Difference in right and left cardio-ankle vascular index as a useful marker for evaluation of leg ischemia in patients with lower extremity arterial disease.

OBJECTIVES: Cardio-ankle vascular index (CAVI) is a blood pressure-independent measure of heart-ankle pulse wave velocity and is used as an indicator of arterial stiffness. However, there is a paradox that CAVI is inversely associated with leg ischemia in patients with lower extremity arterial disease (LEAD). The aim of this study was to clarify the significance of the absolute value of left and right difference in CAVI (diff-CAVI). METHODS: The subjects were 165 patients with LEAD who had received medication therapy. Relationships between diff-CAVI and leg ischemia were investigated. Leg ischemia was evaluated by decrease in leg arterial flow using ankle-brachial index (ABI) and by symptoms using the Rutherford classification. RESULTS: There was a significant inverse correlation between diff-CAVI and ABI. The odds ratio for low ABI of the 3rd versus 1st tertile groups of diff-CAVI was 7.03 with a 95% confidence interval of 2.71 ∼ 18.22. In ROC analysis, the cutoff value of diff-CAVI for low ABI was 1.05 with a sensitivity of 61.1% and a specificity of 87.1%. The median of diff-CAVI was significantly higher in subjects with grade 2 of the Rutherford classification than in subjects with its grade 1. CONCLUSIONS: diff-CAVI showed an inverse association with ABI and a positive association with symptoms of leg ischemia. Thus, diff-CAVI is thought to be a useful indicator of leg ischemia in LEAD patients.

Associations of habitual alcohol drinking with HDL cholesterol and D-dimer in patients with peripheral arterial disease.

BACKGROUND: The risk of cardiovascular disease is lower in light-to-moderate alcohol drinkers than in nondrinkers in the general population. However, it remains to be clarified whether these beneficial effects of alcohol are shown in patients with peripheral arterial disease (PAD). METHODS: The subjects were 153 male outpatients with PAD and they were divided by frequency of drinking into nondrinkers, occasional drinkers (1-4 days/wk) and regular drinkers (5-7 days/wk). Relationships of alcohol drinking with variables related to progression of atherosclerosis and cardiovascular risk were investigated. RESULTS: The levels of HDL cholesterol and d-dimer were significantly higher and lower, respectively, in regular drinkers than in nondrinkers, while there were no significant differences in BMI, blood pressure, total cholesterol, LDL cholesterol, triglycerides, hemoglobin A1c, platelet count, fibrinogen, ankle brachial index and intima-media thickness of the carotid artery in non-, occasional and regular drinkers. Odds ratios of regular drinkers vs. nondrinkers for low HDL cholesterol (0.24 [0.08 âˆ¼ 0.70]) and high d-dimer (0.29 [0.14 âˆ¼ 0.61]) were significantly lower than the reference level. CONCLUSIONS: In patients with PAD, habitual alcohol drinking was associated with increase of HDL cholesterol and suppression of blood coagulability. However, progression of atherosclerosis was not different in nondrinkers and drinkers.

Peptides associated with hypertensive disorders of pregnancy as possible biomarkers for severity of lower extremity arterial disease.

