Critical Issues in Peripheral Arterial Disease Detection and Management&lt;subtitle&gt;A Call to Action&lt;/subtitle&gt;

Belch, J. J. F.; Topol, Eric J.; Agnelli, Giancarlo; Bertrand, Michel; Califf, Robert M.; Clément, Denis; Creager, Mark A.; Easton, J. Donald; Gavin, James R.; Greenland, Philip; Hankey, Graeme J.; Hanrath, Peter; Hirsch, Alan T.; Meyer, Jürgen; Smith, Sidney C.; Sullivan, Frank; Weber, Michael A.

doi:10.1001/archinte.163.8.884

Cited by 506 publications

(379 citation statements)

References 50 publications

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“…For example, 70% (almost all of the remaining patients were on anticoagulants) and 84% of patients included in the recently published Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra‐arterial Supplementation (JUVENTAS) trial were on antiplatelet and statin therapy, respectively 44. The relatively poor incorporation of PAD guidelines probably results from a relative lack of public awareness about PAD, its unappreciated implications on overall cardiovascular risk, and the fact that the benefits of treatment are not well appreciated 45, 46, 47. Furthermore, overestimation of the treatment given by others, lack of education, training, and organizational facilities to implement guidelines properly play a role,48 as well as the beliefs of the physician themselves 49.…”

Section: Trends In Medical Therapy For Padmentioning

confidence: 99%

Critical Limb Ischemia: Current Trends and Future Directions

Teraa

Conte

Moll

et al. 2016

JAHA

207

150

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Section: Trends In Medical Therapy For Padmentioning

confidence: 99%

Critical Limb Ischemia: Current Trends and Future Directions

Teraa

Conte

Moll

et al. 2016

JAHA

207

150

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“…It affects over 27 million people across Europe and North America 7. An estimated 8.5 million Americans aged ≥40 years carry the diagnosis of PAD 8.…”

Section: Introductionmentioning

confidence: 99%

Trimethylamine N ‐Oxide and Mortality Risk in Patients With Peripheral Artery Disease

Senthong

Wang

Fan

et al. 2016

JAHA

144

110

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BackgroundProduction of the proatherogenic metabolite, trimethylamine N‐oxide (TMAO), from dietary nutrients by intestinal microbiota enhances atherosclerosis development in animal models and is associated with atherosclerotic coronary artery disease in humans. The utility of studying plasma levels of TMAO to risk stratify in patients with peripheral artery disease (PAD) has not been reported.Methods and ResultsWe examined the relationship between fasting plasma TMAO and all‐cause mortality (5‐year), stratified by subtypes of PAD and presence of coronary artery disease in 935 patients with PAD who underwent elective angiography for cardiac evaluation at a tertiary care hospital. Median plasma TMAO was 4.8 μmol/L (interquartile range, 2.9–8.0 μmol/L). Elevated TMAO levels were associated with 2.7‐fold increased mortality risk (fourth versus first quartiles, hazard ratio 2.86, 95% CI 1.82–3.97, P<0.001). Following adjustments for traditional risk factors, inflammatory biomarkers, and history of coronary artery disease, the highest TMAO quartile remained predictive of 5‐year mortality (adjusted hazard ratio 2.06, 95% CI 1.36–3.11, P<0.001). Similar prognostic value for elevated TMAO was seen for subjects with carotid artery, non–carotid artery, or lower extremity PAD. TMAO provided incremental prognostic value for all‐cause mortality (net reclassification index, 40.22%; P<0.001) and improvement in area under receiver operator characteristic curve (65.7% versus 69.4%; P=0.013).Conclusions TMAO, a pro‐atherogenic metabolite formed by gut microbes, predicts long‐term adverse event risk and incremental prognostic value in patients with PAD. These findings point to the potential for TMAO to help improve selection of high‐risk PAD patients with or without significant coronary artery disease, who likely need more aggressive and specific dietary and pharmacologic therapy.

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“…Peripheral arterial disease (PAD) is a common atherosclerotic syndrome affecting more than 25 million individuals in Europe and the United States (McDermott et al 2001;Belch et al 2003;Norgren et al 2007); moreover, its incidence has been increasing in Japan (Suzuki and Iso 2013). Critical limb ischemia (CLI) is the most severe complication of PAD, and approximately 1% of PAD patients develop CLI, which is associated with poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of Y-Box-Binding Protein-1 in Hind-Limb Muscles During Regeneration from Ischemic Injury in Mice

Fuke

Narita

Wada

et al. 2018

Tohoku J. Exp. Med.

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Critical limb ischemia (CLI) is the most severe complication of peripheral arterial disease (PAD). Understanding the molecular mechanisms underlying tissue repair after CLI is necessary for preventing PAD progression. Y-box binding protein-1 (YB-1) regulates the expression of many genes in response to environmental stresses. We aimed to determine whether YB-1 is involved in ischemic muscle regeneration. A mouse ischemic hind-limb model was generated; namely, the femoral, saphenous, and popliteal arteries in the left hind limb were ligated. The right hind limb, with skin incisions alone, served as control. Hind limbs (n = 3-5 for each time point) were examined on day 0 (before the operation) and on postoperative days 1, 2, 7, 10, and 14, and the biceps femoris, adductor, rectus femoris, and gracilis muscles were subjected to histopathological and immunohistochemical analyses. In ischemic limbs, myogenesis, triggered by an increase in myotubes, began on day 7; thereafter, regenerated muscles gradually increased in volume. RT-PCR analysis showed that YB-1 mRNA levels were increased in the limbs after ischemic injury, peaked on day 2, and subsequently decreased. On day 7, expression levels of MyoD and alphasmooth muscle actin (αSMA) mRNAs were significantly higher in ischemic muscles than in control muscles. Immunohistochemical analysis revealed increased YB-1 immunoreactivity in myoblasts and myotubes on day 7, which was decreased by day 14. The immunoreactive αSMA and smooth muscle myosin heavy chain were transiently increased in myotubes. This is the first report showing the increased expression of YB-1 during muscle regeneration after ischemic injury.

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Critical Issues in Peripheral Arterial Disease Detection and Management<subtitle>A Call to Action</subtitle>

Cited by 506 publications

References 50 publications

Critical Limb Ischemia: Current Trends and Future Directions

Critical Limb Ischemia: Current Trends and Future Directions

Trimethylamine N ‐Oxide and Mortality Risk in Patients With Peripheral Artery Disease

Increased Expression of Y-Box-Binding Protein-1 in Hind-Limb Muscles During Regeneration from Ischemic Injury in Mice

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