Ischemia In Man Research Articles

ПОЛОВОЙ ДИМОРФИЗМ КЛИНИЧЕСКИХ И ЭЛЕКТРОКАРДИОГРАФИЧЕСКИХ ИЗМЕНЕНИЙ У БОЛЬНЫХ БЕЗБОЛЕВОЙ ИШЕМИЕЙ МИОКАРДА 3 ТИПА

Безболевая ишемия миокарда у больных сахарным диабетом 2-го типа является довольно распространенным явлением, поскольку ее частота колеблется от 15 до 64,7%. Цель исследования заключалась в анализе полового диморфизма клинических и электрокардиографических проявлений у представителей разного пола. Для достижения цели исследования проведен комплекс клинических и инструментальных исследований морфофункционального состояния сердца. В результате проведенных исследований установлено, что половой диморфизм безболевой ишемии миокарда у мужчин появлялся вначале дебютом приступов болевой стенокардии, у женщин, напротив, болевые приступы стенокардии во времени следовали за безболевой ишемией. У мужчин безболевая ишемия сопровождалась классической иррадиацией стенокардической боли в левую руку, челюсть и межлопаточное пространство, ощущением перебоев в деятельности сердца. У женщин безболевая ишемия миокарда сопровождалась сердцебиением, одышкой или отсутствием кардиальных жалоб. Половой диморфизм ЭКГ-признаков проявлялся в виде преобладания у мужчин желудочковой экстрасистолии и гипертрофии/перегрузки левых отделов сердца. У женщин с безболевой ишемией на ЭКГ в отличие от мужчин преобладали синусовая аритмия и суправентрикулярная экстрасистолия.

Neuroimaging evolution of ischemia in men and women: an observational study.

ObjectiveWe present an exploratory study for identification of sex differences in imaging biomarkers that could further refine selection of patients for acute reperfusion therapy and trials based on sex and imaging targets.MethodsThe Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) study included consecutive acute stroke patients who underwent MRI within 24 h of time from last known well and prior to therapy. Those demonstrating a potential therapeutic target on imaging were identified by presence of: (1) arterial occlusion on angiography, (2) focal ischemic region on perfusion maps, or (3) a mismatch of perfusion versus diffusion imaging lesion size. The prevalence of imaging targets within clinically relevant time intervals was calculated for each patient and examined. The relationship of time from stroke onset to probability of detection of imaging targets was evaluated.ResultsOf 7007 patients screened, of which 86.7% were scanned with MRI, 1092 patients (477/615 men/women) were included in LESION. The probability of imaging target detection was significantly different between men and women, with women more likely to present with all assessed imaging targets, odds ratios between 1.36 and 1.59, P < 0.02, adjusted for NIHSS, age, and time from last known well to MRI scan. This trend held for the entire 24‐h studied.InterpretationWomen present more often with treatable ischemic stroke than men. The greater probability of potentially viable and/or treatable imaging targets in women at all time points suggests that tissue injury is slower to evolve in women.

Does gender influence the outcome of ischemic heart disease?

Diseases of the cardiovascular system (myocardial infarction, stroke, heart failure, hypertensive heart disease, cardiomyopathy) account for 40% of all deaths in men and up to 49% of all deaths in women. For a long time it was thought that the clinical picture of ischemic heart disease in men and women was similar. Now, however, there are more reports suggesting that diverse manifestations of the symptoms of ischemic disease may be related to differences between sexes.The disparity between women and men is also evident in the diagnostic process, and various pathological mechanisms of cardiovascular diseases, in particular myocardial ischemia in men and women, affect the differences in the results of diagnostic tests. Vasomotor dysfunction is particularly frequent in women, as their coronary vessels are more sensitive to the catecholamines released during mental stress, resulting in spasm and ischemic myocardium. Moreover, a much lower dose of acetylcholine induced vasoconstriction, which indicates that women are more sensitive to this neurotransmitter. Therefore, coronary vasomotor disorders in the form of epicardial and microvascular dysfunction are more often seen in women. All these mentioned factors resulted in higher mortality and poorer quality of life of women suffering from ischemic heart disease.

