Epidemiology of major lower limb amputation using routinely collected electronic health data in the UK: a systematic review protocol.

INTRODUCTION: It is estimated that peripheral arterial disease occurs in one in five people aged over 60 years in the UK. Major lower limb amputation is a debilitating and life-changing potential outcome of peripheral arterial disease. A number of risk factors are involved in the development of the disease including smoking and diabetes. There is debate over the prevalence of major lower limb amputation in the UK with regional variations unexplained. The choice of data source can affect the epidemiological calculations and sources can also differ in the ability to explain variation. This study will aim to estimate the prevalence/incidence/number of major lower limb amputation in the UK. It will also identify sources of routinely collected electronic health data which report the epidemiology of major lower limb amputation in the UK. METHODS AND ANALYSIS: A systematic search of peer-reviewed journals will be conducted in Medline, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature, Allied and Complementary Medicine Database, The Cochrane Library and Scopus. A grey literature search for government and parliament publications, conference abstracts, theses and unpublished articles will be performed. Articles will be screened against the inclusion/exclusion criteria and data extracted using a pretested extraction form by two independent reviewers. Prevalence, incidence or number of cases (depending on data reported) will be extracted. Disagreements will be resolved by discussion. Data synthesis will be performed either as a narrative summary or by meta-analysis. Heterogeneity will be assessed using the I2 statistic. If heterogeneity is low-moderate, pooled estimates will be calculated using random-effects models. If possible, meta-regression for time trends in the incidence of major lower limb amputation will be performed along with subgroup analysis, primarily in regional variation. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as study data are anonymised and available in the public domain. Dissemination will be by publication in a peer reviewed journal and by appropriate conference presentation.PROSPERO registration numberCRD42020165592.

Changes in co-morbidity pattern in patients starting renal replacement therapy in Europe-data from the ERA-EDTA Registry.

Background: Patients starting renal replacement therapy (RRT) for end-stage renal disease often present with one or more co-morbidities. This study explored the prevalence of co-morbidities in patients who started RRT in Europe during the period from 2005 to 2014. Methods: Using data from patients aged 20 years or older from all 11 national or regional registries providing co-morbidity data to the European Renal Association - European Dialysis and Transplant Association Registry, we examined the prevalence of the following co-morbidities: diabetes mellitus (DM) (primary renal disease and/or co-morbidity), ischaemic heart disease (IHD), congestive heart failure (CHF), peripheral vascular disease (PVD), cerebrovascular disease (CVD) and malignancy. Results: Overall, 70% of 7578 patients who initiated RRT in 2014 presented with at least one co-morbidity: 39.0% presented with DM, 25.0% with IHD, 22.3% with CHF, 17.7% with PVD, 16.4% with malignancy and 15.5% with CVD. These percentages differed substantially between countries. Co-morbidities were more common in men than in women, in older patients than in younger patients, and in patients on haemodialysis at Day 91 when compared with patients on peritoneal dialysis. Between 2005 and 2014 the prevalence of DM and malignancy increased over time, whereas the prevalence of IHD and PVD declined. Conclusions: More than two-thirds of patients initiating RRT in Europe have at least one co-morbidity. With the rising age at the start of RRT over the last decade, there have been changes in the co-morbidity pattern: the prevalence of cardiovascular co-morbidities decreased, while the prevalence of DM and malignancy increased.

Serum phosphorus levels and the spectrum of ankle-brachial index in older men: the Osteoporotic Fractures in Men (MrOS) study.

A higher serum phosphorus level is associated with cardiovascular disease (CVD) events among community-living populations. Mechanisms are unknown. The ankle-brachial index (ABI) provides information on both atherosclerosis and arterial stiffness. In this cross-sectional study (2000-2002), the authors evaluated the association of serum phosphorus levels with low (<0.90) and high (> or =1.40 or incompressible) ABI as compared with intermediate ABI in 5,330 older US men, among whom the mean serum phosphorus level was 3.2 mg/dL (standard deviation, 0.4), 6% had a low ABI, and 5% had a high ABI. Each 1-mg/dL increase in serum phosphorus level was associated with a 1.6-fold greater prevalence of low ABI (95% confidence interval (CI): 1.2, 2.1; P < 0.001) and a 1.4-fold greater prevalence of high ABI (95% CI: 1.0, 1.9; P = 0.03) in models adjusted for demographic factors, traditional CVD risk factors, and kidney function. However, the association of phosphorus with high ABI differed by chronic kidney disease (CKD) status (in persons with CKD, prevalence ratio = 2.96, 95% CI: 1.61, 5.45; in persons without CKD, prevalence ratio = 1.14, 95% CI: 0.81, 1.61; interaction P = 0.04). In conclusion, among community-living older men, higher phosphorus levels are associated with low ABI and are also associated with high ABI in persons with CKD. These associations may explain the link between serum phosphorus levels and CVD events.

