Ayako Nagumo

Effects of body weight reduction on cardio-ankle vascular index (CAVI)

OBJECTIVE Obesity is associated with type 2 diabetes, dyslipidemia and hypertension, contributing to atherogenesis. Weight reduction is the fundamental therapy for obesity. Recently, a novel arterial stiffness parameter called cardio-ankle vascular index (CAVI) has been developed. We hypothesized that CAVI may be a candidate marker of increased vascular stiffness in obese patients. The aim of this study is to investigate the effect of weight reduction on CAVI. SUBJECTS AND METHODS Using CAVI as an indicator, we assessed the changes in arterial stiffness in 47 obese Japanese subjects (aged 46 ± 13 years) who underwent a 12-week weight reduction program consisting of a calorie restriction diet (20-25 kcal/day) and exercise therapy. Visceral fat area (VFA) was evaluated by CT. RESULTS At baseline, CAVI correlated positively with age (r = 0.70), blood pressure (r = 0.23), VFA (r = 0.26) and HbA1c (r = 0.39). After 12 weeks of weight reduction, mean BMI decreased from 33.3 ± 7.5 to 30.7 ± 6.4 kg/m(2) (p < 0.0001), and mean CAVI decreased from 8.3 to 7.9 (p < 0.01). The change in VFA correlated positively with change in CAVI in subjects with decrease in CAVI (r = 0.47). Furthermore, change in VFA was a significant independent predictor for change in CAVI. No significant correlation was observed between change in CAVI and clinical variables such as BMI, HbA1c and lipids. CONCLUSION This study demonstrated that CAVI decreased after weight reduction, and was associated with a decrease in VFA. CAVI reduction maybe a marker of improved vascular stiffness after weight reduction in subjects with visceral adiposity.

Improvement of postprandial hyperglycemia and arterial stiffness upon switching from premixed human insulin 30/70 to biphasic insulin aspart 30/70

Postprandial hyperglycemia is known to be associated with increasing cardiovascular mortality in type 2 diabetes mellitus patients. Cardio-ankle vascular index (CAVI) reflects arterial stiffness and is more useful for predicting coronary atherosclerosis than intima-media thickness. Premixed human insulin 30/70 (BHI30) containing rapid-acting insulin has been used conventionally as a biphasic insulin. Recently, a biphasic insulin analogue preparation, biphasic insulin aspart 30/70 (BIAsp30), containing ultrarapid-acting insulin has been approved and expected to improve postprandial hyperglycemia. The aim of this study was to clarify the effects of switching the biphasic insulin from BHI30 to BIAsp30 on arterial stiffness in type 2 diabetes mellitus patients. Twenty-six type 2 diabetes mellitus patients (glycosylated hemoglobin >6.5%) who were already receiving biphasic insulin therapy with BHI30 twice daily were observed for 3 months. Afterward, BHI30 was switched to BIAsp30. At 3 months after switching, relative mobility of the peak of LDL fraction decreased significantly (from 0.3462 ± 0.041 to 0.3356 ± 0.035, P < .01); and CAVI also decreased significantly (from 9.77 ± 1.11 to 9.35 ± 1.17 m/s, P < .005). A significant negative correlation was observed between the change in CAVI and change in 1,5-anhydroglucitol (1,5-AG) (r = -0.3929, P < .05). A stronger correlation between change in CAVI and change in 1,5-AG was observed in the subgroup of patients whose 1,5-AG levels were elevated after switching (r = -0.6261, P < .05) compared with all subjects. These results suggest that switching biphasic insulin from BHI30 to BIAsp30 improves arterial stiffness, and the improvement of arterial stiffness may be associated with improvement of postprandial hyperglycemia.

Cardio-Ankle Vascular Index is Independently Associated with Future Cardiovascular Events in Outpatients with Metabolic Disorders

