Sustained release verapamil, a once daily preparation: objective evaluation using exercise testing, ambulatory monitoring and blood levels in patients with stable angina.

The efficacy of a once daily, sustained release formulation of verapamil (Verapamil SR, 360 mg) was evaluated in 19 patients with chronic angina pectoris using a double-blind placebo-controlled crossover protocol. Evaluation by exercise testing, 24 hour electrocardiographic ambulatory monitoring and blood drug level assays was performed at the end of each 2 week phase, 21 to 23 hours after the last dose. After the crossover protocol, all patients were given sustained release verapamil for 4 weeks and the evaluation was repeated. Exercise time (mean +/- SEM) increased from 7.4 +/- 0.6 minutes with placebo to 9.6 +/- 0.8 minutes with verapamil (p less than 0.001) and to 9.5 +/- 0.7 minutes (p less than 0.001) after 4 weeks of therapy. The mean time to 1 mm ST depression also increased significantly, from 4.5 +/- 0.4 and 4.8 +/- 0.5 minutes in bipolar leads CM5 and CC5, respectively, with placebo, to 5.5 +/- 0.6 (p less than 0.05) and 6.2 +/- 0.5 minutes (p less than 0.01) with verapamil. Maximal ST depression and rest and peak heart rates were not altered significantly. The mean rate-pressure product was 208 +/- 9.9 with placebo and decreased to 189 +/- 7.7 (p less than 0.05) with verapamil but rose to 200.6 +/- 10.4 (p = NS) after 4 weeks of therapy. The mean hourly heart rates were lower with the drug than with placebo throughout the 24 hour period but there was no significant bradycardia, arrhythmia or heart block.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between plasma cholesterol and coronary artery disease in Asians.

Cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations were measured in 150 male survivors of first myocardial infarction and in 115 age and ethnic matched healthy controls. The total cholesterol concentration was higher in whites than in respective Asian groups and higher in patients than in controls (P less than 0.001). The ratio of cholesterol to HDL cholesterol was significantly higher in patients (P less than 0.001) and in both ethnic groups was a powerful independent predictor of cases. In Asians, the extent of coronary atheroma assessed by arteriography 2-12 weeks after infarction correlated independently with the total cholesterol concentration (P = 0.03). Thus, in Asian men, the lower level of total cholesterol compared to whites may be misleading. In Asian men the extent of atheroma correlated with the total cholesterol concentration and the relative risk of infarction increased with the ratio of total to HDL cholesterol. At a given level of cholesterol different ethnic groups may be at differing levels of cardiac risk and the cholesterol ratio may be a more appropriate means of inter-ethnic comparison.

Hageman factor and risk of myocardial infarction in middle-aged men.

In order to evaluate whether Hageman factor (XII) is increased in survivors of myocardial infarction and whether this in turn influences factor VII coagulant activity (VIIc), we examined the coagulation and lipoprotein profiles in 82 subjects, 51 of whom had a definite history of myocardial infarction and 31 healthy volunteers invited from a local general practice register for a cardiovascular screen. Both serum cholesterol (P = 0.03) and plasma fibrinogen levels (P = 0.02) were significantly elevated in cases compared with controls. There were no significant differences in coagulant activities, and in particular factor XII concentration was not significantly different between groups. Furthermore, in 47 of the subjects, 28 of whom had a history of myocardial infarction, a more detailed analysis, including measurement of VIIc after overnight incubation of plasma at 4 degrees C, was undertaken. Approximately half the subjects in either group showed some evidence of activation, though history of myocardial infarction was not in itself a significant predictor of this. All measures of XII concentration related positively to VIIc after cold activation, the strongest being the measure of amidolytic activity following activation of factor XII (XIIAm) (r = 0.5, P < 0.01). In addition, XIIa, a measure of activity due to enzymes derived from factor XII, related strongly to many of the measured lipoprotein variables, particularly VLDL cholesterol and triglycerides, supporting the hypothesis that negatively charged molecules such as free fatty acids on larger lipoprotein particles provide the contact surface necessary to activate factor XII. The findings confirm the importance of this alternative pathway in leading to activation of factor VII.

Gemfibrozil reduces plasma prothrombin fragment F1 + 2 concentration, a marker of coagulability, in patients with coronary heart disease.