The prevalence of electrocardiographic abnormalities in the Russian population in the early 21st century (the ESSE-RF study)

Electrocardiography (ECG) takes the lead in assessing the prevalence of coronary artery disease (CAD) in the population. ECG disorders, grouped in the Major (certain) and Minor (possible) categories, are prognostic markers of a high risk of cardiovascular diseases and sudden cardiac death. Unified assessing methods of ECG disorders prevalence and their associations with socio-demographic parameters have not previously been made in Russia.Aim. To study the prevalence of ECG parameters of certain and possible coronary artery disease among population of Russia, depending on the socio-demographic characteristics — age, sex, education and place of residence (city or country).Material and methods. We used 17504 ECGs from representative samples of population (25-64 years old), who participated in the epidemiological study “Epidemiology of cardiovascular diseases and their risk factors in the Russian Federation”. The analysis using Minnesota code was carried out among men and women of four age groups, two educational levels, among citizens and countrymen.Results. The highest prevalence was observed in the “Certain” (5,7%) and “Possible signs of CAD” (7,1%) categories, in the “Certain” (3,8%) and “Possible myocardial ischemia” groups (4,9%), the smallest is in the “Rhythm and conduction disorder” (0,7%) and “STT changes in left ventricular hypertrophy” (0,4%) groups. It was shown that the frequency of ECG disorders increases with age, has an sharp increase after 55 years, regardless of sex. In the age dynamics of categories, STT changes and atrial fibrillation have a decrease of gender differences. All groups of ECG disorders are detected more often among men than women, except for STT changes. With an increase in the level of education, the frequency of ECG pathologies decreases, with the exception of the groups of “major” and “minor Q (QS)”, “major rhythm and conduction disorders”. The prevalence of most ECG disorders does not depend on the place of residence. However, signs of major myocardial ischemia in men are more common in country than in the city (3,9% vs. 2,7%, p&lt;0,05).Conclusion. The results confirm the patterns identified earlier. There is a steady association of ECG data with socio-demographic characteristics.

Spontaneous cardiac baroreflex sensitivity is enhanced during post-exercise ischemia in men but not in women.

To investigate the effect of isolated muscle metaboreflex activation on spontaneous cardiac baroreflex sensitivity (cBRS), and to characterize the potential sex-related differences in this interaction in young healthy subjects. 40 volunteers (20 men and 20 women, age: 22 ± 0.4year) were recruited. After 5-min rest period, the subjects performed 90s of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 3min of post-exercise ischemia (PEI). Beat-to-beat heart rate and arterial blood pressure were continuously measured by finger photopletysmography. Spontaneous cBRS was assessed using the sequence technique and heart rate variability was measured in time (RMSSD-standard deviation of the RR intervals) and frequency domains (LF-low and HF-high frequency power). Resting cBRS was similar between men and women. During PEI, cBRS was increased in men (Δ3.0 ± 1.1msmmHg- 1, P = 0.03) but was unchanged in women (Δ-0.04 ± 1.0msmmHg- 1, P = 0.97). In addition, RMSSD and HF power of heart rate variability increased in women (Δ7.4 ± 2.6ms, P = 0.02; Δ373.4 ± 197.3ms2; P = 0.04, respectively) and further increased in men (Δ26.4 ± 7.1ms, P < 0.01; Δ1874.9 ± 756.2ms2; P = 0.02, respectively). Arterial blood pressure increased from rest during handgrip exercise and remained elevated during PEI in both groups, however, these responses were attenuated in women. These findings allow us to suggest a sex-related difference in spontaneous cBRS elicited by isolated muscle metaboreflex activation in healthy humans.

Associations of the serum long-chain omega-3 polyunsaturated fatty acids and hair mercury with exercise-induced myocardial ischemia in men: The kuopio ischaemic heart disease risk factor study

Rationale: Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish is associated with lower risk of coronary heart disease (CHD). Fish may also contain methylmercury, which is associated with higher CHD risk. However, mechanisms underlying these associations are not fully known. We investigated the association of serum long-chain omega-3 PUFA and hair mercury concentrations with the odds for myocardial ischemia during exercise, a predictor of future cardiac events.

