Monitoring of aortic and coronary atherosclerosis in native and non-native males of Yakutsk over 40 years.

We have analyzed the development of aortic and coronary atherosclerosis over 40 years in native and non-native males of Yakutsk by comparing the data obtained in 1963-1965, 1985-1987 and 2001-2003. The research was carried out in compliance with the WHO program for the atherosclerosis epidemiology studies using autopsy material. Subjects (361 natives and 692 non-natives) included in the research died of external causes at the age of 20-59 years and had no history of chronic diseases, which was confirmed by post-mortem examination. The prevalence and the extent of raised atherosclerotic lesions (fibrous plaques, complicated lesions and calcinosis) in the aorta and coronary arteries were determined by visual planimetry after staining with Sudan IV. An accelerated development of aortic and coronary atherosclerosis was revealed in both populations throughout the entire period of 40 years with more severe manifestations in non-native males. The severity of atherosclerosis increased considerably in native and non-native males aged over 40 years. The rate of the increase in the extent of raised atherosclerotic lesions tended to be greater in native than in non-native males.

Incidence and risk of venous thromboembolism in patients with verified arterial thrombosis: a population study based on 23,796 consecutive autopsies.

BACKGROUND: The relationship between atherothrombotic disease and venous thromboembolism (VTE) remains unclear. PATIENTS AND METHODS: In a cohort of 23,796 consecutive autopsies, performed using a standardized procedure and representing 84% of all in-hospital deaths between 1970 and 1982 in an urban Swedish population, we investigated the relationship between verified arterial thrombosis and VTE, with the hypothesis that patients with thrombosis in major artery segments have increased odds of VTE. RESULTS: We found an increased risk of VTE in patients with arterial thrombosis (Odds ratio; OR adjusted for gender and age 1.4, 95% confidence interval; CI 1.3-1.5) (P < 0.001). Patients with cervico-cranial and peripheral artery thrombosis had an excess risk even when controlling for age and major concomitant diseases. A negative association between coronary thrombosis and VTE in the univariate analysis (OR 0.7; 95% CI 0.6-0.8) (P < 0.001), was less pronounced in the multivariate analysis (OR 0.8; 95% CI 0.7-1.0) (P = 0.016). CONCLUSIONS: A positive association between atherothrombosis and VTE was confirmed, except in patients with coronary thrombosis, where IHD as competing death cause is a possible confounder. Our findings indicate a potential for directed prevention, but may also imply similarities in etiology.

Fatal nonocclusive mesenteric ischaemia: population-based incidence and risk factors.

OBJECTIVES: To estimate the incidence and extension of visceral organ infarction, and to evaluate potential causes, in patients with autopsy-verified nonocclusive mesenteric ischaemia (NOMI) and transmural intestinal infarction. SETTING: In Malmö, Sweden, the autopsy rate between 1970 and 1982 was 87%, creating possibilities for a population-based study. DESIGN: Amongst 23 446 clinical autopsies, 997 cases were coded for intestinal ischaemia in a database. In addition, 7569 forensic autopsy protocols were analysed. In a nested case-control study within the clinical autopsy cohort, four NOMI-free controls, matched for gender, age at death and year of death, were identified for each fatal NOMI case to evaluate risk factors. RESULTS: The overall incidence of autopsy-verified fatal NOMI was 2.0/100,000 person-years, increasing with age up to 40/100,000 person-years in octogenarians. Patients with stenosis of the superior mesenteric artery (SMA; n = 25) were older (P = 0.002) than those without (n = 37), and had more often a concomitant stenosis of the coeliac trunk (P < 0.001). Synchronous infarction in the liver, spleen or kidney occurred in one-fifth of all patients. Fatal cardiac failure [OR 2.9 (1.7-5.2)], history of atrial fibrillation [OR 2.2 (1.2-4.0)] and recent surgery [OR 3.4 (1.6-6.9)] were risk factors for fatal NOMI. CONCLUSIONS: Fatal heart failure was the leading cause of intestinal hypoperfusion, although stenosis of the SMA and coeliac trunk, atrial fibrillation and recent surgery contributed significantly. Collaboration across specialties seems to be of utmost importance to improve the prognosis.