AIM We investigated whether cardio-ankle vascular index (CAVI), an arterial stiffness marker, independently predicts future cardiovascular events in subjects with metabolic disorders. METHODS 1562 outpatients underwent CAVI between April 2004 and March 2006 at Toho University, Sakura Medical Center in Chiba, Japan. Patients who already had cardiovascular events at baseline, patients with low ankle brachial index (＜0.9), and patients with atrial fibrillation were excluded. After exclusion, 1080 subjects with metabolic disorders including diabetes mellitus, hypertension and dyslipidemia were screened and followed prospectively. RESULTS Eventually, 1003 subjects (92.9% of 1,080 subjects) followed until March 2012 (follow-up duration 6.7±1.6 years) were analyzed. During the observation period, 90 subjects had new-onset myocardial infarction or angina pectoris confirmed by angiography. All subjects were stratified into quartiles by baseline CAVI (Q1: CAVI ≤8.27, Q2: CAVI 8.28-9.19, Q3: CAVI 9.20-10.08, Q4: CAVI ≥10.09). Age, male ratio and future cardiovascular events increased as CAVI quartile became higher. In Cox proportional hazards regression analysis, the factors independently associated with higher risk of future cardiovascular events were every 1.0 increment of CAVI [hazard ratio (HR) 1.126, p= 0.039], male gender (HR 2.276, p=0.001), smoking (HR 1.846, p=0.007), diabetes mellitus (HR 1.702,p=0.020), and hypertension (HR 1.682, p=0.023). CONCLUSION In individuals with metabolic disorders, CAVI was a predictor of future cardiovascular events, independent of traditional coronary risk factors. CAVI is a potentially valuable tool to identify persons likely to benefit from more intensive therapeutic approaches.

High serum uric acid is associated with increased cardio-ankle vascular index (CAVI) in healthy Japanese subjects: A cross-sectional study

OBJECTIVE To investigate the association of serum uric acid (SUA) with arterial stiffness assessed by cardio-ankle vascular index (CAVI). METHODS We analyzed the cross-sectional data from 27,360 healthy Japanese subjects (12,910 males and 14,450 females) aged between 20 and 74 years without a past history of heart disease, stroke, hypertension, diabetes, nephritis or gout. We investigated whether SUA was independently associated with CAVI in a gender-specific manner. RESULTS BMI, CAVI, systolic/diastolic BP, GOT, GPT, γ-GTP, triglyceride (TG), creatinine and SUA were higher and HDL-C was lower in males than in females. Next, they were stratified by SUA into 3 groups: lower tertile (T1), middle tertile (T2) and upper tertile (T3) and by gender. CAVI increased progressive with increasing SUA tertile, after adjusting for age, BMI and systolic BP (sBP) identified in multiple regression analysis for CAVI. Multivariate analysis showed that the odds ratios (95% CI) relative to T1 for high CAVI (≥90(th) percentile) were 1.233 (0.928-1.638) in T2 and 1.352 (1.031-1.773) in T3 for males, and 1.133 (0.984-1.303) in T2 and 1.361 (1.098-1.687) in T3 for females, after adjusting for confounders. Furthermore, increase in adjusted CAVI was observed in a lower SUA range in females compared to that observed in males. CONCLUSION We demonstrated an independent correlation between SUA and CAVI, and observed gender difference in the SUA range for increase in CAVI. These results may suggest the need to set different target SUA levels for men and women in anti-hyperuricemic treatment for atherosclerosis prevention.

Pioglitazone improves the cardio-ankle vascular index in patients with type 2 diabetes mellitus treated with metformin

Background Type 2 diabetes is known to be associated with elevated cardiovascular mortality. Pioglitazone improves blood pressure (BP) and pulse wave velocity (PWV), which is an arterial stiffness parameter. Arterial stiffness is closely associated with cardiovascular disease. However, PWV is correlated with BP. The cardio-ankle vascular index (CAVI) reflects arterial stiffness independent of BP. Pioglitazone improves PWV but reduces blood pressure. The aim of this study was to re-evaluate the effect of pioglitazone on arterial stiffness with CAVI. Methods Sixty patients with type 2 diabetes mellitus and already on 500 mg/day of metformin received add-on therapy of pioglitazone 15 mg/day or glimepiride 1 mg/day for 6 months, during which time changes in their metabolic parameters and CAVI were observed. Results After 6 months of treatment, both pioglitazone (n=30) and glimepiride (n=30) improved fasting blood glucose and glycated hemoglobin. The changes in fasting blood glucose and glycated hemoglobin between the two groups were greater in the pioglitazone group. Systolic and diastolic BP was decreased in both groups, with no significant between-group differences. Only pioglitazone increased serum adiponectin levels, and the change in adiponectin between the pioglitazone and glimepiride groups was significantly different. CAVI was decreased significantly by pioglitazone but remained unchanged after treatment with glimepiride. The change in CAVI between the two groups was significantly different. Conclusion These results suggest that pioglitazone improves CAVI, a BP-independent arterial stiffness parameter, in patients with type 2 diabetes mellitus treated with metformin.