Higher serum free thyroxine levels are associated with coronary artery disease

Thyroid hormone has many effects on the heart and cardiovascular system. Thyrotoxicosis is associated with increased cardiovascular morbidity and mortality, primarily due to heart failure and thromboembolism. However, the relationship between thyroid hormone excess and the cardiac complications of angina pectoris and myocardial infarction remains largely speculative. Moreover, few studies have been reported on the effect of thyroid hormone levels within normal range on coronary artery disease (CAD). Therefore we examined the association of thyroid function with coronary artery diseases in euthyroid angina patients. Total 192 subjects (mean age; 60.8 yrs) were enrolled in which coronary angiograms were performed due to chest pain. We measured free thyroxine (FT(4)), thyroid stimulating hormone (TSH), serum lipid levels and high-sensitivity C-reactive protein (hsCRP) levels and analyzed their association with the presence of CAD. Serum FT(4) levels were higher in patients with CAD compared with the patients without CAD (1.31 +/- 0.30 vs 1.20 +/- 0.23, p = 0.006), and high FT(4) level was associated with the presence of multi-vessel disease. Multivariate analysis showed that age (odds ratio (OR) 1.04; 95% confidence interval (CI) 1.01-1.07, p = 0.007), hypertension (OR 2.04; 95% CI 1.06-3.90, p = 0.036) and FT(4) (OR 4.23; 95% CI 1.12-15.99, p = 0.033), were the determinants for CAD. The relative risk (RR) for CAD in highest tertile of FT(4) showed increased risk compared with the lowest tertile (RR 1.98; 95% CI 0.98-3.99, p<0.001). Our study showed that FT(4) levels were associated with the presence and the severity of CAD. Also, this study suggests that elevated serum FT(4) levels even within normal range could be a risk factor for CAD. Further studies will be necessary to confirm the relationship of thyroid function and CAD.     

Carotid artery intima media thickness is inversely related to serum free thyroxine in euthyroid subjects

OBJECTIVE: The effect of thyroid function on cardiovascular risk may extend to the euthyroid range. In euthyroid subjects, we determined whether carotid artery intima media thickness (IMT), a measure of subclinical atherosclerosis, is related to thyroid function. DESIGN AND SUBJECTS: Cross-sectional study in a cohort of 78 nonsmoking, predominantly middle-aged, euthyroid subjects (44 men and 34 women, mean age 56 years, TSH between 0.5 mU/l and 4.0 mU/l and FT4 between 11.0 pmol/l and 19.5 pmol/l). MEASUREMENTS: IMT (mean of three segments in both carotid arteries by ultrasonography), clinical factors, insulin resistance (HOMA(ir)), plasma lipids, C-reactive protein (CRP), serum FT4, TSH and thyroid autoantibodies. RESULTS: In several multiple linear regression models, age- and sex-adjusted IMT was found to be independently related to either pulse pressure and body mass index (BMI), to high density lipoprotein (HDL) cholesterol or to FT4, but not to TSH, thyroid autoantibodies, HOMA(ir), CRP, non-HDL cholesterol and triglycerides. In a subsequent model which included age, sex, pulse pressure, body mass index (BMI), HDL cholesterol and FT4, IMT was independently and positively related to age (beta = 0.43, P < 0.001), male sex (beta = 0.34, P = 0.014), pulse pressure (beta = 0.29, P = 0.002), BMI (beta = 0.24, P = 0.007) and inversely related to FT4 (beta = -0.19, P = 0.046). IMT was also inversely related to FT4 in a model which included HDL cholesterol, non-HDL cholesterol and triglycerides. CONCLUSIONS: In euthyroid subjects, IMT is associated with FT(4), after controlling for clinical factors, lipid levels and thyroid autoantibodies. These findings raise the possibility that, even within the euthyroid range, low normal thyroid function may adversely affect cardiovascular risk.     

Evaluation of coronary calcium score by multidetector computed tomography in relation to endothelial function and inflammatory markers in asymptomatic individuals.

