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.

Increased arterial velocity pulse index is an independent factor related to skeletal muscle mass reduction and tissue damage in patients with cardiovascular disease.

Reduced skeletal muscle mass is the most important component of sarcopenia. Aging and chronic diseases, including chronic heart failure, are the causes of reduced skeletal muscle mass. However, little is known about the mechanism of skeletal muscle mass reduction in patients with cardiovascular disease (CVD). The purpose of this study was to assess the associations among skeletal muscle mass reduction, endothelial function, and other markers of advanced vascular damage in CVD patients. This was a retrospective cross-sectional analysis that included 310 inpatients with CVD in our hospital. Flow-mediated vasodilation (FMD) was performed to assess early vascular damage, i.e., endothelial dysfunction. The arterial velocity pulse index (AVI) and arterial pressure volume index (API) were assessed to reveal signs of advanced vascular damage, such as arterial stiffening and increased peripheral resistance. The bioelectrical phase angle (PA), as a marker of tissue damage, and the skeletal muscle index (SMI) were measured. Correlation analyses were performed among these parameters. Sarcopenia was diagnosed in 25.5% of patients according to the Asian Working Group for Sarcopenia criteria. Greater progression of arterial stiffness, shown by a higher AVI, and more severe tissue damage, shown by a narrower PA, were found in individuals with sarcopenia. Stepwise multivariate regression analysis showed that sex, age, PA, hypertension, and AVI were factors independently correlated with SMI. In conclusion, advanced vascular damage, such as increased arterial stiffness and peripheral resistance, might play an important role in the reduction in skeletal muscle mass, possibly through damage to skeletal muscle tissue in CVD patients.

Diagnostic Criteria of Flow-Mediated Vasodilation for Normal Endothelial Function and Nitroglycerin-Induced Vasodilation for Normal Vascular Smooth Muscle Function of the Brachial Artery.

Background Diagnostic criteria of flow-mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin-induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function. Methods and Results We investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no-risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow-Mediated Dilation Japan study and the Flow-Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver-operator characteristic curve analysis of FMD to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no-risk group was 7.1%. Receiver-operator characteristic curve analysis of NID to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no-risk group was 15.6%. Conclusions We propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects. Clinical Trial Registration www.umin.ac.jp Unique identifiers: UMIN000012950, UMIN000012951, UMIN000012952, and UMIN000003409.

Trends in the prevalence of COPD in elderly individuals in an air-polluted city in Japan: a cross-sectional study.

Purpose: The aim of this study was to examine the effects of exposure to air pollution and cigarette smoke on respiratory function, respiratory symptoms, and the prevalence of COPD in individuals aged ≥50 years. Patients and methods: We used spirometry and medical questionnaires to screen 433 individuals from Omuta City, Japan, an area with high levels of air pollution. Results: Non smokers had a high estimated COPD prevalence rate of 16%. Among smokers, the estimated prevalence of COPD was 29% in seniors (50- to 74-years group) and 37% in the elderly (>75 years group). We also found a correlation between levels of suspended particulate matter and COPD. Conclusion: Both smoking and chronic exposure to air pollution (>5 years) decreased respiratory function, exacerbated respiratory symptoms, and increased the prevalence of COPD. We strongly recommend periodic screening for the elderly patients to facilitate early detection of respiratory disease.

Target of Triglycerides as Residual Risk for Cardiovascular Events in Patients With Coronary Artery Disease　- Post Hoc Analysis of the FMD-J Study A.

BACKGROUND: Circulating triglyceride (TG) levels are a current focus as a residual risk for cardiovascular (CV) events. We evaluated the relationship between circulating TG levels and future CV events in patients with coronary artery disease (CAD) who were treated with conventional therapy. Methods and Results: We analyzed data for 652 patients who were enrolled in the FMD-J Study A. We investigated the associations between serum TG levels and first major CV events (death from CV cause, nonfatal acute coronary syndrome (ACS), nonfatal stroke, and CAD) for a 3-year follow-up period. Patients were divided into 4 groups based on serum TG level: low-normal (<100 mg/dL), high-normal (100-149 mg/dL), borderline hypertriglyceridemia (150-199 mg/dL), and moderate hypertriglyceridemia (≥200 mg/dL). During a median follow-up period of 46.6 months, 14 patients died (9 from CV causes), 16 had nonfatal ACS, 6 had nonfatal stroke, and 54 had CAD. The Kaplan-Meier curves for first major CV event among the 4 groups were significantly different (P=0.04). After adjustment for various confounders, serum TG level ≥100 mg/dL were significantly associated with an increased risk of first major CV events compared with serum TG level <100 mg/dL. CONCLUSIONS: Serum TG level may be a surrogate marker for predicting CV events in patients with CAD.

