Characterization of the effect of serum bilirubin concentrations on coronary endothelial function via measurement of high-sensitivity C-reactive protein and high-density lipoprotein cholesterol.

Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P < 0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.

COVID-19 with Rapid Progression to Hypoxemia Likely due to Imbalance between Ventilation and Blood Flow: A Case Report.

BACKGROUND: In COVID-19 pneumonia, cases of severe hypoxemia in the early stage and cases of sudden deterioration in respiratory status due to silent hypoxia leading to death, have been reported. CASE SUMMARY: A 70-year-old Japanese man with essential hypertension, dyslipidemia, chronic kidney disease and emphysema was hospitalized with the novel coronavirus disease. He had hypoxemia that was disproportionate to the severity of pneumonia indicated by computed tomography (CT), along with coagulation abnormalities. We speculated that there was a high possibility that he had developed ventilation and blood flow imbalance due to pulmonary intravascular coagulopathy (PIC) or hypoxic pulmonary vasoconstriction (HPV). In this case, early, short-term combination therapy with remdesivir, nafamostat mesylate and low-dose dexamethasone (Dex) was successful. CONCLUSION: In COVID-19 patients with multiple comorbidities who have hypoxemia and coagulation abnormalities that are disproportionate to the severity of pneumonia on CT, it is important to commence antiviral and anticoagulant therapy as soon as possible, followed by use of a low dose of Dex.

Effects of Eggshell Membrane on Keratinocyte Differentiation and Skin Aging In Vitro and In Vivo.

Skin aging is one of the hallmarks of the aging process that causes physiological and morphological changes. Recently, several nutritional studies were conducted to delay or suppress the aging process. This study investigated whether nutritional supplementation of the eggshell membrane (ESM) has a beneficial effect on maintaining skin health and improving the skin aging process in vitro using neonatal normal human epidermal keratinocytes (NHEK-Neo) and in vivo using interleukin-10 knockout (IL-10 KO) mice. In NHEK-Neo cells, 1 mg/mL of enzymatically hydrolyzed ESM (eESM) upregulated the expression of keratinocyte differentiation markers, including keratin 1, filaggrin and involucrin, and changed the keratinocyte morphology. In IL-10 KO mice, oral supplementation of 8% powdered-ESM (pESM) upregulated the expression of growth factors, including transforming growth factor ß1, platelet-derived growth factor-ß and connective tissue growth factor, and suppressed skin thinning. Furthermore, voltage-gated calcium channel, transient receptor potential cation channel subfamily V members were upregulated by eESM treatment in NHEK-Neo cells and pESM supplementation in IL-10 KO mice. Collectively, these data suggest that ESM has an important role in improving skin health and aging, possibly via upregulating calcium signaling.

Pancreaticoduodenectomy after transcatheter aortic valve implantation in an elderly patient with severe aortic stenosis and pancreas cancer: A case report.

INTRODUCTION AND IMPORTANCE: Not only pancreatic cancer but also aortic stenosis (AS) is increasing with the aging population. There is no optimal strategy for elderly patients with both pancreatic cancer and AS. We report a case of pancreatic head cancer with severe AS undergoing pancreaticoduodenectomy (PD) after transcatheter aortic valve implantation (TAVI). CASE PRESENTATION: An 88-year-old woman was referred to our hospital because of severe AS with symptoms of heart failure. Preoperative examination revealed resectable pancreatic head cancer, so TAVI was performed before PD to reduce the perioperative risk. The patient underwent PD 34 days after TAVI, with no significant postoperative complications, and was transferred to the other hospital for rehabilitation on postoperative day 45. No recurrence was observed at more than 7 months without adjuvant therapy. CLINICAL DISCUSSION: Aortic valve replacement (AVR) is recommended before non-cardiac surgery in patients with symptomatic severe AS. Surgical aortic valve replacement (SAVR) is the standard treatment. However, owing to the highly invasive procedure and increased perioperative risk, SAVR is usually avoided in elderly patients with malignancy and severe AS. We demonstrated that TAVI followed by PD could be safely performed in high-risk elderly patients presenting with both severe AS and pancreatic head cancer. To our knowledge, this is the first case report of PD after TAVI in a patient with severe AS. CONCLUSION: We demonstrated that TAVI followed by PD could be safely performed in high-risk elderly patients presenting with severe AS and co-existing malignancy.

