Cardiac Obesity and Cardiac Cachexia: Is There a Pathophysiological Link?

Obesity is a risk factor for cardiometabolic and vascular diseases like arterial hypertension, diabetes mellitus type 2, dyslipidaemia, and atherosclerosis. A special role in obesity-related syndromes is played by cardiac visceral obesity, which includes epicardial adipose tissue and intramyocardial fat, leading to cardiac steatosis; hypertensive heart disease; atherosclerosis of epicardial coronary artery disease; and ischemic cardiomyopathy, cardiac microcirculatory dysfunction, diabetic cardiomyopathy, and atrial fibrillation. Cardiac expression of these changes in any given patient is unique and multimodal, varying in clinical settings and level of expressed changes, with heart failure development depending on pathophysiological mechanisms with preserved, midrange, or reduced ejection fraction. Progressive heart failure with misbalanced metabolic and catabolic processes will change muscle, bone, and fat mass and function, with possible changes in the cardiac fat state from excessive accumulation to reduction and cardiac cachexia with a worse prognosis. The question we address is whether cardiac obesity or cardiac cachexia is to be more feared.

Time of Anderson-Fabry Disease Detection and Cardiovascular Presentation.

BACKGROUND: Anderson-Fabry disease is an X-linked inherited disease, which manifests in a different manner depending on gender and genotype. Making a working diagnosis of Anderson-Fabry disease is difficult because of several reasons: (a) that it is a multiorgan disease with wide variety of phenotypes, (b) different timelines of presentation, (c) gender differences, and (d) possible coexistence with other comorbidities. Late-onset/cardiac type of presentation with minimal involvement of other organs can additionally make diagnosis difficult. AIM: To describe different cardiac manifestations at different time points in the course of the disease: (1) 72-year-old female (echocardiography detection), heterozygote, significant left and mild right ventricular hypertrophy; (2) 62-year-old male (echocardiography detection), hemizygote, left ventricular hypertrophy, implanted cardiac pacemaker, a performed percutaneous coronary intervention after myocardial infarction, degenerative medium degree aortic valve stenosis; (3) 45-year-old female (asymptomatic/family screening), heterozygote, thickened mitral papillary muscle, mild left ventricular hypertrophy, first degree diastolic dysfunction; and (4) 75-year-old female (symptomatic/family screening), heterozygote, cardiomyopathy with reduced left ventricular ejection fraction after heart surgery (mitral valve annuloplasty and plastic repair of the tricuspid valve). CONCLUSION: All patients have Anderson-Fabry disease but with different clinical presentations depending on the gender, the type of mutation, and the time of detection. All these features can make the patients' profiles unique and delay the time of detection.

Leptin/adiponectin ratio in overweight patients - gender differences.

OBJECTIVE: Obesity-related atherosclerosis is a systemic disease with a background connected to multiple metabolic-neurohumoral pathways. The leptin/adiponectin ratio has been suggested as an atherosclerotic marker in obese patients. The aim of this study was to assess (1) the significance of the L/A ratio in overweight subjects, (2) the relation with anthropometric/metabolic parameters and (3) gender difference. METHOD: The study included 80 adult males and females, overweight, non-diabetic patients. Biochemical blood analysis and anthropometric and cardiovascular measurements were performed. Serum leptin levels were measured with a radioimmunoassay test and total adiponectin levels with enzyme-linked immunosorbent assay. Leptin/adiponectin ratios were calculated as ratios between total serum concentrations of leptin and adiponectin. RESULTS: Differences between leptin, adiponectin serum levels and leptin/adiponectin ratios are presented in overweight persons, where females have a significantly higher leptin/adiponectin ratio than men ( p < 0.001). In men, the leptin/adiponectin ratio showed a positive correlation with total cholesterol levels ( p = 0.011), low-density lipoprotein ( p = 0.013) and triglycerides ( p = 0.032). In females, the leptin/adiponectin ratio correlated with anthropometric parameters of visceral obesity: waist circumference ( p = 0.001) and waist-to-hip ratio ( p = 0.025). CONCLUSION: The leptin/adiponectin ratio could represent an atherosclerotic risk marker of the early stage of obesity. Gender plays a significant role in pathophysiological changes, with different clinical manifestations, where sex hormones have a crucial effect on neurohumoral adipose tissue activity.

Obesity Related Coronary Microvascular Dysfunction: From Basic to Clinical Practice.

