No medication prescription and residential distance from the hospital are important factors associated with nonsurgical weight-loss treatment discontinuance in Japanese patients with high-degree obesity: a retrospective study.

BACKGROUND: Although the percentage of the population with a high degree of obesity (body mass index [BMI] ≥ 35 kg/m2) is low in Japan, the prevalence of obesity-related diseases in patients with high-degree obesity is greater than that in patients with a BMI < 35 kg/m2. Therefore, treatment for high-degree obesity is important. However, clinical studies have reported that 20-50% of patients with obesity discontinue weight-loss treatment in other countries. The circumstances surrounding antiobesity agents are quite different between Japan and other countries. In this study, we investigated the predictors of treatment discontinuation in Japanese patients with high-degree obesity. METHODS: We retrospectively reviewed the medical charts of 271 Japanese patients with high-degree obesity who presented at Toho University Sakura Medical Center for obesity treatment between April 1, 2014, and December 31, 2017. The patients were divided into non-dropout and dropout groups. Patients who discontinued weight-loss treatment within 24 months of the first visit were defined as "dropouts." Multivariate Cox proportional hazards regression analysis and Kaplan-Meier survival analysis were performed to examine the factors predicting treatment withdrawal. RESULTS: Among the 271 patients, 119 (43.9%) discontinued treatment within 24 months of the first visit. The decrease in BMI did not significantly differ between the two groups. No prescription of medication and residential distance from the hospital exceeding 15 km were the top contributors to treatment discontinuation, and the absence of prescription medication was the most important factor. The dropout-free rate was significantly higher in patients with medication prescriptions than in those without and in patients who lived within 15 km of the hospital than in those who lived farther than 15 km from the hospital. CONCLUSIONS: No medication prescription and longer residential distance from the hospital were associated with treatment dropout in Japanese patients with high-degree obesity; therefore, the addition of antiobesity medications and telemedicine may be necessary to prevent treatment discontinuation in such patients.

Enhanced prediction of renal function decline by replacing waist circumference with "A Body Shape Index (ABSI)" in diagnosing metabolic syndrome: a retrospective cohort study in Japan.

BACKGROUND: Abdominal obesity as a risk factor for diagnosing metabolic syndrome (MetS) is conventionally evaluated using waist circumference (WC), although WC does not necessarily reflect visceral adiposity. OBJECTIVE: To examine whether replacing WC with "A Body Shape Index (ABSI)", an abdominal obesity index calculated by dividing WC by an allometric regression of weight and height, in MetS diagnosis is useful for predicting renal function decline. SUBJECTS/METHODS: In total, 5438 Japanese urban residents (median age 48 years) who participated in a public health screening program for 4 consecutive years were enrolled. Systemic arterial stiffness was assessed by cardio-ankle vascular index (CAVI). The predictability of the new-onset renal function decline (eGFR < 60 mL/min/1.73 m2) by replacing high WC with high ABSI (ABSI ≥ 0.080) was examined using three sets of MetS diagnostic criteria: Japanese, IDF and NCEP-ATPIII. RESULTS: In Japanese and NCEP-ATPIII criteria, MetS diagnosed using ABSI (ABSI-MetS) was associated with significantly higher age-adjusted CAVI compared to non-MetS, whereas MetS diagnosed using WC (WC-MetS) showed no association. Kaplan-Meier analysis of the rate of new-onset renal function decline over 4 years (total 8.7%) showed remarkable higher rate in subjects with ABSI-MetS than in those without (log-rank test p < 0.001), but almost no difference between subjects with and without WC-MetS (p = 0.014-0.617). In gender-specific Cox-proportional hazards analyses including age, proteinuria, and treatments of metabolic disorders as confounders, ABSI-MetS (Japanese criteria for both sexes, IDF criteria for men) contributed independently to the new-onset renal function decline. Of these, the contribution of IDF ABSI-MetS disappeared after adjustment by high CAVI in the subsequent analysis. CONCLUSION: In this study, replacing WC with ABSI in MetS diagnostic criteria more efficiently predicted subjects at risk of renal function decline and arterial stiffening.

New index of abdominal obesity, a body shape index, is BMI-independently associated with systemic arterial stiffness in real-world Japanese population.