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.

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.

Oral Administration of Glucosamine Improves Vascular Endothelial Function by Modulating Intracellular Redox State.

Glucosamine, used to treat osteoarthritis, has been shown to have anti-inflammatory and anti-atherosclerotic effects in experimental studies. A recent cohort study has demonstrated that the use of glucosamine was significantly associated with decreased total mortality. Vascular endothelial function is a potent surrogate marker of atherosclerosis and cardiovascular mortality where oxidative stress could participate. Therefore, we investigated whether glucosamine improves vascular endothelial function and intracellular redox state. We examined the effects of oral glucosamine administration (3000 mg/day) for 4 weeks on flow-mediated vasodilation (FMD) and intraerythrocyte glutathione parameters in 20 volunteers. Nineteen age-matched volunteers served as controls. Glucosamine administration significantly increased FMD (from 7.0 ± 2.3 to 8.7 ± 2.3%, P = 0.022). In the control group, FMD did not change. Glucosamine administration significantly increased intraerythrocyte total glutathione levels (from 212.9 ± 46.2 to 240.6 ± 49.4 µmol/L, P = 0.006), intraerythrocyte reduced form of glutathione (GSH) levels (from 124.7 ± 42.6 to 155.2 ± 47.7 µmol/L; P = 0.004) and intraerythrocyte GSH/oxidized form of glutathione (GSSG) ratios (from 3.18 ± 1.64 to 3.88 ± 1.61, P = 0.04). In the control group, any glutathione parameters did not change. Moreover, a stepwise multivariate analysis revealed percent change of GSH/GSSG is the only independent predictor for those of FMD (standardized ß = 0.58, P = 0.007) in the glucosamine group. Glucosamine administration improved FMD in association with amelioration of intraerythrocyte GSH/GSSG ratios. These results suggest that oral glucosamine administration might improve vascular endothelial function by modulating intracellular redox state.

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.

New diagnostic index for sarcopenia in patients with cardiovascular diseases.

BACKGROUND: Sarcopenia is an aging and disease-related syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, with the risk of frailty and poor quality of life. Sarcopenia is diagnosed by a decrease in skeletal muscle index (SMI) and reduction of either handgrip strength or gait speed. However, measurement of SMI is difficult for general physicians because it requires special equipment for bioelectrical impedance assay or dual-energy X-ray absorptiometry. The purpose of this study was, therefore, to explore a novel, simple diagnostic method of sarcopenia evaluation in patients with cardiovascular diseases (CVD). METHODS: We retrospectively investigated 132 inpatients with CVD (age: 72±12 years, age range: 27-93 years, males: 61%) Binomial logistic regression and correlation analyses were used to assess the associations of sarcopenia with simple physical data and biomarkers, including muscle-related inflammation makers and nutritional markers. RESULTS: Sarcopenia was present in 29.5% of the study population. Serum concentrations of adiponectin and sialic acid were significantly higher in sarcopenic than non-sarcopenic CVD patients. Stepwise multivariate binomial logistic regression analysis revealed that adiponectin, sialic acid, sex, age, and body mass index were independent factors for sarcopenia detection. Sarcopenia index, obtained from the diagnostic regression formula for sarcopenia detection including the five independent factors, indicated a high accuracy in ROC curve analysis (sensitivity 94.9%, specificity 69.9%) and the cutoff value for sarcopenia detection was -1.6134. Sarcopenia index had a significant correlation with the conventional diagnostic parameters of sarcopenia. CONCLUSIONS: Our new sarcopenia index using simple parameters would be useful for diagnosing sarcopenia in CVD patients.

Effectiveness of diagnostic screening tests in mass screening for COPD using a cooperative regional system in a region with heavy air pollution: a cross-sectional study.

