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ORIGINAL ARTICLE |
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| Year : 2008 | Volume
: 28
| Issue : 2 | Page : 96-101 |
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Plasma homocysteine concentrations and serum lipid profile as atherosclerotic risk factors in subclinical hypothyroidism
Serpil Turhan, Sevilay Sezer, Gonul Erden, Ali Guctekin, Fatma Ucar, Zeynep Ginis, Ozlem Ozturk, Sezin Bingol
Department of Clinical Biochemistry, Ankara Numune Education and Research Hospital, Ankara, Turkey
| Date of Web Publication | 25-Aug-2009 |
Correspondence Address:
Gonul Erden
Ankara Numune Hastanesi Cebeci Merkez Laboratuvarlari, Ankara
Turkey
doi:10.4103/0256-4947.51750
PMID: 18398274
 Abstract | | |
Background and Objectives: Because subclinical thyroid dysfunction may be a risk factor for cardiovascular disease, we evaluated the atherosclerosis tendency in subclinical hypothyroid (SCH) patients.
Patients and Methods: Fifty-three subclinical hypothyroid patients (serum thyrotropin [TSH] concentrations >4.12 mU/L) were compared with a control group of 50 euthyroid subjects whose age, sex and body mass indices were similar to the patient group. We tested whether serum TSH concentrations were correlated with plasma total homocysteine concentration (tHcy), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and triglycerides (TG).
Results: There was a significant statistical difference between the patient and control groups for normal free T4 (1.02±0.17 vs. 0.86±0.13, P<.001), TSH (1.64±1.02 vs. 6.62±2.61, P<.001), TC (185±39 vs. 206±42, P=.01),TG (103±54 vs. 132±85, P=.04), LDL-C (114±33 vs. 127±36, P=.04), and TC/HDL-C (3.81±106 vs. 4.19±1.02,P=.04), respectively. No statistically significant difference was found between the two groups for HDL-C, VLDL C, LDL-C/HDL-C, and tHcy. Serum TSH was significantly correlated with plasma tHcy (r=0.55; P=.001), TC (r=0.52; P=.001), LDL-C (r=0.49; P=.001), TC/HDL-C (r=0.38; P=.002) and LDL-C/HDL-C (r=0.36; P=.004) across all participants.
Conclusion: Our study suggests that the atherogenicity of SCH is not mediated by hyperhomocysteinemia. Associated hyperlipidemia may explain the observed increased risk of coronary artery disease in patients with SCH.
How to cite this article:
Turhan S, Sezer S, Erden G, Guctekin A, Ucar F, Ginis Z, Ozturk O, Bingol S. Plasma homocysteine concentrations and serum lipid profile as atherosclerotic risk factors in subclinical hypothyroidism. Ann Saudi Med 2008;28:96-101 |
How to cite this URL:
Turhan S, Sezer S, Erden G, Guctekin A, Ucar F, Ginis Z, Ozturk O, Bingol S. Plasma homocysteine concentrations and serum lipid profile as atherosclerotic risk factors in subclinical hypothyroidism. Ann Saudi Med [serial online] 2008 [cited 2010 Sep 3];28:96-101. Available from: http://www.saudiannals.net/text.asp?2008/28/2/96/51750 |
Subclinical hypothyroidism (SCH) and hyperthyroidism represent the earliest stages of thyroid dysfunction. [1] SCH is defined by the finding of elevated serum thyrotropin (TSH) concentrations associated with normal free thyroid hormone levels and a lack of clinical signs and symptoms of hypothyroidism. [2],[3],[4] SCH is usually detected during the followtup of patients with a history of thyroid disease or as a result of biochemical screening for nonspecific symptoms. [5] Whether SCH has any demonstrable effect on serum lipid concentrations has been controversial. [2] ,[3] ,[5],[6],[7],[8],[9],[10] Several reports have shown that patients with SCH have a disturbed lipid metabolism, including elevated serum levels of total cholesterol (TC) [7] ,[11],[12],[13],[14],[15] and lowtdensity lipoproteintcholesterol (LDLtC). [7] ,[12],[13],[14],[15],[16] Such changes are generally recognised as risk factors for atherosclerosis and coronary heart disease. [16]
Homocysteine (Hcy) is formed during the metabolism of methionine, a sulfurtcontaining essential amino acid. [17] Many investigators have reported a significant association between hyperhomocysteinemia and cardiovascular disease. [18],[19],[20],[21],[22],[23] Elevated plasma total homocysteine (tHcy) levels have been reported in overt hypothyroidism, [24] and have been proposed as an independent risk factors for cardiovascular disease. [25] Whether SCH is a risk factor for premature cardiovascular disease is controversial. [2]
We conducted this study to see whether there is a tendency toward atherosclerosis in SCH. The serum lipid profile and plasma tHcy concentrations of SCH patients and a euthyroid control group were compared. We also investigated whether there was a correlation between serum TSH and serum lipid profile or serum TSH and plasma tHcy values in SCH patients.
