Research LettersRisk of acute coronary events and serum concentration of asymmetrical dimethylarginine
Summary
Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor, which has been suggested to be a novel independent risk factor for endothelial dysfunction and coronary heart disease. We investigated the association of ADMA concentration in serum with risk of acute coronary events. We did a prospective, nested, case-control study in middle-aged men from eastern Finland. In an analysis of men who did not smoke, those who were in the highest quartile for ADMA (>0·62 μmol/L) had a 3·9-fold (95% CI 1·25–12·3, p=0·02) increase in risk of acute coronary events compared with the other quartiles. Our findings suggest that ADMA is a predictor of acute coronary events.
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Cited by (531)
Nitric Oxide Precursors and Dimethylarginines as Risk Markers for Accelerated Measured GFR Decline in the General Population
2023, Kidney International ReportsNitric oxide (NO) deficiency is associated with endothelial dysfunction, hypertension, atherosclerosis, and chronic kidney disease (CKD). Reduced NO bioavailability is hypothesized to play a vital role in kidney function impairment and CKD. We investigated the association of serum levels of endogenous inhibitors of NO, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), and precursors of NO, arginine, citrulline, and ornithine, with a decline in glomerular filtration rate (GFR) and new-onset CKD.
In a prospective cohort study of 1407 healthy, middle-aged participants of Northern European origin in the Renal Iohexol Clearance Survey (RENIS), GFR was measured repeatedly with iohexol clearance during a median follow-up time of 11 years. GFR decline rates were analyzed using a linear mixed model, new-onset CKD (GFR < 60 ml/min per 1.73 m2) was analyzed with interval-censored Cox regression, and accelerated GFR decline (the 10% with the steepest GFR decline) was analyzed with logistic regression.
Higher SDMA was associated with slower annual GFR decline. Higher levels of citrulline and ornithine were associated with accelerated GFR decline (odds ratio [OR], 1.43; 95% confidence interval [CI] 1.16–1.76 per SD higher citrulline and OR 1.23; 95% CI 1.01 to 1.49 per SD higher ornithine). Higher citrulline was associated with new-onset CKD, with a hazard ratio of 1.33 (95% CI 1.07–1.66) per SD higher citrulline.
Associations between NO precursors and the outcomes suggest that NO metabolism plays a significant role in the pathogenesis of age-related GFR decline and the development of CKD in middle-aged people.
Assessing the nitric oxide and asymmetric dimethylarginine levels in lifelong premature ejaculation: A prospective study
2022, Revista Internacional de AndrologiaTo evaluate nitric oxide (NO) and asymmetric dimethylarginine (ADMA) levels in men with premature ejaculation (PE), which is a common condition that adversely affects quality of life.
Of the 20–50-year old men presenting to the urology clinic, who were married or had regular sexual intercourse, 40 that were diagnosed with lifelong PE according to the Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT) measured by a stopwatch were included in the study. The results of the PE group were compared to those of the control group formed with 40 healthy hospital personnel. Venous blood samples were centrifuged and stored at −80 °C. The NO and ADMA values were compared between the individuals with and without PE.
There was no statistically significant difference between the groups in terms of age, body mass index (BMI), and The International Erectile Dysfunction Index-5 (IIEF-5) questionnaire scores. The NO and ADMA values were significantly lower in the PE group than in the control group (29.76 ±13.26 μmol/L vs. 48.27 ± 22.71 μmol/L; p < 0.001 and 1.01 ± 0.49 nmol/ml vs. 1.83 ± 1.06 nmol/ml; p < 0.001, respectively). There was a significant correlation between IELT and NO levels (r = 0.407, p = 0.001).
Our study can contribute to the explanation of the pathophysiology of PE having unclear etiology and treatment. Further studies on these molecules with larger case series are required for the diagnosis and treatment of PE.
Evaluar los niveles de óxido nítrico (NO) y dimetilarginina asimétrica en hombres con eyaculación precoz (EP), que es una afección común que afecta negativamente la calidad de vida.
De los hombres de 20 a 50 años que acudieron a la clínica de urología, que estaban casados o tenían relaciones sexuales regulares, se incluyeron en el estudio 40 que fueron diagnosticados con EP de por vida según la Herramienta de Diagnóstico de la Eyaculación Precoz y el tiempo de latencia de la eyaculación intravaginal medidos por un cronómetro. Se compararon los resultados del grupo de EP con los del grupo control formado por 40 personas sanas del hospital. Las muestras de sangre venosa se centrifugaron y almacenaron a −80 °C. Se compararon los valores de NO y dimetilarginina asimétrica entre los individuos con y sin EP.
No hubo diferencias estadísticamente significativas entre los grupos en términos de edad, índice de masa corporal y puntajes del cuestionario International Erectile Dysfunction Index-5. Los valores de NO y dimetilarginina asimétrica fueron significativamente más bajos en el grupo de EP que en el grupo control (29,76 ± 13,26 frente a 48,27 ± 22,71 μmol/l [p < 0,001] y 1,01 ± 0,49 frente a 1,83 ± 1,06 nmol/ml [p < 0,001], respectivamente). Hubo una correlación significativa entre los niveles de tiempo de latencia de la eyaculación intravaginal y NO (r = 0,407, p = 0,001).
Nuestro estudio puede contribuir a la explicación de la fisiopatología de la EP de etiología y tratamiento poco claros. Se requieren más estudios sobre estas moléculas con series de casos más grandes para el diagnóstico y tratamiento de la EP.
