Five-Year Outcomes of the Danish Cardiovascular Screening (DANCAVAS) Trial.

BACKGROUND: Limited data suggest a benefit of population-based screening for cardiovascular disease with respect to the risk of death. METHODS: We performed a population-based, parallel-group, randomized, controlled trial involving men 65 to 74 years of age living in 15 Danish municipalities. The participants were randomly assigned in a 1:2 ratio to undergo screening (the invited group) or not to undergo screening (the control group) for subclinical cardiovascular disease. Randomization was based on computer-generated random numbers and stratified according to municipality. Only the control group was unaware of the trial-group assignments. Screening included noncontrast electrocardiography-gated computed tomography to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation, ankle-brachial blood-pressure measurements to detect peripheral artery disease and hypertension, and a blood sample to detect diabetes mellitus and hypercholesterolemia. The primary outcome was death from any cause. RESULTS: A total of 46,611 participants underwent randomization. After exclusion of 85 men who had died or emigrated before being invited to undergo screening, there were 16,736 men in the invited group and 29,790 men in the control group; 10,471 of the men in the invited group underwent screening (62.6%). In intention-to-treat analyses, after a median follow-up of 5.6 years, 2106 men (12.6%) in the invited group and 3915 men (13.1%) in the control group had died (hazard ratio, 0.95; 95% confidence interval [CI], 0.90 to 1.00; P = 0.06). The hazard ratio for stroke in the invited group, as compared with the control group, was 0.93 (95% CI, 0.86 to 0.99); for myocardial infarction, 0.91 (95% CI, 0.81 to 1.03); for aortic dissection, 0.95 (95% CI, 0.61 to 1.49); and for aortic rupture, 0.81 (95% CI, 0.49 to 1.35). There were no significant between-group differences in safety outcomes. CONCLUSIONS: After more than 5 years, the invitation to undergo comprehensive cardiovascular screening did not significantly reduce the incidence of death from any cause among men 65 to 74 years of age. (Funded by the Southern Region of Denmark and others; DANCAVAS ISRCTN Registry number, ISRCTN12157806.).

Remnant Cholesterol, Not LDL Cholesterol, Explains Peripheral Artery Disease Risk Conferred by apoB: A Cohort Study.

BACKGROUND: Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction. METHODS: apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004-2010). RESULTS: In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5-2.4) and 1.1 (95% CI, 1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4-2.1) and 0.9 (95% CI, 0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%-100%) and 8% (0%-46%), respectively; corresponding results were 63% (30%-100%) and 0% (0%-33%) for risk of chronic limb-threatening ischemia and 41% (27%-55%) and 54% (38%-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. CONCLUSIONS: PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.

Association Between Mental Health Burden, Clinical Presentation, and Outcomes in Individuals With Symptomatic Peripheral Artery Disease: A Scientific Statement From the American Heart Association.

Along with the rising burden of peripheral artery disease (PAD), mental health concerns are increasingly being recognized as a comorbidity to address in the chronic disease management of symptomatic PAD. Apart from a high prevalence of comorbid mental health conditions, the role of pain and changing health behaviors and the broader impacts of illness and adaptation to living with PAD require specialized behavioral health expertise. This scientific statement builds a case that this expertise should be integrated within the multidisciplinary PAD team. Furthermore, areas such as cognitive dysfunction and palliative care are highlighted as needing psychological interventions. Although much of the evidence of the efficacy of psychological and psychotropic interventions has been extrapolated from other cardiovascular populations, evidence for the role of psychological interventions for behavior change, for example, uptake of exercise regimens, is increasingly being accrued within PAD. Areas for behavioral health needs and interactions with PAD treatment are discussed, including the use of opioids, depression management, anxiety and stress reduction interventions, the use of benzodiazepines and antidepressants, smoking cessation, rehabilitation trajectories after amputation, and the role of cognitive decline for PAD treatment and outcomes. A case summary highlights the stigma around mental health and vascular disease and the fragmentation of care. This scientific statement provides remarks for building a road map for integrated behavioral PAD care and potential solutions to overcome these barriers. Instrumental to reaching these changes are interprofessional advocacy efforts and initiatives that help break down the stigma around mental health and promote evidence-based collaborative, nonhierarchical, and multidisciplinary PAD care.