BACKGROUND: Coronary calcification has been correlated with the presence and extent of coronary artery disease (CAD), so in the present study the associations between coronary artery calcification score (CACS) and endothelial dysfunction, as well as the important inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and oxidized low-density lipoprotein (OxLDL), were studied in asymptomatic individuals at intermediate risk for CAD. METHODS AND RESULTS: The study group comprised 177 subjects (103 males) aged 50.6+/-5.9 years. CACS was measured by multidetector computed tomography using the Agatston method. Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent nitroglycerin-mediated dilatation (NMD) were measured by high-resolution external brachial ultrasound. Coronary artery calcification (CAC) was detected in 82 subjects (52 males), and the median CACS was 143 [31-311.25] units. After adjusting for gender and body mass index, log (CACS +1) correlated positively with age (r=0.401, p<0.001) and IL-6 levels (r=0.442, p<0.001), and negatively with FMD (r=-0.511, p<0.001). The correlations of log (CACS +1) with CRP and OxLDL levels, and with NMD, were non-significant. In a multivariate-adjusted logistic regression model, age (odds ratio (OR) =1.083 [1.014-1.156]), serum IL-6 level (OR=3.837 [2.166-6.798]) and FMD (OR=0.851 [0.793-0.913]) were significantly and independently associated with CAC. CONCLUSIONS: Peripheral endothelial function inversely correlated with CACS, whereas IL-6 level was associated with CACS. Testing for endothelial function and IL-6 level may improve cardiovascular risk assessment and help target the therapeutic strategies in asymptomatic patients at intermediate CAD risk.     

冠状动脉钙化积分预测老年冠心病的相关研究

目的进一步探讨预测老年冠心病的新指标,预防心血管事件的发生。方法对≥60岁老年人66例(冠心病48例,非冠心病18例)进行多层螺旋CT(MSCT)冠状动脉扫描和计算机自动测定冠状动脉钙化积分(CACS),对CACS结果进行分析。结果老年冠心病组的CACS明显高于非冠心病组(P<0·01)。3支血管钙化者CACS明显高于1支及2支血管钙化者,且钙化发生在任意血管段都有明确意义(P<0·01,P<0·05)。结论CACS优于传统危险因子,可作为预测冠心病的新指标之一。     

Euthyroid submedian free t4 and subclinical hypothyroidism may have a detrimental clinical effect in down syndrome

Background: Aberrant thyroid function is highly prevalent in Down syndrome (DS). We aimed to find whether subclinical hypothyroidism (SCH) or low-normal free T4 (FT4) are associated with a detrimental clinical outcome in untreated DS patients. Methods: 157 patients assessed at Hadassah Down Syndrome Center between 2004 and 2010 by comprehensive clinical evaluation and tests for hemoglobin, FT4 and thyroid-stimulating hormone (TSH) were subdivided into subgroups including: clinical hypothyroidism, SCH, euthyroid submedian or supramedian FT4, and alternatively for euthyroidism and TSH levels (submedian or supramedian TSH). Results: Hypothyroidism was found in 21.7% and SCH in another 14.9% of the patients. Moderate/severe hypotonia were more frequent among SCH patients compared to euthyroid patients (52.6 vs. 16.4%, p = 0.002). Patient's hemoglobin levels were lower in the euthyroid submedian FT4 group compared to the euthyroid supramedian FT4 group (10.9 vs. 0% below the normal range, p = 0.001). Interestingly, FT4 levels correlated negatively with increasing age among euthyroid DS patients (Pearson's correlation coefficient = -0.324, p = 0.009). Conclusion: SCH and euthyroid submedian FT4 may have significant clinical sequelae, such as hypotonia and anemia. Interventional studies with L-thyroxine replacement may be indicated in these subpopulations. Our finding that FT4 levels decrease with age in DS (contrasting the general population trend) may indicate redefining the normal FT4 levels range in DS.     

