Serum cholesterol level and mortality due to suicide and trauma in the Honolulu Heart Program

BACKGROUND: Recent results from cholesterol level-lowering trials and some, but not all, observational studies support an intriguing link between low or lowered serum cholesterol levels and violent death. The reasons behind this relationship are far from clear. METHODS: In this report, we further investigate this issue by assessing the relationship of baseline serum cholesterol levels with long-term risk of mortality due to trauma and suicide in a cohort of 7309 middle-aged Japanese-American men. RESULTS: After 23 years of follow-up, a total of 75 traumatic fatalities and 24 deaths by suicide were documented. Rather than an inverse relation, a positive association between serum cholesterol level and risk of suicide death was observed. After controlling for potential confounders, the relative risk of suicide associated with an increment of 0.98 mmol/L (38 mg/dL) in serum cholesterol level (1 SD) was 1.46 (95% confidence interval, 1.04 to 2.05; P = .02). Multivariate analysis of traumatic mortality failed to detect a relation with serum cholesterol level (relative risk = 0.89; 95% confidence interval, 0.70 to 1.13; P = .44). Heavy alcohol consumption (> 1200 mL of alcohol per month, top quintile) was an independent risk factor for trauma death relative to abstinence (relative risk = 1.86; 95% confidence interval, 1.07 to 3.22; P = .02). CONCLUSIONS: These findings contradict the hypothesis of an inverse relation between serum cholesterol level and suicide, but they support the hypothesis that heavy alcohol consumption is a risk factor for traumatic fatal events.     

Ethnic differences in risk markers for heart disease in Bradford and implications for preventive strategies

OBJECTIVES: To assess and compare the prevalence of established risk markers for ischaemic heart disease in a sample of Asian and non-Asian men and to relate these observations to preventive strategies. SETTING: Two factories in the textile industry in Bradford, West Yorkshire, UK. Subjects--288 male manual workers aged 20 to 65 years. DESIGN: Cross sectional study within one occupational/social class stratum. MEASUREMENTS AND MAIN RESULTS: Age, body mass index, plasma lipids, fibrinogen and serum insulin values, blood pressure, smoking habits, alcohol consumption, and exercise routines were recorded. Plasma total cholesterol concentrations were significantly lower in Asian than non-Asian men (5.3 mmol/l v 5.8 mmol/l respectively, p < 0.0001), as were low density lipoprotein cholesterol concentrations (3.4 mmol/l v 3.7 mmol/l, p = 0.0150), and high density lipoprotein (HDL) cholesterol (1.1 mmol/l v 1.3 mmol/l, p < 0.0001). Hypercholesterolaemia (concentration > 6.5mM) was present in nearly one quarter of non-Asians but less than one eighth of Asian men. Triglyceride values were not significantly higher in Asians. Smoking rates were high in non-Asians (43.8%) and only slightly lower in Asians (39.1%). Asian smokers smoked fewer cigarettes per day on average (9.3 v 16.1, p = 0.0001). Almost a quarter of non-Asian men (23.1%) and 26.6% of Asian men had raised blood pressure. Systolic pressures were higher in non-Asian men (138.3 mmHg v 133.0 mmHg, p = 0.0070), but diastolic pressures showed no ethnic differences. Diabetes was more prevalent in Asian men (10.9% v 4.4% p < 0.05), who also showed higher serum insulin concentrations after glucose loading (22.3 mU/l v 10.2 mU/l, p < 0.0001). Plasma fibrinogen values were higher in non-Asian men (2.9 g/l v 2.6 g/l, p < 0.0001) and these were associated with smoking. Nearly all non-Asians (92.5%) consumed alcohol at some time whereas 62.5% of Asians habitually abstained from alcohol consumption. Among the drinkers, non-Asian men consumed on average, 23.9 units per week and Asian men 18.4 units per week (p = 0.083). The mean body mass index for Asian men was 24.5 kg/m2 which was not significantly different to the mean in non-Asian men (25.2 kg/m2). The frequency of exercise in leisure time was low in both groups with 44.4% of non-Asian and 21.1% of Asian men taking moderate exercise weekly, and even fewer, regular strenuous exercise (16.3% and 8.6% respectively). CONCLUSIONS: The plasma cholesterol and fibrinogen concentrations, prevalence of hypertension, smoking habits, alcohol intakes, and infrequency of exercise in leisure time in these non-Asian men in Bradford were consistent with an increased risk of heart disease. The pattern of risk markers was clearly different in Asian men. Only their lower HDL cholesterol concentrations, marginally higher triglyceride values, higher prevalence of diabetes, and very low frequency of exercise in leisure time would be consistent with a higher risk of heart disease compared with non-Asians. The implications of these observations for heart disease preventive strategies are discussed.     

