Reactive Oxygen Species in the Aorta and Perivascular Adipose Tissue Precedes Endothelial Dysfunction in the Aorta of Mice with a High-Fat High-Sucrose Diet and Additional Factors.

Metabolic syndrome (Mets) is the major contributor to the onset of metabolic complications, such as hypertension, type 2 diabetes mellitus (DM), dyslipidemia, and non-alcoholic fatty liver disease, resulting in cardiovascular diseases. C57BL/6 mice on a high-fat and high-sucrose diet (HFHSD) are a well-established model of Mets but have minor endothelial dysfunction in isolated aortas without perivascular adipose tissue (PVAT). The purpose of this study was to evaluate the effects of additional factors such as DM, dyslipidemia, and steatohepatitis on endothelial dysfunction in aortas without PVAT. Here, we employed eight-week-old male C57BL/6 mice fed with a normal diet (ND), HFHSD, steatohepatitis choline-deficient HFHSD (HFHSD-SH), and HFHSD containing 1% cholesterol and 0.1% deoxycholic acid (HFHSD-Chol) for 16 weeks. At week 20, some HFHSD-fed mice were treated with streptozocin to develop diabetes (HFHSD-DM). In PVAT-free aortas, the endothelial-dependent relaxation (EDR) did not differ between ND and HFHSD (p = 0.25), but in aortas with PVAT, the EDR of HFHSD-fed mice was impaired compared with ND-fed mice (p = 0.005). HFHSD-DM, HFHSD-SH, and HFHSD-Chol impaired the EDR in aortas without PVAT (p < 0.001, p = 0.019, and p = 0.009 vs. ND, respectively). Furthermore, tempol rescued the EDR in those models. In the Mets model, the EDR is compromised by PVAT, but with the addition of DM, dyslipidemia, and SH, the vessels themselves may result in impaired EDR.

Artificially Created Reentry Circuit by Laser Irradiation Causes Atrial Tachycardia to Persist in Murine Atria.

BACKGROUND: There is a gradual progression from paroxysmal to persistent atrial fibrillation (AF) in humans. To elucidate the mechanism involved, the creation of an artificial atrial substrate to persist AF in mice was attempted.Methods and Results:This study used wild type (WT) mice, but it is difficult to induce AF in them. A novel antegrade perfusion method from the left ventricle (LV) to enlarge both atria for artificial atrial modification was proposed in this study. Short duration AF was induced by burst pacing under this method. Optical mapping analysis revealed non-sustained focal type and meandering spiral reentrants after short duration AF. A tiny artificial substrate (~1.2 mm in diameter) was added in by laser irradiation to create a critical atrial arrhythmogenic substrate. Burst pacing was performed in a non-laser group (n=8), a circular-shape laser group (n=8), and a wedge-shaped dent laser group (n=8). We defined AF and atrial tachycardia (AT) as atrial arrhythmia (AA). Long-lasting AA was defined as lasting for ≥30 min. Long-lasting AA was observed in 0/8, 0/8, and 6/8 (75%) mice in each group. Optical mapping analysis revealed that the mechanism was AT with a stationary rotor around the irradiated margin. CONCLUSIONS: Regrettably, this study failed to reproduce persistent AF, but succeeded in creating an arrhythmic substrate that causes sustained AT in WT mice.

Arterial Stiffness Assessed by Cardio-Ankle Vascular Index.

