Dyslipidaemia is associated with testosterone, oestradiol and androgen receptor CAG repeat polymorphism in men with type 2 diabetes.

OBJECTIVE: There is a high prevalence of low testosterone and dyslipidaemia in men with type 2 diabetes. The androgen receptor CAG repeat polymorphism (AR CAG) affects receptor transcriptional activity (the shorter repeats the more sensitive AR) and is associated with androgenic parameters and obesity. This study describes the relationships between testosterone, AR CAG and serum lipids in men with type 2 diabetes. DESIGN AND PATIENTS: Cross-sectional study of men with type 2 diabetes in a District General Hospital Diabetes Centre. MEASUREMENTS: Correlation between testosterone, AR CAG and serum lipids. RESULTS: HDL cholesterol (HDL-C) correlated with total testosterone (TT) (r = 0·251, P < 0·001), bioavailable testosterone (BT) (r = 0·19, P = 0·001), free testosterone (FT) (r = 0·165, P = 0·005) and sex hormone-binding globulin (SHBG) (r = 0·147, P = 0·014). HDL-C did not correlate with oestradiol, but men with the lowest quartile of oestradiol had lower HDL-C compared to highest quartile (P = 0·046). Triglycerides correlated negatively with TT (r = -0·195, P = 0·001), BT (r = -0·148, P = 0·013) and SHBG (-0·14, P = 0·019) but not with FT or oestradiol. Total and LDL cholesterol (LDL-C) correlated negatively with oestradiol (r = -0·121, P = 0·05) but not with testosterone or SHBG. One-way anova testing across four quartiles of AR CAG showed a trend to alteration in HDL-C across groups of AR CAG (P = 0·08). HDL-C was significantly higher in men with the longest AR CAG compared with the shortest (1·19 vs 1·08 mmol/l, P = 0·02). CONCLUSIONS: Lower testosterone and oestradiol levels in men with diabetes are associated with an adverse lipid profile. Shorter AR CAG is associated with low HDL-C and testosterone. The paradox that HDL-C is associated with low testosterone levels and a more active AR may suggest divergent effect of testosterone on HDL-C via genomic vs nongenomic mechanisms.

Testosterone acts as an efficacious vasodilator in isolated human pulmonary arteries and veins: evidence for a biphasic effect at physiological and supra-physiological concentrations.

BACKGROUND: Testosterone is recognized to elicit vasodilatation in numerous vascular beds, however to date no study has investigated whether testosterone has this effect in the human pulmonary vasculature. AIM: To determine whether isolated human pulmonary arteries and veins dilate in response to testosterone and whether the response differs in relation to gender, endothelial function or location with the pulmonary vasculature. METHODS: Intralobar pulmonary arteries [no.=44, diameter =581 (349) microm] and veins [no.=27, diameter =573 (302) microm] were dissected from lobectomy samples obtained from male and female patients [no.=40, age =69 (8) yr]. Vessels were mounted in an automated wire myograph, bathed in physiological saline at 37 C and pH 7.4, and loaded to their in vivo pressure. Vessels were preconstricted with noradrenaline (10 microM) and exposed to acetylcholine (1 microM) to assess endothelial function, washed and then preconstricted with potassium chloride (1-100 mM) followed by either cumulative concentrations of testosterone (1 nM-100 microM) or ethanol vehicle (<0.1%). RESULTS: Significant marked vasodilatation was seen in all vessels, irrespective of size, gender and endothelial function at micromolar concentrations. Testosterone triggered significant vasodilatation at concentrations > or = 10 nM in pulmonary arteries obtained from males, a response which was not observed in vessels from females. The maximal response at 100 microM was also significantly greater in male pulmonary arteries. Significant vasodilatation was only observed at physiological (nM) concentrations in pulmonary resistance arteries and pulmonary arteries with good endothelial function. CONCLUSION: Testosterone acts as an efficacious vasodilator in the human pulmonary vasculature, with dilatation observed at physiological concentrations in the male arterial resistance bed, dependent on the presence of an intact endothelium.

