Early identification of high-risk or vulnerable atherosclerotic plaques prone to rupture and performing preemptive therapy prior to catastrophic cardiovascular events are optimal goals of plaque imaging. Despite the advances in imaging modalities to identify vulnerable characteristics, the predictive value of the imaging techniques in the clinical setting is still developing. In this regard, reliable and high-sensitive imaging modalities identifying vulnerable plaque characters that may lead to future cardiovascular events will be useful. In this review article, we describe a current non-invasive plaque imaging technique to identify high-risk coronary plaque features.

Plaque calcification develops by the inflammation-dependent mechanisms involved in progression and regression of atherosclerosis. Macrophages can undergo two distinct polarization states, that is, pro-inflammatory M1 phenotype in progression and anti-inflammatory M2 phenotype in regression. In plaque progression, predominant M1 macrophages promote the initial calcium deposition within the necrotic core of the lesions, called as microcalcification, through not only vesicle-mediated mineralization as the result of apoptosis of macrophages and vascular smooth muscle cells (VSMCs), but also VSMC differentiation into early phase osteoblasts. On the other hand, in plaque regression M2 macrophages are engaged in the healing response to plaque inflammation. In association with the resolution of chronic inflammation, M2 macrophages may facilitate macroscopic calcium deposition, called as macrocalcification, through induction of osteoblastic differentiation and maturation of VSMCs. Oncostatin M, which has been shown to promote osteoblast differentiation in bone, may play a pivotal role in the development of plaque calcification. Clinically, two types of plaque calcification have distinct implications. Macrocalcification leads to plaque stability, while microcalcification is more likely to be associated with plaque rupture. Statin therapy, which reduces cardiovascular mortality, has been shown to exert its dual actions on plaque morphology, that is, regression of atheroma and increment of macroscopic calcium deposits. Statins may facilitate the healing process against plaque inflammation by enhancing M2 polarization of macrophages. Vascular calcification has pleiotropic properties as pro-inflammatory “microcalcification” and anti-inflammatory “macrocalcification”. The molecular mechanisms of this process in relation with plaque progression as well as plaque regression should be intensively elucidated.

Aim: All health insurers in Japan are mandated to provide Specific Health Checkups and Specific Health Guidance (SHG) focusing on metabolic syndrome (MetS) in middle-aged adults, beginning in 2008; intensive HG for individuals who have abdominal obesity and two or more additional MetS risk factors, and motivational HG for individuals with one risk factor. The aim of this study is to describe medium-term changes in health indexes for intensive and motivational HG groups using the National Database.

Methods: We compared changes of risk factors and initiation of pharmacological therapy over 3 yr between participants (n=31,790) and nonparticipants (n=189,726) who were eligible for SHG in 2008.

Results: Body weight reduction in intensive HG was 1.98 kg (participants) vs 0.42 kg (nonparticipants) in men (p＜0.01) and 2.25 vs 0.68 kg in women (p＜0.01) after 1 yr. In motivational HG, the respective reduction was 1.40 vs 0.30 kg in men (p＜0.01) and 1.53 vs 0.42 kg in women (p＜0.01). Waist circumference reduction was also greatest among participants in intensive HG (2.34 cm in men and 2.98 cm in women). These reductions were fairly unchanged over 3 yr and accompanied greater improvements in MetS risk factors in participants. We also detected significantly smaller percentages of SHG participants who initiated pharmacological therapy compared with nonparticipants.

Conclusion: Participants in SHG showed greater improvements in MetS profiles with proportionally smaller pharmacological treatment initiations than did nonparticipants for 3 yr. Although selection bias may be present, this study suggests SHG would be a feasible strategy to prevent MetS and its sequelae.

Aim: We investigated whether 2 types of personalized health guidance (repeated and single counseling) in the Japanese nationwide cardiovascular prevention system promoted smoking cessation among smokers.

Methods: The study included 47,745 Japanese smokers aged 40 to 74 years classified into 2 personalized health guidance schemes. After a 1-year follow-up, we compared the rates of smoking cessation between individuals who had received counseling (“supported”) and those who had not received counseling (“unsupported”). Using propensity score matching analysis, we estimated the average treatment effect (ATE) of each approach on smoking cessation after balancing out the characteristics between the supported and unsupported groups. The propensity score regression model included age, medical insurance type, weight gain since the age of 20 years, exercise, eating habits, alcohol intake, quality of sleep, readiness to modify lifestyle, willingness to receive support, and body mass index.

Results: In the repeated counseling scheme, the age-adjusted rates of smoking cessation in the supported and unsupported groups were 8.8% and 6.3% for males, and 9.8% and 9.1% for females respectively. In the single counseling scheme, the corresponding rates were 8.4% and 7.3% for supported and unsupported males, and 11.0% and 11.7% for supported and unsupported females respectively. The ATE of repeated counseling was ＋2.64% (95% confidence interval: ＋1.51% to ＋3.77%) for males and ＋3.11% (－1.85% to ＋8.07%) for females. The ATE of single counseling was ＋0.61% (－1.17% to ＋2.38%) for males and －1.06% (－5.96% to ＋3.85%) for females.

Conclusions: In the Japanese cardiovascular prevention system, repeated counseling may promote smoking cessation among male smokers.

Aim: The present large-scale Japanese population study was performed to evaluate the relation between the serum thyroid stimulating hormone (TSH) level and renal function.

