IJCA-18106; No of Pages 3 International Journal of Cardiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Thyroid stimulating hormone levels and risk of coronary heart disease in patients with type 2 diabetes mellitus Jin Geng a, Tingting Hu a, Bingjian Wang a, Weiping Lu b, Shuren Ma a,⁎ a b
Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical University, PR China Department of Endocrinology, Huai'an First People's Hospital, Nanjing Medical University, PR China
a r t i c l e
i n f o
Article history: Received 12 April 2014 Accepted 17 April 2014 Available online xxxx Keywords: Thyroid stimulating hormone Coronary heart disease Type 2 diabetes mellitus
Mild thyroid dysfunction is associated with adverse cardiovascular outcomes, including coronary heart disease (CHD) events [1–4], CHD deaths [4–6], heart failure [7,8], and atrial fibrillation (AF) [9–11]. In addition, thyroid stimulating hormone (TSH) level within the reference range has a positive and linear association with body mass index [12], blood pressure [13], unfavorable serum lipids [14] and CHD mortality in females without type 2 diabetes mellitus [15]. However, there has been no study concentrating on the relationship between TSH levels and CHD events in diabetic patients. To evaluate this relationship, we conducted a hospital-based study of 803 type 2 diabetic patients hospitalized in the Department of Endocrinology, Huai'an First People's Hospital, China in the year of 2011. Follow-up started when TSH level was measured and the duration was 24–36 months (mean, 29 months). This study was approved by the ethics committee of Huai'an First People's Hospital and all the patients involved signed the informed consent. The normal reference range of TSH levels was 0.45–4.49 mIU/L according to expert consensus [4,10]. CHD events were defined as angina, myocardial infarction, coronary angioplasty, or coronary artery bypass graft surgery. Participants were grouped into 4 groups according to TSH levels: group A, 0.45–1.49 mIU/L; group B, 1.50–2.49 mIU/L; group C, 2.50–3.49 mIU/L; and group D, 3.50–4.49 mIU/L. Inter-group analyses of characteristics were carried out by the Mann–Whitney U test and ANOVA test. In addition, using group A (0.45–1.49 mIU/L) as the
⁎ Corresponding author at: Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, PR China. Tel.: +86 517 84922412. E-mail address: [email protected] (S. Ma).
comparison, we calculated hazard ratios (HRs) of CHD events, AF and all-cause mortality during follow-up in the other three groups using a Cox proportional hazards model. SAS version 9.1 was used for our analyses and statistical significance was considered when p value b 0.05. Baseline characteristics of diabetic patients in this study were given in Table 1. Inter-group analyses found that total cholesterol (TC), triglycerides and low-density lipoprotein cholesterol (LDL-c) levels in group D were significantly higher than in the other three groups. However, no statistical significance was found in other characteristics. 40 patients got CHD events while 16 had new-AF and 11 died during a 2.5-year follow-up, of which the inter-group analyses also showed no statistical difference (Table 1). However, TSH levels were linearly and positively associated with the incidence of CHD events. Compared with individuals in group A, the HRs were 3.66 (1.18–11.33), 2.50 (0.98–6.34), and 1.46 (0.66–3.21) in groups D, C and B, respectively (p for trend = 0.025). This association was unchanged when analyzed using a multivariate model (p for trend = 0.019). There was no obvious correlation between TSH levels and the risk of new-AF (p for trend = 0.894) and all-cause mortality (p for trend = 0.132, Table 2). Asvold and his fellows have suggested that TSH levels within the reference range were linearly and positively associated with TC, triglycerides and LDL-c levels [14], which was similar to our results but not completely the same. The HUNT study [14] was a population-based study with 30,656 volunteers and found a linear and positive association between TSH levels and unfavorable serum lipids. When patients with known cardiovascular disease and DM were excluded, there seemed to be no statistical significance between TSH levels and TC and triglycerides [15]. Besides, 60.6% of the diabetic patients in our study were on statin therapy. It seemed that the imparity of the study population and statin therapy might be a reason for this slight difference. In