Risk Of Peripheral Arterial Disease Research Articles

Screening for Peripheral Artery Disease and Cardiovascular Disease Risk Assessment With the Ankle-Brachial Index: US Preventive Services Task Force Recommendation Statement

U.S. Preventive Services Task Force (USPSTF) reviewed recent studies published between 2002 and 2018 and updated the 2013 USPSTF recommendations. The USPSTF found few data on the accuracy of the ankle-brachial index (ABI) for identifying asymptomatic persons who benefit from treatment of peripheral arterial disease (PAD) or cardiovascular disease (CVD). The USPSTF concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for PAD and CVD disease risk using the ABI in asymptomatic adults.

Abstract 17321: Long-Term Exposures to Air Pollutants and Risk of Peripheral Arterial Occlusive Disease, a Nationwide 10-Year Follow-Up Cohort Study in Taiwan

Objective: Many studies had reported the association between air pollution and cardiovascular diseases. In this current study, we aimed to evaluate the risk of long-term exposure to air pollution (PM2.5, CO and NO2) to the development of PAOD. Methods: We linked two nation-scale databases, the national health insurance database and the air quality-monitoring database of Taiwan to conduct this cohort study between 2003 and 2013. Cox proportional regression with time-dependent model was used to evaluate the hazard ratio (HR) of air pollutants to PAOD. The residential areas were divided into four categories according to the daily average concentration of air pollutants, Q1 to Q4 (Q4 = the worst). The cumulative incidence of PAOD was examined by the Kaplain-Meier analysis with log-rank test. Results: A total of 1,598 PAOD cases were identified during the follow-up period with 98,540 non-PAOD ones (demographic characteristics were showed in Table 1). In the multivariate analysis, after adjusting for age, gender, urbanization level, residential area, baseline comorbidities, and drug use, the adjusted HRs were that PM2.5 = 1.14 (95% CI 1.13-1.16), NO2 = 1.03 (95% CI 1.02-1.04), and CO = 2.35 (95% CI 1.95-2.84), respectively (Table 2). The Kaplain-Meier analysis showed that CO concentration was strongly associated with cumulative incidence rate of PAOD during the follow-up period (Figure 1). Conclusion: Besides of well-known risk factors, air pollutants may also play a potential role in PAOD pathogenesis.

51 - CSE derived sulfur metabolites regulates autophagy in ischemic endothelial cells

Background Peripheral arterial disease (PAD) causes narrowing of blood vessels resulting in restriction of blood flow to lower limbs. Recently, autophagy has progressed as an emerging therapeutic strategy targeted to minimize the risk of PAD. Autophagy is a catabolic process aimed at recycling damaged proteins and organelles. Cystathionine-γ-lyase (CSE) is a major H2S producing enzyme in the vasculature, which is vasoprotective. However, the role of CSE in regulating autophagy remains unknown. Hypothesis CSE derived sulfide metabolites protect endothelial cells from ischemic injury by inducing autophagy. Methods WT and CSE knockout mice were subjected to femoral artery ligation (FAL). Mouse aortic endothelial cells (MAECs) isolated from WT and CSE-/- mice served as in vitro model. Autophagic flux was measured with and without chloroquine (50mg/kg) and bafilomycin (50nM) in animals and cells respectively. Trypan blue assay was used to evaluate cell viability. Annexin V/ PI staining and the cleaved caspase-3 assay were used to evaluate apoptosis. Results In WT and CSE-/- mice subjected to FAL, CSE-/- mice showed defective autophagy. MAECs deficient in CSE-/- also showed impaired autophagy. Transfection with mRFP-GFP tandem fluorescent-tagged LC3 plasmid showed increased autolysosomes in WT compared to CSE-/- MAEC’s. Interestingly, re-expression of human CSE in CSE-/- endothelial cells restored autophagy. Exogenous sulfide treatment, including per/polysulfides were not able to restore autophagy in CSE-/- cells. However, lanthionine ketimine (LK), a novel sulfur metabolite of the transulfuration pathway, restored autophagy in its cell permeable ester form. Lastly, we observed that deficiency of CSE blocks autophagy leading to apoptosis in endothelial cells. Conclusion We reveal for the first time that LK, a CSE derived sulfur metabolite, could regulate autophagy in ischemic endothelial cells. These findings reveal a potential new experimental approach to protect against ischemic injury by activating autophagy during PAD.