Coronary artery calcium and cardiovascular risk in diabetes

Measurement of coronary artery calcium score (CACS) by electron beam tomography has been shown to a powerful predictor of coronary heart disease events in asymptomatic non-diabetic subjects. In type 2 diabetes, measurement of CACS was found to be a powerful predictor of cardiovascular events which could enhance prediction provided by established risk models. 23% of type 2 diabetic subjects with low CACS were found to be at low risk for cardiovascular events. Moreover mortality was similar for type 2 diabetic and non-diabetic subjects with undetectable coronary artery calcification. Conversely type 2 diabetic subjects with high CACS were identified who were at high cardiovascular risk. Thus not all those with type 2 diabetes are at similar cardiovascular risk. Measurement of CACS enables cardiovascular risk in type 2 diabetes to be stratified so that the level of preventive therapy could be reduced in some and intensified in others. Although prospective data for the power of CACS to predict CHD events in type 1 diabetes are lacking, measurement of CACS could help in deciding on preventive therapy in type 1 diabetes.     

The association of coronary calcium score and conventional cardiovascular risk factors in Type 2 diabetic subjects asymptomatic for coronary heart disease (The PREDICT Study).

AIM: To determine the association between coronary calcification score (CACS) obtained by electron beam computed tomography (EBCT) and cardiovascular risk factors in Type 2 diabetic subjects entered into a prospective cohort study. METHODS: Type 2 diabetic subjects attending routine hospital diabetic clinics without known coronary heart disease (CHD) underwent EBCT to measure CACS. Demographic data were obtained and conventional cardiovascular risk factors were measured at baseline. RESULTS: Four hundred and ninety-five subjects were assessed of whom 67.7% were male. They had a mean (SD) age of 62.9 (7.1) years, with median (inter-quartile range) duration of diabetes of 8 (4-13) years. None had a history of coronary artery disease. Forty-five per cent were receiving lipid-lowering agents (including 36% statins). In a univariate analysis, there were significant associations between increased CACS and age, duration of diabetes, male gender, waist-hip ratio (WHR), systolic blood pressure, and the use of statins. In a multivariate model adjusting for the possible interaction of these and other factors, the significant association between CACS and WHR, systolic blood pressure, male gender and statin use remained. CONCLUSIONS: The close association between CACS and WHR and the association with systolic blood pressure suggest that coronary calcification may be particularly linked to the metabolic syndrome in Type 2 diabetes.     

Coronary calcification, homocysteine, C-reactive protein and the metabolic syndrome in Type 2 diabetes: the Prospective Evaluation of Diabetic Ischaemic Heart Disease by Coronary Tomography (PREDICT) Study.

AIMS: The PREDICT Study aims to determine: (i) the association between cardiovascular risk factors and coronary artery calcification score (CACS) obtained by electron beam tomography and (ii) the predictive value of CACS for coronary heart disease (CHD) events in Type 2 diabetes. METHODS: Having previously reported relationships between CACS and conventional risk factors, we have now studied the novel risk factors, plasma high-sensitivity C-reactive protein (CRP) and homocysteine, insulin resistance, serum apoprotein A1 and B concentrations, the serum triglyceride/high-density lipoprotein cholesterol ratio and metabolic syndrome (International Diabetes Federation definition) in 573 subjects of the PREDICT Type 2 diabetes cohort. RESULTS: In univariate analyses, the only significant positive novel correlate of CACS was homocysteine (P = 0.0004). CRP was increased in those with detectable calcification, but decreased with increasing calcification score (P = 0.006). In a multivariate model that included all significant univariate correlates, CACS was independently associated with age (P < 0.0001), waist-hip ratio (P < 0.02), male gender (P < 0.05) and duration of diabetes (P < 0.05), but the association with homocysteine was no longer significant. The negative association between CACS and CRP remained in multivariate analysis, and was independent of statin use. CONCLUSIONS: Age was the major factor influencing CACS in Type 2 diabetes, with weaker contributions from waist hip-ratio and duration of diabetes. Other novel cardiovascular risk factors appear to have little positive effect.     

