OBJECTIVE: A common polymorphism (-1C to T) in the translation initiation sequence of annexin A5 (ANV) gene has recently been associated with a decreased risk of acute myocardial infarction (AMI). The aim of the present study was to analyze the association between the ANV genepolymorphism and the risk of AMI and ischemic sudden cardiac death (SCD) in middle-aged Finnish males. MATERIAL AND METHODS: A case-control study involving three distinct groups of subjects was carried out: (1) victims of SCD (n=98), (2) survivors of AMI (n=212), and (3) randomly selected control subjects without any history of coronary heart disease (n=243). The ANV polymorphism was genotyped in each study group. RESULTS: Among the control group of healthy Finnish males the prevalence rates of the CC, CT, and TT genotypes were 83.1%, 15.2%, and 1.6%, respectively. Among the survivors of AMI, the prevalence rates of CC, CT, and TT were 79.7%, 20.3%, and 0%, respectively, and among the victims of SCD 83.7%, 16.3%, and 0%, respectively. No significant differences in the genotype or allele distributions were observed between the study groups. CONCLUSION: The -1C to T polymorphism in the ANV gene is not associated with the risk of AMI or SCD in middle-aged Finnish males.
OBJECTIVE: To determine the relationship between cardiac size and various measures of adiposity in children and the occurrence of coronary fatty streaks in relation to childhood obesity. DESIGN: A retrospective study based on 210 medico-legal autopsies of 5-15 y old children who had suffered violent death in the Province of Oulu, Finland, in 1970-1995. METHODS: Autopsy reports with attached clinical data and police records were recovered from the archives of the Department of Forensic Medicine, University of Oulu, Finland. All 5-15 y old individuals who had died of external trauma and were not documented as having had any chronic illnesses were chosen for investigation. The following data were extracted from the papers: age, sex, height, body weight, heart weight, liver weight, total weight of the kidneys, thickness of the abdominal subcutaneous fat and description of the coronary arteries. Heart weight was indexed to height2.7, and liver weight and kidney weight were indexed to body weight, body surface area and height. The ponderal index (body weight/height3) was calculated, and relative body weight was determined as the percentage deviation of the weight from the mean weight for height according to a growth chart developed for Finnish children. RESULTS: The average absolute heart weight and heart weight/height2.7 were significantly higher in the boys than in the girls over 12 y of age. Abdominal subcutaneous fat was thicker in the girls, but there were no significant differences in the other indicators of obesity. After adjusting for age, there were significant positive correlations between the ponderal index and heart weight/height2.7 in both the boys (P = 0.000) and the girls (P = 0.038), between relative body weight and heart weight/height2.7 in the boys (P = 0.000) and the girls (P = 0.027), and between abdominal subcutaneous fat thickness and heart weight/height2.7 in the boys (P = 0.045) but not in the girls (P = 0.234). Multiple linear regression analysis showed the ponderal index to be a significant predictor of heart weight/height2.7. Coronary intimal fatty streaks were documented in six individuals (2.9%), five of them having a ponderal index above the average and all of them having a relative weight above the average. Kidney weights were higher in the boys and were positively correlated with the measures of obesity and with heart weight/height2.7. CONCLUSIONS: The results point to an important role of excess body weight and adiposity in the development of early myocardial and coronary changes in childhood: coronary fatty streaks were not found at all in the leanest individuals in this relatively large group and the cardiac size adjusted for body size indicated hypertrophy with increasing adiposity. Prospective autopsy studies are needed in order to determine whether adiposity and the regional distribution of fat, especially intra-abdominal fat accumulation, are associated with the earliest signs of myocardial hypertrophy and the initial phase of lesion development in the arterial intima of children.
OBJECTIVE: To determine the relationship between cardiovascular status and body fat tissue distribution in men without any premortem clinical evidence of cardiovascular disease. SUBJECTS: 30 forensic autopsy cases which consisted of sudden deaths resulting from accidental causes, suicides or homicides or from unexpected natural causes. METHODS: Body height and weight, the circumferences of the waist and hip and the thicknesses of the subscapular and abdominal subcutaneous fat were measured, and Body Mass Index (BMI) and Waist-to-Hip ratio (WHR) were calculated. Perirenal, omental and mesenterial fat deposits were weighed and supraclavicular-pericarotid and perirenal-periadrenal fat was excised and serial samples analyzed for brown adipose tissue (BAT) by computerized image analysis. The heart weight was indexed for height. The degree of coronary narrowing was determined in each artery, and myocardial collagen volume fraction and myocyte cross-sectional area were measured. RESULTS: There were significantly positive correlations between age and the degree of coronary arteriosclerosis and heart weight/height. After adjusting for age, BMI and waist circumference had a significant positive correlation with all the cardiac parameters. The degree of coronary narrowing and heart weight/height were related to tertiles of BMI and waist circumstance. The age-adjusted correlations between the subscapular fat thickness and cardiac parameters were significant and positive, and perirenal fat weight also had a significantly positive association with all the cardiac parameters. BAT decreased with age and when adjusted for age, the cervical BAT percentage had a significant negative correlation with waist circumference and WHR, and a significant negative correlation was also found between cervical BAT and the degree of coronary arteriosclerosis and between perirenal BAT and heart weight/height. CONCLUSIONS: The results suggest that body fatness is associated with coronary and myocardial pathology in men without any clinical evidence of cardiovascular disease. An abdominal accumulation of fat seems to be connected with both the severity of coronary lesions and myocardial hypertrophy in men, in whom there is also a connection between abdominal obesity and a relative scarcity of BAT. Future investigations will require more detailed analyses of the extent and ultrastructural of coronary artery lesions in order to obtain more specific information on the relationship of body fat distribution to the early asymptomatic phase of coronary disease in younger individuals.