Uremic Toxicity
2022, Handbook of Dialysis TherapyThe biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is reviewed. We classified these compounds according to their physicochemical characteristics as small water-soluble compounds or groups of compounds, protein-bound compounds, and middle molecules. In general, several physiologic mechanisms and organ systems were influenced for each individual solute or group of solutes. Most affected were the kidneys and the cardiovascular and inflammatory systems, each major player in the high morbidity and mortality of chronic kidney disease, but they are also the systems/mechanisms that have most frequently been studied. Based on a previous review from the authors published in 2018, a selection is made of the compounds with the most demonstrated clinical and experimental toxicity. We first summarize per solute the knowledge acquired from 2018, together with a selection of key studies, and then summarize the most relevant recent data (2018 until now). The picture emerging is one of a multilayered syndrome, where multiple factors contribute to an overall complicated profile, so that it seems doubtful that a decrease of concentration of one single compound will resolve the issue of uremic toxicity.
Asymmetric dimethyl arginine (ADMA) is an amino acid that acts as an endogenous competitive inhibitor of Nitric oxide synthase, leading to endothelial dysfunction (ED). The aim of this study was to evaluate the relationship between plasma ADMA (p-ADMA) level and ED in diabetic subjects with neuropathic foot ulcer (NFU), and the possible predictors of p-ADMA level.
80 diabetic subjects of matched age, sex and BMI were included; 40 with NFU (G1), 20 with peripheral nerve dysfunction (PND) (G2) and 20 without PND (G3), plus 20 matched healthy subjects (G4). Flow-mediated-dilatation (FMD) of brachial artery and Carotid-intima-media-thickness (CIMT) were measured to evaluate ED and subclinical atherosclerosis, respectively.
G1&2 had a significantly lower FMD than G3&4 [−5.09 (−22.5 to 22.92), 4.67 (−15 to 23.91) vs. 15.74 (8.33−36.59) and 20.1 (10.0–46.15)%, respectively] (p < 0.001), and higher CIMT [0.9 (0.6–1.5), 0.9 (0.6–1.3) vs. 0.6 (0.5−0.8) and 0.7 (0.5−0.9) cm, respectively] (p < 0.001, r = 0.237, p = 0.034, r = 0.330, p = 0.003, respectively), with no significant correlation with FMD (r = −0.176, p = 0.118). FMD was inversely and strongly related to CIMT (r = −0.520, p < 0.001). p-ADMA levels were significantly higher in uncontrolled hypertensive patients in comparison to controlled and normotensive subjects [717 (286−3611) vs. 648 (335−874) and 686 (526−857) ng/L, respectively] (p = 0.026). Metformin users and hypertensive subjects on ACEIs or ARBs had the lowest p-ADMA levels than the non-users (p < 0.001, p = 0.007, respectively).
The remarkable ED in diabetic subjects with NFU is unlikely to be due to alteration in p-ADMA. Further studies are needed in order to conclude a causal association between p-ADMA and ED in this group of patients.
A preliminary study on the relationship between sleep, depression and cardiovascular dysfunction in a 4 sample population
2021, IJC Heart and VasculatureMajor Depressive Disorder (MDD) has been linked in the literature to poorer prognosis in patients with cardiovascular dysfunction, although the mechanisms of this relationship remain unclear. Underlying Sleep Disordered Breathing (SDB) serves as a potential candidate to explain this effect due to its downstream effects on inflammatory activation and decreased nitric oxide (NO) bioavailability, both of which have been shown to contribute to the pathophysiology of both MDD and cardiovascular disease (CVD).
This study utilizes overnight polysomnography and an inflammation panel to examine the links between cardiovascular dysfunction and sleep difficulties in control participants and patients diagnosed with SDB only, MDD only, and both SDB and MDD.
Results demonstrate a strong positive relationship between sleep dysfunction and the nitric oxide synthesis inhibitor Symmetric Dimethyl Arginine (SDMA) in the MDD-only cohort, suggesting a link between SDMA-mediated NO dysregulation and CVD pathogenesis in individuals with MDD. Additionally, hypopneas, a form of sleep impairment characterized by partial reduction of airflow, were found to play a significant role in the relationship between SDB and cardiovascular dysfunction in MDD-only patients.
Results of this study demonstrate the need for widespread screening for SDB in MDD populations to detect predisposition to CVD, and also offer SDMA as a new potential target for CVD treatment in individuals with MDD.
Maternal exposure to ambient air pollution and congenital heart defects in China
2021, Environment InternationalEvidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been mixed and are still relatively limited in developing countries. We aimed to investigate the association between maternal exposure to air pollution and CHD in China.
This longitudinal, population-based, case-control study consecutively recruited fetuses with CHD and healthy volunteers from 21 cities, Southern China, between January 2006 and December 2016. Residential address at delivery was linked to random forests models to estimate maternal exposure to particulate matter with an aerodynamic diameter of ≤ 1 µm (PM1), ≤2.5 µm, and ≤10 µm as well as nitrogen dioxides, in three trimesters. The CHD cases were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia ultrasound. The CHD subtypes were coded using the International Classification Diseases. Adjusted logistic regression models were used to assess the associations between air pollutants and CHD and its subtypes.
A total of 7055 isolated CHD and 6423 controls were included in the current analysis. Maternal air pollution exposures were consistently higher among cases than those among controls. Logistic regression analyses showed that maternal exposure to all air pollutants during the first trimester was associated with an increased odds of CHD (e.g., an interquartile range [13.3 µg/m3] increase in PM1 was associated with 1.09-fold ([95% confidence interval, 1.01–1.18]) greater odds of CHD). No significant associations were observed for maternal air pollution exposures during the second trimester and the third trimester. The pattern of the associations between air pollutants and different CHD subtypes was mixed.
Maternal exposure to greater levels of air pollutants during the pregnancy, especially the first trimester, is associated with higher odds of CHD in offspring. Further longitudinal well-designed studies are warranted to confirm our findings.