| Methods | |  |
We studied 53 SCH patients (47 women and 6 men), aged 40.8±12.1 years and with a mean BMI of 26.2±4.6 kg/m 2 [Table 1]. SCH was established by TSH levels >4.12 mU/mL [26] and normal free T3 (FT3) and T4 (FT4) levels in two consecutive measurements. There was no history of thyroidectomy (total or subtotal) or prior exposure to radioiodine or external radiation in any of the patients included in the study. Thirteen of the female patients were posttmenopausal but none was receiving hormone replacement therapy. None of the participants was diagnosed with neoplastic, renal, liver disease, diabetes mellitus or familial hypercholesterolemia. Subjects receiving any drugs or who smoked were excluded from the study. Fifty aget and sextmatched healthy individuals were used as controls in baseline measurements. The control group consisted of 43 women (9 postmenopausal) and 7 men. The mean age of the controls was 38.2±10.6 years and the mean BMI was 25.1±5.4 kg/m 2 . Informed consent was obtained from all subjects. A local ethics committee approved the study.
Serum samples were collected in the fasting state, immediately put on ice and processed within 30 minutes. Thereafter, they were kept frozen at t20°C. Plasma tHcy concentration was measured by hightperformance liquid chromatography (Agilent 1100 series, Germany). The reference interval was 5t14 µmol/L. The intratassay and intertassay coefficients of variation for tHcy were 2% and 4.2%, respectively. An upper reference limit from a published study for TSH of 4.12 mU/L, [26] which was accepted for a multicultural population, was used in selecting individuals for the SCH group. Serum TSH, FT3, FT4 concentrations were measured by a chemiluminescent microparticle immunassay on an Architect i2000 analyzer (Abbott, Texas, USA). Reference intervals provided by the manufacturer were TSH 0.35t4.94 mU/L, FT3 1.71t3.71 pg/mL, and serum FT4 0.70t1.48 ng/dL. The sensitivities of the TSH, FT3, FT4 were 0.0025 mU/L, 1 pg/mL, and 0.4 ng/dL, respectively. The intratassay coefficients of variation for TSH, FT3, and FT4 were 1.7%, 2.7%, and 3.2%, respectively.
Serum TC (reference range, 112t200 mg/dL) and triglyceride (TG) (reference range, 50t179 mg/dL) were determined by enzymatic colorimetric assay on an Aeroset analyzer (Abbott, Texas, USA). Hightdensity lipoprotein cholesterol (HDLtC) (reference range, 28t 75 mg/dL) was determined enzymatically in the supernatant after precipitation of other lipoproteins. Very lowtdensity lipoprotein cholesterol (VLDLtC) was calculated using the TG/5 formula and LDLtC was calculated using the Friedewald formula. [27] The intratassay coefficients of variation for TC, TG, and HDLtC were 0.7% for high concentration, 1.0% for low concentration, 0.5% for high concentration, 0.8% for low concentration, 1.58% for high concentration, 1.7% for normal concentration, and 1.85% for low concentration, respectively. Serum creatinine (reference interval, 0.6t1.3 mg/ dL) concentration was measured by the Jaffe method on an Aeroset analyzer (Abbott, Texas, USA). Serum vitamin B12 and folic acid were determined by Access fullt automatic chemiluminescent assay (Beckman Coulture, Chaska, USA). Reference intervals were 160t980 pg/ mL for vitamin B12 and 0t3 ng/mL for folic acid.