Italian style brewed coffee: effect on serum cholesterol in young men

BACKGROUND: Increases in blood lipids have been observed in humans when coffee is brewed by the boiling method. The purpose of this study was to evaluate if giving up Italian coffee might reduce blood cholesterol levels. METHODS: Eighty-four normolipidaemic young adult males, after a 3-week baseline (BL), were randomly assigned to three different regimens of coffee consumption: espresso (E), mocha (M), and no coffee, but tea (T). The average coffee consumption during intervention (I) was 3.1 +/- 1.2 and 2.8 +/- 1.1 cups per day for espresso and mocha group respectively (espresso: 25-35 ml/cup; mocha: 40-50 ml/cup). Total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were measured eight times during the study. Dietary pattern, alcohol consumption, smoking habits, drug use, and anthropometric data were also recorded. RESULTS: The changes observed in serum cholesterol concentration between baseline and intervention were not statistically different in all groups. The changes were 0.0 mmol/l (T), +0.01 mmol/l (E) and +0.05 mmol/l (M) for total serum cholesterol; 0 mmol/l (T), -0.02 mmol/l (E) and -0. 03 mmol/l (M) for HDL-C; -0.13 mmol/l (T), +0.02 mmol/l (E) and -0. 05 mmol/l (M) for LDL-C. Serum triglycerides showed a significant increase during intervention (P < 0.01 by ANOVA) in all groups with a change of 0.18 mmol/l, 0.18 mmol/l and 0.22 mmol/l, for tea, espresso and mocha group respectively. CONCLUSIONS: The results indicate that coffee brewed in the Italian way does not alter blood levels of total cholesterol, HDL-cholesterol and LDL-cholesterol, since no significant differences were observed in these blood parameters after a 6-week break from coffee consumption.     

Randomised placebo controlled trial of effect on mood of lowering cholesterol concentration. Oxford Cholesterol Study Group

OBJECTIVE: To evaluate the effects on mood of a substantial and prolonged reduction in total cholesterol concentration. DESIGN: Randomised placebo controlled comparison of patients who had been allocated to receive simvastatin 20 mg or 40 mg daily versus those allocated matching placebo in a ratio of 2:1. Follow up at an average of 152 weeks after randomisation. SUBJECTS: Men and women aged between 40 and 75 years at entry with blood total cholesterol of 3.5 mmol/l or greater, who were considered to be at higher than average risk of coronary heart disease based on medical history. MAIN OUTCOME MEASURES: The shortened profile of mood states questionnaire, reported use of psychotropic medication, and symptoms possibly related to mood. RESULTS: Simvastatin reduced total cholesterol by 1.9 mmol/l (26.7%) at the time of follow up. Among all 621 patients randomised to simvastatin (414 patients) or placebo (207 patients) there were no significant differences in the use of psychotropic medication or in reports of symptoms possibly related to mood. Of these patients, 491 (334 simvastatin, 157 placebo) completed the mood questionnaire, and there were no significant differences between the treatment groups in total or subscale scores, even when patients with low baseline cholesterol concentrations or elderly subjects were considered separately. CONCLUSION: These results do not support the hypothesis that treatment to lower cholesterol concentration causes mood disturbance.     

