Subacute bartonella infection in Swedish orienteers succumbing to sudden unexpected cardiac death or having malignant arrhythmias.

During the period 1979-92, an increasing number of sudden unexpected cardiac deaths (SUCD) occurred in young, Swedish, male elite orienteers. Myocarditis was the most common diagnosis in the 16 victims, and in 4 cases was also associated with fatty infiltration mimicking arrhythmogenic right ventricular cardiomyopathy (ARVC). Tissues from autopsies of 5 orienteers were tested for Bartonella by PCR targeting the gltA (citrate-synthase) gene. The products were then sequenced. Antibodies to B. henselae, B. quintana and B. elizabethae were measured by indirect fluorescence antibody assay. Bartonella spp. DNA was detected in the hearts of 4 deceased orienteers, and in the lung of a fifth deceased case. The sequences were close to B. quintana in 2 cases and identical to B. henselae in 3. Four of these 5 cases, as well as 2 additional cases of elite orienteers with ARVC, indicated antibodies to Bartonella. It is suggested that Bartonella-induced silent subacute myocarditis, eventually leading to electric instability, caused the increased SUCD rate among the Swedish orienteers. It is further suggested that Bartonella infection may be a major pathogenetic factor in the development of ARVC-like disease. Although the mode of transmission is unknown, both zoonotic/vector-borne and parenteral person-to-person transmission may be involved.

Relationship of Chlamydia pneumoniae infection to severity of human coronary atherosclerosis.

BACKGROUND: Infection with Chlamydia pneumoniae has been postulated to play a pathogenic role in atherosclerosis. We examined the role of infection with C pneumoniae in relation to the extent of coronary atherosclerosis. METHODS AND RESULTS: Coronary atherosclerosis was graded microscopically on a postmortem basis in a blinded fashion in 60 subjects as mild (n=18) or severe (n=42) atherosclerosis. Serum antibodies to C pneumoniae were measured by microimmunofluorescence test. Paraffin-embedded coronary artery specimens were examined for the presence of chlamydia by use of a genus-specific direct immunofluorescence monoclonal antibody. Frozen coronary artery specimens were examined by immunoperoxidase for the presence of C pneumoniae by use of a specific monoclonal antibody RR-402. Direct immunofluorescence was reactive in 86% of cases with severe atherosclerosis but in only 6% of cases with mild atherosclerosis (P<0.01), whereas immunoperoxidase staining was reactive in 80% and 38% of cases with severe and mild atherosclerosis, respectively (P<0. 01). Elevated IgG and IgA levels against C pneumoniae were not different in cases with severe and mild atherosclerosis (61% and 30% for severe atherosclerosis and 67% and 42% for mild atherosclerosis, respectively). CONCLUSIONS: This study supports the hypothesis that intracellular infection with C pneumoniae may relate to the severity of atherosclerosis in some subjects. Serum antibody titers against C pneumoniae do not differentiate between severe and mild atherosclerosis.

Cause and manner of death among users of anabolic androgenic steroids.

Medicolegally investigated deaths among 34 male users of anabolic androgenic steroids (AAS) are described. Nine persons were victims of homicide, 11 had committed suicide, 12 deaths were judged as accidental and 2 as indeterminate. In two cases of accidental poisoning, the levels of pharmaceuticals and illicit drugs were considered too low to be the sole cause of death and AAS was considered part of the lethal polypharmacia. Chronic cardiac changes were observed in 12 cases. In two cases of accidental poisonous deaths, these changes were regarded as contributory cause of death. Homicides, suicides, and poisonings determined accidental or indeterminate in manner were related to impulsive, disinhibited behavior characterized by violent rages, mood swings, and/or uncontrolled drug intake. The observations in the present study indicate an increased risk of violent death from impulsive, aggressive behavior, or depressive symptoms associated with use of AAS. There are also data to support earlier reports of possible lethal cardiovascular complications from use of AAS. Furthermore, a contributing role of AAS in lethal polypharmacia is suggested. Finally, the observations indicate that use of AAS may be the gateway of approach to abuse of other psychotropic drugs.

