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Akinori Sairaku Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

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Yukiko Nakano Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

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Yuko Uchimura Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

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Takehito Tokuyama Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

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Hiroshi Kawazoe Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

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Yoshikazu Watanabe Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

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Hiroya Matsumura Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

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Yasuki Kihara Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

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Background

The impact of subclinical hypothyroidism on the cardiovascular risk is still debated. We aimed to measure the relationship between subclinical hypothyroidism and the left atrial (LA) pressure.

Methods

The LA pressures and thyroid function were measured in consecutive patients undergoing atrial fibrillation (AF) ablation, who did not have any known heart failure, structural heart disease, or overt thyroid disease.

Results

Subclinical hypothyroidism (4.5≤ thyroid-stimulating hormone <19.9 mIU/L) was present in 61 (13.0%) of the 471 patients included. More subclinical hypothyroidism patients than euthyroid patients (55.7% vs 40.2%; P=0.04).’euthyroid patients had persistent or long-standing persistent AF (55.7% vs 40.2%; P = 0.04). The mean LA pressure (10.9 ± 4.7 vs 9.1 ± 4.3 mmHg; P = 0.002) and LA V-wave pressure (17.4 ± 6.5 vs 14.3 ± 5.9 mmHg; P < 0.001) were, respectively, higher in the patients with subclinical hypothyroidism than in the euthyroid patients. After an adjustment for potential confounders, the LA pressures remained significantly higher in the subclinical hypothyroidism patients. A multiple logistic regression model showed that subclinical hypothyroidism was independently associated with a mean LA pressure of >18 mmHg (odds ratio 3.94, 95% CI 1.28 11.2; P = 0.02).

Conclusions

Subclinical hypothyroidism may increase the LA pressure in AF patients.

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Jens P Goetze
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Linda M Hilsted
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Jens F Rehfeld
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Urban Alehagen Department of Clinical Biochemistry, Division of Cardiovascular Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Cardiovascular risk assessment remains difficult in elderly patients. We examined whether chromogranin A (CgA) measurement in plasma may be valuable in assessing risk of death in elderly patients with symptoms of heart failure in a primary care setting. A total of 470 patients (mean age 73 years) were followed for 10 years. For CgA plasma measurement, we used a two-step method including a screening test and a confirmative test with plasma pre-treatment with trypsin. Cox multivariable proportional regression and receiver-operating curve (ROC) analyses were used to assess mortality risk. Assessment of cardiovascular mortality during the first 3 years of observation showed that CgA measurement contained useful information with a hazard ratio (HR) of 5.4 (95% CI 1.7–16.4) (CgA confirm). In a multivariate setting, the corresponding HR was 5.9 (95% CI 1.8–19.1). When adding N-terminal proBNP (NT-proBNP) to the model, CgA confirm still possessed prognostic information (HR: 6.1; 95% CI 1.8–20.7). The result for predicting all-cause mortality displayed the same pattern. ROC analyses in comparison to NT-proBNP to identify patients on top of clinical variables at risk of cardiovascular death within 5 years of follow-up showed significant additive value of CgA confirm measurements compared with NT-proBNP and clinical variables. CgA measurement in the plasma of elderly patients with symptoms of heart failure can identify those at increased risk of short- and long-term mortality.

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Xiaoyi Qi Departments of Cardiology, Peking University Shenzhen Hospital, Shenzhen, China
Medical College, Shantou University, Shantou, China

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Liangxian Qiu Departments of Cardiology, Peking University Shenzhen Hospital, Shenzhen, China

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Shijia Wang Departments of Cardiology, Peking University Shenzhen Hospital, Shenzhen, China

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Xiongbiao Chen Departments of Cardiology, Peking University Shenzhen Hospital, Shenzhen, China

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Qianwen Huang Departments of Cardiology, Peking University Shenzhen Hospital, Shenzhen, China

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Yixuan Zhao Departments of Cardiology, Peking University Shenzhen Hospital, Shenzhen, China
Medical College, Shantou University, Shantou, China

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Kunfu Ouyang Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, China

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Yanjun Chen Departments of Cardiology, Peking University Shenzhen Hospital, Shenzhen, China

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Background

Heart failure (HF) is a complex and multifactorial syndrome caused by impaired heart function. The high morbidity and mortality of HF cause a heavy burden of illness worldwide. Non-thyroidal illness syndrome (NTIS) refers to aberrant serum thyroid parameters in patients without past thyroid disease. Observational studies have indicated that NTIS is associated with a higher risk of all-cause mortality in HF. This meta-analysis aimed to investigate the association between NTIS and HF prognosis.