To investigate the effects on the central nervous system of severe cold stress with and without chlorpromazine, guinea pigs were treated with chlorpromazine or 0.9% NaCl and exposed to -20 degrees C or +23 degrees C for 1 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxy-tryptamine (5-HT), 3-methoxy-4-hydroxyphenyl ethylene glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum, urinary and vitreous fluid catecholamines, muscle and liver glycogen, and blood glucose were also measured. Chlorpromazine caused distinct hypothermia at -20 degrees C and slight hypothermia at +23 degrees C. The rise in hypothalamic MHPG, 5-HIAA and MHPG/NA and in 5-HIAA/5-HT ratios in the cold indicate increased noradrenergic and serotonergic activity. The latter was inhibited by chlorpromazine and a drug-induced inhibition of noradrenergic neurons could not be ruled out. Chlorpromazine increased the turnover of DA at room temperature and the same tendency was seen in the cold. The hypothermic animals had low serum catecholamines, indicating diminished sympathetic activity. The chlorpromazine-treated cold-exposed animals did not react to the environmental stress by sympathetic activation, as urinary NA and adrenaline were not elevated, but DA was excreted by all the drug-treated animals. Vitreous fluid NA and DA were elevated as an indicator of cold stress, and no drug effect was seen in this fluid.
The present study was carried out to elucidate the effect of long-term alcohol intake on the oxidative capacity of brown adipose tissue in the rat. Rats housed at room temperature were given water containing 10% ethanol for six months, while controls received water alone. Fully cold-acclimated rats (exposed to +4 degrees C for 6 weeks) served as the second control group. Alcohol did not alter the food intake of the rats compared with the controls kept at room temperature, but it did cause a mean decrease of 8 ml in fluid consumption. There was no difference in the increase in body weight between the groups housed at room temperature. Body weight of the rats exposed to cold did not change during cold acclimation. No morphological liver changes were observed in alcohol-fed rats, but some changes related to long-term alcohol consumption were found in the myocardium. Chronic alcohol intake increased the quantity of brown adipose tissue and its protein content but changes were not as great as in the cold-acclimated rats nor did alcohol increase protein content per unit of the adipose tissue as did cold. On the other hand, the specific activity of mitochondrial cytochrome oxidase increased by 90% and that of succinate dehydrogenase by 130% in alcohol-fed rats, whereas specific activities of these enzymes displayed little or no change in the cold-acclimated rats. Results suggest that chronic alcohol ingestion induces the oxidative capacity of the interscapular brown adipose tissue in the rat, increasing the mass of BAT and specific activities of mitochondrial enzymes.
OBJECTIVE: To determine the relationship between cardiovascular pathology and body fat distribution in healthy women with no ante mortem clinical evidence of cardiovascular disease. SUBJECTS: Thirty-three female forensic autopsy cases of sudden death from violent causes. METHODS: Body height and weight, the circumferences of the waist and hip and the thicknesses of the subscapular and abdominal subcutaneous fat were measured, and Body Mass Index (BMI) and Waist-to-Hip ratio (WHR) were calculated. Omental, mesenterial and perirenal fat deposits were weighted. Heart weight was indexed to height (2.7), the degree of coronary narrowing was determined in each artery, and myocardial collagen volume fraction and myocyte cross-sectional area were measured. RESULTS: The degree of coronary narrowing, heart weight in absolute terms and indexed to height (2.7), myocyte cross-sectional area and all the measures of obesity were significantly positively correlated with age. Regression of coronary narrowing on measures of obesity indicated that a quadratic model fitted the data for BMI, waist circumference and intra-abdominal fat better than a linear one. After adjusting for age, the degree of coronary narrowing was related to tertiles of BMI, waist circumference, WHR and intra-abdominal fat, the severity of the narrowing being most marked in the second tertile of BMI (24.0-31.0), waist circumference (80-96 cm) and intra-abdominal fat (500-1700 g), but in the third tertile of WHR (over 0.92). Regression on heart weight/height (2.7) on the aforementioned measures of obesity indicated a clearly linear association and heart weight indexed to height (2.7) was related to tertiles of BMI, waist circumference and WHR, and also to tertiles of intra-abdominal fat. CONCLUSIONS: The results suggest that body fatness and abdominal accumulation of fat are associated with the severity of coronary atherosclerosis and myocardial hypertrophy in women with no clinical evidence of cardiovascular disease, but the relationship between coronary lesions and BMI is not linear. Both coronary lesions and myocardial hypertrophy are more advanced as the numerical value for WHR increases in women. Future autopsy studies should be directed at young women with increased WHR in order to determine their risk of developing life-threatening lesions in the atherosclerosis-prone regions of the coronary tree.
