Levels of fibrinogen, high sensitive C-reactive protein and lipid parameters as a cardiovascular risk factor in subclinical hypothyroid patients

Year 2016, , 65 - 71, 29.10.2016

Aşkın Güngüneş , Kudret Çelik Mustafa Şahin Mustafa Özbek Erman Çakal Evrim Çakır İsmail Sefa Yıldırım Tuncay Delibaşı

https://doi.org/10.18663/tjcl.34283

Cited By: 1

Abstract

Aim: Subclinical hypothyroidism is defined as mild thyroid failure and it is associated with an increase in cardiovascular risk. The changes in the parameters related to dyslipidemia and coagulation may potentially contribute to the development of atherosclerosis in subclinical hypothyroidism. In this study, we aimed to investigate the difference between the subclinical hypothyroid patients and the control group in terms of fibrinogen, high sensitive C-reactive protein and lipid parameters as a cardiovascular risk factor.

Material and Methods:  The participants of this study were 44 newly-diagnosed subclinical hypothyroid patients. The control group was composed of 44 healthy subjects with no specific disease. Smokers and alcohol consumers were not included in the study. Serum TSH level greater than 4 mIU/L was defined as subclinical hypothyroidism while free thyroid hormones within normal limits. The patient and the control group were compared in terms of fibrinogen, high sensitive C-reactive protein and lipid parameters.

Results: Fibrinogen, high sensitive C-reactive protein and total cholestrol levels in the patient group were found statistically higher than those of the control group (P < 0.001, P < 0.001, P = 0.042, respectively). The average TSH level was 6.3 mIU/L in the patient group. When the sub-groups were examined according to their TSH levels in terms of fibrinogen, high sensitive CRP and total cholestrol, we observed no statistically significant difference between the group with TSH level between 6-10 mIU/L and the group with TSH level higher than 10 mIU/L (P = 0.283, P =  0.140,  P = 0.283, respectively).

Conclusion: The results of this study showed that, in the subclinical hypothyroid patients fibrinogen, high sensitive C-reactive protein and total cholesterol levels were statistically higher than those of the control group. These factors may contribute to increased atherosclerosis in subclinical hypothyroidism.

 Key words: Hypothyroidism, fibrinogen, C-reactive protein, cholesterol, atherosclerosis, subclinical disturbances

Kardiyovasküler risk faktörü olarak fibrinojen, yüksek duyarlılıklı C-reaktif protein ve lipid parametrelerinin subklinik hipotiroidili hastalardaki düzeyi

Abstract

Amaç: Subklinik hipotiroidi hafif orta tiroid yetmezlik durumudur. Kardiyovasküler risk artışı ile ilişkili bir durumdur. Dislipidemi ve koagülasyonla ilgili parametrelerdeki değişiklikler subklinik hipotiroidide potansiyel olarak ateroskleroz gelişiminden sorumlu olabilir. Bu çalışmada, subklinik hipotiroidili hastalar ile kontrol grubu arasında kardiyovasküler risk faktörü olarak fibrinojen, yüksek duyarlılıklı C-reaktif Protein ve lipid parametreleri bakımından fark olup olmadığını araştırmayı amaçladık.

Gereç ve Yöntemler: Yeni tanı almış 44 subklinik hipotiroidili hasta ve kontrol grubu olarak ise bilinen herhangi bir hastalığı olmayan sağlıklı 44 kişi çalışmaya alındı. Sigara ve alkol kullananlar çalışmaya dahil edilmedi. Serbest tiroid hormonları normal sınırlarda iken serum TSH değerinin 4 mIU/L’den büyük olması subklinik hipotiroidi olarak tanımlandı. Vaka ve kontrol grubu fibrinojen, yüksek duyarlılıklı C-reaktif Protein ve lipid parametreleri bakımından birbiriyle karşılaştırıldı.

Bulgular: Vaka grubunda fibrinojen, yüksek duyarlılıklı C-reaktif Protein ve total kolesterol düzeyi kontrol grubuna göre istatistiksel anlamlı olarak daha yüksek saptandı (p<0,001, p<0,001, p=0,042, sırasıyla). Vaka grubunda ortalama TSH düzeyi 6,3 mIU/L olup TSH düzeyine göre alt gruplar incelendiğinde fibrinojen, yüksek duyarlılıklı C-reaktif Protein ve total kolesterol bakımından  TSH  değeri 6-10 mIU/L arasında olan grupla 10 mIU/L ’dan büyük olan grup arasında anlamlı fark izlenmedi (p=0,283, p= 0,140, p=0,283, sırasıyla).

