Incidence and risk factors for venous reflux in the general population: Edinburgh Vein Study.

OBJECTIVE/BACKGROUND: Chronic venous disease (CVD) is common, but the incidence of venous reflux, a precursor to this condition, is unknown. This study measured the incidence of venous reflux and associated risk factors, and examined the association between venous reflux and the incidence of CVD. METHODS: In the Edinburgh Vein Study, a random sample of 1566 men and women aged 18-64 years were examined at baseline. Eight hundred and eighty of these patients were followed up 13 years and underwent an examination comprising clinical classification of CVD and duplex scanning of the deep and superficial systems to measure venous reflux ≥0.5 s. RESULTS: The 13-year incidence of reflux was 12.7% (95% confidence interval [CI] 9.2-17.2), equivalent to an annual incidence of 0.9% (95% CI 0.7-1.3). The 13-year incidence of isolated superficial, isolated deep, and combined deep and superficial reflux was 8.8% (95% CI 5.6-12.0), 2.6% (95% CI 1.2-5.0), and 1.3% (95% CI 0.4-3.2), respectively. The highest incidence was in the great saphenous vein in the lower thigh (8.1%, 95% CI 5.4-11.8). There were no age or sex differences (p > .050). The risk of developing reflux was associated with being overweight (odds ratio [OR] 2.1, 95% CI 1.0-4.4) and with history of deep vein thrombosis (OR 11.3, 95% CI 1.0-132.3). Venous reflux at baseline was associated with new varicose veins at follow up (p < .001): the age- and sex-adjusted OR was 4.4 (95% CI 1.8-10.8) in those with isolated superficial reflux and 7.3 (95% CI 2.6-22.5) in those with combined deep and superficial reflux. CONCLUSION: For every year of follow-up, around 1% of this adult population developed venous reflux. In two thirds of cases, the superficial system was affected. Venous reflux increased the risk of developing varicose veins, especially when combined deep and superficial reflux was present.

Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

Incidence of chronic venous disease in the Edinburgh Vein Study.

BACKGROUND: Epidemiologic research in chronic venous disease has focused on prevalence and associated risk factors. Evidence on the risks and incidence that this condition will develop is limited. The aim of this study was to measure the incidence of new varicose veins and chronic venous insufficiency (CVI) in an adult population and to investigate risk factors associated with the development of these conditions. METHODS: The Edinburgh Vein Study is a cohort study of a random sample of the general population. Invitations were sent to 1456 men and women at baseline to participate in a 13-year follow-up examination. Each participant completed a questionnaire on lifestyle and medical history and underwent an examination that included clinical classification of venous disease. RESULTS: After a mean follow-up of 13.4 (standard deviation, 0.4) years, 880 of 1456 individuals participated (60.4% response). The overall incidence (95% confidence interval [CI]) of C2 varicose veins was 18.2% (15.2%-21.6%), giving an annual incidence rate of 1.4% (1.1%-1.7%), with incidence rates similar in men and women: the 13-year age-adjusted incidence of varicose veins was 15.2% (10.4%-20.0%) in men and 17.4% (13.1%-21.7%) in women (P = .97). The 13-year incidence of varicose veins increased consistently with age from 9.8% in those aged 18 to 34 years to 25.7% in those aged 55 to 64 years (P < .001). The 13-year incidence (95% CI) of CVI was 9.2% (7.0%-11.9%), and the annual incidence rate was 0.7% (0.5%-0.9%). The incidence of CVI was similar in men and women and increased consistently with age (P < .001). Participants with a family history of venous disease were more likely to develop C2 varicose veins (odds ratio, 1.75; 95% CI, 1.12-2.71). Obesity was associated with the development of CVI: the 13-year incidence (95% CI) was 6.1% (3.7%-9.6%) in those who were of normal weight and 23.6% (14.2%-37.0%) in obese participants, with an age-adjusted odds ratio of 3.58 (1.70-7.56). CONCLUSIONS: The Edinburgh Vein Study is one of a few cohort studies to report the incidence of varicose veins and CVI in the general population. The incidence of varicose veins and CVI did not differ significantly by sex and was strongly associated with increasing age. The risk of developing varicose veins was increased in those with a family history, and the risk of CVI was increased in those with higher body mass index.

Telangiectasia and venous reflux in the Edinburgh Vein Study.