BACKGROUND AND AIMS: Seven circulating peptides, consisting of 18-28 amino acids, were identified as possible biomarkers of hypertensive disorders of pregnancy (HDP) in our previous study. However, it is unknown whether these peptides are relevant to cardiovascular disease. The purpose of this study was to clarify the relationships between serum levels of these peptides and leg arterial blood flow in patients with lower extremity arterial disease (LEAD). METHODS: The subjects were 165 outpatients with LEAD. Patients with advanced LEAD (stages 5 and 6 of the Rutherford classification) were not included. Leg arterial blood flow was evaluated by ankle brachial pressure index (ABI) and % decrease in ABI after leg exercise induced by a leg loader or treadmill. Concentrations of the seven peptides with m/z 2081 (P-2081), 2091 (P-2091), 2127 (P-2127), 2209 (P-2209), 2378 (P-2378), 2858 (P-2858) and 3156 (P-3156) were measured simultaneously with a mass spectrometer. RESULTS: P-2081, P-2127 and P-2209 levels showed significant positive correlations with leg arterial blood flow, while P-2091, P-2378 and P-2858 levels showed significant inverse correlations with leg arterial blood flow. There was no significant correlation between P-3156 levels and leg arterial blood flow. The above positive and inverse associations between peptide levels and leg arterial blood flow were also found in logistic regression analysis using tertile groups divided by the concentrations of each peptide. CONCLUSIONS: Serum levels of six HDP-related peptides (P-2081, P-2091, P-2127, P-2209, P-2378 and P-2858) were associated with lower extremity arterial blood flow in patients with LEAD, and thus these peptides are possible biomarkers for severity of LEAD.

Paradox of the Relationship between Cardio-Ankle Vascular Index and Ankle-Brachial Index in Patients with Lower Extremity Artery Disease.

Objectives: Measurements of ankle-brachial index (ABI) and toe-brachial index (TBI) are standard examinations for evaluating arterial blood flow in lower extremities and diagnosing lower extremity artery disease (LEAD). It remains to be clarified whether cardio-ankle vascular index (CAVI), a blood pressure-independent parameter of arterial stiffness, is associated with ABI and TBI in patients with LEAD. Methods: The subjects were 165 outpatients with LEAD. Arterial blood flow in lower extremities was evaluated by using ABI, TBI, and the degree of leg exercise-induced reduction of ABI (%). Results: CAVI showed significant positive correlations with ABI and TBI and showed significant inverse correlations with exercise-induced % decrease in ABI. CAVI was significantly higher in the 3rd tertile groups of ABI and TBI than that in the corresponding 1st tertile groups and was significantly lower in the 3rd tertile group of exercise-induced % decrease in ABI than that in the 1st tertile group. The above relationships remained significant after adjustment for age, body mass index, blood pressure, diabetes history, and habitual smoking. Conclusions: Although CAVI is a general parameter reflecting arterial stiffness, CAVI showed paradoxical associations, namely, positive associations with ABI and TBI and an inverse association with exercise-induced % decrease in ABI in patients with LEAD.

Differences in circulating obesity-related microRNAs in Austrian and Japanese men: A two-country cohort analysis.

Background: The prevalence of obesity is higher in Western countries than in East Asian countries. It remains unknown whether microRNAs (miRNAs) are involved in the pathogenesis of the ethnic difference in obesity. The purpose of this study was to determine whether expression levels of circulating obesity-associated miRNAs are different in Europeans and Asians. Methods: The subjects were middle-aged healthy male Austrians (n = 20, mean age of 49.9 years) and Japanese (n = 20, mean age of 48.7 years). Total miRNAs in serum from each subject were analyzed using the 3D-Gene miRNA Oligo chip. miRNAs that showed significant differences between the Austrian and Japanese groups were uploaded into Ingenuity Pathway Analysis (IPA). Results: Among 16 miRNAs that were revealed to be associated with obesity in previous studies and showed expression levels that were high enough for a reasonable comparison, serum levels of 3 miRNAs displayed significant differences between the Austrian and Japanese groups: miR-125b-1-3p was significantly lower with a fold change of -2.94 and miR-20a-5p and miR-486-5p were significantly higher with fold changes of 1.73 and 2.38, respectively, in Austrians than in Japanese. In IPA including all 392 miRNAs that showed significant differences between Austrians and Japanese, three canonical pathways including leptin signaling in obesity, adipogenesis pathway and white adipose tissue browning pathway were identified as enriched pathways. Conclusions: miRNAs are thought to be involved in the ethnic difference in the prevalence of obesity, which may in part be caused by different expression levels of miR-125b-1-3p, miR-20a-5p and miR-486-5p.

Ethnic Differences in Serum Levels of microRNAs Potentially Regulating Alcohol Dehydrogenase 1B and Aldehyde Dehydrogenase 2.

