Rate and Extent of Recovery from Reproductive and Cardiac Dysfunction Due to Androgen Abuse in Men.

CONTEXT: Androgen abuse impairs male reproductive and cardiac function, but the rate, extent, and determinants of recovery are not understood. OBJECTIVE: To investigate recovery of male reproductive and cardiac function after ceasing androgen intake in current and past androgen abusers compared with healthy non-users. METHODS: Cross-sectional, observational study recruited via social media 41 current and 31 past users (≥3 months since last use, median 300 days since last use) with 21 healthy, eugonadal non-users. Each provided a history, examination, and serum and semen sample and underwent testicular ultrasound, body composition analysis, and cardiac function evaluation. RESULTS: Current abusers had suppressed reproductive function and impaired cardiac systolic function and lipoprotein parameters compared with non- or past users. Past users did not differ from non-users, suggesting full recovery of suppressed reproductive and cardiac functions after ceasing androgen abuse, other than residual reduced testicular volume. Mean time to recovery was faster for reproductive hormones (anti-Mullerian hormone [AMH], 7.3 months; luteinizing hormone [LH], 10.7 months) than for sperm variables (output, 14.1 months) whereas spermatogenesis (serum follicle-stimulating hormone [FSH], inhibin B, inhibin) took longer. The duration of androgen abuse was the only other variable associated with slower recovery of sperm output (but not hormones). CONCLUSION: Suppressed testicular and cardiac function due to androgen abuse is effectively fully reversible (apart from testis volume and serum sex hormone binding globulin) with recovery taking between 6 to 18 months after ceasing androgen intake with possible cumulative effects on spermatogenesis. Suppressed serum AMH, LH, and FSH represent convenient, useful, and underutilized markers of recovery from androgen abuse.

Follow-Up of Pulmonary Hypertension With Echocardiography.

Individual patient response to effective therapies for pulmonary hypertension (PAH) is variable and difficult to quantify. Consequently, management decisions regarding initiation and continuation of therapy are highly dependent on the results of investigations. Registry data show that changes in cardiac index, mean right atrial pressure, and mean pulmonary artery pressure have the greatest influence on survival. It is recognized that pulmonary artery pressure (PASP) responses to PAH-specific drugs are heterogeneous. However, follow-up testing is strongly focused on assessing changes in PASP and functional status (6-min walk). The goals of therapy, which should be highlighted in follow-up imaging, include not only reduction of PASP, decrease in pulmonary vascular resistance, and improvements in right ventricular function, cardiac output, and tricuspid regurgitation. This paper reviews the echocardiographic follow-up of pulmonary hypertension, and especially focuses on right ventricular function-a major determinant of outcome, for which reliable echocardiographic assessment has become more feasible.

Endothelial activation after coronary artery bypass surgery: comparison between on-pump and off-pump techniques.

BACKGROUND: The effects of off-pump coronary artery bypass (OPCAB) surgery on endothelial cell activation are poorly understood. Endothelial cell adhesion molecules (CAMs) are expressed and released when the endothelium is activated. We compared plasma CAMs (E-selectin, ICAM-1 and VCAM-1) and HUVEC expression of the same CAMs when exposed to plasma taken before, during and after OPCAB or on-pump coronary surgery (CABG). METHODS: Patients undergoing first time CABG (n=10) or OPCAB (n=10) had 6 blood samples taken before surgery and up to 24h post-operatively. Plasma samples were assayed for E-selectin, ICAM-1 and VCAM-1. The same plasma samples were exposed to HUVEC cultures and cell-surface expression of E-selectin, ICAM-1 and VCAM-1 measured. Data are expressed as mean+/-SEM of n subjects. RESULTS: Plasma E-selectin was unchanged. Plasma ICAM-1 and VCAM-1 were elevated 24h post-operatively in both groups (P<0.01), with no differences between the groups. Twenty-four hours post-OPCAB plasma increased basal and IL-1beta induced expression of endothelial VCAM-1 by 133+/-16% and 140+/-27% (P<0.05), respectively. Plasma taken 3h post-CABG decreased endothelial VCAM-1 expression by 76+/-10% (P<0.05). Peri-operative plasma had no effect on endothelial expression of E-selectin or ICAM-1 in either group. CONCLUSIONS: OPCAB and CABG with CPB appear to generate qualitatively different inflammatory responses with respect to endothelial activation, which may have clinical implications.

