as well as fasting glucose, glycated hemoglobin were significantly increased and, in comparison with Group 1, these values indicated more pronounced disorders. The levels of total protein, ALT, AST, PTI were within normal limits. All the above-mentioned disorders of the lipid spectrum and other biochemical parameters indicate significant disorders of lipid and carbohydrate metabolism.

Table4. Average values of lipid spectrum and other biochemical blood parameters in patients of group 1 (n=17)

Indicators Average value P, reliability of differences with the norm Control

Total cholesterol 248.4± 12.2 P < 0.0001 117 ± 8.9 mg/dL

(TC)

Triglycerides 250.26± 14.9 P < 0.0001 145 ± 6.3 mg/dL

HDL 53.4± 3.6 P < 0.005 40, 1 ± 3.5 mg/dl

VLDL 65.8± 2.3 P < 0.005 34.2 ± 4.7 mg/dl

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LDL 116.7± 11.7 P < 0.005 65.3 ± 7.2 mg/dl

Atherogenicity 4.6± 0.3 P < 0.005 1.8 ± 0.3

coefficient

ALT 15.4± 2.1 P > 0.05 12.5 ± 0.7 U/L

AST 16.4± 3.4 P > 0.05 23, 2 ± 2.4 U/L

Total protein 83.4± 8.9 P > 0.05 79, 8 ± 5.8 g/l

Total bilirubin 13.8± 2.1 P > 0.05 7.1±1.4 ^mol/l

Direct bilirubin 3.2± 0.8 P > 0.05 2.3±0.6 ^mol/l

Urea 6.4± 0.5 P < 0.0001 0.9 ± 0.02 mg/dL

Creatinine 89.03± 9.5 P < 0.0001 27.7±4.3 ^mol/l

PTI 99.5± 5.9 P > 0.05 95, 5± 6.7%

Fasting glucose 10.6± 1.4 P < 0.0001 4.3± 0.5mmol/l

HbAlC-glycated 8.0± 0.9 P < 0.005 6.2± 0.3%

hemoglobin

P - significant difference compared to the control group (norm).

Conclusions:

1) In group 1 of patients, the average levels of pituitary tropic hormones were significantly reduced -STG (p < 0.005), although the IGF-1 level was within the normal range (p > 0.05), as well as LH levels in men(P < 0.005), FSH was decreased in women(P < 0.005). In the 2nd group of patientslevels were significantly reducedSTGand plasma IGF-1 (P < 0.005, respectively), as well as average LH levels in men(P < 0.005), and FSH was decreased in women(P < 0.005).

2)A decrease in the average values of STH, LH in men and FSH in women in group 1 of patients, and in group 2 a decrease in the average values of STH, IGF-1, LH in men and FSH in women indicates hypopituitarism in both groups of patients, as well as a tendency to develop secondary hypogonadism in men.

3)In patients of groups 1 and 2, there was a significant increase in the levels of TC, VLDL, and the atherogenicity coefficient (P < 0.005), while mean triglyceride values were increased most significantly (P < 0.01), while the most pronounced disturbances of lipid and carbohydrate metabolism were found in patients of group 2. Also, the average values of LDL, HDL, direct bilirubin, urea, blood creatinine, as well as fasting glucose were significantly increased

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References

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2. Colao A, Vitale G, Pivonello R, Ciccarelli A, Di Somma C, Lombardi G. The heart: an end-organ of GH action. // Eur J Endocrinol. 2004;151:93-101. doi: 10.1530/eje.0.151s093

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HORMONAL AND BIOCHEMICAL CHARACTERISTICS OF PATIENTS WITH ISCHEMIC HEART DISEASE AND GROWTH HORMONE DEFICIENCY IN ADULTS" Текст научной статьи по специальности «Клиническая медицина»

Аннотация научной статьи по клинической медицине, автор научной работы — Urmanova Yu.M

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HORMONAL AND BIOCHEMICAL CHARACTERISTICS OF PATIENTS WITH ISCHEMIC HEART DISEASE AND GROWTH HORMONE DEFICIENCY IN ADULTS"

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