OBJECTIVE: The purpose of this study was to correlate the clinical findings in the Edinburgh Vein Study with the results of duplex scanning of the deep and superficial venous systems. METHODS: An age-stratified random sample of 1566 people (699 men and 867 women) aged 16-64 were selected from computerized age-sex registers of participating practices (twelve general practices with catchment areas geographically and socioeconomically distributed throughout Edinburgh). Screening included clinical examination, photography and duplex ultrasonography of the superficial veins and the deep veins down to popliteal level. Telangiectasia and varicose veins were graded 1-3 according to severity. RESULTS: Since there was good agreement between the duplex findings of the right versus left legs, the current analyses are based on 1092 subjects (486 men and 606 women) with complete duplex scan data in their left legs. There was no significant trend of increasing incompetence in either the deep veins only (P = 0.214) or in the combined deep and superficial veins (P = 0.111) with increasing severity of the telangiectasia. There was a statistically significant trend for increasing incompetence in (a) the superficial veins (P = 0.006) and (b) either the superficial or deep veins (P < 0.001) to be associated with advancing grade of telangiectasia. When stratified by gender, significant trends were maintained for male superficial vein incompetence and for either superficial or deep incompetence in both genders. Examination of incompetence in individual venous segments showed that increasing severity of telangiectasia was significantly associated with an increasing proportion of reflux in the upper and lower great saphenous and femoral vein segments. There was no significant association between small saphenous incompetence and increasing grade of telangiectasia. CONCLUSION: There is a significant, but not wholly consistent, association between grade of telangiectasia and reflux in both the deep and superficial systems. This association does not apply to the small saphenous system.

Association of retinal arteriolar dilatation with lower verbal memory: the Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: Retinal vascular calibre changes may reflect early subclinical microvascular disease in diabetes. Because of the considerable homology between retinal and cerebral microcirculation, we examined whether retinal vascular calibre, as a proxy of cerebral microvascular disease, was associated with cognitive function in older people with type 2 diabetes. METHODS: A cross-sectional analysis of 954 people aged 60-75 years with type 2 diabetes from the population-based Edinburgh Type 2 Diabetes Study was performed. Participants underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. The Mill Hill Vocabulary Scale was used to estimate pre-morbid cognitive ability. Retinal vascular calibre was measured from an image field with the optic disc in the centre using a validated computer-based program. RESULTS: After age and sex adjustment, larger retinal arteriolar and venular calibres were significantly associated with lower scores for the Wechsler Logical Memory test, with standardised regression coefficients -0.119 and -0.084, respectively (p < 0.01), but not with other cognitive tests. There was a significant interaction between sex and retinal vascular calibre for logical memory. In male participants, the association of increased retinal arteriolar calibre with logical memory persisted (p < 0.05) when further adjusted for vocabulary, venular calibre, depression, cardiovascular risk factors and macrovascular disease. In female participants, this association was weaker and not significant. CONCLUSIONS/INTERPRETATION: Retinal arteriolar dilatation was associated with poorer memory, independent of estimated prior cognitive ability in older men with type 2 diabetes. The sex interaction with stronger findings in men requires confirmation. Nevertheless, these data suggest that impaired cerebral arteriolar autoregulation in smooth muscle cells, leading to arteriolar dilatation, may be a possible pathogenic mechanism in verbal declarative memory decrements in people with diabetes.

Rupture rates of small abdominal aortic aneurysms: a systematic review of the literature.

BACKGROUND: Small aneurysms of the abdominal aorta (3.0-5.5 cm in diameter) often are managed by regular surveillance, rather than surgery, because the risk of surgery is considered to outweigh the risk of aneurysm rupture. The risk of small aneurysm rupture is considered to be low. The purpose of this review is to summarise the reported estimates of small aneurysm rupture rates. METHODS AND FINDINGS: We conducted a systematic review of the literature published before 2010 and identified 54 potentially eligible reports. Detailed review of these studies showed that both ascertainment of rupture, patient follow-up and causes of death were poorly reported: diagnostic criteria for rupture were never reported. There were only 14 studies from which rupture rates (as ruptures per 100 person-years) were available. These 14 published studies included 9779 patients (89% male) over the time period 1976-2006 but only 7 of these studies provided rupture rates specifically for the diameter range 3.0-5.5 cm, which ranged from 0 to 1.61 ruptures per 100 person-years. CONCLUSIONS: Rupture rates of small abdominal aortic aneurysms would appear to be low, but most studies have been poorly reported and did not have clear ascertainment and diagnostic criteria for aneurysm rupture.

