Pulse wave analysis(PWA) is widely used to investigate systemic arterial stiffness. The augmentation index(AIx), the primary outcome derived from PWA, is influenced by the mean arterial pressure(MAP), age, gender and heart rate(HR). Gender- and age-specific reference values have been devised, and it is recommended that the MAP be used as a statistical covariate. The AIx is also commonly statistically adjusted to a HR of 75 b·min⁻¹; however, this approach may be physiologically and statistically inappropriate. First, there appears to be an important physiological chronic interaction between HR and arterial stiffness. Second, the method used to correct to HR assumes that the relationship with AIx is uniform across populations. A more appropriate practice may be to include HR as an independent predictor or covariate; this approach is particularly recommended for longitudinal studies, in which changes in HR may help to explain changes in arterial stiffness.

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MicroRNAs(miRNAs; miRs) are small, non-protein-coding RNAs that negatively regulate the gene expression. They bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recently, some miRNAs have been shown to be involved in lipid homoeostasis. In particular, miR122 and miR-33 have a significant impact on lipid homeostasis and are potential therapeutic targets for treating lipid disorders and/or atherosclerosis. In this review, we describe the current understanding of the function of miRNAs in lipid homeostasis, with a focus on lipoprotein metabolism.

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Aim: In this study, we investigated the effects of caffeic acid (CAFA), a phenolic acid, on Ca^2＋-antagonistic cyclic nucleotides associated with the phosphorylation of inositol 1,4,5-trisphosphate receptor (IP₃R) and vasodilator-stimulated phosphoprotein (VASP) and the thromboxane A₂ (TXA₂)-associated microsomal cyclooxygenase-1 (COX-1) activity in collagen (10 μg/mL)-stimulated platelet aggregation.
Methods: Washed platelets (10⁸/mL) obtained from Sprague-Dawley rats (6-7 weeks old, male) were preincubated for 3 minutes at 37℃ in the presence of 2 mM exogenous CaCl₂ with or without CAFA or other materials, stimulated with collagen (10 μg/mL) for 5 minutes, then used to determine the levels of intracellular cytosolic Ca^2＋ ([Ca^2＋]_i), TXA₂, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), COX-1 activity, VASP and IP₃R phosphorylation.
Results: CAFA dose-dependently inhibited collagen-induced platelet aggregation and suppressed the production of TXA₂, an aggregation-inducing autacoid associated with the strong inhibition of COX-1 in platelet microsomes exhibiting cytochrome C reductase activity. CAFA dose-dependently inhibited collagen-elevated [Ca^2＋]_i mobilization, which was increased by a cAMP-dependent protein kinase (A-kinase) inhibitor, Rp-8-Br-cAMPS, but not a cGMP-dependent protein kinase (G-kinase) inhibitor, Rp-8-Br-cGMPS. In addition, CAFA significantly increased the formation of cAMP and cGMP, intracellular Ca^2＋-antagonists that function as aggregation-inhibiting molecules. CAFA increased IP3R (320 kDa) phosphorylation, indicating the inhibition of IP₃-mediated Ca^2＋ release from internal stores (i.e. the dense tubular system) via the IP₃R on collagen-activated platelets. Furthermore, CAFA-induced IP₃R phosphorylation was strongly inhibited by an A-kinase inhibitor, Rp-8-Br-cAMPS, but only mildly inhibited by a G-kinase inhibitor, Rp-8-Br-cGMPS. These results suggest that the inhibition of [Ca^2＋]i mobilization by CAFA is resulted from the cAMP/A-kinase-dependent phosphorylation of IP₃R. CAFA elevated the phosphorylation of VASP-Ser¹⁵⁷, an A-kinase substrate, but not the phosphorylation of VASP-Ser²³⁹, a G-kinase substrate. We demonstrate that CAFA increases cAMP and subsequently phosphorylates both IP₃R and VASP-Ser¹⁵⁷ through A-kinase activation to inhibit [Ca^2＋]_i mobilization and TXA₂ production via the inhibition of the COX-1 activity.
Conclusions: These results strongly indicate that CAFA is a potent beneficial compound that elevates the level of cAMP-dependent protein phosphorylation in collagen-platelet interactions, which may result in the prevention of platelet aggregation-mediated thrombotic diseases.

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Aim: The aim of the current study was to develop a predictive model of insulin resistance using general health checkup data in Japanese employees with one or more metabolic risk factors.
Methods: We used a database of 846 Japanese employees with one or more metabolic risk factors who underwent general health checkup and a 75-g oral glucose tolerance test (OGTT). Logistic regression models were developed to predict existing insulin resistance evaluated using the Matsuda index. The predictive performance of these models was assessed using the C statistic.
Results: The C statistics of body mass index (BMI), waist circumference and their combined use were 0.743, 0.732 and 0.749, with no significant differences. The multivariate backward selection model, in which BMI, the levels of plasma glucose, high-density lipoprotein (HDL) cholesterol, log-transformed triglycerides and log-transformed alanine aminotransferase and hypertension under treatment remained, had a C statistic of 0.816, with a significant difference compared to the combined use of BMI and waist circumference (p＜0.01). The C statistic was not significantly reduced when the levels of log-transformed triglycerides and log-transformed alanine aminotransferase and hypertension under treatment were simultaneously excluded from the multivariate model (p=0.14). On the other hand, further exclusion of any of the remaining three variables significantly reduced the C statistic (all p＜0.01).
Conclusions: When predicting the presence of insulin resistance using general health checkup data in Japanese employees with metabolic risk factors, it is important to take into consideration the BMI and fasting plasma glucose and HDL cholesterol levels.

