High ankle brachial index predicts high risk of cardiovascular events amongst people with peripheral artery disease

Ankle-brachial pressure index (ABPI) is commonly measured in people referred to vascular specialists. This study aimed to assess the association of high ABPI (≥ 1.4) with cardiovascular events in people with peripheral artery disease (PAD). 1533 participants with PAD diagnosed by a vascular specialist were prospectively recruited from four out-patient clinics in Australia. ABPI was measured at recruitment and the occurrence of myocardial infarction (MI), stroke or cardiovascular death (major cardiovascular events; MACE) and any amputation were recorded over a median (inter-quartile range) follow-up of 3.3 (1.0–7.1) years. The association of high, compared to normal, low (0.5–0.9) or very low (<0.5), ABPI with clinical events was estimated using Cox proportional hazard analyses, adjusting for traditional risk factors and reported as hazard ratio with 95% confidence intervals. 596 (38.9%), 676 (44.1%), 157 (10.2%) and 104 (6.8%) participants had normal, low, very low and high ABPI, respectively. Participants with high ABPI had increased risk of MACE, MI and death by comparison to those with either normal ABPI [1.69 (1.07, 2.65), 1.93 (1.07, 3.46) and 1.67 (1.09, 2.56)] or either low or very low ABPI [1.51 (1.02, 2.23), 1.92 (1.16, 3.19) and 1.47 (1.02, 2.14)] after adjusting for other risk factors. Findings were similar in a sensitivity analysis excluding people with ABPI only measured in one leg (n = 120). Participants with high ABPI also had an increased risk of MACE and MI compared to those with very low ABPI alone. High ABPI is a strong indicator of excess risk of cardiovascular events amongst people with PAD.

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Traditional and non-traditional risk factors for peripheral artery disease development/progression in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study

Cardiovascular Diabetology ◽

10.1186/s12933-021-01249-y ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Claudia R. L. Cardoso ◽

Juliana V. Melo ◽

Thainá R. M. Santos ◽

Nathalie C. Leite ◽

Gil F. Salles

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Peripheral Artery Disease ◽

Microvascular Complications ◽

Ankle Brachial Index ◽

Peripheral Artery ◽

Prognostic Information ◽

Traditional Risk Factors ◽

Artery Disease

Abstract Background The prognostic importance of non-traditional risk factors for peripheral artery disease (PAD) development/progression is scarcely studied in diabetes. We investigated if carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cf-PWV) added prognostic information beyond traditional cardiovascular risk markers for PAD outcomes. Methods Ankle-brachial index (ABI) was measured at baseline and after a median of 91 months of follow-up in 681 individuals with type 2 diabetes. Multivariate Cox regressions examined the associations between the candidate variables and the outcome. PAD development/progression was defined by a reduction in ABI ≥ 0.15 (to a level < 0.9) or limb revascularization procedures, lower-extremity amputations or death due to PAD. The improvement in risk discrimination was assessed by increases in C-statistics of the models. Results Seventy-seven patients developed/progressed PAD: 50 reduced ABI to < 0.9, seven had lower-limb revascularizations, and 20 had amputations or death. Age, male sex, diabetes duration, presence of microvascular complications (peripheral neuropathy and diabetic kidney disease), baseline HbA1c, 24-h systolic BP (SBP) and mean cumulative office SBP and LDL-cholesterol were associated with PAD development/progression in several models. CIMT and cf-PWV were additionally associated with PAD outcomes, and their inclusion further improved risk discrimination (with C-statistic increases between 0.025 and 0.030). The inclusion of ambulatory 24-h SBP, instead of office SBP, also improved PAD risk discrimination. Conclusions Increased CIMT and aortic stiffness are associated with greater risks of developing/progressing PAD, beyond traditional risk factors, in type 2 diabetes.

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A Targeted Literature Review of the Disease Burden in Patients With Symptomatic Peripheral Artery Disease

Angiology ◽

10.1177/0003319719896477 ◽

2019 ◽

Vol 71 (4) ◽

pp. 303-314

Author(s):

Rupert Bauersachs ◽

Sebastian Debus ◽

Mark Nehler ◽

Maria Huelsebeck ◽

Janita Balradj ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Disease Burden ◽

