Effect of exposure to radiation caused by an atomic bomb on endothelial function in atomic bomb survivors.

Background: The purpose of this study was to evaluate the effects of exposure to radiation caused by an atomic bomb in atomic bomb survivors on vascular function and vascular structure and to evaluate the relationships of radiation dose from the atomic bomb with vascular function and vascular structure in atomic bomb survivors. Methods: Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as indices of vascular function, brachial-ankle pulse wave velocity (baPWV) as an index of vascular function and vascular structure, and brachial artery intima-media thickness (IMT) as an index of vascular structure were measured in 131 atomic bomb survivors and 1,153 control subjects who were not exposed to the atomic bomb. Ten of the 131 atomic bomb survivors with estimated radiation dose in a cohort study of Atomic Bomb Survivors in Hiroshima were enrolled in the study to evaluate the relationships of radiation dose from the atomic bomb with vascular function and vascular structure. Results: There was no significant difference in FMD, NID, baPWV, or brachial artery IMT between control subjects and atomic bomb survivors. After adjustment of confounding factors, there was still no significant difference in FMD, NID, baPWV, or brachial artery IMT between control subjects and atomic bomb survivors. Radiation dose from the atomic bomb was negatively correlated with FMD (ρ = -0.73, P = 0.02), whereas radiation dose was not correlated with NID, baPWV or brachial artery IMT. Conclusion: There were no significant differences in vascular function and vascular structure between control subjects and atomic bomb survivors. Radiation dose from the atomic bomb might be negatively correlated with endothelial function.

Long-Term Effect of Febuxostat on Endothelial Function in Patients With Asymptomatic Hyperuricemia: A Sub-Analysis of the PRIZE Study.

Background: Xanthine oxidase is involved in the production of uric acid and the generation of superoxide anion. We evaluated the long-term effect of febuxostat, a non-purine selective xanthine oxidase inhibitor, on endothelial function in patients with asymptomatic hyperuricemia. Methods: In the PRIZE study, patients with hyperuricemia were randomly assigned to either add-on febuxostat treatment (febuxostat group) or non-pharmacologic hyperuricemia treatment (control group). Among the 514 participants, endothelial function was assessed in 41 patients in the febuxostat group and 38 patients in the control group by flow-mediated vasodilation (FMD) of the brachial artery at the beginning of the study and after 12 and/or 24 months of treatment (63 men; median age, 68.0 years). Results: The least squares mean concentration of serum uric acid was significantly lower in the febuxostat group than in the control group at 6 months (mean between-group difference [febuxostat group - control group], -2.09 mg/dL [95% confidence interval (CI), -2.520 to -1.659]; P < 0.001), 12 months (mean between-group difference, -2.28 mg/dL [95% CI, -2.709 to -1.842]; P < 0.001), and 24 months (mean between-group difference, -2.61 mg/dL [95% CI, -3.059 to -2.169]; P < 0.001). No significant differences were found between groups in the least squares mean estimated percentage change in FMD at 12 months (mean between-group difference, -0.56% [95% CI, -1.670 to 0.548]; P = 0.319) and at 24 months (mean between-group difference, -0.60% [95% CI, -1.886 to 0.685]; P = 0.357). Conclusion: Febuxostat treatment did not alter endothelial function assessed by FMD during a 2-year study period in patients with asymptomatic hyperuricemia.

Six recurrences of myocarditis in 3 years: A case report.

A recent study revealed that recurrence of myocarditis occurs in a significant proportion of patients, but multiple recurrences of myocarditis have rarely been reported. The pathophysiology and best treatments for multiple recurrences of myocarditis remain unclear. A 60-year-old man presented to our emergency department with fever and chest pain. Physical examination, imaging, and laboratory findings were consistent with fulminant myocarditis. Paired titers confirmed adenovirus infection. The patient was treated with intra-aortic balloon pump and percutaneous cardiopulmonary support for 7 days and was discharged with near-normal electrocardiographic and echocardiographic findings on day 26. Over the subsequent 3 years, the patient experienced six episodes of recurrence of myocarditis with a progressive decrease in his ability to perform activities of daily living. At the time of his sixth recurrence, he died of ventricular fibrillation. Autopsy revealed mild enlargement of the left ventricle, extensive inflammatory cell infiltration, and mild interstitial fibrosis, suggesting left ventricle remodeling because of repetitive myocarditis. We have presented a case of multiple recurrences of myocarditis. This is the largest number of recurrences in a single patient reported to date. Further studies are needed to elucidate the underlying pathogenesis and best treatment of this condition. .

