The angiotensin-converting enzyme gene and the angiotensin II type I receptor gene as candidate genes for microalbuminuria. A study in nondiabetic and non-insulin-dependent diabetic subjects.

Familial clustering of microalbuminuria with cardiovascular disease suggests a possible common genetic antecedent. We have tested the hypothesis that the angiotensin-converting enzyme (ACE) DD genotype and the angiotensin II type I receptor (AT1R) gene C allele represent the common link between microalbuminuria and coronary heart disease. The frequency of polymorphisms of the ACE and AT1R genes were investigated in 509 nondiabetic white subjects and in 86 non-insulin-dependent diabetic white patients. There was no significant difference in albumin excretion rate between the genotypes in nondiabetic subjects on either a daytime or an overnight sample or in diabetic subjects expressed as a normalized albumin concentration on an untimed morning urine collection. We have found no evidence for an association between polymorphism of the ACE or AT1R genes and microalbuminuria in two groups of subjects without insulin-dependent diabetes.

Association of proinsulin-like molecules with lipids and fibrinogen in non-diabetic subjects--evidence against a modulating role for insulin.

Elevated concentrations of proinsulin-like molecules, other than insulin, may be associated with abnormalities of cardiovascular risk factors, promoting atherogenesis and thrombosis. Using specific assays we examined the relationship of levels of insulin, intact proinsulin and des-31,32 proinsulin to blood pressure, lipids, fibrinogen, factor VII and albumin excretion rate in 270 europids with normal glucose tolerance. After correcting for age and body mass index, fasting and 2-h insulin concentrations were significantly associated with those of total and LDL-cholesterol (r = 0.18-0.22), HDL-cholesterol (both r = -0.20) and triglycerides (r = 0.21 and 0.18), but not with blood pressure. Concentrations of intact and des-31,32 proinsulin showed significant associations with those of total and LDL-cholesterol (r = 0.20-0.23), HDL-cholesterol (r = -0.31 and -0.32) and triglycerides (r = 0.22 and 0.26). Fasting insulin and intact proinsulin concentrations were significantly associated with fibrinogen (r = -0.15 and 0.18). Concentrations of proinsulin-like molecules comprised less than 10% of all insulin-like molecules, and so were calculated not to influence previously described relationships between insulin concentrations and cardiovascular risk factors measured using non-specific assays. In multiple regression analyses des-31,32 proinsulin concentration was more strongly associated with those of HDL-cholesterol (negatively), LDL-cholesterol and triglycerides than fasting insulin concentrations, while intact proinsulin replaced insulin concentrations in their relationships with fibrinogen. Our results show correlations between dyslipidaemia and proinsulin-like molecules at concentrations at which biological, insulin-like, activity appears unlikely. We also show relationships between LDL-cholesterol and fibrinogen and the proinsulin-like molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Associations of urinary albumin excretion rate with vascular disease in europid nondiabetic subjects.

Microalbuminuria and its association with vascular disease has previously been reported in nondiabetic individuals. The aims of this study were to determine whether there is a cross-sectional relationship between urinary albumin excretion rate and cardiovascular disease in nondiabetic subjects and to investigate hereditary predisposition to microalbuminuria by studying offspring of the main study population. Europid patients, aged 40-70 years, were randomly selected from a large inner-city general practice; there was a 62.6% attendance rate, and a study population of 959 remained after exclusions. Blood pressure, ankle systolic pressure, height, and weight were measured. Albumin excretion rate was calculated from overnight and morning urine collections. Venous blood was taken for lipids, fibrinogen, and factor VII; and resting electrocardiograms were carried out. Offspring (aged 15-40 years) of those found to be microalbuminuric were invited to attend for the same tests, and controls were selected by age and sex matching the parents. There was no association between parents' albumin excretion rate with that of their offspring, and there were no significant differences in albumin excretion rate between offspring subjects and their controls. There were no statistically significant associations of prevalent coronary heart disease (CHD) with albumin excretion rate or microalbuminuria in either sex [CHD in women: odds ratio (OR) 1.85; 95% confidence interval (CI) 0.19,9.0] [CHD in men: OR 2.13; 95% CI (0.64, 6.59)]. In women, there were significant associations between albumin excretion rate and peripheral vascular disease (positive) and fibrinogen (negative). Because established risk factors may not be as strongly associated with CHD in cross-sectional studies, we intend to follow this group prospectively.