Subcutaneous fat accumulation and BMI associated with risk for pulmonary embolism in patients with proximal deep vein thrombosis: a population study based on 23 796 consecutive autopsies.

OBJECTIVE: Although deep vein thrombosis (DVT) and pulmonary embolism (PE) are manifestations of the same disease, far from all patients develop PE. Our objective was to investigate risk-modifying factors. SETTING, SUBJECTS AND DESIGN: Between 1970 and 1982, 23,796 autopsies, representing 84% of all in-hospital deaths in the Malmö City population, were performed, using a standardized procedure. In a case-control study nested in a population-based cohort of patients with proximal DVT, the relationship between PE and body mass index (BMI), thoracic and abdominal subcutaneous (SC) fat thickness was evaluated. RESULTS: Proximal DVT was found in 15%, of which 58% were women. Mean age in men was 4.5 years lower than in women (P<0.001). Fifty per cent of the patients had PE, half of which were fatal. Similar age- and gender distribution was found in cases and controls. Patients in the upper tertile of BMI, abdominal and thoracic SC fat thickness had, in comparison with mid-tertile, and independent of age, gender and death from cancer disease, an increased odds (95% CI) for PE of 1.24 (1.04-1.47) (P=0.014), 1.28 (1.07-1.53) (P=0.006) and 1.35 (1.13-1.61) (P=0.001), respectively, whereas in patients of the lower tertiles, a negative association was found. CONCLUSIONS: We found no differences in age- and gender distribution between PE cases and controls. BMI and SC fat thickness were markers of disease progression from proximal DVT to PE. The highly significant and independent association indicates that SC obesity may be of greater importance in venous thromboembolism as compared with cardiovascular diseases related to visceral (abdominal) obesity with lipid- and glucose metabolic disturbances.

Incidence of acute thrombo-embolic occlusion of the superior mesenteric artery--a population-based study.

OBJECTIVE: To determine the incidence of acute thrombo-embolic occlusion of the superior mesenteric artery (AOSMA) in a population-based study. MATERIAL: All clinical (n=23,446) and forensic (n=7569) autopsies performed in the city of Malmö between 1970 and 1982 (population 264,000-230,000 inhabitants). The autopsy rate was 87%. METHODS: Calculation of the incidence of AOSMA with intestinal gangrene in those autopsies coded for bowel ischaemia (997/23,446 clinical and 9/7569 forensic autopsies). The operative procedures performed in 1970, 1976 and 1982 were also analysed. RESULTS: Two forensic and 211 clinical autopsies demonstrated AOSMA with intestinal gangrene. Previous suspicion of intestinal ischaemia was noted in only 33%. Sixteen patients were operated. The cause-specific mortality was 6.0/1000 deaths. The incidence was 8.6/100,000 person years, increasing exponentially with age (p<0.001). Mortality was 93%. CONCLUSIONS: The incidence and mortality of AOSMA is higher than previously reported from clinical series. There is seldom any suspicion of the diagnosis prior to death.

Hyperplasia of coronary intima in young males in relation to development of coronary heart disease in adults.

UNLABELLED: The aim of the investigation was to study structural features of coronary arteries in young males which may influence the development of stenosing coronary atherosclerosis in older age. We studied the coronary arteries from 84 males, 10-39 years old, who died from accidents in Moscow, Malmo and Riga, and 98 males aged 40 and above from Moscow who died from coronary heart disease (71 cases) or other diseases (27 cases). In children and young males from all three cities, musculo-elastic hyperplasia of the coronary intima took place constantly but with different degrees of expression; a strict relationship of the intimal thickness and age was observed. Histometric investigations of the right coronary artery showed that in young males of Riga, in comparison with those of Malmo, the intima was significantly thicker both outside (69.6+/-2.8 and 58. 2+/-2.5 microm) and within the area of cushion like thickening (118. 8+/-4.0 and 101.9+/-3.8 microm), they had more extended cushion-like thickening of intima (42.6+/-3.0 and 30.8+/-3.3% to the length of the artery circumference) and destroyed parts of the internal elastic lamina (28.3+/-1.9 and 19.1+/-1.7% of its length). In males older than 40 years, severe coronary atherosclerosis and stenosis was also significantly more common in Riga than in Malmo. Our data indicate that with age the intimal musculo-elastic hyperplasia in the coronary arteries is transformed to a fibro-elastic layer. The thickness of this layer in the presence of stenosing plaques (>75% of arterial lumen) was much greater than in the presence of plaques with stenoses less than 50% (188.1+/- 7.3 and 69.8+/-4.5 microm, respectively). CONCLUSION: The development of stenosing coronary atherosclerosis is closely related to the degree of musculo-elastic intimal hyperplasia in childhood and young age. The formation of a fibro-elastic layer in the coronary intima decreases the ability of the artery to dilate during the development of atherosclerosis.