Endothelial function is preserved in light to moderate alcohol drinkers but is impaired in heavy drinkers in women: Flow-mediated Dilation Japan (FMD-J) study.

Light to moderate alcohol consumption has protective effects on all-cause death and coronary artery disease in women. It is thought that light to moderate alcohol consumption has a beneficial effect on vascular function in women. We measured flow-mediated vasodilation (FMD) in 702 women aged 17-86 years who provided information on alcohol consumption. We divided the subjects into four groups: non-drinkers (0 g/week), light drinkers (>0 to 140 g/week), moderate drinkers (>140 to 280 g/week) and heavy drinkers (>280 g/week). There was no significant difference in FMD among the four groups. Multivariate regression analysis revealed that alcohol consumption in non-drinkers and light drinkers was not an independent predictor of FMD (ß = -0.001, P = 0.98). We compared 50 moderate drinkers and 50 non-drinkers matched for age and medical histories and 22 heavy drinkers and 22 non-drinkers in matched pair analysis. There was no significant difference in FMD between moderate drinkers and non-drinkers (8.2±4.3% vs. 8.1±3.5, P = 0.91), while FMD in heavy drinkers was significantly lower than that in non-drinkers (5.9±2.5% vs. 8.9±3.5%, P = 0.002). These findings suggest that heavy alcohol consumption is associated with endothelial dysfunction but that light to moderate alcohol consumption is not associated with endothelial dysfunction in women. Clinical trial registration information This study was approved by principal authorities and ethical issues in Japan (University Hospital Medical Information Network UMIN000012952, 01/12/2009). www.umin.ac.jp/.

Increased arterial stiffness and cardiovascular risk prediction in controlled hypertensive patients with coronary artery disease: post hoc analysis of FMD-J (Flow-mediated Dilation Japan) Study A.

The usefulness of brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, is not fully known for the management of treated hypertensive patients with a history of coronary artery disease (CAD) who have blood pressure less than 130/80 mmHg, a recommended blood pressure target in the updated major hypertension guidelines. We analyzed data for 447 treated hypertensive patients with CAD enrolled in FMD-J Study A for assessment of the predictive value of baPWV for future cardiovascular events. The primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 47.6 months, the primary outcome occurred in 64 patients. Blood pressure less than 130/80 mmHg was significantly associated with a lower risk of the composite outcome independent of other cardiovascular risk factors in treated hypertensive patients with CAD (hazard ratio, 0.59; 95% confidence interval (CI), 0.35-0.99; P = 0.04). In treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, baPWV above the cutoff value of 1731 cm/s, derived from receiver-operator characteristic curve analysis for the composite outcome was significantly associated with a higher risk of the composite outcome independent of conventional risk factors (hazard ratio, 2.83; 95% CI, 1.02-7.91; P = 0.04). baPWV was an independent predictor of cardiovascular events in treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, for whom measurement of baPWV is recommended for cardiovascular risk assessment.

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD-J (Flow-Mediated Dilation Japan) Study A.

BACKGROUND: The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known. METHODS AND RESULTS: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06-0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09-0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01-3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23-3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed. CONCLUSIONS: In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification. CLINICAL TRIAL REGISTRATION: URL: www.umin.ac.jp. Unique identifier: UMIN000012950.

Assessment of Lower-limb Vascular Endothelial Function Based on Enclosed Zone Flow-mediated Dilation.

