Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on peripheral artery disease have emerged, ...enabling us to provide updated estimates of the prevalence and risk factors for peripheral artery disease globally and regionally and, for the first time, nationally.
For this systematic review and analysis, we did a comprehensive literature search for studies reporting on the prevalence of peripheral artery disease in the general population that were published between Jan 1, 2011, and April 30, 2019, in PubMed, MEDLINE, Embase, the Global Health database, CINAHL, the Global Health Library, the Allied and Complementary Medicine Database, and ProQuest Dissertations and Theses Global. We also included the Global Peripheral Artery Disease Study of 2013 and the China Peripheral Artery Disease Study as sources. Peripheral artery disease had to be defined as an ankle–brachial index lower than or equal to 0·90. With a purpose-built data collection form, data on study characteristics, sample characteristics, prevalence, and risk factors were abstracted from all the included studies identified from the sources. Age-specific and sex-specific prevalence of peripheral artery disease was estimated in both high-income countries (HICs) and low-income and middle-income countries (LMICs). We also did random-effects meta-analyses to pool the odds ratios of 30 risk factors for peripheral artery disease in HICs and LMICs. UN population data were used to generate the number of people affected by the disease in 2015. Finally, we derived the regional and national numbers of people with peripheral artery disease on the basis of a risk factor-based model.
We included 118 articles for systematic review and analysis. The prevalence of peripheral artery disease increased consistently with age. At younger ages, prevalence was slightly higher in LMICs than HICs (4·32%, 95% CI 3·01–6·29, vs 3·54%, 1·17–10·24, at 40–44 years), but the increase with age was greater in HICs than LMICs, leading to a higher prevalence in HICs than LMICs at older ages (21·24%, 15·22–28·90, vs 12·04%, 8·67–16·60, at 80–84 years). In HICs, prevalence was slightly higher in women than in men up to age 75 years (eg, 7·81%, 3·97–14·77, vs 6·60%, 3·74–11·38, at 55–59 years), whereas in LMICs little difference was found between women and men (eg, 6·40%, 5·06–8·05, vs 6·37%, 4·74–8·49, at 55–59 years). Overall, the global prevalence of peripheral artery disease in people aged 25 years and older was 5·56%, 3·79–8·55, and the prevalence estimate was higher in HICs than that in LMICs (7·37%, 4·35–13·66, vs 5·09%, 3·64–7·24). Smoking, diabetes, hypertension, and hypercholesterolaemia were major risk factors for peripheral artery disease. Globally, a total of 236·62 million people aged 25 years and older were living with peripheral artery disease in 2015, among whom 72·91% were in LMICs. The Western Pacific Region had the most peripheral artery disease cases (74·08 million), whereas the Eastern Mediterranean Region had the least (14·67 million). More than two thirds of the global peripheral artery disease cases were concentrated in 15 individual countries in 2015.
Peripheral artery disease continues to become an increasingly serious public health problem, especially in LMICs. With the demographic trend towards ageing and projected rise in important risk factors, a larger burden of peripheral artery disease is to be expected in the foreseeable future.
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Estimation of the epidemiological burden of carotid atherosclerosis can serve as a basis for prevention and management of cardiovascular disease. We aimed to provide the first estimation on the ...prevalence, number of cases, and risk factors for carotid atherosclerosis in the general population globally and regionally.
In this systematic review, meta-analysis, and modelling study, we searched PubMed, MEDLINE, Embase, Global Health, and China National Knowledge Infrastructure for articles published from database inception until May 7, 2019, with no language restrictions, for population-based studies that quantified prevalence of carotid atherosclerosis by means of increased carotid intima-media thickness, carotid plaque, and carotid stenosis. Studies were eligible if they included bilaterally scanned carotid arteries using ultrasonography and defined increased carotid intima-media thickness as a thickness of 1·0 mm or more, carotid plaque as a focal carotid intima-media thickness of 1·5 mm or more encroaching into the lumen or at least 0·5 mm or 50% compared with the surrounding carotid intima-media thickness values, and carotid stenosis as 50% or more stenosis. Studies were excluded if the sample was not representative of the general population. We also included studies identified in our previous systematic review and meta-analysis of the prevalence of carotid atherosclerosis in China. We estimated age-specific and sex-specific prevalences of increased carotid intima-media thickness, carotid plaque, and carotid stenosis. We used UN population data to generate the number of people affected in 2000, 2015, and 2020. We did random-effects meta-analyses to assess the effects of risk factors for increased carotid intima-media thickness and carotid plaque. We derived regional numbers of people living with increased carotid intima-media thickness and carotid plaque in 2015 using a risk factors-based model by WHO region. All analyses were done in populations aged 30–79 years due to availability of data. This systematic review and meta-analysis is registered online on PROSPERO, CRD42019134709.