addition, we conducted further analyses in a Cox proportional hazards model and found that TSH levels within the reference range were linearly and positively associated with CHD events, but not with new-AF and all-cause mortality. In the year of 1994, Sawin et al. [11] firstly reported that patients with a TSH level lower than 0.1 mIU/L were at a high risk of developing AF. Recent studies [9,10] also suggested that subclinical hyperthyroidism was associated with a high risk of AF. So we hypothesized that TSH levels within the reference range were negatively associated with the incidence of AF. However, analyses of TSH levels and new-AF showed no statistical significance in a 2.5-year follow-up. The short follow-up duration and the small sample of 803 diabetic patients might be the reason for this negative result. Higher TSH levels within the reference range seemed to be associated
http://dx.doi.org/10.1016/j.ijcard.2014.04.205 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: Geng J, et al, Thyroid stimulating hormone levels and risk of coronary heart disease in patients with type 2 diabetes mellitus, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.205
2
J. Geng et al. / International Journal of Cardiology xxx (2014) xxx–xxx
Table 1 Characteristics at baseline and during follow-up in this study. Thyroid stimulating hormone level (mIU/L) Group A: 0.45–1.49 (n = 346)
Group B: 1.50–2.49 (n = 309)
Group C: 2.50–3.49 (n = 109)
Group D: 3.50–4.49 (n = 39)
At baseline Age, mean (SD), y Men, no. (%) DM duration, mean (SD), y Hypertension, no. (%) Current smokers, no. (%) Atrial fibrillation, no. (%) TC, mean (SD), mmol/L Triglycerides, mean (SD), mmol/L LDL-c, mean (SD), mmol/L Statin therapy, no. (%) Creatinine, mean (SD), mmol/L FBG, mean (SD), mmol/L HbA1c, mean (SD), % Systolic BP, mean (SD), mm Hg Diastolic BP, mean (SD), mm Hg BMI, mean (SD)
57.03 ± 13.79 201 (58.1) 7.28 ± 6.58 168 (48.6) 92 (26.6) 6 (1.7) 4.14 ± 0.97 1.67 ± 0.80 2.29 ± 0.72 215 (62.1) 74.19 ± 48.16 9.74 ± 4.12 9.42 ± 2.29 127.21 ± 13.82 76.62 ± 7.12 25.16 ± 3.45
55.26 ± 12.35 168 (54.4) 7.45 ± 11.10 162 (52.4) 82 (26.5) 1 (0.3) 4.34 ± 1.10 1.92 ± 1.73 2.43 ± 0.86 180 (58.3) 71.27 ± 38.85 9.81 ± 4.63 9.42 ± 2.36 127.92 ± 12.07 77.44 ± 7.10 25.21 ± 3.79
54.46 ± 13.50 55 (50.5) 6.24 ± 6.62 56 (52.8) 29 (26.6) 0 (0) 4.35 ± 1.16 1.92 ± 1.54 2.49 ± 0.87 66 (60.1) 69.41 ± 35.11 10.65 ± 6.04 9.57 ± 2.46 128.59 ± 11.08 77.55 ± 6.86 25.17 ± 3.67
58.41 ± 13.87 16 (41.0) 8.56 ± 6.81 20 (51.3) 6 (16.7) 1 (2.6) 4.61 ± 1.21⁎ 2.30 ± 1.77⁎ 2.67 ± 0.96⁎ 26 (66.7) 71.80 ± 55.89 8.58 ± 4.14 9.32 ± 2.48 126.49 ± 12.70 75.33 ± 7.94 24.30 ± 3.82
During follow-up CHD events, no. (%) New-atrial fibrillation, no. (%) All-cause mortality, no. (%)
13 (3.8) 7 (2.0) 5 (1.4)
14 (4.5) 6 (1.9) 3 (9.7)
8 (7.3) 2 (1.8) 1 (0.9)
5 (12.8) 1 (2.6) 2 (5.1)
DM, diabetes mellitus; TC, total cholesterol; LDL-c, low-density lipoprotein cholesterol; FBG, fasting blood glucose; BP, blood pressure; BMI, body mass, index; CHD, coronary heart disease. ⁎ TC, triglycerides and LDL-c levels in group D were significantly higher than in the other three groups.
with increasing CHD mortality in females [15]. However, another prospective study [5] which analyzed all-cause and circulatory disease mortality showed no association with TSH levels of the reference range, which was similar to our results. To our knowledge, this is the first observational trial that showed convincing evidence supporting that TSH levels in the reference range were linearly and positively associated with CHD events in patients with T2DM. Previous studies [12–14] reported linear and positive associations between TSH levels and BMI, blood pressure and unfavorable serum lipid, all of which had potential influence on the incidence of
CHD events, although the association did not change when additionally adjusted for the three factors. Besides, thyroid hormones also have cardiovascular effects by influencing vascular smooth muscle, endothelial function, coagulability, arterial stiffness, and homocysteine levels [16–18]. In addition to these effect from thyroid hormones, TSH levels may affect the cardiovascular system that is not regulated by thyroxine [15]. In summary, analyses of all data from 803 type 2 diabetic patients without known CHD at baseline suggest that TSH levels within the reference range have a linear and positive association with CHD events, but not with new-AF and all-cause mortality.