Arterial stiffness is an age-related disorder. In the medial layer of arteries, mechanical fracture due to fatigue failure for the pulsatile wall strain causes medial degeneration vascular remodeling. The alteration of extracellular matrix composition and arterial geometry result in structural arterial stiffness. Calcium deposition and other factors such as advanced glycation end product-mediated collagen cross-linking aggravate the structural arterial stiffness. On the other hand, endothelial dysfunction is a cause of arterial stiffness. The biological molecular mechanisms relating to aging are known to involve the progression of arterial stiffness. Arterial stiffness further applies stress on large arteries and also microcirculation. Therefore, it is closely related to adverse outcomes in cardiovascular and cerebrovascular system. Cardio-ankle vascular index (CAVI) is a promising diagnostic tool for evaluating arterial stiffness. The principle is based on stiffness parameter ß, which is an index intended to assess the distensibility of carotid artery. Stiffness parameter ß is a two-dimensional technique obtained from changes of arterial diameter by pulse in one section. CAVI applied the stiffness parameter ß to all of the arterial segments between heart and ankle using pulse wave velocity. CAVI has been commercially available for a decade and the clinical data of its effectiveness has accumulated. The characteristics of CAVI differ from other physiological tests of arterial stiffness due to the independency from blood pressure at the time of examination. This review describes the pathophysiology of arterial stiffness and CAVI. Molecular mechanisms will also be covered.

A Rare Case of Rush Progression of Purulent Pericarditis by Escherichia coli in a Patient with Malignant Lymphoma.

Purulent pericarditis is a rare disease in the antibiotic era. The common pathogens of purulent pericarditis are gram-positive species such as Staphylococcus aureus. Streptococcus pneumoniae, Salmonella, Haemophilus, fungal pathogens/tuberculosis can also result in purulent pericarditis. We report an old male case of purulent pericarditis by Escherichia coli. He came to our hospital suffering from leg edema for 3 months. Echocardiography revealed the large amount of pericardial effusion, and he was admitted to test the cause of pericardial effusion without high fever, tachycardia, and shock vital signs. On the third day, he suddenly presented vital shock. We performed emergency cardiopulmonary resuscitation and pericardiocentesis. Appearance of pericardial effusion was hemorrhagic and purulent. The gram stain revealed remarkable E. coli invasion to pericardial space. Antibiotic therapy was immediately started; however, he died on sixth day with septic shock. The cytological examination of pericardial effusion suggested the invasion of malignant lymphoma to pericardium. This case showed subacute or chronic process of pericarditis without severe clinical and laboratory sings before admission. Nevertheless, bacterial purulent pericarditis usually shows acute clinical manifestation; the first process of this case was very silent. Immunosuppression of malignant lymphoma might make E. coli translocation from gastrointestinal tract to pericardial space, and bacterial pericarditis was progressed to purulent pericarditis. In the latter process, this case showed unexpected rush progression to death by sepsis from purulent pericarditis. Immediate pericardiocentesis should be performed for a prompt diagnosis of purulent pericarditis, and it might have improved the outcome of this case.

Arterial Stiffness Is Significantly Associated With Left Ventricular Diastolic Dysfunction in Patients With Cardiovascular Disease.

Left ventricular (LV) diastolic dysfunction is considered the main cause of heart failure with preserved ejection fraction (HFpEF). There have been few reports on the correlation between LV diastolic dysfunction and arterial stiffness in patients with clinical cardiovascular disease.This cross-sectional study enrolled 100 patients (67 men, 33 women; mean age, 70 years). All participants were diagnosed with cardiovascular disease. A total of 89 (89%) patients had coronary artery disease or HF. Patients with reduced EF and valvular disease were excluded. Arterial stiffness was assessed by the cardio-ankle vascular index (CAVI), and LV diastolic dysfunction was estimated using echocardiography. The patients were divided into two groups based on the median value of CAVI. In all patients the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') was significantly higher in the high CAVI group than in the low CAVI group (15.5 ± 6.4 versus 12.5 ± 2.9, P = 0.003). In the HF subgroup, E/e' was also significantly higher in the high CAVI group than in the low CAVI group (17.2 ± 5.9 versus 13.0 ± 3.1, P = 0.026). In univariate regression analysis, CAVI was significantly associated with E/e' in all patients (ß = 0.28, P = 0.004) and in HF patients (ß = 0.4, P = 0.028). Also in multivariate analysis, CAVI remained as an independent predictive factor of E/e' (ß = 0.252, P = 0.037).A high CAVI was independently associated with LV diastolic dysfunction in patients with clinical cardiovascular disease. These results suggested that arterial stiffness contributed to the development of LV diastolic dysfunction.

