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ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 1  |  Page : 196-202

Relation between serum androgen levels and dyslipidemia in acute coronary syndrome


1 Department of Cardiology, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Biochemistry, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
3 Department of Cardiology, EL-Shohada Hospital, Egypt

Date of Submission11-Mar-2015
Date of Acceptance13-May-2015
Date of Web Publication25-Jul-2017

Correspondence Address:
Ibrahim Elmadbouh
8 El Amin St., Sharaf Square, Private Clinic, Shebin ElKom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_129_15

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  Abstract 


Objectives
The aim of this study was to evaluate the value of serum testosterone (total and free) and dehydroepiandrosterone (DHEA) levels in the diagnosis of patients with acute coronary syndrome (ACS) (acute non-ST-segment elevation myocardial infarction; NSTEMI) and to assess the availability of using serum androgen levels as clinical biomarkers in relation to dyslipidemia.
Background
Testosterone therapy may have beneficial effects on a number of risk factors of atherosclerotic ischemic heart disease.
Patients and methods
The study included 65 ACS patients diagnosed with acute chest pain and with positive troponin I and ECG changes (NSTEMI) and 25 normal (healthy) individuals as the control group. Serum testosterone levels have crucial roles in the diagnosis of ACS during early hours of symptoms.
Results
Patients with proven NSTEMI have significantly lower serum levels of androgens (total testosterone, free testosterone, and DHEA) compared with normal controls. There was a highly significant negative correlation between BMI, total cholesterol, and low density lipoprotein and free testosterone, total testosterone, and DHEA. There was also a highly significant positive correlation of the high density lipoprotein, with free testosterone, total testosterone, and DHEA. Also, serum testosterones and DHEA levels are having the same sensitivity to be decreased significantly in the blood of ACS patients.
Conclusion
Serum androgen levels were found to be decreased significantly in patients with NSTEMI, and this will help in early diagnosis, in making suitable therapeutic decision in few hours, and can be used in follow-up to monitor the progression of the disease.

Keywords: acute coronary syndrome, chest pain, dyslipidemia, testosterone


How to cite this article:
Abdelazez WF, Elmadbouh I, Mena MB, Zewain AA. Relation between serum androgen levels and dyslipidemia in acute coronary syndrome. Menoufia Med J 2017;30:196-202

How to cite this URL:
Abdelazez WF, Elmadbouh I, Mena MB, Zewain AA. Relation between serum androgen levels and dyslipidemia in acute coronary syndrome. Menoufia Med J [serial online] 2017 [cited 2019 Aug 18];30:196-202. Available from: http://www.mmj.eg.net/text.asp?2017/30/1/196/211479




  Introduction Top


Many studies found that low testosterone levels are associated with acute coronary syndrome (ACS) and increased coronary atheroma. Furthermore, low testosterone levels can be measured as a risk factor for the development of ACS. One study showed that low testosterone level is an independent risk factor for the development of ACS in men [1],[2].

Premenopausal women have a lower incidence of ACS, but this rises after menopause, and hence the risk rapidly approaches that of men. One explanation for this phenomenon is that testosterone influences the development and progression of coronary artery disease (CAD) [2].

In men, the increasing incidence of ACS with age is associated with a decline in testosterone levels [2],[3].

Testosterone therapy may have beneficial effects on a number of risk factors for atherosclerotic heart disease. In addition, testosterone may have specific properties that inhibit the progression of atherosclerosis [4].

The lifetime risk for ACS started at the age of 40 years (one in two for men and one in three for women) [5].

Moreover, testosterone has a number of actions on hemostatic/fibrinolytic system apart from the effects on fibrinogen. Androgens and testosterone in particular have antithrombotic actions [6].

After coronary catheterization, men with ACS with an incidence of stenosis have lower testosterone levels in comparison with men of the same age with normal coronary angiogram [7].

Several previous studies documented that plasma levels of testosterone fall transiently in the first 24 h after myocardial infarction. In addition, the profibrinolysis activity of testosterone was noted and a relation with hemostatic factors was confirmed by several subsequent studies [8].