OBJECTIVE: To clarify that the new index of abdominal obesity, a body shape index (ABSI), is associated with obesity-related metabolic disorders and arterial stiffness. MATERIALS: We analyzed the cross-sectional data from 62,514 Japanese subjects (mean age 44.4 years, mean body mass index (BMI) 22.2 kg/m2) without a past history of cardiovascular disease, stroke, or treatment for obesity-related metabolic disorders. METHODS: Various body adiposity indices including BMI, waist circumference (WC), and ABSI were evaluated for abilities to indicate metabolic disorders and arterial stiffness assessed by cardio-ankle vascular index (CAVI). RESULTS: WC, WC/height ratio, and WC/BMI ratio correlated with BMI regardless of gender or obesity, whereas ABSI hardly correlated with BMI. ROC analyses demonstrated that ABSI had the highest discriminatory power in predicting high CAVI (≥ 90th percentile) compared to other body adiposity indices, and the cut-off value was 0.080. Increases in ABSI as well as BMI reflected severity of metabolic disorders. After adjusting for confounders identified by multiple regression analysis, adjusted CAVI correlated positively with ABSI, whereas an inverted relationship was observed between adjusted CAVI and BMI. Additionally, the contribution of high ABSI (≥ 0.080) for high CAVI was independent of gender, age, obesity, and obesity-related metabolic disorders in the multivariate logistic regression model. CONCLUSION: ABSI is an easily calculated index of abdominal obesity which reflects metabolic disorders and systemic arterial stiffening, and may be useful in primary health screening even without any medical equipment for visceral fat quantification.

Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus.

Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies. However, there are few interventional studies in human patients with atherosclerogenic diseases. The cardio-ankle vascular index (CAVI) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis. The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind, randomized, placebo-controlled study, 50 patients with T2DM received supplement of a 100mg resveratrol tablet (total resveratrol: oligo-stilbene 27.97 mg/100 mg/day) or placebo daily for 12 weeks. CAVI was assessed at baseline and the end of study. Body weight (BW), blood pressure (BP), glucose and lipid metabolic parameters, and diacron-reactive oxygen metabolites (d-ROMs; an oxidative stress marker) were also measured.Resveratrol supplementation decreased systolic BP (-5.5 ± 13.0 mmHg), d-ROMs (-25.6 ± 41.8 U.CARR), and CAVI (-0.4 ± 0.7) significantly (P < 0.05) and decreased BW (-0.8 ± 2.1 kg, P = 0.083) and body mass index (-0.5 ± 0.8 kg/m2, P = 0.092) slightly compared to baseline, while there were no significant changes in the placebo group. Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group. Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion, 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM. Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes. However, a large-scale cohort study is required to validate the present findings.

Effects of serotonin on expression of the LDL receptor family member LR11 and 7-ketocholesterol-induced apoptosis in human vascular smooth muscle cells.

Serotonin (5-HT) is a known mitogen for vascular smooth muscle cells (VSMCs). The dedifferentiation and proliferation/apoptosis of VSMCs in the arterial intima represent one of the atherosclerotic changes. LR11, a member of low-density lipoprotein receptor family, may contribute to the proliferation of VSMCs in neointimal hyperplasia. We conducted an in vitro study to investigate whether 5-HT is involved in LR11 expression in human VSMCs and apoptosis of VSMCs induced by 7-ketocholesterol (7KCHO), an oxysterol that destabilizes plaque. 5-HT enhanced the proliferation of VSMCs, and this effect was abolished by sarpogrelate, a selective 5-HT2A receptor antagonist. Sarpogrelate also inhibited the 5-HT-enhanced LR11 mRNA expression in VSMCs. Furthermore, 5-HT suppressed the 7KCHO-induced apoptosis of VSMCs via caspase-3/7-dependent pathway. These findings provide new insights on the changes in the differentiation stage of VSMCs mediated by 5-HT.

Metformin reduces circulating malondialdehyde-modified low-density lipoprotein in type 2 diabetes mellitus.

