Impact on lipoprotein profile after long-term testosterone replacement in hypogonadal men.

Testosterone serum levels may influence the lipoprotein metabolism and possibly atherogenic risk. Our aim was to investigate the effects of long-term testosterone supplementation in hypogonadal men on multiple lipoprotein markers. 18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of treatment with testosterone enanthate. During treatment, serum testosterone and estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively). This was associated with a decrease in HDL cholesterol (from 1.40 +/- 0.10 mmol/l to 1.22 +/- 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2 cholesterol (p < 0.01), as well as apoprotein A1 (from 139 +/- 3.4 mg/dl to 126 +/- 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides, and apoprotein B did not increase. Among the seven patients who completed 18 months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol, as well as total cholesterol/HDL cholesterol ratio values did not differ from baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained decreased and hepatic lipase unchanged. Restoration of testosterone levels in hypogonadal men in this study did not reveal unfavorable changes based on total cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are both atherogenic risk markers. Whether the changes in light of lipoprotein metabolism will adversely influence cardiovascular risk over time remains to be determined.     

Concentration and composition of serum lipoproteins during a low-fat diet at two levels of polyunsaturated fat

A 12-week dietary intervention was carried out among 40 families from North Karelia, a county in Finland with an exceptionally high rate of coronary heart disease and high serum cholesterol values. The proportion of dietary energy derived from fat was reduced during the 12-week intervention period from about 39% to 23% in all families. The families were randomly allocated into two groups. Twenty families consumed a diet with a polyunsaturated to saturated fat (P/S) ratio of 0.9 (group I), while the other 20 families had a diet with a P/S ratio of 0.4 (group II). Total serum cholesterol decreased by 16% and 9% in men of groups I and II, respectively, and by 16% in women of both groups. These changes were due to a decrease in both low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol. LDL cholesterol and phospholipid reached minimum values after 6 weeks on both intervention diets, but LDL protein responded more slowly. Thus, after 6 weeks LDL had an altered composition containing less cholesterol and phospholipids and more protein and triglycerides than during the baseline diet. During the intervention, the linoleic acid content in the serum cholesteryl ester fraction increased, and the magnitude of this change correlated negatively with the changes in total and LDL cholesterol. The decrease in HDL cholesterol during the two intervention diets was due to a fall in the HDL2 cholesterol (29% and 24% in men, and 26% and 25% in women in groups I and II, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Threat of unemployment and cardiovascular risk factors: longitudinal study of quality of sleep and serum cholesterol concentrations in men threatened with redundancy.

OBJECTIVE--To assess whether the threat of unemployment affects risk factors for cardiovascular disease. DESIGN--Longitudinal study of a cohort of middle aged shipyard workers followed up for a mean of 6.2 (SD 1.9) years and a group of controls observed for the same period. The first investigation took place during a period of relative economic stability for the shipyard and the second during the phase of its closure. SETTING--An age cohort health screening programme in Malmö, Sweden. PARTICIPANTS--715 Male shipyard workers and 261 age matched male controls. MAIN OUTCOME MEASURES--Changes in 19 variables related to the risk of cardiovascular disease, and psychological variables, alcohol consumption, smoking, and dietary habits as assessed by questionnaire. RESULTS--Serum cholesterol concentrations increased more (mean 0.25 (SD 0.68) mmol/l v 0.08 (0.66) mmol/l) and serum calcium concentrations decreased less (-0.06 (0.10) mmol/l v -0.08 (0.09) mmol/l) in the shipyard workers than in the controls. A correlation was found between scores for sleep disturbance and changes in serum cholesterol concentration. In the whole series there was a greater increase in serum cholesterol concentrations among men threatened with unemployment (437/976; 44.8%) than among those who were not. In stepwise regression analysis the change in serum cholesterol concentration was correlated with changes in haemoglobin concentration, body weight, and serum triglyceride and calcium concentrations. A positive correlation was found between change in cholesterol concentration and change in blood pressure, indicating that the overall risk profile had worsened among men with increased serum cholesterol concentrations. CONCLUSIONS--Risk of unemployment increases the serum cholesterol concentration in middle aged men, the increase being more pronounced in those with sleep disturbance. The increase in serum cholesterol is related to changes in other established risk factors for cardiovascular disease. These findings might partly explain the excessive mortality due to cardiovascular disease recorded among the unemployed and people with sleep disturbance.     