Comparison of effect of cafetière and filtered coffee on serum concentrations of liver aminotransferases and lipids: six month randomised controlled trial

OBJECTIVE: To study the effects of prolonged intake of cafetière coffee, which is rich in the diterpenes cafestol and kahweol, on serum aminotransferase and lipid concentrations. DESIGN: Randomised parallel controlled trial. SUBJECTS: 46 healthy men and women aged 19 to 69. INTERVENTION: Consumption of five to six strong cups (0.9 litres) a day of either cafetière (22 subjects) or filtered coffee (24 subjects) for 24 weeks. MAIN OUTCOME MEASURES: Mean changes in serum aminotransferase and lipid concentrations. RESULTS: Cafetière coffee raised alanine aminotransferase concentration by up to 80% above baseline values relative to filtered coffee. After 24 weeks the rise was still 45% (9 U/l (95% confidence interval 3 to 15 U/l), P = 0.007). Alanine aminotransferase concentration exceeded the upper limit of normal in eight of the 22 subjects drinking cafetière coffee, being twice the upper limit of normal in three of them. Cafetière coffee raised low density lipoprotein cholesterol concentrations by 9-14%. After 24 weeks the rise was 0.26 mmol/l (0.04 to 0.47 mmol/l) (P = 0.03) relative to filtered coffee. Triglyceride concentrations initially rose by 26% with cafetière coffee but returned close to baseline values within six months. All increases were reversible after the intervention was stopped. CONCLUSIONS: Daily consumption of five to six cups of strong cafetière coffee affects the integrity of liver cells as suggested by small increases in serum alanine aminotransferase concentration. The effect does not subside with prolonged intake. High intakes of coffee brews rich in cafestol and kahweol may thus be responsible for unexplained increases in this enzyme activity in apparently healthy subjects. Cafetière coffee also raises low density lipoprotein cholesterol concentration and thus the risk of coronary heart disease.     

Importance of trends in the interpretation of an overall odds ratio in the meta-analysis of clinical trials

OBJECTIVE: To investigate the predictive value of fasting insulin concentrations for subsequent fatal or non-fatal ischaemic heart disease at five year follow up and to examine the associations between insulin and other indicators of risk. DESIGN: A prospective population study among 2512 men aged 45 to 59 at recruitment. SETTING: A whole population sample of men resident in Caerphilly, South Wales. MEASUREMENTS: At recruitment fasting blood samples were taken for measurement of plasma lipids and serum insulin. Men were re-examined at a five year follow up and ischaemic heart disease events during this period were assessed from hospital notes, death certificates, and electrocardiograms. MAIN RESULTS: Diabetic men and those men with a fasting blood glucose of > or = 8 mmol/l were excluded from all analyses. In a univariate analysis the incidence of ischaemic heart disease increased with increasing concentration of fasting insulin, such that for men in the top 20% of the insulin distribution the odds of developing ischaemic heart disease were 1.87 relative to men in the bottom 20%. On multivariate analysis this relation disappeared on adjusting for plasma triglycerides, body mass index, and evidence of ischaemic heart disease at recruitment. CONCLUSION: In this population in South Wales there was no evidence that the fasting insulin concentration is an independent risk factor for ischaemic heart disease. The univariate association between insulin and incident disease was almost entirely explained by the association of both with triglycerides and body mass index.     

Beer binging and mortality: results from the Kuopio ischaemic heart disease risk factor study, a prospective population based study