We identified 8632 articles through our database search, of which 515 were eligible for full-text review, including 37 articles from our previous study, and 59 articles were eligible for inclusion in our systematic review and meta-analysis. Overall, in people aged 30–79 years in 2020, the global prevalence of increased carotid intima-media thickness is estimated to be 27·6% (95% CI 16·9–41·3), equivalent to 1066·70 million affected people and a percentage change of 57·46% from 2000; of carotid plaque is estimated to be 21·1% (13·2–31·5), equivalent to 815·76 million affected people and a percentage change of 58·97% from 2000; and carotid stenosis is estimated to be 1·5% (1·1–2·1), equivalent to 57·79 million affected people and a percentage change of 59·13% from 2000. The prevalence of increased carotid intima-media thickness, carotid plaque, and carotid stenosis increased consistently with age and was higher in men than in women. Current smoking, diabetes, and hypertension were common risk factors for increased carotid intima-media thickness and carotid plaque. In 2015, the Western Pacific region had the largest share of global cases of increased carotid intima-media thickness (317·62 million 33·36% of 952·13 million affected people) and carotid plaque (240·77 million 33·20% of 725·25 million), whereas the African region had the smallest share of cases of increased carotid intima-media thickness (59·08 million 6·21%) and the Eastern Mediterranean region had the smallest share of carotid plaque cases (44·59 million 6·15%).
A substantial global burden of carotid atherosclerosis exists. Effective strategies are needed for primary prevention and management of carotid atherosclerosis. High-quality epidemiological investigations on carotid atherosclerosis are needed to better address the global burden of carotid atherosclerosis at finer levels.
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Summary Background Lower extremity peripheral artery disease is the third leading cause of atherosclerotic cardiovascular morbidity, following coronary artery disease and stroke. This study provides ...the first comparison of the prevalence of peripheral artery disease between high-income countries (HIC) and low-income or middle-income countries (LMIC), establishes the primary risk factors for peripheral artery disease in these settings, and estimates the number of people living with peripheral artery disease regionally and globally. Methods We did a systematic review of the literature on the prevalence of peripheral artery disease in which we searched for community-based studies since 1997 that defined peripheral artery disease as an ankle brachial index (ABI) lower than or equal to 0·90. We used epidemiological modelling to define age-specific and sex-specific prevalence rates in HIC and in LMIC and combined them with UN population numbers for 2000 and 2010 to estimate the global prevalence of peripheral artery disease. Within a subset of studies, we did meta-analyses of odds ratios (ORs) associated with 15 putative risk factors for peripheral artery disease to estimate their effect size in HIC and LMIC. We then used the risk factors to predict peripheral artery disease numbers in eight WHO regions (three HIC and five LMIC). Findings 34 studies satisfied the inclusion criteria, 22 from HIC and 12 from LMIC, including 112 027 participants, of which 9347 had peripheral artery disease. Sex-specific prevalence rates increased with age and were broadly similar in HIC and LMIC and in men and women. The prevalence in HIC at age 45–49 years was 5·28% (95% CI 3·38–8·17%) in women and 5·41% (3·41–8·49%) in men, and at age 85–89 years, it was 18·38% (11·16–28·76%) in women and 18·83% (12·03–28·25%) in men. Prevalence in men was lower in LMIC than in HIC (2·89% 2·04–4·07% at 45–49 years and 14·94% 9·58–22·56% at 85–89 years). In LMIC, rates were higher in women than in men, especially at younger ages (6·31% 4·86–8·15% of women aged 45–49 years). Smoking was an important risk factor in both HIC and LMIC, with meta-OR for current smoking of 2·72 (95% CI 2·39–3·09) in HIC and 1·42 (1·25–1·62) in LMIC, followed by diabetes (1·88 1·66–2·14 vs 1·47 1·29–1·68), hypertension (1·55 1·42–1·71 vs 1·36 1·24–1·50), and hypercholesterolaemia (1·19 1·07–1·33 vs 1·14 1·03–1·25). Globally, 202 million people were living with peripheral artery disease in 2010, 69·7% of them in LMIC, including 54·8 million in southeast Asia and 45·9 million in the western Pacific Region. During the preceding decade the number of individuals with peripheral artery disease increased by 28·7% in LMIC and 13·1% in HIC. Interpretation In the 21st century, peripheral artery disease has become a global problem. Governments, non-governmental organisations, and the private sector in LMIC need to address the social and economic consequences, and assess the best strategies for optimum treatment and prevention of this disease. Funding Peripheral Arterial Disease Research Coalition (Europe).
