Gillian C. Leng

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.

Accuracy and reproducibility of duplex ultrasonography in grading femoropopliteal stenoses

PURPOSE The aim of this study was to determine the accuracy of Doppler waveform characteristics in grading femoropopliteal stenoses and to determine the interobserver and intraobserver reproducibility of measuring the same waveform characteristics. METHODS Thirty patients with isolated areas of stenosis found by arteriography were evaluated by color duplex sonography. Each patient underwent scanning by two observers on two separate occasions. Each observer was blind to the others results. Doppler spectra were recorded in areas where color change suggested the highest velocity and also at the nearest normal proximal area. Peak systolic velocity, spectral broadening, and waveform configuration were measured at each site. RESULTS An increase in peak systolic velocity of more than 200% accurately predicted a 50% or greater reduction in luminal diameter on angiography (70% sensitivity, 96% specificity). The presence of spectral broadening and an abnormal waveform shape were found to correlate poorly with the degree of stenosis. Analysis of variance showed no significant difference between observers in velocity measurements (p = 0.78). CONCLUSIONS We conclude that although stenoses of greater than 50% can be distinguished from minor stenoses, more precise definition of the degree of narrowing is unlikely. The good repeatability of the velocity ratio makes it an excellent tool for monitoring major changes in the progression of disease.

Plasma essential fatty acids, cigarette smoking, and dietary antioxidants in peripheral arterial disease. A population-based case-control study.

The aim of this study was to determine the levels of plasma fatty acids in patients with peripheral arterial disease and in control subjects and to identify whether any risks of disease related to these differences were influenced by smoking and antioxidant intake. A random sample of 1592 men and women aged 55 to 74 years was selected from the general population (the Edinburgh Artery Study), from which 153 cases of peripheral arterial disease were identified by the presence of intermittent claudication and low ankle systolic pressures at rest and during reactive hyperemia; these were matched by age and sex to 153 control subjects with no evidence of cardiovascular disease. In 113 case and 122 control subjects, fatty acid levels were measured in three plasma fractions (triglyceride, cholesteryl ester, and phospholipid), and smoking habits and dietary antioxidant intake were determined by questionnaire. Arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid (DPA/n-3) were significantly lower in the cases than controls (P < .01). More case than control subjects were current or exsmokers (86% versus 50%; P < .001), and the case subjects had lower vitamin C intake (64.8 mg versus 71.1 mg; P < .05). By logistic regression adjustment for smoking and vitamin C intake, only DPA/n-3 (odds ratio, 0.19; P < .01) and arachidonic acid (odds ratio, 0.44; P < .05) remained significantly related to disease; only DPA/n-3 reduced the risk associated with smoking. We conclude that in subjects with peripheral arterial disease compared with healthy control subjects, the largest differences occurred in fatty acids of the n-3 series, particularly DPA/n-3.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in plasma lipids, lipoproteins and high density lipoprotein subfractions in peripheral arterial disease

The concentrations of the major lipoprotein classes and of high density lipoprotein (HDL) subfractions in 63 male patients with arteriosclerosis of the lower limbs (claudication) were determined and compared with values from 63 healthy controls. The patients with peripheral arterial disease (PAD) had reduced levels of total HDL-cholesterol and HDL2b of large particle size, increased levels of small HDL3c particles and a high ratio of total plasma-cholesterol to HDL-cholesterol (coronary risk factor). The PAD patients, however, had lower levels of low density lipoprotein (LDL)-cholesterol but higher concentrations of very low density lipoprotein (VLDL)-cholesterol and plasma triglyceride than healthy subjects. This study therefore suggests that in PAD, the protective effect of HDL may be more important than the atherogenic effect of LDL. It further suggests that while HDL-cholesterol HDL2b and the ratio of total plasma-cholesterol to HDL-cholesterol may provide valid indices for identifying individuals at risk of PAD, other factors, such as LDL and total cholesterol, may not provide such an appropriate risk indicator.