Thyroid Function and Risk of Non-Alcoholic Fatty Liver Disease in Euthyroid Subjects

Introduction and aims. The association between thyroid function and non-alcoholic fatty liver disease (NAFLD) remained controversial. A large cross-sectional study aimed to explore the relationship in euthyroid population.Material and methods. A total of 1773 euthyroid subjects who underwent health check-up during one-year period were enrolled. NAFLD was diagnosed by ultrasound and fatty liver index (FLI). Fibrosis was estimated by BARD score. Thyroid function parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were recorded. Multivariate logistic regression analyses were performed to identify the independent risk factors. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.Results. NAFLD was diagnosed by ultrasound in 638 (35.98%) subjects and by FLI ≥ 60 in 694 (39.14%) subjects. Regardless of ultrasound or FLI, the overall analysis demonstrated that TSH and FT3 levels were significantly higher in subjects with NAFLD than subjects without NAFLD, but FT4 level was not significantly different between them. This association remained in middle-age subjects, but not elderly subjects. In the multivariate logistic regression analysis, TSH (OR = 1.108, 95%CI = 1.056-1.398, P = 0.024) and FT3 (OR = 1.258, 95%CI = 1.123-1.409, P = 0.000) levels were independently associated with the risk of NAFLD diagnosed by ultrasound; and only FT3 level (OR = 1.252, 95%CI = 1.074 - 1.460, P = 0.004) was independently associated with the risk of NAFLD estimated by FLI ≥ 60. Additionally, FT3 level (OR = 1.178, 95%CI = 1.025 − 1.354, P = 0.021) was independently associated with the risk of fibrosis estimated by BARD score ≥ 2 in NAFLD subjects.Conclusion. Among the euthyroid population, FT3 and TSH levels were positively associated with the risk of NAFLD.     

Retinol binding protein-4 elevation is associated with serum thyroid-stimulating hormone level independently of obesity in elderly subjects with normal glucose tolerance

CONTEXT: Elevated levels of retinol binding protein-4 (RBP4) are positively correlated with insulin resistance, obesity, diabetes mellitus, and cardiovascular disease (CVD). Subclinical hypothyroidism (SCH) has also been associated with CVD; however, the factors linking SCH to CVD are not clear. OBJECTIVE: The objective of the study was to evaluate risk factors for CVD in elderly patients grouped according to thyroid function. DESIGN: 217 subjects (> or =65 yr old) were randomly selected from a population and allocated to a euthyroid group (n = 177) and an SCH group (n = 40) on the basis of plasma concentrations of TSH and free T(4). We included subjects with normal glucose tolerance by a 75-g oral glucose tolerance test and subjects with impaired fasting glucose. We measured anthropometric parameters, levels of fasting glucose and insulin, hemoglobin A(1c), adiponectin, RBP4, lipid profiles, total body fat content, and the area of sc and visceral fat. RESULTS: The SCH group had higher RBP4 levels than the euthyroid group, irrespective of body mass index and fat content. Subcutaneous and visceral fat areas and total body fat percentage did not differ between groups and were not correlated with RBP4 level. Other CVD risk factors did not differ between groups. RBP4 level was positively correlated with TSH level (r = 0.241, P = 0.001) after adjustment for age, sex, and body mass index. CONCLUSIONS: Plasma RBP4 levels were associated with SCH independent of obesity in elderly subjects with normal glucose tolerance, indicating that RBP4 level could be used as an index of CVD risk in SCH.     