Ankle Brachial Index ◽

Peripheral Artery ◽

Economic Burden Of Disease ◽

Surgical Interventions ◽

Treatment Practice ◽

Patient Profile ◽

Increased Risk ◽

Artery Disease

Patients with peripheral artery disease (PAD) have an increased risk of cardiovascular (CV) and limb events, but the disease is frequently underdiagnosed and treatment options are limited. This review examines the disease burden of symptomatic PAD as well as key guideline recommendations. Publications were identified using the ProQuest portal to access the Medline, Medline In-Process, and Embase databases. Search terms for symptomatic PAD were combined with terms relevant to epidemiology, burden, treatment practice, and physiopathology. Articles in English published between January 2001 and September 2016 were screened according to the population, interventions, comparator, outcomes, and study design criteria. Relevant publications (n = 200) were identified. The reported incidence and prevalence of PAD varied depending on the definitions used and the study populations. Patients generally had a poor prognosis, with an increased risk of mortality, CV, and limb events and decreased quality of life. Guideline recommendations included ankle–brachial index measurements, exercise testing, and angiography for diagnosis and risk factor modification, antiplatelets, cilostazol, exercise therapy, or surgical interventions for treatment, depending on the patient profile. The clinical, humanistic, and economic burden of disease in patients with symptomatic PAD is substantial and needs to be reduced through improved PAD management.

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Abstract 11: Effects of Canakinumab in Patients With Peripheral Artery Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.11 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Kerry S Russell ◽

Denise Yates ◽

Andrea Feller ◽

Tianke Wang ◽

Ping Chen ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Vascular Function ◽

Cardiovascular Events ◽

Ankle Brachial Index ◽

Unmet Need ◽

Walking Distance ◽

Plaque Progression ◽

Peripheral Artery ◽

Plaque Volume ◽

Artery Disease

Background: Peripheral artery disease (PAD) affects 8.5 million people in the US. PAD patients are at high risk for cardiovascular events, and their quality of life is often significantly impaired by decreased mobility. Interleukin-1β (IL-1β) may play an important role in this disease by promoting inflammatory responses that drive atherosclerotic plaque progression and impair vascular function. We sought to test whether interruption of IL-1β signaling would improve patient mobility and decrease plaque progression in the lower extremities. Methods: 38 patients (mean age 65; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive Canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. Plaque volume in the superficial femoral artery (SFA) was assessed serially using 3.0T MRI. Mobility was assessed serially using the 6-minute walk test (maximum and pain-free walking distance). Results: Canakinumab was safe and well-tolerated. 12 patients discontinued (8 placebo, 4 Canakinumab). MRI data (from 31 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA at either time point in placebo-treated patients; nor was there a change in plaque volume in the Canakinumab-treated group. There was a serial and significant improvement in placebo-adjusted maximum and pain-free walking distance observed as early as 3 months after treatment with Canakinumab (58-meter improvement over placebo in pain-free distance at 3 months, P=0.01). Two placebo-treated patients required peripheral vascular interventions due to progression of disease; however, no Canakinumab-treated patients required revascularization during the study. Canakinumab decreased markers of systemic inflammation (IL-6 and hsCRP). Conclusions: Treatment with Canakinumab may improve maximum and pain-free walk distance in patients with symptomatic PAD. In conjunction with results soon to be reported for the CANTOS trial of Canakinumab for secondary prevention of cardiovascular events, additional studies may provide support that inhibition of IL-1β signaling can improve symptoms and function in this patient population with high unmet need.

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Abstract 91: Are At Risk Outpatient Cardiology Patients being Appropriately Evaluated for Lower Extremity PAD as Recommended by ACC/AHA Guidelines?

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.5.suppl_1.a91 ◽

2012 ◽

Vol 5 (suppl_1) ◽

Author(s):

Rajesh M Kabadi ◽

Ankitkumar Patel ◽

Rajani Sharma ◽

Rita Schmidt ◽

Elias Iliadis

Keyword(s):

Risk Factors ◽

At Risk ◽

High Risk ◽

Lower Extremity ◽

Peripheral Artery Disease ◽

Ankle Brachial Index ◽

Heart Association ◽

Low Risk ◽

Peripheral Artery ◽

Artery Disease

Background: Lower extremity peripheral artery disease (PAD) is a common syndrome that afflicts many individuals and leads to significant morbidity. Once appropriate at risk patients are identified, ankle-brachial index (ABI) testing is a relatively quick and inexpensive test that is recommended for proper assessment of PAD, per the recommendations outlined in the American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Peripheral Artery Disease (PAD) (JACC, 2006). Outpatient cardiology practices often take care of individuals at risk for PAD and have the opportunity to test and appropriately treat this condition. Methods: A randomly selected group of 367 outpatients seen in a large academic cardiology practice from September 2011 underwent retrospective chart review. Risk factors for PAD that were assessed include history of smoking, hypertension, diabetes, hyperlipidemia, homocysteine levels, and CRP. Those that had three or more risk factors were classified as high risk and those with less than that were classified as low risk and frequency of ABI testing was evaluated. Fishers exact test was utilized for statistical analysis. Results: Fifty-one percent (N=187) of our population were classified as high risk for PAD, forty-three percent (N=158) were low risk, and six percent (N=22) were known to already have PAD. Amongst the high risk individuals, only six percent (N=12) had ABI testing performed while there were three percent (N=6) of low risk individuals that had this test (p=-0.34). Conclusions: There was no difference in ABI testing between high and low risk populations. Limitations of this study include lack of information regarding other diagnostic modalities that may have been used in place of ABI testing. Quality improvement may be achieved by increased use of such testing as this would allow for quicker identification of the disease, prompter treatment, and better outcomes, at a minimal cost.

