Reduced high-density lipoprotein cholesterol: A valuable, independent prognostic marker in peripheral arterial disease

Martínez-Aguilar, E.; Orbe, Josune; Fernández-Montero, Alejandro; Fernández-Alonso, S.; Rodríguez, José Antonio; Fernández-Alonso, Leopoldo; Páramo, José A.; Roncal, Carmen

doi:10.1016/j.jvs.2017.04.056

Cited by 19 publications

(10 citation statements)

References 38 publications

(44 reference statements)

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“…Whereas elevated levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) are widely accepted as risk factors for PAD, reduced high-density lipoprotein cholesterol levels also appear to be associated with increased mortality in PAD patients. 194 A ratio of the two may also be a useful predictor of PAD. 195 Whereas hypertriglyceridemia appears to be atherogenic, 196 its role in the development and progression of PAD remains incompletely defined.…”

Section: Global Epidemiology and Risk Factors For Cltimentioning

confidence: 99%

Global vascular guidelines on the management of chronic limb-threatening ischemia

Conte

Bradbury

Kolh³

et al. 2019

Journal of Vascular Surgery

1,117

865

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Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

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Section: Global Epidemiology and Risk Factors For Cltimentioning

confidence: 99%

Global vascular guidelines on the management of chronic limb-threatening ischemia

Conte

Bradbury

Kolh³

et al. 2019

Journal of Vascular Surgery

1,117

865

View full text Add to dashboard Cite

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“…The clinical and demographic characteristics of the PAD cohort were previously described by Martinez-Aguilar et al . 32,33 . As the cohort has included new cases we include the complete description in supplemental material and methods.…”

Section: Methodsmentioning

confidence: 99%

Trimethylamine-N-Oxide (TMAO) Predicts Cardiovascular Mortality in Peripheral Artery Disease

Roncal

Martínez-Aguilar

Orbe

et al. 2019

Sci Rep

Self Cite

106

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Peripheral artery disease (PAD) is a major cause of acute and chronic illness, with extremely poor prognosis that remains underdiagnosed and undertreated. Trimethylamine-N-Oxide (TMAO), a gut derived metabolite, has been associated with atherosclerotic burden. We determined plasma levels of TMAO by mass spectrometry and evaluated their association with PAD severity and prognosis. 262 symptomatic PAD patients (mean age 70 years, 87% men) categorized in intermittent claudication (IC, n = 147) and critical limb ischemia (CLI, n = 115) were followed-up for a mean average of 4 years (min 1-max 102 months). TMAO levels were increased in CLI compared to IC (P < 0.001). Receiver operating characteristic (ROC) curves for severity (CLI) rendered a cutoff of 2.26 µmol/L for TMAO (62% sensitivity, 76% specificity). Patients with TMAO > 2.26 µmol/L exhibited higher risk of cardiovascular death (subhazard ratios ≥2, P < 0.05) that remained significant after adjustment for confounding factors. TMAO levels were associated to disease severity and CV-mortality in our cohort, suggesting an improvement of PAD prognosis with the measurement of TMAO. Overall, our results indicate that the intestinal bacterial function, together with the activity of key hepatic enzymes for TMA oxidation (FMO3) and renal function, should be considered when designing therapeutic strategies to control gut-derived metabolites in vascular patients.

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“…Among the conventional lipid risk factors, the ratio of total to HDL-C emerged as the strongest determinant of large vessel PAD in both the Physician's Health Study and the San Diego Population Study [39][40][41]. Low levels of HDL-C may predispose to adverse outcomes as a perspective study including 254 patients suffering from PAD concluded that patients with reduced HDL-C levels (<1.0 mmol/L for men and <1.3 mmol/L for women) presented with higher incidences of mortality and major cardiovascular events over a 3-year period [42]. In our study population, none of the traditional lipid parameters was a useful biomarker for the early prediction of mortality in PAD patients.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Efflux Capacity Associates with the Ankle-Brachial Index but Not All-Cause Mortality in Patients with Peripheral Artery Disease

et al. 2021

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Background: Cholesterol efflux is an important mechanism by which high-density lipoproteins (HDLs) protect against cardiovascular disease. As peripheral artery disease (PAD) is associated with high mortality rates, mainly due to cardiovascular causes, we investigated whether cholesterol efflux capacity (CEC) of apolipoprotein B (apoB)-depleted plasma, a widely used surrogate of HDL function, may serve as a predictive marker for mortality in this patient population. Methods: In this prospective single-center study (median follow-up time: 9.3 years), apoB-containing lipoproteins were precipitated from plasma of 95 patients with PAD and incubated with J744-macrophages, which were loaded with radiolabeled cholesterol. CEC was defined as the fractional radiolabel released during 4 h of incubation. Results: Baseline CEC was lower in PAD patients that currently smoked (p = 0.015) and had a history of myocardial infarction (p = 0.011). Moreover, CEC showed a significant correlation with HDL-cholesterol (p = 0.003) and apolipoprotein A-I levels (p = 0.001) as well as the ankle-brachial index (ABI, p = 0.018). However, CEC did not differ between survivors and non-survivors. Neither revealed Kaplan–Meier and Cox regression analyses any significant association of CEC with all-cause mortality rates. Conclusion: Taken together, CEC is associated with ABI but does not predict all-cause mortality in patients with PAD.

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Reduced high-density lipoprotein cholesterol: A valuable, independent prognostic marker in peripheral arterial disease

Cited by 19 publications

References 38 publications

Global vascular guidelines on the management of chronic limb-threatening ischemia

Global vascular guidelines on the management of chronic limb-threatening ischemia

Trimethylamine-N-Oxide (TMAO) Predicts Cardiovascular Mortality in Peripheral Artery Disease

Cholesterol Efflux Capacity Associates with the Ankle-Brachial Index but Not All-Cause Mortality in Patients with Peripheral Artery Disease

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