Anders Vedin

EFFECT ON MORTALITY OF METOPROLOL IN ACUTE MYOCARDIAL INFARCTION: A Double-blind Randomised Trial

The effect of metoprolol on mortality was compared with that of placebo in a double blind randomised trial in patients with definite or suspected acute myocardial infarction. Treatment with metoprolol or placebo started as soon as possible after the patients arrival in hospital and was continued for 90 days. Metoprolol was given as a 15 mg intravenous dose followed by oral administration of 100 mg twice daily. 1395 patients (697 on placebo and 698 on metoprolol) were included in the trial. Definite acute myocardial infarction developed in 809 and probable infarction in 162. Patients were allocated to various risk groups and within each group patients were randomly assigned to treatment with metoprolol or placebo. There were 62 deaths in the placebo group (8.9%) and 40 deaths in the metoprolol group (5.7%), a reduction of 36% (p less than 0.03). Mortality rates are given according to the treatment group to which the patients were initially randomly allocated.

Cessation of smoking after myocardial infarction. Effects on mortality after 10 years.

Ten annual cohorts of men suffering from their first myocardial infarction have been followed up to a maximum period of 10.5 years. One thousand and twenty-three male patients of 1306 were smokers. Three months after the infarction 55% had stopped smoking and 45% continued smoking. These two groups were then compared and followed with regard to non-fatal reinfarctions and deaths. Preinfarction characteristics were shown to be similar for the two groups. The prognostic comparability of the two groups was tested using two multiple logistic models. Those who stopped smoking had a slightly higher predicted two year mortality after the infarction. In different age groups it is shown with life table technique that those who stopped smoking had a considerably higher survival rate and lower cumulative frequency of reinfarction. The present study shows a reversion of the expected prognosis after myocardial infarction caused by changing the smoking habit.

MYOCARDIAL INFARCTION IN WOMEN

In the industrialized countries, the incidence and mortality of myocardial infarction (MI) in young women is much lower than in men of equal ages. This difference decreases with advancing age without any abrupt change at menopause. Scotland and Northern Ireland have the highest mortality rates from coronary heart disease in women, and Scotland the highest in men. Studies on the age variation of the sex ratio based on vital statistics have suggested that male behavior may make a contribution to the elevated mortality in males compared to females regarding not only coronary heart disease but also other causes of death. Studies have shown that uncomplicated angina pectoris has the highest incidence of the various coronary disease manifestations in women. Risk factors include hypertension, serum lipids, smoking, diabetes, obesity, oral contraceptive (OC) use, noncontraceptive estrogen use, and menopause. In a series of 145 women with MI and angina pectoris only 8% had been taking OCs at the time of onset of coronary heart disease. Evidence has been accumulating recently that women using OCs run a higher risk of coronary heart disease with the relative risk increasing with an increasing number of other factors, such as hyperlipemia, hypertension, and cigarette smoking. In 1 study the death rate from circulatory diseases in women who had used OCs was 5 times greater than that of controls who had never used OCs. These findings relate mainly to preparations containing 50 mcg of estrogen. The excess death rate increased with age up to 50 years and with smoking. OCs influence carbohydrate and lipid metabolism in ways similar to those induced by glucocorticoids such as impairment of oral glucose tolerance with hyperinsulinemia and elevated serum pyruvate levels. Serum cholesterol and serum triglyceride levels seem to remain relatively unchanged in OC users with a low estrogen content. In 1 study HDL cholesterol levels appeared to be directly related to the estrogen and conversely related to the progestogen content. OCs with both estrogens and progestogens have an intermediate effect on the level of HDL cholesterol. After menopause, estrogen use has not been conclusively linked with an increased risk, but the importance of estrogen in the causation of the disease should not be ignored. There is support for familial aggregation of coronary heart disease in women but the role of environmental and genetic contributions to this is unclear. Further studies are needed of the sex-related differences in coronary heart disease among men and women of various age groups so that understanding of basic disease factors may be gained.

Low-back pain in relation to other diseases and cardiovascular risk factors.

