Homoarginine and all‐cause mortality: A systematic review and meta‐analysis

Zinellu, Angelo; Paliogiannis, Panagiotis; Carru, Ciriaco; Mangoni, Arduino A.

doi:10.1111/eci.12960

Cited by 30 publications

(28 citation statements)

References 44 publications

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“…Most consistently, low hArg levels are associated with all-cause and cardiovascular mortality, which was shown in subjects referred for coronary angiography, in hemodialysis patients with diabetes mellitus, in stroke patients, but also population-based cohorts [89,[91][92][93][94]. A recent meta-analysis confirmed the inverse association of hArg with all-cause mortality (HR 0.64 [0.57-0.73]) [95]. More specifically, low hArg levels were strongly associated with fatal strokes and revealed a trend to increase stroke risk [96,97].…”

Section: Homoarginine As Marker and Target In Cerebrovascular Diseasesmentioning

confidence: 83%

Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

Große

Schwedhelm

Worthmann

et al. 2020

IJMS

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The amino acid L-arginine serves as substrate for the nitric oxide synthase which is crucial in vascular function and disease. Derivatives of arginine, such as asymmetric (ADMA) and symmetric dimethylarginine (SDMA), are regarded as markers of endothelial dysfunction and have been implicated in vascular disorders. While there is a variety of studies consolidating ADMA as biomarker of cerebrovascular risk, morbidity and mortality, SDMA is currently emerging as an interesting metabolite with distinct characteristics in ischemic stroke. In contrast to dimethylarginines, homoarginine is inversely associated with adverse events and mortality in cerebrovascular diseases and might constitute a modifiable protective risk factor. This review aims to provide an overview of the current evidence for the pathophysiological role of arginine derivatives in cerebrovascular ischemic diseases. We discuss the complex mechanisms of arginine metabolism in health and disease and its potential clinical implications in diverse aspects of ischemic stroke.

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Section: Homoarginine As Marker and Target In Cerebrovascular Diseasesmentioning

confidence: 83%

Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

Große

Schwedhelm

Worthmann

et al. 2020

IJMS

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“…Results from several previous studies in patients with prevalent CVD showed an association between low homoarginine plasma concentrations and a higher risk of CVD (i.e., sudden cardiac death, heart failure, and myocardial infarction), cerebrovascular outcomes, and mortality (both all-cause and CVD-related) [1][2][3][4][5]. In the present investigation, we confirmed the association of homoarginine with all-cause mortality in a large community-based sample that included few people with prevalent CVD, and we extended our analyses to also include CRP, BNP, GDF15, eGFR, and troponin I as covariates.…”

Section: Homoarginine In the Communitymentioning

confidence: 99%

“…Clinical evidence suggests that lower circulating homoarginine concentrations are a risk factor for cardiovascular disease, and all-cause mortality [1,2]. Patients with prevalent ischemic stroke, ischemic heart disease, and congestive heart failure have low blood homoarginine concentrations [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Association of Lower Plasma Homoarginine Concentrations with Greater Risk of All-Cause Mortality in the Community: The Framingham Offspring Study

Schwedhelm

Song

Vasan

et al. 2020

JCM

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Lower circulating homoarginine concentrations have been associated with morbidity and mortality in patients with established cardiovascular disease (CVD). We assayed plasma homoarginine concentrations in 3331 Framingham Offspring Study participants attending examination cycle six (mean age 58.6 years, 53% women). We evaluated correlates of plasma homoarginine and related homoarginine to incident CVD and death. We also classified participants as having higher (upper quartile) versus lower (lower three quartiles) homoarginine and previously assayed asymmetric dimethylarginine (ADMA) concentrations, and created cross-classification groups. We observed 630 incident CVD events and 940 deaths during a median follow-up of 18 years. In multivariable regression analysis, homoarginine was associated positively with male sex, body mass index, anti-hypertensive medication use and systolic blood pressure, but inversely with age and smoking. Higher homoarginine levels were associated with a lower mortality risk (hazard ratio (HR) per SD increment, 0.83, 95% CI: 0.74–0.93) adjusting for standard CVD risk factors, and ADMA. Among the cross-classification groups, participants with higher homoarginine and lower ADMA had a lower mortality risk (HR, 0.81, 95% CI: 0.67–0.98) compared to those with low levels of both. Further studies are needed to dissect the mechanisms of the association of homoarginine and mortality over decades in the community.

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“…52 Recent studies reported low L-homoarginine concentrations to be a risk marker for cardiovascular events and all-cause mortality in the general population and coronary heart disease as well as kidney disease patients. 52,53 So, supplementation with L-homoarginine and L-arginine derivatives (and others selected pharmaceutical supplements), dietary beneficial habits, intake of antioxidant and anti-inflammatory foods and balanced physical activity improved endothelium function. 9,51 At a pathological environment, the endothelium assembly (arrangement of a proatherosclerotic structure) and function (deficit of guarding role) are altered, leading to endothelium dysfunction.…”

Section: On Endothelium Remodelingmentioning

confidence: 99%

Tackling endothelium remodeling in cardiovascular disease

Guľašová

Guerreiro

Link

et al. 2019

J of Cellular Biochemistry

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Endothelial dysfunction is considered an early marker of atherosclerosis. Herein, we address the molecular mechanisms affecting endothelium remodeling in disease. Vascular calcification is highly prevalent in patients with ischemic cardiovascular disease, cerebrovascular disorder, and renal failure, being a common feature in aging, diabetes, dyslipidemia, abnormal valve biomechanics, end‐stage renal disease and atherosclerosis, a major cause of mortality and morbidity. Oxidative stress promotes calcification of vascular smooth muscle cells (SMC) by increasing osteogenic transcription factors expression and activity in atherosclerotic plaques. Various markers of osteogenic differentiation are expressed by SMC in calcified atherosclerotic lesions. Interestingly, decreased levels of some bone factors and microRNAs accelerate vascular calcification and injured tissue regeneration. Another key player in endothelial remodeling is amino acids metabolism. Branched‐chain amino acids are catabolized in several nonhepatic tissues including cardiac muscle. Immune activation and inflammation in cardiovascular disease patients associate with higher phenylalanine/tyrosine ratios. Understanding the whole process that underlies endothelium dysfunction is of paramount importance for the development of new therapeutic approaches.

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Homoarginine and all‐cause mortality: A systematic review and meta‐analysis

Cited by 30 publications

References 44 publications

Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

Association of Lower Plasma Homoarginine Concentrations with Greater Risk of All-Cause Mortality in the Community: The Framingham Offspring Study

Tackling endothelium remodeling in cardiovascular disease

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