Mao Takahashi

Evaluation of Blood Pressure Control using a New Arterial Stiffness Parameter, Cardio-ankle Vascular Index (CAVI)

Arterial stiffness has been known to be a surrogate marker of arteriosclerosis, and also of vascular function. Pulse wave velocity (PWV) had been the most popular index and was known to be a predictor of cardiovascular events. But, it depends on blood pressure at measuring time. To overcome this problem, cardio-ankle vascular index (CAVI) is developed. CAVI is derived from stiffness parameter β by Hayashi, and the equation of Bramwell-Hill, and is independent from blood pressure at a measuring time. Then, CAVI might reflect the proper change of arterial wall by antihypertensive agents. CAVI shows high value with aging and in many arteriosclerotic diseases and is also high in persons with main coronary risk factors. Furthermore, CAVI is decreased by an administration of α1 blocker, doxazosin for 2-4 hours, Those results suggested that CAVI reflected the arterial stiffness composed of organic components and of smooth muscle cell contracture. Angiotensin II receptor blocker, olmesartan decreased CAVI much more than that of calcium channel antagonist, amlodipine, even though the rates of decreased blood pressure were almost same. CAVI might differentiate the blood pressure-lowering agents from the point of the effects on proper arterial stiffness. This paper reviewed the principle and rationale of CAVI, and the possibilities of clinical applications, especially in the studies of hypertension.

Enhanced circulating soluble LR11 in patients with coronary organic stenosis.

LR11, an LDL receptor family member, is expressed in intimal smooth muscle cells. It was found that the soluble form of LR11 (sLR11) is detected in serum, and the circulating sLR11 levels are positively correlated with intima-media thickness of carotid arteries in dyslipidemic subjects. To clarify the significance of serum sLR11, the circulating sLR11 levels in patients with organic coronary stenosis and the contributing risk factors for them were studied. The subjects, 150 patients with symptoms of coronary artery disease, underwent coronary angiographic examination, and were divided into sex- and age-matched two groups; one is organic coronary stenosis group (OCS) and the other is normal coronary group (NC). Serum sLR11 levels were significantly higher in OCS than in NC (4.9+/-2.7 U vs 3.6+/-1.8 U, p<0.05). Multivariate regression analysis showed that circulating sLR11 is independent contributing factor for the OCS, as well as diabetes mellitus and dyslipidemia. Among various coronary risk factors for sLR11 level, HbA1c showed the highest correlation coefficient (p<0.01). These results suggest that the circulating sLR11 might reflect coronary organic stenosis, and that hyperglycemic condition might be promoting factor for expression of LR11 in intimal smooth muscle cells.

Nocturnal Intermittent Serious Hypoxia and Reoxygenation in Proliferative Diabetic Retinopathy Cases

PURPOSE To clarify the relationship between evaluation items of sleep-disordered breathing and diabetic retinopathy in detail. DESIGN Cross-sectional comparative study. METHODS Sixty-eight consecutive nonproliferative diabetic retinopathy and 151 proliferative diabetic retinopathy (PDR) cases who had undergone surgeries in our department were included in this study. Pulse oximetry was conducted overnight and mean oxygen saturation by pulse oximeter (SpO(2); %), the sleeping 4% oxygen desaturation index (4% ODI times/hour), lowest SpO(2) (%), and the cumulative percent time spent at SpO(2) < 90% (CT 90%) were calculated. The results were evaluated and compared between the 2 groups. In addition, these results and preoperative patient background factors were analyzed using logistic regression analysis to clarify risk factor of PDR. RESULTS 4% ODI and CT 90% in the PDR group were significantly higher than in the nonproliferative diabetic retinopathy group (4% ODI, 7.8 vs. 4.9; P = .007; CT 90%, 2.2 vs 0.8; P = .0006). Lowest SpO(2) was significantly lower in the PDR group than in the nonproliferative diabetic retinopathy groups (82.4 vs 87.0; P = .0006). Logistic regression analysis identified being younger, having a lower value for the lowest SpO(2), and a high hemoglobin A1c value to be risk factors for PDR (age: odds ratio, 0.90; 95% confidence interval, -0.86 to -0.94; P < .0001; lowest SpO(2): odds ratio, 0.93; 95% confidence interval, 0.88 to 0.99; P = .02; hemoglobin A1c: odds ratio, 1.00 to 1.69; P = .047). CONCLUSIONS This study indicated that PDR cases had episodes of nocturnal intermittent hypoxia and reoxygenation as a result of sleep-disordered breathing and that low-value lowest SpO(2) were the risk factors for PDR development.

Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans.

Thermogenesis in brown adipose tissue (BAT) is an important component of energy expenditure in mammals. Recent studies have confirmed its presence and metabolic role in humans. Defining the physiological regulation of BAT is therefore of great importance for developing strategies to treat metabolic diseases. Here we show that the soluble form of the low-density lipoprotein receptor relative, LR11/SorLA (sLR11), suppresses thermogenesis in adipose tissue in a cell-autonomous manner. Mice lacking LR11 are protected from diet-induced obesity associated with an increased browning of white adipose tissue and hypermetabolism. Treatment of adipocytes with sLR11 inhibits thermogenesis via the bone morphogenetic protein/TGFβ signalling pathway and reduces Smad phosphorylation. In addition, sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. Given the need for tight regulation of a tissue with a high capacity for energy wastage, we propose that LR11 plays an energy conserving role that is exaggerated in states of obesity.

Relationship between diabetic retinopathy and sleep-disordered breathing.

PURPOSE To clarify the relationships of sleep-disordered breathing (SDB) to nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). DESIGN Cross sectional case-control study. METHODS Forty-eight consecutive NPDR and 118 PDR cases that had undergone surgery in our hospital were included in this study. Pulse oximetry was conducted during the night and the sleeping 4% oxygen desaturation index (ODI) (number of oxygen desaturation events/hour exceeding 4%) and mean SpO(2)% were calculated. If 4% ODI > 5 times/hour, SDB was diagnosed. The results were evaluated and compared between the 2 groups. In addition, these results and preoperative patient background factors were analyzed using multiple regression analysis to identify correlations with the diagnosis of PDR. RESULTS Twenty-nine percent of the NPDR and 48% of the PDR patients were diagnosed as having SDB. The incidence of SDB and the 4% ODI/hour value were significantly higher in the PDR than in the NPDR group (P = .003 and .03, respectively). Multiple regression analysis showed younger age and a higher 4% ODI value to be factors independently contributing to a diagnosis of PDR (age, standard regression coefficient = -0.34; t value = -4.44; P < .0001; 4% ODI, standard regression coefficient = 0.20; t value = 2.15; P = .03, correlation coefficient (R) = 0.43). CONCLUSION Our results suggest that, in diabetic retinopathy patients with nocturnal desaturation, reoxygenation caused by SDB may relate to the development of PDR.

Relationship between Severity of Obstructive Sleep Apnea Syndrome and Retinal Nerve Fiber Layer Thickness

PURPOSE To determine whether there is a significant correlation among the peripapillary retinal nerve fiber layer (RNFL) thickness, foveal thickness, total macular volume, and severity of obstructive sleep apnea syndrome. DESIGN Prospective study. METHODS We studied 124 consecutive subjects who underwent polysomnography. Optical coherence tomography (OCT) was used to measure the peripapillary RNFL, foveal thickness, and total macular volume. The Pearson correlation coefficient was used to determine the relationship between the apnea-hypopnea index and OCT and other parameters. Multiple regression analysis was used to determine the independent factors for the RNFL sectors that were the most strongly correlated with the apnea-hypopnea index. RESULTS The apnea-hypopnea index was significantly and negatively correlated (right eye, r = -0.31, P = 0.0004; left eye, r = -0.39, P < 0.0001) with the nasal RNFL thickness (Pearson correlation analysis). The foveal thickness and total macular volume were not correlated. The intraocular pressure, body mass index, plaque score, and incidence of hypertension were negatively correlated, and the lowest oxygen saturation and mean oxygen saturation were positively correlated with the nasal RNFL thickness in the left eye. Multiple regression analysis showed that the apnea-hypopnea index and age were independent contributors to the nasal RNFL thickness in the left eye (apnea-hypopnea index, standard regression coefficient, -0.30, t value, -2.76, P = 0.007; age, -0.24, -2.36, 0.02, respectively). The nasal RNFL thickness in both eyes decreased significantly based on the severity of the obstructive sleep apnea syndrome. CONCLUSION Exacerbation of obstructive sleep apnea syndrome may produce unique retinal neurodegenerative disorders that decrease the nasal RNFL thickness.