The aim of this study was to present the value of using serum testosterone (total and free) and dehydroepiandrosterone (DHEA) levels in the diagnosis of patients with ACS (acute non-ST-segment elevation myocardial infarction; NSTEMI) and in healthy individuals to assess the availability of using serum androgen levels as clinical biomarkers in relation to dyslipidemia.


  Patients and Methods Top


The study included 65 patients admitted in Shebeen El-Kom University Hospital diagnosed with ACS (acute chest pain and diagnosed with NSTEMI and they represented the diseased groups (with positive troponin I and ECG changes). In addition, the study also included 25 normal (healthy) individuals as the control group. All patients and healthy individuals had one or more risk factors, including diabetes mellitus, hypertension, and obesity (dyslipidemia). Written informed consent was obtained from each participant before inclusion in the study. Ethical approval for this investigation was obtained from the Research Ethics Committee, Faculty of Medicine, Menoufia University.

Exclusion criteria

Patients with ST-segment elevation myocardial infarction, patients with negative troponin I or with no ECG changes or with both, patients with any hormonal disturbance (thyroid diseases, hypergonadism, hypogonadism, etc.), patients on renal dialysis, patients with congenital diseases, patients before puberty, and women during menstrual bleeding were excluded from the study.

Methods

All patients were subjected to full history taking for any ischemic heart attack and risk factors such as hypertension, diabetes mellitus, and dyslipidemia. Full clinical examination and ECG criteria of NSTEMI have been recorded. BMI was calculated according to the formula body weight divided by the square of the height (kg/m 2).

Venous blood sample (10 ml) was drawn by means of sterile venous puncture from the cubital vein of every investigated participant with clean dry syringes. The serum obtained was kept frozen at −80°C until analysis. Lipid profile [serum total cholesterol (TC), triglycerides (TG), and high density lipoprotein (HDL-C)] was evaluated using the standard enzymatic colorimetric kits (Spinreact, Girona, Spain). Serum low density lipoprotein (LDL-C) was calculated using this formula as TG level did not exceed 400 mg/dl: LDL-C = TC−(TG/5+HDL-C). All patients were subjected to evaluation of cardiac enzyme as troponin I (Enzyme-Linked Fluorescent Assay, ELFA; BioMerieux Inc., USA).

Serum levels of total testosterone (Calbiotech, Life Science Company), free testosterone and DHEA [Diagnostics Biochem Canada Inc. (DBC)] were measured using the enzyme-linked immunosorbent assay (ELISA) method using commercially available immunoassays and in accordance with the manufacturer's instructions.

Statistical analysis

The results were statistically analyzed using IBM personal computer and statistical package SPSS, version 11. Mean ± SD, percentage, Student's t-test, and Mann–Whitney test (nonparametric test) were used in the assessment of NSTEMI and controls. Pearson's correlation coefficient (r) was used to study the association between two quantitative variables. The c2-test, sensitivity, specificity, positive and negative predictive values, diagnostic accuracy and receiver operating characteristic curve were used to assess the diagnostic validity of total and free testosterone and DHEA. Results are given as mean ± SD, cutoff values according to sample times (95% confidence interval). P values of less than 0.05 were considered statistically significant.


  Results Top


Ninety patients were included in the study, of whom 63 (70%) were male and 27 (30%) were female. 65 (72.2%) represented the patient group and 25 (27.8%) patients represented the control group. In the patient group, 32.3% of patients had hypertension, 9.2% had diabetes, and 32.3% had both hypertension and diabetes. An overall 20% of controls had hypertension and 80% had no associated disease [Table 1].
Table 1 Clinical and laboratory data of acute coronary syndrome in patients and controls

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There was a highly significant difference between patients with ACS and the control group as regards BMI, free testosterone, total testosterone, DHEA, TC, LDL, and HDL (P = 0.001) [Table 1] and [Figure 1].
Figure 1: Serum of total testosterone (a), free testosterone (b) and dehydroepiandrosterone (DHEA) (c) levels in acute coronary syndrome (ACS) patients versus controls.