Sonuçlar: Bu çalışmanın sonuçları fibrinojen, yüksek duyarlılıklı C-reaktif Protein ve total kolesterol düzeylerinin subklinik hipotiroidili hasta grubunda kontrol grubuna göre anlamlı oranda yüksek olduğunu gösterdi. Bu faktörler, subklinik hipotiroidi varlığında artmış ateroskleroz riskine katkıda bulunabilir.

 Anahtar Kelimeler: Fibrinojen, yüksek duyarlılıklı C-reaktif Protein, total kolesterol, ateroskleroz, subklinik hipotiroidi

Keywords

Hipotiroidi fibrinojen, C-reaktif protein, kolesterol, ateroskleroz, subklinik bozukluklar

References

• Cooper DS. Clinical practice. Subclinical hypothyroidism. N Engl J Med 2001; 345: 260-5.
• Ayala AR, Danese MD, Ladenson PW. When to treat mild hypothyroidism. Endocrinol Metab Clin North Am 2000; 29: 399-415.
• Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001; 344: 501-9.
• 4- Fazio S, Palmieri EA, Lombardi G, Biondi B. Effects of thyroid hormone on the cardiovascular system. Recent Prog Horm Res 2004; 59: 31-50.
• Becker C. Hypothyroidism and atherosclerotic heart disease: pathogenesis,medical management, and the role of coronary artery bypass surgery. Endocr Rev 1985; 6: 432-40.
• Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab 2003; 88: 2438-44.
• Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine 2004; 24: 1-13.
• Iacoviello L, Vischetti M, Zito F, Donati M B. Genes encoding fibrinogen and cardiovascular risk. Hypertension 2001; 38: 1199-203.
• Turek S, Rudan I, Smolej-Narancić N, et al. A large cross-sectional study of health attitudes, knowledge, behaviour and risks in the post-war Croatian population (the First Croatian Health Project). Coll Antropol 2001; 25: 77-96.
• Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. J Am Med Assoc 1998; 279: 1477-82.
• Chadarevian R, Bruckert E, Leenhardt L, Giral P, Ankri A, Turpin G. Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism. J Clin Endocrinol Metab 2001; 86: 732-7.
• Müller B, Tsakiris DA, Roth CB, Guglielmetti M, Staub JJ, Marbet GA. Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. Eur J Clin Invest 2001; 31: 131-7.
• Cantürk Z, Cetinarslan B, Tarkun I, Cantürk NZ, Ozden M, Duman C. Hemostatic system as a risk factor for cardiovascular disease in women with subclinical hypothyroidism. Thyroid 2003; 13: 971-7.
• Monzani F, Di Bello V, Caraccio N, et al. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab 2001;86: 1110-5.
• Razvi S, Ingoe L, Keeka G, Oates C, Mcmillan C, Weaver J. The beneficial effect of l-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab 2007; 92: 1715-23.
• Liu D, Jiang F, Shan Z, et al. A cross-sectional survey of relationship between serum TSH level and blood pressure. J Hum Hypertens 2010; 24: 134-8.
• Baumgartner C, Blum M, Rodondi N. Subclinical hypothyroidism: summary of evidence in 2014. Swiss Med Wkly 2014; 144: w14058.
• Chait A, Bierman EL, Albers JJ. Regulatory role of triiodothyronine in the degradation of low density lipoprotein by cultured human skin fibroblasts. J Clin Endocrinol Metab 1979; 48: 887-9.
• Duntas LH. Thyroid disease and lipids.Thyroid 2002; 12: 287-93.
• Valdemarsson S, Hedner P, Nilsson-Ehle P. Reversal of decreased hepatic lipase and lipoprotein lipase activities after treatment of hypothyroidism. Eur J Clin Invest. 1982; 12: 423-8.
• Shin DJ, Osborne TF. Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element- Binding Protein-2 (SREBP-2). J Biol Chem 2003; 278: 34114-8.
• Sun X, Sun Y, Li WC,et al. Association of Thyroid-stimulating Hormone and Cardiovascular Risk Factors. Internal Medicine 2015; 54: 2537-44.
• Tian L, Song Y, Xing M, et al. A novel role for thyroid-stimulating hormone: up-regulation of hepatic 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase expression through the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-responsive element binding protein pathway. Hepatology 2010; 52: 1401-9.
• Pearce S, Brabant G, Duntas L, et al. 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J 2013; 2: 215-28.
• Canaris G, Manowitz N, Mayor G, Ridgway E. The Colorado Thyroid Disease Prevalence Study. Arch Intern Med 2000; 160: 526-34.