PURPOSE: Type 2 diabetes is known to be associated with increasing cardiovascular mortality. Malondialdehyde-modified LDL (MDA-LDL) is an oxidized LDL and is increased in patients with diabetes or hypertriglyceridemia. Elevated MDA-LDL has been reported to be a risk factor of atherosclerosis or cardiovascular disease. Sitagliptin is a dipeptidyl peptidase-4 inhibitor and a new class of hypoglycemic agents. In this study, the effects of increasing the dose of metformin and add-on sitagliptin on MDA-LDL were examined in type 2 diabetes patients. METHODS: Seventy patients with type 2 diabetes, inadequately controlled despite on-going treatment with metformin 500 mg/day, were enrolled in this randomized controlled trial. The patients received additional metformin (500 mg/day) or sitagliptin (50 mg/day) for 6 months, and changes in metabolic parameters including MDA-LDL were evaluated. RESULTS: After 6 months of treatment, add-on sitagliptin (n=35) improved fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) to significantly greater extent than increasing the dose of metformin (n=35). There were no differences in total cholesterol and low-density lipoprotein cholesterol levels between two groups. MDA-LDL levels (mean ± S.E.) decreased significantly with increasing the dose of metformin (from 94.40 ± 6.35 to 77.83 ± 4.74 U/L, P < 0.005), but remained unchanged with add-on sitagliptin treatment (from 89.94 ± 5.59 to 98.46 ± 6.78 U/L, p > 0.05). Multiple linear regression analysis identified increasing the dose of metformin treatment as the only independent factor associated with decreased MDA-LDL (ß coefficient 0.367, P < 0.0119), and no significant correlation between change in MDA-LDL and fasting blood glucose or HbA1c. CONCLUSION: These results suggest that increasing the dose of metformin improves serum MDA-LDL levels in type 2 diabetes mellitus.

C5 variant is associated with decreased risk of coronary artery disease in outpatients with severe hypercholinesterasemia.

OBJECTIVE: Although the C5 variant of cholinesterase is known to be a cause of hypercholinesterasemia, the pathophysiological significance of the C5 variant and the C5 variant-related hypercholinesterasemia in cardiovascular diseases remain unclear. The present study aimed to clarify the pathophysiological significance of the C5 variant as a risk or protective factor for coronary artery disease (CAD) in patients with severe hypercholinesterasemia. METHODS: Severe hypercholinesterasemia was defined as serum cholinesterase (ChE) activity >= 450 IU/L (>= 2.0 SD). We screened 11,648 consecutive outpatients between 2005 and 2011 at Toho University, Sakura Medical Center. In patients with severe hypercholinesterasemia, phenotyping of the C5 variant was conducted using polyacrylamide gel electrophoresis and alpha-naphthyl butyrate staining. RESULTS: 157 subjects (1.4% of 11,648 outpatients screened) were diagnosed with severe hypercholinesterasemia (mean serum ChE activity 574 ± 109 IU/L), and the frequency of the C5 variant was 45.2%. Subjects with the C5 variant had higher age, lower body mass index, milder dyslipidemia and liver dysfunction, and lower rates of hypertension and CAD compared with subjects without the C5 variant. Multivariate logistic regression model demonstrated that the presence of C5 variant independently lowered the risk of CAD, with odds ratio 0.071 (95% confidence interval (CI) 0.007 - 0.763, p = 0.029). CONCLUSION: The prevalence of the C5 variant was relatively high, and the C5 variant is associated with decreased risk of CAD in outpatients with severe hypercholinesterasemia.

Sarpogrelate hydrochloride decreases cardio-ankle vascular index accompanied by increased serum lipoprotein lipase mass in type 2 diabetic patients.

The 5-hydroxytryptamine2A receptor antagonist sarpogrelate hydrochloride exerts its effect not only by inhibition of platelet aggregation, but also by some pleiotropic effects. We have reported that a low serum lipoprotein lipase (LPL) mass level reflects insulin resistance and may be a risk factor for atherosclerotic diseases. The aim of this prospective study was to clarify the effect of sarpogrelate on serum LPL mass and cardio-ankle vascular index (CAVI) as a marker related to arterial stiffness.Thirty-five type 2 diabetic patients (21 males and 14 females) with ankle brachial indices higher than 0.90 received sarpogrelate hydrochloride 300 mg/day for 6 months. Serum LPL mass and CAVI were measured during the study.After 6 months of sarpogrelate hydrochloride treatment, CAVI decreased significantly (10.11 ± 0.92 to 9.87 ± 0.97, P < 0.05) and serum LPL mass increased significantly (58.2 ± 17.5 to 63.5 ± 21.4, P < 0.05). A negative correlation between change in CAVI and change in serum LPL mass was observed (r = -0.34, P < 0.05). Multiple regression analysis identified a change in serum LPL mass as a significant independent predictor for change in CAVI.We demonstrated that sarpogrelate hydrochloride decreased CAVI accompanied by increased serum LPL mass in type 2 diabetic patients. This result suggests that sarpogrelate hydrochloride improves arterial stiffness and is a potential treatment for diabetic angiopathy.