Essential fatty acids, plasma cholesterol, and fat-soluble vitamins in subjects with age-related maculopathy and matched control subjects.

A matched-control study of plasma retinol, alpha-tocopherol, carotenoid, and cholesterol concentrations and the polyunsaturated fatty acid content of plasma and erythrocyte phospholipids was undertaken in 65 elderly patients with age-related maculopathy and 65 control subjects matched for age and sex. Despite the high statistical power of the study and large variations between subjects in the variables under consideration, no significant differences were noted between patients and control subjects. However, several statistically significant differences were noted between male and female subjects independent of their classification with maculopathy or as controls and age: plasma cholesterol, total phospholipids, alpha-tocopherol, and beta-cryptoxanthin concentrations were higher in females than in males. The mean plasma cholesterol concentration for the upper tertile of the whole sample was 7.6 mmol/L. Plasma concentrations of total carotenoids, alpha-carotene, and beta-carotene, but not alpha-tocopherol, were significantly lower in smokers than in non-smokers. The results of this study do not provide any evidence in favor of changing the dietary intake of polyunsaturated fatty acids or fat-soluble vitamins to protect against age-related maculopathy.

Microalbuminuria: associations with height and sex in non-diabetic subjects.

OBJECTIVES: To study the association(s) between microalbuminuria and cardiovascular risk factors in non-diabetic subjects. DESIGN: Patients aged 40-75 years were randomly selected from a general practice list and invited to participate. SETTING: Health centre in inner city London. SUBJECTS: Of those invited, 1046 out of 1671 (62.6%) attended. Subjects were excluded for the following reasons: not being white (44); urinary albumin excretion rate > 200 micrograms/min (3); having a urinary infection (5); taking penicillamine or angiotensin converting enzyme inhibitors (7); older than 75 (2); having diabetes (25); missing data on glucose concentration (1). MAIN OUTCOME MEASURES: Glucose tolerance test results, albumin excretion rate from overnight and timed morning collections of urine; blood pressure; height. RESULTS: Mean albumin excretion rate was significantly lower in women than men (mean ratio 0.8, 95% confidence interval (0.69 to 0.91)). Mean albumin excretion rate was significantly associated with age, blood pressure, and blood glucose concentration (fasting, 1 hour, and 2 hour) in men and inversely with height. Men who had microalbuminuria in both samples were significantly shorter (by 5 cm (1.3 to 9.3 cm)) than those who had no microalbuminuria in either sample when age was taken into account. In the case of women only systolic pressure was significantly associated with albumin excretion rate. CONCLUSIONS: Microalbuminuria and short stature in men are associated. Cardiovascular risk has been associated with both of these factors and with lower birth weight. The inverse association of microalbuminuria with height is compatible with the suggestion that factors operating in utero or early childhood are implicated in cardiovascular disease. The higher prevalence of microalbuminuria in men compared with women may indicate that sex differences in cardiovascular risk are reflected in differences in albumin excretion rate.

The role of free fatty acids in regulating the tissue availability and synthesis of sex steroids.

Sex steroids and dietary fat intake have been implicated in the growth of breast tumours. We have previously shown that the plasma free oestradiol fraction is increased in women with breast cancer and that the addition of free fatty acids (FFA) to plasma can increase the free oestradiol fraction in vitro. In the present study we have examined the distribution of oestradiol and testosterone in serum obtained from European women (EW) and Asian (Gujarati) women (GW) living in north-west London. Fat intake by these women is similar but GW, who are vegetarians, consume a greater proportion of unsaturated fats. In serum from perimenopausal GW, the free testosterone concentration was significantly higher than for EW (11.1 +/- 3.6 pmol/l vs 8.7 +/- 3.4 pmol/l, p < 0.05). Although a significant correlation was found between the free testosterone and FFA concentrations for GW (r = 0.49, p < 0.05), concentrations of sex-hormone binding globulin (SHBG) were significantly lower in GW than EW. The finding of lower SHBG concentration in GW was confirmed in a second study in postmenopausal women (EW, 60.1 +/- 34.1 nmol/l; GW, 37.8 +/- 20.5 nmol/l, p < 0.05). However, no difference in the free oestradiol fraction or concentration was detected for EW and GW and no correlations with total or individual FFA were found. It is concluded from this study that while dietary fats may have an important role in the development of breast tumours, it is unlikely to be mediated by FFA inhibiting the binding of sex steroids to plasma proteins.