Epidemiology and risk factors for varicose veins among older people: cross-sectional population study in the UK.

BACKGROUND: There are many hypotheses concerning risk factors for the development of varicose veins based mostly on pathophysiological plausibility. Population studies have been carried out mostly on the middle aged with relatively few on elderly populations. OBJECTIVES: To investigate epidemiological risk factors for varicose veins in an elderly population in the UK. METHODS: The South Wales Skin Cancer study - an examination survey undertaken between 1988 and 1991 of a random sample (n = 792) drawn from all patients aged 60 and over registered with a general practitioner in South Glamorgan. Exposure variables were obtained from a structured administered questionnaire combined with clinical examination. Unadjusted and adjusted odds ratios were estimated using logistic regression. RESULTS: The response rate was 71% with an average age of 71 years (range 60-97). The age-adjusted prevalence of trunk varices was 63.2% (95% confidence interval [CI] 57.9-68.4%) in men and 57.0% (95% CI 50.6-63.4%) in women. In a multiple logistic regression the significant risk factors for varicose veins were increasing age (P value = 0.001), obesity (odds ratio [OR] 3.28, 95% CI 1.25-8.63, P = 0.042), self-reported history of deep vein thrombosis (DVT) (OR 3.19, 1.16-8.78, P = 0.024) and history of hypertension (OR 0.58, 0.38-0.89, P = 0.013). The results for gender suggested that women were at greater risk than men, but this was not statistically significant (OR 1.53, 0.99-2.38, P = 0.056). CONCLUSION: Trunk varices occur very commonly in older age groups with increasing age, obesity and possibly female sex as risk factors. Associations found with DVT and hypertension were based on history alone and must be interpreted with caution.

Multicentre randomised controlled trial of the clinical and cost-effectiveness of a bypass-surgery-first versus a balloon-angioplasty-first revascularisation strategy for severe limb ischaemia due to infrainguinal disease. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial.

OBJECTIVE: To compare a 'bypass-surgery-first' with a 'balloon-angioplasty-first' revascularisation strategy in patients with severe limb ischaemia (SLI) due to infrainguinal disease requiring immediate/early revascularisation. DESIGN: A stratified randomised controlled trial. A Delphi consensus study of vascular surgeons' and interventional radiologists' views on SLI treatment was performed before the trial. SETTING: Twenty-seven UK hospitals. PARTICIPANTS: Patients presenting with SLI as the result of infrainguinal atherosclerosis and who, in the opinion of the responsible consultant vascular surgeon and interventional radiologist, required and were suitable for both surgery and angioplasty. INTERVENTIONS: Patients were randomised to either 'bypass-surgery-first' or 'balloon-angioplasty-first' revascularisation strategies. MAIN OUTCOME MEASURES: The primary end point was amputation-free survival (AFS); secondary end points were overall survival (OS), health-related quality of life (HRQoL) and cost-effective use of hospital resources. RESULTS: AFS at 1 and 3 years was not significantly different for surgery and angioplasty. Interim analysis showed that surgery was associated with significantly lower immediate failure, higher 30-day morbidity and lower 12-month reintervention rates than angioplasty; 30-day mortality was similar. Beyond 2 years from randomisation, hazard ratios (HRs) were significantly reduced for both AFS (adjusted HR 0.37; 95% CI 0.17 to 0.77; p = 0.008) and OS (HR 0.34; 95% CI 0.17 to 0.71; p = 0.004) for surgery relative to angioplasty. By 2008 all but four patients had been followed for 3 years, some for over 7 years: 250 (56%) were dead, 168 (38%) were alive without amputation and 30 (7%) were alive with amputation. Considering the follow-up period as a whole, AFS and OS did not differ between treatments but for patients surviving beyond 2 years from randomisation, bypass was associated with reduced HRs for AFS (HR 0.85; 95% CI 0.50 to 1.07; p = 0.108) and OS (HR 0.61; 95% CI 0.50 to 0.75; p = 0.009), equating to an increase in restricted mean OS of 7.3 months (p = 0.02) and AFS of 5.9 months (p = 0.06) during the subsequent follow-up period. Vein bypasses and angioplasties performed better than prosthetic bypasses. HRQoL was non-significantly better in the surgery group; amputation was associated with a significant reduction in HRQoL. Over the first year, hospital costs for bypass were significantly higher (difference 5420 pounds; 95% CI 1547 pounds to 9294 pounds) than for angioplasty. However, by 3 and at 7 years the differences in cost between the two strategies were no longer significant. Patients randomised to surgery lived, on average, 29 days longer at an additional average cost of 2310 pounds. A 36-month perspective showed not significantly different mean quality-adjusted life times for angioplasty and surgery. The Delphi study revealed substantial disagreement between and among surgeons and radiologists on the appropriateness of bypass surgery or balloon angioplasty. CONCLUSIONS: The findings of our study suggest that in patients with SLI due to infrainguinal disease the decision whether to perform bypass surgery or balloon angioplasty first appears to depend upon anticipated life expectancy. Patients expected to live less than 2 years should usually be offered balloon angioplasty first as it is associated with less morbidity and cost, and such patients are unlikely to enjoy the longer-term benefits of surgery. By contrast, those patients expected to live beyond 2 years should usually be offered bypass surgery first, especially where a vein is available as a conduit. Many patients who could not undergo a vein bypass would probably have been better served by a first attempt at balloon angioplasty than prosthetic bypass. The failure rate of angioplasty in SLI is high (c. 25%) and patients who underwent bypass after failed angioplasty fared significantly worse than those who underwent surgery as their first procedure. The interests of a significant proportion of BASIL patients may have been best served by primary amputation followed by high-quality rehabilitation. Further research is required to confirm or refute the BASIL findings and recommendations; validate the BASIL survival prediction model in a separate cohort of patients with SLI; examine the clinical and cost-effectiveness of new endovascular techniques and devices; and compare revascularisation with primary amputation and with best medical and nursing care in those SLI patients with the poorest survival prospects. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45398889.