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Aims: The purpose of this study was to determine the cross-sectional relationship between the cognitive function and cardio-ankle vascular index(CAVI) in Japanese community-dwelling elderly subjects.
Methods: A total of 179 Japanese community-dwelling elderly subjects were recruited for this study. The age, height, weight, gender and past medical history(cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia) of each participant was recorded. In addition, the degree of arterial stiffness was determined according to the CAVI, while the cognitive function was assessed using the Mini-Mental State Examination(MMSE). After dividing the cohort into two groups according to the MMSE score(≤26, ＞26), we used a multiple regression analysis to assign the level of the cognitive function as a dependent variable.
Results: The data were statistically analyzed for the 174 participants(84 men and 90 women) who completed the data collection process without omissions. A multivariate logistic regression analysis showed that a higher weight(Odds Ratio [OR]: 1.05, 95% Confidence Interval [95% CI]: 1.00- 1.11, p=0.03), male gender(OR: 3.13, 95% CI: 1.05-9.34, p=0.04) and lower CAVI(OR: 0.68, 95% CI: 0.48-0.96, p=0.03) were significantly correlated with a higher MMSE score. We also found significant correlations between the MMSE and weight(OR: 1.11, 95% CI: 1.03-1.19, p=0.01) and CAVI(OR: 0.57, 95% CI: 0.33-0.98, p=0.04) in elderly men only using a gender-specific analysis.
Conclusions: We found that the elderly subjects with a high CAVI exhibited a worse cognitive function even after adjusting for age, height, weight and gender. This finding therefore indicates the usefulness of the CAVI in the early detection of dementia.

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Aims: Dolichocarotids(DCs) represent a rare(2-6%) carotid imaging finding in the general population that may be free of clinical significance or be associated with cerebrovascular events. Their detection is traditionally assigned to carotid echo-color Doppler(ECD) and selective angiography(the standard method). The primary aim of this study was to estimate the sensitivity, specificity and accuracy of ECD in detecting DCs. Moreover, we monitored the DC curvature angle and the incidence of TIA, ischemic stroke, myocardial infarction and cardiovascular death over a five-year followup period.
Methods: A total of 112 consecutive patients with DCs(80 men, mean age: 61±7 years) were recruited for carotid ECD and carotid angiography due to the persistence of neurological symptoms not well explained on ultrasound evaluations, according to the current guidelines.
Results: ECD proved to have 100% sensitivity in detecting tortuosity and coiling and 96% sensitivity in detecting kinking, with an overall accuracy ranging from 92% to 100%. The specificity was 75% for tortuosity, 91% for kinking and 100% for coiling. During the five-year follow-up period, there was a statistically significant increase in tortuosity(61±11° at baseline versus 81±11° after five years, p＜0.001) and the kinking curvature angle(97±3° at baseline versus 100±3° at five years, p＜0.001), whilst no differences were observed with respect to coiling(136±10° at baseline versus 138±11° at five years, p=ns). Moreover, kinking was found to be more frequently statistically associated with cardiovascular death than tortuosity(p=0.005).
Conclusions: DCs predispose patients to potentially disabling and fatal events. ECD plays a primary role in the detection of DCs and therefore should be considered to be a secure and reproducible technique.

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Aim: Carriers of the reduced-function CYP2C19 allele receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel exhibit diminished platelet inhibition and an increased risk of events. The purpose of this study was to investigate the effects of CYP2C19 gene variants on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing elective percutaneous coronary intervention (PCI).
Methods: This prospective, observational, multicenter study enrolled 104 consecutive Japanese patients undergoing elective PCI. We examined the CYP2C19 genotype, platelet function tests, the levels of coagulation and inflammatory biomarkers and the serum levels of high-sensitivity troponin T (hs-TnT) before, immediately after and one, two and 28 days after PCI.
Results: A total of 68 (65%) of the 104 enrolled patients were carriers of the CYP2C19 reducedfunction allele. On-clopidogrel platelet aggregation (PA), measured using light transmittance aggregometry and the VerifyNow^® P2Y12 system, and the platelet reactivity index (PRI) were significantly higher at all time points in the carriers than in the noncarriers (p＜0.05), whereas there were no differences in the levels of the coagulation and inflammatory biomarkers or serum hs-TnT. Simple and multiple logistic regression analyses identified on-clopidogrel PA and PRI as being significant predictors of carriers of the CYP2C19 reduced-function allele.
Conclusions: The present study suggests that platelet function tests, but not coagulation, inflammatory or cardiac biomarkers, are useful for identifying carriers of CYP2C19 reduced-function gene variants and monitoring the efficacy of DAPT in patients undergoing elective PCI.

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