Study protocol for a multicentre comparative diagnostic accuracy study of tools to establish the presence and severity of peripheral arterial disease in people with diabetes mellitus: the DM PAD study.

INTRODUCTION: Peripheral arterial disease (PAD) is a key risk factor for cardiovascular disease, foot ulceration and lower limb amputation in people with diabetes. Early diagnosis of PAD can enable optimisation of therapies to manage these risks. Its diagnosis is fundamental, though challenging in the context of diabetes. Although a variety of diagnostic bedside tests are available, there is no agreement as to which is the most accurate in routine clinical practice.The aim of this study is to determine the diagnostic performance of a variety of tests (audible waveform assessment, visual waveform assessment, ankle brachial pressure index (ABPI), exercise ABPI and toe brachial pressure index (TBPI)) for the diagnosis of PAD in people with diabetes as determined by a reference test (CT angiography (CTA) or magnetic resonance angiography (MRA)). In selected centres, we also aim to evaluate the performance of a new point-of-care duplex ultrasound scan (PAD-scan). METHODS AND ANALYSIS: A prospective multicentre diagnostic accuracy study (ClinicalTrials.gov Identifier NCT05009602). We aim to recruit 730 people with diabetes from 18 centres across the UK, covering primary and secondary healthcare. Consenting participants will undergo the tests under investigation. Reference tests (CTA or MRA) will be performed within 6 weeks of the index tests. Imaging will be reported by blinded consultant radiologists at a core imaging lab, using a validated scoring system, which will also be used to categorise PAD severity. The presence of one or more arterial lesions of ≥50% stenosis, or tandem lesions with a combined value of ≥50%, will be used as the threshold for the diagnosis of PAD. The primary outcome measure of diagnostic performance will be test sensitivity. ETHICS AND DISSEMINATION: The study has received approval from the National Research Ethics Service (NRES) (REC reference 21/PR/1221). Results will be disseminated through research presentations and papers. TRIAL REGISTRATION NUMBER: NCT05009602.

Combined impact of elevated arterial stiffness and left ventricular filling pressure on outcomes after off-pump coronary artery bypass grafting.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) and early diastolic transmitral flow velocity to mitral annular tissue velocity (E/e')-which are markers of arterial stiffness and left ventricular (LV) filling pressure, respectively-have been associated with morbidity and mortality. We investigated their combined impact on postoperative complications and long-term survival of patients undergoing off-pump coronary artery bypass grafting (OPCAB). METHODS: A cohort of 164 patients were divided into four groups: baPWV ≤ 19 m/s and E/e' ≤ 15 (reference), baPWV > 19 m/s and E/e' ≤ 15 (high-PWV-only), baPWV ≤ 19 m/s and E/e' > 15 (high-E/e'-only), and baPWV > 19 m/s and E/e' > 15 (high-PWV-and-E/e'). After inverse probability treatment weighting adjustment, each group was compared with the reference group to analyze the odds ratios of postoperative complications and the Kaplan-Meier survival curves, and to identify the group representing an independent prognostic predictor. RESULTS: The median age and follow-up duration were 69 years and 57.2 months, respectively. Both postoperative acute kidney injury (POAKI) and atrial fibrillation (POAF) were higher in the high-PWV-and-E/e' group (adjusted odds ratio (OR) = 89.5; 95% confidence interval (CI), 8.5-942.3; p < 0.001 and OR = 12.5; CI, 2.5-63.8; p = 0.002, respectively). Compared to the reference group, only the high-PWV-and-E/e' group showed significantly lower survival rate (91.0%; CI, 82.8-100% vs. 44.8%; CI, 21.2-94.6%) and a higher hazard for all-cause mortality after adjustment for covariates (hazard ratio = 6.1; p = 0.002). CONCLUSION: Concurrent elevation in PWV and E/e' may independently affect not only the rates of POAKI and POAF but also long-term survival after OPCAB.

Diagnostic Accuracy of Point-of-care Tests Used to Detect Arterial Disease in Diabetes: TEsting for Arterial Disease in Diabetes (TrEAD) Study.

OBJECTIVE: We compared the diagnostic performance of a novel point-of-care duplex ultrasound test (podiatry ankle duplex scan; PAD-scan) against commonly used bedside tests for the detection of PAD in diabetes. BACKGROUND: PAD is a major risk factor for diabetic foot ulceration and amputation. Its diagnosis is fundamental though challenging. Although a variety of bedside tests are available, there is no agreement as to which is the most useful. PAD-scan may be advantageous over current tests as it allows for vessel visualization and more accurate arterial waveform assessment. However, its accuracy has not been previously evaluated. METHODS: From March to October 2019, we recruited 305 patients from 2 diabetic foot clinics. The diagnostic performance of ankle-brachial pressure index, toe-brachial pressure index, transcutaneous pressure of oxygen, pulse palpation, and ankle waveform assessment using PAD-scan and Doppler devices (audible and visual waveform assessment) were assessed. The reference test was a full lower limb duplex ultrasound. RESULTS: Based on the reference test, 202 (66.2%) patients had evidence of PAD. PAD-scan had a significantly higher sensitivity [95%, confidence interval (CI) 90%-97%) as compared to all other tests. Particularly low sensitivities were seen with pulse palpation (43%, CI 36%-50%) and transcutaneous pressure of oxygen (31%, CI 24%-38%). PAD-scan had a lower specificity (77%, CI 67%-84%) compared to toe-brachial pressure index (86%, CI 78%-93%; P < 0.001), but not statistically different when compared to all other tests. CONCLUSIONS: PAD-scan has superior diagnostic utility and is a valid first line investigation.