Smoking, hemorheologic factors, and progression of peripheral arterial disease in patients with claudication

PURPOSE The purpose of the current study was to determine whether hemostatic and rheologic factors are associated with the deterioration of peripheral arterial disease in patients with intermittent claudication and the influence of smoking and severity of underlying disease on these relationships. METHODS We conducted a prospective cohort study with a 6-year follow-up period of a consecutive series of 607 patients with uncomplicated intermittent claudication. The study setting was the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. The main outcome measures were peripheral vascular intervention or onset of severe chronic leg ischemia (rest pain, ulceration, gangrene). RESULTS A total of 210 patients died during follow-up. Two hundred three patients did not have a vascular event or deterioration of limb ischemia, 45 patients underwent a peripheral vascular intervention, and 64 progressed to severe chronic leg ischemia. Median levels (interquartile ranges) of whole blood viscosity were significantly higher in the vascular intervention group (3.75 mPa/sec; range, 3.38 to 4.13 mPa/sec) than in those who did not deteriorate 3.48 mPa/sec; range, 3.06 to 3.83 mPa/sec) (p < or = 0.05), and plasma von Willebrand factor was higher in those with severe chronic leg ischemia (154.0 IU/dl; range, 122.0 to 187.0 IU/dl) than in those who did not deteriorate (131.0 IU/dl; range, 106.0 to 165.0 IU/dl) (p < or = 0.01). After adjustment for age, sex, cigarette smoking, and ankle brachial pressure index, the levels of plasma fibrinogen and blood and plasma viscosities were each associated with an increased risk of vascular intervention (all p < or = 0.05). There were no significant associations between any of the hemorheologic factors and the risk of severe chronic leg ischemia on multivariate analyses. CONCLUSION Elevations in rheologic factors may have important effects on further reduction of blood flow in the legs of patients with claudication and promote worsening ischemia and clinical progression of symptoms.

Relationship between plasma essential fatty acids and smoking, serum lipids, blood pressure and haemostatic and rheological factors

We aimed to determine whether levels of plasma fatty acids are correlated with other potential risk factors for cardiovascular disease, using a sample of patients from a cross-sectional survey of the general population, in the City of Edinburgh. 306 men and women aged 55-74 years of whom half had clinical evidence of arterial disease were tested. The main outcome measures were plasma fatty acids and potential risk factors for cardiovascular disease (age, sex, smoking, blood pressure, serum cholesterol, HDL cholesterol (HDL-C), triglycerides (TGs), lipid peroxides (LPx), plasma fibrinogen, von-Willebrand factor (vWf), beta-thromboglobulin (beta TG), cross-linked fibrin degradation products (FIBDP) and plasminogen activator inhibitor PAI). High levels of several known risk factors for cardiovascular diseases were associated with low levels of certain essential fatty acids. Eicosapentaenoic (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) were negatively associated with smoking and TG levels. High levels of certain haemostatic factors, including plasma fibrinogen, blood viscosity and LPx were also associated with low levels of EPA, DHA, AA and HDL-C. In conclusion, plasma fatty acids show strong correlations with many potential risk factors for cardiovascular disease, emphasising their possible importance in pathogenesis.

Central release of oxytocin and the ventromedial hypothalamus

Recent studies on the regulation of social behaviours by neuropeptides indicate that it is the distribution of peptide receptor expression in particular brain areas that determines the specificity of peptide actions; and that, accordingly, peptides can evoke specific behaviours when administered centrally without temporal or spatial selectivity of administration. The release of neuropeptides at synaptic sites appears irrelevant, and in the brain, some peptides are released mainly from dendrites rather than from nerve endings. Dendritic peptide release can be long lasting, semi-independent of electrical activity, and allows the diffusion of peptides to distant targets. The peptide oxytocin regulates many behaviours; in particular, it inhibits food intake. Centrally, oxytocin is released in large amounts by the dendrites of hypothalamic magnocellular neurons. This mini-review considers the possible involvement of dendritically released oxytocin in the regulation of food intake by its actions on the ventromedial hypothalamus.