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The mean and SD of the studied groups (male and female) as regards age, BMI, and laboratory investigations (n = 90) is presented in [Table 2]. There was a highly significant difference between the two groups as regards free testosterone and total testosterone (P = 0.001), but there was no significant difference as regards other parameters.
Table 2 Lipid profiles and androgen levels in all studied participants as regards sex

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The Pearson's correlation was used in between subjects as ACS versus controls, between males; females and ACS [Table 3]. There was a highly significant negative correlation among patients with ACS and the control group between BMI, TC, and LDL and total testosterone, free testosterone, and DHA, and there was a highly significant positive correlation between HDL and total testosterone, free testosterone, and DHEA (P = 0.001; [Table 3] and [Figure 2].
Table 3 Pearson's correlation of total and free testosterone, and dehydroepiandrosterone with age, BMI, and laboratory investigations of studied groups

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Figure 2: Men sex hormonal levels in acute coronary syndrome (ACS) patients versus controls: Correlation between free testosterone and total cholesterol level (a); correlation between free testosterone and low density lipoprotein (LDL) level (b); correlation between total testosterone and total cholesterol level (c); correlation between total testosterone and LDL level (d); correlation between dehydroepiandrosterone (DHEA) and total cholesterol level (e); and correlation between DHEA and LDL level (f).

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Pearson's correlation was used to test the correlation of total testosterone, free testosterone, and DHEA with age, BMI, and laboratory investigations (TC, LDL, and HDL). In the male group, there was a highly significant negative correlation as regards BMI, total cholesterol, and LDL, and a highly significant positive correlation as regards HDL (P = 0.001), but there was no significant correlation as regards age. Pearson's correlation of total testosterone, free testosterone, and DHEA with age, BMI, and laboratory investigations in the female group was different compared with the male group; moreover, there was no significant correlation different between ACS groups [Table 3].

Moreover, the area under the receiver operating characteristics curve, sensitivity, and specificity of serum total testosterone, free testosterone, and DHEA were highly significant in ACS patients compared with controls [Table 4] and [Figure 3].
Table 4 Diagnostic validity of total and free testosterone, dehydroepiandrosterone in acute coronary syndrome patients and control groups

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Figure 3: The area under the receiver operating characteristics (ROC) curve of total testosterone (a), free Testosterone (b), and dehydroepiandrosterone (DHEA) (c) levels in acute coronary syndrome (ACS) patients versus controls.

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  Discussion Top


Epidemiological studies show that androgens influence cardiac function by acting directly on the heart. In humans, anabolic steroids have been associated with an increased risk for CAD by adversely affecting the plasma lipid and lipoprotein profile, producing thrombosis and cardiac hypertrophy [9],[10],[11].

In particular, the use of elevated doses of testosterone has been related to cardiac hypertrophy, ventricular remodeling, cardiomyopathy, myocardial infarction, and sudden cardiac death. However, with a normal steroid level, androgen actions are necessary for a range of developmental and biological processes, including maintaining the health of cardiomyocytes [11].

In addition, androgens produce direct and rapid vasodilatory effects in human coronary disease and stable angina, increasing the coronary flow between 12 and 17% [12].

Our study shows that patients with proven NSTEMI have significantly lower serum levels of androgens compared with normal controls. We have also found that among patients with NSTEMI, those with lower androgen levels have a greater amount of coronary atherosclerosis, thereby suggesting a possible pathogenetic role of low testosterone levels in the development of NSTEMI. Whether this effect is related to a direct effect of androgens on the progression of atherosclerosis or whether it is dependent on the effect of androgens on surrogate markers of atherosclerosis is still a matter of speculation.

Previous data from observational studies did not show a positive relationship between testosterone and CAD to demonstrate that high levels of this androgen may be a risk factor, but seem to suggest that patients with CAD may have lower testosterone levels [9],[11],[13],[14].

The inverse relationship between testosterone levels and coronary atherosclerosis found in our study suggests a possible protective role of the hormone on the progression of atherosclerosis.

The data described here do not explain any testicular dysregulation but just an association with reduced testosterone levels if compared with the control group.

Previous studies have investigated the effect of androgens on the development and progression of experimentally induced atherosclerosis in different animal models with diet-induced or injury-induced atherosclerosis [15].