Life's Simple 7 and Peripheral Artery Disease Risk: The Atherosclerosis Risk in Communities Study

The American Heart Association's Life's Simple 7 includes seven metrics of ideal cardiovascular health to target for cardiovascular disease prevention. This study determined the relationship between Life's Simple 7 and incident peripheral artery disease in a biracial cohort of middle- and older-aged adults. This analysis included 12,865 participants from the Atherosclerosis Risk in Communities study recruited between 1987 and 1989 (mean age=54years, 55% women, 25% black) and free of peripheral artery disease or other cardiovascular disease at baseline. Overall, Life's Simple 7 score was calculated as the sum of the Life's Simple 7 component scores (two points if ideal, one point if intermediate, and zero if poor) and classified as inadequate (zero to four), average (five to nine), or optimal (ten to 14) cardiovascular health and linked to incident peripheral artery disease identified by hospital discharge diagnosis and leg revascularization. Analysis was conducted in 2017. A total of 434 incident peripheral artery disease cases occurred over a median follow-up of 24.4years. Compared with the inadequate category (n=1,008), participants in the average (n=8,395) and optimal (n=3,462) categories each had a substantially lower risk of developing peripheral artery disease in a Cox proportional hazards model adjusted for potential confounders (hazard ratio=0.36, 95% CI=0.28, 0.46 for average, and hazard ratio=0.09, 95% CI=0.06, 0.15 for optimal). In a similar model, a one-point higher Life's Simple 7 score was associated with a 25% lower risk of incident peripheral artery disease (hazard ratio=0.75, 95% CI=0.72, 0.79). Better cardiovascular health, as defined by higher Life's Simple 7 score, is associated with a substantially lower risk of peripheral artery disease.

COPD is associated with an increased risk of peripheral artery disease and mortality.

Patients with chronic obstructive pulmonary disease (COPD) commonly present with multimorbidity. We aimed to investigate the association between COPD and the development of peripheral arterial disease (PAD) in the general population, and how this might affect mortality among individuals with COPD.We included 3123 participants of the population-based Rotterdam Study without PAD at baseline (mean age 65 years; 57.4% female). The association between COPD at baseline and PAD during follow-up was studied using logistic regression (PAD being indicated by an ankle–brachial index (ABI) of 0.9 or less). Cox regression was used for mortality analysis and interaction terms were used to investigate mortality risk modification by PAD.The presence of COPD was associated with incident PAD (adjusted odds ratio 1.9, 95% CI 1.1–3.2). Mortality rates per 100 000 person-years were as follows: 10.0 in individuals without COPD or PAD, 18.4 in those with COPD only, 16.1 in those with PAD only and 30.1 in individuals with both COPD and PAD. No statistical interaction was found between PAD and COPD on risk of dying.Individuals with COPD have an almost doubled risk of developing PAD. Although PAD does not modify the association between COPD and mortality, people suffering from both diseases have substantially higher mortality rates.

GW29-e0464 Accumulated Effect of Active Smoking combined with Family Smoking Increased Risk of Peripheral Arterial Disease: Results from National Health and Nutrition Examination Survey 1999-2004

Smoking is an acknowledged risk factor for peripheral arterial disease (PAD). The pathophysiological role of smoke in PAD has been established. However, the accumulated effect of active smoking combined with family smoking exposure to PAD is not well studied. We hypothesized that accumulation of

The Association of Severe Diabetic Retinopathy With Cardiovascular Outcomes in Long-standing Type 1 Diabetes: A Longitudinal Follow-up.