Accuracy and reproducibility of duplex ultrasound imaging in a phantom model of femoral artery stenosis

PURPOSE The improvement of management strategies in patients with intermittent claudication might depend on a better understanding of the natural history of femoral atherosclerosis. The grading of stenoses, the monitoring of their progression, and the assessment of response to treatment are critically dependent on a methods accuracy and variability. Duplex ultrasound imaging provides a noninvasive way of measuring localized disease, but there has been relatively little objective evaluation of its accuracy and reproducibility. The aim of this study was to evaluate the accuracy and variability of duplex velocity ratio measurements of stenosis. METHODS In a laboratory flow model of the femoral artery, 14 concentric and eccentric stenoses were examined five times by three sonographers. Measurements were then repeated with a standardized technique in which Doppler angle and aperture position were fixed, giving a total of 420 measurements. RESULTS Velocity ratio showed good correlation with degree of stenosis, R2 = 0.996. Intraobserver variability was low, but interobserver variability was significant with more severe stenosis (p = 0.002, analysis of variance). Standardization of the technique did not improve accuracy or variability. The 95% confidence limit was +/- 20% for a single reading of velocity ratio for stenoses of > 50% diameter reduction. CONCLUSIONS We conclude that duplex ultrasound imaging can be used to accurately grade arterial stenosis in this range, and the potential exists for noninvasive monitoring of the progression of preocclusive femoral atherosclerosis and its response to treatment. In addition, repeated measurements of velocity ratio over time should be made by the same observer.

Randomized controlled trial of antioxidants in intermittent claudication.

Epidemiological evidence suggests that antioxidants protect against the development of atherosclerosis. To determine the effectiveness of antioxidant therapy in patients with lower limb atherosclerosis, a randomized placebo-controlled trial was performed in 120 men and women with intermittent claudication and an ankle/brachial pressure index (ABPI) ≤0.9. The study was analysed on an intention-to-treat basis. After 2 years, there were no significant differences between antioxidant and placebo groups in plasma cholesterol, lipoproteins, haemostatic or rheological factors. However, after 6 months, low density lipoprotein cholesterol was significantly lower in those taking antioxidant (108.0 mg/dl compared with 120.1 mg/dl, p < 0.05). There were no differences in the ABPI or walking distance, although both groups improved slightly with time. The incidence of cardiovascular events and death was nonsignificantly lower in the antioxidant compared with the placebo group: event rates per year were 5.5% (95% Cl 2.4–8.6) in the first year and 9.6% (95% Cl 6.8–12.4) in the second year for those on antioxidants; and 7.7% (95% Cl 5.1–10.3) and 13.3% (95% Cl 8.9–17.7) respectively for those on placebo. Significantly fewer serious adverse events occurred in the antioxidant than the placebo group: 21.8% (95% Cl 16.2–27.4) compared with 40.0% (95% Cl 33.9–46.1). This study therefore suggests that although antioxidants may prevent cardiovascular events in patients with peripheral atherosclerosis, they do not improve lower limb function.

Reproducibility of Duplex Ultrasound in the Measurement of Venous Reflux

Objective: To determine the reproducibility of duplex ultrasound in the measurement of reflux duration in lower limb veins. Design: Repeatability study. Setting: Vascular clinic in a tertiary referral centre. Participants: Twenty-one patients with severe venous disease. Interventions: Patients were scanned using duplex ultrasound by two of three observers, then rescanned by a different pair of observers after a mean interval of 51 days. Main outcome measures: Duration of venous reflux. Results: On a Wilcoxon signed rank test, observers 2 and 3 showed no significant interobserver variability. The other pairs of observers agreed at the majority of segments, but differed at the popliteal vein (p≤0.001), and superficial femoral and common femoral veins (p≤0.05). Observer 2 showed no significant intraobserver variability, but observer 1 differed at the common femoral and superficial femoral veins (p≤0.05), and observer 3 differed at the short saphenous vein (p≤0.05). Conclusions: Reproducibility was reasonable at certain sites, but appeared to be influenced by position of the vein.