A Low Arginine/Ornithine Ratio is Associated with Long-Term Cardiovascular Mortality.

AIMS: The long-term prognostic value of the bioavailability of L-arginine, an important source of nitric oxide for the maintenance of vascular endothelial function, has not been investigated fully. We therefore investigated the relationship between amino acid profile and long-term prognosis in patients with a history of standby coronary angiography. METHODS: We measured the serum concentrations of L-arginine, L-citrulline, and L-ornithine by high-speed liquid chromatography. We examined the relationship between the L-arginine/L-ornithine ratio and the incidence of all-cause death, cardiovascular death, and major adverse cardiovascular events (MACEs) in 262 patients (202 men and 60 women, age 65±13 years) who underwent coronary angiography over a period of ≤ 10 years. RESULTS: During the observation period of 5.5±3.2 years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, while 32 (12%) had MACEs. Cox regression analysis revealed that L-arginine/L-ornithine ratio was associated with an increased risk for all-cause death (unadjusted hazard ratio, 95% confidence interval) (0.940, 0.888-0.995) and cardiovascular death (0.895, 0.821-0.965) (p＜0.05 for all). In a model adjusted for age, sex, hypertension, hyperlipidemia, diabetes, current smoking, renal function, and log10-transformed brain natriuretic peptide level, cardiovascular death (0.911, 0.839-0.990, p=0.028) retained an association with a low L-arginine/ L-ornithine ratio. When the patients were grouped according to an L-arginine/L-ornithine ratio of 1.16, the lower L-arginine/L-ornithine ratio group had significantly higher incidence of all-cause death, cardiovascular death, and MACEs. CONCLUSION: A low L-arginine/L-ornithine ratio may be associated with increased 10-year cardiac mortality.

Association between Smoking and Urine Indole Levels Measured by a Commercialized Test.

Indoles are formed from dietary tryptophan by tryptophanase-positive bacterium. A few amounts of indole are excreted in the urine. On the other hand, cigarette smoke contains indoles, which could also change the urine indole levels. This study sought to elucidate the relationship between urine indole levels and smoking habits. A total of 273 healthy men (46 ± 6 years old) were enrolled in the study. Fasting urine and blood samples were obtained in the morning. The indole concentration was measured by a commercialized kit with a modified Kovac's reagent. The relationship with smoking status was evaluated. The median value of the urine indole test was 29.2 mg/L (interquartile range; 19.6-40.8). The urine indole level was significantly elevated in the smoking subjects (non-smoking group, 28.9 (20.9-39.1) mg/L, n = 94; past-smoking group, 24.5 (15.7-35.5) mg/L, n = 108; current-smoking group, 34.3 (26.9-45.0) mg/L, n = 71). In the current-smoking group, urine indole levels correlated with the number of cigarettes per day (ρ = 0.224, p = 0.060). A multivariate regression test with stepwise method revealed that the factors relating to urine indole level were current smoking (yes 1/no 0) (standardized coefficient ß = 0.173, p = 0.004), blood urea nitrogen (ß = 0.152, p = 0.011), and triglyceride (ß = -0.116, p = 0.051). The result suggests that smoking is associated with increased urine indole levels. The practical test might be used as a screening tool to identify the harmful effect of smoking.

Effectiveness of pulsatility index of carotid Doppler ultrasonography to predict cardiovascular events.