Study of coronary risk factors related to physical activity in 15 171 men.

Physical activity, both at work and during leisure, was assessed in 15 171 men aged 25-74 years. Heavy leisure activity was associated with lower mean serum cholesterol levels and blood pressure. In men under 60 years the same negative association was also noted between leisure activity and relative weight and cigarette smoking. Different degrees of physical activity at work were not associated with any differences in these risk factors, nor did the level of exercise at work seem to influence the negative association between leisure activity and risk factors. Heavy leisure activity in young and middle-aged men is associated with lower levels of certain coronary risk factors and, therefore, a lower risk of coronary heart disease. The often-reported reduction in coronary morbidity and mortality with physical exercise may not be the direct effect of the exercise itself.     

Do changes in cardiovascular risk factors explain changes in mortality from stroke in Finland?

OBJECTIVES--To estimate the extent to which the changes in the main cardiovascular risk factors (blood pressure, smoking, and serum cholesterol concentration) can explain the observed changes in mortality from stroke in Finland during the past 20 years. DESIGN--Predicted changes in mortality from cerebrovascular disease mortality were calculated by a proportional hazards model from data obtained in cross sectional population surveys in 1972, 1977, 1982, 1987, and 1992. Predicted changes were compared with the observed changes in mortality statistics. SETTING--North Karelia and Kuopio provinces, Finland. SUBJECTS--16,741 men and 16,389 women aged 30-59 randomly selected from the national population register, of whom 14,054 men and 14,546 women participated. MAIN OUTCOME MEASURES--Levels of risk factors and predicted and observed changes in mortality from cerebrovascular disease. RESULTS--The observed changes in diastolic blood pressure, total serum cholesterol concentration, and smoking in the population from 1972 to 1992 predicted a 44% fall in mortality from stroke in men and changes in diastolic blood pressure and smoking predicted a 34% fall in women. The observed fall in mortality from stroke was 66% in men and 60% in women. CONCLUSIONS--Two thirds of the fall in mortality from stroke in men and half in women can be explained by changes in the three main cardiovascular risk factors.     

Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity

The roles of polymorphisms of the sitosterolemia genes ABCG5 and ABCG8 in the regulation of cholesterol metabolism and insulin sensitivity were studied in mildly hypercholesterolemic noncoronary subjects (n = 263, 144 men and 119 women) divided into tertiles by baseline serum cholestanol-to-cholesterol ratio (< or = 118.3 and > or = 147.7 10(2) x mmol/mol cholesterol), a surrogate marker of cholesterol absorption efficiency. The lowest cholestanol tertile was associated with high body mass index (BMI), plasma glucose, serum insulin and triglycerides, and cholesterol synthesis markers (cholestenol, desmosterol, lathosterol) and low HDL cholesterol and cholesterol absorption markers (campesterol, sitosterol) (P < 0.01 for all). The 19H allele of the ABCG8 gene accumulated in the lowest cholestanol tertile (P < 0.001) and was associated with low total and LDL cholesterol and absorption markers and with high synthesis markers (P < 0.05 for all). The 604E allele of the ABCG5 gene in men was associated with high BMI, plasma insulin, low serum sitosterol, and high serum cholestenol levels (P < 0.05 for all). In a subgroup of 71 men, the 604E allele was associated with insulin resistance measured with the hyperinsulinemic euglycemic clamp. In conclusion, low cholesterol absorption efficiency was associated with characteristics of the metabolic syndrome. Low serum cholesterol and cholesterol absorption were linked to the D19H polymorphism of the ABCG8 gene, and characteristics of the insulin resistance syndrome in men were linked with the Q604E polymorphism of the ABCG5 gene.     

Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease.