Visual problems in the elderly population and implications for services.

OBJECTIVE: To determine the prevalence of visual disability and common eye disease among elderly people in inner London. DESIGN: Cross sectional random sample survey. SETTING: Inner London health centre. SUBJECTS: Random sample of people aged 65 and over taken from practice's computerised age-sex register. MAIN OUTCOME MEASURES: Presenting binocular Snellen 6 m distance acuity and best monocular 3 m Sonksen-Silver acuity to classify prevalence of blindness by World Health Organisation criteria (less than 3/60 in better eye) and American criteria for legal blindness (better eye equal to 6/60 or less) and of low vision by WHO criteria (best acuity 6/18) and visual impairment by American criteria (less than 6/12 or 20/40 but greater than 6/60 or 20/200 in better eye). Principal cause of visual loss by diagnosis, referral indication by cause to hospital eye service, and proportion of cases known to primary care. RESULTS: 207 of 288 (72%) eligible people were examined. 17 (8%) housebound subjects were examined at home. The prevalence of blindness was 1% by WHO criteria and 3.9% by American criteria. The prevalence of low vision (WHO criteria) was 7.7%. The prevalence of visual impairment (American criteria) was 10.6%. Cataract accounted for 75% of cases of low vision. Only eight out of 16 patients with low vision were known by their general practitioner to have an eye problem. 56 subjects (27%) would probably have benefited from refraction. Comparisons with studies in the United States and Finland suggested higher rates in this sample, mainly due to the prevalence of disabling cataract. CONCLUSION: There seems to be a considerable amount of undetected ocular disease in elderly people in the community.

Student assessment of clinical experience in general surgery.

Forty-two students kept a log diary of all activities during their general surgical firms at a main university hospital in London. The students saw on average 35 patients per week on whom physical aspects were discussed by the consultant with the student after the consultation in 58%, psychological aspects in 4% and social aspects in 1.6%. Students spent an average of 11.2 hours per week with patients. In outpatients students spent most of their time as passive observers, but there were opportunities for more active involvement on the wards. Here the students spent on average 1.5 hours per week personally examining patients and 1 hour per week taking histories. Each student performed on average two short and one long examination per week and 0.5 short and 2.25 long histories per week. The students received on average 2.9 hours per week of consultant teaching in small groups, junior medical staff teaching at 2.2 hours and non-medical staff teaching of 1.1 hour per week. Students spent almost 4 hours per week attending formal traditional lectures in large groups. Some areas identified for improvement were: the relatively little feedback and supervision students received when personally examining patients and taking histories; the passive involvement of students in most educational settings; the small amount of time devoted to discussing social and psychologically relevant factors in the history; the few practical procedures personally performed by students; the relatively large amount of time students reported as unproductive and the small amount of time spent on self-education.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood groups, secretor status and salivary Lewis, Lewis and 19.9 antigen levels in alcoholics and ethnic origin-matched controls.

Blood group and secretor status were determined in 89 heavy drinkers receiving outpatient treatment at a district general hospital in north-west London, and compared with 89 age-, sex- and ethnic origin-matched controls drawn from a panel of 1700 patients from a contiguous general practice. There were no significant differences in the distribution of ABO types and secretor status in the two groups. Differences in salivary mucins were investigated by assaying levels of sialylated and non-sialylated Lewis antigens and blood group antigens ABH in both patients and controls. Although there were no differences in the mean antigen levels for H, A, B Le(a) and Le(b) antigens, using the monoclonal antibody 19.9 (to sialylated Lewis(a) antigen), higher levels were found for groups O and B/AB non-secretors and for group A secretors in alcoholics compared with controls. In addition, inappropriate Le(a) and 19.9 immuno-reactivities were detected in the saliva samples of a group O Le(a)-b- secretor alcoholic and a group A Le(a)-b- secretor alcoholic, respectively. It is suggested that these changes in glycosylation of salivary proteins relate to the increased parotid gland cell proliferation known to occur in chronic alcoholics.