This paper proposes a novel non-invasive method for assessing the vascular endothelial function of lower-limb arteries based on the dilation rate of air-cuff plethysmograms measured using the oscillometric approach. The principle of evaluating vascular endothelial function involves flow-mediated dilation. In the study conducted, blood flow in the dorsal pedis artery was first monitored while lower-limb cuff pressure was applied using the proposed system. The results showed blood flow was interrupted when the level of pressure was at least 50 mmHg higher than the subject's lower-limb systolic arterial pressure and that blood flow velocity increased after cuff release. Next, values of the proposed index, %ezFMDL, for assessing the vascular endothelial function of lower-limb arteries were determined from 327 adult subjects: 87 healthy subjects, 150 subjects at high risk of arteriosclerosis and 90 patients with cardiovascular disease (CAD). The mean values and standard deviations calculated using %ezFMDL were 30.5 ± 12.0% for the healthy subjects, 23.6 ± 12.7% for subjects at high risk of arteriosclerosis and 14.5 ± 15.4% for patients with CAD. The %ezFMDL values for the subjects at high risk of arteriosclerosis and the patients with CAD were significantly lower than those for the healthy subjects (p < 0.01). The proposed method may have potential for clinical application.

Endothelial dysfunction, abnormal vascular structure and lower urinary tract symptoms in men and women.

BACKGROUND: Lower urinary tract symptoms (LUTS) is not only common symptoms in elderly men and women but also risk of future cardiovascular events. The purpose of this study was to evaluate the relationships of vascular function and structure with LUTS in men and women. METHODS: We investigated flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as vascular function, brachial-ankle pulse wave velocity (baPWV) as vascular structure, and LUTS assessed by International Prostate Symptom Score (IPSS) in 287 men and 147 women. RESULTS: IPSS was significantly correlated with traditional cardiovascular risk factors, Framingham risk score, FMD, NID and baPWV. Moderate to severe LUTS was associated with the prevalence of coronary heart disease in men but not in women. In men, FMD and NID were significantly lower in the moderate to severe LUTS group than in the none to mild LUTS group (2.1 ±â€¯2.0% vs. 4.0 ±â€¯3.0% and 9.3 ±â€¯6.1% vs. 12.8 ±â€¯6.6%, P < 0.001, respectively). baPWV was significantly higher in the moderate to severe LUTS group than in the none to mild LUTS group (1722 ±â€¯386 cm/s vs. 1509 ±â€¯309 cm/s, P < 0.001). In multivariate analysis, FMD was independently associated with a decrease in the odds ratio of moderate to severe LUTS in men (OR: 0.83, 95% CI, 0.72-0.95; P = 0.008) but not in women. NID and baPWV were not independently associated with moderate to severe LUTS either in men or women. CONCLUSIONS: These findings suggest that endothelial dysfunction is associated with LUTS in men. LUTS in men may be useful for a predictor of cardiovascular events. CLINICAL TRIAL REGISTRATION INFORMATION: URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409.

Reactive hyperemia-peripheral arterial tonometry is useful for assessment of not only endothelial function but also stenosis of the digital artery.

BACKGROUND: Although reactive hyperemia-peripheral arterial tonometry (RH-PAT) is widely used for assessment of endothelial function, RH index (RHI) cannot be measured in some cases when pulse wave amplitude (PWA) is very low. Decrease in PWA is mainly caused by proper palmar digital artery (PPDA) stenosis. The purpose of this study was to evaluate the relationship between PWA measured by RH-PAT and stenosis of the PPDA measured by digital subtraction angiography and to evaluate the limitation of assessment of endothelial function measured by RHI in patients with PPDA stenosis. METHODS: We measured baseline PWA in 51 fingers including the first to third fingers of both hands in 10 patients who had PPDA stenosis and in 66 fingers that were the first fingers of both hands in 33 subjects who had no PPDA stenosis. Severe stenosis was defined as over 75% by lower percent diameter stenosis between two PPDAs in a finger. RESULTS: PWA was significantly correlated with stenosis of the digital artery (r=-0.55; P<0.0001). A PWV value of 300mV was the optimal cut-off value for severe stenosis (sensitivity, 84.0%; specificity, 88.5%). Log RHI was significantly lower in patients with PPDA stenosis than in subjects without PPDA stenosis (0.33±0.27 versus 0.73±0.27, P=0.007). CONCLUSIONS: RH-PAT may be useful for assessment of not only endothelial function but also PPDA stenosis. RHI may be underestimated in patients with PPDA stenosis. We should pay attention to low baseline PWA when measuring RHI. CLINICAL TRIAL REGISTRATION INFORMATION: URL for clinical trial: http://UMIN; registration number for clinical trial: UMIN000003409.

