Lipoprotein (a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men.

OBJECTIVE--To examine the association between the serum lipoprotein (a) concentration and subsequent coronary heart disease. DESIGN--Prospective case-control study based on a six year follow up of a general population sample of men aged 50 at baseline in 1983-4. Serum samples were frozen at the time of the baseline examination and kept at -70 degrees C for six years, after which the lipoprotein (a) concentrations in the samples were measured in cases and controls. SETTING--City of Gothenburg, Sweden. SUBJECTS--26 Men, from a general population sample of 776 men, who had sustained a myocardial infarction or died of coronary heart disease during the six years and 109 randomly selected controls from the same sample who had remained free of myocardial infarction. In neither cases nor controls was there a history of myocardial infarction at baseline. MAIN OUTCOME MEASURES--Proportion of myocardial infarction or deaths from coronary heart disease, or both, in relation to the serum lipoprotein (a) concentration. RESULTS--Men who suffered coronary heart disease had significantly higher serum lipoprotein (a) concentrations than controls (mean difference 105 mg/l; 95% confidence interval 18 to 192 mg/l). Men with the highest fifth of serum lipoprotein (a) concentrations (cut off point 365 mg/l) suffered a coronary heart disease rate which was more than twice that of men with the lowest four fifths of concentrations. Logistic regression analysis showed the serum lipoprotein (a) concentration to be significantly associated with coronary heart disease independently of other risk factors. CONCLUSION--The serum lipoprotein (a) concentration in middle aged men is an independent risk factor for subsequent myocardial infarction or death from coronary heart disease.     

Antioxidant vitamin levels do not exhibit negative correlation with the extent of acute myocardial infarction

Serum levels of vitamin E (VE), beta-carotene (BC) and vitamin C (VC) were determined in 50 patients with the first acute myocardial infarction (AMI) before starting thrombolytical treatment. VE and BC were determined by HPLC, VC spectrophotometrically. The reperfused patients were divided according to vitamin concentrations into four groups. The lowest quartile was compared with the rest of the studied population (VE: group with high (H)>15.6 microM>group with low (L), BC: H>0.07 microM>L, VC: H>25 microM>L) in the following parameters: extent of myocardial damage (area under the curves of troponin I, CK-MB during 48 h), arrhythmia and congestive heart failure occurrence, size of ejection fraction, positivity of ventricular late potentials. No significant differences between groups H and L for either VE, BC or VC were found (P 0.05). As no correlation between serum concentrations of vitamins E, C and beta-carotene and the extent and clinical course of AMI was found, the actual vitamin concentrations may be important for prevention of ischemic heart a disease, but they do not play a decisive role in the acute phase of myocardial infarction in humans.     

Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50.

OBJECTIVE: To investigate possible risk factors and mechanisms behind the four times higher and diverging mortality from coronary heart disease in Lithuanian compared with Swedish middle aged men. DESIGN: Concomitant cross sectional comparison of randomly selected 50 year old men without serious acute or chronic disease. Methods and equipment were identical or highly standardised between the centres. SETTING: Linköping (Sweden) and Vilnius (Lithuania). SUBJECTS: 101 and 109 men aged 50 in Linköping and Vilnius respectively. MAIN OUTCOME MEASURES: Anthropometric data, blood pressure, smoking, plasma lipid and lipoprotein concentrations, susceptibility of low density lipoprotein to oxidation, and plasma concentrations of fat soluble antioxidant vitamins. RESULTS: Systolic blood pressure was higher (141 v 133 mm Hg, P < 0.01), smoking habits were similar, and plasma total cholesterol (5.10 v 5.49 mmol/l, P < 0.01) and low density lipoprotein cholesterol (3.30 v 3.68 mmol/l, P < 0.01) lower in men from Vilnius compared with those from Linköping. Triglyceride, high density lipoprotein cholesterol, and Lp(a) lipoprotein concentrations did not differ between the two groups. The resistance of low density lipoprotein to oxidation was lower in the men from Vilnius; lag phase was 67.6 v 79.5 minutes (P < 0.001). Also lower in the men from Vilnius were mean plasma concentrations of lipid soluble antioxidant vitamins (beta carotene 377 v 510 nmol/l, P < 0.01; lycopene 327 v 615 nmol/l, P < 0.001; and lipid adjusted gamma tocopherol 0.25 v 0.46 mumol/mmol, P < 0.001. alpha Tocopherol concentration did not differ). Regression analysis showed that the lag phase was still significantly shorter by 10 minutes in men from Vilnius when the influence of other known factors was taken into account. CONCLUSIONS: The high mortality from coronary heart disease in Lithuania is not caused by traditional risk factors alone. Mechanisms related to antioxidant state may be important.     