The progress of coronary heart disease in Type 2 diabetes as measured by coronary calcium score from electron beam computed tomography (EBCT): the PREDICT study

Coronary calcification score (CACS) measured by electron beam tomography is well established in the evaluation of cardiovascular risk in general populations. The PREDICT study aims to evaluate prediction of cardiovascular events by CACS in Type 2 diabetic subjects without previous clinical cardiovascular disease. In the present PREDICT sub-study, the rate of progression of CACS and factors influencing this rate were assessed. CACS was measured at baseline and after a mean interval of 4.0 (range of 2.1-5.0) years in the 202 PREDICT participants who agreed to have a second scan. Participants also had a range of conventional and novel biochemical risk factors measured at baseline. Progression of calcification was apparent in 170 (84%), while in 32 (16%) there was regression or no progression. Those showing progression had a significantly more adverse risk factor profile. Rate of change in CACS was strongly related to baseline CACS (p<0.0001). Rate of change also correlated with, waist:hip ratio (p=0.004), male gender (p=0.009), age (p=0.04), use of antihypertensive drugs (p=0.03) and statins (p=0.05) and, independently of baseline CACS, systolic blood pressure (p=0.0006), waist circumference (p=0.001) and urine albumin:creatine ratio (p=0.04). Most subjects with Type 2 diabetes showed progression of CACS. The absence of a relationship between progression and lipid risk factors and the positive relationship with statin and antihypertensive drug use may reflect earlier risk factor exposure. Independent relationships between progression and established calcification, blood pressure, central adiposity and urine albumin:creatinine ratio suggest areas for risk factor modification that could be especially relevant in Type 2 diabetes.     

The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical hypothyroidism

The aim of our study was to assess the changes in serum lipid profiles after replacement therapy with L-T4 in patients with subclinical hypothyroidism (SCH), and to see whether there is an improvement in dyslipidemia based cardiovascular risk. Thirty non-smoker pre-menopausal women with newly diagnosed SCH (TSH between 4 and 10 microIU/ml) were involved in our study; twenty-six euthyroid healthy subjects were used as control group. TSH, free T3 (FT3), free T4 (FT4), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were measured before and after 6 months of L-T4 (50-100 microg/ day) therapy. TSH levels were targeted as < 2.0 microIU/ml. LDL-C was calculated using the Friedewald formula, while the cardiovascular risk was assessed with the TC/HDL-C ratio. Pre-treatment serum TC and LDL-C concentrations in SCH patients were significantly higher than those of euthyroid subjects (199.8 +/- 22.2 vs 181.5 +/- 24.6 mg/dl, p < 0.01; 146.3 +/- 26.1 vs 124.8 +/- 12 mg/dl, p < 0.001, respectively). TC, LDL-C levels and the TC/HDL-C ratio were reduced significantly after 6-month replacement therapy (-21.1 +/- 34.4 mg/dl or -10.5%, p < 0.01; -21.5 +/- 30.3 mg/dl or -14.7%, p < 0.001, respectively; and TC/HDL-C from 4.8 +/- 0.6 to 4.1 +/- 0.5 mg/dl, p < 0.01), while body mass index (BMI) values did not change. In conclusion, even mild elevations of TSH are associated with changes in lipid profile significant enough to raise the cardiovascular risk ratio, and these changes are corrected once the patients have been rendered euthyroid.     

Difference in atherosclerosis burden in different nations and continents assessed by coronary artery calcium

We utilized coronary artery calcium scores (CACS) to assess differences in atherosclerosis burden between asymptomatic White populations living in continents with different cardiovascular disease rates. The similarities in the genetic pool between Brazilian and Portuguese Caucasian subjects offered an opportunity to assess the influence of environmental factors on the development of atherosclerosis. We reviewed CACS data from 17,563 individuals (12,378 men and 5169 women) collected in the USA (74% of the subjects), Brazil (15% of the subjects) and Portugal (11% of the subjects). CACS was absent in 80 and 88% of Portuguese men and women, compared with 46 and 62% and 33 and 59% of Brazilian and US counterparts (p<0.0001). Although the US subjects showed the lowest prevalence of risk factors they had a higher median (interquartile range) CACS than the Brazilian and the Portuguese cohorts: 4 (0;87), 1 (0;68) and 0 (0;0), respectively (p<0.0001). After adjusting for differences in age and cardiovascular risk factors, US men showed higher relative risk ratios of having any CACS than either Brazilian or Portuguese men. Brazilian and US women did not differ as far as risk of CACS although they demonstrated a greater risk than Portuguese women. In this study, significant differences in CACS were detected among three nations in different continents. The CACS differences paralleled the respective cardiovascular mortality rates.     