OBJECTIVES: This study aimed to evaluate the effectiveness of a cooperative healthcare model for early detection and diagnosis of chronic obstructive pulmonary disease (COPD). METHODS: This was a cross-sectional observational study. We performed diagnosis of COPD at 4 public health centres in Omuta, Japan from March 2015 to March 2016, by adding screening for COPD at the time of routine medical evaluations. All patients aged over 40 years were eligible to participate. Among 397 eligible patients, 293 agreed to participate in the study. RESULTS: The estimated prevalence of COPD in Omuta was 10% among patients aged over 40 years and was 17% among smokers. Among those who were screened, over half of them had questionnaire scores over the cut-off of 17 points and decreased FEV1/FVC%, indicating COPD (p>0.05). 30 patients with suspected COPD were referred for further investigation at a local central hospital, but only 6 underwent further medical examinations. CONCLUSIONS: The combination of a COPD questionnaire and medical examination is effective as a COPD screening tool. Future research should investigate behavioural interventions for smoking cessation that can be offered in a cooperative model, as well as for improving participation in COPD screening and for encouraging early presentation for treatment in those suspected of having COPD.

Effect of Exercise Training on Red Blood Cell Distribution Width as a Marker of Impaired Exercise Tolerance in Patients With Coronary Artery Disease.

Red blood cell distribution width (RDW) can predict mortality in cardiovascular disease. However, the underlying mechanisms of the beneficial prognostic marker remain unknown. The purpose of this study was to investigate whether the RDW is related to impaired exercise tolerance and exercise training (ET) effect on RDW in patients with coronary artery disease (CAD).Seventy-eight patients who underwent ET by supervised bicycle ergometer during 3 weeks served as the ET group whereas 30 patients who did not undergo ET were the control group. Exercise stress test with cardiopulmonary analysis was performed in the ET group. Peak oxygen uptake (from 14.1 ± 4.0 to 15.1 ± 3.8 mL/kg/minute, P < 0.05) significantly increased in the ET group. Although RDW and serum erythropoietin concentration (EP) before the observation period did not differ between the ET and control groups, RDW (from 44.4 ± 4.7 to 43.4 ± 3.8 fL, P < 0.01) and EP (from 27.9 ± 15.8 to 22.9 ± 8.2 mIU/mL, P < 0.005) significantly decreased in the ET group, however, these parameters did not change in the control group. In the ET group, RDW was negatively correlated with peak oxygen uptake (r = -0.55, P < 0.01) and the changes in RDW before and after ET were positively correlated with the changes in EP (r = 0.39, P < 0.005).Thus, ET increases exercise tolerance and decreases RDW in association with increased oxygen uptake in patients with CAD.

Reliability of measurement of endothelial function across multiple institutions and establishment of reference values in Japanese.

AIMS: For the standardization of flow-mediated vasodilatation (FMD) assessment as a clinical tool, validation of its reliability across multiple institutions and the establishment of normal/reference values based on reliable data from multiple institutions are needed. METHODS AND RESULTS: In Study 1, assessment of FMD (scan recording and analysis) using an ultrasonographic semi-automatic measuring system (sFMD) was conducted at 18 participating institutions (sFMD-INST) (n = 981). All of the brachial arterial scans were also analyzed at a core laboratory (sFMD-COLB). After 111 subjects with inadequate sFMD recordings were excluded (n = 880), the correlation between the sFMD-INST and sFMD-COLB improved from R = 0.725 to R = 0.838 (p < 0.001). In Study 2, based on good-quality sFMD data obtained from 6660 subjects without cardiovascular disease (CVD) and 729 subjects with CVD from 27 institutions, reference values of sFMD are proposed by the Framingham risk score (FRS)-based risk categories and according to gender and age. The receiver-operating characteristic curve analysis revealed a significant power of sFMD values in reference ranges to discriminate between subjects with and without CVD (e.g., area under curve = 0.64 in the FRS-low risk group). CONCLUSIONS: When the analysis was limited to cases with clear sFMD recordings, the reliability of the sFMD assessment (scan and its analysis) conducted in individual institutions appeared to be acceptable. Reference sFMD values (lower cuff occlusion) for the Japanese population are proposed based on reliable data derived from multiple institutions, and the reference values may identify patients without advanced vascular damage.