Estimation of the Blood Pressure Response With Exercise Stress Testing

The blood pressure response to exercise has been described as a significant increase in systolic BP (sBP) with a smaller change in diastolic BP (dBP). This has been documented in small numbers, in healthy young men or in ethnic populations. This study examines these changes in low to intermediate risk of myocardial ischaemia in men and women over a wide age range. Consecutive patients having stress echocardiography were analysed. Ischaemic tests were excluded. Manual BP was estimated before and during standard Bruce protocol treadmill testing. Patient age, sex, body mass index (BMI), and resting and peak exercise BP were recorded. 3,200 patients (mean age 58±12years) were included with 1,123 (35%) females, and 2,077 males, age range 18 to 93 years. Systolic BP increased from 125±17mmHg to 176±23mmHg. The change in sBP (ΔsBP) was 51mmHg (95% CI 51,52). The ΔdBP was 1mmHg (95% CI 1, 1), from 77 to 78mmHg, p<0.001). The upper limit of normal peak exercise sBP (determined by the 90th percentile) was 210mmHg in males and 200mmHg in females. The upper limit of normal ΔsBP was 80mmHg in males and 70mmHg in females. The lower limit of normal ΔsBP was 30mmHg in males and 20mmHg in females. In this large cohort, sBP increased significantly with exercise. Males had on average higher values than females. Similar changes were seen with the ΔsBP. The upper limit of normal for peak exercise sBP and ΔsBP are reported by age and gender.

Testosterone and the Heart.

Testosterone (T) has a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular (CV) risk. Low T levels in men may increase their risk of developing coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with congestive heart failure (CHF) portends a poor prognosis and is associated with increased mortality. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk. However, there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men.

Relationship between the ischemic ST-T changes in ECG and the coronary artery diseases

To analyze the relationship between the ischemic ST-T changes in electrocardiogram (ECG) and the coronary artery diseases based on the perspective of diagnostics. A total of 341 patients, who underwent coronary angiography in Department of Cardiology of Xiangya Hospital, Central South University from June 2013 to April 2014, were enrolled for this study. The internationally recognized diagnostic criteria for ischemic ST-T changes in ECG and the Judkins diagnostic criteria for coronary angiography were applied, respectively. The sensitivity and specificity of ECG were analyzed. There were more ischemic ST-T changes in women than that in men (P<0.01). Ischemic changes in coronary angiography were not significantly different between male and female patients (P>0.05). For ischemic diagnostic tests by ECG ST-T, the total sensitivity and specificity was 83.6% and 54.4%, respectively. The sensitivity and specificity was 82.3% and 68.0% or 85.0% and 28.2% in the male or female group, respectively. Ischemic ST-T changes in ECG possess important value in the diagnosis of the coronary artery diseases. The sensitivity of ECG in the diagnosis of myocardial ischemia in women was higher than that in men, whereas the specificity of ECG in the diagnosis of myocardial ischemia in men was higher than that in women.

159 Testosterone Therapy in Men with Coronary Artery Disease

Background Testosterone levels are inversely associated with the severity of coronary artery disease (CAD). Testosterone may cause vasodilatation via the opening of potassium and calcium channels in smooth muscle cells, or via nitric oxide release, although the evidence is inconsistent. Whether testosterone reduces cardiovascular risk in men with CAD, is unclear. Data supports testosterone supplementation in hypogonadal men as a valuable strategy to reduce cardiovascular events. We aimed to review chronic testosterone therapy in patients with CAD and relate this to gonadal status and clinical outcomes. Methods The PubMed/Medline, Embase, Scopus and Cochrane Central Register of Controlled Trials databases were searched. All randomised trials comparing the effects of testosterone therapy and alternative interventions in patient with CAD, and reporting clinical outcomes were included. For the purposes of statistical meta-analysis, only the endpoint of time to 1 mm ST-segment depression on exercise tolerance testing was included. Overall estimates of effect were calculated with a random-effects model. Results Seven trials involving 290 patients with stable angina were included. Baseline gonadal state of patients ranged from true hypogonadism ( Conclusions Testosterone appears to confer no harm and have some anti-ischaemic properties in patients with established CAD. Chronic therapy prolongs the time to ischaemia in men with CAD. Large prospective trials of testosterone in men with CAD are required to understand the true benefit.