Low androgen concentrations are strongly associated with an increase in cardiovascular risks, including the presence of atherogenic lipid profile, insulin resistance, obesity, and prothrombotic profile [13],[16],[17]. Thus, androgens appear to be involved in the regulation of vascular tone. Aging induces a progressive reduction in the plasma testosterone levels along the years, which begins to be deleterious as aging occurs, whereas physiological stress produces acute diminution of androgen levels. These conditions are determinants for clinical manifestation of hypertension [16],[18].

Observational studies in humans indicate that there is an inverse relationship between systolic pressure and the plasma level of testosterone in men. There is also a higher incidence of hypertension in individuals with reduced free circulating androgen [16].

Women over the age of 60 years show gradual increases in blood pressure over a period of 5–20 years, until hypertension is highly prevalent in women as in men. Estrogen reduction after menopause is partially responsible for this effect and experimental data indicate that the change in the estrogen/androgen ratio seems to be the cause [19].

The role of sex steroid hormones in modulating cardiovascular function is of the highest importance, given that androgen deficiency is strongly associated with common medical conditions, including metabolic syndrome, obesity, diabetes, hypertension, and atherosclerosis. Research in this field is necessary to know the real cardiovascular effects of androgens and to elaborate future therapeutic role of testosterone [20].

Controversial information exists about the role of sex hormones on cardiac remodeling during cardiac hypertrophy, including fibrosis. However, these differences are manifested as sex differences in cardiac remodeling. The size of the heart is bigger in men than in women, even when corrected for body weight. Men also have a higher incidence of fibrosis; however, direct effects of androgens are not clear. Men with chronic heart failure have relatively low androgen levels, which may contribute to the pathophysiological process [18],[20].

In our study we found that serum levels of free testosterone, total testosterone, and DHEA in the male group have a highly significant negative correlation with BMI, TC, and LDL, but they have a highly significant positive correlation with HDL.

However, in the female group, we found that serum levels of free testosterone, total testosterone, and DHEA have no significant correlation with BMI. In the female group also we found that serum levels of free testosterone have only a significant correlation with age, but serum levels of total testosterone and DHEA have no significant correlation with age. As in the male group, in the female group there was a highly significant negative correlation between serum levels of free testosterone, total testosterone, and DHEA and TC and LDL, but there was a highly significant positive correlation with HDL.

This explains the faster progression of atherosclerosis occurring in men than in women. However, the abundance of clinical evidence suggests protective effects of androgens during atherosclerosis. For example, high to normal range of testosterone concentrations exhibit preventive role in CAD. In fact, patients with CAD show significantly lower testosterone level compared with patients without CAD [21],[22].

Testosterone deficiency affects ~30% of men under 30 years of age, and, as aging occurs, testosterone level declines even more, a male condition known as andropause [23],[24].

The available information indicates that the evolution of atherosclerosis is faster in men independent of dyslipidemia or evidence of endothelial damage compared with women [2],[14].

In particular, the use of elevated doses of testosterone has been related to cardiac hypertrophy, ventricular remodeling, cardiomyopathy, myocardial infarction, and sudden cardiac death [25].

However, with a normal steroid level, androgen actions are necessary for a range of developmental and biological processes, including maintaining the health of cardiomyocytes [9].

Androgens might also produce additional hemodynamic effects by relaxing vascular bed, reducing after-load, and rapidly increasing cardiac contractility, resulting in increased cardiac output [26].

Both beneficial and pathological effects of androgens are observed clinically. Patients with chronic heart failure suffer considerable morbidity as well as early mortality [27],[28].

They exhibit altered structure and function of cardiac and skeletal muscle and excessive activation of catabolic hormones and inflammatory cytokines [29].





The serum testosterone levels were found to be decreased significantly in early hours of NSTEMI, and this fact will help us in emergency departments in making our diagnosis early as possible, in taking the suitable therapeutic decision in few hours, and helping us to expect the progression of the disease. Our research will give a good new way for accurate and early diagnosis of the NSTEMI as total and free testosterone, and DHEA; this will give superiority of our results in comparison with other laboratory diagnostic tests.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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