World Health Organization (WHO) and the World Heart Federation (WHF) Pathobiological Determinants of Atherosclerosis in Youth Study (WHO/WHF PBDAY Study) 1986-1996. An overview and general considerations.

This paper is an overview of the PBDAY Study--a ten-year multinational collaborative study. It provides condensed information on the background, objectives and methods of the study, as well as a summary of its most significant results and recommendations for further morphometric and special studies.

Pathobiological determinants of atherosclerosis in youth (PBDAY Study), 1986-96.

This article is a summary of the 10-year multinational collaborative WHO/ISFC Study of Pathobiological Determinants of Atherosclerosis in Youth (PBDAY Study). Details are provided of the study design, relevant results, conclusions, and recommendations, as formulated at a consultation of the heads of PBDAY Reference Centres, held in Budapest, Hungary, in October 1996. The WHO/ISFC study provides unique information about the determinants of atherosclerosis and structural changes in the arteries, especially during their early stages, and their progression from early life in populations with vastly different lifestyles. The pilot study covered subjects aged 5-34 years, of both sexes, from 18 centres in 15 countries, while the main study covered 11 centres in 11 countries. Included were both developed and developing countries with different economic, sociocultural and nutritional patterns from five WHO regions. Collected was background epidemiological information, information about cases, and special studies of arteries using various morphometric methods and specialized techniques. Atherosclerotic lesions start to develop early in life independently of race, sex or geographical origin. The rate of fatty streak development is higher between 15 and 25 years of age, while raised lesions begin developing slowly during the second decade of life, progressing steadily during the third and more rapidly during the fourth. Fatty streaks are more prevalent among females and raised lesions among males. The prevalence and extent of raised lesions were greater in countries with a high prevalence of known risk factors and high mortality rates for cardiovascular diseases, coronary heart disease, and cerebrovascular diseases.

Development of atherosclerosis over a 25 year period: an epidemiological autopsy study in males of 11 towns.

We conducted an analysis of the data from two epidemiological autopsy studies of atherosclerosis in men aged 20-59 years in 1963-66 (the first study, 7470 cases) and in 1985-88 (the second study, 9600 cases). The investigations were performed in accordance with a special program of the World Health Organization in 11 town populations: Ashkhabad (Turkmenistan), Bishkek (Kirgizstan), Irkutsk and Yakutsk (Russia), Malmo (Sweden), Prague (Czech Republic), Riga (Latvia), Tallinn and Tartu (Estonia), and Kharkov and Yalta (Ukraine). Native and non-native populations were studied separately in Ashkhabad, Bishkek, and Yakutsk. Atherosclerosis was studied by the visual morphometrical method in the descending thoracic aorta, abdominal aorta and three main coronary arteries. In each vessel the prevalence and extent (percent of intimal surface) of fatty streaks, fibrous plaques, complicated, calcified and also raised lesions (all lesions except fatty streaks) were determined. Coronary stenosis was estimated in arteries as narrowed by more than 50%. Accelerated development of coronary atherosclerosis, especially in the 40-59 year age group, was noted in the second study in the male populations of most towns except Prague and Malmo. In Prague the extent of raised lesions in coronary arteries was practically the same in both studies, in Malmo it decreased in the second study. Aortic atherosclerosis also accelerated the rate of progression in all towns except Prague, where significant differences were not observed between the studies. Accelerated development of atherosclerosis in male populations from towns of Asia was combined with an increase of fatty streaks in all vessels, while in European populations it was not so obvious. In the native populations of Ashkhabad, Bishkek and Yakutsk, atherosclerosis was much less than in non-natives in both studies. In natives of these towns, accelerated development of atherosclerosis begins only from 40 years, in non-natives from 30. For the second study, there was typically an increase of the prevalence and extent of calcified lesions that were combined with an increased prevalence of coronary stenosis in all towns. The average percentage of stenosis in the coronary left anterior descending artery for men of 40-59 years of age was 12% in the first study and 24.9% in the second; for the coronary right artery, 7.4 and 13.8%, respectively. In accordance with findings of more severe atherosclerosis in males in most towns in the second study, there was an increase in the frequency of death from coronary heart disease in the second study in these towns. The data of this study indicate that the development of atherosclerosis in human populations may change very much in the course of the life of one generation.

