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Year : 2017  |  Volume : 5  |  Issue : 1  |  Page : 3-6

Subclinical hypothyroidism and coronary artery disease: In relation to angiographic disease pattern in Indian women

1 Department of Cardiology, Sree Uthram Thirunal Royal Hospital, Thiruvananthapuram, Kerala, India
2 Department of Cardiology, Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India

Date of Web Publication8-Mar-2017

Correspondence Address:
Dr. Biji Soman
Meditrina Hospital, Pallikkal (PO), Kottarakara - 691 566, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2321-449x.201739

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Introduction: Coronary artery disease (CAD) is known to be severe and progress more rapidly in overt hypothyroidism. However, the role of subclinical hypothyroidism (SH) as a risk factor for CAD is controversial. Our aim is to explore association, if any, existing between SH and the angiographic pattern and severity of CAD in women.
Subjects and Methods: We retrospectively studied 100 consecutive female patients with acute coronary syndrome who underwent coronary angiography. Baseline risk factor data and biochemical data were obtained from the hospital records. Patients with SH were compared with those without to assess differences in clinical characteristics and angiographic disease pattern.
Results: Of the 100 women, 50 had SH (58.64 ± 10.92 years), and 50 were euthyroid (58.44 ± 9.34 years). Unstable angina was the most common initial diagnosis (38 vs. 36, P = 0.6484). Hypertension was the most common risk factor among both groups (36 vs. 32, P = 0.3912). Angiographic profile revealed, only euthyroid women had left main stem disease (0 vs. 5, P = 0.0218). Both groups had equal incidence of single vessel disease (7 vs. 7, P = 1), insignificant CAD (6 vs. 6, P = 1) and angiographically normal coronaries (17 vs. 17, P = 1), SH group had greater incidence of multivessel disease (18 vs. 12, P = 0.1904). Left anterior descending was the most commonly involved coronary artery in both groups, (43 vs. 34, P = 0.3991). Segmental distribution pattern showed near similar disease pattern, with proximal segment being the most common in both groups (30 vs. 27, P = 0.9369).
Conclusions: As our study population was small and study had limitations, we cannot convincingly conclude that SH is not associated with the severity and angiographic disease pattern of the CAD.

Keywords: Coronary angiogram, coronary artery disease, subclinical hypothyroidism, women

How to cite this article:
Soman B, Rahaman MA, Vijayaraghavan G. Subclinical hypothyroidism and coronary artery disease: In relation to angiographic disease pattern in Indian women. Heart India 2017;5:3-6

How to cite this URL:
Soman B, Rahaman MA, Vijayaraghavan G. Subclinical hypothyroidism and coronary artery disease: In relation to angiographic disease pattern in Indian women. Heart India [serial online] 2017 [cited 2021 Dec 2];5:3-6. Available from: https://www.heartindia.net/text.asp?2017/5/1/3/201739

  Introduction Top

Subclinical hypothyroidism (SH) is an asymptomatic state and is characterized by elevated levels of thyroid-stimulating hormone (TSH), and normal free thyroxine (T4) levels.[1] Studies have shown that coronary atherosclerosis in subjects with hypothyroidism is more frequent and severe.[2] There has been considerable debate over the relationship between SH and coronary artery disease (CAD). There is no conclusive evidence of a relationship between SH and CAD.[3],[4] The aim of this study was to assess the relationship, if any, between SH and the angiographic pattern and severity of CAD among women.

  Subjects and Methods Top

This retrospective study was carried out at the Department of Cardiology, in a tertiary care centre in Trivandrum, Kerala, India. Totally, 100 consecutive female patients admitted from 2012 January with acute coronary syndrome (ACS), and those who agreed for undergoing coronary angiography for diagnostic and/or revascularization purposes were included in the study. ACS was defined as the presence of unstable angina, myocardial infarction with either ST-segment elevation or non-ST segment elevation. The diagnosis was based on the universal definition of ACS.[5] Patients were considered to have SH if they had no symptoms of thyroid dysfunction, normal levels of T4 (4.5–11.5 μg/dl), and elevated TSH (>5 mU/l). Patients with SH were compared with those without to assess differences in clinical characteristics and angiographic pattern of CAD.

Collection of baseline risk factor data was done systematically from the hospital records. Since none of the patients from either group had smoking history, other conventional risk factors including diabetes mellitus, hypertension, dyslipidemia, and family history for premature CAD as per ACC/AHA guidelines definitions were assessed in this study. Because of insufficient data, nutritional status and obesity could not be assessed. The clinical presentations of the patient were categorized as unstable angina and myocardial infarction as explained above.

As the incidence of ACS is extremely low in the female population under 30 years of age patients under the age of 30 years, known thyroid illness, documented CAD, previous myocardial infarction, renal failure, post coronary artery bypass graft status, and with any other contraindication for coronary angiography, were excluded from the study.

