Cardiovascular diseases and erectile dysfunction: the two faces of the coin of androgen deficiency.

Traditionally, clinical conditions synonymous with the ageing male included cardiovascular disease (CVD), type 2 diabetes mellitus (DM) and sexual dysfunction, and were widely regarded as independent clinical entities. Over the last decade, interrelationship of clinical conditions has been convincingly demonstrated. Declining testosterone levels in the elderly, once regarded as an academic endocrinological question, appear to be central to the listed pathologies. It is now clear that erectile dysfunction is an expression of endothelial dysfunction. Testosterone deficiency is associated with an increased incidence of CVD and DM. The latter is often the sequel of the metabolic syndrome. Visceral obesity, a pivotal characteristic of the metabolic syndrome, suppresses the hypothalamic-pituitary-testicular axis leading to diminished testosterone production. Conversely, substantial androgen deficiency leads to signs and symptoms of metabolic syndrome. It is erroneous not to include testosterone measurements in the progress of the CVD, DM and erectile dysfunction. These conditions correlate strongly with testosterone deficiency.

Day case laparoscopic incisional hernia repair is feasible, acceptable, and cost effective.

BACKGROUND: Day case surgery is increasingly performed in the United Kingdom. Laparoscopic techniques have increased the number of conditions suitable for a day surgical approach. Findings have shown that laparoscopic incisional hernia repair (LIHR) is superior to conventional open techniques. This study aimed to show that day case LIHR is safe, produces a good clinical outcome, and is cost effective. METHODS: Day case laparoscopic repair was performed for 31 consecutive patients (10 men; median age, 67 years; range, 39-80 years). Data were entered prospectively into a database. Patients were discharged within 8 h committed to a 10-day course of oral diclofenac 50 mg three times daily and 2 tablets of codydramol four times daily. Follow-up evaluation was by telephone consultation. Hospital costs for LIHR and open repair were compared. RESULTS: All procedures were completed laparoscopically on a day case basis. Additional unsuspected defects were found in eight cases (25.8%). The median mesh size was 140 cm2 (range, 25-375 cm2), and the median body mass index (BMI) was 28.7 kg/m2 (range, 20-37.1 kg/m2). Operations were performed or supervised by a single consultant surgeon (S.J.W.). Six postoperative seromas resolved spontaneously. Two port-site infections required oral antibiotics, and one diathermy pad burn healed with simple dressings. The median analgesia requirement was 7 days (range, 0-152 days). There were no recurrences during a median follow-up period of 15 months (range, 3-24 months). There was a saving of 616 pounds sterling per procedure. CONCLUSIONS: Day case laparoscopic repair of incisional hernias is feasible and safe and has a good clinical outcome. The hospital costs are less than for open techniques.

Contemporary mortality due to acute myocardial infarction, unstable angina and exertional angina in a population in South East London.

BACKGROUND: Data on the contemporary mortality of coronary heart disease (CHD) are surprisingly sparse. AIM: To describe the contemporary mortality of all manifestations of CHD. DESIGN: Prospective follow-up of patients with a first presentation of CHD in a defined population. METHODS: We studied 537 patients with a first presentation of acute myocardial infarction, unstable angina or new exertional angina in Bromley Health Authority, London (population 295,000). Patients were prospectively monitored for cardiac and non-cardiac mortality for a median of 6 years. RESULTS: During a median 6 years follow-up, there were 88 (16%) deaths. Survival free from cardiac death was not significantly different between unstable angina (92%) and new exertional angina (94%), but was lower for acute myocardial infarction (84%). DISCUSSION: Mortality from CHD appears to be falling. However, efforts to prevent myocardial infarction should continue to be a priority, because on-going early mortality remains high. New exertional angina should be diagnosed and managed promptly, as its mortality is similar to that of unstable angina.

Clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction.

AIMS: We examined the clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary angioplasty or thrombolytic therapy for acute myocardial infarction. METHODS AND RESULTS: We studied 2635 patients enrolled in 10 randomized trials of primary angioplasty (n=1302) vs thrombolytic therapy (n=1333) in acute myocardial infarction, and baseline characteristics of the two groups were comparable. Increase in presentation delay is associated with older age, female gender, diabetes and an increased heart rate. We classified the patients according to the time delay from symptom onset to presentation into three categories: early presentation (<2 h), intermediate presentation (2-4 h), and late presentation (>or=4 h). At 30 days the combined rate of death, non-fatal reinfarction and stroke in patients presenting early was 5.8% in the angioplasty group vs 12.5% in the thrombolysis group, in patients with intermediate presentation, 8.6% vs 14.2%, respectively, and in patients presenting late 7.7% vs 19.4%, respectively. With increasing time from symptom onset to presentation, all major adverse cardiac event rates show a trend to a larger increase in the thrombolysis group compared to the angioplasty group, both at 30 days and at 6 months after the acute event. CONCLUSIONS: Major adverse cardiac event rates are lower after angioplasty compared to thrombolysis, irrespective of time to presentation. With increasing time to presentation major adverse cardiac event rates increase after thrombolysis but appear to remain relatively stable after angioplasty.