Ethnic difference is known in genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B), which cause Asian flushing by blood vessel dilation due to accumulation of acetaldehyde. We investigated ethnic differences in microRNAs (miRNAs) related to ALDH2 and ADH1B. miRNA levels in serum were totally analyzed by using miRNA oligo chip arrays and compared in Austrian and Japanese middle-aged men. There were no ALDH2- and ADH1B-related miRNAs that had previously been reported in humans and that showed significantly different serum levels between Austrian and Japanese men. With the use of miRNA prediction tools, we identified four and five miRNAs that were predicted to target ALDH2 and ADH1B, respectively, and they had expression levels high enough for comparison. Among the ADH1B-related miRNAs, miR-150-3p, -3127-5p and -4314 were significantly higher and miR-3151-5p was significantly lower in Austrian compared with Japanese men, while no significant difference was found for miR-449b-3p. miR-150-3p and miR-4314 showed relatively high fold changes (1.5 or higher). The levels of ALDH2-related miRNAs (miR-30d-5p, -6127, -6130 and -6133) were not significantly different between the countries. miR-150-3p and miR-4314 are candidates of miRNAs that may be involved in the ethnic difference in sensitivity to alcohol through modifying the expression of ADH1B.

Contribution of platelet-derived microRNAs to serum microRNAs in healthy men.

Platelets are a major source of microRNAs (miRNAs) in blood. Relationships between circulating platelet-derived miRNAs were investigated to elucidate their significance as biomarkers. Total miRNAs in serum were analyzed using the 3D-Gene miRNA Oligo chip. Among 22 miRNAs that are included in platelets and play functional roles, sufficient miRNA levels for comparison were detected for 11 miRNAs (let-7b-5p, miR-16-5p, miR-17-5p, miR-24-3p, miR-107, miR-126-3p, miR-150-3p, miR-191-5p, miR-197-3p, miR-223-3p, and miR-326). Among 55 pairs prepared by these miRNAs, relatively strong correlations (Spearman's correlation coefficient >0.8) were shown between miRNAs of 7 pairs including let-7b-5p and miR-16-5p, let-7b-5p and miR-17-5p, let-7b-5p and miR-107, miR-16-5p and miR-17-5p, miR-16-5p and miR-107, miR-17-5p and miR-107, and miR-107 and miR-126-3p. In principal component analysis, the first principal component consisted of let-7b-5p, miR-16-5p, miR-17-5p, miR-107, miR-126-3p, and miR-191-5p. These six miRNAs may be useful biomarkers that reflect platelet condition and function.

Blood levels of microRNAs associated with ischemic heart disease differ between Austrians and Japanese: a pilot study.

Mortality from ischemic heart disease (IHD) is significantly lower in Japan than in Western countries. The purpose of this study was to investigate differences in circulating microRNA (miRNA) levels related to IHD in Austrians and Japanese. Participants were middle-aged healthy male Austrians (n = 20) and Japanese (n = 20). Total miRNAs in serum from each participant were analyzed using the 3D-Gene miRNA Oligo chip. Twenty-one miRNAs, previously reported as associated with IHD, were compared between Austrians and Japanese. The expression levels of miR-106a-5p, miR-135a-3p, miR-150-3p, miR-16-5p, miR-17-5p. miR-191-5p, miR-320b, miR-451a, miR-486-5p, miR-663b, and miR-92a-3p were significantly higher, while the miR-2861 expression level was significantly lower in Austrians as compared to Japanese. Both in Austrians and Japanese, there were significant positive correlations between serum expression levels of each pair of the above miRNAs except for miR-2861. The expression level of miR-2861 showed significant positive correlations with the expression levels of miR-106a-5p, miR-150-3p, miR-17-5p, miR-486-5p, miR-663b and miR-92a-3p in Austrians but not in Japanese. In pathway analysis, proinflammatory cytokine production in foam cells and collagen synthesis in vascular smooth muscle cells were associated with differentially expressed miRNAs. Difference in miRNA levels may contribute to lower cardiovascular risk in Japan than in Western countries.

