IJCRR

IJCRR - 6(10), May, 2014

Pages: 86-89

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APOLIPOPROTEIN B / APOLIPOPROTEIN A1 RATIO: AN IMPROVED MARKER OF CARDIOVASCULAR RISK IN HYPOTHYROIDISM

Author: Priyanka G. Rakshasmare, P. N. Joshi

Category: Healthcare

Abstract:Introduction: Hypothyroidism is a condition with decreased levels of thyroid hormones and elevated levels of Thyroid stimulating Hormone. Hypercholesterolemia is the characteristic feature of hypothyroidism and is also predisposing factor of atherosclerosis. Cholesterol in the body is transported through lipoproteins called Low density lipoprotein (LDL) and High density lipoprotein (HDL). The ratios, LDL/HDL and total cholesterol/HDL reflectthe direction of transport of cholesterol and are conventionally used to assess risk of cardiovascular diseases. ApolipoproteinB (apo B)present in Very low density lipoprotein(VLDL), Intermediate density lipoprotein (IDL), and LDL; is considered as atherogenicwhereas apolipoproteinA1 (apoA1) present in HDL, is antiatherogenic, anti-inflammatory with antioxidative properties. ApoB/apoA1 ratio represents the balance of proatherogenic and antiatherogenic lipoproteins. So the case control study was carried out to know the effectiveness of this improved ratio in hypothyroidism. Objective: To find out levels of total cholesterol (TC), LDL, HDL, apoB,andapo A1 2) To find out ratios- LDL/HDL, TC/HDL and apoB/apoA1 3) To check the effectiveness of apoB/apoA1 ratio as marker of cardiovascular risk in hypothyroidism. Methodology: Group A consists of 30 clinically diagnosed and biochemically confirmed cases of hypothyroidism. The levels of TC, HDL estimated using the kit, LDL using Friedewald formula, apoB and apoA1 byimmuno-turbidimetricmethod and result were compared with Group B (n=30) age and sex matched controls. Results: The levels of TC, LDL, and apoB were found to be increased highly significantly (p< 0.001) and that of HDL and apoA1 decreased highly significantly (p< 0.001). A highly significant increase in ratios namely LDL/HDL, TC /HDL and apoB/apoA1 was also observed. Conclusion: It can be concluded from the present study that apoB/apoA1 ratio is comparable with LDL/HDL and TC/HDL ratios. ApoB/apoA1 ratio can be an improved marker for prediction of cardiovascular risk in hypothyroidism.

Keywords: Hypothyroidism, hypercholesterolemia, apolipoprotein B/ apolipoproteinA1 ratio, cardiovascular risk.

Full Text:

INTRODUCTION

Hypothyroidism is a condition with decreased levels of thyroid hormones (T3, T4) and elevated levels of thyroid stimulating hormone (TSH)1,2 . Hypothyroidism is categorized into: - Primary hypothyroidism - a condition characterized by the failure of the thyroid gland to produce sufficient thyroid hormones.Secondary hypothyroidism (central thyroid disease) occurs as a result of pituitary or hypothalamic disease that produces a

deficiency in Thyroid stimulating hormone (TSH), thyroid releasing hormone (TRH) or both2 . According to various studies on thyroid disease, it has been estimated that about 42 million people in India suffer from thyroid diseases. Recent population-based study reported the prevalence of hypothyroidism as 3.9%3 .Thyroid hormones have significant effects on the synthesis and metabolism of lipids mainly cholesterol4,5,6 . Thyroid hormones regulate lipid metabolism by different ways: 1) up regulation of the low density lipoprotein receptors, which results in enhanced catabolism of the low density lipoproteins (LDL) particles, 2) stimulation of the cholesteryl ester transfer protein (CETP), an enzyme which transports cholesteryl esters from HDL 2 to the very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) and triglyceride to the opposite direction. 3) Activation of the lipoprotein lipase, which hydrolyzes the triglyceride rich lipoproteins.4) Stimulation of hepatic lipase (HL),which catabolises HDL2 to HDL3 and IDL to LDL4,12.Hypercholesterolemia is the characteristic feature of hypothyroidism and is also predisposing factor for atherosclerosis. Cholesterol in the body is transported by low density lipoprotein (LDL) and high density lipoprotein(HDL)4,5,6,7. The ratios, LDL/HDL and TC/HDL reflect thedirection of transport of cholesterol and are conventionally used to assess risk of cardiovascular diseases.Apolipoproteins are the protein moieties of lipoproteins. The various functions of apolipoproteins are 1) theycan form part of the structure of the lipoprotein. 2) They are enzyme cofactors.eg A-1 for lecithin: cholesterolacyltransferase, or enzyme inhibitors.eg A-II for lipoprotein lipase. 3) They act as ligands for interactionwith lipoprotein receptors in tissues.eg, Apo B for LDL receptor, apo A-1 for the HDL receptor1,2 . ApoB is the major protein in VLDL, IDL and LDL,with one protein per particle of lipoprotein. ApoA-I is the major protein in HDL particles. The apoB level indicates the total number of atherogenic particles, while apoA-I