Associations between polymorphisms in five inflammation-related genes and cognitive ability in older persons.

Several studies have found associations between inflammatory biomarker levels and cognitive ability. This study tested the relationship between polymorphisms in genes that are associated with or encode the biomarkers and cognitive ability and estimated lifetime cognitive change. Data came from the aspirin for asymptomatic atherosclerosis trial (n = 2091, mean age = 67.2 years ). Twelve single nucleotide polymorphisms (SNPs) were genotyped from five genes (IL-1alpha, IL-1beta, IL-6, HNF-1A and F13A1). Cognition was assessed via administration of a five-test battery of psychometric tests, which were used to derive a general intelligence factor, g. A vocabulary-based cognitive test was also administered and adjusted for in the analysis to enable an estimation of lifetime cognitive change. Age- and sex-adjusted analyses yielded one weakly significant association between the IL-1alpha rs2856838 SNP and a measure of mental flexibility/processing speed (P = 0.044). Adjustment for the vocabulary-based scores resulted in a single, significant association between the IL-1alpha rs3783546 SNP and a measure of processing speed (P = 0.048). There is little evidence to suggest an association between SNPs in the inflammation-related genes IL-1alpha, IL-1beta, IL-6, TCF-1 and F13A1 and cognition in an elderly population of community-dwelling Scottish citizens.

Symptoms of depression but not anxiety are associated with central obesity and cardiovascular disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: The aim of the study was to identify risk factors for depression and anxiety in a well-characterised cohort of individuals with type 2 diabetes mellitus. METHODS: We used baseline data from participants (n = 1,066, 48.7% women, aged 67.9 +/- 4.2 years) from the Edinburgh Type 2 Diabetes Study. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Obesity was characterised according to both overall (body mass index, fat mass) and abdominal (waist circumference) measurements. Cardiovascular disease was assessed by questionnaire, physical examination and review of medical records. Stepwise multiple linear regression was performed to identify explanatory variables related to either anxiety or depression HADS scores. RESULTS: Abdominal obesity (waist circumference) and cardiovascular disease (ischaemic heart disease and ankle-brachial pressure index) were related to depression but not anxiety. Lifetime history of severe hypoglycaemia was associated with anxiety. Other cardiovascular risk factors or microvascular complications were not related to either anxiety or depressive symptoms. CONCLUSIONS/INTERPRETATION: Depression but not anxiety is associated with abdominal obesity and cardiovascular disease in people with type 2 diabetes mellitus. This knowledge may help to identify depressive symptoms among patients with type 2 diabetes who are at greatest risk.