Chronic atrial fibrillation: a systematic review of medical heart rate control management.

OBJECTIVE: Recent guidelines by the National Institute for Health and Clinical Excellence (NICE) and the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) on rate control management for chronic atrial fibrillation have relegated digoxin to second line treatment, recommending instead the use of beta-blockers or rate limiting calcium antagonists as first line treatment. The objective of this review is to assess the efficacy of these drugs in controlling heart rate, and in improving symptoms and exercise tolerance. DATA SOURCES: We electronically searched the Medline, Embase and Cochrane databases, hand searched journals and relevant bibliographies for articles. SELECTION OF STUDIES: We included all study designs evaluating or comparing oral digoxin, beta-blockers and calcium antagonists, alone or in combination, for rate control in chronic atrial fibrillation. 46 studies satisfied our inclusion and quality criteria. RESULTS: Published studies are small and too heterogeneous to be quantitatively combined. Descriptive synthesis of the data shows little evidence that monotherapy with beta-blockers or calcium antagonists improves symptoms or exercise capacity in patients with chronic atrial fibrillation. Instead it is associated with dose related side effects. CONCLUSION: Based on the limited data available, we conclude that the combination of digoxin with either a beta-blocker or calcium antagonist should be first line management in patients with chronic atrial fibrillation.

The triad of erectile dysfunction, hypogonadism and the metabolic syndrome.

AIM: To identify the relationship of erectile dysfunction, hypogonadism and the metabolic syndrome in the context of men's health. METHODS: An Expert Panel Meeting was held in December 2006 in Vienna, Austria. In addition a comprehensive literature search was conducted. RESULTS: Men have a higher incidence of cardiovascular events than women of similar ages which has led to the belief that testosterone is a risk factor for cardiovascular disease in men. The latter hypothesis is no longer tenable. On the contrary, low testosterone levels are associated with (visceral) obesity, the metabolic syndrome, diabetes mellitus, cardiovascular disease and erectile dysfunction (ED). Testosterone therapy does not lead to an increased incidence of cardiovascular disease or events such as myocardial infarction, stroke or angina. Until recently (visceral) obesity, the metabolic syndrome, diabetes mellitus, cardiovascular disease and ED were viewed as more or less independent entities affecting the ageing male. It was not recognised that hypogonadism is a common denominator. With a more integrative approach to the health situation of middle-aged and elderly men, these conditions appear closely interrelated in their manifestations, hypothetically in their aetiology, diagnostic strategy and also their treatment. CONCLUSION: Improving sexual health is a portal to identify health hazards and improving men's health. Appropriate diagnosis and medical work up of men presenting with sexual symptoms may have the benefit of the diagnosing and treating other important conditions, such as obesity, diabetes, hypertension and hyperlipidaemia.

The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes.

OBJECTIVE: Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men. Furthermore, there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men. Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance. We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein (CRP) in type 2 diabetic men. DESIGN: Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men. Patients were treated with testosterone (sustanon 200 mg) or placebo intramuscularly every 2 weeks for 3 months in random order followed by a washout period of 1 month before the alternate treatment phase. METHODS: Leptin, adiponectin, resistin, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and CRP levels were measured before and after each treatment phase. Body mass index (BMI) and waist circumference were also recorded. RESULTS: At baseline, leptin levels significantly correlated with BMI and waist circumference. There was a significant inverse correlation between baseline IL-6 and total testosterone (r=-0.68; P=0.002) and bioavailable testosterone levels (r=-0.73; P=0.007). CRP levels also correlated significantly with total testosterone levels (r=-0.59; P=0.01). Testosterone treatment reduced leptin (-7141.9 +/- 1461.8 pg/ml; P=0.0001) and adiponectin levels (-2075.8 +/- 852.3 ng/ml; P=0.02). There was a significant reduction in waist circumference. No significant effects of testosterone therapy on resistin, TNF-alpha, IL-6 or CRP levels were observed. CONCLUSION: Testosterone replacement treatment decreases leptin and adiponectin levels in type 2 diabetic men. Moreover, low levels of testosterone in men are associated with pro-inflammatory profile, though testosterone treatment over 3 months had no effect on inflammatory markers.

