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Jie Ding,
Mark W J Strachan,
Rebecca M Reynolds,
Brian M Frier,
Ian J Deary,
F Gerald R Fowkes, Amanda J Lee,
Janet McKnight,
Patricia Halpin,
Ken Swa,
Jackie F Price
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ABSTRACT: Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.
In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60-75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.
After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.
DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation.
Diabetes 11/2010; 59(11):2883-9. · 8.29 Impact Factor
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ABSTRACT: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the metabolic syndrome, but whether circulating cortisol levels predict cardiovascular end points is less clear. People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk.
We aimed to assess whether altered HPA axis activity was associated with features of the metabolic syndrome and ischemic heart disease in people with type 2 diabetes.
We conducted a cross-sectional cohort study in the general community, including 919 men and women aged 67.9 (4.2) yr with type 2 diabetes (the Edinburgh Type 2 Diabetes Study).
We measured fasting morning plasma cortisol.
Associations between cortisol levels, features of the metabolic syndrome, obesity, and ischemic heart disease were determined.
Elevated plasma cortisol levels were associated with raised fasting glucose and total cholesterol levels (P < 0.001). These findings remained significant after adjustment for potential confounding factors (P < 0.001). Elevated cortisol levels were associated with prevalent ischemic heart disease (>800 vs. <600 nmol/liter; odds ratio, 1.58; P = 0.02). This association remained significant after adjustment for duration and control of diabetes and other cardiovascular risk factors (P = 0.03).
The previously described associations between HPA axis activation and features of the metabolic syndrome are present among people with type 2 diabetes. Elevated plasma cortisol is also associated with a greater prevalence of ischemic heart disease, independent of conventional risk factors. Understanding the role of cortisol in the pathogenesis of ischemic heart disease merits further exploration.
The Journal of clinical endocrinology and metabolism 04/2010; 95(4):1602-8. · 6.50 Impact Factor
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Rebecca M Reynolds,
Mark W J Strachan,
Javier Labad, Amanda J Lee,
Brian M Frier,
F Gerald Fowkes,
Rory Mitchell,
Jonathan R Seckl,
Ian J Deary,
Brian R Walker,
Jackie F Price
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ABSTRACT: People with type 2 diabetes are at increased risk of cognitive impairment but the mechanism is uncertain. Elevated glucocorticoid levels in rodents and humans are associated with cognitive impairment. We aimed to determine whether fasting cortisol levels are associated with cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes.
This was a cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes, living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study). Cognitive abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility were tested, and a general cognitive ability factor, g, was derived. Prior intelligence was estimated from vocabulary testing, and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning plasma cortisol levels and cognitive ability and estimated cognitive change were tested. Models were adjusted for potential confounding and/or mediating variables including metabolic and cardiovascular variables.
In age-adjusted analyses, higher fasting cortisol levels were not associated with current g or with performance in individual cognitive domains. However, higher fasting cortisol levels were associated with greater estimated cognitive decline in g and in tests of working memory and processing speed, independent of mood, education, metabolic variables, and cardiovascular disease (P < 0.05).
High morning cortisol levels in elderly people with type 2 diabetes are associated with estimated age-related cognitive change. Strategies targeted at lowering cortisol action may be useful in ameliorating cognitive decline in individuals with type 2 diabetes.
Diabetes care 04/2010; 33(4):714-20. · 8.09 Impact Factor
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Riccardo E Marioni,
Mark W J Strachan,
Rebecca M Reynolds,
Gordon D O Lowe,
Rory J Mitchell,
F Gerry R Fowkes,
Brian M Frier, Amanda J Lee,
Isabella Butcher,
Ann Rumley,
Gordon D Murray,
Ian J Deary,
Jackie F Price
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ABSTRACT: To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes.
A cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary-based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing.
Higher IL-6 and TNF-alpha levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients -0.074 to -0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g.
In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline.