Peripheral arterial disease in women.

Peripheral arterial disease (PAD) is chronic arterial occlusive disease of the lower extremities caused by atherosclerosis whose prevalence increases with age. Only one-half of women with PAD are symptomatic. Symptomatic and asymptomatic women with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Modifiable risk factors that predispose women to PAD include active cigarette smoking, passive smoking, diabetes mellitus, hypertension, dyslipidemia, increased plasma homocysteine levels and hypothyroidism. With regard to management, women who smoke should be encouraged to quit and referred to a smoking cessation program. Hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism require treatment. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in women with PAD and hypercholesterolemia. Anti-platelet drugs such as aspirin or especially clopidogrel, angiotensin-converting enzyme inhibitors and statins should be given to all women with PAD. Beta blockers are recommended if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided as it is ineffective. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery in women are (1) incapacitating claudication interfering with work or lifestyle; and (2) limb salvage in women with limb-threatening ischemia as manifested by rest pain, non-healing ulcers, and/or infection or gangrene. Future research includes investigation of mechanisms underlying why women have a higher risk of graft failure and major amputation.

Breast arterial calcification is a predictive factor of cardiovascular disease in Brazilian postmenopausal women.

OBJECTIVE: The objectives of this study were to evaluate the association between cardiovascular disease (CVD) and breast arterial calcification (BAC), as well as the prevalence rates of these conditions in Brazilian postmenopausal women. METHODS: A cross-sectional study was performed in 307 women over 40 years of age who were receiving care at the gynecology clinic of the Center for Women's Integrated Healthcare (CAISM), ABC School of Medicine. All these women had been amenorrheic for at least 12 months and had undergone mammography in the preceding 12 months. Cardiovascular disease and its subtypes were evaluated, as well as its association with BAC. Means and standard deviations, absolute frequencies and percentages were calculated, and univariate analysis and multiple logistic regression were performed. RESULTS: The mean age of the patients was 55.2 +/- 6.8 years; age at menopause was 48.5 +/- 4 years. Time since menopause was 80.2 +/- 75.4 months; 96.1% of the patients were non-smokers and 46.3% were using hormone therapy. Of the patients, 33.6% had systemic arterial hypertension, 4.9% had diabetes mellitus and 5.2% had hypercholesterolemia. The mean body mass index was 27.3 +/- 4.3 kg/m(2). CVD was found in 6.8% and BAC in 8.5% of the women. Significantly more women with BAC had CVD compared to the women who did not have this condition (23.1% vs. 5.3%, p = 0.0006). BAC was associated with an odds ratio of 8.13 (95% confidence interval 2.68-24.64) for predicting CVD. CONCLUSIONS: In postmenopausal women, breast arterial calcification may represent a higher likelihood of cardiovascular disease.

Serum selenium and peripheral arterial disease: results from the national health and nutrition examination survey, 2003-2004.

The authors conducted a cross-sectional study of the association of serum selenium with the prevalence of peripheral arterial disease among 2,062 US men and women 40 years of age or older participating in the National Health and Nutrition Examination Survey, 2003-2004. Serum selenium was measured by using inductively coupled plasma-dynamic reaction cell-mass spectrometry. Peripheral arterial disease was defined as an ankle-brachial blood pressure index <0.90. The age-, sex-, and race-adjusted prevalence of peripheral arterial disease decreased with increasing serum selenium (P for linear trend = 0.02), but there was an indication of an upturn in risk in the highest quartile of serum selenium. The fully adjusted odds ratios for peripheral arterial disease comparing selenium quartiles 2, 3, and 4 with the lowest quartile were 0.75 (95% confidence interval: 0.37, 1.52), 0.58 (95% confidence interval: 0.28, 1.19), and 0.67 (95% confidence interval: 0.34, 1.31), respectively. In spline regression models, peripheral arterial disease prevalence decreased with increasing serum selenium levels up to 150-160 ng/mL, followed by a gradual increase at higher selenium levels. The association between serum selenium levels and the prevalence of peripheral arterial disease was not statistically significant, although a U-shaped relation was suggested.