Effects of fish oil supplements in NIDDM subjects. Controlled study.

The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo-controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the MaxEPA group (P less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-thromboglobulin and platelet factor IV levels. An increase in clotting factor VII (P = 0.02), without changes in fibrinogen or factor X levels, occurred in the MaxEPA group. Similar reductions in blood pressure were observed in both groups. Dietary supplementation with MaxEPA capsules (10 g/day) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels. Most indices of platelet function are unaffected by this therapy.

Medical student experience of London general practice teaching attachments.

Forty-eight students kept a log diary of activities during their central London general practice teaching attachments associated with the Department of Primary Health Care of University College and Middlesex School of Medicine. The students each saw on average 96 patients per week, of whom 69% were discussed by the general practitioner with the student after the consultation. Students spent an average of 21.5 hours a week sitting in with the general practitioner. While most of this time was as a passive observer, the students were also able to participate more actively, personally taking histories for a median of 1.25 hours a week and personally examining patients for a median of 1.7 hours a week. During these periods of active involvement each student personally took a mean of 10 short and 2.5 long histories per week and performed a mean of 25.5 short and 1.2 long examinations per week. General practitioners to whom the students were attached spent a mean of 4 hours a week on (patient-oriented) teaching. The tuition was highly rated by the students in terms of both usefulness and stimulation. Students also received a mean of 2.3 hours a week of teaching from other members of the primary health care team, which was somewhat less well received. Areas for improvement were: the relatively few home visits (median of 6 per week) per student; the limited time students spent on self-education (average of 65 minutes per week); and the few practical procedures performed by the students. Students could also be encouraged to play a more active role in examining and interviewing patients.

Skinfold thickness, body mass index and ischaemic heart disease.

STUDY OBJECTIVE: To determine the relationship between obesity and subsequent incidence of ischaemic heart disease (IHD). DESIGN: Prospective cohort survey. SETTING: Study of three occupational groups, with follow up examinations. SUBJECTS: 3500 people recruited between 1972 and 1978 (80% response rate), and followed up between 1978 and 1984. This report is based on subgroup of 1511 white men aged 40-64 at entry. MEASUREMENTS AND MAIN RESULTS: Information was obtained on smoking and family history of IHD. Blood pressure, weight, height, skinfold thickness at four sites, fibrinogen, factor VII activity and cholesterol were measured during follow up. Body mass index (BMI) was used as an index of obesity. BMI was found to be more strongly correlated with IHD than any of the skinfold measurements, none of which was significantly associated with IHD when BMI was allowed for. Increase in BMI by 1 SD (approximately 8 kg) was associated with a 44% increase in the risk of IHD. Of the four skinfolds, subscapular was the most closely associated with risk, confirming the relevance of central obesity. The association between obesity and IHD remained when possible mechanisms for its effects were taken into account, and its strength may increase with time: for 1 SD increase in BMI, risk of events within 5 years was increased by 28%, while risk of events after longer than 5 years was increased by 65%. CONCLUSIONS: Preventive strategies for IHD should include avoidance of obesity.

Assessing alcohol consumption in general practice patients--a comparison between questionnaire and interview (findings of the Medical Research Council's general practice research framework study on lifestyle and health).