Enhanced Circulating Soluble LR11 in Patients With Diabetic Retinopathy

PURPOSE To investigate the relationship of circulating levels of soluble form of LR11 (sLR11; also called SorLA or SORL1), with the progression of proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus. DESIGN Cross-sectional study. METHODS Fifty-four patients with type 2 diabetes mellitus were divided into 2 sex- and age-matched groups: one with PDR (n = 29) and the other with nonproliferative diabetic retinopathy (n = 25). The serum sLR11 levels were measured with an immunodetection system followed by chemifluorescence quantification. RESULTS The serum sLR11 levels were higher in the PDR group than in the nonproliferative diabetic retinopathy group (5.8 ± 1.2 U vs 3.7 ± 1.3 U; P < .01). A multivariate regression analysis showed that circulating sLR11 is a factor contributing to the prediction of PDR independent of other classical risk factors, and an area under the receiver operating characteristic curve analysis revealed that the sensitivity and the specificity were equivalent to or more than those of other factors. Among the classical risk factors for PDR, glycosylated hemoglobin levels showed the highest correlation coefficient (P < .01) for the sLR11 concentrations. CONCLUSIONS Serum sLR11 concentration may reflect the progression of PDR in patients with type 2 diabetes mellitus. sLR11, released from immature vascular cells and indicating the development of atherosclerosis, is expected to be a novel candidate biomarker indicating diabetic retinopathy in patients with type 2 diabetes mellitus.

Pulse-Wave Analysis of Optic Nerve Head Circulation Is Significantly Correlated with Kidney Function in Patients with and without Chronic Kidney Disease

Aim. To determine whether there is a significant correlation between the optic nerve head (ONH) circulation determined by laser speckle flowgraphy (LSFG) and kidney function. Materials. Seventy-one subjects were investigated. The estimated glomerular filtration rate (GFR) and serum creatinine, cystatin C, and urinary albumin excretion were measured. The ONH circulation was determined by an analysis of the pulse wave of LSFG, and this parameter was named blowout time (BOT). Chronic kidney disease (CKD) was defined to be present when the estimated GFR was <60 mL/min per 1.73 m2. Pearsons correlation coefficients were used to determine the relationship between the BOT and the kidney function. We also examined whether there were significant differences in all parameters in patients with and without CKD. Results. BOT was significantly correlated with the level of creatinine (r = −0.24, P = 0.04), the estimated GFR (r = 0.42, P = 0.0003), cystatin C (r = −0.29, P = 0.01), and urinary albumin excretion (r = −0.29, P = 0.01). The BOT level in subjects with CKD was significantly lower than that in subjects without CKD (P = 0.002). Conclusion. BOT in ONH by LSFG can detect the organ damage such as kidney dysfunction, CKD.

Relationship Between Sleep-Disordered Breathing and Iris and/or Angle Neovascularization in Proliferative Diabetic Retinopathy Cases

PURPOSE To investigate whether sleep-disordered breathing is a risk factor for iris and/or angle neovascularization in patients with proliferative diabetic retinopathy (PDR). DESIGN Cross-sectional comparative case series. SUBJECTS AND METHODS One hundred fifty-one consecutive patients with PDR who underwent surgery in our hospital were divided based on the presence of iris and/or angle neovascularization (NV group, 37 patients) or absence of NV (non-NV group, 114 patients). Pulse oximetry was conducted during the night and the mean SpO(2), 4% oxygen desaturation index (4% ODI times/hour), the lowest SpO(2)% during sleep (lowest SpO(2)), and the cumulative percentage of time at SpO(2) <90% in analysis times (CT90%) were calculated. When the 4% ODI exceeded 5 times/hour, sleep-disordered breathing was diagnosed. The results were compared between the 2 groups. Preoperative systemic parameters also were analyzed by logistic regression to clarify risk factors for the NV group. RESULTS A mean total of 50% (62% of the NV group and 46% of the non-NV group) was diagnosed with sleep-disordered breathing. The mean SpO(2) and lowest SpO(2) did not differ significantly between the 2 groups; the 4% ODI (12.3 vs 6.6) and CT90% (3.8 vs 1.7) were significantly higher in the NV group (P=.02, for both comparisons). Logistic regression analysis identified insulin therapy (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.26∼7.20; P=.01); and 4% ODI (OR, 1.09; CI, 1.01∼1.16; P=.02) as risk factors for the NV group. CONCLUSIONS In patients with PDR, nocturnal intermittent hypoxia/reoxygenation resulting from sleep-disordered breathing may be a risk factor for iris and/or angle neovascularization.

Constipation and Metaiodobenzylguanidine Myocardial Scintigraphy Abnormality

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