Increased levels of symmetric dimethyl-arginine are associated with all-cause mortality in patients with symptomatic peripheral arterial disease

Staniszewska, Aleksandra; Rajagopalan, Sriram; Al-Shaheen, Abdullah; Thiès, Frank; Brittenden, Julie

doi:10.1016/j.jvs.2015.01.002

Cited by 11 publications

(11 citation statements)

References 37 publications

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“…A total of 2119 patients were investigated comprising both inpatients and outpatients with lower extremity PAD. All-cause mortality was increased with high ADMA levels (HR, 2.23; P =0.024 50 and HR, 1.31; P =0.037). 51 MACE was also increased in patients with higher levels of ADMA (HR, 5.2; P <0.001 52 and HR, 1.70; P =0.043).…”

Section: Resultsmentioning

confidence: 98%

“…The 47 included studies were sorted per biomarker; several studies appeared in different groups as they investigated multiple biomarkers. The following biomarkers were studied: 13 studies investigated high-sensitivity CRP (hs-CRP), 11 , 14 – 26 2 reported on GDF-15 (growth differentiation factor 15), 14 , 27 2 on MPO (myeloperoxidase), 24 , 28 6 on the neutrophil-lymphocyte ratio (NLR), 29 – 34 2 assessed SAA (serum amyloid A), 22 , 35 6 reported on fibrinogen, 19 , 35 – 39 another 7 assessed d -dimer, 22 , 25 , 38 , 40 – 43 7 investigated NT-proBNP, 11 , 15 , 17 , 44 – 47 5 hs-cTnT, 10 , 44 , 45 , 48 , 49 4 asymmetrical dimethylarginine (ADMA), 50 – 53 4 assessed adiponectin, 54 – 57 and 3 homocysteine. 18 , 22 , 58 Investigated outcomes were heterogenous across studies but mainly included all-cause mortality, cardiovascular mortality, cardiovascular events, major adverse cardiovascular events (MACE), major adverse limb events, coronary events, amputation-free survival, amputation, reintervention for lower extremity PAD, and graft patency.…”

Section: Resultsmentioning

confidence: 99%

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Plasma Biomarkers to Predict Cardiovascular Outcome in Patients With Peripheral Artery Disease

Kremers

Wübbeke

Mees

et al. 2020

ATVB

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Objective: Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events. Numerous plasma biomarkers have been investigated in lower extremity PAD, but none are used for clinical risk assessments. We aimed to provide a comprehensive overview of biomarker testing in PAD as a first step to improve risk stratification. Approach and Results: A systematic literature review in MEDLINE/PubMed, Cochrane, and Embase was performed, identifying all studies investigating plasma biomarkers in association with cardiovascular events and mortality in lower extremity PAD. Forty-seven studies comprising 21 473 PAD patients met our criteria and were included. Effect estimates were provided by the studies based on a minimum follow-up of 1 year. Meta-analyses were performed by pooling studies per biomarker for each end point. Patients with increased high-sensitivity CRP (C-reactive protein) levels had a relative risk of 1.86 (1.48–2.33) for major adverse cardiovascular events and a relative risk of 3.49 (2.35–5.19) for mortality. Increased fibrinogen and d -dimer levels were associated with an increased relative risk of mortality of 2.08 (1.46–2.97) and 2.22 (1.24–3.98), respectively. Additionally, patients with increased NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cTnT (cardiac troponin T) levels were at an even higher risk of mortality with relative risks of 4.50 (2.98–6.81) and 3.33 (2.70–4.10), respectively. Conclusions: This systematic review identifies promising biomarkers representing different pathophysiological processes implicated in lower extremity PAD, including high-sensitivity CRP, neutrophil-lymphocyte ratio, fibrinogen, d -dimer, NT-proBNP, and high-sensitivity cTnT. Clinical implementation should be preceded by a management study to test the utility of a combination of these markers for individual risk stratification. Ultimately, this may contribute to tailored treatment and increased effectiveness of current treatment strategies in PAD.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Plasma Biomarkers to Predict Cardiovascular Outcome in Patients With Peripheral Artery Disease

Kremers

Wübbeke

Mees

et al. 2020

ATVB

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“…Increased circulating ADMA levels have been predictive of fatal and nonfatal cardiovascular events in at‐risk populations . SDMA was an independent predictor of all‐cause and cardiovascular mortality in the general population in a large multi‐ethnic cohort study and with all‐cause mortality in patients with symptomatic peripheral arterial disease …”

