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Table of Content - Volume 4 Issue 2 - November 2017

 

Risk of hypertension in subclinical hypothyroidism

 

Smita Kottagi1, Triveni Jambale2*, Srinivas Deshpande3, Amareshwar Malagi4

 

1,2Assistant Professor, 3Professor, 4Associate Professor, Department of Biochemistry, Gadag Institute of Medical Sciences, Gadag, Karnataka, INDIA.

Email: trivenijambale@gmail.com

 

Abstract               Background and Objectives: Hypothyroidism is associated with increased risk for cardiovascular disease by increasing the risk for hypertension, hypercholesterolemia, and increased low-density lipoprotein cholesterol levels. Thyroid hormones play an important role in regulating lipid metabolism and maintaining the blood pressure. Subclinical hypothyroidism is found to progress to overt hypothyroidism. But whether subclinical hypothyroidism (SCH) is associated with increased blood pressure and dyslipidemia is controversial aspect. Studies revealing risk of hypertension leading to cardiovascular disease in subclinical hypothyroidism are conflicting. This study was done to evaluvate the risk of hypertension in subclinical hypothyroidism. Materials and Methods: 30 SCH cases were compared with 30 euthyroid controls. Serums T3, T4, TSH were estimated by ELISA method, Serum Total-Cholesterol, HDL-Cholesterol by enzymatic CHOD-PAP method, Triglycerides by GPO-POD method and LDL-Cholesterol using Friedewald formula, and blood pressure was measured by using mercury sphygmomanometer. Results: Significant increase was found in the mean serum levels of TSH (P<0.001), Total cholesterol (p<0.001), Triglycerides (P<0.001), LDL Cholesterol (P<0.001), HDL-Cholesterol (P<0.001), systolic blood pressure (p<0.001) and diastolic blood pressure (P<0.001). No significant change was observed in levels of serum T4. Percentage of subjects with increased Total Cholesterol, Triglycerides, LDL-C, systolic blood pressure and diastolic blood pressure and decreased HDL-C were more in subclinical hypothyroidism as compared to euthyroid controls indicating the hypertensive changes in subclinical hypothyroidism. Conclusion: The Study revealed that hypertension is seen in subjects with subclinical hypothyroidism. This points to the importance of screening the patients for subclinical hypothyroidism and prevent them from progressing to overt hypothyroidism, hypertension and cardiovascular diseases.

Key Words: Subclinical hypothyroidism, hypothyroidism, hypertension, blood pressure.

 

 

 

INTRODUCTION

Subclinical hypothyroidism is defined as the subclinical status of elevated serum thyrotropin (TSH) levels, with normal levels of thyroxine (T4) and triiodothyronine (T3). It is a more common disorder than overt hypothyroidism. the prevalence rate of subclinical hypothyroidism is 1.4–7.8%1,2. The prevalence increases with age and is higher in women. Cardiovascular diseases (CVDs) are the most common cause of mortality3. Hypothyroidism is associated with higher levels of some cardiovascular risk factors involving higher total cholesterol and low density lipoprotein cholesterol levels as compared to euthyroid subjects. Hypothyroidism is related with increased risk of hypertension and atherosclerosis4 but there are no clear studies about subclinical hypothyroidism and its relation with hypertension. patients with subclinical hypothyroidism advance to hypothyroidism. Lipid abnormalities are more common in patients with hypothyroidism and contribute to the increase in hypertension in these persons. But whether patients with subclinical hypothyroidism show hypertension and dyslipidemia is not very clear. Thyroid hormone increases basal metabolic rate in all the tissues and organs in the body, the increased metabolic demands lead to the changes in cardiac output, Superior venacaval resistance and blood pressure. In hypothyroidism there is the presence of endothelial dysfunction and impaired vascular smooth muscle relaxation lead to increased Superior venacaval resistance5 These effects lead to diastolic hypertension in many patients, and thyroid hormone replacement therapy is found to restore endothelial-derived vasorelaxation and blood pressure to normal in most of the patients.

 

 

MATERIALS AND METHOD

The study was done in the Dept. of Biochemistry, BLDEU’S Shri. B. M. Patil Medical College Hospital and Research Centre, Bijapur (Karnataka) India. 30 subclinical hypothyroid cases with the age of 35 years and above and 30 controls were included in the study according to the inclusion and exclusion criteria considered for the study. This study was approved by the Institutional Ethics Committee. All the subjects gave an informed consent before undergoing further investigations. The study was carried out from November 2011 to May 2013.

Inclusion Criteria: Subclinical hypothyroidism cases having TSH in the range of 4.50 to 14.99 mlU/L, T3 and T4 within normal limits. The euthyroid controls having normal TSH [0.3-4.5 mlU/L.] were included in the study.

Exclusion Criteria: Cases with known hypothyroidism, thyroidectomy cases, patient with radiotherapy, previous radioactive iodine therapy, consumption of drugs known to cause SCH, primary or secondary dyslipidemia, patients with diabetes mellitus, patients with other systemic illness, renal and hepatic failure cases, patients on statins were excluded from the study.