Enjoying hobbies is related to desirable cardiovascular effects.

An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 +/- 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% +/- 77% vs 25% +/- 37%, P < 0.05, 4% +/- 13% vs -3% +/- 20%, P < 0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P < 0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.

Usefulness of the adenosine triphosphate with a sufficient observation period for detecting reconduction after pulmonary vein isolation.

BACKGROUND: Although reconduction after pulmonary vein (PV) isolation is considered to play a key role in the recurrence of paroxysmal atrial fibrillation (AF), there have been few reports regarding the precise time course of early reconduction. Several studies have suggested that transient PV reconduction facilitated by adenosine may predict long-term AF recurrence. This study was designed to clarify the incidence and time course of early reconduction after PVI during the procedure and to confirm whether the use of ATP after a certain observation period was useful to detect early reconduction after PVI. METHODS: In 21 patients (18 males, 56 +/- 11 years) with drug refractory AF, radiofrequency circumferential PV antrum ablation was performed in all 4 PVs. After the completion of isolation, electrograms in each PV were repeatedly recorded (1.98 +/- 0.57 times per PV) using a circular mapping catheter for an observation period of 87 +/- 29 minutes. After isolation of all 4 PVs, 30 mg of adenosine triphosphate (ATP) was administered during isoproterenol infusion. RESULTS: PV electrical isolation was initially achieved in all 81 PVs. During the observation period, 12 (15%) PVs in 10 (48%) of 21 patients exhibited spontaneous reconduction. Among the remaining 69 PVs, 8 (12%) additional PVs had reconduction with the use of ATP. All PV reconduction was successfully eliminated by 4.5 +/- 2.2 additional radiofrequency applications. CONCLUSION: A sufficient observation period and the use of ATP are useful to detect early reconduction after PV isolation.

Association between Toll-like receptors and the extent and severity of coronary artery disease in patients with stable angina.

OBJECTIVES: Toll-like receptors mediate the innate immune response triggered by pathogen-associated molecular patterns, and atherosclerosis can be considered a state of chronic inflammation whereby immune system cells accumulate within the intima of the arterial wall. The goal of this study was to determine the relation of Toll-like receptors to the extent and severity of coronary artery disease. METHODS: Angiographic vessel score and Gensini score were used to evaluate the extent and severity of coronary atherosclerosis. Sixty-two consecutive patients with stable angina were grouped as follows: those with insignificant (<50%) coronary stenosis (group 1), and those with 1 (group 2), 2 (group 3), or 3-vessel disease (group 4). The expression of Toll-like receptor 1, 2, and 4 on circulating CD14+ monocytes was analyzed by flow-cytometry in all patients. RESULTS: Toll-like receptor 2 had a positive correlation with the vessel score and Gensini score (r=0.46, P<0.001; r=0.32, P<0.02, respectively). Toll-like receptor 4 also positively correlated with the vessel score and Gensini score (r=0.47, P<0.001; r=0.29, P<0.05, respectively). No significant correlation existed between the expression of Toll-like receptor 1 and the vessel score or Gensini score. Further, there was no significant correlation between high-sensitivity C-reactive protein and the vessel score or Gensini score. CONCLUSION: These data suggest that Toll-like receptor 2 and 4 expression correlates with the extent and severity of coronary artery disease.

Association of coronary shear stress with endothelial function and vascular remodeling in patients with normal or mildly diseased coronary arteries.