357 RELATIONSHIP BETWEEN SERUM URIC ACID AND SILENT BRAIN ISCHEMIA IN MEN

Background: Although serum uric acid (SUA) level as well as silent brain ischemia is known to a risk factor for cardiovascular events, association between SUA and silent brain ischemia has not been fully elucidated. Methods: We evaluated the association between SUA level and deep and subcortical white matter hyperintensity (DSWMH, Fazekas grade) in 1109 stroke free participants (male 56%, age 24 - 85 years) in the registry of Okinawa general health maintenance association. Results: DSWMH was found in 34% of participants (grade 1, 10%; 2, 21%; 3, 3%, respectively). The SUA level was significantly higher in men than in women (6.5 ± 1.2 vs. 4.8 ± 1.1 mg/dl, P < 0.0001). The prevalence of DSWMH (grade 2 - 3) decreased with increasing quartiles of SUA level (1st, 27%, 2nd, 20%, 3rd, 18%, 4th, 18%; P = 0.1) in men, but increased slightly (1st, 28%, 2nd, 29%, 3rd, 32%, 4th, 32%; P = 0.8) in women. We also found negative association between SUA level and Fazekas grade (no DSWMH, 6.6 ± 1.2; grade 2, 6.3 ± 1.3; grade 3, 6.0 ± 1.2 mg/dl, P < 0.05) in men, but not in women. Conclusion: Gender difference about the relationship between SUA levels and silent brain ischemia was observed. Thus SUA may have a beneficial effect of brain ischemia in men but not in women. The prospective study to elucidate association between SUA level and brain ischemia will be needed in the future.

Lipid Levels as Predictors of Silent Myocardial Ischemia in a Type 2 Diabetic Population in Havana

Silent myocardial ischemia is frequent in type 2 diabetics, therefore, symptoms cannot be relied upon for diagnosis and followup in these patients. Various studies relate blood lipid levels to cardiovascular diseases, and several authors describe certain lipoproteins as independent predictors of ischemia. Identify blood lipid levels that predict silent myocardial ischemia in a type 2 diabetic population in Havana. From May 2005 through May 2009, assessment was done of 220 asymptomatic type 2 diabetics in ten polyclinics in Havana using laboratory tests and Single-Photon Emission-Computed Tomography, synchronized with electrocardiogram, known as gated SPECT (gSPECT). Coronary angiography was used for confirmation when gSPECT detected ischemia. Patients were classified into two groups: gSPECT positive and gSPECT negative. Descriptive statistics (mean and standard deviation) were calculated for all variables and mean comparison tests were conducted. Classification trees were developed relating lipid values to gSPECT results, identifying optimal cutoff points for their use as indicators of silent myocardial ischemia in the total study population and for each sex separately. GSPECT found silent myocardial ischemia in 29.1% of those examined, and 68.4% of angiograms found multivessel disease. gSPECT-positive diabetics had higher levels of total cholesterol, LDL, and triglycerides (p < 0.05). HDL levels were lower in this group (p < 0.05). Classification trees showed optimal cutoff points, indicators for silent ischemia, for: HDL ≤44 mg/dL, LDL >119.9 mg/dL, and triglycerides >107.2 mg/d; 80.4% of diabetics with these HDL and triglyceride values had ischemia. HDL was the most important normalized variable when the entire population was analyzed. Analysis by sex showed a greater percentage of silent ischemia in men (33.3%) than in women (24.8%). The most important normalized variables were LDL of >100.8 mg/dL for men and HDL of ≤44 mg/dL for women. A considerable percentage of the study population had silent myocardial ischemia. Type 2 diabetics with ischemia had higher levels of total cholesterol, LDL and triglycerides. HDL levels were significantly lower in these patients. The association of low HDL with high triglycerides was a strong indicator of myocardial ischemia in type 2 diabetics without clinical cardiovascular signs. KEYWORDS Lipids, type 2 diabetes, silent myocardial ischemia, decision trees, diagnostic imaging, Single-Photon Emission-Computed Tomography, cardiac-gated SPECT, early detection, Cuba.