The data for the SCH and control groups were compared by Student's t test and the Wilcoxon signedtrank test. Student's t test was used for comparison of group means with a normal distribution, while a Wilcoxon signedtrank test was used for comparison of means with nontnormal distributions. The Spearman rank correlation on the entire data set as well as within groups was used to test whether TSH was correlated with TC, LDLtC, HDLtC, TG, VLDLtC, TC/HDLtC, LDLt C/HDLtC, and tHcy. P values less than .05 were considered statistically significant.
| Results | | |
SCH patients had significantly lower FT4 (although within the normal range) and higher TSH levels than the control group [Table 1]. The mean plasma tHcy levels in patients were not significantly different than in controls [Table 2]. Mean serum levels of TC, TG, LDLtC, and the ratio of TC/HDLtC in patients were significantly different from the values in controls. Serum mean levels of VLDLtC, HDLtC, and the ratio of LDLtC/HDLtC were not significantly different from the values in controls. Across all participants TSH was positively correlated with TC, LDLtC, TC/HDLt C, LDLtC/HDLtC, and plasma tHcy concentrations [Table 3]. Correlations were not found between serum TSH concentration and serum TG and VLDLtC values.
| Discussion | | |
Hypothyroidism is a progressive disorder presenting with different degrees of thyroid failure and metabolic consequences. [28] SCH is defined as an elevation in serum TSH above the upper limit of reference range with a normal serum FT4 concentration. [6]
Cardiovascular diseases are the leading cause of death in industrialized nations. [29] Atherosclerosis is a multifactorial disease. Established risk factors include gender, age, smoking, TC, LDLtC, HDLtC, diabetes, [30] and hypertension. [29] In addition, several casetcontrol, crosstsectional and prospective studies have consistently indicated that hyperhomocysteinemia is an independent risk factor for the progression of vascular disease. [29]
Overt hypothyroidism has been found to be associated with cardiovascular disease. [11] Whether SCH is related to the risk for cardiovascular disease is controversial. It is well known that thyroid hormone has pervasive effects on the transport of the plasma lipoproteins. [31] Cholesterol and LDL typically accumulate in the plasma of patients with hypothyroidism because thyroid hormone stimulates LDL receptor activity. [10] ,[31] Thyroid hormone also influences the transport of TGt rich lipoproteins through its effects on the lipoprotein lipase enzyme system. Hepatic lipase has also been shown to decrease in severe thyroid deficiency and to increase after Ltthyroxine administration. [31] Hak et al [11] showed that SCH was present in 10.8% of participants and was associated with a greater agetadjusted prevalence of aortic atherosclerosis (odds ratio, 1.7 [95% CI, 1.1 to 2.6] and myocardial infarction (odds ratio, 2.3 [CI, 1.3 to 4.0]. Miura et al [32] diagnosed 97 patients with CHD by coronary angiography (CHD group) and compared them with 103 healthy subjects matched for age, sex and body mass index (control group). They observed a significant decrease in serum FT3 and FT4 levels in patients with CHD that was associated with increased serum TSH.
Some studies [10] ,[12] ,[16] suggest that high TSH is associated with deleterious changes in serum lipids, which are considered to be an important cardiovascular risk factor, particularly HDLtC, LDLtC, and the ratio of LDLtC to HDLtC. However, few studies [33] ,[34] have suggested that the majority of patients with SCH did not differ from controls in risk factors for coronary heart disease (e.g. TC, LDLtC, TK/HDLtC, LDLtC/HDLtC). Previous studies of thyroid dysfunction and TG levels have also been conflicting. Compared with individuals with normal thyroid function, TG levels have been reported to be high [6] ,[15] or unchanged [3] ,[7] ,[10] ,[13] ,[14] among those with biochemical evidence of SCH. In many previous clinical studies, [3] ,[6] ,[7] ,[12] ,[13] ,[15] ,[34] HDLtC has been reported to be unchanged among SCH patients.
We demonstrated that mean serum levels of TC, TG, LDLtC, and the ratio of TC/HDLtC in patients with SCH were significantly different from the values in controls. Mean serum levels of VLDLtC, HDLtC, and the ratio of LDLtC/HDLtC were not significantly different from the values in controls. TSH was positively correlated with TC, LDLtC, TC/HDLtC, LDLt C/HDLtC, and plasma tHcy concentrations.
