Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. This review summaries the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS

Right Side of the Heart Pulmonary Circulation Unit Involvement in Left-Sided Heart Failure br Diagnostic, Prognostic, and Therapeutic Implications From the Forgotten Chamber to the Chamber of Secrets

Although long neglected, the right side of the heart (RH) is now widely accepted as a pivotal player in heart failure (HF) either with reduced or preserved ejection fraction. The chronic overload of the pulmonary microcirculation results in an initial phase characterized by right ventricular (RV) hypertrophy, right atrial dilation, and diastolic dysfunction. This progresses to overt RH failure when RV dilation and systolic dysfunction lead to RV-pulmonary arterial (RV-PA) uncoupling with low RV output. In the context of its established relevance to progression of HF, clinicians should consider assessment of the RH with information from clinical assessment, biomarkers, and imaging. Notably, no single parameter can predict prognosis alone in HF. Assessments simultaneously should encompass RV systolic function, pulmonary pressures, an estimation of RV-PA coupling, and RH morphologic features. Despite a large volume of evidence indicating the relevance of RH function to the clinical syndrome of HF, evidence-based management strategies are lacking. Targeting RH dysfunction in HF should be an objective of future investigations, being an unmet need in the current management of HF

Clinical characteristics of insulin resistant and non-insulin resistant obese and control children/adolescents.

<p>Data represent mean±SD;</p><p>*, p<0.05 vs controls;</p><p>^†, p<0.05 vs IR-</p><p>IR+, insulin resistant obese subjects; IR-, non-insulin resistant obese subjects; HOMA-IR, homeostasis model assessment of insulin resistance; hsCRP, high sensitivity C-reactive protein; LF_RR, low frequency power of R-R variability; nu, normalized units; HF_RR, high frequency power of R-R variability; LF_SBP, low frequency power of systolic blood pressure variability.</p><p>Clinical characteristics of insulin resistant and non-insulin resistant obese and control children/adolescents.</p

Relationship between the left ventricular e'/a' ratio and HOMA-IR index in the whole group of obese subjects (insulin resistant, circles; non-insulin resistant, triangles).

<p>e’, early peak diastolic tissue Doppler velocity; a’, late peak diastolic tissue Doppler velocity; HOMA-IR, homeostasis model assessment of insulin resistance.</p

Δ Changes induced by tilting on hemodynamics and cardiovascular autonomic regulation in insulin resistant and non-insulin resistant obese and control children/adolescents.

<p>LF_RR, low frequency power of R-R variability; nu, normalized units; HF_RR, high frequency power of R-R variability; LF_SBP, low frequency power of systolic blood pressure variability; IR+, insulin resistant obese subjects; IR-, non-insulin resistant obese subjects; C, control subjects. Individual data in the 3 groups of subjects together with their mean value and relative SD are depicted; tilt-induced Δ changes were compared; *, p<0.05 vs controls; †, p<0.05 vs IR-; ‡, p<0.05 vs baseline.</p

Relationship between tilt-induced Δ changes in the LF_RR/HF_RR ratio and HOMA-IR index in the whole group of obese subjects (insulin resistant, circles; non-insulin resistant, triangles).

<p>LF_RR, low frequency power of R-R variability; HF_RR, high frequency power of R-R variability; HOMA-IR, homeostasis model assessment of insulin resistance.</p

Biomarkers of acute cardiovascular and pulmonary diseases

Acute cardiothoracic and respiratory diseases frequently remain a challenge to diagnose and differentiate in the emergency setting. The main diseases that manifest with chest pain include ischaemic heart disease, myocarditis, acute pericarditis, aortic dissection/rupture and pulmonary embolism (PE). Diseases that primarily present with dyspnoea include heart failure (HF), acute respiratory distress syndrome (ARDS), pneumonia, asthma exacerbations and chronic obstructive pulmonary disease. Pre-test probabilities of clinical findings play a vital part in diagnostic decisions, and the use of a Bayesian approach to these greatly improves the ability to stratify patients more accurately. However, blood tests (biomarkers) are increasingly used to assist in rapid decision-making in the emergency setting in combination with imaging methods such as chest radiograph, ultrasound and increasingly computed tomography, as well as physiological tests such as the electrocardiogram in addition to physical examination. Specific tests for ischaemic heart disease and myocarditis (cardiac troponins), HF (B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP)), aortic dissection (smooth muscle markers) and PE (D-dimer) have been developed. Surfactant protein-D and interleukin-8 have been developed for ARDS. Additionally, circulating microRNAs have emerged as promising biomarker candidates in cardiovascular disease. With this increasing array of biochemical markers to aid in the diagnosis of chest diseases presenting with chest pain and dyspnoea, we herein review the clinical usefulness of these markers, in particular in differentiating cardiac from pulmonary diseases. A symptom-oriented assessment as necessary for use in the critical setting is described in addition to discussion of individual biomarkers

Number of responses and % agreement (strongly agree/agree) to statements relating to patient centred polypharmacy reviews.

<p>Number of responses and % agreement (strongly agree/agree) to statements relating to patient centred polypharmacy reviews.</p

Clinical and biochemical indexes in GH sufficient and GH deficient patients with CHF.

<p>Clinical and biochemical indexes in GH sufficient and GH deficient patients with CHF.</p

Cox-regression analysis.

<p>Cox-regression analysis.</p