Head-to-head comparison of the heart rate variability between the bisoprolol transdermal patch and bisoprolol fumarate tablet.

AIM: The bisoprolol transdermal patch is a newly developed ß-blocker designed to deliver its pharmaceutical ingredient through the skin surface. We aimed to compare the bisoprolol transdermal patch and bisoprolol fumarate tablet using the heart rate variability (HRV). METHOD: Eligible hypertensive patients received a 2-week administration with a 2.5 mg bisoprolol fumarate tablet, followed by 24-hour Holter monitoring. The tablet was then switched to a 4 mg bisoprolol transdermal patch, and after 2 weeks of its administration, the Holter monitoring was repeated. Both drugs were given once daily. Endpoint was any alteration in the HRV caused by a change in the administration route for bisoprolol. RESULTS: There was no difference in the 24-hour time-domain and frequency-domain HRV measurements before and after the drug switching among patients recruited (N = 30). However, the switching significantly altered the time-course curves of the hourly HRV measurements, including the mean normal-to-normal (NN) interval (P = .004), standard deviation of the NN index (P < .001), high frequency component (P = .01), and low frequency component (P = .003). Those alternations were attributed to the slower heart rate and more decreased short-term autonomic fluctuation resulting from the administration of the bisoprolol transdermal patch, which were observed later than 12 hours after the drug initiation. No adverse events were noted throughout the study period. CONCLUSION: The pattern of the autonomic modulation may vary depending on either a transdermal or oral administration even though an equivalent dose of bisoprolol is given.

Chronic kidney disease is associated with vascular smooth muscle dysfunction but not with endothelial dysfunction.

BACKGROUNDS: Nitroglycerine-induced vasodilation (NID) is usually assessed as a control test for flow-mediated vasodilation (FMD). However, NID per se is impaired in patients with high cardiovascular risk. The purpose of this study was to investigate the associations of chronic kidney disease (CKD) with NID and FMD. METHODS: We measured NID and FMD in a total of 1567 adult subjects without end-stage renal disease (ESRD), 28% of whom had CKD as judged by measurements of estimated glomerular filtration rate (995 men and 572 women; mean age, 59.0±16.9years; age range, 18 to 92years). RESULTS: NID was significantly smaller in patients with CKD than in those without CKD (10.8±6.0% vs. 12.7±5.7%, P<0.001). The prevalence of vascular smooth muscle dysfunction, defined as NID of less than the division point for the lowest quartile, was significantly higher in patients with CKD than in those without CKD (37.5% vs. 21.5%, P<0.001). Multivariate analysis revealed that CKD was independently associated with vascular smooth muscle dysfunction (OR: 1.36, 95% CI: 1.02 to 1.81, P=0.04). FMD was significantly smaller in patients with CKD than in those without CKD (3.1±2.8% vs. 4.0±3.0%, P<0.001). The prevalence of endothelial dysfunction, defined as FMD of less than the division point for the lowest quartile, was significantly higher in patients with CKD than in those without CKD (31.7% vs. 23.1%, P=0.002). However, CKD was not independently associated with endothelial dysfunction in an age- and sex-adjusted model (OR: 0.95, 95% CI: 0.71 to 1.26, P=0.72). CONCLUSIONS: Non-ESRD CKD is independently associated with vascular smooth muscle dysfunction but not with endothelial dysfunction.

Brachial artery diameter as a marker for cardiovascular risk assessment: FMD-J study.

