Chronic kidney disease and risk for cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: The EUCLID trial

In patients with symptomatic peripheral artery disease (PAD), the impact of chronic kidney disease (CKD) on major adverse cardiovascular events has not been fully evaluated. The Examining Use of Ticagrelor In PAD (EUCLID) trial randomized 13,885 patients with PAD to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. This post hoc analysis compared the incidence of the primary composite endpoint (cardiovascular death, myocardial infarction (MI), or ischemic stroke) in patients with CKD (eGFR < 60 mL/min/1.73 m2) with those without CKD (eGFR ⩾ 60 mL/min/1.73 m2). The primary safety endpoint was thrombolysis in MI (TIMI) major bleeding. A total of 13,483 patients were included; 3332 (25%) had CKD, of whom 237 had stage 4/5 disease. Median follow-up was approximately 30 months. After statistical adjustment, patients with CKD had a higher rate of the primary endpoint compared with those without CKD (6.75 vs 3.72 events/100 patient-years; adjusted hazard ratio (HR) 1.45, 95% CI 1.30–1.63). CKD was not associated with increased risk of hospitalization for acute limb ischemia (ALI) (adjusted HR 0.96, 95% CI 0.69–1.34) or major amputation (adjusted HR 0.92, 95% CI 0.66–1.28). CKD was not associated with a significantly increased risk of major bleeding (adjusted HR 1.21, 95% CI 0.89–1.64), but minor bleeding was significantly increased (adjusted HR 1.51, 95% CI 1.07–2.15). In conclusion, patients with PAD and CKD had higher rates of cardiovascular death, MI, and ischemic stroke, but similar rates of ALI, major amputation, and TIMI major bleeding when compared with patients without CKD. ClinicalTrials.gov Identifier: NCT01732822

Download Full-text

Abstract 17124: Sex Differences in the Incidence of Peripheral Artery Disease (PAD) in the Chronic Renal Insufficiency Cohort (CRIC)

Circulation ◽

10.1161/circ.132.suppl_3.17124 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Grace J Wang ◽

Pamela A Shaw ◽

Raymond R Townsend ◽

Amanda H Anderson ◽

Dawei Xie ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Insufficiency ◽

Peripheral Artery Disease ◽

Chronic Renal Insufficiency ◽

Cumulative Incidence ◽

Ankle Brachial Index ◽

Peripheral Artery ◽

Increased Risk ◽

Artery Disease

Introduction: Chronic kidney disease (CKD) results in an increased risk of peripheral artery disease (PAD). However, the epidemiology of PAD in CKD, and particularly how the incidence differs according to sex remains incompletely defined. We sought to define how the epidemiology of peripheral arterial disease (PAD) in chronic kidney disease (CKD) differs according to sex and age. Methods: The Chronic Renal Insufficiency Cohort (CRIC) is a multi-center, prospective cohort study of CKD participants. Fine and Gray methods were used to determine the cumulative incidence of PAD, defined by an ankle brachial index (ABI) < 0.90 or a confirmed PAD event, with death as a competing event. Adjusted subdistribution hazard ratios from the Fine and Gray model determined the risk of PAD according to sex. A priori, we hypothesized that the relationship between sex and cumulative incidence of PAD differed according to age. Results: The mean age of the 3,174 participants in this study was 56.6 years and consisted of 55% males. Over a median follow-up of 5.9 years, 17.8% developed PAD and 11.1% died. Females had a 1.72-fold greater adjusted PAD risk compared to men (95% CI 1.44-2.06, p<0.001). These sex-related differences in PAD risk also differed by age (p<0.001, Figure). Women, compared to men, were at a markedly increased risk for PAD at younger ages; however, at ages greater than 70 years, the risk was similar across both sexes. Older men had a substantially greater PAD risk compared to younger men. In women, PAD risk did not vary with age. Conclusions: Females with CKD have a higher PAD risk compared to males at younger ages. There is an important need to improve our understanding of the biological and clinical basis for these differences.