OBJECTIVE--To examine whether method of infant feeding is associated with adult serum lipid concentrations and mortality from ischaemic heart disease. DESIGN--Follow up study of men born during 1911-30. SETTING--Hertfordshire, England. SUBJECTS--5718 men, for 5471 of whom information on infant feeding had been recorded by health visitors and 1314 of whom had died. 485 of the men born during 1920-30 and still living in Hertfordshire who had blood lipid measurements. MAIN OUTCOME MEASURES--Death from ischaemic heart disease; serum cholesterol and apolipoprotein concentrations. RESULTS--474 men had died from ischaemic heart disease. Standardised mortality ratios were 97 (95% confidence interval 81 to 115) in men who had been breast fed and had not been weaned at 1 year, 79 (69 to 90) in breast fed men who had been weaned at 1 year, and 73 (59 to 89) in men who had been breast and bottle fed. Compared with men weaned before one year men not weaned had higher mean serum concentrations of total cholesterol (6.9 (not weaned) v 6.6 (weaned) mmol/l), low density lipoprotein cholesterol (5.0 v 4.6 mmol/l) and apolipoprotein B (1.14 v 1.08 g/l). Men who had been bottle fed also had a high standardised mortality ratio for ischaemic heart disease (95; 68 to 130) and high mean serum concentrations of total cholesterol (7.0 mmol/l), low density lipoprotein cholesterol (5.1 mmol/l), and apolipoprotein B (1.14 g/l). In all feeding groups serum apolipoprotein B concentrations were lower in men with higher birth weight and weight at 1 year. CONCLUSIONS--Age of weaning and method of infant feeding may influence adult serum low density lipoprotein cholesterol concentrations and mortality from ischaemic heart disease. Adult serum apolipoprotein B concentrations are related to growth in fetal life and infancy.     

Increased beef consumption increases apolipoprotein A-I but not serum cholesterol of mildly hypercholesterolemic men with different levels of habitual beef intake

The objective of this research was to compare the effects of a lean beef enriched in oleic acid to a beef that is typical of the commercial beef consumed in the United States. Ten mildly hypercholesterolemic men, ages 34-58 years old, were selected from the Texas A&M University faculty and staff. Subjects were randomly assigned to one of two diets for a 6-week duration followed by a crossover after a 4-week habitual diet washout period. Diets were consumed daily for a 6-week study period. Participants substituted lean beef obtained from Wagyu bullocks or commercial beef for the meat typically consumed. Total cholesterol, apolipoproteins A-I and B, triacylglycerols, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were measured in serum samples collected weekly. Beef type had no effect on any measured variable. There were no significant differences between baseline HDL or LDL cholesterol concentrations after the consumption of the beef test diets. Apolipoprotein A-I, serum glucose, and uric acid concentrations were elevated by the additional dietary beef. Analysis of records of customary diets indicated that one group consumed 160 g of beef daily, whereas the other group consumed only 26 g of beef daily. Therefore, post hoc analyses tested the habitual beef intake x treatment time interaction. LDL cholesterol concentration was markedly higher in the group with low habitual beef intake (180 vs 144 mg/dl), and HDL cholesterol was slightly higher (44 vs 40 mg/dl; post-test values) than for the group with high habitual beef intake, but there were no habitual intake x time interactions for LDL or HDL cholesterol. Creatinine and blood urea nitrogen concentrations also were greater in the individuals habitually consuming less beef. This study had three important findings: i) a lean beef source enriched with oleic acid was no different from commercial beef in its effect on lipoprotein fractions; ii) neither previous level of beef intake nor baseline LDL cholesterol concentration influenced the serum cholesterol response to added dietary beef, which was negative; and iii) apolipoprotein A-I, but not HDL or LDL cholesterol, was sensitive to the additional dietary beef.     

Evaluation of the use of serum lathosterol concentration to assess whole-body cholesterol synthesis in rabbits.

Serum lathosterol concentration in rabbits was assessed as a possible indicator of whole-body cholesterol synthesis. In random-bred New Zealand White (NZW) rabbits fed a control diet or a diet containing either cholesterol, simvastatin, or cholestyramine, neither serum lathosterol concentration nor the serum lathosterol:total cholesterol ratio systematically corresponded with the anticipated rate of cholesterol synthesis. In control rabbits and those fed simvastatin or cholestyramine, whole-body cholesterol synthesis, which was calculated from the sterol balance, was correlated with serum lathosterol concentration when expressed relative to cholesterol in very low, intermediate, and low density lipoproteins (VLDL + IDL + LDL) (r = 0.61; n = 23; P = 0.002). The low correlation coefficient indicates that the predictive value of the lathosterol: (VLDL + IDL + LDL) cholesterol ratio is limited when applied to individual rabbits. Cholesterol and simvastatin feeding reduced the group mean serum lathosterol:(VLDL + IDL + LDL) cholesterol ratio, whereas cholestyramine in the diet raised the group mean ratio in the NZW rabbits. We conclude that the serum lathosterol:(VLDL + IDL + LDL) cholesterol ratio may be an indicator of group mean rates of whole-body cholesterol synthesis in rabbits but may not yield reliable information on individual rabbits. The lathosterol:(VLDL + IDL + LDL) cholesterol ratio predicted that in hyperresponsive inbred rabbits, showing an excessive hypercholesterolemia after cholesterol feeding, baseline whole-body cholesterol synthesis is lower than in hyporesponsive rabbits. Addition of cholesterol to the diet caused a reduction of predicted cholesterol synthesis in hypo- but not in hyper-responsive rabbits.     