The effects of gemfibrozil on several indices of haemostatic activity were explored in male patients with coronary heart disease (CHD). Sixty-three of 71 patients completed a crossover study in which gemfibrozil 1,200 mg/day and matching placebo were each taken in randomised order for 2 months in a double-blind manner, separated by a 2-month washout period. Serum cholesterol decreased by an average (95% confidence interval) of 12 (9 to 15)% and non-fasting triglyceride concentration by 43 (34 to 51)% during active treatment. Plasma prothrombin fragment F1 + 2 concentration, a marker of the in vivo rate of generation of thrombin, was 25 (12 to 37)% lower on average while on gemfibrozil than during the placebo phase. Factor VII coagulant activity (VIIc) and antigen concentration, and fibrinopeptide A concentration were not influenced by gemfibrozil in the group overall. However, the VIIc response appeared to be dependent upon the untreated cholesterol level. Hypercholesterolaemic men (cholesterol greater than 6.5 mmol/l) experienced a significant reduction in VIIc averaging 6% of standard during active therapy. Other effects of gemfibrozil were a 5 (2 to 9)% increase in plasma fibrinogen by a gravimetric method, an 11 (8 to 13)% increase in platelet count, and a 6 (2 to 10)% reduction in white cell count. The reduced incidence of CHD following gemfibrozil therapy in hyperlipidaemic patients may arise in part through a reduction in procoagulant activity and thus the risk of an occlusive coronary thrombosis.

Comparison of nicorandil and atenolol in stable angina pectoris.

The efficacy of nicorandil was compared with atenolol in 37 patients with chronic stable angina using a randomized, placebo-controlled, parallel study design. After a single-blind placebo phase, patients were randomized to receive nicorandil or atenolol using a double-dummy technique. Patients took nicorandil 10 mg twice daily or atenolol 50 mg once daily for the first 3 weeks, and if no adverse effects were encountered they took nicorandil 20 mg twice daily or atenolol 100 mg once daily, for the final 3-week phase. Treadmill exercise tests were performed at the end of each treatment phase immediately before and 2 hours after the morning dose of medication. Groups were demographically similar. Placebo exercise times were 7.06 (0.60) minutes (mean +/- standard error of the mean) in the nicorandil group and 6.81 (0.47) minutes in the atenolol group. After 6 weeks, improvements in exercise time were before dosing: +1.47 (0.40) minutes with nicorandil (p less than 0.005) and +1.33 (0.29) minutes with atenolol (p less than 0.001). Improvements after therapy was administered were +2.45 (0.41) minutes with nicorandil (p less than 0.001) and +2.37 (0.43) minutes with atenolol (p less than 0.0001). Whereas, the predose peak exercise double product (heart rate X systolic blood pressure mm Hg/100) was reduced with atenolol (-43.6 units; p less than 0.001), an increase (+7.56 units; difference not significant) was noted with nicorandil. One patient taking atenolol and 5 taking nicorandil developed persistent headaches. One subject with severe 3-vessel coronary artery disease had fatal myocardial infarction within 3 days of starting nicorandil, 10 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Antianginal efficacy of carvedilol, a beta-blocking drug with vasodilating activity.

The efficacy of carvedilol, a new vasodilating beta-blocking drug, was evaluated in 20 patients with chronic angina using a single-blind, placebo-controlled protocol. A 2-week placebo phase was followed by therapy with carvedilol, 25 mg twice daily for 2 weeks, after which the dose was doubled. There was then a second placebo phase lasting 2 weeks. Treadmill exercise testing, 24-hour ambulatory electrocardiographic monitoring and drug blood level assays were performed at the end of each phase. Exercise time (mean +/- standard error of mean) increased from 7.4 +/- 0.5 minutes during placebo to 9.0 +/- 0.5 minutes carvedilol, 25 mg twice daily (p less than 0.001), and to 9.2 +/- 0.4 minutes with 50 mg twice daily (p less than 0.001). Mean time to 1 mm of ST depression in both bipolar leads CM5 and CC5 increased significantly, but peak ST depression did not change. Heart rate at rest was reduced at both dose levels, from 86 +/- 4 beats/min during placebo to 70 +/- 2 beats/min with 25 mg twice daily (p less than 0.001) and to 67 +/- 3 beats/min with 50 mg twice daily (p less than 0.001). Systolic blood pressure at rest was significantly reduced at both doses (p less than 0.05; p less than 0.01), but blood pressure during exercise was decreased only with the larger dose (p less than 0.001). The exercise rate-pressure product was 182 +/- 9 with placebo and decreased to 153 +/- 5 with 25 mg twice daily (p less than 0.001) and to 138 +/- 6 with 50 mg twice daily (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and pharmacokinetics of ioversol in healthy volunteers.