Relationship of Serum Uric Acid with Kidney Function Decline Mediated by Systemic Arterial Stiffness: A Retrospective Cohort Study in Japan.

Hyperuricemia is associated with kidney function decline (KFD), although whether hyperuricemia directly causes nephrotoxicity or is indirectly mediated by systemic arterial stiffening remains unclear. We examined the detailed relationship of serum uric acid (SUA) with KFD and potential mediation by arterial stiffness. Study population was 27,648 urban residents with an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 at baseline, and they participated in a median of three consecutive annual health examinations. Arterial stiffness was assessed using cardio-ankle vascular index (CAVI). KFD was defined as a decrease in eGFR to below 60. Multivariate analysis showed an association between baseline SUA and CAVI independent of eGFR. During the study period, 6.6% of participants developed KFD. Stratified analysis revealed a linear relationship between the contribution of CAVI or SUA and KFD. ROC analysis determined a cutoff CAVI of 8.0 (males) or 7.9 (females) and a cutoff SUA of 6.3 (males) or 4.5 mg/dL (females) for predicting KFD. The linkage between SUA and CAVI was associated with a greater increase in the hazard ratio for KFD with an increase in SUA. CAVI showed the mediating effect on the relationship of SUA with KFD after an adjustment for confounders. SUA was associated positively with CAVI-mediated KFD. Further studies should verify whether intensive SUA-lowering treatment prevents KFD via improving vascular function.

Effects of Vildagliptin, a Dipeptidyl Peptidase-4 Inhibitor, on the Parameters of Glucose Metabolism and the Cardio-Ankle Vascular Index in Individuals with Type 2 Diabetes.

DPP-4 inhibitors are frequently used as first-line agents for the treatment of type 2 diabetes in Japan. This study aimed to examine the effects of vildagliptin on glucose metabolism and arterial stiffness. Twenty treatment-naïve patients with type 2 diabetes (8 males and 12 females) received vildagliptin 50 mg twice daily for 6 months. Self-monitored blood glucose measurements and a 75 g OGTT were performed. Arterial stiffness was assessed using the CAVI. After the vildagliptin treatment, a significant decrease in the median HbA1c (from 8.3 to 6.4%) and fasting HOMA-ß (from 26.1 to 34.5%), and a marginally significant decrease in the CAVI (from 8.9 to 8.4, p = 0.087) were observed. The glycemic variability parameters also improved, whereas the insulin sensitivity and oxidative stress remained unchanged. Participants with a lower glycemic variability on the 75 g OGTT after vildagliptin treatment showed a significant decrease in their CAVI. The baseline BMI was significantly higher for the participants with a decreased CAVI than in those with no change in their CAVI (24.5 vs. 20.8 kg/m2). After vildagliptin treatment, a decrease in the CAVI was observed, especially in the individuals with improved glycemic variability on the 75 g OGTT. Vildagliptin may be suitable for vascular protection in individuals with high glycemic variability and/or an elevated BMI.

Relationship between Lipoprotein Lipase Derived from Subcutaneous Adipose Tissue and Cardio-Ankle Vascular Index in Japanese Patients with Severe Obesity.