It is well established that diabetic nephropathy increases the risk of cardiovascular disease (CVD), but how severe diabetic retinopathy (SDR) impacts this risk has yet to be determined. The cumulative incidence of various CVD events, including coronary heart disease (CHD), peripheral artery disease (PAD), and stroke, retrieved from registries, was evaluated in 1,683 individuals with at least a 30-year duration of type 1 diabetes drawn from the Finnish Diabetic Nephropathy Study (FinnDiane). The individuals were divided into four groups according to the presence of diabetic kidney disease (DKD) and/or SDR (+DKD/+SDR, +DKD/-SDR, -DKD/+SDR, and -DKD/-SDR) at baseline visit. Furthermore, age-specific incidences were compared with 4,016 control subjects without diabetes. SDR was defined as laser photocoagulation and DKD as estimated glomerular filtration rate <60 mL/min/1.73 m2. During 12,872 person-years of follow-up, 416 incident CVD events occurred. Even in the absence of DKD, SDR increased the risk of any CVD (hazard ratio 1.46 [95% CI 1.11-1.92]; P < 0.01), after adjustment for diabetes duration, age at diabetes onset, sex, smoking, blood pressure, waist-to-hip ratio, history of hypoglycemia, and serum lipids. In particular, SDR alone was associated with the risk of PAD (1.90 [1.13-3.17]; P < 0.05) and CHD (1.50 [1.09-2.07; P < 0.05) but not with any stroke. Moreover, DKD increased the CVD risk further (2.85 [2.13-3.81]; P < 0.001). However, the risk was above that of the control subjects without diabetes also in patients without microvascular complications, until the patients reached their seventies. SDR alone, even without DKD, increases cardiovascular risk, particularly for PAD, independently of common cardiovascular risk factors in long-standing type 1 diabetes. More remains to be done to fully understand the link between SDR and CVD. This knowledge could help combat the enhanced cardiovascular risk beyond currently available regimens.

Marine n-3 Fatty Acids and the Risk of Peripheral Arterial Disease

BackgroundThe content of marine n-3 polyunsaturated fatty acids (PUFAs) in adipose tissue is considered a long-term biomarker for the body’s endogenous exposure to seafood. ObjectivesThis study sought to examine associations between the content of marine n-3 PUFAs in adipose tissue and the risk of incident peripheral arterial disease (PAD). MethodsIn this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, adipose tissue biopsies were taken from the buttocks of all participants at baseline. After a median follow-up of 13.5 years, 870 validated cases of PAD were identified and included together with a randomly drawn subcohort of 3,204 participants using weighted Cox regression. Adipose tissue samples were analyzed by gas chromatography. ResultsIn multivariable analyses using the lowest quintile as the reference and adjusting for established risk factors for PAD, we found a statistically significant lower rate of PAD in the highest quintile of eicosapentaenoic acid (EPA) (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.41 to 0.74) and a nonsignificant lower rate for docosahexaenoic acid (HR: 0.79; 95% CI: 0.59 to 1.06). We observed a lower rate of PAD, when comparing the highest quintile of the combined EPA and docosahexaenoic acid with the reference (HR: 0.71; 95% CI: 0.53 to 0.96). In contrast, docosapentaenoic acid had an HR of 1.31 (95% CI: 0.97 to 1.77) in the highest quintile. ConclusionsA high content of marine n-3 PUFAs in adipose tissue, in particular EPA, was associated with a lower risk of incident PAD.

Substitution of poultry and red meat with fish and the risk of peripheral arterial disease: a Danish cohort study.

The aims of this study were to examine associations between substitutions of poultry and red meat intake with fish (total, lean or fatty) and the risk of peripheral arterial disease (PAD). We hypothesised that a higher intake of fish and a concomitant lower intake of poultry or red meat were associated with a lower risk of incident PAD. We used data from a Danish cohort where middle-aged participants filled in food frequency and lifestyle questionnaires at baseline. During follow-up, we identified participants with valid diagnoses of PAD and analysed data by multivariable Cox regression analyses. Substitutions of 150g/week of either poultry, red meat (processed or unprocessed) with 150g/week of fish (total, lean or fatty) were explored. We followed the cohort (n = 54,597) for a median of 13.6years and identified 897 cases with PAD. We found modest lower rates of PAD when intake of fish replaced a concomitant lower intake of unprocessed (HR 0.94, 95% CI 0.88-1.01) and processed red meat (HR 0.94, 95% CI 0.87-1.02). Replacing unprocessed (HR 0.89, 95% CI 0.79-1.00) or processed red meat (HR 0.88, 95% CI 0.78-1.01) with fatty fish was associated with lower rates of PAD. No associations were observed when fish intake replaced poultry or when lean fish replaced red meat. This study suggests that substituting red meat with fish and especially fatty fish may be associated with a lower risk of PAD, although not statistically significant. Replacing poultry with fish was not associated with the risk of PAD.