A self-administered questionnaire, the Health Survey Questionnaire (HSQ) was distributed to patients registered with 47 group general practices. The HSQ assesses alcohol consumption using a quantity frequency scale and includes the four CAGE questions and a question on whether respondents think they have an alcohol problem. A random stratified sample of those patients who returned an HSQ (2666 men and 1537 women) were subsequently invited to attend their general practice for an interview with the practice nurse, where weekly alcohol consumption was estimated using both a quantity frequency scale and a systematic enquiry about alcohol consumption for the week immediately preceding the interview. The latter method was taken as the 'gold standard'. Excessive drinkers were defined as men whose weekly consumption by this method was not less than 35 units per week and women drinking at least 21 units per week. After weighing the results to take account of the sampling bias in favour of the excessive drinkers, 11.7% of men and 2.9% of women were excessive drinkers according to the estimate of alcohol consumption at interview. This compares with the 7.6% of men and 2.7% of women who were heavy drinkers by the HSQ quantity frequency scale. The two interview estimates were comparable but in general the HSQ tended to underestimate consumption compared with these estimates. The questionnaire was found to be most effective in screening for excessive drinkers if all the patients who indicated concern about their drinking (i.e. those who were with CAGE positive or had a self-assessed drinking problem), as well as all of those who were above the limits for the trial on the quantity frequency scale, were selected as being potentially excessive drinkers. In the weighted sample, 14.8% of men and 6.9% of women were in this group. Using these selection criteria and taking the interview as the standard for determining the excessive drinkers a sensitivity of 58.6% and specificity of 91.08% was obtained for men, with a positive predictive value of 46.1% and a negative predictive value of 94.3%. For women the test was more sensitive (69.7%) and more specific (95.0%) and had a better negative predictive value (99.1%) than for men. The positive predictive value for women at 29.6% was not as good as that obtained for men. This analysis shows that the HSQ is a fairly effective tool for detecting excessive drinkers in general practices with a small proportion of false positive results. It is both economical and acceptable to patients in a wide range of practice settings.

Phobic anxiety and ischaemic heart disease.

A prospective study of the relation between scores on the six subscales of the Crown-Crisp experiential index and subsequent incidence of ischaemic heart disease was undertaken among participants in the Northwick Park heart study. Results from 1457 white men aged 40-64 at recruitment showed that phobic anxiety was strongly related to subsequent major ischaemic heart disease (fatal and non-fatal events combined) when other associated variables were taken into account. The phobic anxiety score alone remained significantly associated with ischaemic heart disease when scores on all the subscales were included in the analysis. Phobic anxiety seemed to be particularly associated with fatal ischaemic heart disease but was not associated with deaths from other causes and was no higher in those with a pre-existing myocardial infarction at recruitment than in those without. There was a consistent increase in risk of fatal ischaemic heart disease with score on the phobic anxiety subscale. The relative risk for those whose score was 5 and above was 3.77 (95% confidence interval 1.64 to 8.64) compared with those whose score was 0 or 1. The 49 participants with evidence of myocardial infarction at recruitment had higher scores on the subscales for free floating anxiety and functional somatic complaint. The Crown-Crisp experiential index is simple to fill out and acceptable to patients. When the results are combined with other known risk factors it may be of use in defining high risk subjects and in planning strategies for prevention.

Drinking patterns in general practice patients.

Patients from 47 group practices recruited from the Medical Research Council's general practice research framework participated in a study involving the collection of information about smoking, drinking, exercise and dieting and weight. This paper is concerned with the data on alcohol consumption obtained in the first stage of the study in which a self-administered questionnaire, the health survey questionnaire, was distributed by hand or by post to patients registered with the participating practices.Of the 25496 men who completed the questionnaire, 83.6% stated that they had been drinking in the previous three months compared with 69.2% of the 36657 women. For both sexes, abstinence rates were significantly lower in the younger age groups (P

Skinfold thickness and cardiovascular risk factors.