Ioversol 320, a new nonionic iodinated contrast medium, was injected intravenously into 24 healthy male volunteers using saline as a control. Physical examination, vital signs, electrocardiogram, biochemical and hematological data were recorded before and at intervals after injection. No significant changes were observed. Seventeen volunteers reported no side effects; six volunteers had mild transitory symptoms considered to be related to the contrast medium. The authors conclude that broader clinical trials can be safely conducted to determine safety and tolerability of ioversol.

Myocardial infarction associated with exercise in young men.

Three male patients age 17, 23 and 27 years developed chest pain during, or in one case, immediately after competitive sport. In all cases myocardial infarction was diagnosed by standard criteria or the diagnosis was made on the basis of indium-111 antimyosin imaging, contrast ventriculogram and thallium scan. Coronary arteriography was normal in two and a blocked right coronary artery was found in one. Exercise-related myocardial infarction can occur in young men and chest pain during exercise in this age-group may not always be innocent.

Ventricular tachycardia induced by Valsalva's manoeuvre in a patient with hypertrophic cardiomyopathy.

We describe a patient with hypertrophic cardiomyopathy who developed reproducible ventricular tachycardia during Valsalva's manoeuvre. This phenomenon has not previously been described.

Endomyocardial fibrosis in a white girl with sero-positive juvenile rheumatoid arthritis.

A white girl with sero-positive juvenile rheumatoid arthritis was subsequently found to have endomyocardial fibrosis. We believe that these two rare conditions were not causally related.

Acute bacterial endocarditis on a normal aortic valve following vaginal delivery.

We present a case of post-partum bacterial endocarditis on a normal aortic valve. Infection occurred following vaginal delivery. This complication, due to group D Streptococcus faecalis, has not been previously described in this context.

Atypical mycobacterial vertebral osteomyelitis in a steroid-dependent adolescent. A case report.

Atypical mycobacterial infections are uncommon, particularly in the spine. The authors present the case of a patient with vertebral osteomyelitis secondary to Mycobacterium chelonae subspecies abscessus that was successfully treated with surgical debridement and stabilization, followed by chemotherapy.

Improvement in indices of myocardial ischaemia in a case of hypertrophic obstructive cardiomyopathy treated with verapamil.

A 42-year-old male with hypertrophic obstructive cardiomyopathy presented with blackouts and chest pain. Investigations revealed no occlusive coronary artery disease. Treadmill exercise electrocardiography and thallium-201 imaging revealed reversible myocardial ischaemia. Exercise radionuclide ventriculography (RNV) revealed exercise-induced apical hypokinesia but normal diastolic function. Chronic therapy with Verapamil (120 mg tds) produced a symptomatic improvement, increased exercise tolerance and improved indices of myocardial ischaemia, without altering diastolic function as assessed by radionuclide ventriculography. This improvement may have been mediated by altering slow channel calcium metabolism, possibly at a microvascular level.

First myocardial infarctions in Asian and white men.