Sudden unexpected cardiac deaths among young Swedish orienteers--morphological changes in hearts and other organs.

During the years 1979-1992 an accumulation of sudden unexpected cardiac deaths (SUD) occurred among young Swedish orienteers. A reevaluation of material saved from 16 autopsies was undertaken. Myocarditis was most frequent. It was found in different stages in the majority of cases, indicating subacute or chronic disease with ongoing reparative processes. There were severe morphological changes in all cases. All but one showed a picture of fibrosis and unspecific hypertrophy and/or degenerative changes in myocytes. The hearts were classified into three groups (A-C), based on the morphological picture of the retrieved heart tissue and the macroscopic description. Group A comprised five cases in which areas with active myocarditis combined with areas of healing or healed myocarditis widely distributed in the left ventricle were the only morphological changes found. Group B comprised four cases demonstrating foci of myocarditis in different stages in the left ventricle and changes resembling those found in arrhythmogenic right ventricular dysplasia (ARVD), including degenerative changes with fibrosis and fatty infiltration located in either ventricle. Group C comprised the remaining seven cases. In none of the cases were coronary artery or valvular anomalies present, nor significant coronary sclerosis or changes outside the heart that could cause SUD.

The population study of women in Gothenburg 1980-81--the third phase of a longitudinal study. Comparison between participants and non-participants.

A representative population sample comprising 1,462 women was studied in Gothenburg, Sweden in 1968-69, and a third follow-up study was carried out in 1980-81. The participation rates in the baseline study and during the follow-up studies were high. In 1980-81 women in two new age strata, aged 26 and 38, were added. Women who had moved to or from Gothenburg during the study period were not found to differ from those who were living in Gothenburg during the total study period, while there were a few differences of statistical significance between refusers and participants in 1980-81. The mortality among initial refusers was about doubled compared to that of those who participated in the baseline study.

Bone mineral content in normally menstruating women with hyperprolactinaemia.

Decreased bone density has been reported in women with hyperprolactinaemia due to pituitary tumours. We identified a number of seemingly healthy women with hyperprolactinaemia, i.e. a serum prolactin concentration exceeding 500 mU/l (25 micrograms/l) on three occasions, during a study in 1980/1981 of a representative population sample of greater than 1,400 women in seven different age strata (range 26-72 years). We compared vertebral bone mineral content and bone mineral areal content in 5 hyperprolactinaemic normally menstruating 50-year-old women with that of 6 controls matched for age and menstrual status but found no difference. Since the degree of prolactin elevation was similar in our study group to that previously reported for hyperprolactinaemic subjects with pituitary tumours and the time of exposure to raised hormone concentration appears to be of the same magnitude, other hormonal changes than hyperprolactinaemia per se seem to be the cause of low bone mineral content in women with hyperprolactinaemia and amenorrhoea.

Smoking--a risk factor for cardiovascular disease in women? Considerations based on a prospective population study of women in Gothenburg, Sweden.

A longitudinal population study of 1462 women aged 38-60 was carried out in Gothenburg, Sweden during 1968-69. The participants have been followed up for 12 years. The relationships between smoking and cardiovascular disease and between smoking and mortality have been evaluated. No significant increased risk was observed for smoking women concerning the 12-year incidence of myocardial infarction, angina pectoris, electrocardiographic changes suggesting ischaemic heart disease, stroke or death from all causes. Multivariate analysis could not demonstrate an independent effect of the cigarette smoking habit in women on these end-points. In agreement with the results from the Framingham prospective study we could not in our prospective study verify the markedly increased risk of myocardial infarction in smoking women, which has been observed in a number of cross-sectional studies of women and also in prospective studies of men.

Relationships between the menopause and risk factors for ischaemic heart disease.