Exercise electrocardiography and aortic Doppler velocimetry in asymptomatic identical twins discordant for type 1 (insulin dependent) diabetes.

OBJECTIVE: To determine the influence of insulin dependent diabetes on the prevalence of myocardial ischaemia and on global left ventricular systolic performance. DESIGN: Stress treadmill electrocardiograms and simultaneous Doppler measurement of aortic maximum acceleration were obtained during exercise on symptom free subjects. The electrocardiograms were scored blindly according to the Minnesota code. PARTICIPANTS: 39 identical twin pairs (22 male) discordant for insulin dependent diabetes and 39 non-diabetic controls of similar age and sex were examined. The twins and controls had a mean age of 37 (range 25-69) with a mean (SD) duration of diabetes in the diabetic twin of 17 (7) years. Those selected were normotensive and had no renal impairment. RESULTS: Systolic blood pressure was significantly higher in the diabetic twins than in their non-diabetic cotwins both at rest (p < 0.05) and at peak exercise (p < 0.01). Electrocardiographic evidence of ischaemia was not correlated within twin pairs and was found in similar numbers of diabetic twins, their non-diabetic cotwins, and control subjects. Abnormal electrocardiograms were found in a similar number of diabetic twins (23%), non-diabetic cotwins (18%), and controls (15%). There was a significant correlation in Doppler measurements of global left ventricular systolic function within the identical twins; no significant difference was found for these Doppler measurements in the diabetic twins, non-diabetic cotwins, or controls. CONCLUSION: Exercise characteristics and cardiac function seem to be subject to shared genetic or shared environmental influences or both, whereas electrocardiographic features of ischaemia seem to be environmentally determined. In a selected cohort of diabetic identical twins without evidence of nephropathy there was no evidence that diabetes influenced the prevalence of myocardial ischaemia or global left ventricular systolic function.

Efficacy of intermittent (eight hours off) transdermal nitrate therapy in stable angina.

The efficacy of intermittent (16 h on/8 h off) transdermal nitrate therapy (0.4 mg/h) was assessed in 46 patients with chronic stable angina, all but one of whom were on concomitant beta-blocker and/or calcium antagonist therapy. The study was a randomised, double-blind placebo-controlled crossover with two consecutive 7-day treatment periods, conducted at two centres. Prior to entry into the study patients were screened for exercise test reproducibility and nitrate response. Patch efficacy was determined by maximal symptom limited treadmill stress testing (Bruce protocol) and subjective diary card data. Analysis of variance showed that active treatment significantly improved time to onset of angina (P < 0.001), time to 1 mm ST-segment depression (P < 0.001) and total exercise duration (P < 0.001) compared with placebo from 385.7, 310.8 and 458.1 s to 455.7, 385.2 and 497.1 s, respectively. Nitrate patch therapy significantly reduced diastolic and systolic blood pressures without significantly increasing resting heart rate. There was a marginal reduction in the incidence of angina attacks and sublingual nitroglycerine consumption during active treatment. We conclude that intermittent transdermal nitrate therapy significantly improves exercise tolerance in patients with chronic angina pectoris and that this improvement occurs in addition to conventional anti-anginal therapy.

Emerging patterns of heart disease in HIV infected homosexual subjects with and without opportunistic infections; a prospective colour flow Doppler echocardiographic study.