BACKGROUND AND AIMS: Baseline brachial artery (BBA) diameter has been reported to be a potential confounding factor of flow-mediated vasodilation (FMD). The purpose of this study was to evaluate the relationships between BBA diameter and cardiovascular risk factors and compare the diagnostic accuracy of BBA diameter in subjects without cardiovascular risk factors and patients with cardiovascular disease (CVD) with that of FMD. METHODS: We measured BBA diameter and FMD in 5695 male subjects. In addition, we retrospectively investigated the incidence of cardiovascular events using another population sample consisting of 440 male subjects, to compare the accuracy of BBA diameter with that of FMD in predicting cardiovascular events. RESULTS: BBA diameter and FMD significantly correlated with age, body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose as well as Framingham risk score. The prevalence of cardiovascular risk factors and CVD increased with the increase in BBA diameter and FMD. Area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for BBA diameter to diagnose subjects without cardiovascular risk factors (0.59 vs. 0.62, p = 0.001) or patients with CVD (0.58 vs. 0.64, p < 0.001) was significantly lower than that for FMD. In the retrospective study, the AUC value of the ROC curve for BBA diameter to predict first major cardiovascular events was significantly lower than that of FMD (0.50 vs. 0.62, p = 0.03). CONCLUSIONS: In men, BBA diameter was inferior to FMD for assessment of cardiovascular risk.

Interrelationships Among Flow-Mediated Vasodilation, Nitroglycerine-Induced Vasodilation, Baseline Brachial Artery Diameter, Hyperemic Shear Stress, and Cardiovascular Risk Factors.

BACKGROUND: Flow-mediated vasodilation (FMD) of the brachial artery has been used for the assessment of endothelial function. Considering the mechanism underlying the vasodilatory response of the brachial artery to reactive hyperemia, hyperemic shear stress (HSS), a stimulus for FMD; nitroglycerine-induced vasodilation (NID), an index of endothelium-independent vasodilation; and baseline brachial artery diameter (BAD) are also involved in vasodilatory response. The purpose of this study was to investigate the interrelationships among FMD, HSS, NID, baseline BAD, and cardiovascular risk factors. METHODS AND RESULTS: We measured FMD, HSS, NID, and baseline BAD simultaneously in 1033 participants (633 men and 400 women; mean age: 58.6±17.0 years). Framingham risk score was negatively correlated with FMD, HSS, and NID and was positively correlated with baseline BAD. HSS and NID were positively correlated with FMD, and baseline BAD was negatively correlated with FMD. In participants with normal NID, FMD was correlated with HSS, NID, and baseline BAD, all of which were independent variables of FMD in multivariate analysis. In participants with impaired NID, FMD was correlated with NID and baseline BAD, both of which were independent variables of FMD in multivariate analysis, but there was no association between FMD and HSS. CONCLUSIONS: NID and baseline BAD were independent variables of FMD regardless of the status of endothelium-independent vasodilation, whereas there was a significant association between FMD and HSS in participants with normal NID but not in those with impaired NID. The influence of HSS on FMD seems to be dependent on the status of endothelium-independent vasodilation.

Endothelial Function Is Impaired in Patients Receiving Antihypertensive Drug Treatment Regardless of Blood Pressure Level: FMD-J Study (Flow-Mediated Dilation Japan).

Hypertension is associated with endothelial dysfunction. Blood pressure significantly correlates with endothelial function in antihypertensive drug-naive subjects. The purpose of this study was to determine whether treatment status affects the relationship between blood pressure and endothelial function. We measured flow-mediated vasodilation (FMD) in 2297 subjects, including 1822 antihypertensive drug-naive subjects and 475 treated hypertensive patients. FMD significantly decreased in relation to increase in systolic blood pressure (8.2±3.1% in subjects with systolic blood pressure of <120 mm Hg, 7.5±2.8% for 120-129 mm Hg, 7.1±2.8% for 130-139 mm Hg, and 6.7±2.6% for ≥140 mm Hg; P<0.001). Systolic blood pressure was independently associated with FMD in untreated subjects. In contrast, there was no significant relationship between systolic blood pressure and FMD in treated hypertensive patients (4.6±3.1% in treated hypertensives with systolic blood pressure of <120 mm Hg, 4.8±2.7% for 120-129 mm Hg, 4.9±2.8% for 130-139 mm Hg, and 4.5±2.3% for ≥140 mm Hg; P=0.77). Propensity score matching analysis revealed that the prevalence of endothelial dysfunction defined as FMD of less than the division point for the lowest tertile, and the middle tertile of FMD was significantly higher in treated hypertensive patients than in untreated subjects in all systolic blood pressure categories. Endothelial function assessed by FMD was impaired regardless of the level of blood pressure achieved by antihypertensive drug treatment in hypertensive patients.