Homocysteine is a sulfurtcontaining intermediate product in the normal metabolism of methionine, an essential amino acid. [22] Numerous retrospective and prospective studies have consistently found a relationship between mild hyperhomocysteinemia (fasting or after oral methionine loading) and cardiovascular disease or alltcause mortality. Starting at a plasma tHcy concentration of approximately 10 µmol/L, an associated risk increase follows a linear dosetresponse relationship with no specific threshold level. [22] Although 30 years have elapsed since hyperhomocysteinemia (and homocysteinuria) were first associated with an increased risk of atherothrombotic vascular disease, it is only recently that sufficient evidence has mounted to suggest that the association is independent and dosetrelated, and it remains to be established whether it is causal and modifiable. [18] If a causal relationship does prove to exist between tHcy and cardiovascular disease, the biological mechanism(s) remains to be established. [35] Several mechanism have been proposed to contribute to the vascular toxicity of homocysteine, including platelet aggregation, increased coagulation or reduced thrombolysis, endothelial dysfunction, and effects on the blood vessel wall. [36] Evidence now indicates that hyperhomocysteinemia, which occurs in approximately 5% to 7% of the general population, is an important, independent risk factor for atherosclerosis and thrombotic disease. [37] Lindeman et al [38] point out that thyroid status may be an important determinant of serum/plasma tHcy concentrations. The tHcy concentration appears to be increased in hypothyroidism and decreased in hyperthyroidism. Deicher and Vierhaper [39] reported that patients with SCH did not demonstrate improvement in fasting homocysteine levels after treatment with levothyroxine. Meek and Smallridge [40] reported that levothyroxine treatment with subclinical hypothyroidism did not alter homocysteine levels in the fasting or posttmethionine states.
Several studies [29] ,[34] ,[38] ,[41] have been published where subjects with SCH were compared against normal euthyroid subjects to determine if there was a continuum of change in serum tHcy concentrations in those with SCH as opposed to an increase that occurs only when overt hypothyroidism exists. Although there were correlations between serum TSH and tHcy in all participants in these studies, there were no significant differences between cases and controls. Aldasouqi et al [42] found no association between subclinical hypothyroidism and hyperhomocysteinemia. The findings of previous studies, as well as our current study, are summarized in [Table 4]. The results of our study confirm the findings of the previous studies.
Published retrospective studies demonstrate a stronger association between tHcy and CHD than prospective studies. [18] ,[35] ,[43] A major concern is that tHcy levels may rise after tissue damage; thus, retrospective studies of CHD patients may show elevated tHcy values as a result of, not a cause of, the coronary events. [43] One published report indicated that patients with SCH had homocysteine levels that were higher than those in normal control subjects and improved significantly with levothyroxine treatment. [44]
The purpose of our prospective study was to examine the effect of SCH on serum tHcy concentrations after adjusting for differences in gender, age and ethnicity. Additionally, serum folate, vitamin B12, and creatinine concentrations were also adjusted. A comparison had been made of selected CHD risk factors in male and female participants with SCH versus those with control group. In the present study, serum TSH levels were positively correlated with tHcy levels. Our study population consisted of adult patients (mean age of 40 years for the SCH group, of 38 years for the control group) who had previously not taken any drug and did not smoke. Serum TSH levels were greater than 4.12 mU/L and both FT3 and FT4 levels were normal in all participitants. Thus, our population was selected more rigoriously than the population in some other studies. There is no consensus on the relationship between SCH and CHD, although many studies have been performed. Only longtterm biochemical monitoring will prove the relationship. However, our study contributes information towards establishing an association between SCH and CHD. We have demonstrated higher serum levels of TC, TG, LDLtC in SCH patients. Research from experimental animals, laboratory investigations, epidemiology, and genetic forms of hypercholesterolemia indicate that elevated LDL cholesterol is a major cause of CHD. In addition, recent clinical trials robustly show that LDLtlowering therapy reduces the risk for CHD. [45] For these reasons, focusing on LDL values in SCH patients is important.
In conclusion, in the present study, homocysteine levels were not elevated in the majority of patients with SCH. We found no differences in plasma tHcy concentrations between the SCH group compared with the control group. Our results suggest that the atherogenicity of SCH is not mediated by hyperhomocysteinemia. Associated hyperlipidemia may explain the observed increased risk of coronary artery disease in patients with SCH.
