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Biomedical subjects

A R Lorimer

Publications and source records attributed to A R Lorimer.

At least 19 recordsLinked to original sources
PubMed1992

Significance of ventricular arrhythmias in systemic hypertension with left ventricular hypertrophy.

Hypertensive patients with the electrocardiographic (ECG) pattern of left ventricular (LV) hypertrophy and strain are at increased risk of sudden death. It has been suggested that ventricular arrhythmias may be responsible. The prevalence and significance of ventricular arrhythmias was therefore studied in 90 hypertensive patients with LV hypertrophy and strain by undertaking 48-hour ambulatory ECG monitoring, ECG signal-averaging and programmed ventricular stimulation. Complex ventricular ectopic activity (Lown grade greater than or equal to 3) was detected in 59 patients (66%). Eleven patients (12%) had episodes of nonsustained ventricular tachycardia. There were no sustained arrhythmias either on ambulatory ECG monitoring or induced by programmed ventricular stimulation. Only 1 patient had ventricular late potentials recorded by the signal-averaged electrocardiogram. Therefore, there was little to suggest an underlying arrhythmogenic substrate in these patients. In conclusion, whereas ventricular arrhythmias occur often in patients with LV hypertrophy associated with systemic hypertension, their significance, if any, remains to be established.

Adult↗
PubMed1992

Probucol reduces plasma lipid peroxides in man.

Although primarily used as a lipid lowering drug, probucol also possesses anti-oxidant activity and has been shown in animal models to inhibit or delay the progression of atherosclerosis. It has been suggested that this anti-atherosclerotic effect may occur through inhibition of free radical oxidation of low density lipoprotein. The aim of this study was to investigate the effects of probucol on free radical activity in hyperlipidaemic patients. Plasma lipid peroxides were measured before probucol treatment, at 4 and 12 weeks treatment and then 4 weeks after stopping probucol. Lipid peroxide concentrations were significantly reduced during and 4 weeks after stopping treatment with probucol, when compared with baseline values. There were no changes in plasma vitamin E concentrations. The results of this study indicate that probucol reduces lipid peroxidation in patients, an effect which may occur through a free radical scavenging action.

Adult↗
PubMed1992

Symptomatic and silent myocardial ischaemia in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE: To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN: Cross sectional study. SETTING: University department of medical cardiology. PATIENTS: 90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. INTERVENTIONS: 48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary arteriography (n = 35). RESULTS: 43 patients had at least one episode of ST segment depression on ambulatory electrocardiographic monitoring. The median number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2 to 17) min. Over 90% of these episodes were clinically silent. 26 patients had positive exercise electrocardiography and 48 patients had reversible thallium perfusion defects despite chest pain during exercise in only five patients. 18 of the 35 patients who had coronary arteriography had important coronary artery disease. Seven of these patients gave no history of chest pain. CONCLUSIONS: Symptomatic and silent myocardial ischaemia are common in hypertensive patients with left ventricular hypertrophy, even in the absence of epicardial coronary artery disease.

Adult↗
PubMed1992

The role of early surgery following myocardial infarction. European Coronary Surgery Bypass Group.

This co-operative study was a prospective randomised study to evaluate the role of coronary bypass surgery following acute myocardial infarction. The criterion for entry was an early positive exercise tolerance test. All patients who satisfied the clinical criteria of acute myocardial infarction but who were excluded had information on survival obtained after two years. A total of 4658 patients were assessed, with 3334 (71%) having a modified exercise test. This test was positive in 728 patients, of whom 598 then underwent coronary angiography. Three hundred and forty-eight patients were randomised (surgery 168, continuing medical treatment 180). At two years the survival in the medical group was 96% and in the surgical group was 93%. At five years the corresponding figures were 88% and 91%. Sub group analyses in terms of age, ejection fraction and extent of vessel disease failed to show any significant differences between those randomised to medicine or surgery. A positive exercise test early after infarction does help to delineate those more likely to require intervention, but a negative exercise test is not an indication for complacency.

Cardiac Surgical Procedures↗
PubMed1992

Candoxatril, a neutral endopeptidase inhibitor: efficacy and tolerability in essential hypertension.