Health Disparities in Peripheral Artery Disease: A Scientific Statement From the American Heart Association.

Peripheral artery disease (PAD) affects 200 million individuals worldwide. In the United States, certain demographic groups experience a disproportionately higher prevalence and clinical effect of PAD. The social and clinical effect of PAD includes higher rates of individual disability, depression, minor and major limb amputation along with cardiovascular and cerebrovascular events. The reasons behind the inequitable burden of PAD and inequitable delivery of care are both multifactorial and complex in nature, including systemic and structural inequity that exists within our society. Herein, we present an overview statement of the myriad variables that contribute to PAD disparities and conclude with a summary of potential novel solutions.

Identifying the highest risk vascular patients: Insights from the XATOA registry.

BACKGROUND: Patients with coronary and peripheral artery disease (PAD) have a residual risk of major adverse cardiovascular and limb events despite standards of care. Among patients with coronary artery disease (CAD) and/or PAD selected for low dose rivaroxaban (2.5 mg BID) and aspirin, we sought to determine the highest risk vascular patients. METHODS: Xarelto pluc Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA) is a single-arm registry of CAD and/or PAD patients. All participants were initiated on low dose rivaroxaban (2.5 mg BID) and aspirin. We report the incidence risk of major adverse cardiovascular events (MACE) or major adverse limb events (MALE) and major bleeding. A classification and regression tree analysis determined independent subgroups. RESULTS: Between November 2018 and May 2020, 5,808 participants were enrolled in XATOA; 5,532 were included in the full analysis. The median follow-up (interquartile range) was 462 (371-577) days. The incidence risk per 100 patient-years of MACE or MALE was highest among participants with polyvascular disease (2 or more vascular beds affected, n = 2,889). The incidence risk was 9.16 versus 2.48 per 100 patient-years in polyvascular and nonpolyvascular patients respectively. Other subgroups of high-risk patients included participants 75 years or older, with a history of diabetes, heart failure, or chronic renal insufficiency (CRI). Rates of major bleeding were low overall. A classification and regression tree analysis showed that polyvascular disease was the most dominant factor separating higher from lower risk participants, and this was heightened with CRI or diabetes. CONCLUSION: Patients with polyvascular disease represent a substantial subset of patients in clinical practice and should be prioritized to receive maximal medical therapy including low dose rivaroxaban (2.5 mg BID) and aspirin.

Regional variation in cause of death in patients with type 2 diabetes: Insights from EXSCEL.

AIMS: Type 2 diabetes (T2D) is a risk factor for cardiovascular and non-cardiovascular mortality. However, global distribution of cause-specific deaths in T2D is poorly understood. We characterized cause-specific deaths by geographic region among individuals with T2D at risk for cardiovascular disease (CVD). METHODS AND RESULTS: The international EXSCEL trial included 14,752 participants with T2D (73% with established CVD). We identified the proportion of deaths over 5-year follow-up attributed to cardiovascular and non-cardiovascular causes, and associated risk factors. During median 3.2-year follow-up, 1,091 (7.4%) participants died. Adjudicated causes of death were 723 cardiovascular (66.3% of deaths), including 252 unknown, and 368 non-cardiovascular (33.7%). Most deaths occurred in North America (N = 356/9.6% across region) and Eastern Europe (N = 326/8.1%), with fewest in Asia/Pacific (N = 68/4.4%). The highest proportional cause-specific deaths by region were sudden cardiac in Asia/Pacific (23/34% of regional deaths) and North America (86/24%); unknown in Eastern Europe (90/28%) and Western Europe (39/21%); and non-malignant non-cardiovascular in Latin America (48/31%). Cox proportional hazards model for adjudicated causes of death showed prognostic risk factors (hazard ratio [95% CI]) for cardiovascular and non-cardiovascular deaths, respectively: heart failure 2.04 (1.72-2.42) and 1.86 (1.46-2.39); peripheral artery disease 1.83 (1.54-2.18) and 1.78 (1.40-2.26); and current smoking status 1.61 (1.29-2.01) and 1.77 (1.31-2.40). CONCLUSIONS: In a contemporary T2D trial population, with and without established CVD, leading causes of death varied by geographic region. Underlying mechanisms leading to variability in cause of death across geographic regions and its impact on clinical trial endpoints warrant future research.