OBJECTIVE: Few data are available on the actual degree of coronary atherosclerosis or its relationship to body composition in young women. The present study was carried out to identify, with the help of simple indicators of obesity and body structure, those women under 50 y of age who have the most advanced coronary lesions. DESIGN: Autopsy reports were analysed including age, height, weight, abdominal subcutaneous fat thickness, heart weight, liver and kidney weights, coronary atherosclerosis, and ovarial status. SUBJECTS: Female cases of sudden unexpected death (n = 599) aged between 15 and 50 y autopsied in 1973-1995 were collected from the files of the Department of Forensic Medicine, University of Oulu, Finland. RESULTS: The percentage of individuals with coronary lesions was 50% in women over 41 years of age, 32% in women from 31 to 40, 17% in women from 21 to 30, and 6% in women under 20 y of age. 2.1% of the women had died from manifestations of coronary heart disease (CHD). The most severe lesions were found in women with body mass index (BMI) between 24.2 and 27.2 when adjusted for age, and when abdominal subcutaneous fat thickness exceeded 35 mm when adjusted for age and BMI. Heart weight indexed to body size increased with BMI and abdominal fat and was positively correlated with the degree of coronary atherosclerosis, which was also associated with short stature and high liver and kidney weights when adjusted for body size. CONCLUSION: Mild to moderate overweight, short stature, increased amounts of abdominal subcutaneous fat, increased components of fat free mass and myocardial hypertrophy are the physical characteristics that indicate more advanced coronary atherosclerosis in women under 50 y of age.
Hypothermia and hyperthermia related cases recorded for the period 1973 to 1984 were collected from the files of the Department of Forensic Medicine, University of Oulu, and the necropsy protocols including toxicological results were analyzed. The fact that similar alcohol concentrations were found in both types of fatalities points to the poikilothermic effect of alcohol in humans, as found in animal studies. Both types of deaths seem to be associated with the alcohol elimination phase. Antidepressants and neuroleptics were most often found in the hypothermia cases, but benzodiazepines were also quite frequently present. In spite of the diminished use of barbiturates, these still appear in hypothermia fatalities. Certain other drugs that affect thermoregulation were also noted in solitary cases. Extended toxicological analysis was seldom made in the cases of hyperthermia deaths, and no firm conclusions on the poikilothermic effect of psychotropic drugs could be reached, for example. Therapeutic drug concentrations did not alone predispose the subjects to hypothermia, but appeared in connection with alcohol consumption or chronic diseases.
Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4 degrees C or +23 degrees C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG:NA and 5-HIAA:5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.
The incidence of coronary disease in premenopausal women is about one-half that in men of similar age. The estrogen receptor-1 (ESR1, c.454-397T>C) CC variant genotype is associated with the severity of coronary artery disease (CAD) and an increased risk of myocardial infarction in men. The purpose of the present study was to investigate whether this ESR1 CC variant also disposes to atherosclerosis in women in terms of increased total coronary artery intima thickness.
A total of 125 forensic autopsy cases of women aged 15 to 49 years were investigated. The thickness of the coronary intima, which reflects the severity of atherosclerosis, was measured by computerized image analysis. The ESR1 c.454-397T>C genotype was determined by polymerase chain reaction (PCR).
The mean intima thicknesses in the three genotype groups were 428+/-298 microm (TT), 494+/-371 microm (CT) and 636+/-436 microm (CC). We found that, on average, women with the CC genotype had a thicker coronary intima compared with that of women with the TT genotype, even after adjusting for age and body mass index (BMI) (p = 0.030). The intermediate group (TC) did not significantly differ from either the CC or the TT genotype group in this respect.
Our results point to the importance of ESR1 genotype in relation to cardiovascular disease susceptibility.