• Boekholdt S, Titan S, Wiersinga W, et al. Initial thyroid status and cardiovascular risk factors: the EPIC-Norfolk Prospective Population Study. Clin Endocrinol 2010; 72: 404-10.
• Bindels A, Westendorp R, Frolich M, Seidell J, Blokstra A, Smelt A. The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding? Clin Endocrinol 1999; 50: 217-20.
• Walsh JP, Bremner AP, Bulsara MK, et al. Thyroid dysfunction and serum lipids: a community-based study. Clin Endocrinol (Oxf) 2005; 63: 670-5.
• Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab 2002; 87: 1533-8.
• Monzani F, Caraccio N, Kozakowa M, et al. Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study. J Clin Endocrinol Metab 2004; 89: 2099-106.
• Tsakadze N L, Zhao Z D, D‘Souza S E. Interactions of intercellular adhesion molecule-1 with fibrinogen. Trends Cardiovasc Med 2002; 12: 101-8.
• Hicks R C, Golledge J, Mir-hasseine R, Powel J T. Vasoactive effects of fibrinogen on saphenous vein. Nature 1996; 379: 818-20.
• Retzinger G, Deangelis A P, Patuto S J. Adsorption of fibrinogen to droplets of liquid hydrophobic phases. Functionality of the bound protein and biological implications. Arterioscler Thromb Vasc Biol 1998; 19: 1948-57.
• Lou XJ, Boonmark NW, Horrigan FT, Degen JL, Lawn RM. Fibrinogen deficiency reduces vascular accumulation of apolipoprotein(a) and development of atherosclerosis in apolipoprotein(a) transgenic mice.Proc. Natl Acad Sci 1998; 95: 12591-5.
• Reinhart W H. Fibrinogen-marker or mediator of vascular disease? Vasc Med 2003; 8: 211-6.
• Scarabin PY, Arveiler D, Amouyel P, et al. Prospective Epidemiological Study of Myocardial Infarction, Plasma fibrinogen explains much of the difference in risk of coronary heart disease between France and Northern Ireland. The PRIME study. Atherosclerosis, 2003; 166: 103-9.
• Palmieri V, Celentano A, Roman MJ, et al. Relation of fibrinogen to cardiovascular events is independent of preclinical cardiovascular disease: the Strong Heart Study. Am Heart J 2003; 145: 467-74.
• Palmieri V, Celentano A, Roman MJ, et al. Fibrinogen and preclinical echocardiographic target organ damage: the strong heart study. Hypertension 2001; 38: 1068-74.
• Gil M, Zarebinski M, Adamus J. Plasma fibrinogen and troponin I in acute coronary syndrome and stable angina. Int J Cardiol 2002; 83: 43-6.
• Bennermo M, Held C, Hamsten A, et al. Prognostic value of plasma C-reactive protein and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis. J Int Med 2003; 254: 244-50.
• Cakal B, Cakal E, Demirbaş B, et al. Homocysteine and fibrinogen changes with L-thyroxine in subclinical hypothyroid patients. J Korean Med Sci 2007; 22: 431-5.
• Vorster H H. Fibrinogen and women's health. Thromb Research 1999; 95: 137-54.
• Koenig W. Fibrin(ogen) in cardiovascular disease: an update. Thromb Haemost 2003; 89: 601-9.
• Krobot K, Hense HW, Cremer P, Eberle E, Keil U. Determinants of plasma fibrinogen: relation to body weight, waist-to-hip ratio, smoking, alcohol, age, and sex. Results from the second MONICA Augsburg survey 1989-1990. Arterioscler Thromb 1992; 12: 780-8.
• Wilkerson W R, Sane D C. Aging and thrombosis. Sem Thromb Hemost 2002; 28: 555-68.
• Tuzcu A, Bahceci M, Gokalp D, Tuzun Y, Gunes K . Subclinical hypothyroidism may be associated with elevated high-sensitive C-reactive protein (low grade inflammation) and fasting hyperinsulinemia. Endocr J 2005; 52: 89-94.
• Rajendra KC, Khatiwada S, Deo Mehta K, Pandey P, Lamsal M, Majhi S. Cardiovascular risk factors in subclinical hypothyroidism: a case control study in Nepalese population. J Thyroid Res doi: 10.1155/2015/305241.
• Sharma R, Sharma TK, Kaushik GG, Sharma S, Vardey SK, and Sinha M. Subclinical hypothyroidism and its association with cardiovascular risk factors. Clin Lab 2011; 57: 719-24.
• Kvetny J, Heldgaard P. E, Bladbjerg EM, Gram J. Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin Endocrinol 2004; 61, 232-8.
• Gupta G, Sharma P, Kumar P, Itagappa M. Study on subclinical hypothyroidism and its association with various inflammatory markers. J Clin Diagn Res. 2015;9: BC04-6.
• Javed Z, Sathyapalan T. Levothyroxine treatment of mild subclinical hypothyroidism: a review of potential risks and benefits. Ther Adv Endocrinol Metab 2016; 7: 12-23.