Table 2 The HRs (95% CI) for CHD events, new AF, and all-cause mortality.
References
Events/ participants, no.
Age- and sex-adjusted HRs (95% CI)
Multivariate modela HRs (95% CI)
CHD eventsb 0.45–1.49 1.50–2.49 2.50–3.49 3.50–4.49 P value for trend
13/341 14/306 8/108 5/38
1 (Reference) 1.46 (0.66–3.21) 2.50 (0.98–6.34) 3.66 (1.18–11.33) 0.025
1 (Reference) 1.53 (0.69–3.41) 2.77 (1.07–7.16) 3.95 (1.26–12.45) 0.019
New-AFc 0.45–1.49 1.50–2.49 2.50–3.49 3.50–4.49 P value for trend
7/340 6/308 2/109 1/38
1 (Reference) 1.08 (0.35–3.30) 1.11 (0.22–5.59) 1.16 (0.14–9.85) 0.894
1 (Reference) 1.14 (0.36–3.56) 1.15 (0.22–5.89) 1.29 (0.15–11.17) 0.817
All-cause mortality 0.45–1.49 1.50–2.49 2.50–3.49 3.50–4.49 P value for trend
5/346 3/309 1/109 2/39
1 (Reference) 0.87 (0.20–3.84) 0.65 (0.07–5.90) 3.84 (0.67–22.10) 0.132
1 (Reference) 0.86 (0.19–3.85) 0.69 (0.08–6.42) 3.32 (0.56–19.86) 0.188
TSH, mIU/L
HR, hazard ratio; CI, confidence interval; TSH, thyroid stimulating hormone; CHD, coronary heart disease; AF, atrial fibrillation; LDL, low density lipoprotein. a Adjusted for age, sex, hypertension, total cholesterol, LDL-cholesterol, smoking status, systolic and diastolic blood pressure, and body mass index. b 11 subjects who died during the follow-up were excluded. c 8 subjects with AF at baseline were excluded.
[1] Walsh JP, Bremner AP, Bulsara MK, et al. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med 2005;165:2467–72. [2] Chen HS, Wu TE, Jap TS, et al. Subclinical hypothyroidism is a risk factor for nephropathy and cardiovascular diseases in type 2 diabetic patients. Diabet Med 2007; 24:1336–44. [3] 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. [4] Rodondi N, den Elzen WP, Bauer DC, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010;304:1365–74. [5] Parle J, Maisonneuve P, Sheppard M, Boyle P, Franklyn J. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 2001;358:861–5. [6] Iervasi G, Molinaro S, Landi P, et al. Association between increased mortality and mild thyroid dysfunction in cardiac patients. Arch Intern Med 2007; 167:1526–32. [7] Rodondi N, Newman AB, Vittinghoff E, et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med 2005; 165:2460–6. [8] Gencer B, Collet TH, Virgini V, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation 2012;126:1040–9. [9] Cappola AR, Fried LP, Arnold AM, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 2006;295:1033–41. [10] Collet TH, Gussekloo J, Bauer DC, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 2012;172:799–809. [11] Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994;331: 1249–52. [12] Knudsen N, Laurberg P, Rasmussen LB, et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab 2005;90:4019–24.
Please cite this article as: Geng J, et al, Thyroid stimulating hormone levels and risk of coronary heart disease in patients with type 2 diabetes mellitus, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.205
J. Geng et al. / International Journal of Cardiology xxx (2014) xxx–xxx [13] Asvold BO, Bjoro T, Nilsen TI, Vatten LJ. Association between blood pressure and serum thyroid-stimulating hormone concentration within the reference range: a population-based study. J Clin Endocrinol Metab 2007;92:841–5. [14] Asvold BO, Vatten LJ, Nilsen TI, Bjoro T. The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT study. Eur J Endocrinol 2007;156:181–6. [15] Asvold BO, Bjoro T, Nilsen TI, Gunnell D, Vatten LJ. Thyrotropin levels and risk of fatal coronary heart disease: the HUNT study. Arch Intern Med 2008;168:855–60.