We studied 124 homosexual men aged 36.7 +/- 7.6 years (range 23-57) using Doppler echocardiography. One hundred and one patients (Group A) had had acquired immunodeficiency syndrome for 1.6 +/- 1.0 years and 23 patients (Group B) had had HIV infection without opportunistic infections for 3.2 +/- 2.3 years. Doppler echocardiography was normal in 31% of Group A patients and in 61% of Group B. Pericardial effusion was found in 44 Group A patients (44%) and two Group B patients (9%). In Group A, left ventricular dilatation and/or dysfunction were found in 20 patients (20%), aortic root dilatation and regurgitation in eight patients (8%) and an intracardiac echogenic mass in seven patients (7%); in Group B one patient (4%) had an intracardiac mass. Forty-four (44%) Group A patients had cardiac presentations, and of these 22 had cardiomegaly with clinical signs of heart failure; 10 patients had tachyarrhythmias compared to only two in Group B. Although the CD4 lymphocyte count (%) was significantly lower in Group A than in Group B (5.4 +/- 6.1 vs 13.3 +/- 7.3, P < 0.001), the presence of pericardial effusion, left ventricular dysfunction, right-sided cardiac enlargement or the duration of HIV infection, did not relate to the CD4 level in either group. Although often not diagnosed clinically, cardiac involvement in patients with AIDS is a clinical reality, with pericardial effusion, cardiomyopathy and left ventricular dysfunction appearing to have a high prevalence in male homosexual patients with AIDS. These clinical and echocardiographic findings are associated with clinically apparent intercurrent opportunistic infections, rather than the HIV virus per se, or the severity of infection as reflected by the CD4 count.

The long-term safety and tolerability of transdermal glyceryl trinitrate, when used with a patch-free interval in patients with stable angina.

The safety and tolerability of intermittent (16 hours on/8 hours off) nitrate patch therapy (0.2, 0.4 or 0.6 mg/hr: dose adjusted as required) was studied for a median duration of 356 days in 106 patients (mean age 60.9 +/- 8.6 years) with angina pectoris. Most patients (82%) were on existing beta-blocker and/or calcium antagonist therapy. Safety, tolerability and efficacy data were obtained by means of patient diary cards and regular clinic visits. Almost 90 treatment years revealed no significant or serious adverse events, and there were no changes in haematology or biochemistry associated with intermittent nitrate patch therapy. The most frequently reported side-effects were headache, skin reactions and dizziness (53%, 20% and 8% of patients respectively). Treatment resulted in a sustained reduction in the frequency and severity of angina attacks, reduced sublingual GTN consumption, an improvement in general wellbeing and a rise in the proportion of patients in whom angina was controlled.

The role of captopril as single therapy in hypertension and angina pectoris.

Eighteen hypertensive patients with a resting diastolic blood pressure between 100 and 120 mmHg who also had angina and proven coronary arterial disease entered a dose titration study to evaluate the efficacy of captopril as a single therapy in hypertension and coexisting stable angina. Captopril was administered for 2 weeks at 25 or 50 mg three times daily and the patients evaluated subjectively and by maximal symptom limited treadmill exercise testing. In comparison to placebo captopril 25 mg and 50 mg dosage increased time to 1 mm ST depression from 188.2 +/- 24.4 sec on placebo to 337.6 +/- 29.5 and 364.2 +/- 36.2 sec respectively (P less than 0.01). The maximum ST segment depression was reduced from 2.5 +/- 0.25 mm on placebo to 1.4 +/- 0.22 mm on captopril 25 mg and 1.2 +/- 0.30 mm on captopril 50 mg (P less than 0.01). Exercise duration increased from 310.3 +/- 21.4 sec on placebo to 438.3 +/- 27.3 sec on captopril 25 mg and to 460.9 +/- 26.5 sec on captopril 50 mg (P less than 0.01). The resting systolic blood pressure decreased from 184.1 +/- 4.7 mmHg on placebo to 159 +/- 4.2 mmHg on captopril 25 mg and to 150.9 +/- 4.6 mmHg on captopril 50 mg (less than 0.01). Similarly, diastolic blood pressure decreased from 111.6 +/- 2.1 mmHg on placebo to 93.8 +/- 1.3 mmHg on captopril 25 mg and to 90.0 +/- 1.7 mmHg on captopril 50 mg (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of nifedipine and isosorbide mononitrate in combination with atenolol in stable angina.