PURPOSE: The pulsatility index (PI) obtained from carotid ultrasonography is considered to be a marker of cerebrovascular resistance. However, the impact of PI on cardiovascular events has yet to be fully addressed. METHOD: Fifty-four patients who underwent both carotid ultrasonography and coronary angiography were followed for 5.9 ± 3.2 years. The relationship between the incidence of cardiovascular events and PI was investigated. RESULT: There were 10 (19%) deaths, four (7%) cardiovascular deaths, and nine (17%) major adverse cardiovascular events (MACEs). The cardiovascular events-defined as all hospitalization for MACEs plus heart failure, revascularization, and cardiovascular surgery-occurred in 21 patients (39%). The patients were divided into two groups according to each threshold of PI value for common carotid arteries (CCA), internal carotid arteries (ICA), and external carotid arteries (ECA), respectively. The thresholds were calculated based on receiver-operating characteristic curves for cardiovascular events. Log-rank test showed that the groups with CCA-PI ≥ 1.71, ICA-PI ≥ 1.20, and ECA-PI ≥ 2.46 had a higher incidence of cardiovascular events, respectively (p < 0.05). ECA-PI ≥ 2.46 was associated with an increased incidence of MACEs. Multivariate Cox regression analysis adjusting for cardiovascular risk factors showed that high PI of CCA, ICA, or ECA was a risk factor for cardiovascular events, respectively (CCA-PI ≥ 1.71, hazard ratio (HR) 3.242, p = 0.042; ICA-PI ≥ 1.20, HR 3.639, p = 0.012; ECA-PI ≥ 2.46, HR 11.322, p = 0.001). CONCLUSION: The results suggested that carotid PIs were independent predictive factors for further cardiovascular events. In particular, high ECA-PI levels may reflect severe arteriosclerosis.

Effectiveness of the d-ROMs oxidative stress test to predict long-term cardiovascular mortality.

BACKGROUND: The long-term prognostic value of the derivatives of reactive oxidative metabolites (d-ROMs) oxidative stress test, which measures hydroperoxide in blood, has not been fully investigated. METHODS AND RESULTS: We administered the d-ROMs test to 265 patients with cardiovascular disease (204 men, 61 women; age, 65 ± 13 years) and followed these patients for up to 10 years. During the observational period of 5.82 (2.47-8.34) years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, and 33 (12%) had major adverse cardiovascular events (MACEs). Cox regression analysis revealed that patients with a d-ROMs value ≥395 U.CARR had a greater risk for all-cause mortality [unadjusted hazard ratio (95% confidence interval), 3.586 (1.772-7.257)], cardiovascular death [7.034 (2.805-17.640)], and MACEs [4.440 (2.237-8.814)] (p < 0.001 for all). In a model adjusted for age, sex, estimated glomerular filtration rate, C-reactive protein, diabetes, hypertension, hyperlipidemia, coronary artery diseases, current smoking, and log-transformed brain natriuretic peptide, all-cause death [2.311 (1.059-5.135), p = 0.036], cardiovascular death [4.398 (1.599-12.099), p = 0.004], MACEs [2.696 (1.266-5.739), p = 0.010] were still significant in patients with high d-ROMS values. CONCLUSION: A high d-ROMs value is an independent predictor of the long-term risk of cardiovascular mortality. A d-ROMs value of 395 U.CARR was considered to be an appropriate threshold for distinguishing prognosis.

Endothelial Extracellular Signal-Regulated Kinase/Thromboxane A2/Prostanoid Receptor Pathway Aggravates Endothelial Dysfunction and Insulin Resistance in a Mouse Model of Metabolic Syndrome.

