The prescribing of cardioprotective medications and the impact on survival for patients with peripheral artery disease that undergo intervention.

BACKGROUND: Cardiovascular disease guidelines recommend that patients with established peripheral artery disease (PAD) are prescribed antihypertensive, lipid-lowering, and antiplatelet medication to reduce cardiovascular ischaemic events. However, the prescribing of these medications for patients with PAD within New Zealand (NZ) remains undefined. METHODS: This was a retrospective observational cohort study of patients in the Midland region of NZ, that underwent PAD-related percutaneous and surgical intervention between 1st January 2010 and 31st December 2021. Patient level data was collected. The primary outcome was prescribing of cardioprotective medications either before or within 1 year of incident procedure. Secondary outcome was overall survival. RESULTS: There were 2547 patients included. Antihypertensive prescription occurred in 80.7%, lipid-lowering in 77.4% and antithrombotic in 89.9%. Concomitant ischaemic heart disease increased prescription of cardioprotective medications. Women were prescribed less lipid-lowering medication compared to men. Maori men were prescribed less antiplatelet medication compared to non-Maori men. On univariate analysis lipid-lowering and antiplatelet medication showed survival advantage, while antihypertensive and anticoagulation did not. After adjustment for age, sex, end stage renal failure and presence of chronic limb-threatening ischaemia, best medical therapy was associated with better survival (HR 0.88, 95% CI 0.79-0.98, P = 0.02). CONCLUSION: This study highlights areas of deficiency in prescribing of cardioprotective medication in this high-risk group. These could be targets for national quality improvement initiatives.

Mortality differences by race over 20 years in individuals with peripheral artery disease.

INTRODUCTION: Racial disparities exist in patients with peripheral artery disease (PAD), with Black individuals having worse PAD-specific outcomes. However, mortality risk in this population has been mixed. As such, we sought to evaluate all-cause mortality by race among individuals with PAD. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES). Baseline data were obtained from 1999 to 2004. Patients with PAD were grouped according to self-reported race. Multivariable Cox proportional hazards regression was performed to calculate adjusted hazard ratios (HR) by race. A separate analysis was performed to study the effect of burden of social determinants of health (SDoH) on all-cause mortality. RESULTS: Of 647 individuals identified, 130 were Black and 323 were White. Black individuals had more premature PAD (30% vs 20%, p < 0.001) and a higher burden of SDoH compared to White individuals. Crude mortality rates were higher in Black individuals in the 40-49-year and 50-69-year age groups compared to White individuals (6.7% vs 6.1% and 8.8% vs 7.8%, respectively). Multivariable analysis demonstrated that Black individuals with both PAD and coronary artery disease (CAD) had a 30% higher hazard of death over 20 years compared to White individuals (HR = 1.3, 95% CI: 1.0-2.1). The cumulative burden of SDoH marginally (10-20%) increased the risk of all-cause mortality. CONCLUSIONS: In a nationally representative sample, Black individuals with PAD and CAD had higher rates of mortality compared to their White counterparts. These findings add further proof to the ongoing racial disparities among Black individuals with PAD and highlight the necessity to identify ways to mitigate these differences.

Racial and ethnic differences in presentation severity and postoperative outcomes in vascular surgery.