Diabetes 12/2009; 59(3):710-3. · 8.29 Impact Factor
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Lindsay Robertson, Amanda J Lee,
Karen Gallagher,
Sarah Jane Carmichael,
Christine J Evans,
Brian H McKinstry,
Simon C A Fraser,
Paul L Allan,
David Weller,
Charles V Ruckley,
Francis G Fowkes
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ABSTRACT: Identifying which patients with varicose veins are at risk of progressing to more severe forms of chronic venous disease could help in assigning clinical priorities and targeting appropriate treatments. The aim of this study was to determine, in subjects with varicose veins, the characteristics of venous disease and other factors associated with an increased risk of ulceration.
One hundred twenty subjects with varicose veins and an open or healed venous leg ulcer were compared with 120 controls with varicose veins and no history of venous ulcer on this case control study. Subjects were recruited from hospital settings and primary care. Each subject completed a questionnaire on lifestyle and medical history and underwent an examination comprising of clinical classification of venous disease (CEAP), duplex scanning, quantitative digital photoplethysmography, and measurement of dorsiflexion. Multiple logistic regression analyses and calculation of receiver operating characteristic (ROC) curves were performed to identify the combination of factors which most accurately predicted which patients with varicose veins will develop leg ulcers.
An increased risk of ulceration was associated with the severity of clinical venous disease, especially with the presence of skin changes (P < .0001). Other significant risk factors included history of deep vein thrombosis (DVT) (P = .001), higher body mass index (BMI) (P = .006), smoking (P = .009), and reflux in the deep veins (P = .0001). Ulceration was associated with reduced volume of blood displaced as reflected by photoplethysmography and a limited range of ankle movement (not wholly due to the effects of an active ulcer) (both P < .05). Multivariate analyses showed that skin changes including lipodermatosclerosis (odds ratio [OR] 8.90, 95% confidence interval [CI] 1.44-54.8), corona phlebectatica (OR 4.52, 95% CI 1.81-11.3) and eczema (OR 2.87, 95% CI 1.12-7.07), higher BMI (OR 1.08, 95% CI 1.01-1.15), and popliteal vein reflux (OR 2.82, 95% CI 1.03-7.75) remained independently associated with increased risk of ulceration while good dorsiflexion of the ankle (OR 0.88, 95% CI 0.81-0.97) and an effective calf muscle pump (OR 0.96, 95% CI 0.92-0.99) remained protective factors. ROC curve analyses indicated that a model based on clinical observation of skin changes, duplex scanning for popliteal reflux, and calf muscle pump tests would be the most accurate in determining which patients with varicose veins develop leg ulcers.
The results of this study confirm that, in patients with varicose veins, those with skin changes of chronic venous insufficiency and deep vein incompetence are at greatly increased risk of ulceration. However, the risks may also be increased in those who smoke, are obese, and have restricted ankle movement and reduced calf muscle pump power.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 07/2009; 49(6):1490-8. · 3.52 Impact Factor
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ABSTRACT: To examine whether personality traits are related to all-cause mortality in a general adult population in Scotland.
The Edinburgh Artery Study began in 1987 to 1988 by recruiting 1592 men and women aged 55 to 74 years to be followed-up for atherosclerotic diseases. The NEO Five-Factor Inventory (NEO-FFI) was completed by 1035 surviving participants in 1995 to 1996. Deaths from all causes were examined in relation to personality traits and social and physical risk factors for mortality.
During follow-up, 242 (37.1%) men and 165 (24.6%) women died. For the whole sample, there was a 28% lower rate of all-cause mortality for each 1 SD increase in NEO-FFI openness (95% CI, 0.61-0.84) and a 18% lower rate of all-cause mortality for each 1 SD increase in NEO-FFI conscientiousness (95% CI, 0.70-0.97). In men, the risk of all-cause mortality was 0.63 (95% CI, 0.5-10.78) for a 1 SD increase in openness and 0.75 (95% CI, 0.61-0.91) for a 1 SD increase in conscientiousness. In women, none of the personality domains were significantly associated with all-cause mortality. Well fitting structural equation models in men (n = 652) showed that the relationships between conscientiousness and openness and all-cause mortality were not substantially explained by smoking, or other variables in the models.
High conscientiousness and openness may be protective against all-cause mortality in men. Further investigations are needed on the mechanisms of these associations, and the influence of personality traits on specific causes of death.