INTRODUCTION: Cardio-ankle vascular index (CAVI) is an arterial stiffness index that correlates inversely with body mass index (BMI) and subcutaneous fat area. Lipoprotein lipase (LPL) that catalyzes the hydrolysis of serum triglycerides is produced mainly in adipocytes. Serum LPL mass reflects LPL expression in adipose tissue, and its changes correlate inversely with changes in CAVI. We hypothesized that LPL derived from subcutaneous adipose tissue (SAT) suppresses the progression of arteriosclerosis and examined the relationship of LPL gene expression in different adipose tissues and serum LPL mass with CAVI in Japanese patients with severe obesity undergoing laparoscopic sleeve gastrectomy (LSG). METHODS: This study was a single-center retrospective database analysis. Fifty Japanese patients who underwent LSG and had 1-year postoperative follow-up data were enrolled (mean age 47.5 years, baseline BMI 46.6 kg/m2, baseline HbA1c 6.7%). SAT and visceral adipose tissue (VAT) samples were obtained during LSG surgery. LPL gene expression was analyzed by real-time PCR. Serum LPL mass was measured by ELISA using a specific monoclonal antibody against LPL. RESULTS: At baseline, LPL mRNA expression in SAT correlated positively with serum LPL mass, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT was correlated, and serum LPL mass tended to correlate inversely with the number of metabolic syndrome symptoms, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT and CAVI tended to correlate inversely in the group with visceral-to-subcutaneous fat ratio of 0.4 or higher, which is considered metabolically severe. Serum LPL mass increased 1 year after LSG. Change in serum LPL mass at 1 year after LSG tended to be an independent factor inversely associated with change in CAVI. CONCLUSIONS: Serum LPL mass reflected LPL mRNA expression in SAT in Japanese patients with severe obesity, and LPL mRNA expression in SAT was associated with CAVI in patients with visceral obesity. The change in serum LPL mass after LSG tended to independently contribute inversely to the change in CAVI. This study suggests that LPL derived from SAT may suppress the progression of arteriosclerosis.

[Hypertriglyceridemia-induced pancreatitis].

In Japan, the frequency of acute pancreatitis is 27.7 per 100,000, which includes 1.4 % of hypertriglyceridemia-induced pancreatitis(HTGP). Severity and complication rates with HTGP have been reported as higher in comparison to acute pancreatitis from other etiologies. Havel has suggested that hydrolysis of excessive triglyceride-rich lipoproteins releases high concentrations of free fatty acid(FFA). The FFA micelles injure the vascular endothelium and acinar cells of the pancreas, producing a self-perpetuating ischemic and acidic environment with resultant toxicity. Lipoprotein lipase (LPL) abnormality has been reported to contribute to severe hypertriglyceridemia. However, patients without any LPL abnormality are often encountered clinically, suggesting that other factors may be involved in the development of severe hypertriglyceridemia. In 21 patients with HTGP, 9 patients(42.9 %) with apolipoprotein AV (ApoAV) Gly185-Cys polymorphism were observed, whereas 14.3 % with LPL gene variants. No patient had ApoCII deficiency. These results suggest that in addition to LPL gene variants, ApoAV variant may be numerously involved in HTGP. It is important for clinicians to routinely investigate pathogenesis of hypertriglyceridemia in case with pancreatitis because specific management may be needed.

Relationship of serum lipid parameters with kidney function decline accompanied by systemic arterial stiffness: a retrospective cohort study.

Background: Dyslipidemia is associated with kidney function decline (KFD), although the non-linear relationship of lipid parameters to KFD has not been fully elucidated. We aimed to determine the detailed relationship of baseline lipid parameters with KFD, considering the mediation of arterial stiffness. Methods: A total of 27 864 urban residents with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at baseline, who participated in a median of three (range two to eight) consecutive annual health examinations were studied. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI). KFD was defined as development of eGFR <60 mL/min/1.73 m2. Results: During the study period, 1837 participants (6.6%) developed KFD. Receiver operating characteristic analysis determined that the cutoff values independently associated with KFD are 123 mg/dL for low-density lipoprotein cholesterol (LDL-C) [area under the curve (95% confidence interval) 0.570 (0.557-0.583)], 65 mg/dL for high-density lipoprotein cholesterol (HDL-C) [0.552 (0.539-0.566)], 82 mg/dL for triglycerides (TG) [0.606 (0.593-0.618)] and 1.28 for TG/HDL-C ratio [0.600 (0.587-0.612)]. These cut-offs were independently associated with KFD in Cox analysis. Regarding the contribution of each lipid parameter to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A adjusted mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed (mediating rate: 2.9% in TG, 2.5% in TG/HDL-C ratio). Regarding the association to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed after adjustment for confounders. Conclusions: TG and TG/HDL-C ratio related linearly to KFD and this was partially mediated by CAVI. A U-shaped relationship was observed between HDL-C and KFD risk. LDL-C showed no significant association. Further study should investigate whether intensive TG-lowering treatment prevents KFD via decreasing CAVI.