Relationships among erythrocyte-derived microRNAs in serum of healthy donors.

BACKGROUND: Circulating microRNAs (miRNAs) have recently been proposed to be biomarkers for various diseases including cancer and cardiovascular disease. Erythrocytes are a major source of miRNAs in blood. However, it remains unknown how miRNA levels in serum are influenced by miRNAs in erythrocytes. In this study, we investigated the relationships among serum levels of miRNAs that are contained in erythrocytes. METHODS: Participants were middle-aged healthy Japanese men. Total miRNAs in serum from each participant were analyzed using the 3D-Gene miRNA Oligo chip. Relationships among the levels of eleven miRNAs (miR-103a-3p, -144-3p, -15a-5p, -16--5p, -26a-5p, -423-5p, -451a, -484, -486-5p, -92a-3p, and -93-5p) that have been reported to exist in erythrocytes were investigated by using correlation analysis. RESULTS: Among 55 pairs prepared by the above 11 miRNAs, there were significant correlations between miRNA levels of 31 pairs. In principal component analysis, 4 major erythrocyte-derived miRNAs, miR-16-5p, -451a, -486-5p and -92a-3p, were included in the first principal component. There were strong correlations between miR-16-5p and -451a levels (Spearman's rank correlation coefficient: 0.920) and between miR-486-5p and -92a-3p levels (Spearman's rank correlation coefficient: 0.863). CONCLUSION: There are significant associations among serum levels of erythrocyte-derived miRNAs, and these associations should be taken into account when considering the miRNAs as disease biomarkers.

Association of Serum Uric Acid Levels with Leg Ischemia in Patients with Peripheral Arterial Disease after Treatment.

AIM: We investigated the relationships of serum uric acid levels with the progression of atherosclerosis in patients with peripheral arterial disease (PAD) after treatment. METHODS: Subjects were male patients diagnosed with PAD. Atherosclerosis at the common carotid artery was evaluated based on its intima-media thickness (IMT). Leg arterial flow was evaluated by measuring ankle-brachial index (ABI) and exercise-induced decrease in ABI. RESULTS: Among various risk factors including age, blood pressure, adiposity, estimated glomerular filtration rate, and blood lipid, blood glucose, uric acid, fibrinogen and C-reactive protein levels, only uric acid levels showed significant correlations with ABI [Pearson's correlation coefficient, -0.292 (p＜0.01)] and leg exercise-induced decrease in ABI [Pearson's correlation coefficient, 0.236 (p＜ 0.05)]. However, there was no significant correlation between uric acid levels and maximum or mean IMT. Odds ratios of subjects with the 3rd tertile versus subjects with the 1st tertile for uric acid levels were significantly higher than the reference level of 1.00 for low ABI [4.44 (95% confidence interval, 1.45-13.65, p＜0.01)] and for high % decrease in ABI after exercise [4.31 (95% confidence interval, 1.34-13.82, p＜0.05)]. The associations of uric acid levels with the indicators of leg ischemia were also found after adjustment for age, history of revascularization therapy, diabetes, smoking, alcohol consumption, body mass index, triglyceride levels, and renal function. CONCLUSION: Uric acid levels are associated with the degree of leg ischemia in patients with PAD. Further interventional studies are needed to determine whether the correction of uric acid levels is effective in preventing the progression of PAD.

[Recent Knowledge of Smoking and Peripheral Arterial Disease in Lower Extremities].