Summary Background Treatment with daily aspirin for 5 years or longer reduces subsequent risk of colorectal cancer. Several lines of evidence suggest that aspirin might also reduce risk of other ...cancers, particularly of the gastrointestinal tract, but proof in man is lacking. We studied deaths due to cancer during and after randomised trials of daily aspirin versus control done originally for prevention of vascular events. Methods We used individual patient data from all randomised trials of daily aspirin versus no aspirin with mean duration of scheduled trial treatment of 4 years or longer to determine the effect of allocation to aspirin on risk of cancer death in relation to scheduled duration of trial treatment for gastrointestinal and non-gastrointestinal cancers. In three large UK trials, long-term post-trial follow-up of individual patients was obtained from death certificates and cancer registries. Results In eight eligible trials (25 570 patients, 674 cancer deaths), allocation to aspirin reduced death due to cancer (pooled odds ratio OR 0·79, 95% CI 0·68–0·92, p=0·003). On analysis of individual patient data, which were available from seven trials (23 535 patients, 657 cancer deaths), benefit was apparent only after 5 years' follow-up (all cancers, hazard ratio HR 0·66, 0·50–0·87; gastrointestinal cancers, 0·46, 0·27–0·77; both p=0·003). The 20-year risk of cancer death (1634 deaths in 12 659 patients in three trials) remained lower in the aspirin groups than in the control groups (all solid cancers, HR 0·80, 0·72–0·88, p<0·0001; gastrointestinal cancers, 0·65, 0·54–0·78, p<0·0001), and benefit increased (interaction p=0·01) with scheduled duration of trial treatment (≥7·5 years: all solid cancers, 0·69, 0·54–0·88, p=0·003; gastrointestinal cancers, 0·41, 0·26–0·66, p=0·0001). The latent period before an effect on deaths was about 5 years for oesophageal, pancreatic, brain, and lung cancer, but was more delayed for stomach, colorectal, and prostate cancer. For lung and oesophageal cancer, benefit was confined to adenocarcinomas, and the overall effect on 20-year risk of cancer death was greatest for adenocarcinomas (HR 0·66, 0·56–0·77, p<0·0001). Benefit was unrelated to aspirin dose (75 mg upwards), sex, or smoking, but increased with age—the absolute reduction in 20-year risk of cancer death reaching 7·08% (2·42–11·74) at age 65 years and older. Interpretation Daily aspirin reduced deaths due to several common cancers during and after the trials. Benefit increased with duration of treatment and was consistent across the different study populations. These findings have implications for guidelines on use of aspirin and for understanding of carcinogenesis and its susceptibility to drug intervention. Funding None.
Summary Background Daily aspirin reduces the long-term risk of death due to cancer. However, the short-term effect is less certain, especially in women, effects on cancer incidence are largely ...unknown, and the time course of risk and benefit in primary prevention is unclear. We studied cancer deaths in all trials of daily aspirin versus control and the time course of effects of low-dose aspirin on cancer incidence and other outcomes in trials in primary prevention. Methods We studied individual patient data from randomised trials of daily aspirin versus no aspirin in prevention of vascular events. Death due to cancer, all non-vascular death, vascular death, and all deaths were assessed in all eligible trials. In trials of low-dose aspirin in primary prevention, we also established the time course of effects on incident cancer, major vascular events, and major extracranial bleeds, with stratification by age, sex, and smoking status. Results Allocation to aspirin reduced cancer deaths (562 vs 664 deaths; odds ratio OR 0·85, 95% CI 0·76–0·96, p=0·008; 34 trials, 69 224 participants), particularly from 5 years onwards (92 vs 145; OR 0·63, 95% CI 0·49–0·82, p=0·0005), resulting in fewer non-vascular deaths overall (1021 vs 1173; OR 0·88, 95% CI 0·78–0·96, p=0·003; 51 trials, 77 549 participants). In trials in primary prevention, the reduction in non-vascular deaths accounted for 87 (91%) of 96 deaths prevented. In six trials of daily low-dose aspirin in primary prevention (35 535 participants), aspirin reduced cancer incidence from 3 years onwards (324 vs 421 cases; OR 0·76, 95% CI 0·66–0·88, p=0·0003) in women (132 vs 176; OR 0·75, 95% CI 0·59–0·94, p=0·01) and in men (192 vs 245; OR 0·77, 95% CI 0·63–0·93, p=0·008). The reduced risk of major vascular events on aspirin was initially offset by an increased risk of major bleeding, but effects on both outcomes diminished with increasing follow-up, leaving only the reduced risk of cancer (absolute reduction 3·13 95% CI 1·44–4·82 per 1000 patients per year) from 3 years onwards. Case-fatality from major extracranial bleeds was also lower on aspirin than on control (8/203 vs 15/132; OR 0·32, 95% CI 0·12–0·83, p=0·009). Interpretation Alongside the previously reported reduction by aspirin of the long-term risk of cancer death, the short-term reductions in cancer incidence and mortality and the decrease in risk of major extracranial bleeds with extended use, and their low case-fatality, add to the case for daily aspirin in prevention of cancer. Funding None.
