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Biomedical subjects

H D White

Publications and source records attributed to H D White.

At least 19 recordsLinked to original sources
PubMed1992

Streptokinase and lifestyle outcome in survivors of myocardial infarction.

Clinical and lifestyle parameters were assessed in 145 patients who were randomised in a double blind study comparing streptokinase or placebo given within four hours of the onset of ischaemic chest pain. Sixty-six percent of patients were in paid employment at the time of their infarct and 79% returned to paid employment. Patients who received streptokinase returned to work 17 days earlier (p less than 0.05) and returned to sport and leisure activities 33 days earlier (p less than 0.05) than those who received placebo. Those who had received streptokinase also tended to leave hospital earlier (0.8 days, p = 0.07). There were no differences in angioplasty or coronary surgery rates or the incidence of reinfarction in the first year (8%). Total community costs were reduced in the patients who received thrombolytic therapy. These findings have important implications in the benefit:cost analysis of thrombolytic therapy.

Activities of Daily Living↗
PubMed1992

Antecedent angina pectoris predicts worse outcome after myocardial infarction in patients receiving thrombolytic therapy: experience gleaned from the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.

The significance of antecedent angina in predicting clinical outcome was assessed in 8,329 patients with acute myocardial infarction who received thrombolytic therapy with either recombinant tissue-type plasminogen activator or streptokinase. There were 2,370 patients with antecedent angina for greater than 1 month, 1,512 patients with antecedent angina for less than or equal to 1 month and 4,447 patients with no antecedent angina. The longer the duration of angina, the worse the baseline characteristics in the three groups: the mean patient age was 65 versus 62 versus 61 years, respectively (p less than 0.0001); the rate of previous myocardial infarction was 37% versus 18% versus 10% (p less than 0.0001); and the rate of hypertension was 40% versus 31% versus 27% (p less than 0.0001). Antecedent angina was associated with a longer hospital stay (11.3 and 11.7 days vs. 10.8 days, p less than 0.0001), a higher incidence of bypass surgery (2.2% vs. 1.2% vs. 0.7%, p = 0.0001), a worse Killip class at discharge (10.6% of patients in class greater than 1 vs. 8.7% vs. 6.4%, p = 0.0001), and a higher hospital and 6-month mortality (12.1% and 18% vs. 8.9% and 11.6% vs. 6.6% and 9.2%, respectively, p less than 0.0001). A multivariate analysis taking into account all baseline characteristics confirmed the independent association of antecedent angina with mortality, with a relative risk of 1.4 to 1.47 (p less than 0.001). Antecedent angina predicts a worse clinical outcome and a more intense use of medical resources in patients with acute myocardial infarction receiving thrombolytic therapy.

Aged↗
PubMed1992

Prognosis after recovery from myocardial infarction: the relative importance of cardiac dilatation and coronary stenoses.

In order to further define clinical and angiocardiographic predictors of long-term survival after myocardial infarction we followed 616 consecutive male patients under 60 years of age, survivors of a first (N = 455) or recurrent (N = 161) myocardial infarction, for 8.8 +/- 2.9 years. Patients had angiocardiography at 4-8 weeks after infarction; none had thrombolysis, but 33% had cardiac surgery, 14% on a clinical trial basis. Left ventricular end-systolic volume was the most powerful predictor of cardiac mortality; ejection fraction and end-diastolic volume added no further information. Myocardial score, a measure of the severity of coronary stenoses in relation to the amount of myocardium supplied, was of only borderline predictive value on multivariate analysis, possibly because any effect had been negated by coronary surgery. Administration of beta-blocker drugs had an independent effect of improving prognosis, while continued cigarette smoking worsened it. Age, status of index infarction (first or recurrent) and serum cholesterol did not affect survival. A trial of surgery, carried out in a subset of 200 of these patients who were relatively asymptomatic but had severe coronary disease, showed no survival advantage for intended surgical over non-surgical management. We conclude that a high left ventricular end-systolic volume remains the most important adverse prognostic factor after recovery from myocardial infarction.

Actuarial Analysis↗
PubMed1992

Remodelling of the heart after myocardial infarction.

In the first few hours after the onset of coronary occlusion the infarct zone stretches due to myocyte slippage. Subsequently the noninfarct zone develops volume overload hypertrophy with series addition of new sarcomeres and fibre elongation. Dilatation is detrimental as it increases ventricular wall stress and oxygen demand, and re-entry of electrical impulses may be influenced by stretching of the ischaemic scar resulting in ventricular fibrillation. Left ventricular remodelling and dilatation is a progressive process which begins early and continues in the months after infarction. The major determinants of the extent of remodelling are infarct size and patency of the infarct-related artery. Late reperfusion may reverse initial infarct dilatation and decrease left ventricular volumes by inducing calcium-activated contracture of the actomyosin complex. Expansion may also be inhibited by acceleration of healing, splinting of the infarct zone by salvage of subepicardial cells, and blood in the coronary arteries and veins supporting the infarct zone. End-systolic volume is the strongest predictor of long-term prognosis after infarction. A number of therapies including thrombolysis, angiotensin-converting enzyme (ACE) inhibition and nitrates have been shown to decrease left ventricular dilatation. The optimal time for commencement, dose, duration and the effects of combinations of therapy are yet to be determined.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Heart failure: to digitalise or not? The view against.