There are still contradictory opinions as to whether there is an association between menopausal age and ischaemic heart disease or not. There is, however, no doubt about the existence of a number of relationships between menstrual status and different risk factors for ischaemic heart disease. Thus, smoking will give rise to an earlier menopause, while the menopause will give rise to increased serum cholesterol and serum triglyceride levels but seems to influence arterial blood pressure and body weight in the opposite way. The relationships between the menopause and risk factors for ischaemic heart disease are complex, which may be one reason for the contradictory results when relating menopausal age to the incidence of ischaemic heart disease.

Triglycerides--main lipid risk factor for cardiovascular disease in women?

A 12-year longitudinal population study of 1462 women, aged 38-60, was carried out in Gothenburg, Sweden in 1968-69. Women with high initial serum triglyceride values had a higher 12-year incidence of myocardial infarction, stroke and total mortality than the others. The findings for serum triglycerides persisted for myocardial infarction, stroke and total mortality after adjustment for other possible risk factors for ischaemic heart disease such as age, systolic blood pressure, smoking, indices of obesity and serum cholesterol, while serum cholesterol did not predict any end-points studied when taking other risk factors including serum triglycerides into account.

Blood glucose, glucose tolerance and manifest diabetes in relation to cardiovascular disease and death in women. A 12-year follow-up of participants in the population study of women in Gothenburg, Sweden.

A longitudinal population study of 1462 women, aged 38-60, was carried out in Gothenburg, Sweden in 1968-69. Women with initially manifest diabetes mellitus had significantly increased 12-year incidence of myocardial infarction and increased mortality while no increased incidence of angina pectoris, ECG changes indicating ischaemic heart disease or stroke was observed. The association to myocardial infarction remained in multivariate analyses and was independent of age, body fat distribution, smoking, serum cholesterol and systolic blood pressure. The association to mortality was independent of these factors and also of serum triglycerides. Women who were diagnosed as "new diabetics" during the 12-year follow-up had a significantly increased 12-year incidence of myocardial infarction but no significant increase was observed for any of the other end-points studied. When women with initially manifest diabetes mellitus were excluded, no association was found between initial fasting blood glucose concentration and the end-points studied. A negative significant association was found between initial fasting blood glucose concentration and smoking.

Serum triiodothyronine and hyperthyroidism in a population sample of women.

The serum T3 assay has been regarded as the most sensitive single test for hyperthyroidism although impaired conversion of T4 to T3 in non-thyroidal illness (NTI) might decrease its diagnostic sensitivity. The present report gives experience from the T3 assay in middle-aged females under conditions similar to those in a general health survey. The assays were performed during two periods with an interval of six years. In 1974-75 we studied a representative sample (n = 1283) of women of ages 44, 52, 56, 60 and 66 years in Göteborg, Sweden. Individuals with serum T3 concentration greater than mean + 2.5 SD were selected for a follow-up study (n = 21). Of 16 individuals with no previous thyroid disease and no present treatment with thyroid hormones or oestrogens, 14 were subjected to a TRH-stimulation test giving a normal TSH response in 10 cases having T3 concentrations up to mean + 3.5 SD. Four women with serum T3 concentration greater than or equal to mean + 3.5 SD had previously unrecognized autonomous function thyroid function, of whom two developed hyperthyroidism after two years. The original population sample was reinvestigated after six years in 1980-81 (n = 1138) together with an additional sample of women giving a total sample of 1422 women of ages 26, 38, 50, 58, 62, 66 and 72 years. Of the females studied in 1974-75 eight had developed hyperthyroidism between the two studies; three of these had raised serum T3 at the investigation in 1974-75. No case of hyperthyroidism had been missed by the T3 assay in the 1974-75 study. Of individuals with serum T3 greater than or equal to mean + 2.5 SD selected for a follow-up (n = 29) at least five were found to have previously unrecognized thyroid autonomy. We found a raised serum T3 to be associated with hyperthyroid (n = 2) and euthyroid Graves' disease, autonomously functioning thyroid adenoma(s), possible painless subacute thyroiditis, possible thyrotoxicosis factitia, diminished thyroid reserve and thyroid substitution therapy.

Morbidity and mortality in relation to blood pressure and antihypertensive treatment. A 12-year follow-up study of a population sample of Swedish women.