Challenges and opportunities in the management of type 2 diabetes in patients with lower extremity peripheral artery disease: a tailored diagnosis and treatment review.

Lower extremity peripheral artery disease (PAD) often results from atherosclerosis, and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Individuals with T2DM exhibit a more severe manifestation and a more distal distribution of PAD compared to those without diabetes, adding complexity to the therapeutic management of PAD in this particular patient population. Indeed, the management of PAD in patients with T2DM requires a multidisciplinary and individualized approach that addresses both the systemic effects of diabetes and the specific vascular complications of PAD. Hence, cardiovascular prevention is of the utmost importance in patients with T2DM and PAD, and encompasses smoking cessation, a healthy diet, structured exercise, careful foot monitoring, and adherence to routine preventive treatments such as statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is also recommended to incorporate glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the medical management of patients with T2DM and PAD, due to their demonstrated cardiovascular benefits. However, the specific impact of these novel glucose-lowering agents for individuals with PAD remains obscured within the background of cardiovascular outcome trials (CVOTs). In this review article, we distil evidence, through a comprehensive literature search of CVOTs and clinical guidelines, to offer key directions for the optimal medical management of individuals with T2DM and lower extremity PAD in the era of GLP-1RA and SGLT2i.

Arterial dissection during peripheral vascular interventions.

OBJECTIVE: Arterial dissection (AD) is a known complication of peripheral vascular interventions (PVIs), but its incidence and significance have not been well-characterized. This study examines AD in the Vascular Quality Initiative database for patients treated for peripheral arterial disease. Our hypothesis is that AD is associated with decreased patency and worse limb outcomes. METHODS: The Vascular Quality Initiative PVI registry (2016-2021) was reviewed. Patients were divided based on the presence or absence of reported AD during the procedure. Trend of incidence and management of AD was derived. The characteristics and outcomes of patients with and without AD were compared. The primary endpoint was primary patency. RESULTS: There was a total of 177,790 cases, and 3% had AD. The incidence of AD significantly increased over the study period from 2.4% to 3.6% (P = .007). Endovascular therapy was used to treat AD in 83.7% of cases, 14.5% were treated medically, and only 1.8% required open surgery. Patients with AD were significantly more likely to be female (47.4% vs 39.7%; P < .001). Patient with AD were more likely to have a history of smoking (79.7% vs 77.2%; P < .001), but were significantly less likely to be on dialysis (8.2% vs 9.3%; P < .001) compared with patients without AD. Patients with AD were more likely to have femoropopliteal disease (45.2% vs 38.0%; P < .001) and undergo treatment of more complex disease as denoted by higher mean number of lesions treated (1.95 ± 1.01 vs 1.71 ± 0.89; P < .001), longer occlusion length (8 ± 16 vs 7 ± 15 cm; P < .001), and more severe TransAtlantic Inter-Society Consensus grade (Grade D: 36.2% vs 29.1%; P < .001). The proportion of stenting as a treatment modality was higher in the dissection group (55.4% vs 41.1%; P < .001). After a mean follow-up of 828 days, patients with AD had significantly lower primary patency than patients without AD. Kaplan-Meier curves demonstrated that the AD group had lower primary patency (86.9% vs 91%; P < .001) and reintervention-free survival (79.5 % vs 84.1%; P < .001) at 1 year with difference in amputation-free survival. Cox proportional hazard regression confirmed the independent association of AD with primary patency and reintervention-free survival. CONCLUSIONS: AD is more common in women and is more likely to occur during treatment of the femoropopliteal segment. AD is associated with decreased primary patency and reintervention-free survival after PVI for peripheral arterial disease.

Psychosocial and socioeconomic factors are most predictive of health status in patients with claudication.