Many patients with angina pectoris whose symptoms are not completely controlled by beta-blockers are treated with several types of drugs, but it is not clear whether addition of a calcium-channel antagonist and/or a nitrate confers any advantage over beta-blockade alone. 18 patients receiving atenolol for stable angina pectoris completed a double-blind, randomised, crossover trial of atenolol treatment plus placebo, isosorbide mononitrate, nifedipine, and mononitrate and nifedipine (triple therapy). The patients were assessed subjectively and by treadmill exercise testing and 24 h ambulatory electrocardiographic recordings at the end of each 4-week treatment period. There were no significant differences among the treatment periods in angina attack rates, glyceryl trinitrate consumption, exercise duration to onset of angina or 1 mm ST depression, or duration of symptomless ischaemia. Total exercise duration was longer on atenolol plus mononitrate than on atenolol alone (mean difference 46 [95% confidence interval 18-88] s; p = 0.005), atenolol plus nifedipine (36 [2-71] s; p = 0.04), or triple therapy (28 [6-61] s; not significant). In 12 patients the exercise time was shorter on triple therapy than on atenolol plus mononitrate alone. Although "maximum" antianginal treatment with two or three drugs is commonly accepted, this approach confers no substantial advantage over optimum beta-blockade as monotherapy. If a second drug is needed, there is a slight advantage in favour of isosorbide mononitrate, but if this is not effective, treatment should be changed rather than added. Many patients with angina pectoris seem to be pharmacologically overtreated.

Raised exercise diastolic blood pressure as indicator of ischaemic left ventricular dysfunction.

91 (16.8%) of 541 consecutive patients investigated for chest pain or after recent uncomplicated myocardial infarction had a rise in diastolic blood pressure (DBP) of more than 15 mm Hg during a symptom-limited treadmill test. 63 also had electrocardiographic evidence of ischaemia, but 28 did not have 1 mm ST segment depression, of whom 24 had angiographic evidence of more than 70% stenosis of two or more major coronary arteries. 55 of these 91 patients underwent coronary artery bypass surgery; repeat angiography in 22 at 12 months showed an improved left ventricular ejection fraction in 18 who had a normal postoperative DBP response, but no change in ejection fraction in the 4 who still had an abnormal rise in DBP on exercise. Exercise-induced ischaemia may cause a reversible fall in cardiac output that sometimes leads to reflex vasoconstriction and a rise in DBP before a fall in systolic blood pressure or ECG evidence of ST segment depression. An abnormal DBP response to exercise may identify some patients at high risk of myocardial infarction who might otherwise have false-negative exercise tests.

Acute and chronic effects of once-daily isosorbide-5-mononitrate on the exercise capacity of patients with angina pectoris treated with a beta-blocking drug.

Forty-four patients with stable effort angina pectoris were included in a double-blind, randomised, placebo-controlled, parallel group study to compare the effect of two slow-release forms of isosorbide-5-mononitrate ('Ismo-Retard' 40 mg and 'Imdur' 60 mg) on exercise capacity when given as an adjunctive treatment to beta adrenoreceptor blocking therapy. In a symptom-limited exercise test performed three hours after the first dose, Ismo-retard increased the total duration of exercise by 92 seconds (confidence interval (CI) 5.1-116.9) p less than 0.006, and the time of onset to anginal pain by 117 seconds (CI 27.8, 156.1) p less than 0.004. A similar improvement in total duration of exercise (by 87 seconds) was noted three hours following 15 consecutive once-daily doses (CI 16.8-128) p less than 0.02, and in the time of onset to anginal pain by 101 seconds (CI 19.8-139.6) p less than 0.01. For Imdur the corresponding results were 53 seconds (CI 12.7-56.3), 84 seconds (CI 15.4-103.7), p less than .02, 54 seconds (CI 1.4-78.4) and 85 seconds (CI 6.9-120.5) respectively. These results would suggest that both active treatments were effective anti-anginal agents.

A randomised double-blind crossover study of isosorbide mononitrate and nifedipine retard in chronic stable angina.

In order to evaluate and compare the efficacy and safety of nifedipine retard and isosorbide-5-mononitrate as monotherapy in the treatment of stable angina, 18 patients with abnormal exercise electrocardiograms and angiographically proven coronary arterial disease were studied in a randomised placebo controlled double-blind crossover study comparing isosorbide 20 mg twice a day, sustained released isosorbide 40 mg once daily and nifedipine 20 mg twice a day each given for two weeks. Patients were assessed subjectively by counting the frequency of anginal attacks and glyceryl trinitrate consumed and objectively by maximal symptom-limited treadmill stress tests performed at "trough" therapeutic blood levels on the last day of each treatment period. There were no significant differences in all parameters between entry and run-out placebo. Compared to placebo, all three active treatments showed significant improvement in exercise time to 1 mm ST segment depression, amount of maximum ST segment depression and exercise duration. All three active treatments also significantly reduced the consumption of glyceryl trinitrate and frequency of anginal attacks. There were no significant differences between active treatments. Thus similar clinical improvements were produced by nifedipine retard and isosorbide, both being shown to be equally effective starting therapy for the treatment of patients with stable angina pectoris. Although anginal frequency was reduced by one third and exercise time increased residual symptoms and exercise ischaemia suggest that nifedipine retard and isosorbide may be more clinically useful in combination therapy. Neither demonstrated tolerance after two weeks of therapy.