Gender Difference in Albuminuria and Ischemic Heart Disease in Type 2 Diabetes

The value of urinary albumin excretion in the prediction of myocardial ischemia in men and women with type 2 diabetes is not well understood. We questioned whether gender influences the albuminuria-ischemic heart disease relationship in patients with type 2 diabetes. We designed a matched case-control study of 926 patients with albuminuria (cases) and 926 age and body mass index matched patients without albuminuria (controls). Ischemic heart disease was defined as the presence of (1) history of angina pectoris or angina equivalent symptoms and critical care unit admission, (2) myocardial infarction and/or electrocardiographic evidence of Q-wave myocardial infarction, (3) coronary revascularization and/or stenting, (4) positive myocardial single-photon emission computed tomography scan, (5) ischemic ST-segment or T-wave changes, and (6) positive stress testing. Patients with albuminuria had a lower glomerular filtration rate and a longer diabetes duration than patients without albuminuria. In the group of cases, there were a greater number of men with ischemic heart disease (120 of 370; 32.4%) compared to women (97 of 559; 17.4%) (P<0.001). The odds ratio of having ischemic heart disease according to the presence or absence of albuminuria was 1.25 [95% CI: 1.01-1.56] (P<0.05) in all studied populations, 0.79 [95% CI: 0.51-1.21] (P=0.14) in women, and 2.84 [95% CI: 1.68-4.79] (P<0.001) in men. We showed that diabetes duration, high-density lipoprotein, low-density lipoprotein, and hemoglobin A(1c) influence albuminuria in women, while diabetes duration, fasting blood sugar, and diastolic blood pressure influence albuminuria in men. Men with albuminuria are at increased risk of ischemic heart disease compared to women. This may be related to the role of high-density lipoprotein on the albuminuria-gender relationship.

Segmental testicular ischaemia: presentation, management and follow‐up

Segmental infarction of the testis is a rare event. Less than 40 cases have been reported in the literature and its aetiology remains largely unknown. The diagnosis is challenging and its identification crucial as partial ischaemia is frequently confused with testicular tumours and unnecessarily treated with orchiectomy. The objectives of this study are to: (i) raise awareness of this rare condition, (ii) provide the distinctive clinical and radiological features enabling pre-operative diagnosis, (iii) promote appropriate screening of causative factors and (iv) propose an alternative management approach to avoid surgery and preserve fertility. We describe three cases of partial testicular ischaemia in men presenting with reduced sperm quality. The cases demonstrate the ultrasound and magnetic resonance imaging appearance of testicular ischaemia. The surveillance strategy adopted for these lesions indicates that over 2 years of follow-up, marginal changes in the lesions can occur. Histology revealed that infiltration by stromal cells, leucocytes and macrophages is responsible for the remodelling of these lesions. Screening of risk factors for thromboembolism revealed that all patients carried a methylenetetrahydrofolate reductase 677C-->T (MTHFR) mutation in a gene involved in folate metabolism, and either borderline or elevated homocysteine levels. Distinctive features permit the pre-operative diagnosis of segmental testicular ischaemia. There are sufficient data to assert that a surveillance strategy is safe and feasible. We speculate that the defects in folate metabolism may pre-dispose individuals to the development of testicular infarction and infertility.

Bone marrow-derived mononuclear cell therapy induces distal angiogenesis after local injection in critical leg ischemia

Critical leg ischemia is associated with a high risk of amputation when revascularization is not possible. Cell therapy based on bone marrow-derived mononuclear cells or with peripheral mononuclear cells, collected after stimulation with G-CSF has been used in an attempt to stimulate angiogenesis. Although several studies have raised the hope that such cell therapy may be effective in critical leg ischemia, no direct demonstration of angiogenesis induced by bone marrow-derived mononuclear cell/peripheral mononuclear cell injection has been reported in man. The aim of this study was to identify and to evaluate the extent of the angiogenic process associated with cell therapy in critical leg ischemia in man. To address this question, this pathological study was conducted in patients enrolled in the OPTIPEC clinical trial (Optimization of Progenitor Endothelial Cells in the Treatment of Critical leg ischemia), an interventional cell therapy study in critical leg ischemia. Amputation specimens from these patients were submitted to a standardized dissection protocol. In three patients, an active angiogenesis was observed in the distal part of the ischemic limb but not in the gastrocnemius muscle, the site of bone marrow cell injection. All the newly formed vessels were positive for endothelial cell markers (CD31, CD34, von Willebrand factor) and negative for markers of lymphatic vessels (podoplanin). Immunohistochemical staining for Ki-67 and c-kit showed extensive endothelial cell proliferation within the new vessels. Bone marrow-derived mononuclear cell therapy in patients with critical leg ischemia induces an active, substained angiogenesis in the ischemic and distal parts of the treated limb, although this may not prevent amputation in some patients with very severe ischemia.