Morbidity and mortality in cardiovascular and cerebrovascular diseases and total mortality have been studied in a longitudinal population study initially comprising 1462 women representative of the general female population. When related to the initial blood pressure (BP) levels of women not on antihypertensive drugs (hypertensives and non-hypertensives), the distributions of women with myocardial infarction (MI) and stroke during the 12-year follow-up period seemed to be U-shaped, with the highest incidences in women with the lowest and the highest BP levels. Women recognized as untreated hypertensives in the initial study were offered regular control by the study team during the whole 12-year period and were treated when treatment was considered indicated. They were found to be similar to the non-hypertensives with regard to the incidence of MI and stroke and total mortality. Our encouraging results may be explained by continuity of medical care, the antihypertensive treatment per se or the types of antihypertensive drugs administered.

Influence of the menopause on ischaemic heart disease and its risk factors and on bone mineral content.

A comprehensive population study of women in Gothenburg, Sweden, was carried out in 1968-69. Altogether 1462 women participated (participation rate 90.1%). Five age strata were studied, i.e. women born in 1930, 1922, 1918, 1914 and 1908. The same women were restudied in 1974-1975 (participation rate 80.3% of the initial sample and 89.1% of those participating in 1968-69). In addition, a study of bone density, using photon absorptiometry, was carried out in a systematic subsample in 1976. The median age at natural menopause in the population sample was found to be 50 years and 3 months. About 5% of women aged 44 or more had stopped menstruating after hysterectomy and a similar proportion were postmenopausal as a consequence of bilateral oophorectomy. Information is also given about the percentages of the women receiving oestrogens either as substitution therapy or as oral contraceptives. Different factors influencing the age at menopause are discussed. Smoking was found to be one of the most important of these. The influence of the menopause on ischaemic heart disease and its risk factors has been studied both cross-sectionally and longitudinally. The most striking differences were found for serum cholesterol and serum triglycerides, with higher values in postmenopausal women than in premenopausal of the same ages. For bone mineral content, higher values were observed in premenopausal or recently postmenopausal women than in women of the same ages who had been postmenopausal for a long time. The observed differences in bone mineral content could not be explained by other factors studied.

Bone mineral content in relation to age and menopause in middle-aged women. A study of bone density in lumbar vertebrae by dual photon absorptiometry in a population sample of women.

As one phase of a comprehensive population study of women, bone density was determined in the third lumbar vertebra by dual photon absorptiometric technique. The method involves the use of two radionuclides, which both emit gamma radiation but with different energies (241Am with 59.6 keV and 137Cs with 662 keV). Women in three age strata were studied: 46, 54 and 62 years. The bone mineral content was higher in premenopausal or recently postmenopausal 54-year-old women than in women of the same age who had been postmenopausal for a long time (p less than 0.02). A similar trend was found for women aged 62. The differences could not be explained by differences in other factors studied, such as body height, body weight, smoking habits, numbers of pregnancies or physical inactivity. No significant differences were found when women with similar menstrual status in different age-groups were compared. In the ages studied, hormonal factors seem to be more important than the age per se for the development of oeteoporosis.

Thyroid disease and high concentration of serum thyrotrophin in a population sample of women. A 4-year follow-up.

In a population study in Göteborg, Sweden, comprising women in the age strata 44, 52, 56, 60 and 66 years, serum thyrotrophin (S-TSH) was determined in 283 women representative of the general population of women of these ages. No women with previously unknown hypothyroidism were found at the clinical examination; 47 (3.7%) were on thyroxine treatment, 9 (0.7%) because of spontaneous hypothyroidism. Sixteen women (1.2%) had markedly elevated S-TSH concentration (less than 14 mU/l). They were studied further by determination of thyroid hormones and circulating antithyroid microsomal and thyroglobulin antibodies, and those with goiter were subjected to fine-needle biopsy of the thyroid gland. They were furthermore followed for four years. Four euthyroid women were given thyroxine because of goiter and abnormal laboratory test results. Of nine individuals with high S-TSH concentration as well as high titers of thyroid antibodies and/or biopsy evidence of autoimmune thyroiditis, seven became hypothyroid within the four years of follow-up. The other two women had consistently elevated basal S-TSH concentration and exaggerated S-TSH response after thyroliberin administration. We conclude that the majority of individuals without previously recognized thyroid disease who have S-TSH concentration above 14 mU/l with the assay used will require thyroxine therapy within a few years. In one woman, however, with multinodular colloid goiter and high titer of antimicrosomal antibodies, the basal S-TSH concentration decreased during follow-up to a high normal value; the S-TSH response to thyroliberin was high borderline. She remained euthyroid during follow-up. The results suggest an annual incidence of spontaneous hypothyroidism of 1-2 cases per 1000 middle-aged females in Swedish west-coast population.