OBJECTIVE: To compare the presentation and natural course of first myocardial infarctions in immigrant Asians and the indigenous white population in Britain and the subsequent risk states of the two groups. DESIGN: Prospective ethnic comparison of consecutive patients with first myocardial infarctions. SETTING: Secondary referrals to a coronary care unit of a district general hospital. PATIENTS: 128 Men (77 white, 54 Asian) presenting consecutively with a first myocardial infarction diagnosed on the basis of clinical, biochemical, and electrocardiographic findings. END POINT: Identification of mechanisms accounting for the increased rate of ischaemic heart disease in Asians. MEASUREMENTS AND MAIN RESULTS: Infarct size was assessed by measuring the release of creatine phosphokinase (all patients), radionuclide ventriculography (50), and contrast ventriculography (103). Risk states after infarction were assessed from the degree of ventricular dysfunction as determined by exercise electrocardiography (82 patients) and from the extent of coronary atheroma as determined by coronary arteriography (103). Glucose state was measured in fasting venous blood samples. Overall the relative rate of infarction was 4.9 times higher in Asians (95% confidence interval 3.4 to 6.9) than in the white population. Moreover, the relative rate of infarction was higher in Asians in all 10 year age groups, the greatest difference being in 30-39 year olds. The mean age of the Asian denominator population was 47.1 years compared with 49.5 years in the white population. Age at infarction was less in Asians (50.2 years) than in white patients (55.5 years; mean difference 5.5 years (95% confidence interval 2.5 to 7.1]. In Asians the mean creatine phosphokinase activity was 777 (95% confidence interval 155 to 1399) U/1 higher, radionuclide ejection fraction 8.9% (1.0% to 16.9%) lower, and left ventricular fractional shortening 4.8% (1.4% to 8.2%) lower than in white patients. The extent of coronary atheroma was significantly greater in Asians. The mean numbers of plaques in vessels not associated with infarction were 3.66 (median 3.0, range 0-10) in Asians compared with 1.97 (median 2.0, range 0-6) in white patients (p less than 0.001), and a higher proportion of Asians had three vessel coronary artery disease (p less than 0.001). Asians with diabetes or impaired glucose tolerance did not differ from those with normal blood glucose values. CONCLUSIONS: Atherogenesis arises earlier in Asians, contributing to premature first myocardial infarctions. The increased incidence of diabetes in Asians may not in itself be relevant in the greater propensity to coronary atheroma in Asians.

Disturbances of insulin in British Asian and white men surviving myocardial infarction.

OBJECTIVE: To examine the role of insulin as a cardiovascular risk factor in British Asian and white men. DESIGN: Case-controlled study of survivors of first myocardial infarction. SETTING: District general hospital. PATIENTS: Consecutive series of 76 white and 74 Asian men who survived first myocardial infarction compared with 58 white and 61 Asian male controls without coronary artery disease who were randomly sampled from the community. RESULTS: More Asians than white subjects had impaired glucose tolerance or overt diabetes as measured by the two hour glucose tolerance test (23/74 (32%) v 11/76 (15%) (p less than 0.001) among patients; 17/61 (28%) v 3/58 (6%) (p less than 0.001) among controls). Insulin and C peptide concentrations were higher in both patient groups than in respective controls (p less than 0.001) and higher in Asian than in white subjects, irrespective of their glucose tolerance. Triglyceride concentrations were higher in patients than in controls (1.92 (SD 1.05) v 1.43 (0.82) mmol/l among Asian men; 1.65 (0.83) v 1.3 (0.61) mmol/l among white subjects; p less than 0.001). Total cholesterol concentrations were lower in both groups of Asians than in respective white subjects (5.78 (0.99) v 6.22 (1.04) mmol/l (p less than 0.01) among patients; 5.54 (1.01) v 5.65 (1.11) mmol/l (p less than 0.6) among controls). High density lipoprotein cholesterol concentrations were lower in Asian than in white subjects. The ratio of total cholesterol to high density lipoprotein cholesterol was significantly higher (p less than 0.001) in both patient groups (6.69 (1.81) in Asian patients and 6.31 (1.91) in white patients) than in respective controls (5.24 (1.19) and 4.77 (1.43)). Regression analysis identified C peptide concentration and the ratio of total to high density lipoprotein cholesterol as powerful independent predictors of myocardial infarction in Asian and white men. Total cholesterol concentration predicted infarction in white but not in Asian men. CONCLUSIONS: Secretion and hepatic extraction of insulin are high in survivors of myocardial infarction and especially high in British Asians. Tissue resistance to the action of insulin, giving rise to increased pancreatic secretion, may be an important risk factor for coronary artery disease in both ethnic groups and may be partly responsible for the high incidence of diabetes and coronary artery disease in Asian populations.

Learning on the Web. Case 9: a mother's heartache.

A 35 year old white woman presented with chest pain and breathlessness 10 days following an elective caesarean section. This was her second pregnancy, which had proceeded to term without complications. Up until then, she had been completely fit and well. Her ECGs were found to be abnormal, and the ultrasound study of her heart gave serious cause for concern. This interactive case report charts the evolution of the patient's clinical course and provides concise and up-to-date literature reviews on two cardiac conditions that share a predilection for women in the peripartum period.