The relationship of low-back pain (LBP) to other diseases and to cardiovascular risk factors was studied in a random sample of 940 men from 40 to 47 years of age. The life-time incidence of LBP was 61%, the prevalence 31%. The prevalence of other diseases was the same as in previous studies in the same region. In a univariate analysis nine variables were found to be correlated to LBP; angina pectoris, calf pain, breathlessness on exertion, smoking, physical activity at work and during leisure time, worry and tension, fatigue at the end of the workday, and perception of stress. When the influence of other variables was assessed by analysis of covariance, four of the variables maintained a direct association with LBP, viz, calf pain on exertion, smoking, a high physical activity at work, and a frequent feeling of worry and tension.

Rupture of the myocardium. Occurrence and risk factors.

The occurrence of myocardial rupture was studied in a well defined unselected population of patients with acute myocardial infarction, and the group of patients who died of rupture of the heart were compared with two control groups. Of a total of 3960 patients, 1746 (44%) fulfilled the diagnostic criteria for acute myocardial infarction. Rupture was defined solely on the basis of the presence of a pathological passage through part of the myocardium, either the free wall of the left ventricle or the septum, found at necropsy or during operation. Two controls were selected for each patient and matched for age and sex, one (control group A) with acute myocardial infarction having died in hospital but not of rupture (non-rupture cardiac death) and one (control group B) with acute myocardial infarction having survived the hospital stay. Necropsy was performed in 75% of all fatal cases with acute myocardial infarction. The total hospital mortality was 19%, the highest mortality being among women over 70 years (29%). Ruptures (n = 56) were found in 17% of the hospital deaths, or 3.2% of all cases of acute myocardial infarction. Women aged less than 70 had the highest incidence of rupture, 42% of deaths being due to rupture. The mean age for patients with rupture and controls was 70.5 years. The median time after admission to death was approximately 50 hours for patients and control group A. Thirty per cent of the patients with rupture occurred within 24 hours of the initial symptoms occurring. Angina and previous acute myocardial infarction were more common among control group A. Patients with rupture and control group B were mostly relatively free of previous cardiovascular or other diseases (chronic angina pectoris ( > 2 months) and previous myocardial infarction). Sustained hypertension during admission to the coronary care unit was more common in patients than in control group A. Hypotension and shock were more common among control group A. Most (79%) of the patients who subsequently ruptured did not receive any corticosteroids at all during the hospital stay. Severe heart failure and antiarrhythmic treatment were more uncommon among patients than among control group A. Patients with rupture received analgesics approximately three times a day throughout their stay. Control group B received analgesics mostly during the first 24 hours. Thus female patients, patients with first infarcts, and patients with sustained chest pain should be investigated for the possibility of rupture. As many as one third (32%) of ruptures may be subacute, and therefore time is available for diagnosis and surgery.

Long-term prognosis after myocardial infarction in men with diabetes.

Men (1306) who survived a first myocardial infarction (Ml) were studied. The mean follow-up time was 6.5 yr, and at the end of the follow-up period survival status was known for all patients. By the time of the Ml the prevalence of diabetes was 5.6%. Patients with and without diabetes were compared. There were no differences in the estimated primary or secondary risk. The cumulative survival rate 1, 2, and 5 yr after the Ml was 82, 78, and 58% among the diabetic subjects compared with 94, 92, and 82% among the nondiabetic subjects (P < 0.001). The difference remained even after allowance for age and estimated secondary risk in a multivariate regression analysis. There were no differences in mortality rates among patients with type I diabetes compared with type II diabetes, nor among patients treated with diet alone, sulfonylurea, or insulin, but the numbers were small. The cumulative rate of reinfarctions after 1, 2, and 5 yr was 18, 28, and 46% in diabetic subjects and 12,17, and 27% in nondiabetic subjects (P = 0.004). A history of diabetes was an independent secondary risk factor among male survivors of a first Ml with respect to deaths and reinfarctions.