OBJECTIVE: To examine the efficacy and tolerability of the neutral endopeptidase inhibitor, candoxatril (UK 79,300) as monotherapy in essential hypertension. DESIGN: Double-blind, placebo-controlled, parallel-group study of 28 days' duration. SETTING: Three hospital outpatient departments participating in the Glasgow Blood Pressure Clinic (Glasgow, UK). PATIENTS: Forty patients with essential hypertension with diastolic blood pressure 95-114 mmHg after a 2-4 week placebo run-in period. INTERVENTIONS: Twenty-eight days' treatment with candoxatril 200 mg twice daily or matching placebo capsules. MAIN OUTCOME MEASURES: Changes in supine and erect blood pressure, and volunteered side effects during double-blind treatment. RESULTS: When measured at the end of the dose interval, the fall in supine blood pressure following candoxatril was not significantly greater than that after placebo. Compared with placebo, a significant effect for candoxatril was seen only for systolic blood pressure in the erect posture; the fall in erect diastolic blood pressure attributable to candoxatril was insignificant. Median plasma atrial natriuretic peptide concentration increased in candoxatril-treated patients and decreased in the placebo group. No stimulation of the renin-aldosterone axis was seen. There was a non-significant trend towards greater urinary excretion of cyclic guanosine monophosphate after candoxatril. Mean plasma concentration of candoxatril at (UK 73,967--the active metabolite of candoxatril) reached a peak of 1010 +/- 437 ng/ml after acute dosing, and 1328 +/- 405 ng/ml after chronic dosing; time to maximum concentration was 2 h in each case. Candoxatril was well-tolerated; numbers of adverse events did not differ between active treatment and placebo. CONCLUSIONS: Although atrial natriuretic peptide levels were significantly increased, candoxatril 200 mg twice daily for 28 days did not produce a clinically relevant fall in blood pressure. Our results cast some doubt upon the role of neutral endopeptidase inhibition in the treatment of unselected hypertensive patients.

Antihypertensive Agents↗
PubMed1991

Felodipine extended release in mild to moderate hypertension.

A multi-centre study was carried out to examine the antihypertensive effect and adverse event profile of felodipine in an extended-release (ER) formulation given once daily as monotherapy. Doses of 5 mg, 10 mg or 20 mg felodipine ER were compared with placebo in 183 patients with mild or moderate hypertension. All antihypertensive medication was discontinued on entering a 4-week placebo run-in period. If, at the end of the run-in period, supine diastolic blood pressure was in the range greater than 95 less than 120 mmHg, patients were randomly allocated to double-blind treatment with felodipine, 5 mg, 10 mg or 20 mg, or placebo, to be taken once daily for 4 weeks. Supine and standing blood pressure, heart rate and body weight were measured every 2 weeks during the trial. Assessments were made 24 hours after intake of the study drug. Adverse events were recorded at each review. Over the 4-week treatment period, a dose-related decrease in supine diastolic blood pressure was observed, this reduction occurring already during the first 2 weeks of active treatment. In the placebo group and the felodipine 5 mg, 10 mg and 20 mg groups, supine blood pressure (systolic/diastolic) decreased by 7/6 mmHg, 9/8 mmHg, 12/10 mmHg and 14/11 mmHg, respectively. Supine diastolic blood pressure reduction in the felodipine 10 mg group and both systolic and diastolic blood pressure reductions in the 20 mg group were significantly greater than with placebo. Standing diastolic blood pressure reduction was significantly greater in all three dose groups on felodipine compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A comparison of the efficacy and safety of ramipril and digoxin added to maintenance diuretic treatment in patients with chronic heart failure.