BACKGROUND: As a key treatment goal for patients with symptomatic peripheral artery disease (PAD), improving health status has also become an important end point for clinical trials and performance-based care. An understanding of patient factors associated with 1-year PAD health status is lacking in patients with PAD. METHODS: The health status of 1073 consecutive patients with symptomatic PAD in the international multicenter PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry was measured at baseline and 1 year with the Peripheral Artery Questionnaire (PAQ). The association of 47 patient characteristics with 1-year PAQ scores was assessed using a random forest algorithm. Variables of clinical significance were retained and included in a hierarchical multivariable linear regression model predicting 1-year PAQ summary scores. RESULTS: The mean age of patients was 67.7 ± 9.3 years, and 37% were female. Variables with the highest importance ranking in predicting 1-year PAQ summary score were baseline PAQ summary score, Patient Health Questionnaire-8 depression score, Generalized Anxiety Disorder-2 anxiety score, new onset symptom presentation, insurance status, current or prior diagnosis of depression, low social support, initial invasive treatment, duration of symptoms, and race. The addition of 19 clinical variables in an extended model marginally improved the explained variance in 1-year health status (from R2 0.312 to 0.335). CONCLUSIONS: Patients' 1-year PAD-specific health status, as measured by the PAQ, can be predicted from 10 mostly psychosocial and socioeconomic patient characteristics including depression, anxiety, insurance status, social support, and symptoms. These characteristics should be validated and tested in other PAD cohorts so that this model can inform risk adjustment and prediction of PAD health status in comparative effectiveness research and performance-based care.

The association of comorbid depression with mortality and amputation risk in patients with chronic limb-threatening ischemia.

OBJECTIVE: There is increasing evidence that depression is a risk factor for worse outcomes in patients with peripheral artery disease. The association of depression in patients with chronic limb-threatening ischemia (CLTI) is not well described, nor is the impact of medical treatment for depression in this patient population. The objective of this study was to investigate the prevalence of depression in patients with CLTI, its association on major amputation and all-cause mortality, and whether medical antidepressant treatment is associated with improvement in these outcomes in patients with depression. METHODS: A retrospective review of all adult patients (≥18 years old) diagnosed with CLTI from January 1, 2007, to December 31, 2018, at a single academic medical center was performed. Collected data included patient demographics, comorbidities, and diagnosis of depression within 6 months of initial CLTI diagnosis. We also collected data on use of antidepressant medications. Outcomes evaluated were need for major lower extremity amputation and all-cause mortality. Multivariable logistic regression models estimated the adjusted effects of comorbid depression and antidepressant medication use on major amputation and all-cause mortality. Kaplan-Meier survival curves illustrated the probabilities of survival and limb salvage over time, stratified by diagnosis of comorbid depression. Multivariable Cox proportional hazards models estimated the adjusted effects of comorbid depression on time to major amputation and all-cause mortality, and the adjusted effect of antidepressant treatment on time to all-cause mortality. RESULTS: A total of 2987 patients with CLTI were identified. Mean age was 68.6 years (standard deviation, 12.9 years); 56.5% were male, and 43.5% were female. Comorbid depression within 6 months of CLTI diagnosis was present in 7.1% of the cohort (212 patients). In multivariable analysis, comorbid depression was associated with a 68% increase in the odds of major amputation (adjusted odds ratio [aOR], 1.68; 95% confidence interval [CI], 1.19-2.37; P < .01), a 164% increase in the odds of all-cause mortality among patients not taking antidepressants (aOR, 2.64; 95% CI, 1.31-5.32; P = .03), and only a 6% increase in the odds of all-cause mortality among patients taking antidepressants (aOR, 1.06; 95% CI, 0.72-1.55; P = .99). The effect of comorbid depression on mortality varied significantly by whether or not the patient was taking an antidepressant medication (P = .02). CONCLUSIONS: Comorbid depression in the patient population with CLTI is associated with a worse prognosis for major lower extremity amputation overall, and a worse prognosis for all-cause mortality among patients not taking an antidepressant. Furthermore, antidepressant treatment in the presence of comorbid depression in this patient population is associated with an improvement in the odds of all-cause mortality, illustrating the potential importance of medical management of depression.

Sex Differences in Peripheral Artery Disease.

Peripheral artery disease (PAD) is a prevalent condition that confers substantial morbidity and mortality and remains underdiagnosed as well as undertreated in the overall population. Although PAD prevalence is similar or higher in women compared with men, associations of traditional and nontraditional risk factors with PAD and clinical manifestations of PAD differ by sex and may contribute to delayed or lack of diagnosis in women. Such sex-based differences in the manifestation of PAD may arise from sexual dimorphism in the vascular substrate in health as well as sex variation in the responses to vascular stressors. Despite the availability of proven therapies for improving symptoms and reducing risk of ischemic cardiovascular and limb events among patients with diagnosed PAD, important sex differences in treatment and outcomes have been observed. We provide an overview of current knowledge regarding sex differences in the epidemiology, pathophysiology, clinical presentation, and management of PAD.