Circulating plasma cortisol concentrations are not associated with coronary artery disease or peripheral vascular disease.

BACKGROUND: Although the prevalence of cardiovascular disease is declining, the obesity epidemic with associated metabolic syndrome may reverse this trend. Hypothalamic-pituitary-adrenal (HPA) axis activation may underlie the metabolic syndrome, but whether circulating cortisol levels predict vascular disease is less clear. A recent study reported a positive correlation between cortisol levels measured prior to coronary angiography and disease severity, but others have not demonstrated such a relationship. This may be due to different sampling conditions, reflecting basal cortisol levels, vs. responsiveness of HPA axis activity, which may have diverse influences on the pathogenesis of atherosclerosis. AIMS: To determine whether basal circulating cortisol levels predict coronary artery (CAD) or peripheral vascular disease. METHODS: Basal plasma cortisol levels were measured in 278 subjects with suspected CAD, who had undergone elective coronary angiography and in 76 cases and 85 controls with and without peripheral vascular disease, respectively. RESULTS: After adjustment for potential confounding factors, circulating cortisol levels tended to be lower in those with confirmed coronary vessel disease at angiography (P = 0.10), and in those requiring intervention following angiography (P = 0.07). Lower cortisol levels also predicted those with more symptoms of angina (P = 0.01). Cortisol levels were no different in those with or without peripheral vascular disease. CONCLUSION: A single measurement of circulating cortisol is a poor predictor of vascular disease. More detailed characterization of the HPA axis is necessary to determine the role of circulating endogenous glucocorticoids and their responsiveness to stress in atherosclerosis.

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts

Peripheral arterial disease and cognitive function.

As a marker of generalized atherosclerosis, peripheral arterial disease (PAD) has implications not only for the affected lower extremity but also to overall cardiovascular health. It confers an increased risk of non-fatal and fatal vascular events which increases with the severity of the disease. Patient-based studies have shown that individuals with advanced PAD tend to perform poorly on cognitive tests compared to controls. In population studies, PAD is associated with an increased cognitive decline independently of previous cerebrovascular disease and cardiovascular risk factors. A low ankle-brachial index (ABI) may be an early predictor of cognitive decline and of potential value in identifying individuals at increased risk of cognitive impairment. In patients with PAD, secondary preventive measures directed at decreasing the long-term systemic vascular complications may also be important to the preservation of cognitive health. However, evidence suggests that PAD patients may be undertreated with regard to atherosclerotic risk factors, as demonstrated by an undue emphasis on symptom relief rather than essential risk factor reduction. More research needs to be carried out to determine the predictors of cognitive function in PAD patients, whether subtle cognitive disturbances are related to activities of daily living, including medical treatment compliance, and whether neuroprotective strategies and atherosclerotic risk factor control positively influence cognitive function in these high-risk patients.

Telangiectasia in the Edinburgh Vein Study: epidemiology and association with trunk varices and symptoms.

OBJECTIVE: Little research has been devoted to telangiectasia. The purpose of this study was to analyse the data in the Edinburgh Vein Study to determine the prevalence of telangiectasia in the general population, to analyse the demographic characteristics and association with symptoms and to compare the findings to those relating to varices of the saphenous systems. DESIGN: Cross-sectional population study. SETTING: Twelve general practices with catchment areas geographically and socioeconomically distributed throughout Edinburgh. PARTICIPANTS: An age stratified random sample of 1566 people (699 men and 867 women) aged 16-64 selected from computerised age-sex registers of participating practices. METHODS: Included in the population screening was a clinical examination, photography and duplex ultrasonography of the superficial veins and the deep veins down to popliteal level. Telangiectases and varicose veins were graded 1-3 according to severity. RESULTS: A total of 1322 (84%) of the population were classified as having telangiectasias in their right legs; 555 (79%) of men and 767 (88%) of women; 1226 (92%) as grade 1 and 96 (8%) as grades 2 and 3. There were no significant differences between left and right legs (p=0.144). The commonest locations for telangiectases were the postero-medial aspects of the thigh, popliteal fossa and upper one third of calf. There was a highly significant association between the degree of severity of varicose veins and the grade of telangiectasia (p<0.001). Less than 1% of subjects with grades 2-3 trunk varices were free of telangiectasia, but 51% of subjects with grades 2-3 telangiectasia had no clinical evidence of varicose veins. There was a significant linear trend in the proportion of subjects reporting heaviness, swelling, aching and cramps being highest among those with neither telangiectasia nor varicose veins, lower in those with telangiectasia or varicose veins only and lowest in subjects having both. The highest frequency of most symptoms was found in subjects with both telangiectasia and varicose veins. CONCLUSIONS: Telangiectasia is so common in the general population, especially in women, as to represent the norm. The anatomical distribution is entirely different from the distribution of the skin and subcutaneous manifestations of chronic venous insufficiency. Our confirmation of a strong association between trunk varices and grades 2-3 telangiectasia suggests the need for controlled studies into which condition should be treated. We found no evidence that telangiectasia per se was entirely responsible for leg symptoms.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Retinal microvascular abnormalities and cognitive dysfunction: a systematic review.