BACKGROUND: We assessed the effect of race and ethnicity on presentation severity and postoperative outcomes in those with abdominal aortic aneurysms (AAAs), carotid artery stenosis (CAS), peripheral arterial disease (PAD), and type B aortic dissection (TBAD). METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception until December 2020. Two reviewers independently selected randomized controlled trials and observational studies reporting race and/or ethnicity and presentation severity and/or postoperative outcomes for adult patients who had undergone major vascular procedures. They independently extracted the study data and assessed the risk of bias using the Newcastle-Ottawa scale. The meta-analysis used random effects models to derive the odds ratios (ORs) and risk ratios (RRs) and their corresponding 95% confidence intervals (CIs). The primary outcome was presentation severity stratified by the proportion of patients with advanced disease, including ruptured vs nonruptured AAA, symptomatic vs asymptomatic CAS, chronic limb-threatening ischemia vs claudication, and complicated vs uncomplicated TBAD. The secondary outcomes included postoperative all-cause mortality and disease-specific outcomes. RESULTS: A total of 81 studies met the inclusion criteria. Black (OR, 4.18; 95% CI, 1.31-13.26), Hispanic (OR, 2.01; 95% CI, 1.85-2.19), and Indigenous (OR, 1.97; 95% CI, 1.39-2.80) patients were more likely to present with ruptured AAAs than were White patients. Black and Hispanic patients had had higher symptomatic CAS (Black: OR, 1.20; 95% CI, 1.04-1.38; Hispanic: OR, 1.32; 95% CI, 1.20-1.45) and chronic limb-threatening ischemia (Black: OR, 1.67; 95% CI, 1.14-2.43; Hispanic: OR, 1.73; 95% CI 1.13-2.65) presentation rates. No study had evaluated the effect of race or ethnicity on complicated TBAD. All-cause mortality was higher for Black (RR, 1.23; 95% CI, 1.01-1.51), Hispanic (RR, 1.90; 95% CI, 1.57-2.31), and Indigenous (RR, 1.24; 95% CI, 1.12-1.37) patients after AAA repair. Postoperatively, Black (RR, 1.54; 95% CI, 1.19-2.00) and Hispanic (RR, 1.54; 95% CI, 1.31-1.81) patients were associated with stroke/transient ischemic attack after carotid revascularization and lower extremity amputation (RR, 1.90; 95% CI, 1.76-2.06; and RR, 1.69; 95% CI, 1.48-1.94, respectively). CONCLUSIONS: Certain visible minorities were associated with higher morbidity and mortality across various vascular surgery presentations. Further research to understand the underpinnings is required.

Rivaroxaban and aspirin vs. aspirin alone in Asian compared with non-Asian patients with chronic coronary artery disease or peripheral arterial disease: the COMPASS trial.

AIMS: It is unknown whether Asian and non-Asian patients with atherosclerotic vascular disease derive similar benefits from long-term antithrombotic therapy. METHODS AND RESULTS: In patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in The Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, the effects of rivaroxaban 2.5 mg b.i.d. plus aspirin 100 mg o.d. were compared with those of aspirin 100 mg o.d. in Asian vs. non-Asian patients (race was self-identified). Asians (n = 4269) vs. non-Asians (n = 23 126) had similar rates of major adverse cardiovascular events (MACEs) (4.85% vs. 4.83%, P = 0.30) and modified International Society on Thrombosis and Haemostasis (ISTH) major bleeding (2.72% vs. 2.58%, P = 0.22), but higher rates of intracranial haemorrhage (ICH) (0.63% vs. 0.29%, P = 0.01) and minor bleeding (13.61% vs. 6.49%, P < 0.001). In Asians vs. non-Asians, the combination of rivaroxaban and aspirin compared with aspirin alone produced consistent reductions in MACE [Asians: hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.45-0.90; non-Asians: HR: 0.78, 95% CI: 0.67-0.90; P(heterogeneity) = 0.29], increases in modified ISTH major bleeding (Asians: HR 2.24, 95% CI: 1.40-3.58; non-Asians: HR: 1.60, 95% CI: 1.30-1.97; P = 0.20), and net clinical outcome (Asians: HR: 0.77, 95% CI: 0.56-1.05; non-Asians: HR: 0.81, 95% CI: 0.70-0.93, P = 0.78), but borderline higher rates of ICH (Asians: HR: 3.50, 95% CI: 0.98-12.56; non-Asians: HR: 0.81, 95% CI: 0.43, 1.53; P = 0.04). CONCLUSION: Asian compared with non-Asian patients with chronic CAD and/or PAD have higher rates of ICH and minor bleeding. The combination of rivaroxaban and aspirin vs. aspirin alone produces similar effects for MACE, modified ISTH major bleeding, and net clinical outcome but may be associated with higher rates of ICH in Asian patients.