A prospective observational study to evaluate a possible relationship between vitamin K antagonist therapy and risk of peripheral arterial disease in patients with type 2 diabetes.

AIM: The use of vitamin K antagonists (VKAs) may increase the risk of peripheral arterial disease (PAD) because vitamin K is a strong inhibitor of medial arterial calcification. Type 2 diabetes (T2D) exposes patients to an increased risk of PAD. We examined how the use of VKAs modulates the risk of incident PAD in people with T2D. MATERIALS AND METHODS: SURDIAGENE is a French cohort including 1468 patients with T2D with a prospective follow-up from 2002 to 2015. The primary outcome of the current analysis was the first occurrence of PAD, a composite of lower-limb amputation (LLA) or lower-limb revascularization. LLA and lower-limb revascularization were considered individually as secondary outcomes. RESULTS: During a 7-year median follow-up, PAD occurred in 147 (10%) of the 1468 participants. The use of VKAs was not significantly associated with the risk of PAD [multivariable adjusted hazard ratio (HR) 1.42, 95% confidence interval (CI), 0.88-2.31]. During the study period, LLA and lower-limb revascularization occurred in 82 (6%) and 105 (7%) participants, respectively. The use of VKAs was significantly associated with increased risk of LLA [multivariable adjusted HR 1.90 (95% CI, 1.04-3.47)], but not lower-limb revascularization [multivariable adjusted HR 1.08 (95% CI, 0.59-1.97)]. CONCLUSIONS: In this prospective study, we did not observe any excess risk of PAD requiring lower-limb revascularization in people with type 2 diabetes using VKAs. However, our data suggest a high risk of LLA in VKA users. Further studies are required to confirm this observation.

Treatment Location Variation for Chronic Limb-Threatening Ischemia in Patients With Kidney Failure.

INTRODUCTION: End-stage kidney disease (ESKD) is an established risk factor for chronic limb-threatening ischemia (CLTI). Procedural location for ESKD patients has not been well described. This study aims to examine variation in index procedural location in ESKD versus non-ESKD patients undergoing peripheral vascular intervention for CLTI and identify preoperative risk factors for tibial interventions. METHODS: Chronic limb-threatening ischemia (CLTI) patients were identified in the Vascular Quality Initiative (VQI) peripheral vascular intervention dataset. Patient demographics and comorbidities were compared between patients with and without ESKD and those undergoing index tibial versus nontibial interventions. A multivariable logistic regression evaluating risk factors for tibial intervention was conducted. RESULTS: A total of 23,480 procedures were performed on CLTI patients with 13.6% (n = 3154) with ESKD. End-stage kidney disease (ESKD) patients were younger (66.56 ± 11.68 versus 71.66 ± 12.09 y old, P = 0.019), more often Black (40.6 versus 18.6%, P < 0.001), male (61.2 versus 56.5%, P < 0.001), and diabetic (81.8 versus 60.0%, P < 0.001) than non-ESKD patients. Patients undergoing index tibial interventions had higher rates of ESKD (19.4 versus 10.6%, P < 0.001) and diabetes (73.4 versus 57.5%, P < 0.001) and lower rates of smoking (49.9 versus 73.0%, P < 0.001) than patients with nontibial interventions. ESKD (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.52-1.86, P < 0.001), Black race (OR 1.19, 95% CI 1.09-1.30, P < 0.001), and diabetes (OR 1.82, 95% CI 1.71-2.00, P < 0.001) were risk factors for tibial intervention. CONCLUSIONS: Patients with ESKD and CLTI have higher rates of diabetes and tibial disease and lower rates of smoking than non-ESKD patients. Tibial disease was associated with ESKD, diabetes, and Black race.

Associations of Cardiac Biomarkers With Peripheral Artery Disease and Peripheral Neuropathy in US Adults Without Prevalent Cardiovascular Disease.