Methods

Medline, Embase, Web of Science, and the Cochrane database were searched for any studies reporting an association between NTIS and HF prognosis from inception to 1 July 2022. A meta-analysis was then performed. The quality of studies was assessed using the Newcastle–Ottawa Scale. The heterogeneity of the results was assessed with I 2 and Cochran's Q statistics. Sensitivity analysis and publication bias analysis were also conducted.

Results

A total of 626 studies were retrieved, and 18 studies were finally included in the meta-analysis. The results showed that NTIS in HF patients was significantly associated with an increased risk of all-cause mortality and major cardiovascular events (MACE), but not with in-hospital mortality. The stability of the data was validated by the sensitivity analysis. There was no indication of a publication bias in the pooled results for all-cause mortality and MACE.

Conclusions

This meta-analysis showed that NTIS was associated with a worse outcome in HF patients. However, the association between NTIS and in-hospital mortality of HF patients requires further investigation.

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Shuang Wan Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
Department of Endocrinology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China

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Chengcheng Zheng Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Tao Chen Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Lu Tan Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Jia Tang Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Haoming Tian Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Yan Ren Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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We applied 24-h Holter monitoring to analyze the characteristics of arrhythmias and heart rate variability in Chinese patients with primary aldosteronism (PA) and compared them with age-, sex-, and blood pressure-matched primary hypertension (PH) patients. A total of 216 PA patients and 261 PH patients were enrolled. The nonstudy data were balanced using propensity score matching (PSM), and the risk variables for developing arrhythmias were then analyzed using logistic regression analysis. Before PSM, the proportion of PA patients with combined atrial premature beats and prolonged QT interval was higher than the corresponding proportion in the PH group. After PSM, the PA group had a larger percentage of transient atrial tachycardia and frequent atrial premature beats, and it had higher heart rate variability metrics. The proportion of unilateral PA combined with multiple ventricular premature beats was higher than that of bilateral PA. Older age, grade 3 hypertension, and hypokalemia were independent risk factors for the emergence of arrhythmias in PA patients. PA patients suffer from a greater prevalence of arrhythmias than well-matched PH patients.

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Shenghe Luo College of Pharmacy, Yanbian University, Yanji, China

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Yunhui Zuo Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China
Department of Cardiology, Yanbian University Hospital, Yanji, China

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Xiaotian Cui Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China

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Meiping Zhang Department of Cardiology, Yanbian University Hospital, Yanji, China

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Honghua Jin Department of Pharmacy, Yanbian University Hospital, Yanji, China

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Lan Hong Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China

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To observe the effects of liraglutide (analog of glucagon-like peptide 1 (GLP-1)) on atrial natriuretic peptide (ANP) secretion and atrial dynamics, an ex vivo isolated rat atrial perfusion model was used to determine atrial ANP secretion and pulse pressure. DPP-4−/− mice were also established in vivo. ANP levels were determined by radioimmunoassay; GLP-1 content was determined by Elisa. The expression levels of GLP-1 receptor (GLP-1R), PI3K/AKT/mTOR, piezo 1, and cathepsin K were analyzed by Western blot. In the clinical study, patients with acute coronary syndrome (ACS) had low levels of plasma GLP-1 but relatively high levels of plasma ANP. In ex vivo (3.2 nmol/L) and in vivo (30 μg/kg) models, liraglutide significantly decreased ANP levels and atrial pulse pressure. Exendin9–39 alone (GLP-1R antagonist) reversibly significantly increased ANP secretion, and the reduction effect of liraglutide on the secretion of ANP was significantly alleviated by Exendin9–39. Exendin9–39 demonstrated slightly decreased atrial pulse pressure; however, combined liraglutide and Exendin9–39 significantly decreased atrial pulse pressure. Ly294002 (PI3K/AKT inhibitor) inhibited the increase of ANP secretion by liraglutide for a short time, while Ly294002 didn't counteract the decrease in pulse pressure by liraglutide in atrial dynamics studies. Liraglutide increased the expression of GLP-1R and PI3K/AKT/mTOR in isolated rat atria and the hearts of mice in vivo, whereas Exendin9–39 reversibly reduced the expression of GLP-1R and PI3K/AKT/mTOR. Piezo 1 was significantly decreased in wild type and DPP-4−/− mouse heart or isolated rat atria after being treated with liraglutide. Cathepsin K expression was only decreased in in vivo model hearts. Liraglutide can inhibit ANP secretion while decreasing atrial pulse pressure mediated by GLP-1R. Liraglutide probably plays a role in the reduction of ANP secretion via the PI3K/AKT/mTOR signaling pathway. Piezo 1 and cathepsin K may be involved in the liraglutide mechanism of reduction.

