Objective— Endothelial dysfunction is an initial step in atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans because of the lack of diagnostic modality to noninvasively evaluate vascular inflammation. We assessed the relationship between endothelial function and vascular inflammation evaluated by [ 18 F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging. Approach and Results— We examined endothelial function and vascular inflammation by flow-mediated dilation (FMD) of the brachial artery and [ 18 F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging of carotid arteries, respectively, in 145 subjects (95 men and 50 women; mean age, 61.8±9.5 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target:background ratio (TBR). We investigated whether absolute changes from baseline of %FMD after antihypertensive treatment for 6 months (Δ%FMD) were correlated with those of TBR in 33 drug-naive patients with essential hypertension. Multiple logistic regression analysis revealed that age (odds ratio, 1.767 for 10-year increase), male sex (odds ratio, 0.434), low-density lipoprotein-cholesterol (odds ratio, 1.630 for 26-mg/dL increase), and TBR values (odds ratio, 1.759 for 0.2 increase) were independently associated with %FMD in 145 patients. There was an inverse correlation between Δ%FMD and ΔTBR; ΔTBR was a sole independent associate of Δ%FMD in hypertensive patients ( r =−0.558; P <0.001). Conclusions— The present study showed that vascular inflammation in the carotid arteries evaluated by [ 18 F]-fluorodeoxyglucose-positron emission tomography/computed tomography was one of the independent correlates of decreased %FMD, thus suggesting the association of vascular inflammation with endothelial dysfunction in humans.

The present study suggests that switching DPP-4 inhibitors to tofogliflozin ameliorates arterial stiffness in T2DM patients partly via improvement of liver function. Baseline serum levels of AGEs may identify patients who improve arterial stiffness more after treatment with tofogliflozin.

Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear. Non-diabetic subjects underwent a physical examination, determination of blood chemistry and anthropometric variables, including AGEs, sRAGE, TMA and TMAO. Multiple regression analyses revealed that HbA1c, uric acid and AGEs were independently associated with log TMA, whereas log AGEs to sRAGE ratio and statin non-use were independently correlated with log TMAO. Our present findings indicated that AGEs to sRAGE ratio was correlated with log TMAO, a marker of cardiometabolic disorders.

The present study suggests that anagliptin may exert a beneficial effect on arterial stiffness in patients with T2DM, which is independent of its blood glucose-lowering property. Anagliptin may ameliorate arterial stiffness partly via reduction of RLP cholesterol and improvement of liver function.

Electrocardiogram (ECG) has been widely used for assessment of right ventricular (RV) hypertrophy (RVH) in patients with pulmonary hypertension (PH). However, it still remains unclear which ECG criteria of RVH are useful to predict for the severity of PH. The aim of our study was to examine the utility of ECG findings of RVH in assessment of PH. A total of 53 patients (42 women, mean age; 57.6 ± 16.4 years) with pre-capillary PH, who were diagnosed by right heart catheterization, underwent blood sampling, ECG, and cardiac magnetic resonance within a week before the right heart catheterization. We assessed the traditional ECG criteria of RVH in PH patients, and compared to age- and gender-matched control subjects without PH confirmed by 2-dimensional echocardiography (n = 42, mean age 55.3 ± 15.9 years). We also analyzed the clinical variables associated with ECG findings in patients with PH. Mean pulmonary arterial pressure (mPAP), cardiac index, and pulmonary vascular resistance (PVR) in PH patients were 35.3 ± 11.9 mmHg, 2.82 (2.09–3.45) L/min/m2, and 576 ± 376 dyne·sec·cm-5, respectively. The prevalence of right axis deviation (43.4%), R:S ratio V1 > 1 (32.1%), and RV1+SV5/6 > 10.5 mm (69.8%) in PH patients was greater than those in control subjects (p < 0.001). In univariate analysis, mPAP, PVR, RV wall thickness, RV mass index, RV volume, and RV ejection fraction (EF) (inversely) were significantly correlated with the amplitude of RV1+SV5/6. Multiple regression analysis revealed that mPAP and RVEF (inversely) were independently associated with the amplitude of RV1+SV5/6 (R2 = 0.282). Also, we performed the survival analysis among pre-capillary PH patients. During a mean follow-up of 3.7 years, patients with ≥ 16.4 mm of RV1+SV5/6 had worse prognosis than those with < 16.4 mm (Log rank p = 0.015). In conclusion, the amplitude of SV1+RV5/6 could be the most useful factor reflected for RV remodeling, hemodynamics and survival in patients with pre-capillary PH.

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In recent years, several treatment options for patients with pre-capillary pulmonary hypertension (PH) have improved the short-term prognosis. However, the long-term survival for pre-capillary PH has not been well investigated. This study sought to investigate the long-term survival for pre-capillary PH in Kurume University Hospital. A total of 144 patients with pre-capillary PH (110 women, mean age; 55.1 ±17.9 years) was enrolled. The maximal duration of follow-up was 15 years with a mean follow-up of 5.77 years. The 15-year survival was 59.1% for pre-capillary PH, 68.5 % for pulmonary arterial hypertension (PAH) and 44.3 % for chronic thromboembolic PH. The 5-year survival was 50.9% for PH due to lung disease (PH-LD) indicating the worst in the pre-capillary PH subgroups. The survival for portopulmonary hypertension was the lowest among PAH groups, and PAH associated with connective-tissue disease and congenital heart disease became to decrease 10 years after diagnosis. Six-minute walk distance and elevated brain natriuretic peptide were significantly associated with survival outcome in pre-capillary PH patients, and that diastolic pulmonary arterial pressure was related with survival for PH-LD. The survivals were different among pre-capillary PH groups in our hospital. Above all, the long-term survival was better than previous reports.