Tobacco and myocardial infarction: is snuff less dangerous than cigarettes?

OBJECTIVE--To estimate the risk of myocardial infarction in snuff users, cigarette smokers, and non-tobacco users in northern Sweden, where using snuff is traditional. DESIGN--Case-control study. SETTING--Northern Sweden. SUBJECTS--All 35-64 year old men who had had a first myocardial infarction and a population based sample of 35-64 year old men who had not had an infarction in the same geographical area. MAIN OUTCOME MEASURE--Tobacco consumption (regular snuff dipping, regular cigarette smoking, non-tobacco use) and risk of acute myocardial infarction. RESULTS--59 of 585 (10%) patients who had a first myocardial infarction and 87 of 589 (15%) randomly selected men without myocardial infarction were non-smokers who used snuff daily. The age adjusted odds ratio for myocardial infarction was 0.89 (95% confidence interval 0.62 to 1.29) for exposure to snuff and 1.87 (1.40 to 2.48) for cigarette smoking compared with non-tobacco users, showing an increased risk in smokers but not in snuff dippers. Regular cigarette smokers had a significantly higher risk of myocardial infarction than regular snuff dippers (age adjusted odds ratio 2.09; 1.39 to 3.15). Smoking, but not snuff dipping, predicted myocardial infarction in a multiple logistic regression model that included age and level of education. CONCLUSIONS--In middle aged men snuff dipping is associated with a lower risk of myocardial infarction than cigarette smoking.     

Short-term and long-term vitamin C supplementation in humans dose-dependently increases the resistance of plasma to ex vivo lipid peroxidation

To assess the effects of short-term and long-term vitamin C supplementation in humans on plasma antioxidant status and resistance to oxidative stress, plasma was obtained from 20 individuals before and 2h after oral administration of 2g of vitamin C, or from eight subjects enrolled in a vitamin C depletion-repletion study using increasing daily doses of vitamin C from 30 to 2500 mg. Plasma concentrations of ascorbate, but not other physiological antioxidants, increased significantly after short-term supplementation, and increased progressively in the long-term study with increasing vitamin C doses of up to 1000 mg/day. Upon incubation of plasma with a free radical initiator, ascorbate concentrations were positively correlated with the lag phase preceding detectable lipid peroxidation. We conclude that vitamin C supplementation in humans dose-dependently increases plasma ascorbate concentrations and, thus, the resistance of plasma to lipid peroxidation ex vivo. Plasma and body saturation with vitamin C in humans appears desirable to maximize antioxidant protection and lower risk of oxidative damage.     

Risk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case-control analysis of prospective data.

The independent and joint associations of serum selenium and vitamin A (retinol) and E (alpha tocopherol) concentrations with the risk of death from cancer were studied in 51 case-control pairs--that is, 51 patients with cancer, each paired with a control matched for age, sex, and smoking. Case-control pairs came from a random sample of some 12000 people aged 30-64 years resident in two provinces of eastern Finland who were followed up for four years. Patients who died of cancer during the follow up period had a 12% lower mean serum selenium concentration (p = 0.015) than the controls. The difference persisted when deaths from cancer in the first follow up year were excluded. The adjusted risk of fatal cancer was 5.8-fold (95% confidence interval 1.2-29.0) among subjects in the lowest tertile of selenium concentrations compared with those with higher values. Subjects with both low selenium and low alpha tocopherol concentrations in serum had an 11.4-fold adjusted risk. Among smoking men with cancer serum retinol concentrations were 26% lower than in smoking controls (p = 0.002). These data suggest that dietary selenium deficiency is associated with an increased risk of fatal cancer, that low vitamin E intake may enhance this effect, and that decreased vitamin or provitamin A intake contributes to the risk of lung cancer among smoking men with a low selenium intake.     