Psychosomatic Medicine 06/2009; 71(6):631-41. · 3.97 Impact Factor
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ABSTRACT: The role of metabolic syndrome and associated haemostatic and inflammatory markers in risk of atherosclerosis in different vascular beds is controversial. We used modified National Cholesterol Education Program criteria to define metabolic syndrome in a population-based cohort of men and women aged 55-74 years with up to 15 years of follow-up to investigate whether metabolic syndrome is associated with risk of cerebrovascular and peripheral arterial disease and the role of inflammatory and haemostatic factors in these relationships. Data were available for 762 participants, of whom 267 (35%) had metabolic syndrome at baseline and 69 (9.0%) and 108 (14%) had cerebrovascular and peripheral arterial disease events, respectively, during follow-up. We used Cox proportional hazards modelling to estimate hazard ratios (HRs). Metabolic syndrome was associated with several haemostatic and inflammatory variables and with cerebrovascular disease both after adjusting for age and sex (HR 2.12 (1.31-3.41) and after further adjustment for conventional cardiovascular risk factors and inflammatory and haemostatic markers (HR 1.77 (1.05-2.96). The association between metabolic syndrome and peripheral arterial disease was not statistically significant either with adjustment for age and sex (HR 1.33 (0.90-1.96) or after full adjustment (HR 0.89 (0.57-1.38). We conclude that metabolic syndrome was more strongly related to risk of atherosclerosis in the cerebrovascular than the peripheral circulation and the association was independent of conventional risk factors, haemostatic and inflammatory markers in this population. Improving insulin sensitivity may reduce cerebrovascular disease risk.
Atherosclerosis 09/2008; 203(2):604-9. · 3.79 Impact Factor
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ABSTRACT: Prospective validation of prognostic scoring systems for ruptured abdominal aortic aneurysm (AAA) is lacking. This study assesses the validity of three established risk scores and a new prognostic index.
Patients admitted with ruptured AAA during a 26-month period (August 2002-December 2004) were recruited prospectively. The Glasgow Aneurysm Score (GAS), Hardman Index, Physiological and Operative Severity Score for enUmeration of Mortality and Morbidity (POSSUM) scores, and the Edinburgh Ruptured Aneurysm Score (ERAS) were recorded and related to outcome.
During the study period, 111 patients were admitted with ruptured AAA. Of these, 84 (76%) underwent attempted operative repair and were included in the study; 37 (44%) died after operation. The GAS, Hardman Index, and the ERAS were statistically related to mortality. However, analysis by receiver-operator characteristic curve revealed the ERAS to have an area under the curve (AUC) of 0.72 (95% confidence interval [CI], 0.61-0.83). The vascular (V)-POSSUM and ruptured AAA (RAAA)-POSSUM models had an AUC of 0.70 (95% CI, 0.59-0.82). The Hardman Index and GAS had an AUC of 0.69 (95% CI, 0.57-0.80) and 0.64 (95% CI, 0.52-0.76), respectively. Although the V-POSSUM equation predicted mortality effectively (P = .086), the RAAA-POSSUM derivative demonstrated a significant lack of fit (P = .009).
Prospective validation shows that the Hardman Index, GAS, and V-POSSUM and RAAA-POSSUM scores do not perform well as predictors for death after ruptured AAA. The ERAS accurately stratifies perioperative risk but requires further validation.
Journal of Vascular Surgery 03/2008; 47(2):282-6. · 3.21 Impact Factor
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ABSTRACT: To compare the predictive value of the ankle brachial index (ABI) and carotid intima media thickness (IMT) for cardiovascular events.
Population-based cohort study. New cardiovascular events (myocardial infarction [MI], stroke, angina, and intermittent claudication) were ascertained over a 12-year period in 1,007 men and women aged 60-79 and free of MI or stroke.