The efficacy and safety of ramipril were compared with that of digoxin in a prospective, randomized, double-blind, crossover study of 35 patients with congestive heart failure (CHF), New York Heart Association (NYHA) grades II to IV, stabilized on diuretic maintenance therapy. Major assessments were conducted at baseline and at the end of each 10-week treatment period: primary efficacy variables were total exercise duration (modified Bruce, treadmill), NYHA grade, and clinical signs and symptoms (by visual analogue score) of heart failure. Twenty-seven patients completed the study. There were two deaths (one on each study drug) and six patient withdrawals (one on ramipril and five on digoxin). Although the NYHA grade was significantly better on ramipril than on digoxin, there were no other important differences in the relief of either signs or symptoms of heart failure. A significant order effect was observed with the exercise testing data and therefore only data in the first active treatment period were analyzed; no significant differences were noted. There were fewer reports of adverse effects, and no clinically significant episodes of hyperkalemia or renal impairment on ramipril. We conclude that ramipril seems to be better tolerated and marginally more effective than digoxin in the management of patients with moderate to severe chronic CHF, stabilized on maintenance diuretic therapy.

Adult↗
PubMed1990

Simultaneous measurement of left ventricular function and perfusion.

A new radiopharmaceutical, methylisobutyl isonitrile (MIBI), has been developed as a technetium-99m-labelled alternative to thallium 201 for myocardial imaging. By virtue of the high specific activity of 99mTc, some 600 MBq may be administered as a 0.3 ml bolus, permitting the acquisition of a first-pass nuclear angiogram at rest and at peak exercise. The agent was assessed in ten sequential patients referred for routine cardiac catheterisation, who also underwent an exercise electrocardiographic (ECG) test. Good quality nuclear angiograms, planar perfusion and tomographic perfusion images were obtained; the results correlated well with the catheterisation data. Of 30 myocardial segments for which wall motion was judged normal/abnormal from the nuclear angiogram, results concordant with contrast studies were obtained in 27 (90%). In the case of the 50 segments analysed from the perfusion images, concordant results were obtained in 43 (86%) from the planar studies and in 42 (84%) from the tomographic studies. All normal segments were classified correctly.

Adult↗
PubMed1990

The effects of felodipine in angina pectoris.

The clinical response to felodipine, in addition to a beta-blocker, was evaluated and compared with placebo in this double-blind cross-over study. Twenty patients with exertional angina pectoris completed the study. Felodipine reduced the number of angina attacks and the Glyceryl Trinitrate (GTN) consumption. The median exercise capacity was increased 33% after 4 weeks' felodipine treatment compared with placebo. At maximal exercise, systolic blood pressure and rate pressure product were reduced by felodipine while no change was seen in heart rate or ST-depression. Felodipine reduced both supine and erect blood pressure. The mean supine blood pressure at rest was 138/82 mm Hg after four weeks' placebo treatment compared with 114/71 mmHg after felodipine 5-10 mg b.i.d. Felodipine has overall a modest but significant anti-anginal benefit when combined with a beta-blocker.

Adult↗
PubMed1990

Postprandial lipemia, fenofibrate and coronary artery disease.

This report describes the response of patients with severe coronary artery disease to a dynamic fat load test and monitors the change induced by fenofibrate therapy. The presence of disease was associated with prolonged and exaggerated hypertriglyceridemia following the meal and with lower basal HDL cholesterol and HDL subfraction masses. A further indicator of risk was the persistence of increased amounts of retinyl palmitate in the plasma of severely affected individuals 24 h after its ingestion with the meal. These observations are consistent with the proposal that the clearance of chylomicrons and their remnants is impaired in coronary atherosclerosis. Fenofibrate reduced alimentary lipemia following the fat load in both normo- and hypercholesterolemic subjects. This was associated with a 10% rise in plasma HDL cholesterol levels. The improvement in chylomicron catabolism probably derived from a 37% increase (P less than 0.001) in lipoprotein lipase activity induced by fenofibrate. Hepatic lipase on the other had was only slightly affected by treatment.

Adult↗
PubMed1990

Left ventricular hypertrophy and mortality in hypertension: an analysis of data from the Glasgow Blood Pressure Clinic.