Dietary ascorbic acid deficiency in guinea pigs: No effect on ethanol preference,spiroperidol binding,or monoamine oxidase activity

Ascorbic acid levels are commonly reported to be decreased in alcoholics. Although this deficiency could be due to dietary factors, there is evidence that ascorbic acid may be involved in the metabolism and acute effects of ethanol, possibly related to the pathogenesis of alcoholism. Therefore, we examined ethanol preference in guinea pigs receiving an ascorbate deficient $\text{vs}$ a normal diet. Brain and spleen ascorbic acid levels were dramatically decreased, but ethanol preference was not altered by the acute dietary deficiency of this vitamin. In addition, an acute stressor (cold water swim), alone or in combination with ascorbate deficiency, had no effect on ethanol preference. At termination of the experiment, two measures of brain aminergic function (MAO activity and ³H-spiroperidol binding), purportedly altered by ethanol or ascorbic acid or both, were not associated with tissue ascorbate levels.     

Aspirin use and chronic diseases: a cohort study of the elderly.

OBJECTIVE--To evaluate the associations between the use of aspirin and the incidences of cardiovascular diseases, cancers, and other chronic diseases. DESIGN--Postal questionnaire survey to elicit details of aspirin use. SETTING--Californian retirement community. SUBJECTS--All 22,781 residents of the community (white, affluent, and well educated) were sent a questionnaire that included questions on medical history and the use of drugs such as analgesics, laxatives, and vitamin supplements. In all 61% responded (13,987, 8881 women and 5106 men; median age 73). They formed the cohort that was followed up for 6 1/2 years using discharge summaries from three hospitals serving the area and death certificates from the health department. Only 13 respondents were lost to follow up but seemed not to have died. MAIN OUTCOME MEASURES--Incidences of cardiovascular diseases, cancers, gastrointestinal bleeding, ulcers, and cataracts were compared in participants who did and did not take aspirin daily. RESULTS--Age adjusted incidences were computed with an internal standard and five age groups. By 1 January 1988 there had been 25 incident cases of kidney cancer among all participants; 341 incident cases of stroke, 253 of acute myocardial infarction, 220 of ischaemic heart disease, and 317 of other heart disease were reported among respondents without a reported history of angina, myocardial infarction, or stroke. The incidence of kidney cancer was raised among those who took aspirin daily compared with those who did not take it, although the increase was significant only in men (relative risks = 6.3, 95% confidence interval 2.2 to 17, for men and 2.1, 0.53 to 8.5, for women). Those who took aspirin daily showed no increased risk of any other cancer, except colon cancer for both sexes combined (relative risk = 1.5, 1.1 to 2.2). The risk of acute myocardial infarction was reduced slightly among regular users of aspirin in men but not women. The risk of ischaemic heart disease was almost doubled in those who took aspirin daily compared with non-users (relative risks = 1.9, 1.1 to 3.1, for men and 1.7, 1.1 to 2.7, for women). Small, non-significant increased risks of stroke were observed in both sexes. CONCLUSION--The daily use of aspirin increased the risk of kidney cancer and ischaemic heart disease.     

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men.

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the "Antioxidant Supplementation in Atherosclerosis Prevention" (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of D-alpha-tocopheryl acetate daily), both vitamins (CellaVie), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9-30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.     

Vitamin D deficiency in adult British Hindu Asians: a family disorder.

The vitamin D state of 60 apparently healthy adult Hindu Asian couples living in Britain was studied on a community basis. Twenty six (22%) of the Asian subjects had pronounced vitamin D deficiency, defined as 25-hydroxycholecalciferol concentrations below 10 nmol/l (4 ng/ml), while none of the white controls had such low concentrations. Asian men and women were equally affected, and plasma concentrations were similar in husbands and wives. Vitamin supplements were being taken by only 31 (26%) subjects, most of whom were women. It is suggested that the spouses of patients with osteomalacia should be screened for vitamin D deficiency.     

Sex related differences in short and long-term prognosis after acute myocardial infarction: 10 year follow up of 3073 patients in database of first Danish Verapamil Infarction Trial.

