F. Gerald R. Fowkes

BACKGROUND: Intervention to reduce abdominal aortic aneurysm (AAA) expansion and optimization of screening intervals would improve current surveillance programs. The aim of this study was to characterize AAA growth in a national cohort of patients with AAA both overall and by cardiovascular risk factors. METHODS AND RESULTS: In this study, 1743 patients were monitored for changes in AAA diameter by ultrasonography over a mean follow-up of 1.9 years. Mean initial AAA diameter and growth rate were 43 mm (range 28 to 85 mm) and 2.6 mm/year (95% range, -1.0 to 6.1 mm/year), respectively. Baseline diameter was strongly associated with growth, suggesting that AAA growth accelerates as the aneurysm enlarges. AAA growth rate was lower in those with low ankle/brachial pressure index and diabetes but higher for current smokers (all P<0.001). No other factor (including lipids and blood pressure) was associated with AAA growth. Intervals of 36, 24, 12, and 3 months for aneurysms of 35, 40, 45, and 50 mm, respectively, would restrict the probability of breaching the 55-mm limit at rescreening to below 1%. CONCLUSIONS: Annual, or less frequent, surveillance intervals are safe for all AAAs < or =45 mm in diameter. Smoking increases AAA growth, but atherosclerosis plays a minor role.

The aim was to determine if certain risk factors in the general population are more strongly related to peripheral arterial disease than to ischemic heart disease. Arterial disease in the lower limbs was measured by means of the World Health Organization questionnaire on intermittent claudication, the ankle brachial pressure index, and a reactive hyperemia test in 1,592 men and women aged 55-74 years selected randomly in 1988 from the age-sex registers of 10 general practices in Edinburgh, Scotland. Peripheral arterial disease was strongly related to lifetime cigarette smoking, with additional risks in current and exsmokers of less than 5 years. Multiple regression of risk factors on measures of peripheral arterial disease showed associations with diabetes mellitus (but not impaired glucose tolerance), systolic blood pressure, and serum cholesterol; inverse association with high-density lipoprotein cholesterol; and only univariate association with triglycerides. In multiple logistic regressions of risk factors on six separate indicators of cardiovascular disease, the only consistent difference was that smoking increased the risk of peripheral arterial disease (range of odds ratios, 1.8-5.6) more than heart disease (range of odds ratios, 1.1-1.6). Diabetes mellitus was not a stronger risk factor for peripheral arterial disease.

BACKGROUND: The relationship between levels of circulating inflammatory markers and risk of progressive atherosclerosis is relatively undetermined. We therefore studied inflammatory markers as predictors of peripheral atherosclerotic progression, measured by the ankle-brachial index (ABI) at 3 consecutive time points over 12 years. METHODS AND RESULTS: The Edinburgh Artery Study is a population cohort study of 1592 men and women aged 55 to 74 years. C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin were measured at baseline. Valid ABI measurements were obtained on 1582, 1081, and 813 participants at baseline and 5-year and 12-year follow-up examinations, respectively. At baseline, a significant trend was found between higher plasma levels of CRP (P< or =0.05) and increasing severity of peripheral arterial disease (PAD), after adjustment for baseline cardiovascular risk factors. IL-6 at baseline (P< or =0.001) was associated with progressive atherosclerosis at 5 years (ABI change from baseline), and CRP (P< or =0.01), IL-6 (P< or =0.001), and ICAM-1 (P< or =0.01) were associated with changes at 12 years, independently of baseline ABI, cardiovascular risk factors, and baseline cardiovascular disease. Only IL-6 independently predicted ABI change at 5 years (P< or =0.01) and 12 years (P< or =0.05) in analyses of all inflammatory markers simultaneously and adjusted for baseline ABI, cardiovascular risk factors, and cardiovascular disease at baseline. CONCLUSIONS: These findings suggest that CRP, IL-6, and ICAM-1 are molecular markers associated with atherosclerosis and its progression. IL-6 showed more consistent results and stronger independent predictive value than other inflammatory markers.

BACKGROUND: Increased blood and plasma viscosity, hematocrit, fibrinogen, and activation of coagulation and leukocytes have been reported in patients with claudication; however, their associations with symptomatic and asymptomatic peripheral arterial disease have not been reported in an epidemiological study. METHODS AND RESULTS: Blood and plasma viscosity, hematocrit, fibrinogen, urinary fibrinopeptide A, plasma leukocyte elastase, and uric acid were measured in a random sample of 1,581 men and women aged 55-74 years in Edinburgh, Scotland, and related to peripheral arterial stenosis (ankle-brachial systolic pressure index, ABPI) and to lower limb ischemia (intermittent claudication and reactive hyperemia test). Each variable (except fibrinopeptide A) was significantly related to prevalent symptomatic and asymptomatic peripheral arterial disease. On multivariate analysis, blood viscosity (p < 0.05) and fibrinogen (p < 0.01) were independently associated with peripheral arterial narrowing (ABPI); a positive interaction was found between fibrinogen and smoking in the association with ABPI. Plasma viscosity was associated with claudication in the presence of a given degree of arterial narrowing (odds ratio of claudication in top quintile compared with bottom quintile of plasma viscosity, 3.35; 95% CI, 1.32, 8.51). Leukocyte elastase and uric acid were each associated with reactive hyperemia independently of arterial narrowing (p < 0.01). CONCLUSIONS: Blood rheological factors and leukocyte activation as well as arterial narrowing are associated with lower limb ischemia in the general population and may be implicated in its pathogenesis.