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[16] Klein I, Danzi S. Thyroid disease and the heart. Circulation 2007;116:1725–35. [17] Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab 2003;88:2438–44. [18] Dagre AG, Lekakis JP, Protogerou AD, et al. Abnormal endothelial function in female patients with hypothyroidism and borderline thyroid function. Int J Cardiol 2007;114:332–8.
Please cite this article as: Geng J, et al, Thyroid stimulating hormone levels and risk of coronary heart disease in patients with type 2 diabetes mellitus, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.205
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Thyroid stimulating hormone levels and risk of coronary heart disease in patients with type 2 diabetes mellitus Jin Geng a, Tingting Hu a, Bingjian Wang a, Weiping Lu b, Shuren Ma a,⁎ a b
Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical University, PR China Department of Endocrinology, Huai'an First People's Hospital, Nanjing Medical University, PR China
a r t i c l e
i n f o
Article history: Received 12 April 2014 Accepted 17 April 2014 Available online xxxx Keywords: Thyroid stimulating hormone Coronary heart disease Type 2 diabetes mellitus
Mild thyroid dysfunction is associated with adverse cardiovascular outcomes, including coronary heart disease (CHD) events [1–4], CHD deaths [4–6], heart failure [7,8], and atrial fibrillation (AF) [9–11]. In addition, thyroid stimulating hormone (TSH) level within the reference range has a positive and linear association with body mass index [12], blood pressure [13], unfavorable serum lipids [14] and CHD mortality in females without type 2 diabetes mellitus [15]. However, there has been no study concentrating on the relationship between TSH levels and CHD events in diabetic patients. To evaluate this relationship, we conducted a hospital-based study of 803 type 2 diabetic patients hospitalized in the Department of Endocrinology, Huai'an First People's Hospital, China in the year of 2011. Follow-up started when TSH level was measured and the duration was 24–36 months (mean, 29 months). This study was approved by the ethics committee of Huai'an First People's Hospital and all the patients involved signed the informed consent. The normal reference range of TSH levels was 0.45–4.49 mIU/L according to expert consensus [4,10]. CHD events were defined as angina, myocardial infarction, coronary angioplasty, or coronary artery bypass graft surgery. Participants were grouped into 4 groups according to TSH levels: group A, 0.45–1.49 mIU/L; group B, 1.50–2.49 mIU/L; group C, 2.50–3.49 mIU/L; and group D, 3.50–4.49 mIU/L. Inter-group analyses of characteristics were carried out by the Mann–Whitney U test and ANOVA test. In addition, using group A (0.45–1.49 mIU/L) as the
⁎ Corresponding author at: Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, PR China. Tel.: +86 517 84922412. E-mail address: [email protected] (S. Ma).
comparison, we calculated hazard ratios (HRs) of CHD events, AF and all-cause mortality during follow-up in the other three groups using a Cox proportional hazards model. SAS version 9.1 was used for our analyses and statistical significance was considered when p value b 0.05. Baseline characteristics of diabetic patients in this study were given in Table 1. Inter-group analyses found that total cholesterol (TC), triglycerides and low-density lipoprotein cholesterol (LDL-c) levels in group D were significantly higher than in the other three groups. However, no statistical significance was found in other characteristics. 