An evaluation of the effects of Tai Chi Chuan and Chi Kung training in patients with symptomatic heart failure: a randomised controlled pilot study.

OBJECTIVE: To study the effect of Tai Chi on exercise tolerance in patients with moderate heart failure. DESIGN: Randomised parallel group study balanced for baseline variables. SETTING: Cardiology Department, Royal Hallamshire Hospital. PATIENTS AND METHODS: 52 patients (42 men, mean age (68.9 years), range (46-90 years), and 10 women, mean age (70.0 years), range (58-82)) with chronic heart failure (New York Heart Association symptom class II-III) were studied. Patients were randomised to Tai Chi Chuan twice a week for 16 weeks or to standard medical care without exercise rehabilitation. MAIN OUTCOME MEASURES: The primary outcome measure was the change in the distance walked in the shuttle walk test. Secondary outcome measures were changes in symptom scores and quality of life indices. RESULTS: Objective measures of exercise tolerance did not improve significantly with Tai Chi, but patients having Tai Chi exercise had an improvement in symptom scores of heart failure measured by the Minnesota Living with Heart Failure Questionnaire (comparison of deltas, -2.4 control vs -14.9; p = 0.01), and depression scores measured by the SCL-90-R questionnaire (-2.9 vs -6.8; p = 0.12) compared with those patients in the control group. CONCLUSION: In patients with chronic heart failure, 16 weeks of Tai Chi training was safe, with no adverse exercise related problems. It was enjoyed by all taking part and led to significant improvements in symptoms and quality of life.

Selective inhibition of L-type Ca2+ channels in A7r5 cells by physiological levels of testosterone.

Testosterone has marked beneficial cardiovascular effects, many of which have been attributed to a vasodilatory action. However, the molecular target of testosterone underlying this effect is subject to debate. In this study, we have used microfluorimetry as a noninvasive means of examining whether testosterone could exert dilatory effects via inhibition of voltage-gated Ca2+ entry in the model vascular smooth muscle cell line, A7r5. Rises of [Ca2+]i evoked by 50 mm K+ -containing solution were suppressed in a concentration-dependent manner by testosterone (IC50, 3.1 nm) and by the nonaromatizable analog, 5beta-dihydrotestosterone (IC50, 6.9 nm). The effects of testosterone were apparent in the presence of pimozide (to block T-type Ca2+ channels) but not nifedipine (to block L-type Ca2+ channels). Testosterone did not alter Ca2+ mobilization from intracellular stores by the prostaglandin analog U46619 or capacitative Ca2+ entry in cells pretreated with thapsigargin. Our results indicate that testosterone, at physiological concentrations, can selectively suppress Ca2+ entry into A7r5 cells via L-type Ca2+ channels. We suggest this effect is a likely mechanism underlying its vasodilatory actions and beneficial cardiovascular effects.

The influence of sex hormones on pulmonary vascular reactivity: possible vasodilator therapies for the treatment of pulmonary hypertension.

Pulmonary hypertension is a rare disease of the pulmonary vasculature defined as a mean pulmonary artery pressure >25 mmHg at rest or 30 mmHg with exercise. Recent therapies such as epoprostenol, bosentan and sildenafil are directed at the arterial vascular bed, causing vasodilatation and reducing pulmonary vascular resistance. However idiopathic pulmonary artery hypertension (IPAH) occurs predominantly in women, with three times the incidence compared to men and this suggests that sex hormones may be involved in the pathogenesis. 17beta -oestradiol is a pulmonary vasodilator, proposed to act via an endothelium-dependant pathway, involving nitric oxide (NO) and has also been shown to alter responses to hypoxia. Progesterone is also a pulmonary vasodilator but differs from 17beta-oestradiol in having endothelial-dependant and independent processes implicated. Interestingly testosterone has been shown to be a vasodilator in both the coronary and pulmonary circulation with a mechanism of action involving calcium channel blockade of the vascular smooth muscle and without endothelial involvement. In clinical trials testosterone confers symptomatic benefits in patients with coronary heart disease and heart failure, acting as a vasodilator. These observations lend support to the notion that testosterone could be a potential treatment for patients with PAH as vasodilator therapy remains the mainstay of treatment. Other potential beneficial effects of testosterone in the pulmonary circulation include immuno-modulation, altering expression of cytokines and an anti-thrombotic action. In this review the influence of sex hormones on the pulmonary vasculature will be discussed, with specific focus on pulmonary hypertension and the potential treatment of this condition.

Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes.

OBJECTIVE: Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes. DESIGN: This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes. METHODS: Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone. RESULTS: Testosterone therapy reduced the HOMA index (-1.73 +/- 0.67, P = 0.02, n = 14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (-0.37 +/- 0.17%, P = 0.03), as was the fasting blood glucose (-1.58 +/- 0.68 mmol/l, P = 0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (-1.63 +/- 0.71 cm, P = 0.03) and waist/hip ratio (-0.03 +/- 0.01, P = 0.01). Total cholesterol decreased with testosterone therapy (-0.4 +/- 0.17 mmol/l, P = 0.03) but no effect on blood pressure was observed. CONCLUSIONS: Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.

The role of vasopressin in cardiorespiratory arrest and pulmonary hypertension.

Vasopressin is a peptide synthesized in the hypothalamus whose primary role is in fluid homeostasis. It has recently gained interest as a potential agent in the treatment of cardiorespiratory arrest. Initial human studies have shown benefits with vasopressin in patients with out of hospital ventricular fibrillation and asystolic cardiac arrest. One subgroup of patients not included in these trials is patients with pulmonary hypertension, who have a five-year mortality rate of 50%. Animal studies have shown vasopressin to be a vasodilator in the pulmonary vascular system of rats, under normoxic and hypoxic conditions, with conflicting results in canines. Human studies have shown conflicting results with increases, decreases and no changes seen in pulmonary artery pressures of patients with a variety of clinical conditions. Research needs to be done in patients with pulmonary hypertension regarding the potential role of vasopressin during cardiac arrest in this subgroup.

Junior doctors and the full shift rota--psychological and hormonal changes: a comparative cross-sectional study.

We studied the hormonal and psychological effect of the full shift rota on junior doctors after implementation of the European Working Time Directive, using a comparative, cross-sectional study design of male doctors in South Yorkshire. Cortisol and testosterone levels were measured and subjects completed the general health questionnaire (GHQ-12) and the androgen deficiency in the aging male screening questionnaire (ADAM), after a week of holiday (baseline), a week of nights, and a normal working week. The results showed that cortisol levels decreased from 480.6 +/- 33.1 nmol/l at baseline (after a week of holiday), to 355.7 +/- 29.1 nmol/l post normal working week (p = 0.003); to 396.7 +/- 32.5 nmol/l post nights (p = 0.03). GHQ-12 scores increased from 0.5 +/- 0.3 at baseline, to 1.8 +/- 0.5 post normal working week (p = 0.02) and to 2.3 +/- 0.5 post nights (p = 0.005). These results suggest that there are still appreciable physiological consequences with new work patterns.

Revascularization with percutaneous coronary intervention does not affect androgen status in males with chronic stable angina pectoris.