Menstrual status and menopausal age of middle-aged Swedish women. A population study of women in Göteborg 1968--69 and 1974--75.

A population study of women in Göteborg, Sweden, was carried out in 1968--69. Altogether 1 462 women participated (participation rate 90.1 per cent). Five age strata were studied: 38, 46, 50, 54 and 60 (women born in 1930, 1922, 1918, 1914 and 1908, respectively). The same women were re-studied in 1974--75. At this time 1 302 women participated, corresponding to 89.1 per cent of those studied in 1968--69 and 80.3 per cent of those initially sampled. The vast majority of the women had a natural menopause. The median age at the menopause was found to be about 50. The criteria for definition of menopause are discussed. No support was found for the theory of increased menopausal age with time. Estrogen therapy of postmenopausal women was found to be much more common in 1974--75 than in 1968--69.

Menopausal effects on risk factors for ischaemic heart disease.

Women of almost identical age but with a different menopausal state were compared in a population study of women, which was carried out in Goteborg, Sweden. The group of women aged 50 comprised about the same number of still menstruating and postmenopausal women and was, therefore, especially suitable for such a comparison. Serum cholesterol and serum triglycerides were higher in postmenopausal than in premenopausal 50-yr-old women and seemed to increase with postmenopausal time. The differences between premenopausal and postmenopausal women were hightly significant. Systolic blood pressure was slightly but significantly different (lower in postmenopausal women), while no difference was found for diastolic blood pressure. It seems that differences in risk factors for ischaemic heart disease could explain part of but not all the association between early menopause and ischaemic heart disease.

The effect of smoking on menopausal age.

A comprehensive population study of women in Goteborg, Sweden was carried out in 1968--1969. Altogether 1462 women in five age strata were studied. The age stratum 50 comprised about the same number of postmenopausal women (n = 161) and women who still menstruated (n = 168). A comparison could, therefore, be made between still menstruating and postmenopausal women of almost identical age. In postmenopausal 50-yr-old women 50% were smokers compared to 26% in 50-yr-old women who still menstruated. The difference was highly significant. Almost all the postmenopausal women had been smokers for many years, which means that they did not start smoking as a consequence of the menopause. It thus seemed that an earlier menopause was a consequence of smoking. The difference could not or only to a small extent be explained by other factors such as differences in body weight between smokers and non-smokers.

Age at menopause and its relation to osteoporosis.

As one phase of a comprehensive population study of women, bone density was determined in the third lumbar vertebra by dual photon absorptiometric technique. The method involves the use of two radionuclides, which both emit gamma radiation but with different energies (241Am with 59.6 keV and 137Cs with 662 keV). Women in three age strata were studied: 46, 54 and 62 yr. All women aged 46 were still menstruating, while the age strata 54 and 62 were subdivided into two groups: those who still menstruated or had been postmenopausal for a short time and those who had been postmenopausal for many years. The bone mineral content was higher in premenopausal or recently postmenopausal 54-yr-old women than in women of the same age who had been postmenopausal for a long time (P less than 0.01). A similar trend was found for women aged 62 (P less than 0.10). The differences could not be explained by differences in other factors studied, such as body weight, body height, smoking habits or physical activity. No significant differences were found when women with similar menopausal status in different age groups were compared.