E. Housley

Smoking, haemostatic factors and lipid peroxides in a population case control study of peripheral arterial disease

The aim of this study was to determine differences between cases of peripheral arterial disease and healthy controls in levels of haemostatic factors and lipid peroxides and the influence of cigarette smoking. The study groups were selected from the Edinburgh Artery Study which is a random sample survey of men and women aged 55-74 years. Mean levels of plasma fibrinogen, von Willebrand factor, beta-thromboglobulin, plasminogen activator inhibitor (type I), cross-linked fibrin degradation products and lipid peroxides were markedly elevated in 121 study cases compared with 126 age- and sex-matched controls. For example, cross-linked fibrin degradation products had a geometric mean of 106.8 ng/ml (95% confidence interval (CI) 95.3, 119.8) in study cases and 74.7 ng/ml (95% CI 67.0, 83.4) in controls (P < 0.001). Inclusion of smoking in logistic regressions of each factor on peripheral arterial disease significantly reduced the odds of disease for von Willebrand factor and for cross-linked fibrin degradation products, but had little effect on the increased odds associated with fibrinogen, beta-thromboglobulin, plasminogen activator inhibitor and lipid peroxides. We conclude that, in men and women in Edinburgh, peripheral atherosclerosis is associated with lipid peroxidation, endothelial disturbance, platelet activation, elevated fibrinogen, fibrin formation and increased inhibition of fibrinolysis. The most important effects of cigarette smoking in promoting atherosclerosis may be endothelial disturbance and fibrin formation.

Physical activity and risk of peripheral arterial disease in the general population: Edinburgh Artery Study.

STUDY OBJECTIVE--To determine associations between physical activity at age 35-45 years with peripheral arterial disease and cardiovascular risk factors at age 55-74 years. DESIGN--Cross sectional survey of the general population--Edinburgh Artery Study. The presence of peripheral arterial disease was determined using the WHO/Rose questionnaire on intermittent claudication, and the ankle brachial pressure index at rest and during reactive hyperaemia. Levels of physical activity undertaken at the time of the survey and at the times the subjects were aged 35-45 years were measured by self administered recall questionnaire. SETTING--City of Edinburgh, Scotland. PARTICIPANTS--Altogether 1592 men and women aged 55 to 74 years, selected from the age-sex registers of 10 general practices spread geographically and socioeconomically throughout the city. MAIN RESULTS--Participation in moderate or strenuous activity when aged 35-45 years was reported by 66% of men and 40% of women. In men, but not in women, less peripheral arterial disease (measured by an increasing trend in the ankle brachial pressure index) was found with increasing amounts of exercise at age 35-45 years (p < 0.001). Higher levels of exercise at age 35-45 years were associated with lower blood viscosity (p < 0.05) and plasma fibrinogen levels (p < 0.05) in men and women aged 55-74 years, and also with higher current alcohol intake (p < 0.001) and high density lipoprotein cholesterol concentrations (p < 0.01) in women aged 55-74 years. After adjustment for age, sex, life-time smoking, social class, body mass index, and alcohol intake, the association between leisure activity aged 35-45 years and the ankle brachial pressure index aged 55-74 years remained highly significant in men who had at some time smoked (p < 0.001) but not in men or women who had never smoked (p > 0.05). CONCLUSION--The risk of peripheral arterial disease, particularly among male smokers, is inversely related to previous physical activity in early middle age, suggesting a protective effect of exercise.

Alcohol intake as a risk factor for peripheral arterial disease in the general population in the Edinburgh Artery Study

The aim of this study was to determine the relationship between alcohol consumption and occurrence of peripheral arterial disease in the general population. During 1988 in a cross sectional survey, the Edinburgh Artery Study, 1,592 men and women aged 55–74 years were selected at random from the age-sex registers of ten general practices distributed geographically and socio-economically across the city. Participants were asked to recall the number of units of wine, beer and spirits consumed in the previous week and whether or not this was typical. Peripheral arterial disease was measured using the ankle brachial pressure index (ABPI). Men and women were analysed separately because of large differences in alcohol consumption. There was no association between ABPI and alcohol consumption in women but, in men, increasing alcohol consumption was associated with a higher ABPI (test for trend,p=0.03) indicating less severe disease. This relationship was linear rather than U-shaped. In multiple regression analysis, after age-adjustment the ABPI was related to wine consumption but not beer or spirits in men (p⩽0.01). On adjusting for age and cumulative lifetime cigarette smoking, the association of wine consumption with the ABPI was diminished but remained statistically significant (p<0.05). On adjusting for age and social class, the relationship of total alcohol intake and wine consumption with the ABPI became non significant (p>0.05). We conclude that in males, greater alcohol consumption is related to a higher ABPI and that any protective ‘effect’ of alcohol relates to wine consumption rather than beer or spirits. However, wine consumption could simply be an indicator of other social class differences affecting the risk of disease.

Sex differences in susceptibility to etiologic factors for peripheral atherosclerosis. Importance of plasma fibrinogen and blood viscosity.

