Thyroid hormones have a central role in cardiovascular homeostasis. In myocardium, these hormones stimulate both diastolic myocardial relaxation and systolic myocardial contraction, have a pro-angiogenic effect and an important role in extracellular matrix maintenance. Thyroid hormones modulate cardiac mitochondrial function. Dysfunction of thyroid axis impairs myocardial bioenergetic status. Both overt and subclinical hypothyroidism are associated with a higher incidence of coronary events and an increased risk of heart failure progression. Endothelial function is also impaired in hypothyroid state, with decreased nitric oxide-mediated vascular relaxation. In heart disease, particularly in ischemic heart disease, abnormalities in thyroid hormone levels are common and are an important factor to be considered. In fact, low thyroid hormone levels should be interpreted as a cardiovascular risk factor. Regarding ischemic heart disease, during the late post-myocardial infarction period, thyroid hormones modulate left ventricular structure, function and geometry. Dysfunction of thyroid axis might even be more prevalent in the referred condition since there is an upregulation of type 3 deiodinase in myocardium, producing a state of local cardiac hypothyroidism. In this focused review, we summarize the central pathophysiological and clinical links between altered thyroid function and ischemic heart disease. Finally, we highlight the potential benefits of thyroid hormone supplementation as a therapeutic target in ischemic heart disease.
Madalena von Hafe, João Sergio Neves, Catarina Vale, Marta Borges-Canha, and Adelino Leite-Moreira
Peter Wolf, Yvonne Winhofer, Martin Krššák, and Michael Krebs
Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.
Marianne Aa Grytaas, Kjersti Sellevåg, Hrafnkell B Thordarson, Eystein S Husebye, Kristian Løvås, and Terje H Larsen
Primary aldosteronism (PA) is associated with increased cardiovascular morbidity, presumably due to left ventricular (LV) hypertrophy and fibrosis. However, the degree of fibrosis has not been extensively studied. Cardiac magnetic resonance imaging (CMR) contrast enhancement and novel sensitive T1 mapping to estimate increased extracellular volume (ECV) are available to measure the extent of fibrosis.
To assess LV mass and fibrosis before and after treatment of PA using CMR with contrast enhancement and T1 mapping.
Fifteen patients with newly diagnosed PA (PA1) and 24 age- and sex-matched healthy subjects (HS) were studied by CMR with contrast enhancement. Repeated imaging with a new scanner with T1 mapping was performed in 14 of the PA1 and 20 of the HS median 18 months after specific PA treatment and in additional 16 newly diagnosed PA patients (PA2).
PA1 had higher baseline LV mass index than HS (69 (53–91) vs 51 (40–72) g/m2; P < 0.001), which decreased significantly after treatment (58 (40–86) g/m2; P < 0.001 vs baseline), more with adrenalectomy (n = 8; −9 g/m2; P = 0.003) than with medical treatment (n = 6; −5 g/m2; P = 0.075). No baseline difference was found in contrast enhancement between PA1 and HS. T1 mapping showed no increase in ECV as a myocardial fibrosis marker in PA. Moreover, ECV was lower in the untreated PA2 than HS 10 min post-contrast, and in both PA groups compared with HS 20 min post-contrast.
Specific treatment rapidly reduced LV mass in PA. Increased myocardial fibrosis was not found and may not represent a common clinical problem.
Sahar Hossam El Hini, Yehia Zakaria Mahmoud, Ahmed Abdelfadel Saedii, Sayed Shehata Mahmoud, Mohamed Ahmed Amin, Shereen Riad Mahmoud, and Ragaa Abdelshaheed Matta
Angiopoietin-like proteins (ANGPTL) 3, 4 and 8 are upcoming cardiovascular biomarkers. Experimental studies showed that thyroid hormones altered their levels. We assessed ANGPTL3, 4 and 8 as predictors of cardiovascular functions among naïve subclinical and naïve overt hypothyroidism (SCH and OH) and altered ANGPTL levels with levothyroxine replacement (LT4) and their association with improved cardiovascular risk factors and cardiovascular function.
