Search Results
Search for other papers by Tsuneo Ogawa in
Google Scholar
PubMed
Search for other papers by Adolfo J de Bold in
Google Scholar
PubMed
The concept of the heart as an endocrine organ arises from the observation that the atrial cardiomyocytes in the mammalian heart display a phenotype that is partly that of endocrine cells. Investigations carried out between 1971 and 1983 characterised, by virtue of its natriuretic properties, a polypeptide referred to atrial natriuretic factor (ANF). Another polypeptide isolated from brain in 1988, brain natriuretic peptide (BNP), was subsequently characterised as a second hormone produced by the mammalian heart atria. These peptides were associated with the maintenance of extracellular fluid volume and blood pressure. Later work demonstrated a plethora of other properties for ANF and BNP, now designated cardiac natriuretic peptides (cNPs). In addition to the cNPs, other polypeptide hormones are expressed in the heart that likely act upon the myocardium in a paracrine or autocrine fashion. These include the C-type natriuretic peptide, adrenomedullin, proadrenomedullin N-terminal peptide and endothelin-1. Expression and secretion of ANF and BNP are increased in various cardiovascular pathologies and their levels in blood are used in the diagnosis and prognosis of cardiovascular disease. In addition, therapeutic uses for these peptides or related substances have been found. In all, the discovery of the endocrine heart provided a shift from the classical functional paradigm of the heart that regarded this organ solely as a blood pump to one that regards this organ as self-regulating its workload humorally and that also influences the function of several other organs that control cardiovascular function.
Search for other papers by Hugo R Ramos in
Google Scholar
PubMed
Department of Internal Medicine, Section of Metabolic Vascular Medicine, Division of Diabetes and Nutritional Sciences, Cardiovascular Endocrinology Laboratory, Faculty of Medicine, Hospital de Urgencias, National University of Córdoba, X5000 Córdoba, Argentina
Search for other papers by Andreas L Birkenfeld in
Google Scholar
PubMed
Search for other papers by Adolfo J de Bold in
Google Scholar
PubMed
Since their discovery in 1981, the cardiac natriuretic peptides (cNP) atrial natriuretic peptide (also referred to as atrial natriuretic factor) and brain natriuretic peptide have been well characterised in terms of their renal and cardiovascular actions. In addition, it has been shown that cNP plasma levels are strong predictors of cardiovascular events and mortality in populations with no apparent heart disease as well as in patients with established cardiac pathology. cNP secretion from the heart is increased by humoral and mechanical stimuli. The clinical significance of cNP plasma levels has been shown to differ in obese and non-obese subjects. Recent lines of evidence suggest important metabolic effects of the cNP system, which has been shown to activate lipolysis, enhance lipid oxidation and mitochondrial respiration. Clinically, these properties lead to browning of white adipose tissue and to increased muscular oxidative capacity. In human association studies in patients without heart disease higher cNP concentrations were observed in lean, insulin-sensitive subjects. Highly elevated cNP levels are generally observed in patients with systolic heart failure or high blood pressure, while obese and type-2 diabetics display reduced cNP levels. Together, these observations suggest that the cNP system plays a role in the pathophysiology of metabolic vascular disease. Understanding this role should help define novel principles in the treatment of cardiometabolic disease.
Section of Pacing and Electrophysiology, Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Search for other papers by Ling Sun in
Google Scholar
PubMed
Search for other papers by Wenwu Zhu in
Google Scholar
PubMed
Search for other papers by Yuan Ji in
Google Scholar
PubMed
Search for other papers by Ailin Zou in
Google Scholar
PubMed
Dalian Medical University, Dalian, Liaoning, China
Search for other papers by Lipeng Mao in
Google Scholar
PubMed
Dalian Medical University, Dalian, Liaoning, China
Search for other papers by Boyu Chi in
Google Scholar
PubMed
Search for other papers by Jianguang Jiang in
Google Scholar
PubMed
Search for other papers by Xuejun Zhou in
Google Scholar
PubMed
Search for other papers by Qingjie Wang in
Google Scholar
PubMed
Search for other papers by Fengxiang Zhang in
Google Scholar
PubMed
Objective
Post-treatment contrast-induced acute kidney injury (CI-AKI) is associated with poor outcomes in patients with acute myocardial infarction (AMI). A lower free triiodothyronine (FT3) level predicts a poor prognosis of AMI patients. This study evaluated the effect of plasma FT3 level in predicting CI-AKI and short-term survival among AMI patients.