The Process of Plaque Rupture: The Role of Vasa Vasorum and Medial Smooth Muscle Contraction Monitored by the Cardio-Ankle Vascular Index.

A warning sign for impending cardiovascular events is not fully established. In the process of plaque rupture, the formation of vulnerable plaque is important, and oxidized cholesterols play an important role in its progression. Furthermore, the significance of vasa vasorum penetrating the medial smooth muscle layer and being rich in atheromatous lesions should be noted. The cardio-ankle vascular index (CAVI) is a new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. The CAVI reflects functional stiffness, in addition to structural stiffness. The rapid rise in the CAVI means medial smooth muscle cell contraction and strangling vasa vasorum. A rapid rise in the CAVI in people after a big earthquake, following a high frequency of cardiovascular events has been reported. There are several cases that showed a rapid rise in the CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis: a rapid rise in the CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading to ischemia and the necrosis of vulnerable plaque, and then the plaque ruptures. In individuals having a high CAVI, further rapid rise in the CAVI might be a warning sign for impending cardiovascular events. In such cases, treatments to decrease the CAVI better be taken soon.

Cumulative Cigarette Consumption is Associated with Cardio-Ankle Vascular Index (CAVI) Mediated by Abdominal Obesity Assessed by A Body Shape Index (ABSI): A Cross-Sectional Study.

AIM: To elucidate the mechanism by which cigarette smoking causes vascular damage, we examined the relationship between cumulative cigarette consumption and abdominal obesity, and the possible mediating effect of smoking on arterial stiffness. METHODS: Cross-sectional data from 19499 never smokers and 5406 current smokers receiving health screening was analyzed. Abdominal obesity was assessed by ABSI, and arterial stiffness by CAVI. High CAVI was defined as CAVI ≥ 9.0. RESULTS: Current smoker showed higher ABSI than never smokers after propensity score matching. Cumulative cigarette consumption expressed in pack-years correlated with ABSI (Rs: 0.312 in men, 0.252 in women), and was also extracted as an independent factor associated with ABSI by multiple regression analysis. A linear relationship between pack-year and CAVI was observed (Rs: 0.544 in men, 0.423 in women). Pack-year had almost equal discriminatory power in predicting high CAVI in both sexes (C-statistic: 0.774 in men, 0.747 in women), and the best cut-offs of pack-year for high CAVI were 24.5 in men and 14.7 in women. Bivariate logistic regression models revealed that the association between pack-year higher than cut-off and high CAVI was independent of traditional risks. A mediating effect of ABSI (mediation rate: 9.9% in men and 11.2% in women), but not waist circumference (WC), on the association of pack-year with CAVI was observed, after adjusting for traditional risks. CONCLUSION: Cumulative cigarette smoking in pack-years was independently associated with ABSI. ABSI partially mediates the association between pack-year and CAVI, suggesting that abdominal obesity partially mediates smoking-related vascular dysfunction.