Pathomorphometrical characteristics of atherosclerosis in youth. A multinational investigation of WHO/World Heart Federation (1986-1996), using atherometric system.

BACKGROUND AND AIM: From 1986 to 1996, 1339 autopsies were performed on children and young adults, aged 5-34 years, in 18 countries of five continents in the course of the multinational investigation of the World Health Organization/International Society and Federation Cardiology (WHO/ISFC), "Pathobiological Determinants of Atherosclerosis in Youth" (PBDAY). A set of 966 left-half thoracic and 947 left-half abdominal aortae and 958 right coronary arteries were processed in the Center of Investigations and References of Atherosclerosis of Havana (CIRAH), i.e., one of the Reference Centers of the PBDAY. Pathomorphological and morphometrical analyses were carried out by a well-established method, the Atherometric System (AS). METHODS AND RESULTS: By qualitative analysis AS permitted the identification of each type of atherosclerotic lesions (AL). The quantitative analysis, using a digitizer (MYPAC-Japan, a PC-Pentium 200 Mhz-32 MB RAM), and the software Atherosoft, allowed the measurement of the intima surface occupied by any kind of AL, and estimation of the volume occupied and thus the degree of obstruction and stenosis of the lumen. The autopsy data were divided into three age groups: a) 5 to 14 years; b) 15 to 24 years and c) 25 to 34 and processed by age and sex. The commercial package NCSS was utilized for statistical analysis of the data. CONCLUSIONS: Of particular interest were the following findings: a) Atherosclerosis increases with age; b) Fatty streaks (FS) were always present already at 5 years of age, independent of the country, climate, state of nourishment, type and amount of foods and the habits and lifestyle of the population studied. FS progressed most rapidly from 15 to 24 years. The fibrous plaque began to appear slowly at the end of the second and rapidly progressed after the third decades. The severe plaque was rarely observed before 30 years of age; it appeared in the fourth decade and then progressed slowly, but steadily.

Feasibility and quality of biological banking of human normal and tumor tissue specimens as sources of DNA for the Malmö Diet and Cancer Study.

Human tumor and normal tissue specimens, which were collected from autopsy material 1-6 days postmortem, were compared with similar tissue specimens collected within 2 h after surgical resection and transport to the pathology department. The end point criteria used to evaluate the quality of the specimens for biological banking purposes were the extractability and yield of high molecular weight DNA and UV absorption ratios at 260:280 after collection and immediate storage of the specimens at -80 degrees C. The data demonstrated that autopsy material was a quality source of DNA, although of not such high quality as surgical biopsy specimens <2 h after resection. The advantages of using autopsy material to supplement surgical specimen collection sent to pathology, as opposed to using specimen collection at surgery wards or formalin-fixed material, as sources of DNA are: (a) large amounts of tumor and normal tissues from a variety of organ sites can be obtained without regard to the patient's health status; (b) a higher percentage of retrieval of incident cases of cancer in prospective designed trials is more likely to be achieved; and (c) the extractable DNA is of sufficiently high enough quality to permit direct analyses by molecular hybridization and sequence methodologies.