Genetic segregation analysis of familial mitral valve prolapse shows no linkage to fibrillar collagen genes.

Three pedigrees were identified in which mitral valve prolapse seemed to be inherited as a mendelian autosomal dominant trait. The segregation of the genes encoding the major fibrillar collagens present in valve tissue, collagens I and III, was analysed by use of restriction enzyme site variants as genetic markers. In one pedigree there was discordance between the segregation of the disease and markers for all three collagen genes. In another, there was discordance between the disease and markers for both collagen I loci. This is evidence against the disease being generally the result of mutations of the genes encoding the major fibrillar collagens.

Epanolol. A new once-daily antianginal agent: dose finding and long term efficacy.

Epanolol is a new once-daily agent for the treatment of angina pectoris. This study was conducted in 2 parts. Firstly, a dose-finding study was performed using placebo and epanolol 100, 200, 300 and 400mg to assess the efficacy and safety of the drug. Once-daily epanolol 200mg was an effective dose, significantly reducing angina attack rate and increasing exercise duration and work output. At the same time, an improvement was noted in the patients' well-being and their ability to undertake normal daily activities. The 200mg dose regimen was used in a long term (12 months) assessment of the efficacy and safety of epanolol in the second part of this study. The efficacy of epanolol was clearly maintained throughout the full treatment period without adverse events or withdrawals as a result of treatment. The effectiveness and safety of epanolol are attributed to its selective beta 1-partial agonist activity. At rest, the degree of agonist activity (about 20% of that of isoprenaline) may prevent some of the untoward effects occasionally seen with full beta-blockers. During exercise, the antagonist activity becomes apparent and cardiac ischaemia is reduced.

Effect of partial agonist activity on the side effects of beta-blockade in patients with chronic stable angina.

Some side effects of the beta 1-adrenoceptor blocker atenolol may result from depression of cardiac output at rest. They may, therefore, be reduced by the use of drugs with beta 1-partial agonist activity, such as epanolol. We compared once-daily atenolol 100mg and epanolol 200mg in 20 patients reporting side effects while taking atenolol for chronic stable angina. A double-dummy, double-blind, crossover design was used to assess side effects by use of visual analogue scales and interviews, and antianginal efficacy by treadmill exercise tests and diary cards. In a comparison with atenolol, no significant differences in exercise time (686 +/- 11 seconds vs 685 +/- 10 seconds, maximum ST depression (1.02 +/- 0.09mm vs 1.07 +/- 0.08mm), time to 1mm ST depression (8.4 +/- 1.9 minutes vs 9.0 +/- 2.0 minutes), or days without angina (median 100% in both) were shown. All visual analogue scores were higher with epanolol (subjective energy 58.3 +/- 1.7 vs 54.3 +/- 1.5, well-being 61.8 +/- 1.8 vs 58.6 +/- 1.5 and warmth of extremities 68.4 +/- 3.6 vs 62.0 +/- 3.1). Although these differences did not attain statistical significance, 11 patients expressed a preference for epanolol and only 6 for atenolol. We conclude that, in this study, epanolol is as effective as atenolol as an antianginal agent for chronic stable angina. It improved the side effect profile in some but not all patients.

Physical and psychological correlates of severe heart disease in men.

Seventy eight men were assessed one month before coronary artery bypass graft surgery using standardized measures of psychiatric morbidity and personality as well as a measure of emotional expression (the CECS). All patients had at least one coronary vessel occluded by 75% or more of its diameter, and functional capacity was assessed by calculating the exercise treadmill time (in seconds) for each patient. Most of the variance in exercise treadmill time was accounted for by the following variables: young age, short duration of symptoms, and less severe angina. Only one of five men was designated a psychiatric 'case'. The only psychological measure significantly associated with atherosclerosis was expression of fear (on the CECS). A measure of Type A behaviour (Bortner score) was related to exercise treadmill time, but not to any of the angiographic or clinical indices of coronary heart disease (CHD). Like other measures of Type A behaviour, the Bortner scale is psychometrically impure and has doubtful validity. More valid behavioural variables (such as those measured by the CECS) require further investigation. Future studies on the relation between psychological factors and the extent of CHD should take account of not only sex differences but also patients without significant CHD: high rates of psychiatric morbidity in such patients confound the relation between psychological trait measures and atherosclerosis.