OBJECTIVE: To examine the association between beer binging (regular sessions of heavy beer drinking) and mortality. DESIGN: Prospective population based study with the baseline assessment of level of alcohol intake (dose), by type of drink and drinking pattern, previous and existing diseases, socioeconomic background, occupational status, involvement in organisations during leisure time, physical activity in leisure time, body mass index, blood pressure, serum lipids and plasma fibrinogen concentration, during an average of 7.7 years' follow up of mortality. SETTING: Finland. SUBJECTS: A population sample of 1641 men who consumed beer who were aged 42, 48, 54, or 60 years at baseline. MAIN OUTCOME MEASURES: All cause mortality, cardiovascular mortality, death due to external causes, fatal myocardial infarctions. RESULTS: The risk of death was substantially increased in men whose usual dose of beer was 6 or more bottles per session compared with men who usually consumed less than 3 bottles, after adjustment for age and total alcohol consumption (relative risk 3.01 (95% confidence interval 1.54 to 5.90) for all deaths; 7.10 (2.01 to 25.12) for external deaths; and 6.50 (2.05 to 20.61) for fatal myocardial infarction). The association changed only slightly when smoking, occupational status, previous diseases, systolic blood pressure, low density lipoprotein and high density lipoprotein cholesterol concentration, plasma fibrinogen concentration, body mass index, marital status, leisure time physical activity, and involvement in organisations were controlled for. CONCLUSION: The pattern of beer binging is associated with increased risk of death, independently of the total average consumption of alcoholic drinks. The relation is not explained by known behavioural, psychosocial, or biological risk factors. Death due to injuries and other external causes is overrepresented among beer bingers, but a strong association with fatal myocardial infarction suggests that the pathway may also involve other acute triggers of severe health events.     

Female voice communications in high level aircraft cockpit noises--part II: vocoder and automatic speech recognition systems

BACKGROUND: The purpose of the present study was to assess the implications of cholesterol distribution and its change on coronary heart disease (CHD) mortality and disease prevention at a population level. METHODS AND RESULTS: In five independent risk factor surveys (1972, 1977, 1982, 1987, and 1992) in eastern Finland, serum cholesterol was measured in 27721 randomly selected men and women aged 30 to 59 years. The association between cholesterol level and CHD risk and the prediction of the effect of different prevention strategies was estimated by use of logistic regression models. The entire cholesterol distribution of the population shifted markedly toward lower levels between 1972 and 1992. The proportion of subjects with a very high cholesterol level (> or =8.0 mmol/L), also decreased markedly, from 16% to 3%. The risk of CHD death among subjects with cholesterol > or =8.0 mmol/L was approximately 5-fold that of those individuals having cholesterol <5.0 mmol/L. Nevertheless, because CHD risk increases continuously as serum cholesterol increases, and because the number of people having only slightly or moderately increased serum cholesterol was large, most CHD deaths occurred among them. A 10% reduction in cholesterol levels in the entire population would subsequently reduce CHD mortality by 20%, as much as an effective treatment as a 25% decrease in serum cholesterol among all subjects with cholesterol >6.5 mmol/L and four times more than similar treatment of all subjects with cholesterol > or =8.0 mmol/L. CONCLUSIONS: The community-based population strategy in cardiovascular disease prevention was effective in decreasing cholesterol levels among the entire population, including the subjects with the highest cholesterol values. The balanced application of both high-risk and population strategies is needed for the effective prevention of CHD.     

Low total serum cholesterol and intracerebral hemorrhagic stroke: is the association confined to elderly men? The Kaiser Permanente Medical Care Program

BACKGROUND AND PURPOSE: Epidemiological studies indicate a higher incidence of intracerebral (but not subarachnoid) hemorrhagic stroke among persons with low total serum cholesterol levels. This report further examines the prospective relationship of total serum cholesterol with subsequent intracerebral hemorrhage in a large, well-defined population. METHODS: The cohort included 61756 enrollees in a health plan from the San Francisco-Oakland metropolitan area (46% men, 63% white), aged 40 to 89 years and free of cardiovascular disease at baseline. Sixteen-year incidence of combined nonfatal and fatal intracerebral hemorrhagic stroke (International Classification of Diseases [ICD], 8th revision, code 431, or ICD, 9th revision, codes 431 and 432) was investigated in relation to serum cholesterol measured in multiphasic health checkups made in 1977 through 1985. Intracerebral hemorrhagic events were ascertained using hospital discharge records and as underlying cause of death by the California Mortality Linkage Information System. RESULTS: From 1978 through 1993 (average of 10.7 years), there were 386 events (201 in men, 29% fatal; 185 in women, 42% fatal). By multivariate proportional hazards life-table regression analysis, serum cholesterol level below the sex-specific 10th percentile (< 4.62 mmol/L [178 mg/dL] in men), compared with higher cholesterol level, was associated with a significantly increased risk of intracerebral hemorrhage in men aged 65 years or older (relative risk, 2.7; 95% confidence interval, 1.4 to 5.0). An excess risk was also observed among elderly women at the lowest cholesterol range, but a chance finding could not be ruled out. No relationship was seen among men or women aged 40 to 64, and no statistical interaction of low serum cholesterol with hypertension was found in either sex. CONCLUSIONS: In these data, the association between low serum cholesterol level and intracerebral hemorrhage was confined to elderly men.     