Racial and Ethnic Disparities in Peripheral Artery Disease.

Peripheral artery disease is an obstructive, atherosclerotic disease of the lower extremities causing significant morbidity and mortality. Black Americans are disproportionately affected by this disease while they are also less likely to be diagnosed and promptly treated. The consequences of this disparity can be grim as Black Americans bear the burden of lower extremity amputation resulting from severe peripheral artery disease. The risk factors of peripheral artery disease and how they differentially affect certain groups are discussed in addition to a review of pharmacological and nonpharmacological treatment modalities. The purpose of this review is to highlight health care inequities and provide a review and resource of available recommendations for clinical management of all patients with peripheral artery disease.

Outcome of Femoral-popliteal Bypass Procedures in Different Ethnic Groups in England: A Retrospective Analysis of Hospital Episode Statistics.

BACKGROUND: Previous studies, mainly from the United States, have reported worse outcomes from lower limb bypass procedures in ethnic minority populations. Limited nationwide data are available from ethnic minority populations from Europe. The aim of this study is to investigate outcomes from lower limb bypass procedures in ethnic minorities from England. METHODS: We enquired the "Hospital Episode Statistics" database, using ICD-10 codes to identify all cases of femoral-popliteal bypass operations from English NHS Hospitals from 01/01/2006 to 31/12/2015. Every case was followed up for 2 years for subsequent events. The primary outcomes were mortality and major leg amputation. Patients were broadly categorised according to Black, Asian and White ethnicity. Chi-square test was used to the ethnic groups and odds ratios (OR) were calculated using White ethnic group with the largest numbers of participants as a reference category. RESULTS: In the examined 10-year period, 20825 femoral-popliteal bypass procedures (250 of Black, 167 of Asian, and 20.408 of White ethnicity) were recorded. Thirty-day and 2-year mortality were 2.8% and 16.8% with no significant ethnic differences. Patients of Black ethnicity had higher risk of limb loss compared to Whites (23.2% vs. 15.6%, OR = 1.63, 95% confidence interval (CI) 1.21-2.19, P < 0.01). There was no significant difference in amputation rates between Asians and Whites (16.2% vs.. 15.6%, P = 0.94). CONCLUSIONS: Patients of Black ethnicity are at higher risk of limb loss after a femoropopliteal bypass procedure. Further research is needed to identify the causes of this discrepancy.

Association Between Genetic Variation in Blood Pressure and Increased Lifetime Risk of Peripheral Artery Disease.

[Figure: see text].

Associations between macrovascular and renal microvascular dysfunction in type 2 diabetes and non-diabetes: the HELIUS study.

BACKGROUND: Although the associations between measures of macrovascular and microvascular dysfunctions are well characterized in diabetes, there is limited data on these associations in individuals without diabetes. We compared the associations between macrovascular dysfunction and renal microvascular dysfunction in individuals with type 2 diabetes (T2D) and without diabetes. METHODS: Cross-sectional analyses of baseline data from the multiethnic Healthy Life in an Urban Setting (HELIUS) study (Amsterdam, the Netherlands), including 986 participants with T2D and 7680 participants without diabetes were done. Logistic regression analyses were used to examine the associations between macrovascular dysfunction [aortic stiffness, coronary artery disease (CAD), peripheral artery disease (PAD), and stroke] and renal microvascular dysfunction [albuminuria] with adjustments for age, sex, ethnicity, waist-to-hip ratio, systolic blood pressure, LDL-cholesterol, and smoking (and HbA1c and diabetes duration for the T2D group). RESULTS: In the fully adjusted models, aortic stiffness was associated with albuminuria in individuals with T2D [OR 2.55; 95% CI,1.30-4.98], but not without diabetes [0.96; 0.63-1.45]; stroke was associated with albuminuria in T2D [2.40;1.10-5.25], but not in non-diabetes [1.39;0.83-2.33]. In age-sex adjusted models, CAD was associated with albuminuria in T2D [1.65;1.09-2.50] and in non-diabetes [1.56;1.13-2.15]; the associations were no longer significant in the fully adjusted model. There were no associations between PAD and albuminuria in T2D and non-diabetes. CONCLUSIONS: Our study shows important differences in the associations between measures of macrovascular and renal microvascular dysfunction in T2D and non-diabetes. These findings provide opportunities for future research aimed at prevention and treatment strategies for individuals with vascular dysfunction.