Nutrition impacts the prevalence of peripheral arterial disease in the United States.

OBJECTIVE: Traditional recommendations for peripheral arterial disease (PAD) risk factor reduction include smoking cessation, low-fat/low-salt diet, exercise, and optimal medical management of chronic disease. Little attention has been paid to the role of dietary supplementation of specific nutrients in the prevention of PAD. METHODS: This cross-sectional study used the National Health and Nutrition Examination Survey (NHANES) to determine specific nutrients that are associated with prevalent PAD in the United States (US) population. NHANES data include nationwide sampling of the US population, using physical examination, questionnaire, and laboratory testing. PAD status was defined by an ankle-brachial index (ABI) of <0.9. Nutritional information was collected by 24-hour dietary recall using the US Department of Agriculture dietary collection instrument. Data were linked to a database of foods and their nutrient composition. Univariate and multivariate logistic regression analyses were performed to evaluate associations between specific nutrient intake and the presence of PAD. Multivariate models adjusted for the effects of age, gender, hypertension, coronary vascular disease, diabetes, and smoking. RESULTS: NHANES data for 1999 to 2004 included 7203 lower extremity examinations, of which 422 individuals had prevalent PAD (5.9%). Examinees with PAD had significantly higher rates of hypertension, coronary artery disease, diabetes, and smoking than those without PAD. Univariate analysis revealed that consumption of all nutrients considered were associated with lower odds of PAD, including antioxidants (vitamins A, C, and E), folate, other B vitamins (B(6), B(12)), fiber, and polyunsaturated and saturated fatty acids. After adjustment for traditional risk factors, nutrients associated with reduced prevalence of PAD were vitamin A (odds ratio [OR], 0.79; P = .036), vitamin C (OR, 0.84; P < .001), vitamin E (OR, 0.78; P = .011), vitamin B(6) (OR, 0.71; P = .023), fiber (OR, 0.65; P < .001), folate (OR, 0.67; P = .006), and omega-3 (alpha-linolenic) fatty acid (OR, 0.79; P = .028). CONCLUSIONS: Improved nutrition is associated with a reduced prevalence of PAD in the US population. Higher consumption of specific nutrients, including antioxidants (vitamin A, C, and E), vitamin B(6), fiber, folate, and omega-3 fatty acids have a significant protective effect, irrespective of traditional cardiovascular risk factors. These findings suggest specific dietary supplementation may afford additional protection, above traditional risk factor modification, for the prevention of PAD.

Clinical, cellular, and molecular aspects of arterial calcification.

Arterial calcification is a complex and independently regulated process with risk factors similar to those for atherosclerotic occlusive disease. It may develop either within the atherosclerotic intima or in the media. When calcification is found in coronary or lower extremity arteries, it is an independent predictor of cardiovascular events and lower extremity amputation. Recent evidence suggests a role for several endogenous stimulators and inhibitors in the pathogenesis of arterial calcification. Inflammatory mediators and matrix-degrading enzymes are also thought to control the progression of calcification in humans. Current research involves efforts to define the complex interactions between cellular and molecular mediators of arterial calcification.

Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons.

Pre-clinical studies suggest that both omega-6 and omega-3 fatty acids have beneficial effects on peripheral nerve function. Rats feed a diet rich in polyunsaturated fatty acids (PUFAs) showed modification of phospholipid fatty acid composition in nerve membranes and improvement of sciatic nerve conduction velocity (NCV). We tested the hypothesis that baseline plasma omega-6 and omega-3 fatty acids levels predict accelerated decline of peripheral nerve function. Changes between baseline and the 3-year follow-up in peripheral nerve function was assessed by standard surface ENG of the right peroneal nerve in 384 male and 443 female participants of the InCHIANTI study (age range: 24-97 years). Plasma concentrations of selected fatty acids assessed at baseline by gas chromatography. Independent of confounders, plasma omega-6 fatty acids and linoleic acid were significantly correlated with peroneal NCV at enrollment. Lower plasma PUFA, omega-6 fatty acids, linoleic acid, ratio omega-6/omega-3, arachidonic acid and docosahexanoic acid levels were significantly predicted a steeper decline in nerve function parameters over the 3-year follow-up. Low plasma omega-6 and omega-3 fatty acids levels were associated with accelerated decline of peripheral nerve function with aging.

Unsupervised walking therapy and atherosclerotic risk-factor management for patients with peripheral arterial disease: a pilot trial.