40 patients got CHD events while 16 had new-AF and 11 died during a 2.5-year follow-up, of which the inter-group analyses also showed no statistical difference (Table 1). However, TSH levels were linearly and positively associated with the incidence of CHD events. Compared with individuals in group A, the HRs were 3.66 (1.18–11.33), 2.50 (0.98–6.34), and 1.46 (0.66–3.21) in groups D, C and B, respectively (p for trend = 0.025). This association was unchanged when analyzed using a multivariate model (p for trend = 0.019). There was no obvious correlation between TSH levels and the risk of new-AF (p for trend = 0.894) and all-cause mortality (p for trend = 0.132, Table 2). Asvold and his fellows have suggested that TSH levels within the reference range were linearly and positively associated with TC, triglycerides and LDL-c levels [14], which was similar to our results but not completely the same. The HUNT study [14] was a population-based study with 30,656 volunteers and found a linear and positive association between TSH levels and unfavorable serum lipids. When patients with known cardiovascular disease and DM were excluded, there seemed to be no statistical significance between TSH levels and TC and triglycerides [15]. Besides, 60.6% of the diabetic patients in our study were on statin therapy. It seemed that the imparity of the study population and statin therapy might be a reason for this slight difference. In addition, we conducted further analyses in a Cox proportional hazards model and found that TSH levels within the reference range were linearly and positively associated with CHD events, but not with new-AF and all-cause mortality. In the year of 1994, Sawin et al. [11] firstly reported that patients with a TSH level lower than 0.1 mIU/L were at a high risk of developing AF. Recent studies [9,10] also suggested that subclinical hyperthyroidism was associated with a high risk of AF. So we hypothesized that TSH levels within the reference range were negatively associated with the incidence of AF. However, analyses of TSH levels and new-AF showed no statistical significance in a 2.5-year follow-up. The short follow-up duration and the small sample of 803 diabetic patients might be the reason for this negative result. Higher TSH levels within the reference range seemed to be associated
http://dx.doi.org/10.1016/j.ijcard.2014.04.205 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: Geng J, et al, Thyroid stimulating hormone levels and risk of coronary heart disease in patients with type 2 diabetes mellitus, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.205
2
J. Geng et al. / International Journal of Cardiology xxx (2014) xxx–xxx
Table 1 Characteristics at baseline and during follow-up in this study. Thyroid stimulating hormone level (mIU/L) Group A: 0.45–1.49 (n = 346)
Group B: 1.50–2.49 (n = 309)
Group C: 2.50–3.49 (n = 109)
Group D: 3.50–4.49 (n = 39)
At baseline Age, mean (SD), y Men, no. (%) DM duration, mean (SD), y Hypertension, no. (%) Current smokers, no. (%) Atrial fibrillation, no. (%) TC, mean (SD), mmol/L Triglycerides, mean (SD), mmol/L LDL-c, mean (SD), mmol/L Statin therapy, no. (%) Creatinine, mean (SD), mmol/L FBG, mean (SD), mmol/L HbA1c, mean (SD), % Systolic BP, mean (SD), mm Hg Diastolic BP, mean (SD), mm Hg BMI, mean (SD)
57.03 ± 13.79 201 (58.1) 7.28 ± 6.58 168 (48.6) 92 (26.6) 6 (1.7) 4.14 ± 0.97 1.67 ± 0.80 2.29 ± 0.72 215 (62.1) 74.19 ± 48.16 9.74 ± 4.12 9.42 ± 2.29 127.21 ± 13.82 76.62 ± 7.12 25.16 ± 3.45
55.26 ± 12.35 168 (54.4) 7.45 ± 11.10 162 (52.4) 82 (26.5) 1 (0.3) 4.34 ± 1.10 1.92 ± 1.73 2.43 ± 0.86 180 (58.3) 71.27 ± 38.85 9.81 ± 4.63 9.42 ± 2.36 127.92 ± 12.07 77.44 ± 7.10 25.21 ± 3.79
54.46 ± 13.50 55 (50.5) 6.24 ± 6.62 56 (52.8) 29 (26.6) 0 (0) 4.35 ± 1.16 1.92 ± 1.54 2.49 ± 0.87 66 (60.1) 69.41 ± 35.11 10.65 ± 6.04 9.57 ± 2.46 128.59 ± 11.08 77.55 ± 6.86 25.17 ± 3.67
58.41 ± 13.87 16 (41.0) 8.56 ± 6.81 20 (51.3) 6 (16.7) 1 (2.6) 4.61 ± 1.21⁎ 2.30 ± 1.77⁎ 2.67 ± 0.96⁎ 26 (66.7) 71.80 ± 55.89 8.58 ± 4.14 9.32 ± 2.48 126.49 ± 12.70 75.33 ± 7.94 24.30 ± 3.82
During follow-up CHD events, no. (%) New-atrial fibrillation, no. (%) All-cause mortality, no. (%)
13 (3.8) 7 (2.0) 5 (1.4)
14 (4.5) 6 (1.9) 3 (9.7)
8 (7.3) 2 (1.8) 1 (0.9)
5 (12.8) 1 (2.6) 2 (5.1)
DM, diabetes mellitus; TC, total cholesterol; LDL-c, low-density lipoprotein cholesterol; FBG, fasting blood glucose; BP, blood pressure; BMI, body mass, index; CHD, coronary heart disease. ⁎ TC, triglycerides and LDL-c levels in group D were significantly higher than in the other three groups.