Peripheral arterial disease (PAD) is an atherosclerotic obstructive disease of the arteries in lower extremities. Patients with PAD show high rates of mortality from coronary artery disease (CAD) and stroke. Smoking as well as diabetes is an important risk factor for PAD. A lesion of PAD in the lower extremities tends to be more proximal in smokers than in nonsmokers and to be more distal in patients with diabetes than in nondiabetics. By a systematic review, the odds ratio for PAD of smokers vs nonsmokers has been reported to be in the range of 1.7-7.4. Previous epidemiological studies suggest a stronger association of smoking with PAD than that with CAD. Nitric oxide (NO) is an important molecule suppressing the progression of atherosclerosis, but this function is compromised by smoking. Smoking decreases the bioactivity of NO and the expression level of NO synthase. In addition, smoking results in deteriorations of risk factors for atherosclerosis such as decreases in blood HDL (high-density lipoprotein) cholesterol and tissue plasminogen activator levels and increases in the levels of blood triglycerides, LDL (low-density lipoprotein) cholesterol, fibrinogen and the von Willebrand factor. Thus, smoking increases blood coagulability and deteriorates the blood lipid profile, resulting in thrombogenetic proneness and dyslipidemia. Smoking also increases the generation of atherogenic oxidized LDL in blood and decreases antiatherogenic prostacyclin production in the vascular endothelium. Smoking cessation is important for the prevention and therapy of PAD, and to this end, counseling by physicians and nicotine replacement therapy are useful and strongly recommended for patients with PAD.

Association between cardiometabolic index and atherosclerotic progression in patients with peripheral arterial disease.

BACKGROUND: Cardiometabolic index (CMI), calculated as a product of waist-to-height ratio and triglycerides-to-HDL cholesterol ratio, is a new index for discriminating diabetes mellitus. Patients with peripheral arterial disease (PAD) are prone to have other atherosclerotic diseases such as coronary artery disease and stroke. The purpose of this study was to clarify the relationships between CMI and indicators of atherosclerotic progression in patients with PAD. METHODS: The subjects were 63 outpatients with PAD. Relationships of CMI with variables related to atherosclerotic progression were investigated using multivariate linear regression analysis and analysis of covariance with adjustment for age, sex and histories of smoking and alcohol drinking. RESULTS: Log-transformed CMI was significantly correlated with mean intima-media thickness of the common carotid artery (IMT) (standardized regression coefficient: 0.350, p < 0.01) and % decrease in ankle-brachial systolic pressure index (ABI) after treadmill exercise (standardized regression coefficient: 0.365, p < 0.01). Mean IMT and % decrease in ABI by treadmill exercise were significantly higher (p < 0.01) in the group of the 3rd tertile for CMI than in the group of its 1st tertile (mean ± SE: mean IMT (mm), 0.94 ± 0.06 (1st tertile) vs. 0.94 ± 0.06 (2nd tertile) vs. 1.19 ± 0.06 (3rd tertile); % decrease in ABI, 14.1 ± 3.4 [1st tertile] vs. 26.0 ± 3.5 [2nd tertile] vs. 30.0 ± 3.5 [3rd tertile]). CONCLUSION: CMI was shown to be associated with the degrees of atherosclerosis in the common carotid artery and ischemia in leg arteries and is therefore a useful discriminator of atherosclerotic progression in patients with PAD.

[Alcohol drinking and peripheral arterial disease of lower extremity].