BACKGROUND: The relationship between coronary remodeling, shear stress and endothelial function remains unclear. OBJECTIVE: The present study investigated the effects of mechanical factors on structure and function of epicardial coronary arteries. METHODS: Patients (group 1: %area stenosis<40%, n=55; or group 2: %area stenosis>or=40%, n=17) with a discrete mildly stenotic lesion (%diameter stenosis<30%) underwent intravascular ultrasound examination of the left anterior descending coronary artery for determination of vessel area, lumen area, plaque area, cross-sectional areas at reference segments, and remodeling index (the ratio of vessel area at the culprit lesion to vessel area at the proximal reference site). Further, vascular reactivity was examined using intracoronary administration of acetylcholine, papaverine, and nitroglycerin. RESULTS: Vessel area significantly correlated with plaque area in both groups (r=0.65, P<0.0001 and r=0.85, P<0.0001). Group 1 showed significantly greater acetylcholine-induced percentage changes in coronary blood flow (67+/-70 vs. 16+/-75%, P<0.05) and coronary artery diameter (-7+/-18 vs.-32+/-31%, P<0.01) and also significantly smaller coronary wall shear stress (65+/-27 vs. 81+/-32 dynes/cm, P<0.05) than group 2. The percentage increase in coronary blood flow induced by acetylcholine was significantly and positively correlated with remodeling index in group 1 (r=0.64, P<0.0001) but not in group 2 (r=-0.03, P=0.90) and was also significantly and positively correlated with coronary wall shear stress in group 1 (r=0.46, P<0.001) but not in group 2 (r=-0.33, P=0.19). CONCLUSIONS: Endothelium-dependent vasodilation in the resistance coronary artery correlates with remodeling via increased wall shear stress when target lesions %area stenosis is <40%.

Contribution of increased minimal coronary resistance and attenuated vascular adaptive remodeling to myocardial ischemia in patients with systemic hypertension and ventricular hypertrophy.

This study assessed the impact of coronary vascular adaptive remodeling and coronary vascular reactivity on myocardial ischemia in patients with hypertension and left ventricular hypertrophy. Myocardial ischemia is associated with impaired endothelium-independent vasodilation of resistance coronary arteries and increased minimal coronary resistance. These changes may occur in association with lumen reduction caused by attenuated adaptive remodeling in response to plaque accumulation.

Reactive hyperemia following coronary balloon angioplasty, but not dipyridamole-induced hyperemia, predicts resolution of exercise-induced ST-segment depression.

OBJECTIVES: To characterize delayed restoration of coronary blood flow following successful percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Delayed restoration of coronary blood flow following successful PTCA is common and likely the result of multiple factors. Temporary myocardial ischemia and dipyridamole administration both result in increased coronary blood flow, but by different mechanisms. The relationship between these phenomena and exercise-induced ST-segment depression after PTCA was investigated to determine if any correlation existed. METHODS: Forty consecutive patients with single-vessel coronary artery disease underwent treadmill exercise testing before and after PTCA. The percentage change in coronary blood flow before and after 90 s balloon inflation was assessed. After a new steady state had been reached, dipyridamole was infused and changes in coronary blood flow were again determined. The relationship between changes in coronary blood flow and the presence of ST-segment depression during exercise testing after PTCA was determined. RESULTS: Peak coronary blood flow induced by reactive hyperemia was significantly greater than that in the steady state after balloon inflation (48.5+/-38.8 compared with 15.1+/-13.2 ml/min, P<0.0001). Dipyridamole administration also resulted in significant increases in coronary blood flow (15.1+/-13.2 ml/min compared with 31.0+/-24.9 ml/min, P<0.0001). ST-segment depression after PTCA was significantly less than before (0.10+/-0.07 mV compared with 0.19+/-0.08 mV, P<0.001). Further, reactive hyperemia, but not dipyridamole-induced hyperemia, correlated with attenuation of exercise-induced ST-segment depression after PTCA (r=0.62, P<0.0001). CONCLUSIONS: Reactive hyperemia following temporary coronary occlusion recreates local conditions associated with delayed resolution of myocardial ischemia following successful PTCA. Further, this phenomenon appears to be distinct from changes in coronary blood flow induced by dipyridamole.

Advancing age is associated with diminished vascular remodeling and impaired vasodilation in resistance coronary arteries.

