Asymmetric dimethylarginine levels in children with sickle cell disease and its correlation to tricuspid regurgitant jet velocity

El-Shanshory, Mohamed; Badraia, Ibrahim M; Donia, Amr; El-hameed, Faten Abd; Mabrouk, Mokhtar

doi:10.1111/ejh.12114

Cited by 19 publications

(12 citation statements)

References 45 publications

(57 reference statements)

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“…A total of 45 studies (Delclaux et al, 2005;Kato et al, 2006;Akgul et al, 2007;Aleem et al, 2007;Nelson et al, 2007;Voskaridou et al, 2007;Zilberman et al, 2007;Aliyu et al, 2008;Beers et al, 2008;Caldas et al, 2008;Klings et al, 2008;Pashankar et al, 2008;Aessopos et al, 2009;Billy-Brissac et al, 2009;Lee et al, 2009;Liem et al, 2009;Minniti et al, 2009;Sedrak et al, 2009;Colombatti et al, 2010;Dahoui et al, 2010;Johnson et al, 2010;Chaudry et al, 2011;Gordeuk et al, 2011;Knight-Perry et al, 2011;Parent et al, 2011;Sachdev et al, 2011;Abdul-Mohsen, 2012;Anjum et al, 2012;Blanc et al, 2012;Caughey et al, 2012;Eddine et al, 2012;Fonseca et al, 2012;Forrest et al, 2012;Garrido et al, 2012;Oguanobi et al, 2012;Tantawy et al, 2012;Cabrita et al, 2013;El-Shanshory et al, 2013;Sharma et al, 2013;Agha et al, 2014;Cox et al, 2014;…”

Section: Resultsunclassified

Estimated pulmonary artery systolic pressure and sickle cell disease: a meta‐analysis and systematic review

et al. 2015

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SummaryMany studies report estimated pulmonary artery systolic pressure (ePASP) in patients with sickle cell disease (SCD) screened by echocardiography. To better understand the prevalence and outcomes of elevated ePASP in clinically stable SCD patients, we conducted a random-effects meta-analysis. A total of 45 studies, representing 15 countries and including 6109 individuals, met our inclusion criteria. In most (70%) studies, elevated ePASP was defined by a tricuspid regurgitant velocity of 2Á5 m/s. The prevalence of elevated ePASP was 21% (17-26%) in children and 30% (26-35%) in adults. After adjustment for sex, SCD genotype, haemoglobin, hydroxycarbamide (hydroxyurea) treatment, country and publication year, age remained associated with elevated ePASP, yielding a 12% (0Á4-23%) higher adjusted prevalence in adults. Few studies reported 6-min walk tests or mortality outcomes, and estimates were highly heterogeneous. In random effects meta-analyses, patients with elevated ePASP walked an estimated 30Á4 (6Á9-53Á9) metres less than those without elevated ePASP and had an associated mortality hazard ratio of 4Á9 (2Á4-9Á7).Keywords: sickle cell disease, pulmonary hypertension, echocardiography, meta-analysis.The American Thoracic Society (ATS) recommends screening patients with sickle cell disease (SCD) every 1-3 years by echocardiography, for the detection of possible pulmonary hypertension (PHT) and increased mortality risk (Klings et al, 2014). Although right heart catheterization remains the gold standard for PHT detection, echocardiography is non-invasive and relative inexpensive, making it suitable for prospective screenings and implementation in less developed countries. To assess pulmonary artery systolic pressure (PASP) by echocardiography, the tricuspid regurgitant jet velocity (TRV) is quantified and PASP is estimated with the modified Bernoulli equation: ePASP = 4 9 (TRV) 2 + right atrial pressure (with 5 or 10 mmHg generally assumed for the right atrial pressure). Numerous echocardiography screening programmes of patients with SCD have been initiated worldwide, but to date, the prevalence and outcomes of elevated ePASP associated with SCD have not been assessed by a formal meta-analysis. Methods Literature searchPublished articles were identified using MEDLINE (PubMed) and BIOSIS (Web of Science) search engines, by entering the key term 'sickle' with 'tricuspid', 'pulmonary hypertension' or 'echocardiography'. Our initial search retrieved 757 articles published between 1964 and 2014. Reviews, duplicate citations, non-human studies, highly selected study populations and articles written in languages other than English were excluded. To avoid elevated pulmonary pressures due to vaso-occlusive pain crisis or acute chest syndrome , we omitted studies with hospitalized patients, patients presenting with cardiopulmonary symptoms and retrospective chart reviews of hospital records. We limited our analysis to steady-state prospective screenings, and publications not specifying clinically stable conditions dur...