The positive and negative predictive values for an ABI<or=0.9, an IMT>or=0.9mm and for both tests abnormal were not substantially different. However, event rates in subjects with one test normal were increased when the alternate test proved positive (in people with a normal ABI test, 20.8% with an abnormal IMT developed MI/stroke compared with only 10.3% with a normal IMT). The area under the receiver operator curves (AUC) increased significantly between a model containing only age and sex (AUC 0.60, 95% confidence interval [CI] 0.55, 0.65) and that with either ABI (AUC 0.63, 95% CI 0.58, 0.69, P=0.002) or IMT (AUC 0.62, 95% CI 0.57, 0.67, P=0.005) added. The AUC increased further when both tests were added simultaneously (AUC 0.65, 95% CI 0.60, 0.70, P<0.001).
The ability of the ABI to predict cardiovascular disease was similar to that of the IMT. Combination of the two tests may be advantageous when the second test is applied to people with a negative first test and/or when the results are used as continuous variables.
Journal of Clinical Epidemiology 11/2007; 60(10):1067-75. · 4.27 Impact Factor
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ABSTRACT: The aim of our present study was to compare the association of a wide range of 17 biomarkers of inflammation, hemostasis, and blood rheology with incident heart disease and stroke after accounting for an indicator of subclinical atherosclerotic disease and traditional risk factors and also to determine their incremental predictive ability.
We used data from the Edinburgh Artery Study, a population cohort study started in 1987 that comprised 1592 men and women aged 55 to 74 years. Subjects were followed for a mean of 17 years, and 416 of them suffered at least 1 cardiovascular event. In analyses adjusted for cardiovascular risk factors and history of cardiovascular disease (CVD): C-reactive protein, interleukin-6, fibrinogen, fibrin D-dimer, tissue plasminogen activator (t-PA), leukocyte elastase, and lipoprotein(a) (all P<0.01), as well as von Willebrand factor and plasma viscosity (both P<0.05), had significant hazard ratios for incident CVD. Further adjustment for a measure of subclinical atherosclerosis (ankle brachial index) had little impact on these associations. The hazard ratios (95% CI) for incident CVD between top and bottom tertiles in the latter analysis were 1.78 (1.30 to 2.45) for C-reactive protein, 1.85 (1.33 to 2.58) for interleukin-6, and 1.76 (1.35 to 2.31) for fibrinogen. Single biomarkers provided little additional discrimination of incident CVD to that obtained from cardiovascular risk factors and the ankle brachial index. An incremental score of multiple markers [interleukin-6, t-PA, intercellular adhesion molecule 1, and lipoprotein(a)] provided some added discrimination.
Several "novel" risk factors predicted CVD after adjustments for conventional risk factors and also for a measure of asymptomatic disease. However, their incremental predictive ability was modest and their clinical utility remains uncertain.
Circulation 04/2007; 115(16):2119-27. · 14.74 Impact Factor
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ABSTRACT: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies.
In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for.
Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.
European Heart Journal 02/2007; 28(3):354-62. · 10.48 Impact Factor
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ABSTRACT: To investigate whether a low ankle-brachial pressure index (ABI) predicts increased risk of cardiovascular disease (CVD) independent of the metabolic syndrome and conventional cardiovascular risk factors.
The Edinburgh Artery Study is a population-based cohort study in which subjects were followed up until their death or for approximately 15 years. Low ABI at baseline was defined as <0.9; subjects with ABI >1.4 (n = 13) were excluded from the analyses. We used a modified version of the definition of the metabolic syndrome published in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, replacing waist circumference criteria with BMI criteria. Data on relevant parameters were available for 1,467 men and women ages 55-74 years at baseline. Cox proportional hazards models were used to study cardiovascular morbidity and mortality before and after adjusting for potential confounding factors.
We determined that 25% of the study population had the metabolic syndrome and that a low ABI was more prevalent among people with than without the metabolic syndrome (24 vs. 15%; P < 0.001). During the follow-up period, there were 226 deaths from CVD and 462 nonfatal cardiovascular events. The hazard ratio (95% CI) for low ABI after adjusting for age, sex, baseline CVD, diabetes, smoking status, LDL cholesterol, and metabolic syndrome was 1.5 (1.1-2.1) for CVD mortality and 1.5 (1.2-1.8) for all CVD outcomes.