Elective coronary angiography was performed through standard femoral or radial artery approach. Angiographic data were collected by analyzing the angiograms by two interventional cardiologists. CAD was defined as ≥1 epicardial coronary segment with stenosis ≥50% and was diagnosed visually. All analyses were performed using Statistica software Version 12 (Statsoft, DELL, Tulsa, OK, USA). Results were expressed as mean ± standard deviation for numerical variables and frequencies (percentages) for categorical variables in the forms of tables. Chi-square P < 0.05 was considered statistically significant.

  Results Top

One hundred female patients were studied, of which 50 had SH with a mean age of 58.64 ± 10.92 years, the other 50 females who were euthyroid had a mean age of 58.44 ± 9.34 years. We analyzed the initial clinical presentation of these two groups [Table 1] and found that majority of the patients in both groups presented with unstable angina (38 vs. 36, P = 0.6484), there was no statistically significant difference in their initial presentation.
Table 1: Initial clinical presentation profile of study population

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Risk factor analysis did not reveal much as the risk factor profile was same in both groups [Table 2]. Hypertension was the most common risk factor among both groups (36 vs. 32, P = 0.3912) and with the incidence of dyslipidemia more among euthroid group (18 vs. 25, P = 0.1574). The presence of CAD in the absence of any risk factor was more common among euthyroid females (6 vs. 10, P = 0.2752).
Table 2: Risk factor profile of the study population

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We analyzed the coronary angiography of these patients to assess the severity of the CAD and the disease pattern [Table 3]. We found that only the euthyroid patients had left main stem disease and this was statistically significant (0 vs. 5, P = 0.0218). Other than this, there was no significant difference in the pattern of the CAD among the two groups. Both groups had equal incidence of single vessel disease (7 vs. 7, P = 1), insignificant CAD (6 vs. 6, P = 1), and angiographically normal coronaries (17 vs. 17, P = 1), SH group had greater incidence of multivessel disease (18 vs. 12, P = 0.1904).
Table 3: Coronary angiographic profile

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Left anterior descending artery and its branches were the most commonly involved coronary artery [Table 4] in both groups, (43 vs. 34, P = 0.3991), only euthyroid women had left main stem CAD, (0 vs. 5, P = 0.0178).
Table 4: Distribution of coronary artery disease

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On assessment of the disease severity [Table 5] in these groups of females, we found that the SH group had more severe disease as they had more lesions of >90% stenosis (21 vs. 14, P = 0.3039) when compared with the euthyroid group.
Table 5: Degree of severity of coronary artery lesions

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Further assessment of the segmental distribution pattern [Table 6] showed near similar disease pattern, with proximal segment being the most common in both groups (30 vs. 27, P = 0.9369) and ostioproximal being the least involved segment (5 vs. 2, P = 0.2989). SH females had greater number of lesions when compared with euthyroid women (1.9 vs. 1.74).
Table 6: Segmental distribution pattern of the coronary artery disease

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  Discussion Top

The relationship between CAD and overt hypothyroidism is well known. In these patients, the CAD occurs more frequently and progresses rapidly. It is characterized by high levels of low-density lipoprotein cholesterol,[6] which in turn increases the atherogenicity and the arterial stiffness,[7] this, along with, the increase in systemic vascular resistance causes systemic arterial hypertension in hypothyroidism.[8] The hypothyroid state is also associated with amplification of cardiovascular risks associated with insulin resistance.[9]

SH was considered as a risk factor for CAD nearly 45 years ago,[10] but since then, many studies have come out with different results, adding on the controversy and confusion. The Whickham Survey, in over 20 years of follow-up, found no association between SH and the development of CAD,[11] Ochs et al.[12] and Razvi et al.[13] found in their meta-analysis that SH is associated with increased CAD in younger patients. Ochs et al.[12] found that CAD was significantly higher in subjects younger than 65 years. Cappola et al. found no relationship between TSH levels and risk of coronary disease from their study on elderly patients from the Cardiovascular Health Study,[14] while the Rotterdam study, assessing women aged over 55, concluded that SCH was a strongly associated with risk of atherosclerosis and myocardial infarction.[15] Imaizumi et al. concluded that SCH contributed to risk of ischemic heart disease in men but not in women.[16] Rodondi et al., on 4 year-follow-up, found high levels of TSH was associated with incidence of heart failure but not with other cardiovascular events.[17] However, Singh et al., in a meta-analysis, concluded that SH is associated with a greater prevalence of coronary disease as well as with a greater frequency of coronary events during follow-up.[18]

In our study, there were no significant differences between the groups in terms of age.[4],[19] As seen in many studies before, with regard to SH and conventional cardiovascular risk factors, there was no relation between SH and other conventional risk factors,[4],[17],[20],[21] and also, there was no significant difference in the incidence of dyslipidemia between SH and euthyroid patients.[2],[4],[16],[22] Nearly half the women in our study had significant coronary disease as was observed by Fiarresga et al.,[4] but contrary to their findings, in our study, SH group had greater incidence of multivessel disease although this was not statistically significant. Our study did show that euthyroid women were more prone to have left main stem disease, but we do not have conclusive evidence as we have not done a detailed analysis of the risk factor profile of this subset of patients, and the numbers were too small to attribute it to thyroid status alone.