Cardiovascular risk factors in men, such as cigarette smoking, hypercholesterolemia, and hypertension, also increase risk in women, but the relative susceptibility to risk factors between the sexes is not established. Our aim was to investigate a wide range of possible etiologic factors in a single population study and identify those that were more strongly related to peripheral atherosclerosis in men or women. We studied personal factors (age and social class), lifestyle factors (smoking, exercise, alcohol intake, and dietary nutrients), and intermediary factors (obesity, diabetes, serum lipids, coagulation, and rheological factors). In the Edinburgh Artery Study in 1988 we measured cardiovascular risk factors in a random population sample of 1592 men and women aged 55 to 74 years. The ankle-brachial pressure index (ABPI), which is inversely related to the degree of peripheral atherosclerosis, was assessed in each subject. Lifetime cigarette smoking was correlated with a lower ABPI equally in men and women (r = -.27, P < .001). Dietary nutrients and alcohol intake were not related differently between the sexes with ABPI. However, recall of strenuous and moderate leisure time exercise during the age range of 35 to 45 years was related more strongly to a higher ABPI in men than in women (P < .05). Plasma fibrinogen, plasma viscosity, and blood viscosity were the only intermediary factors that had stronger univariate correlations with lower ABPI in men than in women. On multivariate analysis, the sex differences persisted for plasma fibrinogen (P < .05) and blood viscosity (P < .001); high-density lipoprotein cholesterol was related to ABPI in men only (sex difference, P < .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Inter-Relationships of Plasma Fibrinogen, Low-Density Lipoprotein Cholesterol, Cigarette Smoking and the Prevalence of Cardiovascular Disease

Background The magnitude of the cardiovascular risk associated with plasma fibrinogen concentration is influenced separately by cigarette smoking and by low-density lipoprotein (LDL) cholesterol levels. The effects of combinations of these factors on risk and the extent to which inclusion of the plasma fibrinogen level further refines the risks associated with smoking and high LDL cholesterol levels are not known. Objective To determine the inter-relationships among all of the three factors smoking, LDL cholesterol level and fibrinogen level with respect to the occurrence of cardiovascular disease. Methods The study was part of the Edinburgh Artery Study, which was a cross-sectional random sample survey of 1592 men and women aged 55–74 years. The assessment of cardiovascular disease included recall of diagnosis by a doctor of angina or myocardial infarction, intermittent claudication determined by a questionnaire and measurement of ankle systolic blood pressure. Results The odds ratio for disease in smokers in the top tertiles of plasma fibrinogen and LDL cholesterol levels was 7.7 (95% confidence interval 3.0–19.8; P ≤ 0.001). Neither a multiplicative nor a synergistic effect of the three factors on the odds of disease was observed but the level of each contributed to the risk. For example, in current smokers in the bottom tertile of LDL cholesterol level, the odds of disease were 6.1 (95% confidence interval 2.2–17.0; P ≤ 0.001) in the top tertile, 2.9 (95% confidence interval 1.0–8.6; P ≤ 0.05) in the middle tertile and 1.6 (95% confidence interval 0.5–4.8; P > 0.05) in the bottom tertile of plasma fibrinogen level. Subjects in the bottom tertile of plasma fibrinogen level did not have significantly elevated (P <0.05) risks irrespective of LDL cholesterol levels and smoking status. Conclusion The incorporation of plasma fibrinogen level permitted more precise delineation of the odds of disease within categories of smoking and LDL cholesterol concentration. These relationships need to be investigated further in prospective studies.

Reactive hyperemia test in a random sample of the general population

PURPOSE The purpose of this article is to determine the performance of a reactive hyperemia test in the general population in terms of validity, increase in case identification, and test refusal; and to identify differences between the two major ways of expressing the results (the postocclusive ankle index and the percentage change in ankle systolic pressure). METHODS Changes in ankle pressures were measured during reactive hyperemia in 1460 men and women aged 55 to 74 years, who were randomly sampled in the Edinburgh Artery Study. The validity of the test was determined in 91 cases identified by the presence of intermittent claudication and a low resting ankle pressure and in 91 controls matched by age and sex. RESULTS The mean postocclusive ankle index was 0.98 (SD 0.20), and the mean drop in ankle pressure was 9.89% (SD 12.79%). In examining the validity of the test, differences occurred in the two ways of expressing the results: the postocclusive ankle index was 90% sensitive and 97% specific and the percentage drop in ankle pressure was 52% sensitive and 86% specific in detecting disease. The postocclusive ankle index increased the overall identification of cases in the Edinburgh Artery Study from 6.5% to 11.5%, but the percentage drop in ankle pressure increased identification to only 9.5%. Eight percent of subjects refused the test because of discomfort; this group contained more women, more elderly, and more obese subjects. CONCLUSIONS The reactive hyperemia test is an appropriate test to use in the general population. The results are more accurate when expressed as the postocclusive ankle index rather than the percentage drop in ankle pressure.

Influence of High-Density Lipoprotein Cholesterol and Rheological Factors on the Sex Difference in Cardiovascular Disease

Background It is well established that the incidence of cardiovascular disease among men is higher than that among women. Objective To determine whether differences between men and women in terms of a range of conventional and rheological risk factors could explain this sex difference. Design This was a population-based cohort study (the Edinburgh Artery Study). Methods Men and women aged 55–74 years (n = 1592) were selected at random from the general population of Edinburgh and followed up for 5 years. Baseline cardiovascular risk factors were measured and related to incidence of disease among men and women. Results Men had higher levels of cigarette smoking, haematocrit and blood viscosity and lower levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and plasma fibrinogen than did women. The incidences of cardiovascular events among men and women were 48.3 and 26.1 per 1000 person-years, respectively. Adjustment for level of HDL cholesterol reduced the male: female ratio for sex-specific incidence rates of cardiovascular events from 1.80 [95% confidence interval (Cl) 1.43–2.27] to 1.34 (95% Cl 1.04–1.73). This reduction was partially reversed after further adjustment for the other cardiovascular risk factors. The impact of blood viscosity, plasma viscosity and plasma level of fibrinogen on the risk of cardiovascular disease was higher for men than it was for women (multivariate relative risk for blood viscosity were 1.24, 95% Cl 1.08–1.43, for men and 0.81, 95% Cl 0.61–1.06, for women). Conclusions Levels of HDL cholesterol levels in women being higher than those in men may explain some, but not all, of the sex difference in incidence of cardiovascular disease. Greater susceptibility of men to rheological factors might also be important.