Decreased hepatosplanchnic antioxidant uptake during hepatic ischaemia/reperfusion in patients undergoing liver resection

Oxidative stress mediates cell injury during ischaemia/reperfusion. On the other hand, experimental findings suggest that ROS (reactive oxygen species) induce processes leading to ischaemic preconditioning. The extent and source of oxidative stress and its effect on antioxidant status in the human liver during intermittent ischaemia and reperfusion remains ill-defined. Therefore the aim of the present study was to investigate the occurrence of oxidative stress in humans undergoing liver resection. Liver biopsies, and arterial and hepatic venous blood samples were taken from ten patients undergoing hepatectomy with an intermittent Pringle manoeuvre. Plasma MDA (malondialdehyde) and hepatic GSSG levels were measured as markers of oxidative stress and plasma uric acid as a marker of xanthine oxidase activity. In addition, changes in hepatosplanchnic consumption of plasma antioxidants and hepatic levels of carotenoids and glutathione (GSH) were measured. After ischaemia, hepatosplanchnic release of MDA and increased hepatic GSSG levels were found. This was accompanied by the release of uric acid, reflecting xanthine oxidase activity. During reperfusion, ongoing oxidative stress was observed by further increases in hepatic GSSG content and hepatosplanchnic MDA release. Uric acid release was minimal during reperfusion. A gradual decrease in plasma antioxidant capacity and net hepatosplanchnic antioxidant uptake was observed upon prolonged cumulative ischaemia. Oxidative stress occurs during hepatic ischaemia in man mainly due to xanthine oxidase activity. Interestingly, the gradual decline in plasma antioxidant capacity and net hepatosplanchnic antioxidant uptake during prolonged cumulative ischaemia, preserved both hydrophilic and lipophilic hepatic antioxidant levels. Decreasing plasma levels and net hepatosplanchnic uptake of plasma antioxidants may warrant antioxidant supplementation, although it should be clarified to what extent limitation of oxidative stress compromises ROS-dependent pathways of ischaemic preconditioning.

Androgen Deficiency as a Predictor of Metabolic Syndrome in Aging Men

The prevalence of metabolic syndrome is increasing globally and is an important risk factor for the development of cardiovascular disease. Longitudinal population studies have found that low testosterone status in men is a risk factor for the later development of metabolic syndrome. Men with metabolic syndrome and type 2 diabetes mellitus have a higher incidence of hypotestosteronaemia. Furthermore, in men, testosterone levels are inversely associated with the degree of carotid and aortic atherosclerosis. Early interventional, short-term studies have shown that testosterone replacement therapy has a beneficial effect on visceral obesity, insulin sensitivity, glycaemic control and lipid profiles in men with diagnosed hypogonadism with and without diabetes. The effect of testosterone therapy on atherogenesis in men is unknown; however, animal studies have shown that testosterone is atheroprotective and can ameliorate the degree of atherosclerosis. Testosterone is an arterial vasodilator and has been shown to improve myocardial ischaemia in men with coronary artery disease. This review discusses the role that testosterone may play in the pathogenesis of metabolic syndrome in men and also examines the potential role of testosterone replacement therapy in this condition.

Effects of Oral Testosterone Treatment on Myocardial Perfusion and Vascular Function in Men With Low Plasma Testosterone and Coronary Heart Disease