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Risk factors and clinical outcomes in chronic coronary and peripheral artery disease: An analysis of the randomized, double-blind COMPASS trial

European Journal of Preventive Cardiology ◽

10.1177/2047487319882154 ◽

2019 ◽

Vol 27 (3) ◽

pp. 296-307 ◽

Cited By ~ 11

Author(s):

Thomas Vanassche ◽

Peter Verhamme ◽

Sonia S Anand ◽

Olga Shestakovska ◽

Keith AA Fox ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Peripheral Artery Disease ◽

Low Dose ◽

Cardiovascular Death ◽

Peripheral Artery ◽

Double Blind ◽

Artery Disease ◽

Risk Factor Status ◽

Ischemic Events

Aims Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. Methods and results We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8–2.6) and cardiovascular death (hazard ratio 2.0; 1.5–2.7) were more than twofold higher in patients with 4–6 compared with 0–1 risk factors ( p < 0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors ( p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. Conclusion More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.

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Response to “Re: A Systematic Review and Meta-analysis of the Association Between C-reactive Protein and Major Cardiovascular Events in Patients with Peripheral Artery Disease”

European Journal of Vascular and Endovascular Surgery ◽

10.1016/j.ejvs.2017.07.019 ◽

2017 ◽

Vol 54 (5) ◽

pp. 661-662

Author(s):

Tejas P. Singh ◽

Dylan R. Morris ◽

Samuel Smith ◽

Joseph V. Moxon ◽

Jonathan Golledge

Keyword(s):

Systematic Review ◽

Peripheral Artery Disease ◽

Cardiovascular Events ◽

Meta Analysis ◽

C Reactive Protein ◽

Peripheral Artery ◽

Reactive Protein ◽

Major Cardiovascular Events ◽

Artery Disease

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Burden of hospitalization in clinically diagnosed peripheral artery disease: A community-based study

Vascular Medicine ◽

10.1177/1358863x17736152 ◽

2017 ◽

Vol 23 (1) ◽

pp. 23-31 ◽

Cited By ~ 5

Author(s):

Adelaide M Arruda-Olson ◽

Homam Moussa Pacha ◽

Naveed Afzal ◽

Sara Abram ◽

Bradley R Lewis ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Ankle Brachial Index ◽

Inception Cohort ◽

Peripheral Artery ◽

Community Based ◽

Increased Risk ◽

Artery Disease ◽

Recurrent Hospitalization ◽

Over Time

The burden and predictors of hospitalization over time in community-based patients with peripheral artery disease (PAD) have not been established. This study evaluates the frequency, reasons and predictors of hospitalization over time in community-based patients with PAD. We assembled an inception cohort of 1798 PAD cases from Olmsted County, MN, USA (mean age 71.2 years, 44% female) from 1 January 1998 through 31 December 2011 who were followed until 2014. Two age- and sex-matched controls ( n = 3596) were identified for each case. ICD-9 codes were used to ascertain the primary reasons for hospitalization. Patients were censored at death or last follow-up. The most frequent reasons for hospitalization were non-cardiovascular: 68% of 8706 hospitalizations in cases and 78% of 8005 hospitalizations in controls. A total of 1533 (85%) cases and 2286 (64%) controls ( p < 0.001) were hospitalized at least once; 1262 (70%) cases and 1588 (44%) controls ( p < 0.001) ≥ two times. In adjusted models, age, prior hospitalization and comorbid conditions were independently associated with increased risk of recurrent hospitalizations in both groups. In cases, severe PAD (ankle–brachial index < 0.5) (HR: 1.25; 95% CI: 1.15, 1.36) and poorly compressible arteries (HR: 1.26; 95% CI: 1.16, 1.38) were each associated with increased risk for recurrent hospitalization. We demonstrate an increased rate of hospitalization in community-based patients with PAD and identify predictors of recurrent hospitalizations. These observations may inform strategies to reduce the burden of hospitalization of PAD patients.

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