[A comparative study of the evolution of atherosclerosis in men over a 25-year period in 11 European and Asiatic cities]. / Sravnitel'noe izuchenie évoliutsii ateroskleroza u muzhchin za 25-letnii period v 11 evropeiskikh i aziatskikh gorodakh.

Repeated epidemiologic study of atherosclerosis in males on the basis of autopsy material with 25-year interval (1963-66 and 1985-89) has been performed in 7 European cities (Malmö, Praha, Riga, Tallinn, Tartu, Kharkov, Yalta) and 4 Asia cities (Ashkhabad, Bishkek, Irkutsk, Yakutsk). Accelerated development of atherosclerosis in the 2nd study has been revealed in males in the majority of cities except Malmö and Praha. No significant differences in atherosclerosis of aorta and coronary arteries were found in these two cities. An increase of the calcinosis surface in the coronary arteries combined with a higher incidence of coronary stenosis was typical for the 2nd study. Atherosclerosis was less pronounced in the indigenous population of Ashkhabad, Bishkek and Yakutsk in both studied than in non-indigenous populations. There was a positive correlation in males between lethality of coronary heart disease and other cardiovascular diseases and the degree of coronary atherosclerosis. Thus, the course of atherosclerosis can change within the life of one generation.

Declining autopsy rate in Sweden: a study of causes and consequences in Malmö, Sweden.

OBJECTIVE: In Sweden there has been a continuous decrease in the autopsy rate during the last 15-20 years. The autopsy rate in the city of Malmö has declined from 81% in 1984 to 34% in 1993. The intention of this study was to improve our understanding of the causes of the decline, and to assess its consequences with regard to cause of death surveillance and case retrieval in epidemiological and clinical research. DESIGN: A retrospective study. SETTING: The University Hospital in Malmö, a city in southern Sweden with 230000 inhabitants. SUBJECTS: All deceased in 1984 (2900) and 1993 (3198). Cancer incidence 1984 and 1993. MAIN OUTCOME MEASURES: Changes in autopsy rate in relation to age, sex, place of death and cause of death 1984 and 1993. Changes in the distribution of underlying causes of death in cases submitted and not submitted for a post mortem 1984 and 1993. Changes in cancer incidence and the number of incidentally-detected new tumours 1984 and 1993. RESULTS: Patients who died in nursing homes were less often sent for a post mortem than were patients who died at the hospital. From 1984 to 1993 the percentage of people dying in nursing homes increased from 1 to 29%. Care of the elderly has been reorganized, and the number of terminally ill patients who die in nursing homes has increased during the last 20 years in Sweden. This shift in place of death seems to be the single major explanation of the declining autopsy rate in Malmö. The overall autopsy rate in 1993 remained, however, lower than it was in 1984 when a shift in place of death was taken into account. During the period of study there was a decline in the autopsy rate at all departments within the hospital. The distribution of underlying causes of death according to the death certificates was similar in 1984 and in 1993. However, in cases not submitted for autopsy in 1993 there were greater proportions dying from pulmonary and circulatory diseases, respectively, than there were in 1984. The lower autopsy rate in 1993 was for several cancer sites also associated with a reduced number of new cancer cases. The percentage of tumours incidentally detected at autopsy went down in men from 40 to 19% and in women from 39 to 17%. CONCLUSION: Patients submitted for autopsy represented, with regard to age, sex, cause and place of death, a selected group of all deceased. The declining autopsy rate was associated with a difference in the distribution of underlying cause of death and of the incidence of cancer. It is concluded that the changes in the autopsy rate have to be taken into account in studies dealing with time trends of causes of death and incidence of cancer.

Pancreatic carcinoma following gastric resection. A case-control study based on 21,660 consecutive clinical necropsies at Malmö University Hospital.