Disparities in amputation in patients with peripheral arterial disease.

BACKGROUND: To describe peripheral arterial disease-related amputation as a marker for health disparities.

Association between Cystatin C and Peripheral Artery Disease in the Chinese Han Population.

BACKGROUND: Recent studies of the association between cystatin C and peripheral artery disease (PAD) have produced inconsistent results, and few studies have been conducted to investigate this association in the Chinese Han population. Therefore, we evaluated the relationship between cystatin C and PAD using Chinese data. METHODS: We performed a secondary analysis of the data from a previously published case-control study about PAD in our center. We examined the relationship between cystatin C and PAD by logistic regression models and subgroup and interaction analyses. We also constructed a propensity score-matched population by matching the conventional risk factors to further validate this association. In addition, we explored the relationship between cystatin C level and ankle-brachial index (ABI) strata (<0.4, ≥0.4) to shed light on a possible dose-dependent relationship between cystatin C levels and PAD severity. RESULTS: In total, 426 participants were included for evaluation. The mean serum cystatin C concentration was significantly lower in the control group than that in the case group (1.06 ± 0.19 mg/L vs. 1.24 ± 0.34 mg/L, P < 0.001). After adjustment for conventional risk factors, the risk of PAD was significantly higher in individuals with a cystatin C level of ≥1.25 mg/L. A 17% higher risk of PAD was associated with each 100-µg/L increase in the serum cystatin C level. Similar results were seen in the analyses of the propensity score-matched population comprising 164 participants. Furthermore, patients with an ABI <0.4 had higher cystatin C level than those with an ABI ≥0.4 (1.31 ± 0.05 mg/L vs. 1.18 ± 0.03 mg/L, P = 0.03). CONCLUSIONS: Our analysis indicated that an elevated cystatin C level is significantly associated with an increased risk of PAD in the Chinese Han population. Larger Chinese prospective cohort studies are needed to validate these findings.

Underuse of Cardiovascular Medications in Individuals With Known Lower Extremity Peripheral Artery Disease: HCHS/SOL.

Background Underuse of cardiovascular medications for secondary prevention among individuals with peripheral artery disease (PAD) has been reported. Little is known about PAD treatment status in the Hispanic/Latino population in the United States, who may have limited access to health care and who have worse clinical outcomes than non-Hispanic individuals. Methods and Results We studied the use of cardiovascular therapies in 1244 Hispanic/Latino individuals recruited from 4 sites in the United States, including 826 individuals who reported diagnosis of PAD by physician and 418 individuals with coronary artery disease alone, in the Hispanic Community Health Study/Study of Latinos. We compared the prevalence of using antiplatelet therapy, lipid-lowering therapy and antihypertensive therapy by PAD and coronary artery disease status. Among those with PAD, we studied factors associated with taking cardiovascular medications, including demographic and socioeconomic factors, acculturation, access to health care and comorbidities, using multivariable regression models. The overall prevalence for individuals with PAD taking antiplatelet therapy, lipid-lowering therapy and, among hypertensive individuals, antihypertensive therapy was 31%, 26% and 57%, respectively. Individuals of Mexican background had the lowest use for all classes of cardiovascular medications. Older age, number of doctor visits and existing hypertension and diabetes mellitus were significantly associated with taking cardiovascular therapies in adjusted models. Compared with those with PAD alone, individuals with PAD and concurrent coronary artery disease were 1.52 (95% CI, 1.20-1.93) and 1.74 (1.30-2.32) times more likely to use antiplatelet agents and statins according to multivariable analysis. No significant difference of antihypertensive medication use was found among PAD patients with or without coronary artery disease. Conclusions Hispanic/Latino individuals with known PAD underuse cardiovascular medications recommended in clinical guidelines. More efforts should be directed to improve treatment in this important group.