OBJECTIVE--To re-examine the prevailing hypothesis that women fare worse than men after acute myocardial infarction. DESIGN--10 year follow up of all patients with confirmed acute myocardial infarction registered in the database of the Danish verapamil infarction trial in 1979-81. SETTING--16 coronary care units, covering a fifth of the total Danish population. PATIENTS--3073 consecutive patients with acute myocardial infarction, 738 (24%) women and 2335 (76%) men. MAIN OUTCOME MEASURES--Early mortality (before day 15). For patients alive on day 15: mortality, cause of death, admission with recurrent infarction, and mortality after reinfarction. RESULTS--Early mortality increased significantly with age (P < 0.0001) but was not significantly related to sex, with a 15 day mortality of 17% in women and 16% in men. Adjustment for age and sex simultaneously revealed a significant interaction (P = 0.02) between these variables, with a greater increase with age in early mortality for men than for women (early mortality was equal for the two sexes at age 64 years). Ten year mortality in patients alive on day 15 was 58.8%. The overall age adjusted hazard ratio (95% confidence interval) for women versus men was 0.90 (0.80 to 1.01); 0.90 (0.78 to 1.04) for 10 year reinfarction (48.8%); and 0.98 (0.82 to 1.16) for 10 year mortality after reinfarction (82.3%). No difference in cause of death was found between the sexes. With a follow up of up to 10 years for patients alive on day 15 mortality, rate of reinfarction, and mortality after reinfarction increased with increasing age (P < 0.0001). CONCLUSION--Sex by itself is not a risk factor after acute myocardial infarction.     

Cost effectiveness of lowering cholesterol concentration with statins in patients with and without pre-existing coronary heart disease: life table method applied to health authority population.

OBJECTIVES--To estimate the cost effectiveness of statins in lowering serum cholesterol concentration in people at varying risk of fatal cardiovascular disease and to explore the implications of changing the criteria for intervention on cost and cost effectiveness for a purchasing authority. DESIGN--A life table method was used to model the effect of treatment with a statin on survival over 10 years in men and women aged 45-64. The costs of intervention were estimated from the direct costs of treatment, offset by savings associated with a reduction in coronary angiographies, non-fatal myocardial infarctions, and revascularisation procedures. The robustness of the model to various assumptions was tested in a sensitivity analysis. SETTING--Population of a typical district health authority. MAIN OUTCOME MEASURE--Cost per life year saved. RESULTS--The average cost effectiveness of treating men aged 45-64 with no history of coronary heart disease and a cholesterol concentration > 6.5 mmol/l for 10 years with a statin was 136,000 pounds per life year saved. The average cost effectiveness for patients with pre-existing coronary heart disease and a cholesterol concentration > 5.4 mmol/l was 32,000 pounds. These averages hide enormous differences in cost effectiveness between groups at different risk, ranging from 6000 pounds per life year in men aged 55-64 who have had a myocardial infarction and whose cholesterol concentration is above 7.2 mmol/l to 361,000 pounds per life year saved in women aged 45-54 with angina and a cholesterol concentration of 5.5-6.0 mmol/l. CONCLUSIONS--Lowering serum cholesterol concentration in patients with and without preexisting coronary heart disease is effective and safe, but treatment for all those in whom treatment is likely to be effective is not sustainable within current NHS resources. Data on cost effectiveness data should be taken into account when assessing who should be eligible for treatment.     

Interaction of 0.1-Hz oscillations in heart rate variability and distal blood flow variability

Biophysical features of 0.1-Hz oscillations of heart rate variability (HRV) and distal blood flow (DBF) variability were compared in healthy subjects and patients after acute myocardial infarction (MI). Patients with acute MI (72 men and 53 women; 125 in total) and healthy subjects (23 men and 10 women; 33 in total) aged 30?C83 and 20?C46 years, respectively, participated in the study. The patients were involved in the study for a year after acute MI. The delay in coupling 0.1-Hz oscillations of HRV and DBF variability was estimated. In healthy subjects, the delay in the heart ?? DBF coupling proved to be less than the delay in the DBF ?? heart coupling. Acute MI results mainly in disruption of the heart ?? DBF coupling, which is partially restored by the end of the first year after acute MI, though it remains lower than in healthy subjects. The DBF ?? heart coupling is rapidly restored to the level of healthy subjects within three weeks after acute MI.     

The relevance of malondialdehyde as a biochemical index of lipid peroxidation of postischemic tissues in the rat and human beings

By using a recently developed ion-pairing high-performance liquid chromatographic method for the direct determination of malondialdehyde (MDA) and several other acid-soluble low-mol-wt compounds (ascorbate, oxypurines, nucleosides, nicotinic coenzymes, high-energy phosphates), the variations of tissue and plasma MDA as a function of ischemia and reperfusion were determined in the rat (isolated Langendorff-perfused hearts and short-term incomplete cerebral ischemia) and in human beings (patients suffering from acute myocardial infarction subjected to fibrinolysis). In the rat, the data obtained indicate that, contrary to what had been previously reported in literature, MDA is not present either in control heart or in control brain. Oxygen deprivation induces the production of a low, but detectable amount of MDA in both heart and brain, whereas reperfusion causes a marked increase of MDA in both tissues. In human beings, plasma MDA was deeply affected only in patients suffering from acute myocardial infarction with successful thrombolysis, thus indicating the occurrence of oxygen radical-mediated tissue injury also in humans. On the whole, these results suggest that MDA is a valid biochemical marker of lipid peroxidation of postischemic tissues, which however needs a reliable analytical technique for its determination.     