BACKGROUND: Although only a small percentage of patients with peripheral arterial disease (PAD) have claudication, many more suffer from atypical leg symptoms. PURPOSE: This pilot trial evaluated a risk-factor modification program to improve walking ability in patients with PAD and leg symptoms other than intermittent claudication. METHODS: Patients 18 years or older with an ankle-brachial index (ABI) of 0.50 to 0.89 completed a baseline assessment of current walking ability, physical activity level, health-related quality of life, glycosylated hemoglobin values, and fasting lipid profiles. Patients were randomized to usual care (control group) versus usual care plus an educational intervention on risk-factor management (intervention group). We compared functional outcomes between and within groups using the Student's t test and control and intervention group outcomes at 12 weeks using analysis of covariance with the baseline value as the covariate. RESULTS: We randomized 50 patients into two treatment arms. There was no difference in the mean age of patients in each group. At baseline, mean ABI for the control versus the intervention group was 0.72 (SD = 0.10) and 0.75 (SD = 0.10), respectively, and mean stair-climbing values did not differ between groups. At 12 weeks, mean stair-climbing values were 40.2 (SD = 30.2) for the control and 61.2 (SD = 32.8) for the intervention group. The difference in adjusted mean walking distance between groups at 12 weeks was not significant. Analysis of covariance associated assignment to the intervention versus the control arm with a significant increase at 12 weeks in the ABI (p = .008) and stair-climbing ability (p = .02). CONCLUSIONS: Patients in the intervention group improved objective measures of blood flow and reported stair-climbing ability.

Peripheral arterial disease in the elderly.

Smoking should be stopped and hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism treated in elderly patients with peripheral arterial disease (PAD) of the lower extremities. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in patients with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, angiotensin-converting enzyme inhibitors, and statins should be given to all elderly patients with PAD without contraindications to these drugs. Beta blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery are (1) incapacitating claudication in patients interfering with work or lifestyle; (2) limb salvage in patients with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and (3) vasculogenic impotence.

Peripheral arterial disease: a high risk - but neglected - disease population.

Peripheral arterial disease (PAD) is a common, progressive manifestation of atherothrombotic vascular disease, which should be managed no different to cardiac disease. Indeed, there is growing evidence that PAD patients are a high risk group, although still relatively under-detected and under treated. This is despite the fact that PAD patients are an increased mortality rate comparable to those with pre-existing or established cardiovascular disease [myocardial infarction, stroke]. With a holistic approach to atherothrombotic vascular disease, our management of PAD can only get better.

Determination of urinary trace elements (arsenic, copper, cadmium, manganese, lead, zinc, selenium) in patients with Blackfoot disease.

To determine the relationship of arsenic, copper, cadmium, manganese, lead, zinc and selenium to Blackfoot disease (BFD, a peripheral vascular disorder endemic to areas of Taiwan, which has been linked to arsenic in drinking water) the authors measured the amount of these substances in urine from BFD patients, using atomic absorption spectrometry. Results indicate significantly higher amounts of urinary arsenic, copper, cadmium, manganese, and lead for BFD patients than for normal controls, also significantly lower urinary zinc and selenium.

A high-score Mediterranean dietary pattern is associated with a reduced risk of peripheral arterial disease in Italian patients with Type 2 diabetes.

BACKGROUND: The 'Mediterranean diet' is considered to exert protective effects on cardiovascular disease, although a wide range of dietary patterns exists among subjects living even in the same Mediterranean country. OBJECTIVE: To investigate the association between specific dietary patterns and peripheral arterial disease (PAD) in Italian Type 2 diabetes patients. DESIGN: From a cohort of 944 patients with Type 2 diabetes, 144 patients with PAD were selected, and matched for age and sex with 288 Type 2 diabetic control patients without macrovascular complications. A dietary score was elaborated from a semiquantitative food frequency questionnaire. The higher the final score, the healthier the eating habit. RESULTS: In multivariate analysis, a higher score was independently associated with a significant reduction in PAD risk [odds ratio (OR) = 0.44; 95% confidence interval (CI) 0.24, 0.83]. Diabetes duration (OR > 15 years = 2.49; 95% CI 1.45, 4.25), hypertension (OR = 2.12; 95% CI 1.31, 3.45) and butter consumption (OR = 2.6; 95% CI 1.15, 3.68) were also significantly associated with PAD. The dietary score significantly improved the predictive value of models based on duration of diabetes and hypertension. (LSR = 2.19, DF = 7, P < 0.001). The effect of a high dietary score on the risk of PAD was independent of diabetes duration and hypertension. CONCLUSION: In Italian Type 2 diabetics, a higher dietary score has a protective role against PAD. The use of butter increases the risk of PAD even in patients regularly consuming olive oil. Dietary advice may be helpful for the prevention of PAD in diabetics even in populations traditionally accustomed to a Mediterranean dietary habit.