Prevention of cardiovascular disease within the primary health care system--feasibility of a prevention programme within the Sollentuna primary health care catchment area

OBJECTIVE: To integrate prevention of cardiovascular disease within the primary health care. DESIGN: A prevention programme which combines population and individual high-risk strategy. SETTING: The Primary Health Care in Sollentuna, Stockholm, Sweden. MAIN OUTCOME MEASURE: Characteristics of, and risk factor prevalence among, persons registered in the prevention programme. RESULTS: During the first year more than 2000 persons, representing every tenth visitor and 6% of the population aged 15-60 years, were registered in the prevention programme. 90% were < or = 60 years and 62% were women. A large proportion (70%) had risk factors that required advice, treatment, and follow up. 24% of the men and 27% of the women were smokers, 68% and 62% respectively, had serum cholesterol > or = 5.2 mmol/l, and 33% and 22% had a diastolic blood pressure > or = 90 mmHg. CONCLUSION: The present study implies that it is possible to integrate a large scale prevention programme in the existing primary health care organization. The prevalence of risk factors in those who enter the prevention programme is high, which places great demands for treatment and follow up.     

Lack of relations of hostility, negative affect, and high-risk behavior with low plasma lipid levels in the Coronary Artery Risk Development in Young Adults Study

BACKGROUND: Previous studies have suggested that low plasma cholesterol levels or cholesterol lowering may increase the risk of suicide and violent death. Increased aggression, risk-taking behavior, or depression has been associated with low cholesterol levels in some studies. METHODS: A total of 4240 subjects of the Coronary Artery Risk Development in Young Adults study, aged 23 to 35 years, were included in the study. Analyses were stratified by race (black or white) and sex. Persons in the lowest 10% of plasma total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were compared with the other participants in each race/sex group, using standardized measures of hostility, anger suppression, depressive symptoms, and anxiety. The relations between 5-year change in hostility and 5-year change in lipid levels also were examined. The relations between lipid levels and high-risk behavior (e.g., violent arguments or having a gun at home) were examined in a subset of subjects. All analyses were adjusted for relevant covariates. RESULTS: In cross-sectional analyses, low total cholesterol levels were not related to any of the psychological measures in any race/sex group. Among black women only, low low-density lipoprotein cholesterol was related to greater anxiety, and low triglycerides were related to lower anger suppression (P < or = .002). Among white men only, increases in hostility during the 5-year follow-up were related to increases in triglycerides (P < .01), but changes in hostility were unrelated to changes in cholesterol levels. Among a subset of 371 subjects with initially elevated total cholesterol (> or = 5.17 mmol/L [> or = 200 mg/dL]) and a non-medicated decrease of 0.52 mmol/L (> or = 20 mg/dL) or more during 5 years, hostility decreased in a univariate analysis (P < .001). High-risk behaviors also were not associated with low lipid levels. CONCLUSION: The results do not support a consistent relation between hostility, negative affect, or high-risk behaviors with low lipid levels or lipid-lowering among young adults.     