Methods
Coronary arteriography or percutaneous coronary intervention was performed in patients with AMI. A 1:3 propensity score (PS) was used to match patients in the CI-AKI group and the non-CI-AKI group.
Results
Of 1480 patients enrolled in the study, 224 (15.1%) patients developed CI-AKI. The FT3 level was lower in CI-AKI patients than in non-CI-AKI patients (3.72 ± 0.88 pmol/L vs 4.01 ± 0.80 pmol/L, P < 0.001). Compared with those at the lowest quartile of FT3, the patients at quartiles 2–4 had a higher risk of CI-AKI respectively (P for trend = 0.005). The risk of CI-AKI increased by 17.7% as FT3 level decreased by one unit after PS-matching analysis (odds ratio: 0.823; 95% CI: 0.685–0.988, P = 0.036). After a median of 31 days of follow-up (interquartile range: 30–35 days), 78 patients died, including 72 cardiogenic deaths and 6 non-cardiogenic deaths, with more deaths in the CI-AKI group than in the non-CI-AKI group (53 vs 25, P < 0.001). Kaplan–Meier survival analysis showed that patients at a lower FT3 quartile achieved a worse survival before and after matching.
Conclusion
Lower FT3 may increase the risk of CI-AKI and 1-month mortality in AMI patients.
Search for other papers by Agnieszka Adamska in
Google Scholar
PubMed
Search for other papers by Vitalii Ulychnyi in
Google Scholar
PubMed
Search for other papers by Katarzyna Siewko in
Google Scholar
PubMed
Search for other papers by Anna Popławska-Kita in
Google Scholar
PubMed
Search for other papers by Małgorzata Szelachowska in
Google Scholar
PubMed
Search for other papers by Marcin Adamski in
Google Scholar
PubMed
Search for other papers by Angelika Buczyńska in
Google Scholar
PubMed
Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
Search for other papers by Adam Jacek Krętowski in
Google Scholar
PubMed
Cardiovascular risk factors could be present in mild adrenal autonomous cortisol secretion (MACS). However, the most frequent cardiovascular risk factors in MACS have not been established. The aim of the presseent study was to analyse the difference in cardiovascular risk factors in patients with MACS in comparison to those with non-functioning adrenal tumour (NFAT). A total of 295 patients with adrenal incidentaloma were included in this retrospective study. We divided our group into those who showed suppression in 1 mg overnight dexamethasone suppression test (DST) (NFAT) (serum cortisol level ≤1.8 μg/dL) and those who did not show suppression in the DST (MACS) (serum concentration of cortisol > 1.8 μg/dL and ≤5 μg/dL). In the studied groups, we analysed the presence of cardiovascular risk factors, such as obesity, prediabetes, type 2 diabetes mellitus (T2DM), hypertension, hyperlipidaemia, chronic kidney disease and cardiovascular events. In our study, 18.9% of patients were defined as MACS. Importantly, T2DM was diagnosed in 41% of MACS vs 23% of NFAT (P < 0.01) and higher frequency of occurrence of hyperlipidaemia in NFAT (72.4%) vs MACS (53.6%) (P = 0.01) was observed. We did not observed differences in the frequency of obesity, hypertension, chronic kidney disease, prediabetes, atrial fibrillation, stroke, ST and non-ST elevation myocardial infarction and coronary angioplasty between patients with MACS and NFAT (all P > 0.05; respectively). In MACS, T2DM is more prevalent than in NFAT; hyperlipidaemia is more prevalent in NFAT. Accordingly, no differences were found in the incidence of obesity, hypertension, prediabetes, chronic kidney disease between studied groups as well as cardiovascular events.
Search for other papers by Thera P Links in
Google Scholar
PubMed
Search for other papers by Trynke van der Boom in
Google Scholar
PubMed
Search for other papers by Wouter T Zandee in
Google Scholar
PubMed
Search for other papers by Joop D Lefrandt in
Google Scholar
PubMed
Thyroid hormone stimulates cardiac inotropy and chronotropy via direct genomic and non-genomic mechanisms. Hyperthyroidism magnifies these effects, resulting in an increase in heart rate, ejection fraction and blood volume. Hyperthyroidism also affects thrombogenesis and this may be linked to a probable tendency toward thrombosis in patients with hyperthyroidism. Patients with hyperthyroidism are therefore at higher risk for atrial fibrillation, heart failure and cardiovascular mortality. Similarly, TSH suppressive therapy for differentiated thyroid cancer is associated with increased cardiovascular risk. In this review, we present the latest insights on the cardiac effects of thyroid suppression therapy for the treatment of thyroid cancer. Finally, we will show new clinical data on how to implement this knowledge into the clinical practice of preventive medicine.
Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA
Search for other papers by Alexander V Amram in
Google Scholar
PubMed
Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA
Search for other papers by Stephen Cutie in
Google Scholar
PubMed
Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA
Search for other papers by Guo N Huang in
Google Scholar
PubMed
Research conducted across phylogeny on cardiac regenerative responses following heart injury implicates endocrine signaling as a pivotal regulator of both cardiomyocyte proliferation and heart regeneration. Three prominently studied endocrine factors are thyroid hormone, vitamin D, and glucocorticoids, which canonically regulate gene expression through their respective nuclear receptors thyroid hormone receptor, vitamin D receptor, and glucocorticoid receptor. The main animal model systems of interest include humans, mice, and zebrafish, which vary in cardiac regenerative responses possibly due to the differential onsets and intensities of endocrine signaling levels throughout their embryonic to postnatal organismal development. Zebrafish and lower vertebrates tend to retain robust cardiac regenerative capacity into adulthood while mice and other higher vertebrates experience greatly diminished cardiac regenerative potential in their initial postnatal period that is sustained throughout adulthood. Here, we review recent progress in understanding how these three endocrine signaling pathways regulate cardiomyocyte proliferation and heart regeneration with a particular focus on the controversial findings that may arise from different assays, cellular-context, age, and species. Further investigating the role of each endocrine nuclear receptor in cardiac regeneration from an evolutionary perspective enables comparative studies between species in hopes of extrapolating the findings to novel therapies for human cardiovascular disease.
Search for other papers by M L M Barreto-Chaves in
Google Scholar
PubMed
Search for other papers by N Senger in
Google Scholar
PubMed
Search for other papers by M R Fevereiro in
Google Scholar
PubMed
Search for other papers by A C Parletta in
Google Scholar
PubMed
Search for other papers by A P C Takano in
Google Scholar
PubMed
The cardiac growth process (hypertrophy) is a crucial phenomenon conserved across a wide array of species and is critically involved in the maintenance of cardiac homeostasis. This process enables an organism to adapt to changes in systemic demand and occurs due to a plethora of responses, depending on the type of signal or stimuli received. The growth of cardiac muscle cells in response to environmental conditions depends on the type, strength and duration of stimuli, and results in adaptive physiological responses or non-adaptive pathological responses. Thyroid hormones (TH) have a direct effect on the heart and induce a cardiac hypertrophy phenotype, which may evolve to heart failure. In this review, we summarize the literature on TH function in the heart by presenting results from experimental studies. We discuss the mechanistic aspects of TH associated with cardiac myocyte hypertrophy, increased cardiac myocyte contractility and electrical remodeling, as well as the associated signaling pathways. In addition to classical crosstalk with the sympathetic nervous system (SNS), emerging work pointing to the new endocrine interaction between TH and the renin-angiotensin system (RAS) is also explored. Given the inflammatory potential of the angiotensin II peptide, this new interaction may open the door for new therapeutic approaches which target the key mechanisms responsible for TH-induced cardiac hypertrophy.
Search for other papers by Peter D Mark in
Google Scholar
PubMed
Search for other papers by Mikkel Andreassen in
Google Scholar
PubMed
Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark
Search for other papers by Claus L Petersen in
Google Scholar
PubMed
Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark
Search for other papers by Andreas Kjaer in
Google Scholar
PubMed
Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark
Search for other papers by Jens Faber in
Google Scholar
PubMed
Purpose
The aim of this study was to investigate structure and function of the heart in subclinical hyperthyroidism (SH) before and after obtaining euthyroidism by radioactive iodine treatment, using high precision and observer-independent magnetic resonance imaging (MRI) technology.
Methods
Cardiac MRI was performed before and after euthyroidism was obtained by radioactive iodine treatment in 12 otherwise healthy patients (11 women and one man, mean age 59 years, range 44–71 years) with a nodular goiter and SH, and compared with eight healthy controls investigated at baseline. Cardiac data were expressed as an index, as per body surface area, except for heart rate (HR) and ejection fraction.
Results
Post-treatment cardiac MRI was performed in median 139 days after a normalized serum TSH value had been recorded. During treatment, serum TSH increased from (median (range)) 0.01 (0.01–0.09) to 0.88 (0.27–3.99) mU/l. Patients with untreated SH had increased resting HR (P<0.01) as well as cardiac index (cardiac output as per body surface area) (P<0.01) compared with controls. Obtaining euthyroidism resulted in a significant decrease in left ventricular mass index (LVMI) of 2.7 g/m2 (P=0.034), in HR of 8 bpm (P=0.001), and in cardiac index of 0.24 l/min per m2 (P=0.017).