Factors Associated with Relapse of Type 2 Diabetes Mellitus after Laparoscopic Sleeve Gastrectomy in Japanese Subjects: A Subgroup Analysis of J-SMART Study.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) for morbidly obese patients often results in remission of type 2 diabetes (T2DM), but diabetes relapses in some of those patients. The frequency of T2DM relapse in Asians and the factors involved have not been adequately investigated. METHODS: The J-SMART study was conducted on 322 Japanese subjects with body mass index (BMI) ≥32 kg/m2 who underwent LSG at 10 accredited centers in Japan between 2011 and 2014. Of these, 82 T2DM subjects with diabetes in complete or partial remission at 1 year after LSG and followed postoperatively for 5 years were included in the subgroup analysis and classified into two groups: diabetes remission-maintained and diabetes relapse. RESULTS: The mean age of all included subjects was 49.2 years, median BMI was 41.5 kg/m2, and median HbA1c was 6.7%. Compared with the diabetes remission-maintained group, the diabetes relapse group at 5 years after LSG had significantly higher preoperative HbA1c, number of antidiabetic medications, and high-density lipoprotein cholesterol level; and lower BMI and homeostasis model assessment-beta cell function (HOMA-ß). As many as 83.0% of the subjects were able to achieve HbA1c <7% at 5 years after LSG, but 26.8% of the subjects had diabetes relapse. Preoperative HbA1c significantly contributed to diabetes relapse (odds ratio 1.54, p = 0.049). In addition, the diabetes relapse group tended to have lower percentage total weight loss (%TWL) at 1 year after LSG and higher percentage weight regain (%WR) from postoperative nadir weight, compared with the diabetes remission-maintained group. The hazard ratio for diabetes relapse was 3.14-fold higher in subjects with %TWL ≥20% and %WR ≥25%, and 5.46-fold higher in those with %TWL <20% and %WR ≥25%, compared with %TWL ≥20% and %WR <25%. CONCLUSION: While LSG provides a high remission rate for T2DM, relapse is not uncommon. Preoperative HbA1c, poor weight loss, and excess weight regain after LSG contribute to diabetes relapse, suggesting the importance of treatment strategies focusing on these factors.

Various Obesity Indices and Arterial Function Evaluated with CAVI - Is Waist Circumference Adequate to Define Metabolic Syndrome?

Obesity has been known to relate to various diseases and metabolic disorders. Since the implication of body shape has been mentioned, obesity can be divided into visceral obesity and subcutaneous obesity. The former is considered the upstream pathophysiology of metabolic syndrome (MetS), and has been emphasized worldwide for the prevention of cardiovascular diseases in the last quarter century. However, some prospective studies have shown that cardiovascular mortality and morbidity are not necessarily higher in patients with MetS compared to those without. Recently, cardio-ankle vascular index (CAVI) has been established as an indicator of arteriosclerosis. This parameter is independent of blood pressure at the measuring time, and reflects systemic arterial stiffness from the aortic origin to the ankle. However, since CAVI is not necessarily high in MetS patients, attempts have been made to clarify this unexpected phenomenon. In several studies, CAVI was found to correlate negatively with body mass index (BMI), and also with waist circumference (WC) which is a widely used representative visceral obesity index. On the other hand, a body shape index (ABSI) is also a visceral obesity index designed to be minimally associated with BMI, and is calculated by dividing WC by an allometric regression of weight and height. Replacing high WC with high ABSI in MetS diagnosis promoted the identification of MetS patients with increased CAVI in cross-sectional studies on Japanese and Korean populations. Additionally, the incidence of MetS diagnosed using high ABSI was associated with significant increase in CAVI after 1 year of observation. Enhanced predictive ability for renal function decline by replacing WC with ABSI in MetS diagnosis was also observed in a longitudinal study in Japanese urban residents. These findings suggest that MetS diagnosis using high ABSI instead of high WC as a visceral obesity index needs to be reconsidered. However, further research is desirable on Caucasian, whose body shape differs slightly from that of Asians.

Comparison of Predictive Ability of Arterial Stiffness Parameters Including Cardio-Ankle Vascular Index, Pulse Wave Velocity and Cardio-Ankle Vascular Index0.

Cardio-ankle vascular index (CAVI) was developed to reflect the stiffness of the arterial tree from the aortic origin to the ankle. This arterial stiffness parameter is useful for assessing the severity of cardiovascular disease (CVD) and its risk. However, compared to pulse wave velocity (PWV), the conventional gold standard of arterial stiffness parameter, there has been a concern regarding CAVI that there are fewer longitudinal studies for CVD. Furthermore, the accuracy of CAVI for atherosclerotic diseases compared to other parameters has not been well validated. This review article aims to summarize recent findings to clarify the predictive ability of CAVI in longitudinal studies. First, several large longitudinal studies have found that not only baseline CAVI but also CAVI changes during the observation period predict cardiovascular events. Second, CAVI may have superior discriminatory power for all-cause mortality and major adverse cardiovascular endpoints compared to PWV. Furthermore, one large longitudinal study found CAVI to be a stronger predictor for renal function decline compared to PWV as well as CAVI0, a variant of CAVI that mathematically excludes BP dependence. Additionally, CAVI shows the properties that allow the elucidation of specific hemodynamics in aortic valve disease or hypovolemia. In conclusion, CAVI may be a modifiable arterial stiffness parameter not only for predicting and preventing atherosclerotic diseases but also for elucidating specific hemodynamic pathophysiology.