Influence of human low density and high density lipoprotein cholesterol on the in vitro prostaglandin I2 synthetase activity

We investigated in vitro the influence of low density lipoprotein (LDL) cholesterol and high density lioprotein (HDL) cholesterol separated from human serum on prostaglandin I2 synthetase activity studied by the conversion of prostaglandin H2 to prostaglandin I2 by the microsomal fraction of pig aorta. 6-Oxo-prostaglandin F1 alpha was analyzed by gas-liquid chromatography using prostaglandin F1 alpha as internal standard. We found a linear negative correlation (P less than 0.001) between the amount of LDL cholesterol in the incubation solution and prostaglandin I2 synthetase activity, whereas there was a positive correlation (P less than 0.01) between HDL cholesterol and prostaglandin I2 synthesis. A very low concentration of LDL cholesterol and a high concentration of HDL cholesterol stimulated prostaglandin I2 synthesis, whereas a high LDL cholesterol concentration inhibited prostaglandin I2 biosynthesis by 64%. The concentration range of LDL and HDL cholesterol was representative of physiologically low, normal or elevated levels of lipoproteins.     

Cholesterol and mortality in New Zealand Maoris.

The relation between serum cholesterol concentration and mortality was studied prospectively over 11 years in 630 New Zealand Maoris aged 25-74. Serum cholesterol concentration was measured at initial examination in 1962-3 in 94% of the subjects and whether each was dead or alive was determined in 1974. The causes of death were divided into three categories: cancer, cardiovascular disease, and "other." The Mantel-Haenszel method of analysis of survivorship data showed a significant inverse relation between serum cholesterol concentration and overall mortality in men (x 2/2 = 11.6; p = 0.003) and women (x 2/2 = 7.6; p = 0.02) with odds ratios of 2.3 and 1.9 respectively. Similar significant inverse relations were found for cancer and "other" causes of death. These relations remained significant when baseline age, systolic blood pressure, and the Quetelt index were controlled in Cox''s proportional hazards regression model. The results of this study provide evidence for a potentially deleterious effect of low serum cholesterol concentration. Hence, further research is needed before indiscriminate efforts are made to lower serum cholesterol concentrations in New Zealand Maoris.     

Changes in Waist Circumference and Mortality in Middle-Aged Men and Women

Background

Waist circumference (WC) adjusted for body mass index (BMI) is positively associated with mortality, but the association with changes in WC is less clear. We investigated the association between changes in WC and mortality in middle-aged men and women, and evaluated the influence from concurrent changes in BMI.

Methodology/Principal Findings

Data on 26,625 healthy men and women from the Danish Diet, Cancer and Health study was analyzed. WC and BMI were assessed in 1993–97 and in 1999–02. Information on mortality was obtained by linkage to the Danish central Person Register. Hazard ratios (HR) were estimated with Cox regression models. During 6.7 years of follow-up, 568 and 361 deaths occurred among men and women, respectively. Changes in WC were positively associated with mortality (HR per 5 cm for the sexes combined  = 1.09 (1.02∶1.16) with adjustment for covariates, baseline WC, BMI and changes in BMI), whereas changes in BMI were inversely associated with mortality (HR per kg/m2 for the sexes combined  = 0.91 (0.86, 0.97) with adjustment for covariates, baseline WC, BMI and changes in WC). Associations between changes in WC and mortality were not notably different in sub-groups stratified according to changes in BMI, baseline WC or when smokers or deaths occurring within the first years of follow-up were excluded.

Conclusions/Significance

Changes in WC were positively associated with mortality in healthy middle-aged men and women throughout the range of concurrent changes in BMI. These findings suggest a need for development of prevention and treatment strategies targeted against redistribution of fat mass towards the abdominal region.     