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Section: Resultsunclassified

Estimated pulmonary artery systolic pressure and sickle cell disease: a meta‐analysis and systematic review

et al. 2015

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“…Low global arginine bioavailability may be exacerbated further by the presence of elevated ADMA, an established biomarker of cardiovascular disease. Circulating ADMA levels are high in several conditions of endothelial dysfunction, including SCD 77 , 100 , 101 and thalassemia, 102 and are also linked to increased mortality 77 . Although hemolysis is clearly a path to creating an arginine deficiency syndrome, arginine deficiency is also induced through other mechanisms that contribute to endothelial dysfunction and cardiovascular disease.…”

Section: Physiology Of Conditionally Essential Amino Acidsmentioning

confidence: 99%

Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

et al. 2017

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Nonessential amino acids are synthesized de novo and therefore not diet dependent. In contrast, essential amino acids must be obtained through nutrition since they cannot be synthesized internally. Several nonessential amino acids may become essential under conditions of stress and catabolic states when the capacity of endogenous amino acid synthesis is exceeded. Arginine and glutamine are 2 such conditionally essential amino acids and are the focus of this review. Low arginine bioavailability plays a pivotal role in the pathogenesis of a growing number of varied diseases, including sickle cell disease, thalassemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, certain cancers, and trauma, among others. Catabolism of arginine by arginase enzymes is the most common cause of an acquired arginine deficiency syndrome, frequently contributing to endothelial dysfunction and/or T-cell dysfunction, depending on the clinical scenario and disease state. Glutamine, an arginine precursor, is one of the most abundant amino acids in the body and, like arginine, becomes deficient in several conditions of stress, including critical illness, trauma, infection, cancer, and gastrointestinal disorders. At-risk populations are discussed together with therapeutic options that target these specific acquired amino acid deficiencies.

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“…Indeed, high plasma ADMA levels were previously reported in SCA patients (Schnog et al , ; Landburg et al , ) and related to proteolysis following haemolytic stress in sickle red blood cells (D'Alecy & Billecke, ). In accordance to the general view that ADMA inhibits nitric oxide synthase activity leading to increased arteriolar tone and, ultimately, endothelial dysfunction (Kielstein et al , ), a relevant link between high ADMA concentration and SCA haemolytic phenotype (noteworthy pulmonary hypertension) has been reported by several authors (Landburg et al , ; El‐Shanshory et al , ). ADMA decrease under ACEI medication would thus be a key event contributing to endothelial function improvement through an increased nitric oxide bioavailability.…”

Section: Discussionmentioning

confidence: 56%

Renin‐angiotensin system blockade promotes a cardio‐renal protection in albuminuric homozygous sickle cell patients

et al. 2017

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The management of sickle cell nephropathy (SCN) at an early stage is an important issue to prevent renal and cardiovascular morbidity and mortality. This study aimed to evaluate in this population, whether angiotensin converting enzyme inhibitors (ACEIs) treatment could exert a cardio-renal protection in a SCN cohort. Forty-two SCN patients (urine albumin:creatinine ratio (ACR) > 10 mg/mmol) were treated with ACEIs for 6 months, then evaluated for ACR, measured glomerular filtration rate (mGFR) together with haematological and cardiovascular parameters. A 1-month washout was also performed in order to differentiate short- and long-term ACEIs effects. A decrease in ACR baseline value (>30%) was detected in 62% of cases (mean ACR: 46·4 ± 7·6 and 26·4 ± 3·9 mg/mmol at baseline and 6 months respectively; P = 0·002), whereas mGFR values were unchanged. ACR decrease was detected at 1 month following ACEI initiation (32·9 ± 6·9, P = 0·02) with a persistent trend after withdrawal (P = 0·08). ACEIs also decreased diastolic blood pressure (P = 0·007), pulse wave velocity (P = 0·01), tricuspid regurgitation velocity (TRV; P = 0·04), asymmetric dimethyl arginine (ADMA: P = 0·001) and haemoglobin (P = 0·01) while conventional haemolytic biomarkers were unchanged. Our data suggest that ACEIs are safe and effective at decreasing albuminuria in sickle cell patients with a beneficial effect on specific mortality risk factors, such as TRV and asymmetric dimethyl arginine.

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Asymmetric dimethylarginine levels in children with sickle cell disease and its correlation to tricuspid regurgitant jet velocity

Abstract: High plasma ADMA levels may be implicated in the pathogenesis of increased tricuspid regurgitant jet velocity in children with SCD.

Cited by 19 publications

References 45 publications

Estimated pulmonary artery systolic pressure and sickle cell disease: a meta‐analysis and systematic review

Estimated pulmonary artery systolic pressure and sickle cell disease: a meta‐analysis and systematic review

Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

Renin‐angiotensin system blockade promotes a cardio‐renal protection in albuminuric homozygous sickle cell patients

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