Peripheral arterial disease (PAD) is defined as an atherosclerotic disease in the lower extremities and is characterized by its symptom of intermittent claudication with discomfort and pain at posterior cruris. Various abnormalities of vascular endothelial cells, smooth muscle cells and platelets induced by risk factors of PAD are involved in its pathogenesis. The most important risk factors are ageing, smoking and diabetes mellitus. Dyslipidemia and hypertension are also classical risk factors of PAD. A lesion of PAD in the lower extremity is prone to be more distal in patients with diabetes than in non-diabetics and to be more proximal in smokers than in nonsmokers. In addition, race/ethnicity, increased inflammatory marker levels, homocysteinemia and abdominal obesity are known to be risk factors of PAD. Light-to-moderate alcohol drinking has been demonstrated to reduce the risks of coronary artery disease and ischemic type of stroke, while excessive alcohol drinking increases the risks of hemorrhagic type of stroke (cerebral hemorrhage and subarachnoid hemorrhage), hypertension, cardiac arrhythmia and sudden cardiac death. In most previous epidemiological studies, the risk of PAD has been shown to be lower in light-to-moderate drinkers than in abstainers. Moreover, drinkers with PAD reportedly showed lower mortality than did nondrinkers with PAD. On the other hand, heavy drinking has been reported to be positively associated with the risk of PAD. Increase in HDL cholesterol, decrease in LDL cholesterol, inhibition of platelet aggregation, decrease in blood coagulability, increase in blood fibrinolitic activity, and increase in insulin sensitivity are known as mechanisms for suppression of atherosclerosis by alcohol drinking. These mechanisms are also thought to contribute to reduction of the risk of PAD by alcohol drinking. Further studies are needed to clarify pathophysiological mechanisms for dose-dependent diverse effects of alcohol on the risk of PAD.

[Tricuspid valve endocarditis following osteomyelitis; report of a case].

A 71-year-old man was admitted with complaints of high fever and lumbago. Echocardiography showed vegetation about 16×7 mm in size attached to the tricuspid valve. Magnetic resonance imaging showed osteomyelitis. As serial echocardiography showed the progression of valvular lesion despite antibiotic therapy, the patient underwent endoscopic removal of intervertebral disc 1st, and then tricuspid valve plasty was performed 3 days later. As of the last follow-up observation at 3 years, the patient has been doing well.

[Perforated aneurysm of the non-coronary cusp with aortic regurgitation in a patient with infective endocarditis; report of a case].

This case report describes a 77-year-old man who developed infective endocarditis resulting in perforated aneurysm of the non-coronary cusp with aortic regurgitation. Diagnosis was made by transesophageal echocardiogram and successful surgical valve replacement was performed.

[Mixed type ( type + pseudo) left ventricular aneurysm; report of a case].

True left ventricular aneurysms are thought to arise from the expansion and thinning of the transmural infarct area, whereas false aneurysms result from containment of ventricular rupture by pericardial adhesions. We reported a case of true left ventricular aneurysm with pseudoaneurysm( mixed type aneurysm) which was treated surgically.

[Thoracoabdominal aortic thrombi as a source of peripheral embolization; report of a case].

We reported a case of peripheral embolization arising from diffuse thoracoabdominal aortic thrombi with minimal evidence for atherosclerosis or other aortic pathology. After the patient was treated with anticoagulation therapy, surgical removal of peripheral embolus was performed.

[Residual inferior sinus venosus atrial septal defect after surgical closure of atrial septal defect; report of a case].

Sinus venosus atrial septal defect( SVD) represent 5~10% of atrial septal defect( ASD). In contrast to the more common superior type in which the superior vena cava overrides the pathological interatrial communication, the inferior type with overriding inferior vena cava is extremely rare. We describe a case of residual inferior SVD after surgical closure of ASD.

[Ascending aortic aneurysm associated with von recklinghausen disease].

We report a case of ascending aortic aneurysm complicated with von Recklinghausen disease. A 57-year-old man was referred to our institution for further evaluation of the atrial fibrillation. Computed tomography (CT) revealed an aneurysm of the ascending aorta. The patient underwent resection of aneurysm to prevent rupture. Vascular complications in von Recklinghausen disease and the treatment for the vessels were discussed.

Intramuscular hemangioma in the right ventricle.

Intramuscular cardiac hemangiomas are extremely rare. We describe a 74-year-old man with a tumor occupying the apex of the right ventricle that was incidentally diagnosed by echocardiography. Computed tomography and coronary angiography showed that the tumor arose from the ventricular septum and that the feeding artery was a branch of the right coronary artery. The tumor was completely excised, and the postoperative course was uneventful. Histological examination revealed that the tumor was a cardiac hemangioma (intramuscular type). To our knowledge, this is only the second case report of an intramuscular cardiac hemangioma in the world literature.