BACKGROUND: NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T (hs-troponin T), and high-sensitivity cardiac troponin I (hs-troponin I) are increasingly being recommended for risk stratification for a variety of cardiovascular outcomes. The aims of our study were to establish the prevalence and associations of elevated NT-proBNP, hs-troponin T, and hs-troponin I with lower extremity disease, including peripheral artery disease (PAD) and peripheral neuropathy (PN), in the US general adult population without known cardiovascular disease. We also assessed whether the combination of PAD or PN and elevated cardiac biomarkers was associated with an increased risk of all-cause and cardiovascular mortality. METHODS: We conducted a cross-sectional analysis of the associations of NT-proBNP, hs-troponin T, and hs-troponin I with PAD (based on ankle-brachial index <0.90) and PN (diagnosed by monofilament testing) in adult participants aged ≥40 years of age without prevalent cardiovascular disease in NHANES (National Health and Nutrition Examination Survey) 1999 to 2004. We calculated the prevalence of elevated cardiac biomarkers among adults with PAD and PN and used multivariable logistic regression to assess the associations of each cardiac biomarker, modeled using clinical cut points, with PAD and PN separately. We used multivariable Cox proportional hazards models to assess the adjusted associations of cross categories of clinical categories of each cardiac biomarker and PAD or PN with all-cause and cardiovascular mortality. RESULTS: In US adults aged ≥40 years, the prevalence (±SE) of PAD was 4.1±0.2% and the prevalence of PN was 12.0±0.5%. The prevalence of elevated NT-proBNP (≥125 ng/L), hs-troponin T (≥6 ng/L), and hs-troponin I (≥6 ng/L for men and ≥4 ng/L for women) was 54.0±3.4%, 73.9±3.5%, and 32.3±3.7%, respectively, among adults with PAD and 32.9±1.9%, 72.8±2.0%, and 22.7±1.9%, respectively, among adults with PN. There was a strong, graded association of higher clinical categories of NT-proBNP with PAD after adjusting for cardiovascular risk factors. Clinical categories of elevated hs-troponin T and hs-troponin I were strongly associated with PN in adjusted models. After a maximum follow-up of 21 years, elevated NT-proBNP, hs-troponin T, and hs-troponin I were each associated with all-cause and cardiovascular mortality, with higher risks of death observed among adults with elevated cardiac biomarkers plus PAD or PN compared with elevated biomarkers alone. CONCLUSIONS: Our study establishes a high burden of subclinical cardiovascular disease defined by cardiac biomarkers in people with PAD or PN. Cardiac biomarkers provided prognostic information for mortality within and across PAD and PN status, supporting the use of these biomarkers for risk stratification among adults without prevalent cardiovascular disease.

Epidemiology of Non-Traumatic Lower Extremities Amputations in West Africa: Nationwide Data from Togo.

OBJECTIVE: Non-traumatic lower limb amputation (NT-LLA) has consequences at individual and public health levels. Population based studies in sub-Saharan Africa are scarce and often related to single centre series. This study aimed to estimate the incidence of NT-LLA (minor and major) and to describe epidemiological, clinical, and prognostic aspects in Togo. METHODS: This was a population based observational study conducted among all patients who underwent NT-LLA. Traumatic amputations were excluded. Sociodemographic, clinical, and work up data were collected from clinical files in any Togolese health centre from 1 January 2016 to 31 December 2021. Incidence rates were adjusted for age. RESULTS: Over the six year period, 352 patients (59% males) underwent NT-LLA (mean ± standard deviation age 60 ± 15.7 years). The average age adjusted incidence rate of NT-LLA was 8.5 per million/year (95% confidence interval [CI] 7.6 - 9.4). Men were 1.7 times more likely to undergo a NT-LLA than women. The relative risk of NT-LLA was 48 times higher in patients with diabetes than in patients without diabetes. Around 61.0% of the NT-LLAs occurred within the 50 - 74 age group and 54.3% had diabetes mellitus. Among amputees, 54.5% had a diagnosis of peripheral artery disease (PAD) and 52.8% had diabetic ulcers, with co-existence of several factors. Less than 5% of participants had a history of smoking tobacco. Average length of hospital stay was 12 days. The in hospital mortality rate was 8.8% (9.0% for major, 6.7% for minor amputations). Only 18.2% had duplex ultrasound performed and 1.7% angiography prior to amputation. No patient underwent vascular intervention prior to amputation. CONCLUSION: This is the first study to report nationwide and contemporary epidemiological data on NT-LLAs in West Africa, highlighting several specificities. Large scale interventions are needed to ameliorate the care of diabetes and PAD and improve facilities for optimal management of patients at risk of amputation in Africa.