The relation of blood pressure, serum cholesterol, plasma fibrinogen, and coagulation factor VIIc with skinfold thickness at four sites (forearm, triceps, suprailiac, and subscapular) was examined in 2,948 white participants in the Northwick Park Heart Study. When considered separately, all four skinfolds were significantly associated with the four cardiovascular risk factors in males. Of the two limb skinfolds, forearm was consistently more strongly associated than triceps with the risk factors. The magnitude of the association between forearm skinfold and the risk factors was similar to that of the two trunk skinfolds, suprailiac and subscapular. Multiple regression analysis suggested an independent association of forearm skinfold with cholesterol and blood pressure in males when the other skinfolds were taken into account. There was no consistent difference in the strength of the associations of the two trunk skinfolds with the risk factors. With the exception of systolic blood pressure, the associations between the cardiovascular risk factors and skinfold thickness in males were stronger at younger ages. In the case of females the findings were somewhat different. The associations with the four risk factors were consistently stronger for the two trunk skinfolds than the limb skinfolds. Triceps was somewhat more strongly associated with the risk factors than forearm skinfold except for plasma fibrinogen. Thus there are sex differences in the association of the distribution of subcutaneous fat with cardiovascular risk factors.

Blood pressure, smoking, obesity and alcohol consumption in black and white patients in general practice.

A comparison of blood pressure (BP), smoking, alcohol consumption and obesity between whites and blacks of Caribbean origin aged 17-70 was undertaken in a general practice in North West London. Mean systolic and diastolic blood pressures (DBP) showed no consistent overall differences between the two ethnic groups, though DBP rose significantly more with age in black males than white males. Somewhat higher proportions of the black patients were receiving anti-hyper-tensive treatment compared with the whites, the difference was statistically significant in the case of males (P less than 0.02). This observation did not appear to be due to more effective detection of hypertension amongst black males. Overall, fewer than one-third of black females were current cigarette smokers compared with around one-half of white females (P less than 0.001). Amongst males, however, the proportions of never, ex and current smokers were similar in the two ethnic groups. Young black patients of both sexes were more likely to smoke than older blacks. Blacks who smoked tended to smoke fewer cigarettes than white smokers. Eleven of 190 (5.8%) black males had consumed 35 units or more of alcohol within the last week compared with 87 of 452 (19.2%) of white males, (P less than .001). Amongst females the differences were smaller, 5 of 227 (2.2%) of black females had consumed 21 units or more in the last week compared with 23 of 490 (4.7%) of white females (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Are general practitioners doing enough to promote healthy lifestyle? Findings of the Medical Research Council's general practice research framework study on lifestyle and health.

The health survey questionnaire was used to collect information about cigarette smoking, alcohol consumption, physical exercise, and dieting and weight. Completed questionnaires were received from 25,496 men and 36,657 women registered with 47 group practices in England and Scotland. The proportions of respondents who stated that they had a problem ranged from 1% (women and drinking, n = 406) to 34% (women and weight, n = 12,526). Between 49% (women and drinking, n = 18,048) and 67% (men (n = 17,095) and women (n = 24,550) and weight) thought that their general practitioners should be interested in their lifestyle. The proportions who could recall having received relevant advice ranged from 2% (women and drinking, n = 591) to 24% (women and weight, n = 8946). Advice about smoking had been given to 4055 (40%) of the women and 2941 (39%) of the men who smoked. Only 96 (10%) of the 989 women and 331 (17%) of the 1948 men who drank excessively could recall having received advice about alcohol consumption. These results suggest that patients are concerned about their lifestyle, that most would welcome relevant counselling, and that doctors should become more concerned with prevention of this kind.

Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study.

The Northwick Park Heart Study (NPHS) has investigated the thrombotic component of ischaemic heart disease (IHD) by the inclusion of measures of haemostatic function. Among 1511 white men aged between 40 and 64 at the time of recruitment, 109 subsequently experienced first major events of IHD. High levels of factor VII coagulant activity and of plasma fibrinogen were associated with increased risk, especially for events occurring within 5 years of recruitment. These associations seemed to be stronger than for cholesterol, elevations of one standard deviation in factor VII activity, fibrinogen, and cholesterol being associated with increases in the risk of an episode of IHD within 5 years of 62%, 84%, and 43% respectively. Multiple regression analyses indicated independent associations between each of the clotting factor measures and IHD but not between the blood cholesterol level and IHD incidence. The risk of IHD in those with high fibrinogen levels was greater in younger than in older men. Much of the association between smoking and IHD may be mediated through the plasma fibrinogen level. The biochemical disturbance leading to IHD may lie at least as much in the coagulation system as in the metabolism of cholesterol.