| References | | |
| 1. | Col NF, Surks MI, Daniels GH. Subclinical thyroid disease. JAMA 2004;291(2):239-243.  |
| 2. | Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH et al. Subclinical thyroid disease. JAMA 2004;291(2):228-238. |
| 3. | Caraccio N, Ferrannini E, Monzani F. Lipopprotein profile in subclinical hypothyroidism: Response to Levothyroxine Replacement, a Randomized Placebo-Controlled Study. The journal of endoc and metab 2002;87(4):1533-1538. |
| 4. | Pacchiarotti A, Martino E, Bartalena L, Aghini-Lombardi F, Grasso L, Buratti M, et al. Serum free thyroid hormones in subclinical hypothyroidism. Journal of Endocrinological Investigation 1986;315(9):315-319. |
| 5. | Kahaly GJ. Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid 2000;10(8):665-679. |
| 6. | Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-534. [PUBMED] [FULLTEXT] |
| 7. | Efstathiadou Z, Bitsis S, Milionis HJ, Kukuvitis A, Bairaktari ET, Elisaf MS et al. Lipid profile in subclinical hypothyroidism: is L-thyroxine substitution beneficial? European Journal of Endocrinology 2001;145:705-710. |
| 8. | Kek PC, Ho SC, Khoo DH. Subclinical thyroid disease. Singapore Med J 2003;44(11):595-600. |
| 9. | Helfand M. Screening for subclinical thyroid disfunction in non-pregnant adults: A summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004;140(2):128-141. |
| 10. | Bauer DC, Ettinger B, Browner WS. Thyroid function and serum lipids in older women: A population-based study. Am J Med 1998;104:546-551. [PUBMED] [FULLTEXT] |
| 11. | Hak AE, Pols HAP, Visser TJ, Drexhage HA, Hofman A, Witteman JCM. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: The Rotterdam Study. Ann Intern Med 2000;132:270-278. |
| 12. | Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, et al. Impaired endothelium-dependent vasodilatation in subclinical hyppothyroidism: Beneficial effect of Levothyroxine therapy. The Journal of Clinical Endocrinology and Metabolism 2003;88(8):3731-3737. |
| 13. | Yildirimkaya M, Ozata M, Yilmaz K, Kilinc C, Gündogan MA, Kutluay T. Lipoprotein(a) concentration in subclinical hypothyroidism before and after levo-thyroxine therapy. Endocrine Journal 1996;43(6):731-736. |
| 14. | Hueston WJ, Pearson WS. Subclinical hypothyroidism and the risk of hypercholesterolemia. Annals of Family Medicine 2004;2(4):421-426. |
| 15. | Cabral MD, Costa AJL, Santos M, Vaisman M. Lipid profile alterations in subclinical hypothyrroidism. The Endocrinologist 2004;14(3):121-125. |
| 16. | Miura S, Iitaka M, Yoshimura H, Kýtahama S, Fukasawa N, Kawakami Y, et al. Disturbed lipid metabolism in patients with subclinical hypothyrroidism: Effect of L-thyroxine therapy. Internal Medicine 1994;33:413-417. |
| 17. | Haynes WG. Symposium: Vitamin therapy and ischemic heart disease. Hyperhomocysteiinemia, Vascular Function and Atherosclerosis: Effects of Vitamins. Cardiovascular Drugs and Therapy 2002; 16: 391-399. |
| 18. | Hankey GJ, Eilboom JW. Homocysteine and vascular disease. The Lancet 1999;354:407-413. |
| 19. | Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337:230-236. |
| 20. | Boushey CJ, Beresford SAA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease:Probable benefits of increasing folic acid intake. JAMA 1995;274:1047-1057. |
| 21. | Graham IM, Daly LE, Refsum HM. Plasma homocysteine as a risk factor for vascular disease: the European Concerted Action Project. JAMA 1997;277:1775-1781. |
| 22. | Stranger O, Herrmann W, Pietsik K, Fowler B, Geisel J, Dierkes J, et al. DACH-LIGA Hommocysteine (German, Austrian and Swiss Homocysteine Society): Consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med 2003;41(11): 1392-1403. |
| 23. | Ogawa M, Abe S, Biro MS, Toda H, Matsuoka T, Hiroyuki T, et al. Homocysteine and hemostatic disorder as a risk factor for myocardial infarction at a young age. Thrombosis Research 2003; 109: 253-258. |
| 24. | Morris MS, Bostom AG, Jacques PF, Selhub J, Rosenberg IH. Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in the third US National Health and Nutrition Examination Survey. Atherosclerosis 2001; 155:195-200. [PUBMED] [FULLTEXT] |