BACKGROUND: Compensatory enlargement of the coronary arterial wall has been described in the early stages of native atherosclerosis. However, little is known about the specific effect of aging on this adaptive process in atherosclerosis. The purpose of the current study was to characterize the effects of advancing age on vascular remodeling and endothelium-dependent and -independent coronary vasodilation in patients without coronary artery disease risk factors. METHODS: Twenty-six patients without coronary risk factors and with normal and mildly diseased coronary arteries were studied. Vessel, lumen and atherosclerotic plaque areas were evaluated by intravascular ultrasound and coronary flow response was assessed using papaverine and acetylcholine in the left anterior descending coronary artery. RESULTS: There was a weak but significant correlation between plaque area and age (r = 0.29, P<0.01). Vessel area was also weakly but significantly correlated with age (r = 0.22, P<0.05). However, lumen area had no correlation with age. Vessel area in the younger group (<50 years) and the older group (> or =50 years) increased 1.64 and 0.55 mm2 for every 1 mm2 increase in plaque area (r = 0.62, P<0.0001 and r = 0.39, P<0.05, respectively). With regard to vascular reactivity, there was an inverse correlation between the percentage increases in coronary blood flow (CBF) evoked by acetylcholine and aging (r = -0.49, P<0.05). The percentage increases in CBF evoked by papaverine also inversely correlated with aging (r=-0.53, P<0.01). However, the percentage changes in coronary artery diameter evoked with acetylcholine did not correlate with aging. CONCLUSION: This study suggests that endothelium-dependent and -independent vasodilation of the resistance coronary artery are impaired with advancing age, which may be in association with attenuated coronary vascular remodeling with aging.

The association between renal atherosclerotic plaque characteristics and renal function before and after renal artery intervention.

OBJECTIVE: To evaluate the effect of plaque composition on renal function after renal artery intervention (RAI). PATIENTS AND METHODS: In 33 consecutive patients with atherosclerotic renal artery stenosis (enrolled between January 1, 2007, and April 30, 2009), renal angiography, pressure gradients across the lesion, and intravascular ultrasonography (IVUS) with virtual histology (VH)-derived plaque characteristics were assessed. In 25 patients who underwent RAI, estimated glomerular filtration rate (eGFR) was evaluated at baseline and at 3 months. RESULTS: Mean pressure gradients across the lesion were poorly associated with baseline eGFR (r=-0.37; P=.07). In gray scale IVUS data, only remodeling index was significantly correlated with baseline eGFR (r=-0.38; P=.03). Plaque components classified by VH-IVUS had no correlation with baseline eGFR. During follow-up of 25 patients, the improvement in eGFR after RAI was observed in 9 patients, unchanged in 3, and deteriorated in 13. Overall, follow-up eGFR (median, 49.0 mL/min/1.73 m(2); interquartile range [IQR], 40.6-63.9 mL/min/1.73 m(2)) was unchanged compared with baseline eGFR (median, 53.8 mL/min/1.73 m(2); IQR, 41.4-63.4 mL/min/1.73 m(2); P=.38). The percent change in eGFR (median, -0.2%; IQR, -16.0% to 16.0%) after RAI had a significant negative correlation with the mean percentage of necrotic core classified by VH-IVUS (r=-0.47; P=.02), and the mean percentage of necrotic core was significantly larger in patients with deterioration of eGFR than in patients without deterioration of eGFR (median, 12.7%; IQR, 9.5%-19.5%; vs median, 8.3%; IQR, 5.5%-11.6%; P=.04). CONCLUSION: In patients with atherosclerotic renal artery stenosis, the change in eGFR after RAI was related to plaque composition classified by VH-IVUS. The evaluation of plaque composition may provide more insights into the change in renal function after RAI.

Relationship between bilirubin concentration, coronary endothelial function, and inflammatory stress in overweight patients.