Optimal Target Level of Low-density Lipoprotein Cholesterol for Vascular Function in Statin Naïve Individuals.

We investigated (1) the relationship between low-density lipoprotein cholesterol (LDL-C) and vascular function in patients receiving and those not receiving statin therapy and (2) optimal level of LDL-C for maintenance of vascular function. Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were inversely correlated with LDL-C in the 957 statin naïve subjects but not in the 392 subjects receiving statin therapy. In statin naïve subjects, non-high LDL-C (≤100 mg/dL) was independently associated with a decrease in adjusted odds ratio of the low tertile of FMD (OR: 0.62, 95% CI: 0.45-0.85; P = 0.003) and NID (OR: 0.69, 95% CI: 0.50-0.96; P = 0.03). Adjusted odds ratio of the low tertile of FMD was significantly lower in the low LDL-C group (≤70 mg/dL) (OR: 0.47, 95% CI, 0.27-0.81; P = 0.006) and in the moderate LDL-C group (70.1-100 mg/dL) (OR: 0.66, 95% CI, 0.48-0.94; P = 0.02) than in the high LDL-C group (>100 mg/dL). There was no significant difference in FMD between the low LDL-C group and moderate LDL-C group. There were significant relationships of FMD and NID with LDL-C levels in statin naïve subjects. In a general population, LDL-C of ≤100 mg/dL may be the optimal target level for maintenance of endothelial function.

Relation of the Bilateral Earlobe Crease to Endothelial Dysfunction.

The presence of an earlobe crease (ELC) may be a simple sign to predict atherosclerosis. We evaluated the relation between ELC and vascular function. We measured flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) and observed bilateral earlobes in 400 consecutive subjects. At first, the subjects were divided into 3 groups: non-ELC group, unilateral ELC group, and bilateral ELC group. FMD and NID were significantly lower in the unilateral and bilateral ELC groups than those in the non-ELC group. After adjustment of cardiovascular risk factors, bilateral ELC, but not unilateral ELC, was associated with lower FMD and lower NID. We also investigated whether an increase in the number of ELCs worsens endothelial function, whether the difference in ELC structure (cross stripes and/or ramification) affects endothelial function, and whether endothelial function is impaired in subjects with superficial wrinkles depending on age. The number of ELCs, shape of the ELC, and superficial wrinkles were not associated with endothelial dysfunction. In conclusion, these findings suggest that the presence of bilateral ELCs is associated with vascular dysfunction.

Decreased frequency and duration of tooth brushing is a risk factor for endothelial dysfunction.

BACKGROUND: Periodontal disease is associated with endothelial dysfunction, leading to cardiovascular disease. The effect of detailed tooth brushing behavior, not only frequency but also duration of tooth brushing, on endothelial function is unclear. The purpose of this study was to evaluate the relationships of detailed methods of tooth brushing with vascular function. METHODS: We evaluated flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation, and frequency and duration of tooth brushing in 896 subjects. We divided the subjects into three groups according to the frequency and duration of tooth brushing: low frequency and short duration group (

Increasing Risk of Osteoporotic Fracture Is Associated With Vascular Dysfunction and Abnormal Vascular Structure in Both Men and Women.

BACKGROUND: Osteoporosis and cardiovascular disease are major public health problems. A number of clinical studies have shown a link between osteoporosis and cardiovascular disease, but there is no information on the associations of risk of osteoporotic fracture with vascular function and vascular structure.Methods and Results:The risk of major osteoporotic fracture was calculated using the World Health Organization fracture risk assessment tool (FRAX); vascular function was assessed using flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID), and vascular structure was assessed on brachial artery intima-media thickness (IMT) in 414 subjects (241 men and 173 women) who underwent health examinations. On univariate regression, FRAX was negatively correlated with FMD (total, r=-0.16, P<0.001; men, r=-0.19, P=0.003; women, r=-0.25, P<0.001) and NID (total, r=-0.22, P<0.001; men, r=-0.19, P=0.003; women, r=-0.30, P<0.001) and was positively correlated with brachial artery IMT (total, r=0.12, P=0.02; men, r=0.22, P<0.001; women, r=0.33, P<0.001). On multivariate analysis FRAX remained an independent predictor of FMD, NID, and brachial artery IMT in both men and women. CONCLUSIONS: Increase in the risk of osteoporotic fracture evaluated on FRAX is associated with vascular dysfunction and abnormal vascular structure in both men and women. Osteoporosis should be monitored in order to reduce the risk of cardiovascular events.