Collection of blood samples: Venous blood samples were drawn at 8 a.m. following a 12 hours of fasting, in a plain bulb from the subjects, with all the aseptic precautions. Blood samples were centrifuged within 30 minutes at 3000 rpm for 5 min. and serum was separated. Serum samples were stored at -20°C until assayed. Serum T3, T4, TSH were estimated by ELISA method.(6-8) Serum total cholesterol estimation and HDL-C was done by enzymatic COD-PAP method.9 LDL-C was calculated by using Friedewald formula.10


 

RESULTS

Table 1: Comparison of parameters between subclinical hypothyoidism subjects and healthy controls

PARAMETER

SCH Patients

(Mean±SD)

Euthyroid controls

(Mean±SD)

P value

Statistical significance

TSH (mIU/L)

8.18 ± 1.46

2.64 ± 1.01

P<0.0001

HS

T3 (ng/dL)

1.86 ± 0.51

1.03 ± 0.17

P<0.0030

HS

T4 (µg/dL)

88.12 ± 17.72

90.27 ± 22.78

P<0.4160

NS

TC (mg/dL)

250.72 ± 38.36

173.66 ± 39.13

P<0.0001

HS

TG (mg/dL)

169.25 ± 18.74

101.37 ± 31.58

P<0.0001

HS

LDL-C (mg/dL)

191.63 ± 37.94

120.24 ± 36.39

P<0.0001

HS

HDL-C (mg/dL)

26.03 ± 4.07

34.23 ± 6.63

P<0.0001

HS

SBP (mm Hg)

130.36 ± 5.65

121.73 ± 4.35

P=0.0002

HS

DBP (mm Hg)

96.43 ± 3.08

81.86 ± 4.16

P<0.0001

HS

p<0.001- Highly Significant. T3=Tri-iodothyronine, T4=Tetra iodo- thyronine, TSH=Thyroid stimulating hormone, TC=Total cholesterol, LDL=Low density lipoproteins, HDL=High density lipoproteins, SBP= Systolic Blood Pressure, DBP= Diastolic Blood Pressure.

 

Table 2: Risk factors for hypertension in sch patients

Variable

SCH Patients (%)

Euthyroid controls (%)

TC (> 200 mg/dL)

88.3

32

TG (> 150 mg/dL)

70.3

13

LDL (> 130 mg/dL)

96

30.3

HDL (< 30 mg/dL)

65.3

12.3

SBP (≥ 140 mm Hg)

8.6

0

DBP (≥ 90 mm Hg)

77.6

0

Shows the percentage of cases with higher blood pressure and lipid profile parameters in the study group. The percentage of subjects having hypertension (>140/90 mm Hg), elevated TC (>200 mg/dL), LDL (130> mg/dL), TG (150> mg/dL), and decreased HDL (<30 mg/dL) was higher in SCH patients than in controls.

 

Legend

Figure 1: Shows comparison of risk factors for hypertension in SCH and controls

Figure 2: Shows comparison of lipid profile in SCH and Euthyroids

 


DISCUSSION                           

Subclinical Hypothyroidism (SCH) is more common than overt hypothyroidism. Thought overt hypothyroidism causes secondary hyperlipidemia and promotes atherosclerosis is generally accepted11, studies examining the relationships between hyperlipidemia, atherosclerosis, and SCH have yielded less convincing results. In recent times subclinical hypothyroidism is being diagnosed more frequently than overt hypothyroidism12. Overt hypothyroidism is associated with abnormalities of lipid metabolism, which can predispose to the development of atherosclerosis and coronary artery disease (CAD)13. Subclinical hypothyroidism has been associated with increased risk for atherosclerosis. studies on coronary heart disease (CHD) in subjects with subclinical hypothyroidism are conflicting14. The effects of alterations of thyroid function as in SCH on lipid profile and atherogenesis remain unclear15. Present study demonstrated that patients with SCH have significantly higher systolic and diastolic blood pressure than the control group (table 1 and fig 2 ). We found that approximately 8.6% of SCH patients had elevated systolic blood pressure and 77.6% had elevated diastolic blood pressure compared with 0% in the euthyroid, control group (table2 and fig1).our study is similar to the study done by Rafael Luboshitzky16 in which they demonstrated that percentage of subjects with increased systolic and diastolic blood pressure were more in sub clinical hypothyroidism as compared to controls. Many studies have proved impaired left ventricular diastolic and systolic myocardial functions in subclinical hypothyroidism leading to elevated diastolic and systolic blood pressure16,17,18. Exposure of aortic endothelial and vascular smooth muscle cells to triiodothyronine (T 3) can cause cellular relaxation. Two binding sites specific for T 3 have been identified. When cells are exposed to T 3, no effect on phosphorylation or nitric oxide production were observed, suggesting that T 3 has a direct action on the vascular smooth muscle cells to cause vascular relaxation16. Study done by Rafael Luboshitzky et al17 showed that the percentage of subjects with increased total cholesterol, triglycerides, LDL-C were more in SCH as compared euthyroid controls our study showed the similar results. Study done by Nadia Caraccio19 showed the similar results as our study indicating increased levels of Total cholesterol and LDL-C in subclinical hypothyroidism. Rafael Luboshitzky17 demonstrated that percentage of subjects with elevated systolic and diastolic blood pressure were more in sub clinical hypothyroidism as compared to controls. Several studies have reported impaired left ventricular diastolic and systolic myocardial functions in subclinical hypothyroidism leading to elevated diastolic and systolic blood pressure16,18,19 our study showed similar results.

 

CONCLUSION

Our study reveals that significantly higher levels of serum TSH, Total Cholesterol, Triglycerides, LDL-C, systolic blood pressure, and diastolic blood pressure and lower levels of HDL-C are seen in subclinical hypothyroidism as compared to euthyroid controls indicating hypertensive and dyslipidemic state associated with SCH leading to increased risk for cardiovascular disease This indicates the importance of checking the patients of subclinical hypothyroidism for hypertension and treating them so that the development of cardiovascular disorders in future can be avoided.


 

 

 

 

 

 

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