Combination of the ankle-brachial index and percentage of mean arterial pressure to improve diagnostic sensitivity for peripheral artery disease

The ankle-brachial index (ABI) is a noninvasive method for screening for peripheral artery disease (PAD). However, false-negative findings of the ABI may limit its clinical use. The percentage of mean arterial pressure (%MAP) calculated from pulse volume recording has been reported to predict all-cause mortality. We hypothesized that the %MAP would be helpful to screen for PAD in subjects with a normal ABI. We examined whether using a combination of the ABI and %MAP would provide greater diagnostic sensitivity for PAD than using the ABI alone.In this cross-sectional study, we retrospectively reviewed the medical records of patients who had undergone multiple detector computed tomography (MDCT) angiography of the lower extremities following measurement of the ABI with pulse volume recording. PAD was diagnosed based on MDCT angiography.A total of 215 lower extremities of 114 patients were included in our analyses. An optimal cut-off %MAP value of 42.5% was used to diagnose PAD based on MDCT in patients with an ABI > 0.90. Using a combination of an ABI < 0.90 and a %MAP ≥ 42.5% as diagnostic criteria for PAD resulted in better sensitivity (76.9%) than using the ABI alone (56.5% for an ABI < 0.90 and 63.4% for an ABI < 1.00). Using logistic regression analysis, we found that patients having both an ABI < 0.90 and an ABI > 0.90 with a %MAP ≥ 42.5% had a significantly higher risk of PAD than those having an ABI > 0.90 with a %MAP < 42.5% (odds ratio = 7.165, P = .006; odds ratio = 12.544, P < .001; respectively).Both the sensitivity and specificity were better when using a combination of an ABI ≤ 0.90 and a %MAP ≥ 42.5% than when using a low or borderline ABI. The %MAP is helpful for PAD screening in subjects with an ABI > 0.90.

Associations of Obesity With Incident Hospitalization Related to Peripheral Artery Disease and Critical Limb Ischemia in the ARIC Study.

BackgroundWe conducted an analysis of data from the ARIC (Atherosclerosis Risk in Communities) study to assess the independent association of obesity with peripheral artery disease (PAD) and critical limb ischemia (CLI).Methods and ResultsAll black and white ARIC participants without prevalent PAD at baseline (1987–1989) were included. We used Cox proportional hazards models adjusting for potential confounders and then potential mediators to quantify the association between body mass index (BMI) and incident hospitalizations related to PAD without CLI and with CLI through 2013. Our analysis included 13 988 men and women followed for a median of 24 years. Incident PAD without CLI and PAD with CLI occurred in 373 and 201 participants, respectively. After adjusting for potential confounders, higher BMI at baseline was associated with increased risk of PAD without CLI when BMI was modeled continuously (hazard ratio per 1‐SD increment in BMI: 1.23; 95% confidence interval, 1.11–1.37) and with PAD with CLI regardless of whether BMI was modeled categorically (P<0.05) or continuously (hazard ratio per 1‐SD increment in BMI: 1.51; 95% confidence interval, 1.34–1.69). The associations of BMI with PAD without CLI and with CLI were attenuated after further accounting for potential mediators but remained significant for PAD with CLI when BMI was linearly modeled (hazard ratio per 1‐SD increment in BMI: 1.19; 95% confidence interval, 1.04–1.36). The positive association between BMI and PAD with CLI was stronger than the association between BMI and PAD without CLI for all models (P<0.001).ConclusionsIn the general population, BMI is positively associated with incident hospitalized PAD after adjusting for potential confounders, particularly its most severe form of CLI. Maintaining an optimal weight, in addition to controlling other cardiovascular risk factors, may play a role in reducing risk of PAD with CLI.