Impact of insulin sensitivity in relationship with prolactin and thyroid stimulating hormone.

INTRODUCTION: It is well recognized that there is a close relationship between TSH and PRL levels. The aim of this study was to evaluate the impact of insulin sensitivity on the association between TSH and PRL in euthyroid obese subjects. MATERIAL AND METHODS: Retrospective cross-sectional analysis was carried out on 165 euthyroid obese or overweight female patients. Prolactin, TSH, free thyroxine (FT4), free triiodothyronine (FT3), fasting plasma levels of insulin and glucose, postprandial levels of glucose, homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR) and insulin secretion (HOMA-beta cell), body weight, height, body mass index (BMI) and waist circumference were assessed. Statistical tests used were unpaired Student's t-test adjusted by Bonferroni's method and Pearson correlations with Bonferroni corrections. RESULTS: There was no significant difference in prolactin levels between insulin sensitive and resistant subjects. Compared to insulin sensitive subjects, TSH levels were higher in insulin resistant subjects but it was not statistically significant. We observed significant positive correlation between prolactin and TSH in insulin sensitive and normoglycemic subjects (r=0.273, p=0.039 and r=0.253, p=0.023, respectively) but this correlation was lost in insulin resistant subjects and subjects who had fasting glucose levels >or=100 mg/dl (r=0.057, p=0.609 and r=0.090, p=0.404, respectively). CONCLUSIONS: The findings of this study provide some clues about the relationship between PRL and TSH in insulin sensitive obese subjects. The insulin sensitivity and carbohydrate homeostasis seem to be involved in relationship with PRL and TSH by the brain via serotoninergic and dopaminergic system.     

Coronary artery calcium scoring: an evidence-based guide for primary care physicians

Primary care physicians often must decide whether statin therapy would be appropriate (in addition to lifestyle modification) for managing asymptomatic individuals with borderline or intermediate risk for developing atherosclerotic cardiovascular disease (ASCVD), as assessed on the basis of traditional risk factors. In appropriate subjects, a simple, noninvasive measurement of coronary artery calcium can help clarify risk. Coronary atherosclerosis is a chronic inflammatory disease, with atherosclerotic plaque formation involving intimal inflammation and repeated cycles of erosion and fibrosis, healing and calcification. Atherosclerotic plaque formation represents the prognostic link between risk factors and future clinical events. The presence of coronary artery calcification is almost exclusively an indication of coronary artery disease, except in certain metabolic conditions. Coronary artery calcification can be detected and quantified in a matter of seconds by noncontrast electrocardiogram-gated low-dose X-ray computed tomography (coronary artery calcium scoring [CACS]). Since the publication of the seminal work by Dr. Arthur Agatston in 1990, a wealth of CACS-based prognostic data has been reported. In addition, recent guidelines from various professional societies conclude that CACS may be considered as a tool for reclassifying risk for atherosclerotic cardiovascular disease in patients otherwise assessed to have intermediate risk, so as to more accurately inform decisions about possible statin therapy in addition to lifestyle modification as primary preventive therapy. In this review, we provide an overview of CACS, from acquisition to interpretation, and summarize the scientific evidence for and the appropriate use of CACS as put forth in current clinical guidelines.     

冠状动脉钙化积分相关临床因素分析

目的 评价冠状动脉(冠脉)钙化积分(CACS)的相关因素.方法 入选疑诊冠心病的患者141例,3个月内完成多层螺旋CT、脉搏波传导速度(PWV)、超声心动图及血生化检查,MDRD方程计算患者入院时估算肾小球滤过率(eGFR).根据冠脉钙化程度将病例分为3组:A组(CACS=0～10),B组(CACS=11～400),C组(CACS>400).结果 3组比较年龄、高血压病史、糖尿病史、二尖瓣钙化、主动脉瓣钙化、两侧臂踝指数低值、臂到踝的PWV高值、臂及踝平均动脉压高值、波形上升支时间高值差异均有统计学意义(P值均<0.05).多因素logistic回归分析显示:主动脉瓣钙化(P=0.000)、二尖瓣钙化(P=0.002)、波形上升支时间高值(P=0.009)和糖尿病(P=0.032)是严重冠脉钙化的独立相关因素.结论 疑诊冠心病的患者行多层螺旋CT检查前可行PWV和超声心动图检查,结合病史评估患者冠脉钙化的可能性及严重程度.     