Factors associated with future amputation among patients undergoing hemodialysis: results from the Dialysis Morbidity and Mortality Study Waves 3 and 4.

BACKGROUND: Amputation is more common in hemodialysis patients than in the general population, but risk factors for amputation in this population have not been studied extensively. METHODS: We used the US Renal Data System Dialysis Morbidity and Mortality Study Waves 3 and 4 in combination with Medicare discharge data to identify factors associated with lower-extremity amputation (excluding toe amputations) in hemodialysis patients. We used stepwise multivariable logistic regression analysis to identify variables most strongly associated with amputation within 2 years of the study start date. RESULTS: Male sex, diabetes, previous diagnosis of peripheral vascular disease (PVD), mean systolic blood pressure, and elevated serum phosphorus level were associated with the outcome of amputation within 2 years of the study start date. Among patients without diabetes, a previous diagnosis of cardiac disease, longer time from initiation of dialysis therapy (vintage), and previous hospitalization for limb ischemia were associated with increased risk for future amputation. CONCLUSION: The importance of preventing amputation in this population cannot be overemphasized. The strength of the association of amputation with PVD makes a strong case for screening all dialysis patients for this disease. The association of amputation with serum phosphorus level reported here should be explored further because this may offer an avenue for future intervention to reduce amputation rates.

Is erectile dysfunction predictive of peripheral vascular disease?

The association between erectile dysfunction (ED) and peripheral vascular disease (PVD) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, Health Insurance Portability and Accountability Act compliant database and includes complete medical histories for more than 17 million managed-care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 12 825 ED patients and an equal number of male patients without ED were included in the retrospective cohort study. Logistic regression analyses were performed to assess the adjusted risk of PVD that accounted for age at ED diagnosis, smoking, obesity and medications including angiotensin converting enzyme (ACE) inhibitors, beta blockers and statins. The cohort of men with ED were observed to have a 75% increase in risk for PVD (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.06, 2.90) after adjusting for age at ED diagnosis, smoking, obesity and use of ACE inhibitors, beta blockers and statins. Some evidence of a possible trend towards increased risk was detected by age group. After controlling for the aforementioned covariates and compared to men aged 30-39 years, it was noted that patients aged 40-44 years were 2.1 times more likely to develop PVD (OR = 2.07, 95% CI = 0.89, 4.81), 45-49-year-old men were also more than twice as likely to have PVD (OR = 2.32, 95% CI = 1.03, 5.22), and 50-55-year-old patients had a three-fold increased risk of developing PVD (OR = 3.00, 95% CI = 1.40, 6.43). The results of this study indicate that ED may serve as a marker for PVD. The risk becomes more pronounced with increasing age, indicating the need for cardiologists and internists to monitor ED patients who may not necessarily present with cardiovascular symptoms.

Changing patterns in the predisposition for amputation of the lower extremities.

The purpose of this study was to evaluate and determine the role of diabetes and other common predisposing factors in amputation of the lower extremities. A retrospective review of 110 patients with peripheral vascular disease who underwent amputation between 1987 and 1990 at Hahnemann University Hospital (Philadelphia, PA) was performed. Patients who underwent amputations for trauma or cancer were excluded from this analysis. The patients were divided into four groups according to the site of amputation: Above Knee (n = 43), Below Knee (n = 26), Foot (n = 7) and Transmetatarsal (n = 34). The mean age was 60 years. Fifty-five patients (51%) were white. Sixty-four patients (58%) were men. Twenty-nine patients (26%) were cigarette smokers; sixteen smokers (55%) had above-knee amputation. Thirty-five patients (32%) had previous vascular surgery of the lower extremities. The combination of diabetes and hypertension was present in 40 patients (36%). When either diabetes or hypertension alone was present in a patient, hypertension, not diabetes, was more commonly the dominant underlying medical condition in patients with amputation (32 hypertension-alone patients vs. 10 diabetes-alone patients). The high frequency of hypertension suggests that enhanced control of this disease may affect peripheral vascular disease and related amputations in the future.