Despite extensive clinical experience the role of digoxin is still not well defined. In patients with atrial fibrillation digoxin is beneficial for ventricular rate control. For patients in sinus rhythm and heart failure the situation is less clear. Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs. Also, digoxin has undesirable effects such as increasing peripheral resistance and myocardial demands, and causing arrhythmias. There is a paucity of data from well-designed trials. The trials that are available are generally small with limitations in design and these show variation in patient benefit. More convincing evidence is required showing that digoxin improves symptoms or exercise capacity. Furthermore, no trial has had sufficient power to evaluate mortality. Pooled analysis of the effects of other inotropic drugs shows an excess mortality and there is a possibility that digoxin may increase mortality after myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors should be used first as they are safer, do not require blood level monitoring, modify progression of disease, relieve symptoms, improve exercise tolerance and reduce mortality. Caution should be exercised in using digoxin until large mortality trials are completed showing either benefit or harm. Until then digoxin should be considered a third-line therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Reduced synthesis of tissue plasminogen activator by vascular endothelium during acute myocardial infarction.

We measured levels of tissue plasminogen activator (t-PA) antigen in 100 patients within six hours of the onset of acute myocardial infarction, in 34 patients with chronic angina but no recent infarction, and in 36 normal subjects. We also assayed von Willebrand factor in the acute patients and in the normal subjects. Measurements were repeated in 40 acute patients at three weeks after myocardial infarction. Although resting levels of t-PA antigen were not significantly different from normal during myocardial infarction, the capacity of the vascular endothelium to release t-PA after five minutes of venous occlusion was impaired (p less than 0.01). The acute phase vessel wall release of von Willebrand factor was increased during acute infarction (p less than 0.01). We conclude that impairment of t-PA production is associated with acute coronary thrombosis, although it is not possible to differentiate between a causative role or a secondary response due to exhaustion of the t-PA producing mechanism.

Adult↗
PubMed1992

Light chain 2 profile and activity of human ventricular myosin during dilated cardiomyopathy. Identification of a causal agent for impaired myocardial function.

BACKGROUND: A number of parameters reflecting the effects of idiopathic dilated cardiomyopathy (IDC) on the structure and function of myosin from the human myocardium were analyzed. METHODS AND RESULTS: The content of the regulatory light chain, LC2, was reduced in myopathic heart myosin in contrast to the controls in which it was present in stoichiometric amounts relative to the essential light chain, LC1. In IDC hearts, the absence or significant reduction in amount of LC2 was related to the presence of an active protease, which was isolated and purified about 130-fold. The protease exhibited a significant degree of specificity: It cleaved LC2 almost totally (but not the heavy chains) in human control heart myosin but only partially cleaved LC2 in canine heart or in rabbit skeletal muscle myosins. The protease was present at a very low level or was inactive in control heart tissue. When the LC1/LC2 molar ratio was calculated, it was found to be 1:1.0 in control heart myosin and remained constant in various samples analyzed, whereas in myopathic myosin from different individuals, this ratio varied from 1:0.1 to 1:0.69. The rates of ATP binding to control and myopathic myosins were similar, whereas the Vm of actin-activated ATPase of myopathic myosin was about 25% less than that of the control. However, ATP binding and its hydrolysis by control S1, i.e., the myosin head, were faster by a factor of 2 than that of the myopathic S1. In addition, control myosin synthetic thick filament length as well as turbidity in solution, measured by light scattering, were twice as large as those of the myopathic heart myosin. These effects induced by myopathy in both filament assembly and turbidity were reversed upon reassociation of IDC myosin with LC2. CONCLUSIONS: The changes in myosin structure and function were linked to a protease-mediated cleavage of LC2 in myosin; a possible role for the protease in the degenerative effects of idiopathic dilated cardiomyopathy is thus defined.

Adenosine Triphosphate↗
PubMed1991

Comparative safety of thrombolytic agents.

Three available thrombolytic agents, streptokinase, alteplase, and anistreplase, have been shown to have similar effects on preservation of left ventricular function and mortality reduction after acute myocardial infarction (AMI). The agents are, however, quite different with respect to their safety profiles. Clinical trials to date suggest that alteplase (tissue plasminogen activator) or anistreplase administration is associated with a high incidence of cerebral hemorrhage. In contrast, streptokinase is associated with a low rate of cerebral hemorrhage. Streptokinase and anistreplase are associated with a higher risk of allergic reaction when compared with alteplase. Hypotension is also more common with streptokinase and anistreplase, but occurs significantly with alteplase as well. Alteplase is associated with a lower reinfarction rate when compared with streptokinase and anistreplase. The Third International Study of Infarct Survival (ISIS-3), a direct comparison of 3 thrombolytic agents (streptokinase, anistreplase, and duteplase), may provide some insight regarding the safety of these agents. Because these agents have been shown to be equally effective, selection of an appropriate agent for an individual patient may depend more on assessment of the likelihood of an adverse event or other factors, such as cost or convenience of administration, rather than assessment of the probability of greater benefit with a particular agent.