Initial thyroid status and cardiovascular risk factors: The EPIC‐Norfolk prospective population study

Context Thyroid status affects several aspects of cardiovascular risk profile, including lipid levels and blood pressure. Whether thyroid status affects the risk of coronary heart disease (CHD) and all‐cause mortality remains controversial. Design The EPIC‐Norfolk prospective population study. Mean follow‐up was 10·6 years. Patients Study participants were 11 554 men and women aged 45–79 years, who were living in Norfolk, UK. Measurements Baseline cardiovascular risk factors were recorded and concentrations of thyroid‐stimulating hormone (TSH) and free thyroxine (FT4) were measured in baseline samples. Regression analyses were performed to assess the association between thyroid hormone levels and cardiovascular risk factors. A proportional hazards model was used to estimate the risk of CHD and all‐cause mortality by baseline thyroid status. No information was available on thyroid treatment during follow‐up. Results Thyroid abnormalities were common, particularly among women. Thyroid abnormalities were associated with an altered cardiovascular risk profile. Even within the normal range, thyroid hormone levels, TSH more strongly than FT4, were associated with lipid levels and blood pressure among both men and women. We did not observe a significant association between subclinical thyroid abnormalities and risk of CHD or all‐cause mortality. Conclusions Despite the association between thyroid hormone levels and cardiovascular risk factors, thyroid status was not statistically significantly associated with the risk of future CHD or all‐cause mortality in this large cohort.     

Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hsCRP

The mechanism(s) by which low circulating levels of thyroid hormones may lead to development of premature atherosclerosis remain to be established. These mechanisms include indirect effects of thyroid hormones on cardiovascular risk factors such as plasma lipoproteins, homocysteine and fibrinogen. High-sensitivity C-reactive protein (hsCRP) has been identified as an independent predictor of cardiovascular events. We presently investigated the relationship between hsCRP and free thyroxine (FT4) levels in a large population of euthyroid hyperlipidemic patients (n=429, mean age: 47.1 years, 28% of current smokers). None of these subjects presented a recent history of infection or inflammatory disease and those taking drugs known to influence thyroid or hsCRP were excluded. Serum FT4 levels were measured by radioimmunoassay and CRP, by a high-sensitivity immunoassay. In the population of non-smokers, plasma FT4 levels were negatively and significantly correlated with those of hsCRP (r=-0.13, P=0.02). Significant correlations between FT4 levels and age (r=-0.16, P=0.003), glycemia (r=-0.14, P=0.01), and fibrinogen (r=-0.18, P=0.001) were equally observed. Upon division of the population on the basis of FT4 tertiles, the mean level of hsCRP was significantly higher in non-smoker patients with the lowest FT4 tertile as compared to those displaying the highest FT4 level (3.04mg/l versus 1.77mg/l, respectively, P<0.05). No correlation between FT4 levels and CRP was found in smokers.In conclusion, we demonstrate that hsC-reactive protein is significantly negatively correlated with free thyroxine levels in non-smoker hyperlipidemic patients, suggesting that low thyroxine levels in euthyroid hyperlipidemic subjects constitute a new biomarker of elevated cardiovascular risk.     