The Modified Frailty Index Does Not Predict Mortality After Major Lower Extremity Amputation for Peripheral Arterial Disease in an Asian Population.

BACKGROUND: Patients with critical limb ischemia (CLI) who undergo major lower extremity amputation (LEA) have been associated with high one-year mortality rates. Previous western-based studies have identified risk factors that exponentiate these poor outcomes, including nonambulatory status and cardiovascular morbidity. We assessed the effect of frailty, using the modified frailty index (mFI) in a cohort undergoing major LEA for CLI to predict mortality, perioperative complications, and unplanned readmissions in a tertiary institution from Singapore. METHODS: Data on patients who had undergone major LEA from January 2016 to December 2017 were collected retrospectively. Inclusion criteria were below-knee amputations (BKAs) or above-knee amputations (AKAs) performed for peripheral arterial disease-related tissue loss or sepsis only. Patients were categorized into 3 risk groups based on the 11-variable mFI: low mFI, 0-0.27; moderate mFI, 0.36-0.54; and high mFI ≥0.63. Univariate and multivariate analysis was performed using logistic regression analysis. RESULTS: 211 patients underwent major LEA, of whom 133 (63.0%) had undergone BKA. The mean mFI was 0.41 (range 0-0.81). 84/211 (39.8%) died within 1 year after the procedure, with mortality rates of 25/65 (38.4%), 49/127 (38.6%), and 10/19 (52.6%) in the low-, moderate-, high-mFI categories, respectively. High and moderate mFI had failed to demonstrate an increased risk of mortality when compared with the low-mFI group (P > 0.05). 91/211 (43.1%) patients had perioperative complications, whereas 27/211 (12.8%) patients were readmitted within 30 days of discharge. Myocardial infarction, chronic kidney disease, and atrial fibrillation were found to be predictive of poor outcomes after major LEA. CONCLUSIONS: Frailty as measured with the mFI did not predict outcome after major LEA. This could be due to confounding effects such as high prevalence of renal dysfunction and the constancy of diabetes and peripheral vascular disease in this population that would reduce the differentiation of patients using the mFI.

Epidemiology and Risk of Amputation in Patients With Diabetes Mellitus and Peripheral Artery Disease.

Peripheral artery disease (PAD) stems from atherosclerosis of lower extremity arteries with resultant arterial narrowing or occlusion. The most severe form of PAD is termed chronic limb-threatening ischemia and carries a significant risk of limb loss and cardiovascular mortality. Diabetes mellitus is known to increase the incidence of PAD, accelerate disease progression, and increase disease severity. Patients with concomitant diabetes mellitus and PAD are at high risk for major complications, such as amputation. Despite a decrease in the overall number of amputations performed annually in the United States, amputation rates among those with both diabetes mellitus and PAD have remained stable or even increased in high-risk subgroups. Within this cohort, there is significant regional, racial/ethnic, and socioeconomic variation in amputation risk. Specifically, residents of rural areas, African-American and Native American patients, and those of low socioeconomic status carry the highest risk of amputation. The burden of amputation is severe, with 5-year mortality rates exceeding those of many malignancies. Furthermore, caring for patients with PAD and diabetes mellitus imposes a significant cost to the healthcare system-estimated to range from $84 billion to $380 billion annually. Efforts to improve the quality of care for those with PAD and diabetes mellitus must focus on the subgroups at high risk for amputation and the disparities they face in the receipt of both preventive and interventional cardiovascular care. Better understanding of these social, economic, and structural barriers will prove to be crucial for cardiovascular physicians striving to better care for patients facing this challenging combination of chronic diseases.