Adherence and Persistence to Antiplatelet Therapy in Lower Extremity Peripheral Arterial Disease: A Danish Population Based Cohort Study.

OBJECTIVE: Adherence to antiplatelet therapy is recommended but unexplored in patients with symptomatic lower extremity peripheral arterial disease (PAD). Therefore, this study aimed to determine adherence and persistence to antiplatelet therapy in patients with PAD, defined as intermittent claudication and chronic limb threatening ischaemia. DESIGN: Population based nationwide cohort study. METHODS: This study included all Danish citizens aged ≥ 40 years with a first inpatient or outpatient diagnosis of symptomatic PAD between 2010 - 2017, and who had at least one prescription claim for aspirin and/or clopidogrel within 90 days after diagnosis. Adherence was determined by the proportion of days covered (PDC) during the first year after diagnosis. Persistence was defined as no treatment gap ≥ 30 days between prescription renewals over three year follow up. RESULTS: A total of 39 687 patients were eligible for inclusion, of whom 23 279 (58.7%) claimed a prescription for aspirin and/or clopidogrel within 90 days of diagnosis. Among these, 12 898 (55.4%) were prevalent users, while the remainder comprised new users who initiated the therapy after the index PAD diagnosis. The mean PDC was 74.5% (SD 35.0%) for prevalent users and 60.5% (SD 30.5%) for new users. Adherence increased with age and number of concomitant drugs. The overall one year cumulative incidence treatment discontinuation was 13.0% (95% CI 12.5 - 13.4%) overall, 17.2% (CI 16.6 - 17.9%) for prevalent users, and 7.9% (CI 7.4 - 8.4%) for new users. At three year follow up, the cumulative incidence of discontinuation was 31.5% (CI 30.9 - 32.2%) overall, 44.6% (CI 43.7 - 45.4%) for prevalent users, and 14.6% (CI 13.9 - 15.3) for new users. CONCLUSION: Less than 60% of patients with newly diagnosed symptomatic PAD claimed a prescription for antiplatelet therapy within 90 days of diagnosis, and both adherence and persistence were moderate during the first year after diagnosis. These findings underscore the importance of efforts to improve the initiation and continuation of antiplatelet therapy in patients with PAD.

A Practical Guide to Understanding and Treating Peripheral Artery Disease.

ABSTRACT: Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic morbidity after coronary heart disease and stroke yet is widely underdiagnosed and undertreated. Treatment of risk factors such as diabetes and cigarette smoking can benefit patients with PAD. Patients should have adequate blood pressure and lipid control to decrease clinical manifestations and symptoms of PAD. Use of antithrombotic medications should be individualized to the patient depending on the presence of symptoms, revascularization, and comorbidities. All patient care providers, including physicians, pharmacists, nurse practitioners, and physician assistants, should incorporate PAD screening in their at-risk patients to improve access for appropriate earlier diagnosis, initiation of guideline directed therapy, and risk factor modification to reduce both major adverse CV and limb outcomes. The purpose of this narrative review is to provide an overview of PAD and summarize clinical trial evidence and guideline recommendations for screening and treatment to increase awareness among health care providers to ultimately have a positive impact on patient care.

Impact of comorbid opioid use disorder and major depressive disorder on healthcare utilization outcomes in patients with peripheral artery disease: A National Readmission Database analysis.