Hyperinsulinemia and clustering of cardiovascular risk factors in middle-aged hypertensive Finnish men and women

OBJECTIVE: To examine the relationship between hyperinsulinemia and clusters of cardiovascular risk factors in middle-aged hypertensive patients. DESIGN: A population-based study. SETTING: Pieks?m?ki District Health Center, and the Community health Center of the city of Tampere, in central Finland. SUBJECTS: Hypertensive men and women aged 36, 41, 46, and 51 years (n = 18) in the town of Pieks?m?ki, and a normotensive control population of 177 subjects aged 40 and 45 years in the city of Tampere. MAIN OUTCOME MEASURES: Clusters of obesity (body mass index > 30.0 kg/m2), abdominal adiposity (waist:hip ratio > 1.00 for men and > 0.88 for women), hypertriglyceridemia (> 1.70 mmol/l), a low level of high-density lipoprotein cholesterol (< 1.0 mmol/l in men and < 1.20 mmol/l in women) and abnormal glucose metabolism (impaired glucose tolerance or noninsulin-dependent diabetes as defined by World Health Organization criteria) according to statistical quartiles of the fasting plasma insulin concentration. RESULTS: Among the hypertensives, there was a 2.0- to 3.6-fold higher risk of having a clustering of the insulin-resistance associated cardiovascular risk factors compared with that of the normotensives. Among the hypertensive subjects in the highest quartile of fasting plasma insulin there was a six- to 12-fold increase in risk associated with having two or more insulin resistance-associated cardiovascular risk factors compared with the subjects in the lowest quartile. There was a positive correlation between a high number of ascertained risk factors and high levels of fasting plasma insulin. CONCLUSION: In clinical practice, knowledge of the close relationship between risk-factor cluster status and fasting plasma insulin levels offers a tool to evaluate the occurrence of hyperinsulinemia in middle-aged hypertensive men and women.     

Treatment of dyslipoproteinaemia in diabetes mellitus

Coronary heart disease (CHD) is the most common cause of premature death in diabetes. Hypercholesterolaemia occurs in diabetes with about the same frequency as in the general population, but it confers a greater risk of CHD in diabetes. Hypertriglyceridaemia and low serum high density lipoprotein (HDL) cholesterol levels are more common in diabetes, particularly non-insulin-dependent diabetes. Nephropathy increases the severity of dyslipoproteinaemia. There remains a reluctance to apply the results of cholesterol-lowering trials to diabetes. No trial has been specifically in diabetes, but this should not constrain the treatment of diabetic patients at clearly high CHD risk. It is suggested that fasting lipids should be measured in all diabetic patients aged less than 70 years with established CHD or whose non-fasting cholesterol is >6.00 mmol I(-1) or triglycerides >3.00 mmol I(-1). For those with raised lipids glycaemic control should be improved, if possible, and dietary therapy aimed at a decrease in fat intake, particularly saturated fat, and weight reduction in the obese. Lipid-lowering drugs are required in patients with CHD and serum cholesterol >5.5 mmol I(-1) with the aim of decreasing non-HDL to <4.00 mmol I(-1). In patients without CHD lipid-lowering drugs should be considered when serum cholesterol exceeds 6.5 mmol I(-1) and the risk of CHD is greater than 20 % over the next 10 years. There is no evidence that pursuing this policy beyond the age of 70 years is beneficial. Diabetic women with dyslipoproteinaemia should, however, be treated in the same way as men. The knowledge that hypertriglyceridaemia and low serum HDL cholesterol are present helps in the assessment of CHD risk and the choice of medication to decrease non-HDL cholesterol, but there is no evidence that their treatment in the absence of raised cholesterol is of benefit.     