Obesity related coronary microvascular disease is a medical entity which is not yet fully elucidated. The pathophysiological basis of coronary microcirculatory dysfunction consists of a heterogeneous group of disorders with individual morphologic/functional/clinical presentation and prognosis. Coronary microcirculatory changes include mechanisms connected with vascular dysfunction, as well as extravascular and vasostructural changes in responses to neural, mechanical, and metabolic factors. Cardiometabolic changes that include obesity, dyslipidemia, diabetes mellitus type II, and hypertension are associated with atherosclerosis of epicardial coronary arteries and/or microvascular coronary dysfunction, with incompletely understood underlying mechanisms. In obesity, microvascular disease is mediated via adipokines/cytokines causing chronic, subclinical inflammation with (a) reduced NO-mediated dilatation, (b) changed endothelial- and smooth muscle-dependent vasoregulating mechanisms, (c) altered vasomotor control with increased sympathetic activity, and (d) obesity related hypertension with cardiomyocytes hypertrophy and impaired cardiac vascular adaptation to metabolic needs. From a clinical point of view it can present itself in acute or chronic form with different prognosis, as a practice problem for real-life diagnosis and treatment.

Visfatin serum level and expression in subcutaneous and visceral adipose tissue in prepubertal boys.

BACKGROUND: The biological role of visfatin in humans, especially in eutrophic and healthy children, is not understood yet, except for its link to obesity-related disorders in adolescents and adults. OBJECTIVES: To determine the physiological values of serum visfatin concentrations, and visfatin mRNA expression in subcutaneous (SAT) and visceral adipose tissue (VAT), and to correlate them with anthropometric/metabolic data in prepubertal healthy boys. METHODS: The study included 59 healthy boys, age 1-10 years, hospitalized for elective surgery, divided according to age into group I (1-3 years old), group II (3-7 years old) and group III (7-10 years old). Anthropometric and biochemical measurements, and the visfatin serum and mRNA level in SAT and VAT were determined in all patients. RESULTS: Visfatin mRNA expression was higher in SAT compared with VAT in all three studied groups. Highest visfatin mRNA was found in SAT of group III compared with group II (P = 0.030). VAT visfatin mRNA expression negatively correlates with body weight (P = 0.039), waist circumference (P = 0.027) and morning glucose level (P = 0.007). CONCLUSION: Lack of changes in serum visfatin level despite the changes in visfatin mRNA expression of adipose tissue suggests paracrine effect of visfatin rather than endocrine. Negative correlation of visfatin VAT mRNA expression with anthropometric parameters indicates important role of VAT visfatin in maturation and in glucose metabolism.

Myocardial fat as a part of cardiac visceral adipose tissue: physiological and pathophysiological view.

Thoracic fat includes extra-pericardial (outside the visceral pericardium) and intra-pericardial (inside the visceral pericardium) adipose tissue. It is called ectopic adipose tissue although it is a normal anatomical structure. Intra-pericardial adipose tissue, which is predominantly composed of epicardial and pericoronary adipose tissue, has a significant role in cardiovascular system function. It provides metabolic-mechanical support to the heart and blood vessels in physiological conditions, while it represents metabolic-cardiovascular risk in case of qualitative and quantitative structural changes in the tissue: it correlates with coronary atherosclerotic disease, left ventricular mass, left atrium enlargement and atrial fibrillation presence. In the last decade there has been mounting evidence of fat cells presence in the myocardium of healthy (non-diseased) persons as well as in persons with both cardiovascular and non-cardiovascular diseases. Thus, it is necessary to clarify the incidence, aetiology, physiological role of fat cells in the myocardium, as well as the clinical significance of pathological fatty infiltration of the myocardium.

The interplay between sympathetic overactivity, hypertension and heart rate variability (review, invited).

The control of arterial pressure is a complex interaction of the long- and short-term influences of hormones, local vascular factors, and neural mechanisms. The autonomic nervous system and its sympathetic arm play important roles in the regulation of blood pressure, and overactivity of sympathetic nerves may have an important role in the development of hypertension and related cardiovascular disorders. The baroreceptor system opposes either increases or decreases in arterial pressure, and the primary purpose of the arterial baroreflex is to keep blood pressure close to a particular set point over a relatively short period of time. The ability of the baroreflex to powerfully buffer acute changes in arterial pressure is well established, but the role of the arterial baroreceptor reflex in long-term control of arterial pressure has been a topic of many debate and controversy for decades. The sympathetic nervous system and arterial baroreceptor reflex control of renal sympathetic nerve activity has been proposed to play a role in long-term control of arterial pressure. The aim of this paper has been to review the postulated role of sympathetic activation.