Atherosclerotic Peripheral Artery Disease in the United States: Gender and Ethnic Variation in a Multiple Cause-of-Death Analysis.

BACKGROUND: Atherosclerotic peripheral artery disease (PAD) is an important cause of morbidity in the United States. In this article, we conducted a multiple cause-of-death analysis of PAD to determine patterns and trends in its contribution to mortality. METHODS: The Centers for Disease Control and Prevention statistics data were used to determine the number of deaths with the following 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes selected as an underlying cause of death (UCOD) or a contributing cause considering multiple causes of death (MCOD): 170.2, 170.9, 173.9, 174.3, and 174.4. The age-adjusted death rates per 100 000 population by age, gender, race, ethnicity, and region were computed for the United States between the years 1999 and 2017. In these years, there were 47 728 569 deaths from all causes. RESULTS: In 1999 to 2017 combined, there were a total of 311 175 deaths associated with PAD as an UCOD. However, there were 1 361 253 deaths with PAD listed as an UCOD or a contributing cause in MCOD, which is 4.3 times higher than UCOD. Age-adjusted MCOD rates were higher in males (25.6) than in females (19.4). Among non-Hispanics, the rate in African American males and females was 1.2 times higher than in Caucasians. Age-adjusted MCOD rates have declined in African Americans and Caucasians irrespective of gender from 2000 to 2017. CONCLUSION: Peripheral artery disease is mentioned 4 times as often on death certificates as a contributing cause of death as it is chosen as the UCOD. Overall, age-adjusted MCOD rates were higher in African Americans than Caucasians, males than females, and declined between 2000 and 2017.

Early and Midterm Experience With the Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold in Asian Patients With Chronic Limb-Threatening Ischemia: One-Year Clinical and Imaging Outcomes From the DISAPEAR Registry.

Purpose: To report an experience with the Absorb bioresorbable vascular scaffold (BVS) in an Asian cohort with chronic limb-threatening ischemia (CLTI) from the DISAPEAR (Drug Impregnated Bioresorbable Stent in Asian Population Extremity Arterial Revascularization) registry. Materials and Methods: A retrospective analysis was conducted of 41 patients (median age 64 years; 23 men) with CLTI owing to >50% de novo infrapopliteal lesions (n=53) treated with the Absorb BVS between August 2012 and June 2017. The majority of patients (37, 90%) had diabetes, 24 (59%) had ischemic heart disease, and 39 (95%) had Rutherford category 5/6 ischemia with tissue loss. The mean lesion length was 22.7±17.2 mm; 10 (24%) lesions were severely calcified. Assessments included technical success, primary patency, freedom from clinically-driven target lesion revascularization (CD-TLR), amputation-free survival, limb salvage, complete wound healing, resolution of rest pain, and resolution of CLTI without TLR at 6 and 12 months after the index intervention. Results: Overall, 69 scaffolds were implanted in the 53 lesions, with 100% technical success. There were no deaths within 30 days of the index procedure. The primary patency rates at 6 and 12 months were 95% and 86%, respectively. The corresponding rates of freedom from CD-TLR were 98% and 93%, respectively. Freedom from major amputation was 98% at both time points, and amputation-free survival was 93% and 85% at 6 and 12 months after the index procedure. Wound healing occurred in 31 patients (79%) with Rutherford category 5/6 ischemia by the end of 12 months. Conclusion: The Absorb BVS demonstrated good 1-year patency and clinical outcomes in CLTI patients with complex infrapopliteal disease.

Examination of race and infrainguinal bypass conduit use in the Society for Vascular Surgery Vascular Quality Initiative.