| 25. | Ebstein FH. Homocysteine and atherothrombosis. The New England Journal of Medicine 1998;338(15):1042-1050. |
| 26. | Hollowell JG, Staehling NW, Flanders D, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T4, and thyroid antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NH ANES III ). The Journal of Clin Endoc and Metab 2002;87(2):489-499. |
| 27. | Tietz Textbook of Clinical Chemistry. Editor: Burtis CA, Ashood ER. Third Edition. p. 843. Philadelphia, Pennsylvania 1999. |
| 28. | Gao TS, Teng WP, Shan ZY, Jin Y, Guan HX, Teng XC. Effect of differentiodine intake on schoolchildren's Thyroid disease and intelligence in rural areas. Chin Med J (Engl) 2004;117(10):1518-1522. |
| 29. | Christ-Crain M, Meier C, Guglielmetti M, Huber PR , Riesen W, Staub JJ et al. Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo- controlled trial. Atherosclerosis 2003;166:379-386. |
| 30. | Scheuner MT. Clinical application of genetic risk assessment strategies for coronary artery disease: genotypes, phenotypes, and family histtory. Primary Care 2004;31(3):321-340. |
| 31. | Liu X-Q, Rahman A, Bagdade JD, Alaupovic P, Kannan CR . Effect of thyroid hormone on plasma apolipoproteins and apoA and apoB-containing lipoprotein particles. European Journal of Clinical Investigation 1998;28(4):266-270. |
| 32. | Miura S, Iitaka M, Suzuki S, Fukasawa N, Kıtahama S, Kawakami Y, et al. Decrease in serum levels of thyroid hormone in patients with coronary heart disease. Endocrine Journal 1996;43(6):657-663. |
| 33. | Stubbs PJ, Mulrooney BD , Collinson PO, Fowler PB S, Noble MIM. Serum lipids and thyrotropin in women with coronary artery disease. European Heart Journal 1994;15:468-471. |
| 34. | Luboshitsky R, Aviv A, Herer P, Lavie L. Risk factors for cartiovascular disease in women with subclinical hypothyroidism. Thyroid 2002;12(5):421-425. |
| 35. | Eikelboom JW, Hankey GJ. Associations of homocysteine, C-reactive protein and cardiovascular disease in patients with renal disease. Current Opinion in Nephrology and Hypertension 2001;10:377-383. [PUBMED] [FULLTEXT] |
| 36. | Young IS, Woodside JV. Folate and homoccysteine. Curr Opin Nutr Metab Care 2000;3:427-432. |
| 37. | Koning L, Werstuck GH, Zhou J, Austin RC. Hyperhomocysteinemia and its role in the development of atherosclerosis. Clinical Chemistry 2003;36:431-441. |
| 38. | Lindeman RD , Romero LJ, Schade DS, Wayne S, Baumgartner RN , Garry PJ. Impact of subclinical hypothyroidism on serum total homocysteine concentrations, the prevalence of coronary heart disease (CHD ), and CHD risk factors in the New Mexico elder health survey. Thyroid 2003;13(6):595-600. |
| 39. | Deicher R, Vierhapper H. Homocysteine:a risk factor for cardiovascular disease in subclinical hypothyroidism? Thyroid 2002;12:733-736. [PUBMED] [FULLTEXT] |
| 40. | Meek S and Smallridge RC . Effect of thyroid hormone replacement on methionine-stimulated homocysteine levels in patients with subclinical hypothyroidism: A randomized, double-blind, placebo-controlled study. Endocr Pract 2006;12:529-534. |
| 41. | Auer J, Berent R, Weber T, Lassnig E, Eber B. Thyroid function is associated with presence and severity of coronary atherosclerosis. Clin Cardiol 2003;26(12):569-573. |
| 42. | Aldasouqi S, Nkansa-Dwamena D, Bokhari S, et al. Endocr Pract 2004;10(5): 399-403. |
| 43. | Lee R, Frenkel EP. Hyperhomocysteinemia and thrombosis. Hematol Oncol Clin N Am 2003; 17(1):85-102. |
| 44. | Sengul E, Cetinarslan B, Tarkun I, Canturk Z, Turemen E. Homocysteine concentrations in subclinical hypothyroidism. Endocr Res 2004;30:351-359. |
| 45. | Executive Summary of the Third Report of the National Cholesterol Education Program (NC EP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III ) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholestterol in Adults. JAMA 2001;285(19):2486-2497. |
[Table 1], [Table 2], [Table 3], [Table 4]
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