Background Metabolic syndrome is characterized by insulin resistance, which impairs intracellular signaling pathways and endothelial NO bioactivity, leading to cardiovascular complications. Extracellular signal-regulated kinase (ERK) is a major component of insulin signaling cascades that can be activated by many vasoactive peptides, hormones, and cytokines that are elevated in metabolic syndrome. The aim of this study was to clarify the role of endothelial ERK2 in vivo on NO bioactivity and insulin resistance in a mouse model of metabolic syndrome. Methods and Results Control and endothelial-specific ERK2 knockout mice were fed a high-fat/high-sucrose diet (HFHSD) for 24 weeks. Systolic blood pressure, endothelial function, and glucose metabolism were investigated. Systolic blood pressure was lowered with increased NO products and decreased thromboxane A2/prostanoid (TP) products in HFHSD-fed ERK2 knockout mice, and Nω-nitro-l-arginine methyl ester (L-NAME) increased it to the levels observed in HFHSD-fed controls. Acetylcholine-induced relaxation of aortic rings was increased, and aortic superoxide level was lowered in HFHSD-fed ERK2 knockout mice. S18886, an antagonist of the TP receptor, improved endothelial function and decreased superoxide level only in the rings from HFHSD-fed controls. Glucose intolerance and the impaired insulin sensitivity were blunted in HFHSD-fed ERK2 knockout mice without changes in body weight. In vivo, S18886 improved endothelial dysfunction, systolic blood pressure, fasting serum glucose and insulin levels, and suppressed nonalcoholic fatty liver disease scores only in HFHSD-fed controls. Conclusions Endothelial ERK2 increased superoxide level and decreased NO bioactivity, resulting in the deterioration of endothelial function, insulin resistance, and steatohepatitis, which were improved by a TP receptor antagonist, in a mouse model of metabolic syndrome.

Association of serum nitric oxide metabolite level with mortality in patients undergoing coronary angiography.

BACKGROUND: Nitric oxide (NO) is a relevant molecule for vascular homeostasis. The level of serum NO metabolites (NOx), which consist of nitrite and nitrate, has been investigated as an alternative biomarker of NO production, but its clinical value has not yet been determined. METHODS AND RESULTS: 143 patients (66 ±â€¯12 years old) were followed up after coronary catheterization. During a median (inter-quartile range) observation period of 6.13 (3.32-9.21) years, there were 20 (14 %) all-cause deaths, including 11 (8 %) cardiovascular deaths, 17 (12 %) major adverse cardiovascular events, and 17 (12 %) hospital admissions for heart failure. Median NOx level was 34.5 µmol/L (23.9-54.3). NOx was a risk factor for all-cause death [hazard ratio (HR) by unit increase, 1.010, 95 % confidence interval (CI) 1.001-1.018; p = 0.021] and heart failure (HR 1.010, CI 1.001-1.019; p = 0.029). Even after adjustment for age, sex, coronary risk factors, C-reactive protein, log-transformed brain natriuretic peptide, estimated glomerular filtration rate, and nitrate treatment, NOx was a risk factor for all-cause death (HR 1.015, CI 1.004-1.027; p = 0.008) and admission with heart failure (HR 1.018, CI 1.005-1.018, p = 0.007). CONCLUSIONS: An increase in serum NOx level does not herald a benign clinical course but is an independent predictor of high risk of any-cause mortality and heart failure.

Characterization of tolvaptan response and its impact on the outcome for patients with heart failure.

BACKGROUND: Conventional diuretic therapy such as loop diuretics is a cornerstone of the treatment for heart failure (HF). Diuretic response is an important factor in determining resistance to HF therapy and has been shown to be associated with subsequent clinical outcome. Tolvaptan (TVP), a vasopressin V2 receptor antagonist, has a favorable profile in terms of rapid fluid removal and less aggravation of renal function. We hypothesized that the response to TVP might be associated with the subsequent clinical outcome. METHOD: In this single-center retrospective study, 148 consecutive HF patients who were administered TVP from 2014 through 2018 [age 79 (69-86) years, male 89 (60%)] were included. Ninety-six patients were divided into TVP responder [N = 39 (41%)] and non-responder groups based on the cut-off value of gained urine output (+ 93 ml/mg TVP /day) on the day after TVP was introduced. RESULTS: Early TVP introduction (p = 0.012) and lower dose of loop diuretics (p = 0.043) were predictors of TVP responder. For 2 years after discharge, TVP responders showed more favorable outcomes regarding the primary endpoint defined as the composite of all-cause death and HF readmission (p = 0.034, log-rank test) and HF readmission (p = 0.005). A multivariable Cox model analysis revealed that TVP responder was an independent predictor of the primary endpoint (hazard ratio 0.48, p = 0.041). TVP responders had a lower number of HF readmissions over a 1-year period (p = 0.002). TVP response was independently associated with the number of HF readmissions (p = 0.015). The proportion of patients with an extended period between discharge and HF readmission after TVP administration was higher in responders than non-responders (67% vs. 23%, p = 0.006). These associations of TVP response and post-discharge outcomes were more evident in patients who continued TVP after discharge. CONCLUSION: TVP response can be indicative of subsequent clinical outcomes and may be informative when considering advanced care planning.