The effect of long-term thyroxine on bone mineral density and serum cholesterol

The effect of thyrotrophin suppression on bone mineral density (BMD) and serum cholesterol concentration was assessed in 31 treated hypothyroid women. Measurements of the BMD of the lumbar spine and femoral neck were repeated in seven of those with the lowest value after an average period of 22.7 months. Final cholesterol concentrations were compared with values before thyroxine was started. The dose of thyroxine was based on clinical assessment, serum triiodothyronine concentrations kept within the normal range, and thyrotrophin values within the normal range or suppressed. The patients had taken thyroxine replacement for a mean of 12.7 years. Two-thirds (21 subjects) had suppressed thyrotrophin concentrations, and it was normal in one-third (10). Fifteen subjects had a past history of thyrotoxicosis. BMD and cholesterol concentrations were compared between those with suppressed and normal thyrotrophin concentrations and between those with and without a past history of thyrotoxicosis. No patient had a pathological fracture. One had a Z value for the femoral neck of -1.6, denoting early but definite osteoporosis, and five had borderline osteoporosis with Z values for one or other site between -1.1 and -1.5. None of the seven with the lowest BMDs had any significant change when measurements were repeated. The difference in Z values between subjects with suppressed and normal thyrotrophin concentrations was not significant for either the lumbar spine (p = 0.68) or the femoral neck (p = 0.28). A past history of thyrotoxicosis had a greater effect on BMD for both sites than thyrotrophin suppression, but again the difference between those with and without a past history of thyrotoxicosis was significant neither for the lumbar spine (p = 0.18) nor for the femoral neck (p = 0.34). The combination of thyrotrophin suppression and a past history of thyrotoxicosis also failed significantly to reduce the BMD of the lumbar spine (p = 0.38) or femoral neck (p = 0.30) in comparison with those who had neither thyrotrophin suppression nor a past history of thyrotoxicosis. The mean fall in serum cholesterol concentration was 2.1 mmol/l (SD 1.78) (p = 0.001) in those with a suppressed thyrotrophin concentration taking a mean daily dose of thyroxine of 171 micrograms (SD: 34.7), compared with a fall of 0.89 mmol/l (SD: 1.04) (p = 0.065) in those whose thyrotrophin concentration was not suppressed on a mean daily thyroxine dose of 140 micrograms (SD: 50). No patient had atrial fibrillation or cardiographic evidence of coronary artery disease (CAD). The serum cholesterol concentration should play at least as important a part in influencing the dose of thyroxine as a fear of osteoporosis. Fractures are not a feature in the natural history of treated hypothyroidism, whereas CAD is a common cause of death in these patients.     

The effect of a low-fat, high-carbohydrate diet on serum high density lipoprotein cholesterol and triglyceride

OBJECTIVE: To determine whether substituting carbohydrate for saturated fat has any adverse effects on serum high density lipoprotein (HDL) cholesterol and triglycerides in free-living individuals. DESIGN: Randomised crossover trial. SETTING: General community. SUBJECTS: Volunteer sample of 38 healthy free-living men with mean (s.d.) age 37 (7) y, moderately elevated serum total cholesterol 5.51 (0.93) mmol/l and body mass index 26.0 (3.6) kg/m2. INTERVENTIONS: Participants completed two six week experimental periods during which they consumed either a traditional Western diet (36%, 18%, and 43% energy from total, saturated, and carbohydrate, respectively) or a low-saturated fat high-carbohydrate diet (22%, 6% and 59% energy from total, saturated, and carbohydrate, respectively). Dietary principles were reinforced regularly, but food choices were self-selected during each experimental period. MAIN OUTCOME MEASURES: Serum lipids, body weight and plasma fatty acids. RESULTS: Reported energy and nutrient intakes, plasma fatty acids, and a drop in weight from 79.1 (12.5) kg on the Western diet to 77.6 (12.0) kg on the high-carbohydrate diet (P < 0.001) confirmed a high level of compliance with experimental diets. Total and low density lipoprotein (LDL) cholesterol fell from 5.52 (1.04) mmol/l and 3.64 (0.88) mmol/l, respectively on the Western diet to 4.76 (1.10) mmol/l and 2.97 (0.94) mmol/l on the high-carbohydrate diet (P < 0.001). HDL cholesterol fell from 1.21 (0.27) mmol/l on the Western diet to 1.07 (0.23) mmol/l on the high-carbohydrate diet (P = 0.057), but the LDL:HDL cholesterol ratio improved from 3.17 (1.05) on the Western diet to 2.88 (0.97) on the high-carbohydrate diet (P = 0.004). Fasting triglyceride levels were unchanged throughout the study. CONCLUSIONS: Replacement of saturated fat with carbohydrate from grains, vegetables, legumes, and fruit reduces total and LDL cholesterol with only a minor effect on HDL cholesterol and triglyceride. It seems that when free living individuals change to a fibre rich high-carbohydrate diet appropriate food choices lead to a modest weight reduction. This may explain why the marked elevation of triglyceride and reduction of HDL cholesterol observed on strictly controlled high-carbohydrate diets may not occur when such diets are followed in practice.     