Ankle-brachial index predicts renal outcomes and all-cause mortality in high cardiovascular risk population: a nationwide prospective cohort study in CORE project.

BACKGROUND: Low ankle-brachial index (ABI) related ischemic events are common among individuals with chronic kidney disease (CKD). It is also associated with an increased risk of rapid renal function decline. The presence of peripheral artery disease (PAD) with low ABI among patients with high cardiovascular (CV) risk increases limb loss and mortality. AIMS: To estimate the association between abnormal ABI and renal endpoints and all-cause mortality. METHODS: A multicenter prospective cohort study was conducted among subjects with high CV risk or established CV diseases in Thailand. The subjects were divided into 3 groups based on ABI at baseline > 1.3, 0.91-1.3, and ≤ 0.9, respectively. Primary composite outcome consisted of estimated glomerular filtration rate (eGFR) decline over 40%, eGFR less than 15 mL/min/1.73 m2, doubling of serum creatinine and initiation of dialysis. The secondary outcome was all-cause mortality. Cox regression analysis and Kaplan-Meier curve were performed. RESULTS: A total of 5543 subjects (3005 men and 2538 women) were included. Cox proportional hazards model showed a significant relationship of low ABI (ABI ≤ 0.9) and primary composite outcome and all-cause mortality. Compared with the normal ABI group (ABI 0.91-1.3), subjects with low ABI at baseline significantly had 1.42-fold (95% CI 1.02-1.97) and 2.03-fold (95% CI 1.32-3.13) risk for the primary composite outcome and all-cause mortality, respectively, after adjusting for variable factors. CONCLUSION: Our study suggested that PAD independently predicts the incidence of renal progression and all-cause mortality among Thai patients with high CV risk.

Comprehensive cardiac rehabilitation program for peripheral arterial diseases.

Peripheral arterial disease (PAD) is a phenotype of atherosclerotic disease often associated with cerebrovascular or coronary artery disease. The incidence of cardiovascular events in patients with PAD is 5.4% per year, which is higher than that of cerebrovascular or coronary artery disease. The most useful screening method for PAD is the ankle brachial pressure index (ABI). The ABI should be measured in (1) all patients with lower limb symptoms such as claudication, (2) all patients aged 65 years and over, and (3) those aged 50 to 65 years who have risk factors such as smoking and diabetes mellitus. PAD is diagnosed if the ABI is <0.9. A comprehensive cardiac rehabilitation program includes complete smoking cessation, blood pressure control with antihypertensive medications and salt reduction for hypertension, glycemic control for diabetes mellitus, and appropriate medications such as antiplatelet agents and statins. A multidisciplinary team approach is effective in comprehensive cardiac rehabilitation for patients with PAD, even those with critical limb ischemia (CLI). Exercise therapy is a crucial and essential treatment for PAD, except in CLI. Exercise therapy is contraindicated in patients with acute arterial occlusion and CLI with infection. PAD is often associated with other atherosclerotic diseases; the patient should be monitored for ischemic heart disease during the initial exercise stress test using the Gardner treadmill protocol. Supervised exercise therapy is highly recommended (Class I, Level of Evidence A). Alternatively, a home-based exercise program is feasible (Class IIa, Level of Evidence A). The exercise type (treadmill, track walking, ergometer), frequency (3 to 5 days per week), intensity (speed and incline), and duration (30 minutes) are determined based on the exercise stress test results for each patient. Exercise should be continued at least 3 times a week for at least 12 weeks. Cilostazol is highly recommended (Class I, Level of Evidence A).

Carotid intima-media thickness and plagues are associated with indicators of peripheral artery diseases in patients with diabetes.