The degree of SH could be another important factor. SH subjects with a TSH ≥ 10 mU/l could also have an increased CAD risk.[23] One of the common causes of SH is chronic autoimmune thyroiditis. It has been suggested that the inflammatory response to this autoimmunity could be the association between SH and CAD,[10],[24] at the same time, there are other studies which do not support this association.[16],[25] Our study did not test for the presence of antithyroid antibodies, and so we are not able to comment on the presence of any such association.

Our study has certain limitations, first, the retrospective study design. Second, since this study was conducted on patients who presented with ACS, we could not evaluate the association between SCH and CAD risk in subjects with a low-risk profile of CAD. Third, the sample size was small for a statistical analysis of degrees of SH; there have been studies indicating that only TSH value >10 mlU/L have increased cardiovascular risk. Finally, the presence of antithyroid antibodies and free T3 levels were not investigated.

  Conclusions Top

Since ours was a retrospective study, with limited number of patients (n = 100), there were a lot of limitations for our study. We cannot categorically say there is no association between SH and degree of severity of CAD among women.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ross DS. Serum thyroid-stimulating hormone measurement for assessment of thyroid function and disease. Endocrinol Metab Clin North Am 2001;30:245-64, vii.  Back to cited text no. 1
Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab 2003;88:2438-44.  Back to cited text no. 2
Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: Scientific review and guidelines for diagnosis and management. JAMA 2004;291:228-38.  Back to cited text no. 3
Fiarresga AJ, Feliciano J, Fernandes R, Martins A, Pelicano N, Timóteo AT, et al. Relationship between coronary disease and subclinical hypothyroidism: An angiographic study. Rev Port Cardiol 2009;28:535-43.  Back to cited text no. 4
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics-2015 update: A report from the American Heart Association. Circulation 2015;131:e29-322.  Back to cited text no. 5
Staub JJ, Althaus BU, Engler H, Ryff AS, Trabucco P, Marquardt K, et al. Spectrum of subclinical and overt hypothyroidism: Effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues. Am J Med 1992;92:631-42.  Back to cited text no. 6
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.  Back to cited text no. 7
Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine 2004;24:1-13.  Back to cited text no. 8
Bakker SJ, ter Maaten JC, Popp-Snijders C, Slaets JP, Heine RJ, Gans RO. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J Clin Endocrinol Metab 2001;86:1206-11.  Back to cited text no. 9
Bastenie PA, Vanhaelst L, Bonnyns M, Neve P, Staquet M. Preclinical hypothyroidism: A risk factor for coronary heart-disease. Lancet 1971;1:203-4.  Back to cited text no. 10
Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al. The spectrum of thyroid disease in a community: The Whickham survey. Clin Endocrinol (Oxf) 1977;7:481-93.  Back to cited text no. 11
Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, et al. Meta-analysis: Subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med 2008;148:832-45.  Back to cited text no. 12
Razvi S, Shakoor A, Vanderpump M, Weaver JU, Pearce SH. The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: A metaanalysis. J Clin Endocrinol Metab 2008;93:2998-3007.  Back to cited text no. 13
Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 2006;295:1033-41.  Back to cited text no. 14
Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: The Rotterdam Study. Ann Intern Med 2000;132:270-8.  Back to cited text no. 15
Imaizumi M, Akahoshi M, Ichimaru S, Nakashima E, Hida A, Soda M, et al. Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J Clin Endocrinol Metab 2004;89:3365-70.  Back to cited text no. 16
Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med 2005;165:2460-6.  Back to cited text no. 17
Singh S, Duggal J, Molnar J, Maldonado F, Barsano CP, Arora R. Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: A meta-analysis. Int J Cardiol 2008;125:41-8.  Back to cited text no. 18
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-34.  Back to cited text no. 19
Walsh JP, Bremner AP, Bulsara MK, O'Leary P, Leedman PJ, Feddema P, et al. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med 2005;165:2467-72.  Back to cited text no. 20
Toruner F, Altinova AE, Karakoc A, Yetkin I, Ayvaz G, Cakir N, et al. Risk factors for cardiovascular disease in patients with subclinical hypothyroidism. Adv Ther 2008;25:430-7.  Back to cited text no. 21
Bigos ST, Ridgway EC, Kourides IA, Maloof F. Spectrum of pituitary alterations with mild and severe thyroid impairment. J Clin Endocrinol Metab 1978;46:317-25.  Back to cited text no. 22
Park YJ, Lee YJ, Choi SI, Chun EJ, Jang HC, Chang HJ. Impact of subclinical hypothyroidism on the coronary artery disease in apparently healthy subjects. Eur J Endocrinol 2011;165:115-21.  Back to cited text no. 23
Tièche M, Lupi GA, Gutzwiller F, Grob PJ, Studer H, Bürgi H. Borderline low thyroid function and thyroid autoimmunity. Risk factors for coronary heart disease? Br Heart J 1981;46:202-6.  Back to cited text no. 24
Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community. Thyroid 1996;6:155-60.  Back to cited text no. 25


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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