Design and methods
The study was a prospective follow-up study that assessed ANGPTL3, 4 and 8 levels, vascular status (flow-mediated dilation% of brachial artery (FMD%), carotid intima-media thickness (CIMT), aortic stiffness index (ASI)), left ventricle (LV) parameters (ejection fraction (EF), myocardial performance index (MPI), and LV mass), well-known cardiovascular risk factors and homeostatic model for the assessment of insulin resistance, at two time points, that is, among naïve SCH, naïve OH, and healthy subjects groups; and at 6 months after achieving the euthyroid state with LT4 by calculating their increased or decreased delta changes (∆↑ or ∆↓) in longitudinal arm among LT4-hypothyroid groups.
Significantly elevated levels of ANGPTL3, 4 and 8 among hypothyroid groups than the healthy subjects were reduced with LT4. Multivariate analysis revealed ANGPTLs as independent predictors of cardiovascular functions and the contributors for ANGPTL level included ANGPTL3 and 4 for impaired FMD%, and ANGPTL8 for LV mass among naïve SCH; ANGPTL3 for EF% and ANGPTL8 for CIMT in naïve OH; ∆↓ANGPTL3 for ∆↓ASI meanwhile ∆↑freeT4 for ∆↓ANGPTL3, ∆↓fasting glucose, ∆↓triglyceride, and ∆↓thyroid peroxidase antibody for ∆↓ANGPTL4 among LT4-SCH. ∆↓ANGPTL4 for ∆↓MPI and ∆↓LV mass, meanwhile ∆↓TSH and ∆↓triglyceride for ∆↓ANGPTL3, ∆↑free T3 and ∆↓HOMA-IR for ∆↓ANGPTL4, and systolic blood pressure and waist circumference for ∆↓ANGPTL8 among LT4-OH.
Elevated ANGPTL3, 4 and 8 levels are differentially independent predictors of endothelial and cardiac function and are reduced with LT4 in SCH and OH.
L E Zijlstra, D M van Velzen, S Simsek, S P Mooijaart, M van Buren, D J Stott, I Ford, J W Jukema, and S Trompet
Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes.
In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45–4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45–60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke.
Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24–1.07) comparing subclinical hyperthyroidism and 0.90 (0.58–1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism).
In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.
Wang Chengji and Fan Xianjin
To investigate the biological mechanism of the effect of different intensity exercises on diabetic cardiomyopathy.
87 raise specific pathogen SPF healthy 6-week-old male Sprague–Dawley rats, fed 6 weeks with high-fat diet for rats were used, and a diabetic model was established by intraperitoneal injection of streptozotocin – randomly selected 43 rats were divided into Diabetic control group (DCG, n = 10), Diabetic exercise group 1 (DEG1, n = 11), Diabetic exercise group 2 (DEG2, n = 11) and Diabetic exercise group 3 (DEG3, n = 11). The rats in DEG1 were forced to run on a motorized treadmill, the exercise load consisted of running at a speed of 10 m/min, the exercise load of the rats in DEG2 were running at a speed of 15 m/min, the exercise load of the rats in DEG3 were running at a speed of 20 m/min, for one hour once a day for 6 weeks. After 6 weeks of exercise intervention, glucose metabolism-related indexes in rats such as blood glucose (FBG), glycosylated serum protein (GSP) and insulin (FINS); cardiac fibrinolytic system parameters such as PAI-1 (plasminogen activator inhibitor 1), Von Willebrand factor (vWF), protein kinase C (PKC) and diacylglycerol (DAG); and serum level of NO, eNOS and T-NOS were measured.
Compared with DCG, fasting blood glucose and GSP were decreased, while insulin sensitivity index and insulin level were increased in all rats of the three exercise groups. FBG decrease was statistically significant (P < 0.01), only GSP decrease was statistically significant (P < 0.05) in DEG1 and DEG2, PAI-1 in three exercise groups were significantly reduced (P < 0.05), plasma vWF levels in the three exercise groups were significantly lower than those in the DCG group (P < 0.01); PKC levels decreased dramatically in the three exercise groups and DAG levels decrease slightly (P < 0.05), but with no significant difference. Compared with DCG, the serum level of NO was significantly higher (P < 0.05), and eNOS level was significantly elevated (P < 0.05). T-NOS elevation was statistically significant in DEG1 (P < 0.05).