Predictive ability of arterial stiffness parameters for renal function decline: a retrospective cohort study comparing cardio-ankle vascular index, pulse wave velocity and cardio-ankle vascular index 0.

OBJECTIVE: The relative usefulness of arterial stiffness parameters on renal function remains controversial. This study aimed to compare the predictive ability of three arterial stiffness parameters at baseline; cardio-ankle vascular index (CAVI), heart-ankle pulse wave velocity (haPWV) and CAVI 0 , a variant of CAVI that theoretically excludes dependence on blood pressure, for renal function decline in Japanese general population. METHODS: A total of 27 864 Japanese urban residents without renal impairment at baseline who participated in two to eight consecutive (mean 3.5 ±â€Š1.7 times) annual health examinations were studied. RESULTS: During the study period, 6.6% of participants developed renal function decline (estimated glomerular filtration rate <60 ml/min per 1.73 m 2 ), all of whom had relatively high values in all arterial stiffness parameters. In receiver-operating characteristic curve analysis, the discriminatory power for renal function decline showed a decreasing trend of CAVI to haPWV to CAVI 0 (C-statistic: 0.740 vs. 0.734 vs. 0.726). The cut-offs were CAVI 8.0, haPWV 7.23 and CAVI 0 11.6. In Cox-proportional hazards analysis for increase of each parameter above cut-off or by 1 standard deviation (SD) adjusted for two models of confounders, only CAVI always contributed significantly to renal function decline. Restricted cubic spline regression analysis suggested that CAVI most accurately reflected the risk of renal function decline. CONCLUSION: Increase in arterial stiffness parameters, especially CAVI, may represent a major modifiable risk factor for renal function decline in the general population. Further research is needed to examine whether CAVI-lowering interventions contribute to the prevention of chronic kidney disease.

Issue of Waist Circumference for the Diagnosis of Metabolic Syndrome Regarding Arterial Stiffness: Possible Utility of a Body Shape Index in Middle-Aged Nonobese Japanese Urban Residents Receiving Health Screening.

INTRODUCTION: Abdominal obesity as a risk factor for diagnosing metabolic syndrome (MetS) is evaluated using waist circumference (WC), although WC does not necessarily reflect visceral adiposity. This cross-sectional study aimed to clarify whether replacing WC with "A Body Shape Index (ABSI)," an abdominal obesity index, in MetS diagnosis detects individuals with arterial stiffening assessed by cardio-ankle vascular index (CAVI). METHODS: A retrospective cross-sectional study was conducted in 46,872 Japanese urban residents (median age 40 years) who underwent health screening. Exclusion criteria were current treatments and a past history of cardiovascular disease (CVD). The Japanese, International Diabetes Federation, and NCEP-ATPIII criteria were used to diagnose MetS. High CAVI was defined as CAVI ≥9.0. RESULTS: CAVI correlated positively with ABSI (ß = 0.127), but negatively with WC (ß = -0.186), independent of age, sex, systolic blood pressure, fasting plasma glucose, and high-density lipoprotein--cholesterol. Receiver operating characteristic (ROC) analysis showed that ABSI had a stronger contribution to high CAVI (area under the ROC curve [AUC] = 0.730) than WC (AUC = 0.595) and body mass index (AUC = 0.520). ABSI ≥0.080 was defined as abdominal obesity based on the results of ROC analysis for high CAVI and estimated glomerular filtration rate <60 mL/min/1.73 m2. Logistic regression analysis revealed that replacing high WC with ABSI ≥0.080 in MetS diagnosis enhanced the detection of subjects with high CAVI. DISCUSSION/CONCLUSION: Use of ABSI can detect subjects with arterial stiffening, which may lead to efficient stratification of CVD risk. Further studies are needed to confirm whether MetS diagnosis using ABSI predicts CVD morbidity and mortality.