Incidence and determinants of myocardial infarction following percutaneous coronary interventions according to the revised Joint Task Force definition of troponin T elevation.

BACKGROUND: Elevations in troponin T (TnT) occur frequently following percutaneous coronary intervention (PCI) and are associated with an adverse prognosis. The Joint ESC/ACC/AHA/WHF Task Force have released a proposal for a universal definition of myocardial infarction (MI), including diagnostic criteria for PCI associated MI. This is based on a TnT cut-point of more than three times the 99th percentile (0.03 ng/ml), which better reflects the precision of the assay. Our study investigated the incidence and predictive factors of a PCI associated MI, using the revised definition. METHODS: 325 patients were studied following PCI with stenting. TnT was collected at both 8 and 18 h following PCI in patients with either stable or unstable angina and normal baseline TnT levels. Comparison was made of both clinical and procedural characteristics of patients with and without a rise in TnT following intervention, using cut points of 0.01 and 0.03 ng/ml. RESULTS: TnT was elevated > or = 0.03 ng/ml in 27% and > or = 0.01 ng/ml in 39% of patients following PCI. Troponin elevation was significantly more likely in those patients who experienced peri-procedural ischemic symptoms or EKG changes, or in whom abciximab was used. The variables associated with a troponin rise showed a greater difference between TnT positive and negative patients when using 0.03 ng/ml compared to 0.01 ng/ml, suggesting that this may be a better definition of PCI-related MI. CONCLUSIONS: Approximately one-quarter of low risk patients experience a procedural MI according to the revised definition. Rises in troponin were significantly associated with peri-procedural ischemic symptoms and EKG changes, and abciximab use, consistent with this level of TnT reflecting true myocardial necrosis.

Quantitative and temporal differences in coagulation, fibrinolysis and platelet activation after on-pump and off-pump coronary artery bypass surgery.

BACKGROUND: With the increasing use of OPCAB, potentially devastating thromboembolic events, including graft thrombosis may become increasingly evident. We present a study of the quantitative and temporal differences of the coagulation system, fibrinolysis and platelet activation after coronary artery surgery with or without cardiopulmonary bypass. METHODS: Patients undergoing on-pump CABG (n=10) or OPCAB (n=10) had six blood samples taken before surgery and up to 24h post-operatively. Activation of the coagulation cascade (tissue factor pathway-factor VIIa), endothelial injury (von Willebrand Factor antigen), thrombin generation (prothrombin fragments FI+II), fibrinolysis (decreased plasminogen levels), fibrin degradation (D-Dimer), platelet counts and platelet activation (soluble P-selectin) were quantified. RESULTS: CABG caused earlier and more significant generation of thrombin, however OPCAB caused a late and sustained generation of thrombin. CABG caused intraoperative activation of fibrinolysis and fibrin degradation, however, at 24h these parameters were equally elevated in both groups. Platelet activation was significant in the CABG group, but did not occur in the OPCAB group. CONCLUSIONS: Late thrombin generation and reduced fibrinolysis in the presence of intact, functioning platelets may contribute to adverse thromboembolic events after OPCAB surgery. Thromboembolic prophylaxis and anti-platelet therapy may need to be more aggressive after OPCAB surgery.

Oxidized lipoproteins and macrophages.

Macrophages are important participants in the development of atherosclerotic lesions, in cholesterol accumulation, as mediators of the immune response, and as sources of secreted enzymes and growth factors. Besides potentially contributing to local oxidation of lesion lipoproteins, many aspects of macrophage function can be affected by interaction with oxidized lipoproteins. Here we review macrophage responses to oxidized lipoproteins and provide novel data on the effects of a major oxidation product, 7-ketocholesterol, on high-density lipoprotein (HDL) function in cholesterol removal from macrophages.