OBJECTIVE: To examine the evidence for an association between cognitive impairment or dementia and the presence of retinal microvascular abnormalities. METHODS: A systematic review of observational studies identified through searching five electronic databases and reference lists. Studies were required to have both a recognised cognitive function assessment (either a structured neuropsychological test or a clinical evaluation of dementia), and assessment of the retinal microvasculature (either characteristics associated with generalised retinopathy or changes specific to arterioles or venules). RESULTS: 6 studies were included. Studies were clinically and methodologically heterogeneous and of variable quality. Some degree of cognitive impairment was found to be associated with the presence of retinal microvascular abnormalities in all studies, although the extent of the association varied. The presence of retinal vascular signs was mostly associated with poorer verbal memory, mental speed and executive function in the general population, but not consistently associated with other cognitive modalities. CONCLUSIONS: There is some evidence suggesting a positive association between retinal microvascular abnormalities and cognitive impairment or dementia in elderly people and in patients with diabetes. Findings are inconclusive, and further better designed studies are required, with standardised and objective retinal vascular assessment and a range of sensitive cognitive tests.

Epidemiology of chronic venous disease.

Chronic venous disease of the legs occurs commonly in the general population in the Western world. Estimates of the prevalence of varicose veins vary widely from 2-56% in men and from 1-60% in women. These variations reflect differences in variability of study populations including age, race and gender, methods of measurement and disease definition. Definitions of chronic venous disease may rely on reports of varicose veins by study participants, based on self-diagnosis or recall of a diagnosis, or on a standardized physical examination. Venous ulceration is less common, affecting approximately 0.3% of the adult population. Age and pregnancy have been established as risk factors for developing varicose veins. Evidence on other risk factors for venous disease is inconclusive. Prolonged standing has been proposed, but results of studies should be interpreted with caution given the difficulty in measuring levels of posture. Obesity has been suggested as a risk factor in women, but appears to be an aggravating factor rather than a primary cause. Other postulated risk factors include dietary intake and smoking, but evidence is lacking. Longitudinal studies using standardized methods of evaluation are required before the true incidence of chronic venous disease and associated risk factors can be determined.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Final 12-year follow-up of surgery versus surveillance in the UK Small Aneurysm Trial.

BACKGROUND: The aim was to determine whether early open surgical repair would benefit patients with small abdominal aortic aneurysm compared with surveillance on long-term follow-up. METHODS: The 1090 patients who were enrolled into the UK Small Aneurysm Trial between 1991 and 1995 were followed up for aneurysm repair and mortality until November 2005. RESULTS: By November 2005, 714 patients (65.5 per cent) had died, 929 (85.2 per cent) had undergone aneurysm repair, 150 (13.8 per cent) had died without aneurysm repair and 11 (1.0 per cent) remained alive without aneurysm repair. After 12 years, mortality in the surgery and surveillance groups was 63.9 and 67.3 per cent respectively, unadjusted hazard ratio 0.90 (P = 0.139). Three-quarters of the surveillance group eventually had aneurysm repair, with a 30-day elective mortality of 6.3 per cent (versus 5.0 per cent in the early surgery group, P = 0.366). Estimates suggested that the cost of treatment was 17 per cent higher in the early surgery group, with a mean difference of 1326 pounds. The death rate in these patients was about twice that in the population matched for age and sex. CONCLUSION: There was no long-term survival benefit of early elective open repair of small abdominal aortic aneurysms. Even after successful aneurysm repair, the mortality among these patients was higher than in the general population.