with increasing CHD mortality in females [15]. However, another prospective study [5] which analyzed all-cause and circulatory disease mortality showed no association with TSH levels of the reference range, which was similar to our results. To our knowledge, this is the first observational trial that showed convincing evidence supporting that TSH levels in the reference range were linearly and positively associated with CHD events in patients with T2DM. Previous studies [12–14] reported linear and positive associations between TSH levels and BMI, blood pressure and unfavorable serum lipid, all of which had potential influence on the incidence of
CHD events, although the association did not change when additionally adjusted for the three factors. Besides, thyroid hormones also have cardiovascular effects by influencing vascular smooth muscle, endothelial function, coagulability, arterial stiffness, and homocysteine levels [16–18]. In addition to these effect from thyroid hormones, TSH levels may affect the cardiovascular system that is not regulated by thyroxine [15]. In summary, analyses of all data from 803 type 2 diabetic patients without known CHD at baseline suggest that TSH levels within the reference range have a linear and positive association with CHD events, but not with new-AF and all-cause mortality.
Table 2 The HRs (95% CI) for CHD events, new AF, and all-cause mortality.
References
Events/ participants, no.
Age- and sex-adjusted HRs (95% CI)
Multivariate modela HRs (95% CI)
CHD eventsb 0.45–1.49 1.50–2.49 2.50–3.49 3.50–4.49 P value for trend
13/341 14/306 8/108 5/38
1 (Reference) 1.46 (0.66–3.21) 2.50 (0.98–6.34) 3.66 (1.18–11.33) 0.025
1 (Reference) 1.53 (0.69–3.41) 2.77 (1.07–7.16) 3.95 (1.26–12.45) 0.019
New-AFc 0.45–1.49 1.50–2.49 2.50–3.49 3.50–4.49 P value for trend
7/340 6/308 2/109 1/38
1 (Reference) 1.08 (0.35–3.30) 1.11 (0.22–5.59) 1.16 (0.14–9.85) 0.894
1 (Reference) 1.14 (0.36–3.56) 1.15 (0.22–5.89) 1.29 (0.15–11.17) 0.817
All-cause mortality 0.45–1.49 1.50–2.49 2.50–3.49 3.50–4.49 P value for trend
5/346 3/309 1/109 2/39
1 (Reference) 0.87 (0.20–3.84) 0.65 (0.07–5.90) 3.84 (0.67–22.10) 0.132
1 (Reference) 0.86 (0.19–3.85) 0.69 (0.08–6.42) 3.32 (0.56–19.86) 0.188
TSH, mIU/L
HR, hazard ratio; CI, confidence interval; TSH, thyroid stimulating hormone; CHD, coronary heart disease; AF, atrial fibrillation; LDL, low density lipoprotein. a Adjusted for age, sex, hypertension, total cholesterol, LDL-cholesterol, smoking status, systolic and diastolic blood pressure, and body mass index. b 11 subjects who died during the follow-up were excluded. c 8 subjects with AF at baseline were excluded.
[1] Walsh JP, Bremner AP, Bulsara MK, et al. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med 2005;165:2467–72. [2] Chen HS, Wu TE, Jap TS, et al. Subclinical hypothyroidism is a risk factor for nephropathy and cardiovascular diseases in type 2 diabetic patients. Diabet Med 2007; 24:1336–44. [3] 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. [4] Rodondi N, den Elzen WP, Bauer DC, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010;304:1365–74. [5] Parle J, Maisonneuve P, Sheppard M, Boyle P, Franklyn J. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 2001;358:861–5. [6] Iervasi G, Molinaro S, Landi P, et al. Association between increased mortality and mild thyroid dysfunction in cardiac patients. Arch Intern Med 2007; 167:1526–32. [7] Rodondi N, Newman AB, Vittinghoff E, et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med 2005; 165:2460–6. [8] Gencer B, Collet TH, Virgini V, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation 2012;126:1040–9. [9] Cappola AR, Fried LP, Arnold AM, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 2006;295:1033–41. [10] Collet TH, Gussekloo J, Bauer DC, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 2012;172:799–809. [11] Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994;331: 1249–52. [12] Knudsen N, Laurberg P, Rasmussen LB, et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab 2005;90:4019–24.
Please cite this article as: Geng J, et al, Thyroid stimulating hormone levels and risk of coronary heart disease in patients with type 2 diabetes mellitus, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.205
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Please cite this article as: Geng J, et al, Thyroid stimulating hormone levels and risk of coronary heart disease in patients with type 2 diabetes mellitus, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.205