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Willem de Ronde Department of Internal Medicine, Spaarne Gasthuis, Haarlem, the Netherlands

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Diederik L Smit Department of Internal Medicine, Spaarne Gasthuis, Haarlem, the Netherlands

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This review summarizes 10 years experience with male abusers of anabolic androgenic steroids (AAS). The typical user of AAS is male, aged between 20 and 40 and lifting weights. Illegal AAS are cheap and easily obtained via internet or local suppliers. AAS are mostly used in cycles with a duration between 6 and 18 weeks. Most AAS cycles contain multiple agents, used simultaneously in a dose vastly exceeding a substitution dose. A variety of other performance and image-enhancing drugs are commonly used, including human growth hormone, thyroid hormone, tamoxifen, clomiphene citrate and human chorionic gonadotrophin. Short-term clinical and biochemical side effects are well established. Long-term side effects are uncertain, but may include heart failure, mood-and anxiety disorders, hypogonadism and subfertility. We share our views on the management of common health problems associated with AAS abuse.

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Melinda Kertész Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Szilárd Kun Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Eszter Sélley Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Zsuzsanna Nagy Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Tamás Kőszegi Department of Laboratory Medicine, Medical School, University of Pécs, Pécs, Baranya, Hungary

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István Wittmann Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Background

Type 2 diabetes is characterized, beyond the insulin resistance, by polyhormonal resistance. Thyroid hormonal resistance has not yet been described in this population of patients. Metformin is used to decrease insulin resistance, and at present, it is assumed to influence the effect of triiodothyronine, as well.

Methods

In this open-label, pilot, hypothesis-generating, follow-up study, 21 patients were included; all of them were euthyroid with drug naïve, newly diagnosed type 2 diabetes. Before and after 4 weeks of metformin therapy, fructosamine, homeostasis model assessment for insulin resistance (HOMA-IR), thyroid hormones, T3/T4 ratio, and TSH, as well as blood pressure and heart rate using ambulatory blood pressure monitor were measured. We also conducted an in vitro study to investigate the possible mechanisms of T3 resistance, assessing T3-induced Akt phosphorylation among normal (5 mM) and high (25 mM) glucose levels with or without metformin treatment in a human embryonal kidney cell line.

Results

Metformin decreased the level of T3 (P < 0.001), the ratio of T3/T4 (P = 0.038), fructosamine (P = 0.008) and HOMA-IR (P = 0.022). All these changes were accompanied by an unchanged TSH, T4, triglyceride, plasma glucose, bodyweight, blood pressure, and heart rate. In our in vitro study, T3-induced Akt phosphorylation decreased in cells grown in 25 mM glucose medium compared to those in 5 mM. Metformin could not reverse this effect.

Conclusion

Metformin seems to improve T3 sensitivity in the cardiovascular system in euthyroid, type 2 diabetic patients, the mechanism of which may be supracellular.

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Chaiho Jeong Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Bongseong Kim Department of Medical Statistics, Soongsil University of Korea, Seoul, Republic of Korea

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Jinyoung Kim Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Hansang Baek Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Mee Kyoung Kim Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Tae-Seo Sohn Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Ki-Hyun Baek Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Ki-Ho Song Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Hyun-Shik Son Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Kyungdo Han Department of Medical Statistics, Soongsil University of Korea, Seoul, Republic of Korea

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Hyuk-Sang Kwon Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Objective

Real-world-based population data about the optimal low-density lipoprotein cholesterol (LDL-C) level for preventing cardiovascular disease in very high-risk populations is scarce.

Methods

From 2009 to 2012, 26,922 people aged ≥ 40 years with type 2 diabetes mellitus (T2DM) who had a history of percutaneous coronary intervention (PCI) were analyzed. Data from the Korean National Health Insurance System were used. They were followed up to the date of a cardiovascular event or the time to death, or until December 31, 2018. Endpoints were recurrent PCI, newly stroke or heart failure, cardiovascular death, and all-cause death. Participants were divided into the following categories according to LDL-C level: <55 mg/dL, 55–69 mg/dL, 70–99 mg/dL, 100–129 mg/dL, 130–159 mg/dL, and ≥ 160 mg/dL.