BACKGROUND: Prior research has demonstrated that individuals with peripheral artery disease (PAD) often have comorbid opioid use disorder (OUD) and major depressive disorder (MDD), with limited data regarding their impact on readmission outcomes, length of stay, and cost. This study aimed to investigate these healthcare utilization outcomes in patients with PAD who have comorbid OUD and MDD. METHODS: Data were obtained from the National Readmission Database from 2011 through 2018. The study population included all hospitalizations with PAD as the primary or secondary diagnosis, from which hospitalizations with OUD and MDD were extracted using appropriate ICD-9/10 diagnosis codes. Primary outcomes were 30-day and 90-day readmission, total cost, and total length of stay within the calendar year. We created hierarchical multivariable logistic regression models examining OUD with and without MDD, with a random effect for healthcare facility location. RESULTS: From 2011 to 2018, 13,265,817 weighted admissions with PAD were identified. These admissions were segmented into four categories: No OUD/No MDD (12,056,466), OUD/No MDD (323,762), No OUD/MDD (867,641), and OUD/MDD (17,948). The group with No OUD/No MDD was used as the reference group for all subsequent comparisons. Regarding 30-day and 90-day readmissions, patients with OUD/MDD had odds of 1.14 (95% CI 1.10, 1.18) and 1.09 (95% CI 1.06, 1.13), respectively. Patients with OUD/No MDD bore the highest median cost of $64,354 (IQR $30,797-137,074), and patients with OUD/MDD marked the lengthiest median stay of 6.01 days (IQR 2.01-13.30). CONCLUSION: This study found a significant association between these comorbidities and outcomes and therefore calls for targeted interventions and pain management strategies.

Impact of preexisting coronary artery and peripheral artery disease on outcomes in diabetic patients after kidney transplant.

BACKGROUND: Atherosclerotic cardiovascular disease is highly prevalent in patients with end-stage kidney disease (ESKD). Kidney transplant (KT) improves patient survival and cardiovascular outcomes. The impact of preexisting coronary artery disease (CAD) and peripheral artery disease (PAD) on posttransplant outcomes remains unclear. METHODS: This is a retrospective study utilizing the United States Renal Data System. Adult diabetic dialysis patients who underwent first KT between 2006 and 2017 were included. The study population was divided into four cohorts based on presence of CAD/PAD: (1) polyvascular disease (CAD + PAD); (2) CAD without PAD; (3) PAD without CAD; (4) no CAD or PAD (reference cohort). The primary outcome was 3-year all-cause mortality. Secondary outcomes were incidence of posttransplant myocardial infarction (MI), cerebrovascular accidents (CVA), and graft failure. RESULTS: The study population included 19,329 patients with 64.4% men, mean age 55.4 years, and median dialysis duration of 2.8 years. Atherosclerotic cardiovascular disease was present in 28% of patients. The median follow up was 3 years. All-cause mortality and incidence of posttransplant MI were higher with CAD and highest in patients with polyvascular disease. The cohort with polyvascular disease had twofold higher all-cause mortality (16.7%, adjusted hazard ratio (aHR) 1.5, p < 0.0001) and a fourfold higher incidence of MI (12.7%, aHR 3.3, p < 0.0001) compared to the reference cohort (8.0% and 3.1%, respectively). There was a higher incidence of posttransplant CVA in the cohort with PAD (3.4%, aHR 1.5, p = 0.01) compared to the reference cohort (2.0%). The cohorts had no difference in graft failure rates. CONCLUSIONS: Preexisting CAD and/or PAD result in worse posttransplant survival and cardiovascular outcomes in patients with diabetes mellitus and ESKD without a reduction in graft survival.

Association of prognostic nutritional index with peripheral artery disease in US adults: a cross-sectional study.

BACKGROUND: The objective of this study was to investigate the relationship between the prognostic nutritional index (PNI) and peripheral artery disease (PAD). METHODS: The present study is a cross-sectional study based on the National Health and Nutrition Survey (1999-2004). The laboratory-calculated PNI was divided into four groups based on quartiles(Q1:PNI ≤ 50.00; Q2: 50.01-53.00; Q3:53.01-56.00; Q4: > 56.00). PAD was defined as an ankle brachial pressure index (ABPI) ≤ 0.9 on the left or right. The relationship between PNI and PAD was examined using multifactor weighted logistic regression analysis, as well as subgroup analysis. Subgroup analyses were conducted based on demographic and clinical variables. RESULTS: A total of 5,447 individuals were included in our final analysis. The age of the participants was 59.56 ± 13.10 years, and males accounted for 52.8% (n = 2820). The prevalence of PAD was 6.7% (n = 363). After adjusting for all factors, participants with Q1 still had an increased risk of PAD, with an OR value of 1.593 and a 95% CI of 1.232-1.991. Subgroup analysis showed no significant interaction among multiple factors. CONCLUSIONS: In summary, we report that lower PNI are associated with a higher risk of PAD in US adults. It is hoped that this discovery can provide a reference for the prevention of PAD.