AIM: Bilirubin has antioxidant properties and may protect against atherosclerosis and coronary heart disease (CHD). Further, in patients with metabolic syndrome, hyperbilirubinemia is associated with attenuation of insulin resistance. The aim of the present study was to determine the relationship between serum bilirubin concentration and coronary endothelial function in overweight patients. METHODS: The study population consisted of 107 patients without CHD who underwent coronary flow studies. Vascular reactivity was examined by intra-coronary administration of papaverine and nitroglycerin. Coronary endothelial function was evaluated by assessing the change in coronary artery diameter to papaverine [percent change in flow-mediated dilatation (%FMD)] and nitroglycerin (%NTG). Serum total bilirubin, high-sensitivity C-reactive protein (hs-CRP), high density lipoprotein-cholesterol (HDL-C), fasting plasma glucose and immunoreactive insulin levels were also measured, and the homeostasis model assessment insulin resistance (HOMA-IR) index was calculated. Patients were divided into two groups according to body mass index (BMI): an overweight group (BMI ≥ 25; n = 36) and a normal weight group (BMI < 25; n = 71). RESULTS: In the overweight group, univariate analysis revealed that log-transformed total bilirubin was positively correlated with %FMD and HDL-C (r = 0.38, p< 0.05; r = 0.30, p < 0.05, respectively) and was inversely correlated with log-transformed hs-CRP and HOMA-IR (r = -0.45, p < 0.01; r = -0.45, p< 0.05, respectively). Multivariate analysis revealed that log-transformed hs-CRP was the only independent predictor of log-transformed total bilirubin (p< 0.05). CONCLUSIONS: These results suggest that a high bilirubin level was associated with favorable coronary endothelial function in overweight patients. Further, the anti-inflammatory effects of bilirubin may mediate this effect.

Catheter ablation of persistent atrial fibrillation solely guided by complex fractionated atrial electrograms in a patient with persistent left superior vena cava.

Catheter ablation in patients with persistent atrial fibrillation (AF) is challenging. There are few reports of catheter ablation for persistent AF with persistent left superior vena cava (PLSVC). We report an ablation case of persistent AF with PLSVC solely guided by complex fractionated atrial electrogram (CFAE). The subject was a 65-year-old man. Electroanatomic mapping system was used to integrate computed tomography data with 3D mapping data. We identified the CFAE sites on the electroanatomic mapping. Radiofrequency ablation was applied to the CFAE sites; the posterior aspect of left superior pulmonary vein (LSPV), the anterior ridge of left atrial appendage, and the roof at the anterior to the LSPV. After those ablations, AF was finally terminated by ablation in the middle of the PLSVC. Previous investigators have reported that pulmonary vein antrum isolation (PVAI) is effective for the management of patients with either paroxysmal or persistent AF. However, some patients experience episodes of AF despite successful PVAI, which implies that important triggers and perpetuators remain in the posterior left atrium, crista terminalis, superior vena cava, coronary sinus ostium, interatrial septum, and the ligament of Marshall/PLSVC. In conclusion, CFAE ablation was useful in a patient with persistent AF with PLSVC.

Left atrium volume index and pathological features of left atrial appendage as a predictor of failure in postoperative sinus conversion.

BACKGROUND: Previous studies showed that some parameters, including left atrium diameter and left atrium volume index (LAVI), predicted the success of sinus conversion. However, no previous studies have investigated the association of sinus conversion with LAVI and histopathological findings. This study was designed to investigate the relationship among LAVI, pathological assessment, and failure in sinus conversion after surgery for valvular atrial fibrillation (AF). METHODS AND RESULTS: A total of 78 patients with left atrium enlargement and valvular AF who underwent maze procedure concomitantly with various cardiac surgeries were classified into one of two groups: those who successfully underwent sinus conversion (Group 1; n=40) and those who did not achieve sinus conversion (Group 2; n=38). Histopathological assessment was performed in 9 cases using tissues derived from the left atrial appendage (LAA). The degree of histopathological change was classified into 1 of 4 grades. LAVI was significantly less in Group 1 than in Group 2 (81 + or - 22 ml/m(2) vs. 122 + or - 49 ml/m(2), p<0.001). Preoperative LAVI predicted 100% failure of sinus conversion after surgery with a cut-off value of 135 ml/m(2). Histopathological analyses clearly showed that the grades for intercellular fibrosis, fatty infiltration, endocardial thickening, and nuclear enlargement/abnormalities were significantly and positively correlated with LAVI (r=0.75, p<0.05; r=0.74, p<0.05; r=0.69, p<0.05; r=0.77, p<0.05, respectively). CONCLUSIONS: LAVI associated with histopathological features of the resected LAA is a predictor of failure in sinus conversion following surgical intervention in patients with valvular AF.

High expression level of Toll-like receptor 2 on monocytes is an important risk factor for arteriosclerotic disease.