Impact of cardiovascular risk factors on coronary heart disease and mortality among middle aged diabetic men: a general population study.

OBJECTIVE--To investigate the effect of cardiovascular risk factors on coronary heart disease and all cause mortality in middle aged diabetic men. DESIGN--Prospective population study based on data collected from second screening (from 1974 to 1977) in the multifactor primary prevention trial and follow up until March 1983. SETTING--Gothenburg, Sweden. SUBJECTS--6897 Men aged 51 to 59, of whom 232 were self reported diabetics and 6665 were non-diabetic; none had a history of myocardial infarction. MAIN OUTCOME MEASURES--Incidences of coronary heart disease and mortality from all causes. RESULTS--Diabetic men with a serum cholesterol concentration greater than 7.3 mmol/l had a significantly higher incidence of coronary heart disease during follow up than those with a concentration less than or equal to 5.5 mmol/l (28.3% v 5.4%; p = 0.020); corresponding figures for non-diabetic men were 9.4% and 2.4% respectively. In multivariate logistic regression analyses serum cholesterol concentration and smoking habit were independent predictors of coronary heart disease (odds ratio serum cholesterol concentration 6.1 (95% confidence interval 2.1 to 17.6) current smoking 2.9 (1.1 to 7.5)) and of all cause mortality (3.2 (1.3 to 7.9), 3.0 (1.4 to 6.7) respectively) in diabetic men whereas systolic blood pressure, body mass index, family history, marital state, and alcohol abuse were not. Low occupational class was an independent predictor of mortality (2.4 (1.01 to 5.5)), but not of coronary heart disease, in diabetic men. CONCLUSIONS--Middle aged diabetic men with hypercholesterolaemia are at very high risk of developing coronary heart disease and of dying prematurely. Lowering serum cholesterol concentration in such subjects seems to be warranted.     

Acute sex steroid withdrawal increases cholesterol efflux capacity and HDL-associated clusterin in men

Exogenous androgens can lower HDL-cholesterol (HDL-C) concentrations, yet men with low serum testosterone have elevated rates of cardiovascular disease (CVD). HDL function may better predict CVD risk than absolute HDL-C quantity. We evaluated the acute effects of medical castration in men on HDL-C, cholesterol efflux capacity and HDL protein composition. Twenty-one healthy men, ages 18-55, received the GnRH antagonist acyline and one of the following for 28days: Group 1: placebo, Group 2: transdermal testosterone gel and placebo, Group 3: transdermal testosterone gel and an aromatase inhibitor. Sex steroids, fasting lipids, and cholesterol efflux to apoB-depleted serum were measured in all subjects. The HDL proteome was assessed in Group 1 subjects only. In Group 1, serum testosterone concentrations were reduced by >95%, and HDL-C and cholesterol efflux capacity increased (p=0.02 and p=0.03 vs. baseline, respectively). HDL-associated clusterin increased significantly with sex steroid withdrawal (p=0.007 vs. baseline). Testosterone withdrawal in young, healthy men increases HDL-C and cholesterol efflux capacity. Moreover, sex steroid deprivation changes HDL protein composition. Further investigation of the effects of sex steroids on HDL composition and function may help resolve the apparently conflicting data regarding testosterone, HDL-C, and CVD risk.     

An almond-enriched diet increases plasma α-tocopherol and improves vascular function but does not affect oxidative stress markers or lipid levels

Abstract

Vascular dysfunction is one of the major causes of cardiovascular (CV) mortality and increases with age. Epidemiological studies suggest that Mediterranean diets and high nut consumption reduce CV disease risk and mortality while increasing plasma α-tocopherol. Therefore, we have investigated whether almond supplementation can improve oxidative stress markers and CV risk factors over 4 weeks in young and middle-aged men.

Healthy middle-aged men (56 ± 5.8 years), healthy young men (22.1 ± 2.9 years) and young men with two or more CV risk factors (27.3 ± 5 years) consumed 50 g almond/day for 4 weeks. A control group maintained habitual diets over the same period.