reflects the anti-atherogenic potential in HDL particleswhich has anti-inflammatory and anti oxidativeproperties. The apoB/apoAI ratio indicates the balance between atherogenic and anti-atherogenic particles. Thus higher the ratio, higher the cardiovascular risk in hypothyroidism8,9,10. There are some methodological advantages of using these apoB/apoA1 ratio 1) direct measurement of apo B and apo A-1 by internationally standardized methods. 2) Fasting sample is not required for the analysis. 3) Apo B and apo A-1 can be analysed on frozen samples8,9 . Considering these facts, present study was conducted to find theeffectiveness of this Apo B/ApoA1 ratio over conventional LDL/HDL and TC/HDL ratios in hypothyroidism. Objectives: 1) To estimate levels of TC, LDL, HDL, ApoB and ApoA1. 2) To find out ratiosLDL/HDL, TC/HDL and apo B/apoA1. 3) To check the effectiveness ofapoB /apoA1 ratio as a marker of cardiovascular risk in patients with hypothyroidism.

MATERIALS AND METHODS

This study was carried out after approval from the Institutional Ethics Committee and prior consentfrom all participants.Study design: case control study consists of total 60 subjects they were dividedin two groups. Group A: consists of 30 clinically diagnosed and biochemically confirmed casesof hypothyroidism. Group B: consists of 30 age and sex matched healthy controls with normal thyroid function tests. Exclusion criteria - patients suffering from diabetes, obesity, polycystic ovarian diseases, liver, renal disease, congestive cardiac failure, taking oral contraceptive pills, statins, and other medications that alter thyroid function were excluded from this study. Research methods-Venous blood samples were obtained from each participant after 12 to 14 hour fasting period.TC and HDLwere measured by

enzymatic kitmethods,LDL was estimated by theFriedewald equation, and apo B, apoA-1, measured by using immuno -turbidimetric method11. The assays were performed in the clinical laboratory of the institute. Statistical analysis SPSS software was used to analyze all statistical data. The continuous data was expressed as Mean ± SD and a comparison was done by using an unpaired t test. P value <0.01 considered as significant, p<0.001 considered as highly significant.

RESULTS

The data obtained was compared between group A and group B. It was found that serum levels of TC,LDL, andapo B were increased highly significantly in group A as compared to group B (P<0.001) . Serum levels of HDL and apo A-1 were decreased. This decrease was also highly significant in group A as compared to group B (P<0.001). The ratios TC/HDL, LDL/HDL, apo B/apoA1 were also increased highly significantly in group A as compared to group B (P<0.001). see table no.1

DISCUSSION

LDL /HDL and TC/HDL are conventionally used to know the status of cholesterol in the body.Apo B is theapoprotein of atherogenic lipoproteins VLDL, IDL, LDL while apoA1 is theapoprotein component of antiatherogenic lipoproteins HDL.The role of apoB/apoA1 ratio in predicting risk of cardiovascular diseases is well documented9,10. In the present studyapoB was highly significantly increased while apoA1 was highly significantly decreased in patients with hypothyroidism. Thus apoB/apoA1 ratio was highly significantly increased, indicating levels of apoB, atherogenic component of LDLincreased and levels of apoA1 antiatherogenic component of HDL decreased highly significantly (table no-1). This indicates that in patients of hypothyroidismwith hypercholesterolemia, theratio of apoB/ apoA1 was significantly increased and they may have the risk of cardiovascular disease in the future.Treating these patients will decrease apoB to apo A1 ratio and thus may minimize risk of cardiovascular disease. Monitoring the levels of apo B, apoA1 and ratio of apo B to apoA1 will throw light on the response of the patients of hypothyroidism to the treatment.

CONCLUSION

It can be concluded from thepresent study that apo B / apoA1 ratio is comparable with LDL/HDL and TC/HDL ratios, which are conventionally used for the prediction of cardiovascular risk. Considering the above advantages of apo B/apoA1ratio over LDL/HDL and TC/HDL ratios, apoB /apoA1 ratio can be an improved marker for prediction of cardiovascular risk in hypothyroidism. It can also be used in monitoring the treatment of hypothyroid patients.

ACKNOWLEDGEMENT

Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

References:

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