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F₂-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the “Antioxidant Supplementation in Atherosclerosis Prevention” (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of d-α-tocopheryl acetate daily), both vitamins (CellaVie^®), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F₂-isoprostane concentration was lowered by 17.3% (95% CI 3.9–30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F₂-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.     

Metabolism of vitamin A in the heart increases after a myocardial infarction

The supply of vitamin A to the myocardium by storage organs during increased oxidative stress subsequent to myocardial infarction (MI) was examined in hemodynamically assessed rats using compartment analysis of a radio-labeled vitamin A. 3H-Vitamin A was injected into two groups of rats: an MI group and a control group. There were no differences in the plasma or myocardial content of total vitamin A (unlabeled + labeled) between the two groups. However, the proportion of 3H-vitamin A was greater in the myocardium as well as plasma of MI rats. Rats with MI also had significantly lower 3H-vitamin A levels in liver and kidney than sham controls. The greatest difference in vitamin A content was in the concentrations of 3H-labeled storage forms of vitamin A in the liver of MI animals. Activity of bile salt-dependent retinyl ester hydrolase, an enzyme responsible for hydrolyzing vitamin A storage forms, was significantly increased in the liver of MI animals. These data indicate that analysis of plasma concentrations of vitamin A to ascertain links to cardiac conditions may be inappropriate. Specifically, during MI, increased amounts of vitamin A are mobilized from the liver to the heart without changing plasma concentrations. This is facilitated by an increase in the activity of an enzyme that hydrolyzes vitamin A storage forms.     

Decline in ischaemic heart disease in Iceland and change in risk factor levels.

OBJECTIVE--To monitor trends in mortality and morbidity due to ischaemic heart disease and compare these with observed levels of risk factors from population surveys. DESIGN--Analysis of trends in death rates from ischaemic heart disease in Iceland compared with expected rates computed from population surveys. Risk factor levels together with beta factors obtained from Cox''s regression analysis were used to compute expected death rates. Trends in morbidity due to acute myocardial infarction were assessed and secular trends in dietary consumption compared with trends in cholesterol concentrations. SETTING--Reykjavik, Iceland (total population 250,000; over half the population live in Reykjavik). SUBJECTS--12,814 randomly selected residents in the Reykjavik area aged 45-64 (6623 men, 6191 women; 72% and 80% of those invited). MAIN OUTCOME MEASURES--Age adjusted rates of myocardial infarction and deaths from ischaemic heart disease. Expected risk from risk factor levels (smoking, total serum cholesterol concentration, systolic blood pressure) at each unique survey visit. RESULTS--Mortality from ischaemic heart disease has decreased by 17-18% since 1970. During 1981-6 the myocardial infarction attack rate in men under 75 decreased by 23%. A decrease occurred in the level of all three major risk factors after 1968. The fall in the serum cholesterol concentration coincided with a reduction in consumption of dairy fat and margarine. The calculated reduction in risk for the age group 45-64 was about 35%, which was closely similar to the observed decrease in mortality due to ischaemic heart disease in that age group. CONCLUSION--The reduction in mortality from ischaemic heart disease was substantially due to a decreased incidence of myocardial infarction and could be attributed largely to the reduction in risk factors.     

Does plasma cholesterol concentration predict mortality from coronary heart disease in elderly people? 18 year follow up in Whitehall study.