Section: Underlying Mechanisms Contributing To the Antihypertensive Ementioning

confidence: 97%

Mechanisms underlying blood pressure reduction by dietary inorganic nitrate

2018

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Nitric oxide (NO) importantly contributes to cardiovascular homeostasis by regulating blood flow and maintaining endothelial integrity. Conversely, reduced NO bioavailability is a central feature during natural ageing and in many cardiovascular disorders, including hypertension. The inorganic anions nitrate and nitrite are endogenously formed after oxidation of NO synthase (NOS)-derived NO and are also present in our daily diet. Knowledge accumulated over the past two decades has demonstrated that these anions can be recycled back to NO and other bioactive nitrogen oxides via serial reductions that involve oral commensal bacteria and various enzymatic systems. Intake of inorganic nitrate, which is predominantly found in green leafy vegetables and beets, has a variety of favourable cardiovascular effects. As hypertension is a major risk factor of morbidity and mortality worldwide, much attention has been paid to the blood pressure reducing effect of inorganic nitrate. Here, we describe how dietary nitrate, via stimulation of the nitrate-nitrite-NO pathway, affects various organ systems and discuss underlying mechanisms that may contribute to the observed blood pressure-lowering effect.

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“…The remaining 14 studies underwent fulltext review, and eight studies were further excluded because two studies were not relevant studies to the current meta-analysis, one was not prospective cohort study, four did not report the outcome of interest, and the other one was not performed in patients with PAD. Finally, six prospective cohort studies 9,[16][17][18][19][20] were included in the present meta-analysis.…”

Section: Searching Resultsmentioning

confidence: 99%

“…16 However, inconsistent results were retrieved regarding the prognostic role of circulating ADMA at baseline in patients with PAD. 9,[16][17][18][19][20] Therefore, in study, we aimed to quantitatively evaluate the prognostic efficacy of circulating ADMA for cardiovascular outcome in patients with PAD by combining available evidence in a meta-analysis.…”

Section: Introductionmentioning

confidence: 99%

Prognostic efficacy of circulating asymmetric dimethylarginine in patients with peripheral arterial disease: A meta-analysis of prospective cohort studies

Chu¹,

Yu²,

Chu³

et al. 2017

Vascular

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Background Asymmetric dimethylarginine is suggested to be a marker of poor prognosis in patients with atherosclerosis. However, the predictive role of circulating asymmetric dimethylarginine for clinical outcome in patients with peripheral arterial disease has not been determined. Aims To quantitatively assess the predictive value of circulating asymmetric dimethylarginine for clinical outcome in patients with peripheral arterial disease in a meta-analysis of prospective cohort studies. Methods Relevant studies were identified by systematically searching of PubMed and Embase databases. A random-effect model was used to synthesize the results. Sensitivity analyses by omitting one study at a time were performed to evaluate the robustness of the results. Results Six studies with 2535 peripheral arterial disease patients were included. Patients with higher circulating asymmetric dimethylarginine at baseline were associated with higher risk of all-cause mortality (adjusted hazard ratio: 1.63, 95% confidence interval: 1.28-2.06, I = 16%), and major adverse cardiovascular events (adjusted hazard ratio: 2.01, 95% confidence interval: 1.08-3.73, I = 78%) as compared with those with lower circulating asymmetric dimethylarginine at baseline. Specifically, every increment of 0.1 µmol/l of asymmetric dimethylarginine was associated with 18% (adjusted hazard ratio: 1.18, 95% confidence interval: 1.06-1.31) increased risk for all-cause mortality and 14% (adjusted hazard ratio: 1.14, 95% confidence interval: 1.04-1.25) increased risk for major adverse cardiovascular disease. Sensitivity analyses by omitting one study at a time did not significantly change the results. Conclusion Higher circulating asymmetric dimethylarginine at baseline may be associated with higher incidence of cardiovascular events and mortality in patients with peripheral arterial disease.

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Increased levels of symmetric dimethyl-arginine are associated with all-cause mortality in patients with symptomatic peripheral arterial disease

Abstract: The novel finding of this study is that SDMA levels were predictive of all cause-mortality and correlated with disease severity. Further studies should assess the role of nitric oxide donors in patients with high levels of SDMA.

Cited by 11 publications

References 37 publications

Plasma Biomarkers to Predict Cardiovascular Outcome in Patients With Peripheral Artery Disease

Plasma Biomarkers to Predict Cardiovascular Outcome in Patients With Peripheral Artery Disease

Mechanisms underlying blood pressure reduction by dietary inorganic nitrate

Prognostic efficacy of circulating asymmetric dimethylarginine in patients with peripheral arterial disease: A meta-analysis of prospective cohort studies

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