Conclusions
Normalization of thyroid function by radioactive iodine treatment of SH resulted in significant reductions in clinically important heart parameters such as LVMI, HR, and cardiac index. SH should be regarded as a condition in which aggressive treatment should be considered to protect cardiac function.
Search for other papers by Mette Faurholdt Gude in
Google Scholar
PubMed
Steno Diabetes Centre Odense, Odense University Hospital, Odense, Denmark
Search for other papers by Rikke Hjortebjerg in
Google Scholar
PubMed
Search for other papers by Mette Bjerre in
Google Scholar
PubMed
Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Morten Haaning Charles in
Google Scholar
PubMed
Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Daniel R Witte in
Google Scholar
PubMed
Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Annelli Sandbæk in
Google Scholar
PubMed
Search for other papers by Jan Frystyk in
Google Scholar
PubMed
Objective
Physiologically, pregnancy-associated plasma protein-A (PAPP-A) serves to liberate bound IGF1 by enzymatic cleavage of IGF-binding proteins (IGFBPs), IGFBP4 in particular. Clinically, PAPP-A has been linked to cardiovascular disease (CVD). Stanniocalcin-2 (STC2) is a natural inhibitor of PAPP-A enzymatic activity, but its association with CVD is unsettled. Therefore, we examined associations between the STC2–PAPP-A–IGFBP4–IGF1 axis and all-cause mortality and CVD in patients with type 2 diabetes (T2D).
Design
We followed 1284 participants with T2D from the ADDITION trial for 5 years.
Methods
Circulating concentrations of STC2, PAPP-A, total and intact IGFBP4 and IGF1 and -2 were measured at inclusion. End-points were all-cause mortality and a composite CVD event: death from CVD, myocardial infarction, stroke, revascularisation or amputation. Survival analysis was performed by Cox proportional hazards model.
Results
During follow-up, 179 subjects presented with an event. After multivariable adjustment, higher levels of STC2, PAPP-A, as well as intact and total IGFBP4, were associated with all-cause mortality; STC2: hazard ratio (HR) = 1.84 (1.09–3.12) (95% CI); P = 0.023, PAPP-A: HR = 2.81 (1.98–3.98); P < 0.001, intact IGFBP4: HR = 1.43 (1.11–1.85); P = 0.006 and total IGFBP4: HR = 3.06 (1.91–4.91); P < 0.001. Higher PAPP-A levels were also associated with CVD events: HR = 1.74 (1.16–2.62); P = 0.008, whereas lower IGF1 levels were associated with all-cause mortality: HR = 0.51 (0.34–0.76); P = 0.001.
Conclusions
This study supports that PAPP-A promotes CVD and increases mortality. However, STC2 is also associated with mortality. Given that STC2 inhibits the enzymatic effects of PAPP-A, we speculate that STC2 either serves to counteract harmful PAPP-A actions or possesses effects independently of the PAPP-A–IGF1 axis.
Significance statement
PAPP-A has pro-atherosclerotic effects and exerts these most likely through IGF1. IGF1 is regulated by the STC2–PAPP-A–IGFBP4–IGF1 axis, where STC2, an irreversible inhibitor of PAPP-A, has been shown to reduce the development of atherosclerotic lesions in mice. We examined the association of this axis to mortality and CVD in T2D. We demonstrated an association between PAPP-A and CVD. All components of the STC2–PAPP-A–IGFBP4–IGF1 axis were associated with mortality and it is novel that STC2 was associated with mortality in T2D. Our study supports that inhibition of PAPP-A may be a new approach to reducing mortality and CVD. Whether modification of STC2 could serve as potential intervention warrants further investigation.
Search for other papers by Lasse Oinonen in
Google Scholar
PubMed
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Search for other papers by Antti Tikkakoski in
Google Scholar
PubMed
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Search for other papers by Jenni Koskela in
Google Scholar
PubMed
Search for other papers by Arttu Eräranta in
Google Scholar
PubMed
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Search for other papers by Mika Kähönen in
Google Scholar
PubMed
Search for other papers by Onni Niemelä in
Google Scholar
PubMed
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Search for other papers by Jukka Mustonen in
Google Scholar
PubMed
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Search for other papers by Ilkka Pörsti in
Google Scholar
PubMed
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.