OBJECTIVE--To explore the extent to which the relation between plasma cholesterol concentration and risk of death from coronary heart disease in men persists into old age. DESIGN--18 year follow up of male Whitehall civil servants. Plasma cholesterol concentrations and other risk factors were determined at first examination in 1967-9 when they were aged 40-69. Death of men up to 31 January 1987 was recorded. SUBJECTS--18,296 male civil servants, 4155 of whom died during follow up. MAIN OUTCOME MEASURES--Cause and age of death. Cholesterol concentration in 1967-9 and number of years elapsed between testing and death. RESULTS--1676 men died of coronary heart disease. The mean cholesterol concentration in these men was 0.32 mmol/l higher than that in all other men (95% confidence interval 0.26 to 0.37 mmol/l). This difference in cholesterol concentrations fell 0.15 mmol/l with every 10 years'' increase in age at screening. The risk of raised cholesterol concentration fell with age at death. Compared with other men cholesterol concentration in those who died of coronary heart disease was 0.44 mmol/l higher in those who died aged less than 60 and 0.26 mmol/l higher in those aged 60-79 (p = 0.03). For a given age at death the longer the gap between cholesterol measurement and death the more predictive the cholesterol concentration, both for coronary heart disease and all cause mortality (trend test p = 0.06 and 0.03 respectively). CONCLUSION--Reducing plasma cholesterol concentrations in middle age may influence the risk of death from coronary heart disease in old age.     

Disturbances of insulin in British Asian and white men surviving myocardial infarction.

OBJECTIVE--To examine the role of insulin as a cardiovascular risk factor in British Asian and white men. DESIGN--Case-controlled study of survivors of first myocardial infarction. SETTING--District general hospital. PATIENTS--Consecutive series of 76 white and 74 Asian men who survived first myocardial infarction compared with 58 white and 61 Asian male controls without coronary artery disease who were randomly sampled from the community. RESULTS--More Asians than white subjects had impaired glucose tolerance or overt diabetes as measured by the two hour glucose tolerance test (23/74 (32%) v 11/76 (15%) (p less than 0.001) among patients; 17/61 (28%) v 3/58 (6%) (p less than 0.001) among controls). Insulin and C peptide concentrations were higher in both patient groups than in respective controls (p less than 0.001) and higher in Asian than in white subjects, irrespective of their glucose tolerance. Triglyceride concentrations were higher in patients than in controls (1.92 (SD 1.05) v 1.43 (0.82) mmol/l among Asian men; 1.65 (0.83) v 1.3 (0.61) mmol/l among white subjects; p less than 0.001). Total cholesterol concentrations were lower in both groups of Asians than in respective white subjects (5.78 (0.99) v 6.22 (1.04) mmol/l (p less than 0.01) among patients; 5.54 (1.01) v 5.65 (1.11) mmol/l (p less than 0.6) among controls). High density lipoprotein cholesterol concentrations were lower in Asian than in white subjects. The ratio of total cholesterol to high density lipoprotein cholesterol was significantly higher (p less than 0.001) in both patient groups (6.69 (1.81) in Asian patients and 6.31 (1.91) in white patients) than in respective controls (5.24 (1.19) and 4.77 (1.43)). Regression analysis identified C peptide concentration and the ratio of total to high density lipoprotein cholesterol as powerful independent predictors of myocardial infarction in Asian and white men. Total cholesterol concentration predicted infarction in white but not in Asian men. CONCLUSIONS--Secretion and hepatic extraction of insulin are high in survivors of myocardial infarction and especially high in British Asians. Tissue resistance to the action of insulin, giving rise to increased pancreatic secretion, may be an important risk factor for coronary artery disease in both ethnic groups and may be partly responsible for the high incidence of diabetes and coronary artery disease in Asian populations.     

A radioimmunoassay for plasma dehydroepiandrosterone sulphate incorporating placental steroid sulphatase as a hydrolysing reagent

We describe a method for the measurement of plasma dehydroepiandrosterone sulphate (DHAS) which incorporates a Triton X-100 solubilised preparation of human placental steroid sulphatase as a hydrolysing agent and a direct radioimmunoassay of liberated DHA using a specific antiserum. The hydrolysis procedure is carried out at 50 degrees C for 1 h and an assay run can be completed in 4 h. As determined by the method, plasma concentrations of DHAS in 32 normal adult men (ages 23-58 yr) had a mean value +/- SD of 5.5 +/- 1.89 mumol/l. For 30 normal adult cyclic women (ages 22-35 yr) the mean plasma concentration of DHAS +/- SD was 3.1 +/- 1.35 mumol/l which was significantly lower (P less than 0.01) than found for men. Plasma DHAS concentration were also measured in 50 hirsute female patients. The mean value +/- SD was 5.03 +/- 2.52 mumol/l which was significantly higher (P less than 0.01) than the value for the normal female group. Some 42% of the hirsute patients had DHAS concentrations above the upper 95% probability limit of the normal range for premenopausal women.