Familial Hypercholesterolemia and Risk of Peripheral Arterial Disease and Chronic Kidney Disease.

Individuals with familial hypercholesterolemia (FH) have a high risk of coronary artery disease, but their risk of peripheral arterial disease (PAD) and chronic kidney disease (CKD) is unknown. In individuals with clinical FH, we tested the hypotheses (1) that the risks of PAD and CKD are elevated and (2) that low ankle-brachial index (ABI) and estimated glomerular filtration rate (eGFR) are associated with a high risk of myocardial infarction. Prospective cohort study of the general population. A total of 106,172 individuals, of whom 7109 were diagnosed with FH. PAD, CKD, and myocardial infarction. Compared with individuals with unlikely FH, multivariable adjusted ORs (95% CIs) of PAD were 1.84 (1.70 to 2.00) in those with possible FH and 1.36 (1.00 to 1.84) in individuals with probable/definite FH. For CKD, the corresponding ORs (95% CIs) were 1.92 (1.78 to 2.07) and 2.42 (1.86 to 3.26). Compared with individuals with unlikely FH and ABI >0.9, the multivariable adjusted hazard ratio (95% CI) of myocardial infarction was 4.60 (2.36 to 8.97) in those with possible/probable/definite FH and ABI ≤0.9. Compared with individuals with unlikely FH and eGFR ≥60 mL/min/1.73 m2, the corresponding value was 2.19 (1.71 to 2.82) in those with possible/probable/definite FH and eGFR <60 mL/min/1.73 m2. Individuals with clinical FH have increased risks of PAD and CKD, and low ABI and eGFR are associated with high risk of myocardial infarction. Consequently, individuals with FH should be screened for PAD and CKD, and ABI and eGFR may be used as prognostic tools in the management and treatment of FH to identify those at very high risk of myocardial infarction.

Excess risk of peripheral arterial disease in familial hypercholesterolemia

Aim: It is unknown to what degree the risk of peripheral arterial disease (PAD) is increased in familial hypercholesterolemia (FH) and the risk in relation to age and sex is unknown. The aim of this study was to explore the role of LDL in PAD in relation to age and sex using FH as a model disease.

Familial hypercholesterolaemia and risk of peripheral arterial disease and chronic kidney disease: The Copenhagen General Population Study

Familial hypercholesterolaemia and risk of peripheral arterial disease and chronic kidney disease: The Copenhagen General Population Study

P1639Dietary intake of alpha-linolenic acid and the risk of peripheral arterial disease among middle-aged men and women - a danish cohort study

P1639Dietary intake of alpha-linolenic acid and the risk of peripheral arterial disease among middle-aged men and women - a danish cohort study

Alpha-linolenic acid and risk of peripheral arterial disease

Alpha-linolenic acid and risk of peripheral arterial disease

Comparative analysis of the comorbidities importance in patients with peripheral artery disease

Aim: Evaluation of the comorbidities impact in assessing the current vascular risk in peripheral artery disease (PAD).

High LDL cholesterol levels and risk of peripheral vascular diseases - A mendelian randomization study including 106,548 individuals from the general population

Aim: High LDL cholesterol is causally involved in the pathogenesis of atherosclerosis and is causally related to an increased risk of cardiovascular disease. It is unknown whether high LDL cholesterol levels are causally related to an increased risk of peripheral vascular diseases, such as retinopathy, neuropathy, chronic kidney disease(CKD), and peripheral arterial disease(PAD). We hypothesized that high LDL cholesterol is causally related to the risk of retinopathy, neuropathy, CKD and PAD in the general population.