High-level resistance of cytomegalovirus to ganciclovir is associated with alterations in both the UL97 and DNA polymerase genes

The study describes rates of coronary heart disease death and nonfatal coronary events over five years in a cohort of random sample population and relates them to levels of three major risk factors. It is based on a longitudinal follow-up of survey conducted initially in 1990 in all geographic regions of Turkey. Two-thirds of the original cohort aged 20 years or over 2259 adults comprising 1146 women was followed up by physical examination and an ECG recording at rest. New coronary events were defined to include myocardial infarction and stable angina with or without associated myocardial ischemia developed during the follow-up period. Overall annual death rate was nine per 1000 adults. Coronary deaths numbered 55 (of which 26 were women) representing 4.1 per year and were found high in women. New coronary events were registered in 37 men and 32 women (annual rates 7.2 and 5.8 per 1000, respectively). Among male participants aged initially 40 years or over, high systolic blood pressure (> or = 130 mmHg) at baseline significantly predicted coronary death (age-adjusted risk ratio (RR) 3.3) while high cholesterol concentrations (> or = 5.2 mmol l-1) predicted new coronary events alone (RR almost 2). In women systolic pressure again strongly predicted coronary death (age-adjusted RR 3.9), whereas abnormal cholesterol levels discriminated for coronary death and new coronary events (RR around 2.3 for each). High diastolic pressure (> or = 85 mmHg) was of predictive value for the combined outcome of coronary death and events in women (RR 1.9) but not in men. Multivariate analysis by logistic regression identified systolic blood pressure in men as significant independent predictor of coronary death, while total cholesterol concentration in both genders and systolic blood pressure in men were independent predictors of the combined outcome of coronary death or nonfatal coronary events. It was concluded that known major risk factors act in similar magnitudes commensurate with the specific risk increments also in populations with essentially low cholesterol levels. The relatively high coronary morbidity and mortality in Turkish women approaching that in men may be accounted for by an inherent greater risk burden.     

Influenza virus inhibits cleavage of the HSP70 pre-mRNAs at the polyadenylation site

BACKGROUND: Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory. OBJECTIVE: To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease. DESIGN: In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L. RESULTS: Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change. CONCLUSION: The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations.     

Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.     

Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP)

BACKGROUND: The association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and, to a lesser extent, in similar women. Less well defined are lipid variables predictive of CHD in individuals of age > or = 60 years. METHODS AND RESULTS: The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years; 14% were black; and 43% were men). Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. Baseline mean total cholesterol was 6.11 mmol/L (236 mg/dL); HDL cholesterol, 1.39 mmol/L (54 mg/dL); and non-HDL cholesterol, 4.72 mmol/L (182 mg/dL). Triglyceride levels were 1.62 mmol/L (144 mg/dL) for fasting participants and 1.78 mmol/L for the total group. LDL cholesterol, estimated in fasting samples with triglycerides of < 4.52 mmol/L, averaged 3.98 mmol/L (154 mg/dL). Mean follow-up was 4.5 years. In multivariate Cox regression analyses, baseline total, non-HDL, and LDL cholesterol levels and the ratios of total, non-HDL, and LDL to HDL cholesterol were significantly related to CHD incidence. HDL cholesterol and triglycerides were not significant in these analyses. In fasting participants with triglyceride levels of < 4.52 mmol/L, a 1.03 mmol/L (40 mg/dL) higher baseline total, non-HDL, or LDL cholesterol was associated with a 30% to 35% higher CHD event rate. CONCLUSIONS: The results of this study support the concept that serum lipids are CHD risk factors in older Americans.