Low- and moderate-intensity exercise can better control blood glucose level in diabetic rats; myocardial PAI-1 in DEG1, DEG2 and DEG3 rats decreased significantly (P < 0.05), serum NO increased (P < 0.05) and eNOS increased (P < 0.05) significantly. Therefore, it is inferred that exercise improves the biological mechanism of diabetic cardiomyopathy by affecting the levels of PAI-1 and eNOS, and there is a dependence on intensity.
Satoshi Higuchi, Hideki Ota, Yuta Tezuka, Kazumasa Seiji, Hidenobu Takagi, Jongmin Lee, Yi-Wei Lee, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Masataka Kudo, Fumitoshi Satoh, and Kei Takase
This study compared cardiac function, morphology, and tissue characteristics between two common subtypes of primary aldosteronism (PA) using a 3T MR scanner.
A retrospective, single-center, observational study.
We retrospectively reviewed 143 consecutive patients with PA, who underwent both adrenal venous sampling and cardiac magnetic resonance. We acquired cine, late gadolinium enhancement, and pre- and postcontrast myocardial T1-mapping images.
PA was diagnosed as unilateral aldosterone-producing adenoma (APA) in 70 patients and bilateral hyperaldosteronism (BHA) in 73. The APA group showed significantly higher plasma aldosterone concentration (PAC) and aldosterone to renin rate (ARR) than the BHA group. After controlling for age, sex, antihypertensive drugs, systolic and diastolic blood pressure, and disease duration, the parameters independently associated with APA were: left ventricular end-diastolic volume index (EDVI: adjusted odds ratio (aOR) = 1.06 (95% CI: 1.030–1.096), P < 0.01), end-systolic volume index (ESVI: 1.06 (1.017–1.113), P < 0.01), stroke index (SI: 1.07 (1.020–1.121), P < 0.01), cardiac index (CI: 1.001 (1.000–1.001), P < 0.01), and native T1 (1.01 (1.000–1.019), P = 0.038). Weak positive correlations were found between PAC and EDVI (R = 0.28, P < 0.01), ESVI (0.26, P < 0.01), and SI (0.18, P = 0.03); and between ARR and EDVI (0.25, P < 0.01), ESVI (0.24, P < 0.01), and native T1 (0.17, P = 0.047).
APA is associated with greater LV volumetric parameters and higher native T1 values, suggesting a higher risk of volume overload and myocardial damage.
Satoshi Higuchi, Hideki Ota, Takuya Ueda, Yuta Tezuka, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Masataka Kudo, Fumitoshi Satoh, and Kei Takase
Regional differences in cardiac magnetic resonance, which can reveal catecholamine-induced myocardial injury in patients with pheochromocytoma, have not yet been assessed using 3T magnetic resonance imaging. We evaluated these differences using myocardial T1-mapping and strain analysis.
Design and Methods
We retrospectively reviewed 16 patients newly diagnosed with catecholamine-producing tumors (CPT group) and 16 patients with essential hypertension (EH group), who underwent cardiac magnetic resonance imaging between May 2016 and March 2018. We acquired 3T magnetic resonance cine and native T1-mapping images and performed feature-tracking-based strain analysis in the former.
Global cardiac function, morphology, global strain and peak strain rate were similar, but end-diastolic wall thickness differed between groups (CPT vs EH: 10.5 ± 1.7 vs 12.6 ± 2.8 mm; P < 0.05). Basal, but not apical, circumferential strain was significantly higher in the CPT than the EH group (19.4 ± 3.2 vs 16.8 ± 3.6 %; P < 0.05). Native T1 values were significantly higher in CPT than in EH patients, in both the basal septum (1307 ± 48 vs 1241 ± 45 ms; P < 0.01) and the apical septum (1377 ± 59 vs 1265 ± 58 ms; P < 0.01) mid-walls. In the CPT, but not in the EH group, native T1 values in the apical wall were significantly higher than those in the basal wall (P < 0.01).