Improving outcomes in patients with peripheral arterial disease

The benefits of risk-factor reduction associated with peripheral arterial disease (PAD) is established and supported by the literature. The purpose of this quality-improvement project was to reduce modifiable risk factors such as diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLD), and tobacco use in patients with PAD, as well as to demonstrate improvement in quality of life (QoL) and 6-minute-walk distances. For this quality-improvement project, 29 patients from three providers within a cardiology office were identified over a 6-week period. Those patients had a baseline 6-minute-walk test and completed a vascular quality-of-life (Vas QoL-6) questionnaire at visit 1. They were assessed for their Rutherford classification, a clinical staging system used to describe PAD. In visit 2, patients underwent endovascular intervention as per cardiologist recommendation. At clinic visit 3, an individualized plan was initiated to address all risk factors including diabetes mellitus, hypertension, hyperlipidemia, and tobacco use. Medications were adjusted to meet current guidelines appropriate for disease processes. Patients were also asked to start a regimented walking program as used by the Cleveland Clinic. At clinic visit 4, 90days from patient's first visit, they were assessed for improvement in blood pressure, cholesterol, diabetes, and tobacco use. Vas QoL-6 and 6-minute-walk test were repeated at visit 4 for comparison. A total of 24 participants were included in the study. The average age was 66.92years (standard deviation=8.75), and the majority reported their race as white (n=18, 75.0%). There were 10 (41.7%) males and 14 (58.3%) females. No statistically significant improvement was shown for A1c levels (P=.091) and total cholesterol (P=.066). Statistically significant improvement was revealed for low-density lipoprotein cholesterol (P=.007). Of the seven patients (29.2%) who used tobacco at visit 3, four (57.1%) reported a reduction in their tobacco use by the end of the study. Vas QoL-6 scores improved significantly (P<0.001), and the distance during 6-minute walk also increased significantly (P=0.03). There was a statistically significant decrease in Rutherford class scores from visit 1 to visit 4 (P<.001). Regarding compliance with the PAD Walking Program, 13 (54.2%) of the patients walked 10 or fewer times total. In conclusion, these data indicate that PAD risk factors can be improved, including control of blood pressure, cholesterol, A1c levels, and smoking cessation. Controlling risk factors that contribute to the progression of PAD is not only important for improving morbidity and mortality but may contribute to improved quality of life. This quality-improvement study also suggests that close follow-up and management after endovascular intervention increases the distance patients can ambulate without claudication symptoms. These results suggest that compliance with an unsupervised walking program is difficult, and supervised exercise programs should be considered as an alternative.

The different relations of PCSK9 and Lp(a) to the presence and severity of atherosclerotic lesions in patients with familial hypercholesterolemia

Background and aimsThe relation of lipoprotein (a) [Lp(a)] and proprotein convertase substilisin/kexin type 9 (PCSK9) levels to coronary artery disease (CAD) has been well established in the general population, while little is known about the association between Lp(a) or PCSK9 and atherosclerotic lesions of different artery sites in patients with familial hypercholesterolemia (FH). MethodsOne hundred and fifty-one patients with verified genotyped heterozygous FH (HeFH) were enrolled. There were available data regarding coronary angiography and carotid ultrasonography in 151 patients and femoral ultrasonography in 55 patients. Coronary and carotid severity was evaluated by Gensini score and Crouse score. PCSK9 and Lp(a) concentrations were determined by ELISA and immunoturbidimetry, respectively. Finally, the correlation of PCSK9 and Lp(a) with the presence and severity of CAD and peripheral artery disease (PAD) was assessed. ResultsThe distributions of PCSK9 and Lp(a) were skewed and a close correlation between them in HeFH patients was found. PCSK9 levels were significantly higher in patients with coronary and carotid atherosclerotic lesions compared to their non-atherosclerotic groups, while no difference was found in femoral atherosclerotic lesions groups. Lp(a) levels only differed between patients with or without coronary atherosclerotic lesions. Patients with highest PCSK9 and Lp(a) concentrations had the highest prevalence and severity of atherosclerotic lesions. Multivariate regression analysis showed that PCSK9 was independently associated with CAD and PAD, while Lp(a) was only associated with CAD. ConclusionsCirculating PCSK9 concentrations were associated with an increased risk of CAD and PAD, while Lp(a) was only a marker for CAD in HeFH patients.