CONCLUSION: In this necropsy-based case-control study, there was no relationship between pancreatic carcinoma and previous gastric resection. Based on the association between lung cancer and gastric resection, it is suggested that the relationship between pancreatic carcinoma and gastric resection shown in other studies may have been confounded by smoking. BACKGROUND: This case-control study was designed to assess whether in patients dying from pancreatic carcinoma, there is a relationship to previous gastric resection for peptic ulcer disease. METHODS: By linking the autopsy data base in Malmö with the national Cause of Death Register, we identified 439 autopsied individuals who had died of pancreatic carcinoma between 1970 and 1982. The 21,660 individuals in the data base represent 64% of all deaths during that time period. For each of these individuals who died of pancreatic carcinoma, we randomly chose three controls who were matched for age at death, gender, and year of death. In order to assess the specificity of the assumed relationship, we also used as a control group the 1337 autopsied individuals who had died of lung cancer. RESULTS: The prevalence of previous gastric resections was 3.4% in patients dying from pancreatic carcinoma, 7.6% in patients dying from lung cancer, and 4.4% in the age- and sex-matched control group. The odds for previous gastric resection in patients dying from pancreatic carcinoma was 0.9 [95% confidence interval (CI) 0.5-1.7] in comparison with this age- and sex-matched control group. The lower odds for previous gastric resection in patients dying of pancreatic carcinoma than in patients dying of lung cancer remained in the logistic regression analysis after controlling for age at death, gender, and year of death (odds ratio [OR] 0.5; 95% CI 0.3-0.9).

An experimental study of gastric stump carcinoma in Wistar rats.

The risk of gastric stump carcinoma is increased 15-20 years after gastric resection for benign disease. Reflux of duodenal juice, bacterial overgrowth and formation of N-nitroso compounds are possible etiological factors. There is a geographical variation in the incidence of gastric cancer, possibly explained by differences in food intake. Experimentally it is possible to induce gastric stump carcinoma in rats without the addition of exogenous carcinogens. The aim of this study was: 1) to find the incidence of gastric carcinoma in rats subjected to BII resection and followed for 10 months, and 2) to examine if acetic acid, a common dietary factor, could influence the development of gastric carcinoma. Amongst BII-operated male Wistar rats, infiltrating carcinoma was found in 5/20 on a normal diet and in 5/24 exposed to acetic acid (NS). Benign mucosal changes were seen in 12/20 and 16/24 respectively (NS). With the exception of a profound inflammation in one sham-operated animal, no mucosal pathological changes were found in 24 sham-operated and 24 control animals where no operation was performed.

Intraplaque haemorrhage at carotid artery surgery--a predictor of cardiovascular mortality.

OBJECTIVE: To ascertain whether carotid intraplaque haemorrhage (IH) in patients undergoing carotid artery surgery is a predictor of increased cardiac mortality over a 5.5 year follow-up. DESIGN AND SUBJECTS: Carotid artery plaques were obtained at surgery from 47 consecutive patients (41 men, six women), median age 67 (range 48-81) years, with symptoms of carotid transient ischaemic attacks (TIAs) or carotid territory minor stroke. As determined at preoperative angiography, the degree of stenosis was 50-99%. Specimens were classified histologically as manifesting severe atherosclerosis, fibrous plaque, IH, or residual IH debris. SETTING: Medical Angiology and Vascular Surgery Units, Malmö General Hospital. INTERVENTION: Carotid endarterectomy. MAIN OUTCOME MEASURE: Correlation between mortality and IH. RESULTS: At follow-up after 5.5 years, mortality was 28% (13/47) overall, 92% (12/13) in the IH subgroup [of stroke (n = 1) or myocardial infarction (n = 11)], but only 3% (1/34), of pancreatic cancer, in the non-IH subgroup (P = 0.0001). Mortality was also significantly higher in the severe atherosclerosis than in the fibrous plaque subgroup, 39% (12/31) vs. 6% (1/16) (P = 0.044), but not significantly increased in any other subgroup (fibrous plaque, residual IH, TIA, minor stroke, or acetylsalicylic acid or anticoagulant treatment). No correlation existed between IH or death and haemoglobin value or platelet count. CONCLUSIONS: Evidence of recent IH seen at carotid artery surgery may be a marker of cardiovascular mortality. As IH was also found in a post-mortem control subgroup, the difference may be due to abnormality in blood components (e.g., coagulation factors) or impaired vessel-wall healing capacity (e.g. endothelial dysfunction).