Download Full-text

Unique aspects of peripheral artery disease in patients with chronic kidney disease

Vascular Medicine ◽

10.1177/1358863x18824654 ◽

2019 ◽

Vol 24 (3) ◽

pp. 251-260 ◽

Cited By ~ 5

Author(s):

Nkiruka V Arinze ◽

Andrew Gregory ◽

Jean M Francis ◽

Alik Farber ◽

Vipul C Chitalia

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Peripheral Artery Disease ◽

Clinical Aspects ◽

Peripheral Artery ◽

Health Care Burden ◽

High Prevalence ◽

Novel Biomarkers ◽

Artery Disease ◽

Poor Outcomes

Peripheral artery disease (PAD) represents a major health care burden. Despite the advent of screening and interventional procedures, the long-term clinical outcomes remain suboptimal, especially in patients with chronic kidney disease (CKD). While CKD and PAD share common predisposing factors, emerging studies indicate that their co-existence is not merely an association; instead, CKD represents a strong, independent risk factor for PAD. These findings implicate CKD-specific mediators of PAD that remain incompletely understood. Moreover, there is a need to understand the mechanisms underlying poor outcomes after interventions for PAD in CKD. This review discusses unique clinical aspects of PAD in patients with CKD, including high prevalence and worse outcomes after vascular interventions and the influence of renal allograft transplantation. In doing so, it also highlights underappreciated aspects of PAD in patients with CKD, such as disparities in revascularization and higher peri-procedural mortality. While previous reviews have discussed general mechanisms of PAD pathogenesis, focusing on PAD in CKD, this review underscores a need to probe for CKD-specific pathogenic pathways that may unravel novel biomarkers and therapeutic targets in PAD and ultimately improve the risk stratification and management of patients with CKD and PAD.

Download Full-text

Incremental effects of diabetes mellitus and chronic kidney disease in medial arterial calcification: Synergistic pathways for peripheral artery disease progression

Vascular Medicine ◽

10.1177/1358863x19842276 ◽

2019 ◽

Vol 24 (5) ◽

pp. 383-394 ◽

Cited By ~ 1

Author(s):

Prakash Krishnan ◽

Pedro R Moreno ◽

Irene C Turnbull ◽

Meerarani Purushothaman ◽

Urooj Zafar ◽

...

Keyword(s):

Diabetes Mellitus ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Peripheral Artery Disease ◽

Arterial Calcification ◽

Peripheral Artery ◽

Fetuin A ◽

Artery Disease ◽

Protein Density ◽

Medial Arterial Calcification

Diabetes mellitus (DM) and chronic kidney disease (CKD) separately are known to facilitate the progression of medial arterial calcification (MAC) in patients with symptomatic peripheral artery disease (PAD), but their combined effect on MAC and associated mediators of calcification is not well studied. The association of MAC and calcification inducer bone morphogenetic protein (BMP-2) and inhibitor fetuin-A, with PAD, is well known. Our aim was to investigate the association of MAC with alterations in BMP-2 and fetuin-A protein expression in patients with PAD with DM and/or CKD. Peripheral artery plaques (50) collected during directional atherectomy from symptomatic patients with PAD were evaluated, grouped into no-DM/no-CKD ( n = 14), DM alone ( n = 10), CKD alone ( n = 12), and DM+CKD ( n = 14). MAC density was evaluated using hematoxylin and eosin, and alizarin red stain. Analysis of inflammation, neovascularization, BMP-2 and fetuin-A protein density was performed by immunohistochemistry. MAC density, inflammation grade and neovessel content were significantly higher in DM+CKD versus no-DM/no-CKD and CKD ( p < 0.01). BMP-2 protein density was significantly higher in DM+CKD versus all other groups ( p < 0.01), whereas fetuin-A protein density was significantly lower in DM+CKD versus all other groups ( p < 0.001). The combined presence of DM+CKD may be associated with MAC severity in PAD plaques more so than DM or CKD alone, as illustrated in this study, where levels of calcification mediators BMP-2 and fetuin-A protein were related most robustly to DM+CKD. Further understanding of mechanisms involved in mediating calcification and their association with DM and CKD may be useful in improving management and developing therapeutic interventions.

Download Full-text