Low ABI is associated with increased risk of CVD independent of the metabolic syndrome and other major CVD risk factors.
Diabetes Care 04/2006; 29(3):637-42. · 8.09 Impact Factor
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ABSTRACT: Abdominal aortic aneurysms often coexist with reduced lung function and chronic obstructive pulmonary disease (COPD). These conditions are each associated with cigarette smoking, cardiovascular disease, and evidence of increased inflammatory and hemostatic activity. The aim of this study was to determine if these factors accounted for the link between aneurysms and pulmonary disease.
The design was a case-control study comparing patients with an asymptomatic abdominal aortic aneurysm with population-based controls without an aneurysm. Aneurysms were diagnosed by ultrasound scan, and pulmonary function was measured by respiratory questionnaire and spirometry. Activation of inflammation and hemostasis was measured by assay of plasma interleukin-6 (IL-6), fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (tPA) antigen, fibrin D-dimer, and plasmin antiplasmin complexes.
Cases with an abdominal aortic aneurysm (n = 89) had more COPD and worse expiratory lung function as measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) than controls (n = 98) (FEV1, 1.9 vs 2.2 L, P < .01; FEV1/FVC, 0.67 vs 0.75, P < .001) and did not differ in restrictive function (FVC, 2.9 vs 3.0 L, P = .33). Cases also had higher levels of lifetime cigarette smoking (30 vs 24 pack-years, P < 0.01), cardiovascular disease (35% vs 18%, P = .01), plasma fibrinogen (3.5 vs 3.1 g/L, P = .02), IL-6 (2.8 vs 1.8, pg/mL, P < .001), plasmin antiplasmin complexes (596 vs 384 microg/L, P = .01), and D-dimer (442 vs 93 ng/mL, P < .001). On multiple logistic regression analysis of lung function and COPD on the risk of aneurysm, both cigarette smoking and cardiovascular disease had little effect on the relationships. For the markers of activated inflammation and hemostasis, plasmin antiplasmin complexes and D-dimer had the most important confounding effect on the odds ratios. All markers combined had a substantial effect: odds ratio of aneurysm for a one standard deviation decrease in FEV1 fell from 2.3 (95% confidence interval [CI], 1.5 to 3.5) (P < .01) to 1.3 (95% CI, 0.55 to 2.4) (P > or = .05).
The association between reduced respiratory function and abdominal aortic aneurysm was not accounted for by cigarette smoking or cardiovascular disease. We hypothesize that activation of inflammation and hemostasis in response to injury may be an important explanation of the association between aneurysm formation and reduced respiratory function. Further studies are required to test this hypothesis.
Journal of Vascular Surgery 03/2006; 43(3):474-80. · 3.21 Impact Factor
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ABSTRACT: The interplay between inflammatory and hemostatic mechanisms may play a crucial role in the development and progression of atherosclerosis. The authors evaluated the separate and joint associations of hemostatic and inflammatory variables on peripheral atherosclerotic progression in the Edinburgh Artery Study, a population cohort study of 1,592 men and women aged 55-74 years that started in 1987. Levels of fibrinogen, fibrin D-dimer, von Willebrand factor, tissue plasminogen activator antigen, factor VII, prothrombin fragment 1 + 2, urinary fibrinopeptide A, C-reactive protein, and interleukin-6 were measured at baseline. Arm and ankle blood pressures were measured, and atherosclerotic progression was assessed by computing ankle brachial index (ABI) at baseline (1,582 participants) and after 12 years of follow-up (813 participants). Fibrinogen (p = 0.05) and D-dimer (p < or = 0.05) were significantly associated with ABI change independently of baseline ABI and cardiovascular disease risk factors. However, these associations were no longer significant when analyses were adjusted for either C-reactive protein or interleukin-6. Moreover, subjects with higher levels of both D-dimer and interleukin-6 at baseline had the greatest ABI decline. In conclusion, fibrinogen and D-dimer, but not other hemostatic factors, were associated with progressive peripheral atherosclerosis. Since D-dimer and fibrinogen are acute phase reactants, these data support the hypothesis that inflammation is more related to atherosclerosis than is hypercoagulation.