BACKGROUND: Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns to initiate an innate immune response. We previously reported upregulation of TLR2 expression level on monocytes of stable angina pectoris patients with significant coronary artery disease (CAD) relative to control patients without significant CAD. In this study we aimed to determine whether high level of Toll-like receptor 2 (TLR2) is a risk factor for atherogenesis, independent of established risk factors including smoking, diabetes mellitus (DM), hypertension (HT), and hyperlipidemia (HL). METHODS: TLR2 expression level on circulating monocyte surfaces was measured by using our developed flow cytometry assay. Patients were classified into two groups: "Arteriosclerotic disease" group (n=108) and "Control" group (n=70). Patients of the first group had arteriosclerotic disease such as CAD, aortic aneurysm, or peripheral arterial disease (PAD). The "Control" group was sex- and age-matched to the "Arteriosclerotic disease" group. RESULTS: TLR2 expression was significantly higher in the "Arteriosclerotic disease" group than in the "Control" group (p<0.001). Multivariate ordinal logistic regression analysis was performed; other known risk factors, which were represented to two nominal score points, 0 or 1, for patients with and without it, respectively, and TLR2 level, which was treated as a metric variable. DM (p=0.002), HT (p=0.001), HL (p<0.001), and TLR2 level (p<0.001) were identified as significant contributors for arteriosclerotic disease. CONCLUSIONS: High TLR2 expression level on monocytes may be an independent risk factor for atherogenesis.

Effect of uric acid on coronary microvascular endothelial function in women: association with eGFR and ADMA.

AIM: The aim of this study was to investigate the role of uric acid (UA) in coronary endothelial function via its effects on renal function, other coronary risk factors and asymmetric dimethylarginine (ADMA) in men and women. METHODS: The study population consisted of 194 consecutive patients (119 men and 75 women) without coronary artery disease. The relationships between UA and coronary endothelial function, estimated glomerular filtration rate (eGFR), ADMA or other biochemical or anthropometric parameters were investigated. RESULTS: Monovariate analysis of female participants demonstrated that % change in coronary blood flow (CBF) induced by acetylcholine (ACh) was inversely correlated with UA, ADMA and age (r=-0.32, p<0.01; r=-0.31, p<0.05; r=-0.23, p<0.05, respectively), and positively correlated with eGFR (r=0.27, p<0.05). Stepwise regression analysis showed that UA was the only independent predictor of % change in CBF induced by ACh (F value 4.969, p<0.05). Similar analysis of male participants failed to show significant correlations of these variables except for age in monovariate analysis (r=-0.19, p<0.05). Meanwhile, UA was inversely correlated with eGFR in both men and in women (r=-0.25, p<0.01; r=-0.59, p<0.0001, respectively), and ADMA was positively correlated with UA and inversely correlated with eGFR (r=0.36, p<0.05; r=-0.42, p<0.01, respectively) in women but not in men. CONCLUSION: High concentrations of UA correlate with coronary endothelial microvascular dysfunction in women. Further, serum UA concentration is related to eGFR and ADMA only in women, which may result in impaired endothelial function in resistance coronary arteries in women but not in men.

Relationship between hyperglycemia and coronary vascular resistance in non-diabetic patients.

BACKGROUND: Hyperglycemia upon hospital admission in patients with acute myocardial infarction is associated with the no-reflow phenomenon after successful reperfusion, and increased mortality. However, the mechanism underlying this phenomenon remains unclear. Therefore, the aim of this study was to characterize coronary hemodynamics in a homogenous group of non-diabetic patients without coronary artery disease. METHODS AND RESULTS: A total of 104 consecutive non-diabetic patients (mean age, 62+/-14 years) without coronary artery disease underwent Doppler flow study of the left anterior descending coronary artery. Vascular reactivity was examined by intra-coronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Coronary vascular resistance (CVR) was calculated as the mean arterial pressure divided by coronary blood flow (CBF). Baseline CVR was shown as CVR at control and minimal CVR was shown as CVR with papaverine administration. Fasting plasma glucose (FPG) level had a significant, positive correlation with baseline CVR and minimal CVR (r=0.24, p<0.02 and r=0.21, p<0.05, respectively). Hemoglobin A1c (HbA1c) also had a significant, positive correlation with baseline CVR and minimal CVR (r=0.31, p<0.01 and r=0.32, p<0.01, respectively). The percent change in CBF induced by Ach was inversely correlated with HbA1c but not with FPG (r=0.22, p<0.05 and r=0.06, p=0.57, respectively). By contrast, neither FPG nor HbA1c had significant correlation with coronary flow reserve to papaverine. CONCLUSION: These data demonstrate that elevated glucose levels are associated with increases in baseline and minimal coronary vascular resistance. These changes may contribute to unfavorable coronary hemodynamics in non-diabetic patients without coronary heart disease.