Intracoronary testosterone infusions induce coronary vasodilatation and increase coronary blood flow. Longer term testosterone supplementation favorably affected signs of myocardial ischemia in men with low plasma testosterone and coronary heart disease. However, the effects on myocardial perfusion are unknown. Effects of longer term testosterone treatment on myocardial perfusion and vascular function were investigated in men with CHD and low plasma testosterone. Twenty-two men (mean age 57 ± 9 [SD] years) were randomly assigned to oral testosterone undecanoate (TU; 80 mg twice daily) or placebo in a crossover study design. After each 8-week period, subjects underwent at rest and adenosine-stress first-pass myocardial perfusion cardiovascular magnetic resonance, pulse-wave analysis, and endothelial function measurements using radial artery tonometry, blood sampling, anthropomorphic measurements, and quality-of-life assessment. Although no difference was found in global myocardial perfusion after TU compared with placebo, myocardium supplied by unobstructed coronary arteries showed increased perfusion (1.83 ± 0.9 vs 1.52 ± 0.65; p = 0.037). TU decreased basal radial and aortic augmentation indexes (p = 0.03 and p = 0.02, respectively), indicating decreased arterial stiffness, but there was no effect on endothelial function. TU significantly decreased high-density lipoprotein cholesterol and increased hip circumference, but had no effect on hemostatic factors, quality of life, and angina symptoms. In conclusion, oral TU had selective and modest enhancing effects on perfusion in myocardium supplied by unobstructed coronary arteries, in line with previous intracoronary findings. The TU-related decrease in basal arterial stiffness may partly explain previously shown effects of exogenous testosterone on signs of exercise-induced myocardial ischemia.

Inverse Relationship between Serum Levels of Interleukin-1β and Testosterone in Men with Stable Coronary Artery Disease

To examine the relationship between serum levels of inflammatory cytokines and testosterone in men with stable coronary artery disease (CAD). Evidence supports a beneficial effect of testosterone upon objective measures of myocardial ischaemia in men with CAD, and in animal models of atherosclerosis. Inflammatory cytokines are involved in many stages of the atherosclerotic process, however, the effect of testosterone upon inflammatory cytokines within the cardiovascular system is largely unknown. Serum was collected from 69 men (59+/-1 years) having >75% occlusion of 1, 2, or 3 coronary arteries. Levels of total testosterone (TT), bioavailable testosterone (BT), tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1-beta (IL-1beta), IL-6 and IL-10 were measured and analysis made between men with 1, 2, or 3 vessel CAD, and between men with hypogonadal, borderline hypogonadal and eugonadal serum levels of testosterone. In patients with 1, 2, or 3 vessel CAD, significant stepwise increases were observed in levels of IL-1beta: 0.16+/-0.03, 0.22+/-0.06, and 0.41+/-0.08 pg/ml (p=0.035), and IL-10: 0.93+/-0.11, 1.17+/-0.14, and 2.94+/-0.65 pg/ml (p=0.008). A significant stepwise increase in levels of IL-1beta was also observed in eugonadal, borderline hypogonadal, and hypogonadal men: 0.19+/-0.05, 0.29+/-0.05, and 0.46+/-0.13 pg/ml (p=0.047). Consequently this data implicates IL-1beta and IL-10 in the pathogenesis of CAD and suggests that testosterone may regulate IL-1beta activity in men with CAD.

Do mechanical markers of myocardial ischaemia predict the transmural extent of myocardial infarction in man?

The present study aimed to explore the relationship between the transmural extent of myocardial necrosis and mechanical markers of myocardial ischaemia in man. A group of 40 patients with previous Q-wave myocardial infarction and a left ventricular ejection fraction (LVEF) of 27 +/- 11% was studied by cine and contrast-enhanced magnetic resonance imaging. Necrotic areas of delayed contrast enhancement were present in every patient and involved 20 +/- 8% of left ventricular myocardium. In involved segments, the transmural extent of contrast enhancement varied from 5% to 100%, being on average 38 +/- 25% of the wall thickness. End-diastolic left ventricular wall thickness and systolic wall thickening were lower in contrast-enhanced segments than in the other segments (P < 0.001). Furthermore, although left ventricular wall thickness and systolic wall thickening decreased as the transmural extent of contrast enhancement increased, the correlations were weak (r = -0.382 and -0.45, respectively). Finally, a delayed contrast enhancement was present in 89% of akinetic and in 94% of dyskinetic segments; however, contrast enhancement was also present in 18% of the segments with normal wall motion and in 56% of hypokinetic segments. Although mechanical markers of myocardial ischaemia substantially reflect the transmural extent of myocardial infarction, none of them can be considered as a substitute for the direct observation of necrotic tissue and its transmural extent, as provided by contrast-enhanced magnetic resonance imaging.