There is a clear association between low serum testosterone and coronary artery disease (CAD) in men. Hypotestosteronaemia is associated with accelerated atherosclerosis and a quarter of men with CAD are biochemically hypogonadal. Amongst those with CAD, hypotestosteronaemia is associated with increased mortality. Testosterone vasodilates coronary arteries, and exogenous testosterone reduces ischaemia. Whether hypotestosteronaemia is a cause or a consequence of CAD remains unanswered. The aim of this prospective observational study was to investigate whether coronary revascularization affected androgen status in men with stable angina pectoris. Twenty five men (mean age 62.7, SD 9.18) with angiographically significant CAD and symptomatic angina underwent full coronary revascularization by percutaneous coronary intervention. Androgen status and symptoms of angina, stress, depression and sexual function were assessed before, and at one and 6 months after the coronary revascularization. All patients underwent complete revascularization which was associated with a significant reduction in angina symptoms and ischaemia. No significant difference was seen in total testosterone (11.33 nmol/L baseline; 12.56, 1 month post; 13.04 at 6 months; p = 0.08). A significant and sustained rise in sex hormone-binding globulin was seen (33.99 nm/L baseline; 36.11 nm/L 1 month post PCI; 37.94 nm/L at 6 months; p = 0.03) Overall, there was no significant alteration in any other marker of androgen status including free testosterone or bioavailable testosterone. There was no change in symptoms of anxiety, depression or sexual function. Coronary revascularization has no sustained effect on androgen status. This supports the hypothesis that hypotestosteronaemia is not a consequence of angina pectoris or myocardial ischaemia.

Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Experimental studies suggest that androgens induce coronary vasodilatation. We performed this pilot project to examine the clinical effects of long-term low-dose androgens in men with angina. METHODS AND RESULTS: Forty-six men with stable angina completed a 2-week, single-blind placebo run-in, followed by double-blind randomization to 5 mg testosterone daily by transdermal patch or matching placebo for 12 weeks, in addition to their current medication. Time to 1-mm ST-segment depression on treadmill exercise testing and hormone levels were measured and quality of life was assessed by SF-36 at baseline and after 4 and 12 weeks of treatment. Active treatment resulted in a 2-fold increase in androgen levels and an increase in time to 1-mm ST-segment depression from (mean+/-SEM) 309+/-27 seconds at baseline to 343+/-26 seconds after 4 weeks and to 361+/-22 seconds after 12 weeks. This change was statistically significant compared with that seen in the placebo group (from 266+/-25 seconds at baseline to 284+/-23 seconds after 4 weeks and to 292+/-24 seconds after 12 weeks; P:=0.02 between the 2 groups by ANCOVA). The magnitude of the response was greater in those with lower baseline levels of bioavailable testosterone (r=-0. 455, P:<0.05). There were no significant changes in prostate specific antigen, hemoglobin, lipids, or coagulation profiles during the study. There were significant improvements in pain perception (P:=0.026) and role limitation resulting from physical problems (P:=0.024) in the testosterone-treated group. CONCLUSIONS: Low-dose supplemental testosterone treatment in men with chronic stable angina reduces exercise-induced myocardial ischemia.

Novel platelet membrane glycoprotein VI dimorphism is a risk factor for myocardial infarction.

BACKGROUND: Glycoprotein (GP) VI plays a crucial role in platelet activation and aggregation. We investigated whether polymorphic variation at the GP VI locus confers an increased risk of myocardial infarction (MI). METHODS AND RESULTS: Coding and 5' and 3' non-coding regions of the GP VI gene were analyzed by polymerase chain reaction and conformation sensitive gel electrophoresis in 21 healthy subjects. Ten dimorphisms, 5 of which predicted amino acid substitutions (T13254C, A19871G, A21908G, A22630T, C22644A), were identified. Two core haplotypes involving 7 dimorphisms (C10781A and G10873A and all those predicting amino acid substitutions) were apparent. The contribution of the T13254C dimorphism, which predicted the substitution of serine 219 by proline, to risk of MI was assessed in 525 patients with acute MI and 474 controls, all aged <75 years. The allelic odds ratio (OR) for MI associated with the 13254C allele was 1.16 (95% CI, 0.91 to 1.46; P=0.23). Compared with corresponding control subgroups, the 13254CC genotype was more common among cases who were female (OR, 4.52; 95% CI, 1.23 to 16.64; P=0.029), nonsmokers (OR, 2.50; 95% CI, 0.98 to 6.38; P=0.048), aged >/=60 years (OR, 6.48; 95% CI, 1.47 to 28.45; P=0.009) or carried the beta-fibrinogen -148T allele associated with increased fibrinogen levels (OR, 10.49; 95% CI, 1.32 to 83.42; P=0.02). In logistic regression analysis that took other cardiovascular risk factors into account, the interactions of GP VI genotype with age (P=0.005) and beta-fibrinogen genotype (P=0.035) remained significant. CONCLUSIONS: The GP VI 13254CC genotype increases the risk of MI, particularly in older individuals, and the interaction of the GP VI 13254C allele with other candidate risk alleles may accentuate this risk.