Plasma α-tocopherol/cholesterol ratios were not different between groups at baseline and were significantly elevated by almond intervention with 50 g almond/day for 4 weeks (p < 0.05). Plasma protein oxidation and nitrite levels were not different between groups whereas, total-, HDL- and LDL-cholesterols and triglycerides were significantly higher in healthy middle-aged and young men with CV risk factors but were not affected by intake. In the almond-consuming groups, flow-mediated dilatation (FMD) improved and systolic blood pressure reduced significantly after 50 g almonds/day for 4 weeks, but diastolic blood pressure reduced only in healthy men.

In conclusion, a short-term almond-enriched diet can increase plasma α-tocopherol and improve vascular function in asymptomatic healthy men aged between 20 and 70 years without any effect on plasma lipids or markers of oxidative stress.     

Non-fasting serum triglyceride concentration and mortality from coronary heart disease and any cause in middle aged Norwegian women.

OBJECTIVE--To study the association between non-fasting serum triglyceride concentrations and mortality in women from coronary and cardiovascular disease and all causes. DESIGN--Follow up by ambulatory teams of men and women who underwent cardiovascular screening for a mean of 14.6 years. SETTING--National health screening service in Norway. SUBJECTS--25,058 men and 24,535 women aged 35-49 years. MAIN OUTCOME MEASURE--Predictive value of non-fasting serum triglyceride concentrations. RESULTS--At initial screening total serum cholesterol concentration, serum triglyceride concentration, blood pressure, height, and weight were measured, and self reported information about smoking habits, physical activity, and time since last meal were recorded. During subsequent follow up 108 women died from coronary heart disease, 238 from cardiovascular diseases, and 931 from all causes. In women mortality increased steadily with increasing triglyceride concentration for all three causes of death. With the proportional hazards model and adjustment for age, systolic blood pressure, total cholesterol concentration, time since last meal, and number of cigarettes a day the relative risk between triglyceride concentration > or = 3.5 mmol/l and < 1.5 mmol/l was 4.7 (95% confidence interval 2.5 to 8.9) for deaths from coronary heart disease, 3.0 (1.9 to 4.8) for deaths from cardiovascular disease, 2.3 (1.8 to 2.9) for total deaths in all women. CONCLUSIONS--A raised non-fasting concentration of triglycerides is an independent risk factor for mortality from coronary heart disease, cardiovascular disease, and any cause mortality among middle aged Norwegian women in contrast to what is seen in men.     

Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer

Androgen deprivation therapy (ADT) for prostate cancer is now used in earlier disease stages and as adjuvant treatment. Recognizing and reducing the toxicity of this therapy, including worsened lipid levels and cardiovascular disease (CVD) risks, has become an important clinical concern. Oral estrogen therapy induces hypogonadism and mitigates many side effects of ADT, but has a high thrombosis risk. Transdermal estrogen therapy (TDE) has a lower thrombosis risk than oral estrogen and may improve CVD risk compared with ADT. This prospective pilot study of 18 men with androgen-independent prostate cancer receiving ADT measured effects of TDE on lipid and inflammatory CVD risk factors before and after 8 weeks of TDE (estradiol 0.6 mg/day). During treatment, estradiol levels rose 17-fold; total cholesterol, LDL cholesterol, and apolipoprotein B levels decreased. HDL2 cholesterol increased, with no changes in triglyceride or VLDL cholesterol levels. Dense LDL cholesterol decreased and LDL buoyancy increased in association with a decrease in HL activity. Highly sensitive C-reactive protein levels and other inflammatory markers did not worsen. Compared with ADT, short-term TDE therapy of prostate cancer improves lipid levels without deterioration of CVD-associated inflammatory markers and may, on longer-term follow-up, improve CVD and mortality rates.     

The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life.

OBJECTIVE--To determine how fetal growth is related to death from cardiovascular disease in adult life. DESIGN--A follow up study of men born during 1907-24 whose birth weights, head circumferences, and other body measurements were recorded at birth. SETTING--Sheffield, England. SUBJECTS--1586 Men born in the Jessop Hospital. MAIN OUTCOME MEASURE--Death from cardiovascular disease. RESULTS--Standardised mortality ratios for cardiovascular disease fell from 119 in men who weighed 5.5 pounds (2495 g) or less at birth to 74 in men who weighed more than 8.5 pounds (3856 g). The fall was significant for premature cardiovascular deaths up to 65 years of age (chi 2 = 5.0, p = 0.02). Standardised mortality ratios also fell with increasing head circumference (chi 2 = 4.6, p = 0.03) and increasing ponderal index (weight/length3) (chi 2 = 3.8, p = 0.05; for premature deaths chi 2 = 6.0, p = 0.01). They were not related to the duration of gestation. Among men for whom the ratio of placental weight to birth weight was in the highest fifths the standardised mortality ratio was 137. CONCLUSION--These findings show that reduced fetal growth is followed by increased mortality from cardiovascular disease. They suggest that reduction in growth begins early in gestation. They are further evidence that cardiovascular disease originates through programming of the body''s structure, physiology, and metabolism by the environment during fetal life. Maternal nutrition may have an important influence on programming.     