Impact of oxidative posttranslational modifications of SERCA2 on heart failure exacerbation in young patients with non-ischemic cardiomyopathy: A pilot study.

BACKGROUND: Oxidative posttranslational modifications (OPTM) impair the function of Sarcoplasmic/endoplasmic reticulum (SR) calcium (Ca2+) ATPase (SERCA) 2 and trigger cytosolic Ca2+ dysregulation. We investigated the extent of OPTM of SERCA2 in patients with non-ischemic cardiomyopathy (NICM). METHODS AND RESULTS: Endomyocardial biopsy (EMB) was obtained in 40 consecutive patients with NICM. Total expression and OPTM of SERCA2, including sulfonylation at cysteine-674 (S-SERCA2) and nitration at tyrosine-294/295 (N-SERCA2), were examined by immunohistochemical analysis. S-SERCA2 increased in the presence of late gadolinium enhancement on cardiac magnetic resonance imaging. S-SERCA2/SERCA2 and N-SERCA2/SERCA2 correlated with cardiac fibrosis evaluated by Masson's trichrome staining of EMB. SERCA2 expression modestly increased in parallel with an upward trend in OPTM of SERCA2 with aging. This tendency became prominent only in patients aged >65 years. OPTM of SERCA2 positively correlated with brain natriuretic peptide (BNP) values only in patients aged ≤65 years. Composite major adverse cardiac events (MACE) increased more in the high OPTM group of younger patients; however, MACE-free survival was similar irrespective of the extent of OPTM in older patients. CONCLUSIONS: OPTM of SERCA2 correlate with myocardial fibrosis in NICM. In younger patients, OPTM of SERCA2 correlate with elevated BNP and increased composite MACE.

Computed tomography-measured pulmonary artery to aorta ratio and EUTOS score for detecting dasatinib-induced pulmonary arterial hypertension.

BACKGROUND: Periodic echo-based screening to detect early stages of a rare complication of dasatinib, pulmonary arterial hypertension (PAH), is inefficient and weakens the potential benefit of dasatinib as a potent drug for chronic myelogenous leukemia (CML). This study aimed to identify the predisposing factors of DASA-PAH to stratify high-risk patients for dasatinib-induced PAH (DASA-PAH). METHODS: Sixty consecutive adult patients who received dasatinib were enrolled in this case-control study. We defined DASA-PAH when at least one of the following four criteria was met: (1) recent electrocardiographic changes indicating right ventricular pressure overload, (2) estimated systolic pulmonary arterial pressure > 40 mmHg measured by Doppler echocardiography; (3) computed tomography (CT)-measured pulmonary artery to aorta diameter (PaD/AoD) ratio > 1; and (4) mean pulmonary arterial pressure > 25 mmHg and pulmonary artery wedge pressure < 15 mmHg measured by right heart catheterization. RESULTS: We identified 13 patients with DASA-PAH among 59 patients analyzed. Baseline PaD/AoD ratios of patients who developed DASA-PAH (PH group) were significantly larger than those who did not (NPH group). A dramatic rise in PaD/AoD ratio after dasatinib treatment was observed. Interestingly, the EUTOS score and spleen size were significantly smaller in the PH than in the NPH group. CONCLUSION: High baseline PaD/AoD ratio and low EUTOS score were associated with DASA-PAH development. The spleen might play a protective role against DASA-PAH.