American Journal of Epidemiology 02/2006; 163(4):334-41. · 5.22 Impact Factor
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ABSTRACT: 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.
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.
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.
Circulation 08/2005; 112(7):976-83. · 14.74 Impact Factor
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ABSTRACT: Previous studies investigating the health-related quality of life of those with peripheral arterial disease have focused on patients recruited from hospital clinics. The health-related quality of life of people with peripheral arterial disease in the general population is unknown.
We aimed to determine the health-related quality of life of people with intermittent claudication and asymptomatic peripheral arterial disease in the general population and to compare it with those with angina and those with no peripheral arterial disease or angina. Design of study: Analysis of cross-sectional data from the 12-year follow-up of a population-based cohort.
Edinburgh, Scotland.
Data from the Edinburgh Artery Study cohort's 12-year follow-up was analysed. Participants' peripheral arterial disease status was measured using the World Health Organisation intermittent claudication questionnaire and the ankle brachial pressure index. Self-assessed health-related quality of life data was collected using the SF-36 generic questionnaire. Health-related quality of life scores were calculated and their associations with peripheral arterial disease status groups were tested.
Subjects with intermittent claudication had significantly worse median health-related quality of life scores than patients without claudication in all domains except social functioning and mental health. Patients with claudication had a significantly lower physical component summary score than those without claudication (P </= 0.001). This association remained after adjustment for age, sex, social class, body mass index, smoking, and angina. Those with angina and claudication had significantly worse physical component summary scores than those with no peripheral arterial disease or angina (P </= 0.001). No significant difference was found in health-related quality of life scores between those with asymptomatic peripheral arterial disease and those with no peripheral arterial disease even after multiple adjustment for confounding factors.
People with intermittent claudication in the community had impaired health-related quality of life related to reduced physical health, but asymptomatic peripheral arterial disease did not significantly affect health-related quality of life.
British Journal of General Practice 11/2004; 54(508):826-31. · 1.83 Impact Factor
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ABSTRACT: There is continuing controversy as to whether surgical bypass or angioplasty should be first-line treatment of severe limb ischemia. We undertook this study to examine angiographic and clinical factors that influence the treatment of severe limb ischemia by vascular surgeons and interventional radiologists.
Twenty consultant vascular surgeons and 17 consultant vascular interventional radiologists evaluated 596 hypothetical clinical or angiographic scenarios, and recorded whether, in their opinion, the most appropriate first-line treatment was surgical bypass, angioplasty, or primary amputation. Stepwise multiple linear regression was used to identify the factors that significantly affected responses from the entire group and from surgeons and radiologists separately.
There were significant differences between surgeons and radiologists with regard to how clinical and angiographic variables determined treatment preferences. Increasing disease severity, absence of runoff into the foot, presence of a suitable vein, and tissue loss as opposed to rest pain only (the latter only significant to surgeons) all increased the response score toward surgery. However, surgeons and radiologists weighted each of these factors quite differently. Even in the most complex statistical model, 19% of surgical and 13% of radiologic response variations remained unexplained.
Individual surgeons and radiologists vary considerably in their views of the relative merits of surgery and angioplasty in patients with severe limb ischemia. This broad gray area mandates the need for randomized controlled trial data to inform joint decision-making and to optimize patient outcome.
Journal of Vascular Surgery 06/2004; 39(5):1026-32. · 3.21 Impact Factor
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ABSTRACT: To determine changes over time in the ankle brachial index (ABI) among subjects with and without intermittent claudication in the general population.
Population cohort study.
General population in Edinburgh, Scotland.
A total of 1592 men and women aged 55 to 74 years selected at random from age-sex registers of 11 general practices and followed up over 12 years. Main outcome measures Changes in ABI for each leg recorded at baseline in 1988 and at subsequent 5-year and 12-year clinical examinations.