BACKGROUND: Vein conduit is known to have better patency than prosthetic for infrainguinal bypass. Here we explore if racial disparities exist in infrainguinal bypass vein conduit use amid preoperative patient and systemic factors. METHODS: Retrospective Society for Vascular Surgery Vascular Quality Initiative data for 23,959 infrainguinal bypasses between 2003 and 2017 for occlusive disease were analyzed. For homogeneity, only infrainguinal bypasses originating from the common femoral artery were included. Demographics of patients receiving vein vs prosthetic were compared and logistic regression analyses were performed with race and preoperative factors to evaluate for predictors of vein conduit use. RESULTS: Adjusted regression models demonstrated black patients were 76% as likely (p < .001) and Hispanic patients 79% as likely (p = .003) to have vein conduit compared to white patients. Factors positively correlating with vein use included vein mapping, more distal bypass target, tissue loss or acute ischemia bypass indications, commercial insurance, and weight. Factors against vein use included advanced age, female gender, ASA class 4, urgent procedure, preoperative mobility limitation, prior CABG or leg bypass, prior smoking, preoperative anticoagulation, and a bypass performed in the Southern US or before 2012. While black and Hispanic patients were less likely to receive vein, they were vein mapped at similar or higher rates than other groups. CONCLUSION: Racial disparities exist in conduit use for infrainguinal bypass, with black and Hispanic patients less likely to receive vein bypasses. However, the contribution of race to conduit selection is small in adjusted and unadjusted models. Overall, pre-operative variables in the Vascular Quality Initiative poorly predicted vein conduit use for infrainguinal bypass.

Association of Circulating Hepatocyte Growth Factor and Risk of Incident Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis.

Higher levels of hepatocyte growth factor (HGF) have been associated with the presence of peripheral arterial disease (PAD), but prospective associations are unknown. We examined the association of circulating HGF levels with incident PAD. Between 2000 and 2002, HGF was measured in 6742 Multi-Ethnic Study of Atherosclerosis participants without PAD. Incident clinical PAD, adjudicated on the basis of a positive history for the presence of disease-related symptoms or treatment, was ascertained through 2015. Incident low ankle-brachial index (ABI), defined as an ABI < 0.9 and a decline of ≥ 0.15, was assessed among 5736 individuals who had an ABI > 0.9 at baseline and ≥1 follow-up ABI measurement 3 to 10 years later. There were 116 clinical PAD and 197 low ABI events that occurred over a median follow-up of 14 and 9 years, respectively. After adjustment for demographic and clinical variables, a standard deviation increment of HGF (303 ng/L) was associated with an increased risk of clinical PAD (hazard ratio: 1.21; 95% confidence interval [CI]: 1.05-1.39) but not a low ABI (rate ratio: 1.03; 95% CI: 0.85-1.25). In conclusion, higher HGF levels were modestly associated with an increased risk of developing clinical PAD.

Cholesterol mass efflux capacity and risk of peripheral artery disease: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: We aimed to assess the relationship of HDL (high-density lipoprotein)-mediated cholesterol mass efflux capacity (CMEC) with risk of incident peripheral artery disease (PAD). METHODS: CMEC was measured in 1458 Multi-Ethnic Study of Atherosclerosis participants between 2000 and 2002 as part of a case-control study matched for incident cardiovascular disease and progression of carotid plaque by ultrasound. Incident clinical PAD, adjudicated on the basis of a positive history for the presence of disease-related symptoms or treatment, was ascertained through 2015 in 1419 individuals without clinical PAD at baseline. Subclinical PAD, defined as an ankle-brachial index (ABI) ≤1.0, was assessed among 1255 individuals with a baseline ABI >1.0 and at least one follow-up ABI measurement 3-10 years later. Cox proportional hazards and relative risk regression modeling per SD increment of CMEC were used to determine the association of CMEC with clinical and subclinical PAD, respectively. RESULTS: There were 38 clinical PAD and 213 subclinical PAD events that occurred over a mean follow-up of 6.0 and 6.5 years respectively. After adjustment for age, gender, and race, higher CMEC levels were not associated with clinical PAD (hazard ratio 1.25; 95% CI 0.89, 1.75) or subclinical PAD (risk ratio 1.02; 95% CI, 0.94, 1.11). CONCLUSIONS: These findings suggest that HDL-mediated cholesterol efflux is not significantly associated with incident clinical and subclinical PAD.