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.
CONTEXT A low ankle brachial index (ABI) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events. Screening for a low ABI can identify an asymptomatic higher risk ...group potentially amenable to preventive treatments. OBJECTIVE To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population. DESIGN, SETTING, AND PARTICIPANTS The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind randomized controlled trial conducted from April 1998 to October 2008, involving 28 980 men and women aged 50 to 75 years living in central Scotland, free of clinical cardiovascular disease, recruited from a community health registry, and had an ABI screening test. Of those, 3350 with a low ABI (≤0.95) were entered into the trial, which was powered to detect a 25% proportional risk reduction in events. INTERVENTIONS Once daily 100 mg aspirin (enteric coated) or placebo. MAIN OUTCOME MEASURES The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization. Two secondary end points were (1) all initial vascular events defined as a composite of a primary end point event or angina, intermittent claudication, or transient ischemic attack; and (2) all-cause mortality. RESULTS After a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1000 person-years, 95% confidence interval CI, 12.2-15.0). No statistically significant difference was found between groups (13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group; hazard ratio HR, 1.03; 95% CI, 0.84-1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1000 person-years; 95% CI, 21.0-24.8) and no statistically significant difference between groups (22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group; HR, 1.00; 95% CI, 0.85-1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77-1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1000 person-years) in the aspirin group and 20 (1.5 per 1000 person-years) in the placebo group (HR, 1.71; 95% CI, 0.99-2.97). CONCLUSION Among participants without clinical cardiovascular disease, identified with a low ABI based on screening a general population, the administration of aspirin compared with placebo did not result in a significant reduction in vascular events. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN66587262
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.
OBJECTIVES: To determine whether circulating markers of activated inflammation and hemostasis are associated with cognitive decline in older people.
DESIGN: Prospective cohort study (Edinburgh Artery ...Study).
SETTING: Eleven general practices in Edinburgh, Scotland.
PARTICIPANTS: A sample of 452 men and women followed for 16 years.
MEASUREMENTS: Biomarker data were collected in 1987/88, and cognitive assessment was first conducted in 1998/99, when the mean age of the sample ± standard deviation was 73.1±5.0), and subsequently in 2002/03. Information was obtained on verbal declarative memory (Wechsler Logical Memory Test (LMT)), nonverbal reasoning (Raven's Standard Progressive Matrices), verbal fluency (Verbal Fluency Test), information processing speed (Wechsler Digit Symbol Test), and a general cognitive factor representing the variance common to the individual test scores.
RESULTS: In age‐adjusted analyses, plasma fibrinogen, interleukin‐6 (IL‐6), and intercellular adhesion molecule 1 (ICAM‐1) were negatively associated with performance on all cognitive measures in 2002/03 except the LMT (correlation coefficients from −0.10 to −0.24). In multivariate analyses controlling for demographic characteristics, depression, and cardiovascular morbidity and risk factors, fibrinogen independently predicted 4‐year decline in nonverbal reasoning (P<.05). Also, when cognitive change was estimated from peak prior level, IL‐6 turned out to be inversely related to decline in information processing speed (P<.05). Similarly, ICAM‐1 was associated with a greater decline in general cognitive ability (P<.05) and nonverbal ability (P<.05).
CONCLUSION: Systemic markers of inflammation and hemostasis are associated with a progressive decline in general and specific cognitive abilities in older people, independent of major vascular comorbidity.
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.
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%.
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.
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