Laronidase replacement therapy and left ventricular function in mucopolysaccharidosis I.

We assessed the effects of long-term laronidase replacement therapy (LRT) on the left ventricular (LV) function of a 52-year-old adult woman with mucopolysaccharidosis I (MPS I). The urinary uronic acid concentration significantly decreased by 78.7% (from 75 to 16 mg/g creatinine) after LRT; thereafter, estimated LV weight as assessed by two-dimensional (2D) echocardiography significantly decreased by 33.3% (from 189 to 126 g). Although systolic LV function of the ejection fraction as assessed by 2D echocardiogram did not change after LRT, the diastolic LV function parameters of the deceleration time (DcT) and the ratio of early (E) to late (A) ventricular filling velocities (E/A ratio) significantly improved. The DcT significantly decreased from 355 to 300 ms and the E/A ratio significantly decreased from 1.8 to 0.98. These diastolic parameters were normalized. In the contraction synchrony assessed by 2D speckle tracking imaging, the maximum time delay of contraction decreased from 148 to 14 ms. In addition, the LV weight significantly correlated with the E/A ratio (p < 0.001, r = 0.63), DcT (p < 0.05, r = 0.48), and contraction synchrony (p < 0.001, r = 0.61), respectively. This is the first study to report that LRT significantly improves diastolic LV function and contraction synchrony in a patient with MPS I.

Systolic blood pressure during recovery from exercise is related to flow-mediated dilatation in patients with coronary artery disease.

OBJECTIVE: To assess the relationship between exercise-induced parameters obtained from the routine exercise stress testing (EST) and flow-mediated vasodilatation (FMD) as an index of endothelial function. DESIGN: A retrospective study. SETTING: Kurume University Medical Center, Kurume, Japan. PATIENTS: All patients with stable coronary artery disease (CAD) who were admitted to Kurume University Medical Center. MAIN OUTCOME MEASURE: Results of EST and FMD. RESULTS: We studied 66 patients (35 male/31 female) with CAD. All patients underwent symptom-limited EST and measurement of FMD. Exercise parameters included exercise-induced heart rate and systolic blood pressure (SBP). FMD did not differ between male and female groups. In univariate analysis, determinants of FMD included age and the change in SBP at 1 min after exercise. In Cox hazard model analysis, the change in SBP at 1 min after exercise (p=0.011) was an independent determinant of FMD. FMD in patients with abnormal SBP response group was significantly lower than that in normal SBP response group (4.2±1.8 ns. 6.1±2.6%, p<0.05). CONCLUSIONS: These findings suggest that SBP during recovery from exercise is associated with endothelial function in patients with CAD.

New methodological approach to improve reproducibility of brachial artery flow-mediated dilatation.

BACKGROUND: Measurement of flow-mediated dilation (FMD) is well known as a noninvasive method for an assessment of vascular endothelial function. However, the reproducibility is a major issue of FMD measurement. The purpose of this study is to examine the reproducibility of the new FMD measurement with medial epicondyle method. METHODS: First, to evaluate the variability of the brachial artery diameter, 23 volunteers recruited from 32 healthy volunteers were examined for a brachial artery diameter at rest using with FMD equipment. Second, to evaluate the reproducibility of the FMD measurement, all volunteers underwent the FMD measurement, which was repeated at 2-week interval using the traditional method and the medial epicondyle method. The reproducibility in both methods was evaluated by 2 independent observers who measured on the same subject to assess the inter-observer reproducibility, and 1 observer who measured the same subject twice to assess the intra-observer reproducibility regarding the baseline value of arterial diameter and FMD. RESULTS: The variability of brachial artery diameter was 0.57 ± 0.27 mm in 23 healthy volunteers. In the study of inter- and intra-observer reproducibility, 2 parameters including intra-class correlation coefficient and Pearson's correlation coefficient by medial epicondyle method are superior to those by traditional method. CONCLUSIONS: These results suggest that medial epicondyle methodological approach to measure FMD is superior to traditional method.

Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging.