Fibrinolytic Agents↗
PubMed1991

Treatment of primary hypercholesterolaemia with simvastatin. New Zealand multicentre evaluation.

OBJECTIVE: To assess the efficacy of simvastatin in a large patient cohort. DESIGN: In an open multicentre study, after a four week placebo phase, patients were treated with simvastatin for 24 weeks; a subgroup continued therapy for a further 24 weeks. Efficacy of simvastatin (a) with prolonged use over three years, and (b) in combination with bezafibrate was assessed in an open single site study. SETTING: Lipid or cardiology specialist hospital outpatient clinics. PATIENTS: For the open multicentre study, 228 patients with primary hypercholesterolaemia (total cholesterol level greater than 6.5 mmol/L) were recruited, of whom 224 met entry criteria and completed the study. Forty-seven of these patients continued therapy for one year. In the open single site study, 22 patients (with low density lipoprotein [LDL] cholesterol levels greater than 4.3 mmol/L) participated in studies of long term use (n = 9) or of combined therapy (n = 13). INTERVENTION: Therapy in the open multicentre study began with 10 mg of simvastatin per day, doubling to 20 mg after six weeks and then 40 mg after 12 weeks of therapy if total cholesterol levels persisted above 5.2 mmol/L. In the study of long term use, simvastatin (40 mg daily) was taken continuously over three years. In the study of combination therapy, bezafibrate (600 mg daily) was taken in addition to simvastatin (40 mg daily) for 10 months. MAIN OUTCOME MEASURES: Plasma lipid and lipoprotein concentrations. RESULTS: In the multicentre study, total plasma cholesterol levels were reduced by 32.8% from 9.11 +/- 1.84 (in mmol/L, mean +/- SD) to 6.12 +/- 1.25 (P less than 0.001), and LDL cholesterol levels by 41.4% from 6.90 +/- 1.92 to 4.04 +/- 0.31 (P less than 0.001). The effect of therapy was sustained in those patients continuing therapy to 48 weeks. The study of long term use found no significant attenuation of effect over three years of monotherapy. Combined simvastatin/bezafibrate therapy reduced the LDL cholesterol concentration by a further 19.9% (P less than 0.001) from levels achieved on simvastatin alone. CONCLUSIONS: Simvastatin is an effective, well tolerated lipid lowering drug, without significant attenuation of effect with prolonged use. Simvastatin plus bezafibrate appears to be a potentially useful drug combination.

Adult↗
PubMed1991

Comparison of the effects of streptokinase and tissue plasminogen activator on regional wall motion after first myocardial infarction: analysis by the centerline method with correction for area at risk.

In a trial of streptokinase versus recombinant tissue-type plasminogen activator (rt-PA) for a first myocardial infarction, 270 patients were randomized. Regional left ventricular function was assessed in 214 patients at 3 weeks. The infarct-related artery was the left anterior descending artery in 78 patients, the right coronary artery in 122 and a dominant left circumflex artery in 14. Analysis was by the centerline method with a novel correction for the area of myocardium at risk, whereby the search region was determined by the anatomic distribution of the infarct-related artery. Infarct-artery patency at 3 weeks was 73% in the streptokinase group and 71% in the rt-PA group. Global left ventricular function did not differ between the two groups. Mean chord motion (+/- SD) in the most hypokinetic half of the defined search region was similar in the streptokinase and rt-PA groups (-2.4 +/- 1.5 versus -2.3 +/- 1.3, p = 0.63). There were no differences in hyperkinesia of the noninfarct zone. Compared with conventional centerline analysis, regional wall motion in the defined area at risk was significantly more abnormal. The two methods correlated strongly, however (r = 0.99, p less than 0.0001), and both methods produced similar overall results. Patients with a patent infarct-related artery and those with an occluded artery at the time of catheterization had similar levels of global function (ejection fraction 58 +/- 12% versus 57 +/- 12%, p = 0.58).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗
PubMed1990

Simvastatin therapy for hypercholesterolaemia in patients with coronary heart disease.

The efficacy of simvastatin therapy for hypercholesterolaemia was evaluated in 26 patients with coronary heart disease, 20 of whom had undergone coronary artery bypass grafting. Simvastatin reduced total- and low-density lipoprotein (LDL) cholesterol from 8.3 to 5.1 (38%) and 6.3 to 3.3 mmol/L (48%) respectively, p less than 0.001; high-density lipoprotein (HDL) cholesterol increased from 1.19 to 1.24 mmol/L, p = NS. The changes in apoproteins A1 and B paralleled those of HDL- and LDL-cholesterol. There were no clinically important adverse effects. We conclude that simvastatin is effective lipid lowering therapy and can be used safely, in the short term, in patients with coronary heart disease.

Anticholesteremic Agents↗