Methods: Out of 1,374 residents who participated in a free public physical examination between 2010 and 2011, we evaluated the data of 888 participants for whom the serum TSH level and estimated glomerular filtration rate (eGFR) were successfully measured. The participants were categorized into three groups based on TSH levels (normal TSH, ≤2.4; high-normal TSH, 2.5–4.4; and subclinical hypothyroid, ≥4.5 μIU/mL). Multiple linear regression analysis adjusted for cardiovascular risk factors was performed to determine the relationship between serum TSH level and renal function.

Results: The mean±SD TSH level was 2.0±1.4 μIU/mL, and 75.9% (n=674) of the participants had normal, 17.9% (n=159) had high-normal, and 6.2% (n=55) had subclinical hypothyroid TSH levels. The mean eGFR significantly decreased with increased TSH levels (normal TSH, 79.3±14.1; high-normal TSH, 77.4±13.0; and subclinical hypothyroid, 72.3±12.2 mL/min/1.73 m²: P for trend ＜0.01). Multiple linear regression analysis extracted log-transformed TSH level as an independent factor correlated with eGFR in the high-normal TSH group (beta=−0.18, P=0.02).

Conclusions: Our findings demonstrated a significant correlation between serum TSH levels and eGFR in high-normal TSH participants. In healthy individuals, high-normal TSH levels indicate increased the risk of chronic kidney disease.

Aim: We investigated 2-year clinical outcomes after implantaton of Epic^TM self-expanding nitinol stents for patients with peripheral artery disease (PAD) due to the aortoiliac occlusive disease (AIOD).

Methods: This study was a multicenter and retrospective study. From February 2013 through October 2014, 292 lesions (chronic total occlusion, 21%; TASC Ⅱ C/D, 35%) in 217 consecutive patients (74±8 years; male, 81%; diabetes mellitus, 47%; dialysis, 21%; critical limb ischemia, 29%) who had undergone endovascular therapy (EVT) with Epic^TM self-expanding nitinol stents for PAD with AIOD were analyzed. The primary endpoints were 2-year primary patency and target lesion revascularization (TLR)-free rate. The primary patency and freedom from TLR were determined by Kaplan-Meier analysis. Additionally, predictors for loss of patency were estimated by Cox proportional hazard model.

Results: The mean follow-up duration was 19.1±8.5 months. Primary patency was 87.3% at 2 years. Freedom from TLR rate was 94.1% at 2 years. Multivariate analysis revealed that the presence of diabetes mellitus was associated with a loss of patency.

Conclusion: The Epic^TM self-expanding nitinol stent was demonstrated to be safe and effectivene for AIOD when tested for two years in patients with PAD.

Aims: Alpha-2-macroglobulin (_α2MG) is thought to be associated with inflammatory reactions and procoagulant properties that might cause ischemic stroke. Endothelial dysfunction plays an important role in atherosclerosis development and in the occurrence of cardiovascular events. In this study, we investigated whether serum _α2MG levels, endothelial function, and endothelial progenitor cell (EPC) number were associated in patients with chronic stroke or cardiovascular risk factors.

Methods: Patients with a history of stroke or any established cardiovascular risk factors were enrolled in this study (n=102; 69 men, 70.1±9.2 years). Endothelial function was assessed by flow-mediated dilation (FMD). EPC numbers (CD34＋/CD133＋) were measured using flow cytometry (n=91). Serum _α2MG levels were measured by nephelometry.

Results: Patients in the highest tertile of serum _α2MG levels were older (P=0.019) and more frequently exhibited dyslipidemia (P=0.021). Univariate-regression analysis revealed that increased _α2MG levels were negatively associated with FMD values (r=−0.25; P=0.010), whereas increased EPC numbers were positively associated (r=0.21; P=0.044). Multivariate-regression analysis adjusted for male gender, hypertension, and severe white-matter lesions showed that serum _α2MG levels were independently associated with FMD values (standardized partial regression coefficient [β] −0.185; P=0.033), although not significantly associated with EPC numbers.

Conclusion: Serum _α2MG levels might reflect endothelial dysfunction evaluated by FMD in patients with chronic stroke or cardiovascular risk factors.

Aims: There may be ethnic differences in carotid atherosclerosis and its contributing factors between Asian and other populations. The purpose of this study was to examine intima-media complex thickness (IMT) of the carotid artery and associated clinical factors in Japanese stroke patients with hyperlipidemia from a cohort of the Japan Statin Treatment Against Recurrent Stroke Echo Study.

Methods: Patients with hyperlipidemia, not on statins, who developed noncardioembolic ischemic stroke were included in this study. Mean IMT and maximum IMT of the distal wall of the common carotid artery were centrally measured using carotid ultrasonography. Significant factors related to mean IMT and maximum IMT were examined using multivariable analysis.

Results: In 793 studied patients, mean IMT was 0.89±0.15 mm and maximum IMT was 1.19±0.32 mm.Age (per 10 years, parameter estimate=0.044, p＜0.001), smoking (0.022, p=0.004), category of blood pressure (0.022, p=0.006), HDL cholesterol (per 10 mg/dl, －0.009, p=0.008), and diabetes mellitus (0.033, p=0.010) were independently associated with mean IMT. Age (per 10 years, 0.076, p＜0.001), smoking (0.053, p=0.001), HDL cholesterol (－0.016, p=0.036), and diabetes mellitus (0.084, p=0.002) were independently associated with maximum IMT.

Conclusion: Baseline mean and maximum values of carotid IMT in Japanese noncardioembolic stroke patients with hyperlipidemia were 0.89±0.15 mm and 1.19±0.32 mm, respectively, which were similar to those previously reported from Western countries. Age, smoking, hypertension, HDL cholesterol, and diabetes mellitus were associated with mean IMT, and those, except for hypertension, were associated with maximum IMT.