Three thousand seven hundred and eighty-three patients with non-malignant hypertension attending the Glasgow Blood Pressure Clinic between 1968 and 1983 were followed prospectively for an average of 6.5 years. Left ventricular hypertrophy (LVH) was present at the outset in 34.5% of the men, and 12.8% had ST-T changes. The corresponding figures for women were 21.5% and 8.8%. The prevalence of LVH increased with the severity of hypertension and was higher for a given blood pressure level in men than in women. All-cause age-adjusted mortality, expressed as deaths per 1000 patient-years, was 27.6 for men with normal electrocardiographs, 43.2 for men with LVH only (P less than 0.001) and 56.9 for men with LVH and ST-T changes (P less than 0.001). Similar trends were seen in women. The excess risk associated with LVH, with or without ST-T changes, could not be explained by age, increased blood pressure at referral to the clinic, or smoking habit, when these factors were considered either separately or in combination (regression analysis). Thus, our study demonstrates that LVH, with or without ST-T changes is an independent risk factor for mortality in hypertensive patients.

Age Factors↗
PubMed1990

The safety of felodipine.

Hypertensive patients, particularly the elderly, may often suffer from other diseases. Therefore, antihypertensive compounds should not negatively affect such disorders. Felodipine is a calcium antagonist that has potentially beneficial effects in angina pectoris and congestive heart failure. Further, it does not adversely affect lung function in asthmatic patients or glucose tolerance in patients with diabetes. Preliminary investigations also indicate that felodipine has no negative influence on plasma lipid levels. Although felodipine seems to be safe in most patients, treatment with felodipine should at present be avoided in pregnant women, since digital anomalies have been observed in rabbit fetuses. The adverse effects seen during treatment with felodipine are usually mild and transient and generally related to the vasodilatory action of the drug, the most common being ankle edema, headache, flushing, dizziness, and palpitations. The only significant drug interactions with felodipine occur with inducers and inhibitors of the cytochrome P-450 system, which is responsible for the metabolism of felodipine.

Animals↗
PubMed1990

Acipimox in combination with low dose cholestyramine for the treatment of type II hyperlipidaemia.

1. This study was designed to examine the effects of acipimox 250 mg three times daily and cholestyramine 4 g three times daily on plasma lipids and lipoproteins in 28 hypercholesterolaemic individuals in a prospective double-blind placebo controlled parallel group fashion. 2. Combined treatment with the two agents produced a mean reduction of 27% in plasma total cholesterol and a 32% fall in LDL cholesterol. Plasma triglyceride was reduced by 13% due to a 38% decrement in VLDL cholesterol. 3. In comparison treatment with cholestyramine alone resulted in a 12% fall in plasma cholesterol and a 15% fall in LDL cholesterol. In this group triglycerides and VLDL showed no significant change. 4. Studies of HDL subfraction mass showed that the addition of acipimox to resin therapy produced a mean increment of 45% in HDL2. 5. These results demonstrate the effectiveness of such a well tolerated low dosage combination therapy.

Cholesterol↗
PubMed1989

Comparison of enalapril and atenolol in mild to moderate hypertension.

PURPOSE: Short-term therapy with angiotensin converting enzyme (ACE) inhibitors for hypertension is effective and well tolerated, and compared with beta blockers, may cause fewer adverse reactions. Furthermore, enalapril has been observed to have a greater effect on systolic blood pressure than beta blockers. We therefore decided to compare the ACE inhibitor enalapril and the beta blocker atenolol as monotherapy in a double-blind study of patients with mild to moderate hypertension. PATIENTS AND METHODS: After a four-week placebo run-in period, 162 patients were allocated randomly to receive atenolol (50 to 100 mg daily) or enalapril (20 to 40 mg daily) for 12 weeks. To assess the influence of these drugs on quality of life, a series of psychologic tests was performed, and a subset of patients also underwent treadmill exercise and pulmonary function tests. RESULTS: In 147 patients who completed the study, enalapril reduced supine blood pressure by 19/12 mm Hg, compared with 9/7 mm Hg for atenolol (p less than 0.001/p less than 0.005). The modest blood pressure response to atenolol was not due to poor compliance. A target blood pressure of 140/90 mm Hg or less was achieved by 35 percent of enalapril-treated atenolol (p less than 0.01). The frequency and severity of adverse effects with the two drugs were similar, and few important differences emerged from the quality-of-life assessments. CONCLUSION: At the doses used, enalapril induced a greater short-term blood pressure response than atenolol; long-term studies of its safety and efficacy are required.

Adolescent↗