Tranexamic Acid Controlled Chronic Disseminated Intravascular Coagulation Associated with Aortic Dissection and Patent False Lumen for Three Years.

The management of chronic disseminated intravascular coagulation (DIC) caused by aortic dissection has not yet been established. Even in cases where surgical correction is performed, therapeutic control of systemic hemorrhaging is still required. We herein report the successful treatment of a case of aortic dissection with a patent false lumen using tranexamic acid for acute exacerbation of chronic DIC. Oral administration of 1,500 mg tranexamic acid per day stabilized the coagulative and fibrinolytic parameters and relieved bleeding tendencies with no side effects. Heparin was administered periodically for the management of hemodialysis. This favorable result continued for up to 3 years.

Usefulness of the d-ROMs test for prediction of cardiovascular events.

BACKGROUND: d-ROMs test developed to determine the degree of individual oxidative stress may predict cardiovascular events. METHODS AND RESULTS: 265 patients (204 men, 61 women; age, 65±13years) who had been treated for cardiovascular disease were divided evenly by quartile of baseline d-ROMs levels, and were followed up. During the observation periods of 2.66±1.47years, there were 14 (5%) deaths, 8 (3%) cardiovascular deaths, 13 (5%) major adverse cardiovascular events (MACEs), and 51 (19%) all cardiovascular events including heart failure, cardiovascular surgery, and revascularization. Log-rank tests demonstrated that the patients in the 4th quartile (d-ROMs≧395.00U.CARR) had a higher incidence rate of cardiovascular death than those in the 2nd quartile (d-ROMs 286.00-335.00, p=0.022). In multivariate Cox regression analysis, even after adjustment for age, sex, coronary risk factors, C-reactive protein, and renal function, high d-ROMs was a risk factor for all-cause death [adjusted HR of 4th vs. 1st quartile, 10.791 (95% confidence interval 1.032-112.805), p=0.047], and all cardiovascular events [HR of 4th vs. 1st quartile, 2.651 (95% confidence interval 1.138-6.177), p=0.024]. CONCLUSIONS: Our results suggest that d-ROMs is a useful oxidative stress marker to assess prognosis and risk of further cardiovascular events.

Association between brachial-ankle pulse wave velocity and the ratio of l-arginine to asymmetric dimethylarginine in patients undergoing coronary angiography.

BACKGROUND: Endothelial dysfunction causes vasomotor dysregulation and vascular stiffening in addition to structural changes. By influencing NO synthesis, deficiency of l-arginine relative to asymmetric dimethylarginine (ADMA), which is an l-arginine derivative that acts as a competitive NO synthase inhibitor, may lead to the promotion of arterial stiffness. This study investigated the relationship between the l-arginine/ADMA ratio and brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness. METHODS AND RESULTS: This cross-sectional study enrolled 74 patients (62 men, 12 women; mean age, 67±10 years) undergoing elective coronary angiography. A total of 54 (73%) patients had coronary artery disease. Serum l-arginine and ADMA were measured by high-performance liquid chromatography with fluorescence detection. The ratio of l-arginine to ADMA and the serum l-arginine level was associated with baPWV in univariate regression analysis (l-arginine/ADMA ratio: ß=-0.323, p=0.005; l-arginine: ß=-0.247, p=0.034). In addition, baPWV was related to blood hemoglobin concentration, hematocrit, brain natriuretic peptide level, symmetric dimethylarginine, renal function, blood pressure, and heart rate. In multivariate analysis, the l-arginine/ADMA ratio was a significant predictor of baPWV (ß=-0.310, p<0.001). In subgroup analyses, the l-arginine/ADMA ratio was associated with baPWV in elderly patients (n=46, ß=-0.359, p=0.004), and in younger patients (n=28, ß=-0.412, p=0.006). CONCLUSION: A low l-arginine/ADMA ratio may be associated with high baPWV in patients undergoing coronary angiography.