Lifetime socioeconomic position and mortality: prospective observational study.

OBJECTIVES: To assess the influence of socioeconomic position over a lifetime on risk factors for cardiovascular disease, on morbidity, and on mortality from various causes. DESIGN: Prospective observational study with 21 years of follow up. Social class was determined as manual or non-manual at three stages of participants'' lives: from the social class of their father''s job, the social class of their first job, and the social class of their job at the time of screening. A cumulative social class indicator was constructed, ranging from non-manual social class at all three stages of life to manual social class at all three stages. SETTING: 27 workplaces in the west of Scotland. PARTICIPANTS: 5766 men aged 35-64 at the time of examination. MAIN OUTCOME MEASURES: Prevalence and level of risk factors for cardiovascular disease; morbidity; and mortality from broad causes of death. RESULTS: From non-manual social class locations at all three life stages to manual at all stages there were strong positive trends for blood pressure, body mass index, current cigarette smoking, angina, and bronchitis. Inverse trends were seen for height, cholesterol concentration, lung function, and being an ex-smoker. 1580 men died during follow up. Age adjusted relative death rates in comparison with the men of non-manual social class locations at all three stages of life were 1.29 (95% confidence interval 1.08 to 1.56) in men of two non-manual and one manual social class; 1.45 (1.21 to 1.73) in men of two manual and one non-manual social class; and 1.71 (1.46 to 2.01) in men of manual social class at all three stages. Mortality from cardiovascular disease showed a similar graded association with cumulative social class. Mortality from cancer was mainly raised among men of manual social class at all three stages. Adjustment for a wide range of risk factors caused little attenuation in the association of cumulative social class with mortality from all causes and from cardiovascular disease; greater attenuation was seen in the association with mortality from non-cardiovascular, non-cancer disease. Fathers having a manual [corrected] occupation was strongly associated with mortality from cardiovascular disease: relative rate 1.41 (1.15 to 1.72). Participants'' social class at the time of screening was more strongly associated than the other social class indicators with mortality from cancer and from non-cardiovascular, non-cancer causes. CONCLUSIONS: Socioeconomic factors acting over the lifetime affect health and risk of premature death. The relative importance of influences at different stages varies for the cause of death. Studies with data on socioeconomic circumstances at only one stage of life are inadequate for fully elucidating the contribution of socioeconomic factors to health and mortality risk.     

Sialic acid content of low density lipoprotein and its relation to lipid concentrations and metabolism of low density lipoprotein and cholesterol

A low sialic acid content in low density lipoprotein (LDL) has been associated with atherogenicity and coronary artery disease (CAD) in many but not all studies. We investigated associations of the sialic acid-to-apolipoprotein B (apoB) ratio of LDL with lipoprotein lipid concentrations, kinetics of LDL, metabolism of cholesterol, and the presence of CAD in 98 subjects (CAD(+), n = 56; CAD(-), n = 42). The sialic acid ratios of total, dense, and very dense LDL were lower in the CAD(+) than CAD(-) subjects, especially at high sialic acid ratios. The LDL sialic acid ratio was inversely associated with respective lipid and apoB concentrations and positively with lipid-to-apoB ratios of LDL. The transport rates (TRs) for total and dense LDL apoB were negatively associated with their sialic acid ratios. The sialic acid ratio of dense LDL, but not that of total LDL, was inversely correlated with serum levels of cholesterol precursor sterols, indicators of cholesterol synthesis, and positively with serum levels of plant sterols, indicators of cholesterol absorption. In addition, the TR for dense LDL was positively correlated with cholesterol synthesis.In conclusion, a low LDL sialic acid ratio was associated with CAD, high numbers of small LDL particles, and a high TR for LDL apoB, and in dense LDL also with high synthesis and low absorption of cholesterol.