Results

Compared to LDL-C < 55 mg/dL, the hazard ratios (HR) for re-PCI and stroke increased linearly with increasing LDL-C level in the population < 65 years. However, in ≥ 65 years old, HRs for re-PCI and stroke in LDL-C = 55–69 mg/dL were 0.97 (95% CI: 0.85–1.11) and 0.96 (95% CI: 0.79–2.23), respectively. The optimal range with the lowest HR for heart failure and all-cause mortality were LDL-C = 70–99 mg/dL and LDL-C = 55–69 mg/dL, respectively, in all age groups (HR: 0.99, 95% CI: 0.91–1.08 and HR: 0.91, 95% CI: 0.81–1.01).

Conclusion

LDL-C level below 55 mg/dL appears to be optimal in T2DM patients with established cardiovascular disease aged < 65 years, while an LDL-C level of 55–69 mg/dL may be optimal for preventing recurrent PCI and stroke in patients over 65 years old.

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Leyre Lorente-Poch Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain
Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain

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Sílvia Rifà-Terricabras Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain

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Juan José Sancho Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain
Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain

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Danilo Torselli-Valladares Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain

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Sofia González-Ortiz Department of Radiology, Hospital del Mar, Barcelona, Spain

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Antonio Sitges-Serra Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain
Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain

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Objective:

Permanent hypoparathyroidism is an uncommon disease resulting most frequently from neck surgery. It has been associated with visceral calcifications but few studies have specifically this in patients with post-surgical hypoparathyroidism. The aim of the present study was to assess the prevalence of basal ganglia and carotid artery calcifications in patients with long-term post-thyroidectomy hypoparathyroidism compared with a control population.

Design:

Case–control study.

Methods:

A cross-sectional review comparing 29 consecutive patients with permanent postoperative hypoparathyroidism followed-up in a tertiary reference unit for Endocrine Surgery with a contemporary control group of 501 patients who had an emergency brain CT scan. Clinical variables and prevalence of basal ganglia and carotid artery calcifications were recorded.

Results:

From a cohort of 46 patients diagnosed with permanent hypoparathyroidism, 29 were included in the study. The mean duration of disease was 9.2 ± 7 years. Age, diabetes, hypertension, smoking and dyslipidemia were similarly distributed in case and control groups. The prevalence of carotid artery and basal ganglia calcifications was 4 and 20 times more frequent in patients with permanent hypoparathyroidism, respectively. After propensity score matching of the 28 the female patients, 68 controls were matched for age and presence of cardiovascular factors. Cases showed a four-fold prevalence of basal ganglia calcifications, whereas that of carotid calcifications was similar between cases and controls.

Conclusion:

A high prevalence of basal ganglia calcifications was observed in patients with post-surgical permanent hypoparathyroidism. It remains unclear whether carotid artery calcification may also be increased.

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Ermina Bach Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Niels Møller Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Jens Otto L Jørgensen Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Mads Buhl The Neonatal Intensive Care Unit, Aarhus University Hospital, Aarhus, Denmark

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Holger Jon Møller Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

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Aims/hypothesis

The macrophage-specific glycoprotein sCD163 has emerged as a biomarker of low-grade inflammation in the metabolic syndrome and related disorders. High sCD163 levels are seen in acute sepsis as a result of direct lipopolysaccharide-mediated shedding of the protein from macrophage surfaces including Kupffer cells. The aim of this study was to investigate if low-grade endotoxinemia in human subjects results in increasing levels of sCD163 in a cortisol-dependent manner.

Methods

We studied eight male hypopituitary patients and eight age- and gender-matched healthy controls during intravenous low-dose LPS or placebo infusion administered continuously over 360 min. Furthermore, we studied eight healthy volunteers with bilateral femoral vein and artery catheters during a 360-min infusion with saline and low-dose LPS in each leg respectively.

Results:

Systemic low-grade endotoxinemia resulted in a gradual increase in sCD163 from 1.65 ± 0.51 mg/L (placebo) to 1.92 ± 0.46 mg/L (LPS) at 220 min, P = 0.005 and from 1.66 ± 0.42 mg/L (placebo) to 2.19 ± 0.56 mg/L (LPS) at 340 min, P = 0.006. A very similar response was observed in hypopituitary patients: from 1.59 ± 0.53 mg/L (placebo) to 1.83 ± 0.45 mg/L (LPS) at 220 min, P = 0.021 and from 1.52 ± 0.53 mg/L (placebo) to 2.03 ± 0.44 mg/L (LPS) at 340 min, P < 0.001. As opposed to systemic treatment, continuous femoral artery infusion did not result in increased sCD163.

Conclusion:

Systemic low-grade endotoxinemia resulted in increased sCD163 to levels seen in the metabolic syndrome in both controls and hypopituitary patients. This suggests a direct and cortisol-independent effect of LPS on the shedding of sCD163. We observed no effect of local endotoxinemia on levels of serum sCD163.

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