Association of plaque composition and vessel remodeling in atherosclerotic renal artery stenosis: a comparison with coronary artery disease.

OBJECTIVES: The current study was designed to investigate the relationship between renal arterial structure and vessel remodeling in patients with atherosclerotic renal artery stenosis (RAS), compared with that seen in coronary artery disease (CAD). BACKGROUND: The nature and the tissue characterization of atherosclerotic RAS lesions have not been fully explored. METHODS: Gray scale and virtual histology (VH) intravascular ultrasound imaging was used to assess 23 lesions in 14 consecutive RAS patients and 20 left main trunk lesions in age-matched CAD patients. Analysis included assessment of vessel area and atherosclerotic plaque area of the main renal artery or left main trunk. Plaque was characterized as fibrous tissue, fibro-fatty tissue, necrotic core, and dense calcium. Remodeling was assessed by means of the remodeling index (RI). RESULTS: Positive remodeling (defined as RI > or =1.05) was present in 15 RAS and 9 CAD lesions, whereas intermediate/negative remodeling (RI <1.05) was present in 8 RAS and 11 CAD lesions. VH showed that the fibrous tissue was the most prominent plaque composition, followed by fibro-fatty, necrotic core, and dense calcium in both vascular beds. Greater vascular adaptive enlargement was observed in slices with plaque burden < or =40% compared with plaque burden >40% (p < 0.001 for all). Vessel area had a positive association with the area of all VH components (p < 0.001, for all). VH analysis shows that the most powerful determinant of adaptive vessel enlargement is dense calcium in RAS (p < 0.001), while that is necrotic core in CAD (p < 0.001). Necrotic core and dense calcium areas were greater in lesions with positive remodeling compared with intermediate/negative remodeling (p = 0.03, p = 0.03, respectively, in RAS; p = 0.005, p = 0.03, respectively, in CAD). CONCLUSIONS: The current study demonstrates in humans that plaque composition as assessed by VH intravascular ultrasound has an important role of adaptive vessel enlargement, and it is related to renal artery remodeling in RAS in a pattern similar to CAD.

Comparison of effect between nitrates and calcium channel antagonist on vascular function in patients with normal or mildly diseased coronary arteries.

The comparative long-term antianginal efficacy of long-acting nitrates versus calcium channel antagonists remains unclear. The goal of the present study was to compare the coronary endothelial cell function and coronary artery vasoconstriction between patients with normal or mildly diseased coronary arteries treated with long-acting nitrates or calcium channel antagonists. Forty-two patients suspected to have angina pectoris and with normal or mildly diseased coronary arteries underwent Doppler flow study of the left anterior descending coronary artery. All patients were suspected to have angina pectoris and were receiving either long-acting nitrates (n = 18; Nitrates group) or calcium channel antagonists (n = 24; Ca-antagonists group) for at least 1 year. Vascular reactivity was assessed by intracoronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Segments that showed the greatest constrictive response to Ach were used for assessment of vasoconstriction. The percent increase in coronary blood flow (CBF) and coronary artery diameter (CAD) induced by Ach was significantly smaller in the Nitrates group than in the Ca-antagonists group (33% +/- 74% vs 83% +/- 77%, P < 0.05; -3% +/- 16% vs 11% +/- 12%, P < 0.01, respectively). The percent diameter reduction in the region of greatest constrictive response to Ach was significantly greater in the Nitrates group than in the Ca-antagonists group (44% +/- 39% vs 15% +/- 32%, P < 0.02). Long-term treatment with long-acting nitrates may produce less favorable effects on coronary endothelial function and the constrictive response to Ach when compared with long-acting calcium channel antagonists in patients with normal or mildly diseased coronary arteries.