Endothelial dysfunction and abnormal vascular structure are simultaneously present in patients with heart failure with preserved ejection fraction.

BACKGROUND: Endothelial dysfunction and abnormal vascular structure may be involved in the pathogenesis of chronic heart failure (HF). The purpose of this study was to evaluate simultaneously vascular function and vascular structure in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We measured flow-mediated vasodilatation (FMD) and nitroglycerine-induced vasodilation as indices of vascular function and intima-media thickness (IMT) as an index of vascular structure of the brachial artery in 41 patients with HFpEF (23 men and 18 women; mean age, 66±12yr) and 165 patients without HF (95 men and 70 women; mean age, 54±16yr). RESULTS: FMD was significantly smaller in patients with HFpEF than in patients without HF (2.9±2.1% versus 4.6±2.7%, P=0.0002). Nitroglycerine-induced vasodilation was significantly smaller in patients with HFpEF than in patients without HF (9.3±4.1% versus 12.9±4.9%, P<0.0001). Brachial artery IMT was significantly larger in patients with HFpEF than in patients without HF (0.35±0.06mm versus 0.31±0.07mm, P=0.0002). After adjustment for age, sex, hypertension, dyslipidemia, and diabetes mellitus, the associations remained significant between HFpEF and FMD (odds ratio, 0.79; 95% confidence interval, 0.66-0.92; P=0.0032), nitroglycerine-induced vasodilation (odds ratio, 0.88; 95% confidence interval, 0.80-0.96; P=0.0039), and brachial artery IMT (odds ratio, 1.08; 95% confidence interval, 1.01-1.17; P=0.033). CONCLUSIONS: These findings suggest that both endothelial dysfunction and abnormal vascular structure may contribute to the pathogenesis and maintenance of HFpEF. Endothelial function and vascular structure may be potential therapeutic targets for HFpEF.

Endothelial function is impaired in relation to alcohol intake even in the case of light alcohol consumption in Asian men; Flow-mediated Dilation Japan (FMD-J) Study.

BACKGROUND: Heavy drinking should be a predictor of endothelial dysfunction. However, there is little information on the effects of light to moderate alcohol consumption on endothelial function. The purpose of this study was to estimate the effects of dose-dependent alcohol consumption on endothelial function. METHODS: We measured flow-mediated vasodilation (FMD) in 2734 men aged 21-81years who provided information on alcohol intake at 3 general hospitals. The subjects were divided into 5 groups; non-drinkers (0g/week), light drinkers (>0 to 140g/week), moderate drinkers (>140 to 280g/week), heavy drinkers (>280 to 420g/week), and excessive heavy drinkers (>420g/week). RESULTS: FMD showed a gradual decrease in accordance with alcohol consumption in the entire study population (non-drinkers, 6.6±3.4%; light drinkers, 6.2±3.0%; moderate drinkers, 6.0±3.0%; heavy drinkers, 5.5±2.9%; excessive heavy drinkers, 5.3±3.0%; P<0.001). There was a significant difference in FMD between the light alcohol drinker group and the non-drinker group (P=0.015). After adjustment for other risk factors, the odds of having FMD in the lowest quartile was found to be significantly increased in the 4 drinker groups than in the non-drinker group: light (OR, 1.38; 95% CI, 1.10 to 1.75), moderate (OR, 1.36; 95% CI, 1.01 to 1.82), heavy (OR, 2.05; 95% CI, 1.46 to 2.87), excessive (OR, 2.04; 95% CI, 1.43 to 2.89). CONCLUSION: These findings suggest that FMD is impaired in relation to alcohol consumption and that FMD is significantly smaller even in light alcohol drinkers than in non-drinkers. Alcohol intake per se may be harmful for vascular function.