Testosterone does not adversely affect fibrinogen or tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) levels in 46 men with chronic stable angina.

OBJECTIVE: In women, sex hormones cause increased morbidity and mortality in patients with coronary heart disease (CHD) and adversely affect the coagulation profile. We have studied the effect of physiological testosterone replacement therapy in men on coagulation factor expression, to determine if there is an increased risk of thrombosis. METHODS: Double-blind, randomized, placebo-controlled trial of testosterone in 46 men with chronic stable angina. Measurements of free, total and bioavailable testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH), estradiol, plasminogen activator inhibitor-1 (PAI-1), fibrinogen, tissue plasminogen activator (tPA) and full blood count were made at 0, 6 and 14 weeks. RESULTS: Bioavailable testosterone levels were: 2.58 +/- 0.58 nmol/l at baseline, compared with 3.35 +/- 0.31 nmol/l at week 14 (P < 0.001) after treatment compared with 2.6 +/- 0.18 nmol/l and 2.44 +/- 0.18 nmol/l in the placebo group (P was not significant). There was no change in fibrinogen (3.03 +/- 0.18 g/l at baseline and 3.02 +/- 0.18 g/l at week 14, P = 0.24), tPA activity (26.77 +/- 4.9 Iu/ml and 25.67 +/- 4.4 Iu/ml, P = 0.88) or PAI-1 activity (0.49 +/- 0.85 Iu/ml and 0.36 +/- 0.06 Iu/ml, P = 0.16) with active treatment and no differences between the groups (at week 14, P value 0.98, 0.59 and 0.8 for fibrinogen, PAI-1 and tPA respectively). Haemoglobin concentration did not change over time, in the testosterone group (1.44 +/- 0.02 g/l and 1.45 +/- 0.02 g/l, P = 0.22). CONCLUSION: Physiological testosterone replacement does not adversely affect blood coagulation status.

Life-saving or life-prolonging? Interpreting trial data and survival curves for patients with congestive heart failure.

Chronic heart failure is responsible for considerable suffering and mortality throughout the world. Clinical trials have consistently demonstrated the benefits of pharmacological therapies such as angiotensin-converting enzyme inhibitors and beta-adrenoceptor blockers. These drugs are often quoted as reducing mortality from heart failure, yet all patients with heart failure deteriorate and most will die because of their disease. Therapies in heart failure are not truly life saving; they modify the natural history of the disease and delay the time to deterioration. The time benefit in survival is not usually reported in clinical trials, which are conducted over fixed time points and report risk reductions during this period only. In this paper, we discuss the use of prolongation of life statistics as an outcome measure in clinical trials and review simple techniques for calculating the lifetime benefit of pharmacological intervention in heart failure using data from a number of major studies

Pitfalls and problems of relying on serum troponin.

Cardiac troponin (cT) is released after myocardial damage. In the appropriate clinical setting, a measured elevation of cT can increase the diagnostic rate of myocardial infarction and acute coronary syndrome. Elevations of cT, however, can occur in a wide variety of other clinical situations. Failure to recognize this can lead to an over-diagnosis of myocardial infarction (MI). We present clinical cases from our institution that illustrate this diagnostic problem, and review similar cases in the literature. We also discuss the implications of an erroneous diagnosis of myocardial infarction, for the patient and for the health services.