Overall, 695 subjects (348 men and 347 women) had valid ABI measurements on both legs at all three examinations. At baseline, the ABI was on average.03 higher in the right leg than the left (P < or =.001). Men had a mean ABI that was.07 higher than women (P < or =.001). Mean ABI in the worse leg showed little change over 12 years in both men and women. However, in the whole population, the ABI in the better leg showed a significant drop, 1.15 to 1.08 (P < or =.001). A total of 179 cases of intermittent claudication were identified during the 12-year follow-up. At baseline, ABI in the worse leg of the claudicants was significantly lower than in healthy subjects (.99 vs 1.08; P < or =.01). In claudicants, mean ABI in the worse leg fell by.04 over 5 years (P < or =.05) and in the better leg showed a highly significant drop of.09 (P < or =.001) to levels similar to those of the worse leg.
The mean ABI in the worse leg of study subjects showed little progression over 12 years. Individuals with intermittent claudication experienced a greater decline in both legs compared with those without claudication. Deterioration occurred more rapidly in the limb with a higher ABI at baseline, which possibly indicates a systemic tendency to atherosclerosis.
Journal of Vascular Surgery 01/2004; 38(6):1323-30. · 3.21 Impact Factor
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ABSTRACT: The objective of this study was to determine the inter-relationships between a range of lifestyle factors and risk of varicose veins to identify which factors may be implicated in the etiology. An age-stratified random sample of 1566 subjects (699 men and 867 women) aged 18 to 64 years was selected from 12 general practices throughout Edinburgh. A detailed self-administered questionnaire was completed, and a comprehensive physical examination determined the presence and severity of varicose veins. The slightly higher age-adjusted prevalence of varicose veins in men than in women (39.7% versus 32.2%) was not explained by adjustment for an extensive range of lifestyle risk factors (male odds ratio [OR] 2.11, 95% confidence interval [CI] 1.51-2.96). In both sexes, increasing height showed a significant relationship with varicose veins (male OR 1.50, 95% CI 1.18-1.93 and female OR 1.26, 95% CI 1.01-1.58). Among women, body mass index was associated with an increased risk of varicose veins (OR 1.26, 95% CI 1.02-1.54). The current study casts doubt as to whether varicose veins occur predominantly in women. In addition, no consistent relationship with any lifestyle factor was shown. Self-reported evidence suggested a familial susceptibility, thereby warranting future genetic studies.
Journal of Clinical Epidemiology 03/2003; 56(2):171-9. · 4.27 Impact Factor
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ABSTRACT: A more accurate means of prediction of abdominal aortic aneurysm (AAA) rupture would improve the clinical and cost effectiveness of prophylactic repair. The purpose of this study was to determine whether AAA wall distensibility can be used to predict time to rupture independently of other recognized risk factors.
A prospective, six-center study of 210 patients with AAA in whom blood pressure (BP), maximum AAA diameter (Dmax), and AAA distensibility (pressure strain elastic modulus [Ep] and stiffness [beta]) were measured at 6 months with an ultrasound scan-based echo-tracking technique. A stepwise, time-dependent, Cox proportional hazards model was used to determine the effect on time to rupture of age, gender, BP, Dmax, BP, Ep, beta, and change in Dmax, Ep, and beta adjusted for time between follow-up visits.
Median (interquartile range) AAA diameter was 48 mm (41 to 54 mm), median age was 72 years (68 to 77 years), and median follow-up period was 19 months (9 to 30 months). In the Cox model, female gender (hazards ratio [HR], 2.78; 95% CI, 1.23 to 6.28; P =.014), larger Dmax (HR, 1.36 for 10% increase in Dmax; 95% CI, 1.12 to 1.66; P =.002), higher diastolic BP (HR, 1.13 for 10% increase in BP; 95% CI, 1.13 to 1.92; P =.004), and a decrease in Ep (increase in distensibility) over time (HR, 1.38 for 10% decrease in Ep over 6 months; 95% CI, 1.08 to 1.78; P =.010) significantly reduced the time to rupture (had a shorter time to rupture).
Women have a shorter time to AAA rupture. The measurement of AAA distensibility, diastolic BP, and diameter may provide a more accurate assessment of rupture risk than diameter alone.
Journal of Vascular Surgery 02/2003; 37(1):112-7. · 3.21 Impact Factor