AIMS: We investigated associations of carotid intima-media thickness (CIMT) and carotid plaque with ankle-brachial index (ABI) and toe-brachial index (TBI) in Chinese adults. METHODS: A cross-sectional analysis was performed in 6688 participants from a well-defined Chinese community. CIMT and carotid plaque was measured with a high-resolution B-mode tomographic ultrasound system. Low ABI was defined as ABI ≤ 0.90. Low TBI was defined as TBI ≤ 0.60. Carotid plaques were classified as normal, homogeneous or heterogeneous according to morphology. RESULTS: After adjusting for age, sex and body mass index, each 0.10 mm CIMT increase was associated with 0.0123 unit decrease in TBI (P = 0.004) and 0.0063 in ABI (P = 0.04) in patients with diabetes. After further adjustments for waist circumference, smoking and drinking habits, hypertension, lipids and hemoglobin A1c, the associations between CIMT and TBI remained significant; while those with ABI were disappeared. Meanwhile, each 0.10 mm increment of CIMT or rank of carotid plaque morphology was associated with a risk of presence of low TBI (CIMT: odds ratio: 1.21, 95% confidence interval: 1.05-1.40; carotid plaque morphology: 1.45, 1.01-2.08) in patients with diabetes after adjustments. However, no associations were found between CIMT or carotid plaque morphology and TBI or ABI in non-diabetic participants. CONCLUSIONS: CIMT and carotid plaque morphology were significantly associated with TBI in patients with diabetes.

Screening for Peripheral Artery Disease Using the Ankle-Brachial Index: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Peripheral artery disease (PAD) is associated with a high risk for cardiovascular events and poor ambulatory function, even in the absence of symptoms. Screening for PAD with the ankle-brachial index (ABI) may identify patients in need of treatment to improve health outcomes. Objective: To systematically review evidence for the US Preventive Services Task Force on PAD screening with the ABI, the diagnostic accuracy of the test, and the benefits and harms of treatment of screen-detected PAD. Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant English-language studies published between January 2012 and May 2, 2017. Surveillance continued through February 7, 2018. Study Selection: Studies of unselected or generally asymptomatic adults with no known cardiovascular disease. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Main Outcomes and Measures: Cardiovascular morbidity; PAD morbidity; mortality; health-related quality of life; diagnostic accuracy; and serious adverse events. Results: Five studies (N = 5864 participants) were included that examined the indirect evidence for the benefits and harms of screening and treatment of screen-detected PAD. No population-based screening trials evaluated the direct benefits or harms of PAD screening with the ABI alone. A single diagnostic accuracy study of the ABI compared with magnetic resonance angiography gold-standard imaging (n = 306) found low sensitivity (7%-34%) and high specificity (96%-100%) in a screening population. Two adequately powered trials (n = 4626) in asymptomatic populations with and without diabetes with a variably defined low ABI (≤0.95 or ≤0.99) showed no statistically significant effect of aspirin (100 mg daily) for composite CVD outcomes (adjusted hazard ratio [HR], 1.00 [95% CI, 0.81-1.23] and HR, 0.98 [95% CI, 0.76-1.26]). One trial (n = 3350) demonstrated no statistically significant increase in major bleeding events with the use of aspirin (adjusted HR, 1.71 [95% CI, 0.99- 2.97]) and no statistically significant increase in major gastrointestinal bleeding (relative risk, 1.13 [95% CI, 0.44-2.91]). Two exercise trials (n = 932) in screen-relevant populations reported no differences in quality of life, Walking Impairment Questionnaire walking distance, or symptoms at 12 and 52 weeks; no harms were reported. Conclusions and Relevance: There was no direct evidence and limited indirect evidence on the benefits of PAD screening with the ABI in unselected or asymptomatic populations. Available studies suggest low sensitivity and lack of beneficial effect on health outcomes, but these studies have important limitations.

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

Importance: Peripheral artery disease (PAD) is a manifestation of atherosclerosis in the lower limbs. It can impair walking and, in severe cases, can lead to tissue loss, infection, and amputation. In addition to morbidity directly caused by PAD, patients with PAD are at increased risk for cardiovascular disease (CVD) events, because atherosclerosis is a systemic disease that also causes coronary and cerebrovascular events. Objective: To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on screening for PAD and CVD risk with the ankle-brachial index (ABI). Evidence Review: The USPSTF reviewed the evidence on whether screening for PAD with the ABI in generally asymptomatic adults reduces morbidity or mortality from PAD or CVD. The current review expanded on the previous review to include individuals with diabetes and interventions that include supervised exercise and physical therapy intended to improve outcomes in the lower limbs. Findings: The USPSTF found few data on the accuracy of the ABI for identifying asymptomatic persons who can benefit from treatment of PAD or CVD. There are few studies addressing the benefits of treating screen-detected patients with PAD; 2 good-quality studies showed no benefit of using the ABI to manage daily aspirin therapy in unselected populations, and 2 studies showed no benefit from exercise therapy. No studies addressed the harms of screening, although the potential exists for overdiagnosis, labeling, and opportunity costs. Studies that addressed the harms of treatment showed nonsignificant results. Therefore, the USPSTF concludes that the current evidence is insufficient and that the balance of benefits and harms of screening for PAD with the ABI in asymptomatic adults cannot be determined. Conclusions and Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for PAD and CVD risk with the ABI in asymptomatic adults. (I statement).