Bias due to non-participation and heterogenous sub-groups in population surveys

A random sample of men in the age-group 30-39 years from the general population in Göteborg, Sweden, has been investigated with respect to socioeconomic factors and risk factors for coronary artery disease. The total sample could well be characterized with socioeconomic variables obtained from public registers. All the individuals of the sample were invited to an examination which 68% attended (participants). It was found that those not attending the examination (non-participants) greatly differed from the participants. The non-participants were more often unmarried, and had lower annual incomes and more sickness benefit days. There were more foreigners and more individuals registered for intemperance among the non-participants than the participants. Among the participants the foreigners reported lower physical activity and had higher serum cholesterol than the participating Swedes and individuals registered for intemperance stated a higher tobacco consumption and had higher systolic and diastolic blood pressures than those not registered. This highlights that consideration of factors discriminating participants and non-participants is important for proper estimation of population parameters. The same is true for comparisons between cases and controls recruited from cross-sectional population surveys.

Psychosocial outcome one year after a first myocardial infarction

Psychosocial outcome in terms of mental state, health preoccupation, leisure activity, avoidance behaviour, sexual activity and attitude towards life and the future one year after a myocardial infarction (MI) was studied in 177 consecutive male, able-bodied patients below 61 yr of age with a first MI. Questionnaires and a brief interview covered the psychological and social data while the somatic variables were recorded in a standardized medical examination. Emotional distress, self-reported symptoms, avoidance behaviour, overprotection, pessimism and a diminished sexual activity were frequent, indicating a poor adaptation. These disturbances were apparent two months after the MI and remained stable. Psychological factors were stronger determinants of maladjustment than smoking, angina pectoris and recorded somatic illness. Neither severity of the infarction nor social and demographic factors determined maladjustment. Intervention must take place early and be directed to psychological factors as well as to the cardiac condition.

Effect of metoprolol on indirect signs of the size and severity of acute myocardial infarction

In a double-blind randomized trial, 1,395 patients with suspected acute myocardial infarction (MI) were investigated to evaluate the possibility of limiting indirect signs of the size and severity of acute MI with the beta 1-selective adrenoceptor antagonist metoprolol. Metoprolol (15 mg) was given intravenously and followed by oral administration for 3 months (200 mg daily). Placebo was given in the same way. The size of the MI was estimated by heat-stable lactate dehydrogenase (LD[EC 1.1.1.27]) analyses and precordial electrocardiographic mapping. Lower maximal enzyme activities compared with placebo were seen in the metoprolol group (11.1 +/- 0.5 mukat X liter-1) when the patient was treated within 12 hours of the onset of pain (13.3 +/- 0.6 mukat X liter-1; n = 936; p = 0.009). When treatment was started later than 12 hours, no difference was found between the 2 groups. Enzyme analyses were performed in all but 20 patients (n = 1,375). Precordial mapping with 24 chest electrodes was performed in patients with anterior wall MI. The final total R-wave amplitude was higher and the final total Q-wave amplitude lower in the metoprolol group than in the placebo group. Patients treated with metoprolol less than or equal to 12 hours also showed a decreased need for furosemide, a shortened hospital stay, and a significantly reduced 1-year mortality compared with the placebo group, whereas no difference was observed among patients treated later on. After 3 months, however, there was a similar reduction in mortality among patients in whom therapy was started less than or equal to 12 hours and greater than 12 hours after the onset of pain. The results support the hypothesis that intravenous metoprolol followed by oral treatment early in the course of suspected myocardial infarction can limit infarct size and improve long-term prognosis.

A retrospective study of low-back pain in 38- to 64-year-old women. Frequency of occurrence and impact on medical services.

The occurrence of low-back pain (LBP) was investigated in a retrospective cross sectional study of a random sample of 1,760 38 to 64-year-old women. The lifetime incidence of LBP was 66% and the prevalence was 35%. Neither the lifetime incidence nor the prevalence rates were significantly associated with age. Inability to work because of LBP was found in 2.6% of the women In the 38-to 49-year age group and 5.9% among 50− to 64-year-old women (P < 0.05). The utilization of medical services because of LBP was high, but only 1% of all investigated women had had a back operation. Forty-seven percent of the women In the prevalence group had experienced leg pain (sciatica), the frequency being significantly higher among the older women (P < 0.01). Increased LBP when performing certain activities of daily living was common, and significantly more pronounced in the older age group.