Effect of treatment of carotid artery stenosis on blood pressure: a comparison of hemodynamic disturbances after carotid endarterectomy and endovascular treatment.

BACKGROUND AND PURPOSE: Carotid intervention by carotid endarterectomy (CEA) or endovascular treatment may cause hemodynamic change. The immediate and long-term effects on blood pressure after these procedures were assessed. METHODS: Patients were randomized to CEA (n=49) or endovascular treatment (n=55) that comprised percutaneous transluminal angioplasty alone (n=31), balloon-expandable stent (n=13), or self-expandable stent (n=11). A baseline 24-hour ambulatory blood pressure recording was made before carotid intervention and repeated at 24 hours, 1 month, and 6 months after the procedure. RESULTS: In the first 24 hours after the procedure, episodes of hypotension occurred in 75% of the CEA group and 76% of the endovascular group; hypertension occurred in 11% and 13%, respectively. There was a significant fall in blood pressure at 1 hour after the procedure in both groups (24 and 16 mm Hg fall in CEA and endovascular groups, respectively), but this was only sustained in the endovascular group. The pattern of blood pressure response in the first 24 hours was significantly different (P<0.0001, ANCOVA). Systolic blood pressure was significantly lower at 1 and 6 months only in the surgical group (6 and 5 mm Hg fall, respectively). CONCLUSIONS: Both CEA and endovascular treatment have an effect on blood pressure stability, particularly within the first 24 hours after the procedure.

Effect of delayed esophageal transit on acetaminophen absorption.

Twenty patients awaiting cardiac catheterization swallowed a single tablet containing acetaminophen and barium sulfate. The first 11 subjects swallowed the tablet while supine; its progress down the esophagus was followed by fluoroscopy. In 10 of these subjects, transit of the tablet was delayed in the esophagus. The other nine subjects swallowed the tablet while standing; it entered the stomach immediately. The plasma concentration profile of acetaminophen was measured in all subjects. When there was delayed esophageal transit of tablets, the initial absorption of acetaminophen (measured as the AUC over the first 60 min) was lower than that after normal esophageal transit of tablets. The peak plasma acetaminophen concentration was also lower and occurred on average 70 min later when transit was delayed. These kinetic changes decrease the effectiveness of acetaminophen as an analgesic. We recommend that, to ensure rapid and complete drug absorption, patients be advised to swallow tablets with a large amount of water while standing.

Analysis of the postulated interaction between the angiotensin II sub-type 1 receptor gene A1166C polymorphism and the insertion/deletion polymorphism of the angiotensin converting enzyme gene on risk of myocardial infarction.

A synergistic interaction between the insertion/deletion (I/D) polymorphism within the angiotensin-converting enzyme (ACE) gene and an A/C transversion at nucleotide position 1166 within the angiotensin II sub-type 1 receptor (AT1R) gene on risk of myocardial infarction has been reported. The risk associated with the ACE DD genotype increased with the number of AT1R C alleles present. To investigate this further, ACE I/D and AT1R A1166C genotypes were determined in 541 cases recruited at the time of infarction and 507 population-based controls. There was no difference in either the genotype distribution or allele frequencies between cases and controls for either the ACE polymorphism (P=0.48 and 0.35 respectively) or the AT1R polymorphism (P=0.35 and 0.21 respectively). Odds ratios for risk of MI associated with the ACE DD and AT1R CC genotypes were 1.09 (95% CI, 0.82-1.45) and 1.06 (0.67-1.68) respectively. 3.1% of cases versus 3.6% of controls were homozygous for both the D and C alleles (P=0.71). There was no increase in risk associated with the DD genotype in the presence of either one or two AT1R C alleles in the whole cohorts (OR 0.99, 95% CI 0.65-1.51 and 0.76, 95% CI 0.30-1.88, respectively) nor in sub-groups defined by specific risk factors. In conclusion, no evidence was found to support any interaction between the ACE gene I/D polymorphism and the ATIR gene A1166C transversion in determining the risk of myocardial infarction in the population studied.