3T magnetic resonance-based T1-mapping can sensitively detect subclinical catecholamine-induced myocardial injury; the influence of catecholamines may be greater in the apical than in the basal wall.
Elin Kahlert, Martina Blaschke, Knut Brockmann, Clemens Freiberg, Onno E Janssen, Nikolaus Stahnke, Domenika Strik, Martin Merkel, Alexander Mann, Klaus-Peter Liesenkötter, and Heide Siggelkow
Turner syndrome (TS) is characterized by the complete or partial loss of the second sex chromosome and associated with a wide range of clinical manifestations. We aimed to assess the medical care of adult patients with TS in Germany.
Retrospective multicenter observational study.
Data were collected from medical records of 258 women with TS treated between 2001 and 2017 in five non-university endocrinologic centers in Germany.
Mean age was 29.8 ± 11.6 years, mean height 152 ± 7.7 cm, and mean BMI 26.6 ± 6.3 kg/m2. The karyotype was known in 50% of patients. Information on cholesterol state, liver enzymes, and thyroid status was available in 81–98% of women with TS; autoimmune thyroiditis was diagnosed in 37%. Echocardiography was performed in 42% and cardiac MRI in 8.5%, resulting in a diagnosis of cardiovascular disorder in 28%. Data on growth hormone therapy were available for 40 patients (15%) and data concerning menarche in 157 patients (61%).
In 258 women with TS, retrospective analysis of healthcare data indicated that medical management was focused on endocrine manifestations. Further significant clinical features including cardiovascular disease, renal malformation, liver involvement, autoimmune diseases, hearing loss, and osteoporosis were only marginally if at all considered. Based on this evaluation and in accordance with recent guidelines, we compiled a documentation form facilitating the transition from pediatric to adult care and further medical management of TS patients. The foundation of Turner Centers in March 2019 will improve the treatment of TS women in Germany.
Lasse Oinonen, Antti Tikkakoski, Jenni Koskela, Arttu Eräranta, Mika Kähönen, Onni Niemelä, Jukka Mustonen, and Ilkka Pörsti
Parathyroid hormone has been related with the risk of hypertension, but the matter remains controversial. We examined the association of parathyroid hormone with central blood pressure and its determinants in 622 normotensive or never-treated hypertensive subjects aged 19–72 years without diabetes, cardiovascular or renal disease, or cardiovascular medications. The methods were whole-body impedance cardiography and analyses of pulse wave and heart rate variability. Cardiovascular function was examined in sex-specific tertiles of plasma parathyroid hormone (mean concentrations 3.0, 4.3 and 6.5 pmol/L, respectively) during head-up tilt. Explanatory factors for haemodynamics were further investigated using linear regression analyses. Mean age was 45.0 (s.d. 11.7) years, BMI 26.8 (4.4) kg/m2, seated office blood pressure 141/90 (21/12) mmHg, and 309 subjects (49.7%) were male. Only five participants had elevated plasma parathyroid hormone and calcium concentrations. Highest tertile of parathyroid hormone presented with higher supine and upright aortic diastolic blood pressure (P < 0.01) and augmentation index (P < 0.01), and higher upright systemic vascular resistance (P < 0.05) than the lowest tertile. The tertiles did not present with differences in pulse wave velocity, cardiac output, or measures of heart rate variability. In linear regression analyses, parathyroid hormone was an independent explanatory factor for aortic systolic (P = 0.005) and diastolic (P = 0.002) blood pressure, augmentation index (P = 0.002), and systemic vascular resistance (P = 0.031). To conclude, parathyroid hormone was directly related to central blood pressure, wave reflection, and systemic vascular resistance in subjects without cardiovascular comorbidities and medications. Thus, parathyroid hormone may play a role in the pathophysiology of primary hypertension.