OBJECTIVES: The aim of this study was to compare the effect of pioglitazone with glimepiride on coronary arterial inflammation with serial (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) angiography. BACKGROUND: Recent studies have shown that FDG-PET combined with CT is a reliable tool to visualize and quantify vascular inflammation. Although pioglitazone significantly prevented the progression of coronary atherosclerosis and reduced the recurrence of myocardial infarction in patients with type 2 diabetes mellitus (DM), it remains unclear whether pioglitazone could attenuate coronary artery inflammation. METHODS: Fifty atherosclerotic patients with impaired glucose tolerance or type 2 DM underwent determination of blood chemistries, anthropometric and inflammatory variables, and FDG-PET/CT angiography, and then were randomized to receive either pioglitazone or glimepiride for 16 weeks. Effects of the treatments on vascular inflammation of the left main trunk were evaluated by FDG-PET/CT angiography at baseline and end of the study. Vascular inflammation of the left main trunk was measured by blood-normalized standardized uptake value, known as a target-to-background ratio. RESULTS: Three patients dropped out of the study during the assessment or treatment. Finally, 25 pioglitazone-treated patients and 22 glimepiride-treated patients (37 men; mean age: 68.1 ± 8.3 years; glycosylated hemoglobin: 6.72 ± 0.70%) completed the study. After 16-week treatments, fasting plasma glucose and glycosylated hemoglobin values were comparably reduced in both groups. Changes in target-to-background ratio values from baseline were significantly greater in the pioglitazone group than in the glimepiride group (-0.12 ± 0.06 vs. 0.09 ± 0.07, p = 0.032), as well as changes in high-sensitivity C-reactive protein (pioglitazone vs. glimepiride group: median: -0.24 [interquartile range (IQR): -1.58 to -0.04] mg/l vs. 0.08 [IQR: -0.07 to 0.79] mg/l, p = 0.031). CONCLUSIONS: Our study indicated that pioglitazone attenuated left main trunk inflammation in patients with impaired glucose tolerance or DM in a glucose-lowering independent manner, suggesting that pioglitazone may protect against cardiac events in patients with impaired glucose tolerance or DM by suppressing coronary inflammation. (Anti-Inflammatory Effects of Pioglitazone; NCT00722631).

Effects of pioglitazone on visceral fat metabolic activity in impaired glucose tolerance or type 2 diabetes mellitus.

CONTEXT: Excess visceral fat is associated with chronic systemic inflammation and cardiovascular complications. Pioglitazone has been reported to variably influence visceral fat volume; however, its effect on metabolic activity of the visceral fat remains uncharacterized. OBJECTIVE: The aim of this study was to assess the effects of pioglitazone on glucose metabolism of fat tissue by using (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography imaging. DESIGN, SETTING, AND PARTICIPANTS: FDG-PET and computed tomography imaging were performed in 56 patients with impaired glucose tolerance or type 2 diabetes mellitus; lipid and glycemic profiles and inflammatory biomarkers were obtained in all patients. These patients were randomized to treatment with either pioglitazone or glimepiride for 16 weeks. MAIN OUTCOME MEASURES: The metabolic activity of the visceral fat tissues as assessed by FDG uptake was expressed as a target-to-background ratio (TBR) of blood-normalized standardized uptake value. RESULTS: The study was completed in 32 pioglitazone-treated and 21 glimepiride-treated patients (40 men and 13 women; mean age, 67.7 ± 8.1 y; body mass index, 25.0 ± 3.6 kg/m(2); glycated hemoglobin, 6.78 ± 0.70%). Both treatments were well-tolerated and comparably improved glycemic control. At baseline, visceral fat exhibited a higher TBR value than subcutaneous fat (0.55 ± 0.14 vs 0.30 ± 0.07, P < .001). Pioglitazone, but not glimepiride, significantly decreased the visceral fat volume (130.5 ± 53.0 to 122.1 ± 51.0 cm(2), P = .013) and TBR values (0.57 ± 0.16 to 0.50 ± 0.11, P = .007). Neither pioglitazone nor glimepiride treatment showed any effect on the volume or TBR values of subcutaneous fat. After 16 weeks of treatment with pioglitazone, reduction in visceral fat TBR was correlated to the increase in high-density lipoprotein cholesterol levels. CONCLUSIONS: Our study indicated that pioglitazone decreased the visceral fat volume and its metabolic activity in patients with impaired glucose tolerance or type 2 diabetes mellitus. The beneficial effects of pioglitazone on visceral fat may be independent of its glucose-lowering effect.