Sedentary time and peripheral artery disease: The Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Experimental evidence suggests that sedentary time (ST) may contribute to cardiovascular disease by eliciting detrimental hemodynamic changes in the lower limbs. However, little is known about objectively measured ST and lower extremity peripheral artery disease (PAD). METHODS: We included 7,609 Hispanic/Latinos (ages 45-74) from the Hispanic Community Health Study/Study of Latinos. PAD was measured using the ankle brachial index (≤0.9). ST was measured using accelerometry. We used multivariable logistic regression to assess associations of quartiles of ST and PAD, and then used the same logistic models with restricted cubic splines to investigate continuous nonlinear associations of ST and PAD. Models were sequentially adjusted for traditional PAD risk factors, leg pain, and moderate- to vigorous-intensity physical activity (MVPA). RESULTS: Median ST was 12.2 h/d, and 5.4% of individuals had PAD. In fully adjusted restricted cubic splines models accounting for traditional PAD risk factors, leg pain, and MVPA, ST had a significant overall (P = .048) and nonlinear (P = .024) association with PAD. A threshold effect was seen such that time spent above median ST was associated with higher odds of PAD. That is, compared to median ST, 1, 2, and 3 hours above median ST were associated with a PAD odds ratio of 1.16 (95% CI = 1.02-1.31), 1.44 (1.06-1.94), and 1.80 (1.11-2.90), respectively. CONCLUSIONS: Among Hispanic/Latino adults, ST was associated with higher odds of PAD, independent of leg pain, MVPA, and traditional PAD risk factors. Notably, we observed a threshold effect such that these associations were only observed at the highest levels of ST.

The effect of rurality on the risk of primary amputation is amplified by race.

OBJECTIVE: Primary amputation (ie, without attempted revascularization) is a devastating complication of peripheral artery disease. Racial disparities in primary amputation have been described; however, rural disparities have not been well investigated. The purpose of this study was to examine the impact of rurality on risk of primary amputation and to explore the effect of race on this relationship. METHODS: The national Vascular Quality Initiative amputation data set was used for analyses (N = 6795). The outcome of interest was primary amputation. Independent variables were race/ethnicity (non-Latinx whites vs nonwhites) and rural residence. Multivariable logistic regression examined impact of rurality and race/ethnicity on primary amputation after adjustment for relevant covariates and included an interaction for race/ethnicity by rural status. RESULTS: Primary amputation occurred in 49% of patients overall (n = 3332), in 47% of rural vs 49% of urban patients (P = .322), and in 46% of whites vs 53% of nonwhites (P < .001). On multivariable analysis, nonwhites had a 21% higher odds of undergoing primary amputation overall (adjusted odds ratio [AOR], 1.21; 95% confidence interval [CI], 1.05-1.39). On subgroup analysis, rural nonwhites had two times higher odds of undergoing primary amputation than rural whites (AOR, 2.06; 95% CI, 1.53-2.78) and a 52% higher odds of undergoing primary amputation than urban nonwhites (AOR, 1.52; 95% CI, 1.19-1.94). In the urban setting, nonwhites had a 21% higher odds of undergoing primary amputation than urban whites (AOR, 1.21; 95% CI, 1.05-1.39). CONCLUSIONS: In these analyses, rurality was associated with greater odds for primary amputation in nonwhite patients but not in white patients. The effect of race on primary amputation was significant in both urban and rural settings; however, the effect was significantly stronger in rural settings. These findings suggest that race/ethnicity has a compounding effect on rural health disparities and that strategies to improve health of rural communities need to consider the particular needs of nonwhite residents to reduce disparities.