Abnormalities of hypothalamic-pituitary-thyroid axis in patients with primary empty sella

Primary empty sella (PES) is a very frequent neuroradiological finding in the general population, that can induce hypopituitarism. Some studies focused on the association of PES with GH deficiency (GHD) or hypogonadotropic hypogonadism (HH), while data regarding the involvement of hypothalamic-pituitary-thyroid (HPT) axis, despite sporadic reports of central hypothyroidism, or the occurrence of hypoadrenalism (HA) are scanty. In this study, thyroid function and TSH response to exogenous TRH injection (TRH/TSH) were investigated in 43 patients [10 men and 33 women; aged (mean +/- SD), 48+/-12 yr] with PES: 22 patients had total and 21 partial PES. Forty healthy subjects (9 men and 31 women; aged 46+/-12 yr) were enrolled as a control group. Central hypothyroidism was found only in 2/43 cases, whereas one patient showed primary hypothyroidism. In euthyroid patients, mean serum TSH levels were significantly lower than controls (TSH: 1.0+/-0.7 vs 1.4+/-0.6 mU/l, p<0.01) and 79% of them showed abnormal TRH/TSH responses (TRH test was performed in 34 euthyroid patients: 17 cases with total and 17 cases with partial PES), but mean serum free T4 (FT4) and free T3 (FT3) values were not significantly lower than controls (FT4: 15.9+/-0.4 vs 15.0+/-2.1 pmol/l, p=NS; FT3: 5.3+/-1.2 vs 5.8+/-1.5 pmol/l, p=NS). Moreover, no significant differences were evident in mean serum TSH, FT4 and FT3 between patients with total and partial PES (TSH: 1.1+/-0.7 vs 0.9+/-0.8 mU/l, p=NS; FT4: 16.3+/-2.6 vs 15.7+/-2.2 pmol/l, p=NS; FT3: 5.4+/-1.3 vs 5.2+/-0.8 pmol/l, p=NS) and the TRH/TSH peak was impaired or exaggerated/delayed in 9 and 3 patients with total and in 12 and 3 cases with partial PES. No significant differences in the prevalence of abnormal TRH/TSH responsiveness were found between patients with partial or total PES (chi2=1.6, p=NS). Other impairment of pituitary function was detected in 23/43 patients: GHD was present in 15 cases, HH in 11 and central HA in 5 patients. Isolated or combined hypopituitarism was present in 17 and in 6 patients, respectively. In conclusion, pituitary dysfunction is very frequent in patients with PES, but central hypothyroidism occurs rarely. The entity of arachnoid herniation into the sellar fossa does not play a significant role on the degree of HPT axis dysfunction.     

Thyroid function is associated with carotid intima-media thickness in euthyroid subjects

To investigate the relationship between thyroid function and carotid intima-media thickness (CIMT) in a relatively large general population with euthyroid status we initially enrolled 1772 Japanese adults (421 men and 1351 women) who participated in a medical screening program for the general population over 40 years old. To evaluate only euthyroid subjects without vascular diseases and/or its major risk factors, 1129 were excluded and 643 participants (175 men and 468 women) were included for further analysis. Simple and multivariate linear regression analyses were performed to evaluate free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels and other existing parameters, including carotid intima-media thickness. By multivariate linear regression analysis adjusted for age and sex, free thyroxine was significantly correlated with triglycerides (beta=0.07, p=0.015), carotid intima-media thickness (beta=-0.091, p=0.049), and thyroid-stimulating hormone (beta=-0.091, p=0.003). Thyroid-stimulating hormone was significantly correlated with high-density lipoprotein cholesterol (HDL-C) (beta=-0.001, p=0.015), HbA(1c) (beta=0.038, p=0.045), carotid intima-media thickness (beta=0.27, p=0.001), and free thyroxine (beta=-0.15, p=0.003). When adjusted for confounding factors, free thyroxine was significantly correlated only with carotid intima-media thickness (beta=-0.13, p=0.043) and thyroid-stimulating hormone was significantly correlated with HDL-C (beta=-0.001, p<0.001), HbA(1c) (beta=0.04, p=0.021), and carotid intima-media thickness (beta=0.29, p=0.001). We have demonstrated that carotid intima-media thickness is independently associated with thyroid function within the normal reference range, which suggests an increased cardiovascular risk in subjects with low normal thyroid function.