Mitsukoshi Health and Welfare Foundation

Although heart failure (HF) with preserved ejection fraction (HFpEF) is more common in postmenopausal women than in men, the effect of sex hormones on cardiac diastolic function remains unclear. We examined the effect of gonadectomy with or without the angiotensin receptor blocker olmesartan (Olm) in an isoproterenol (ISO) -induced mouse model of left ventricular hypertrophy (LVH) and cardiac diastolic dysfunction. ISO or ISO with Olm were administered for 28 days in sham-operated male and female, castrated (CAS), and ovariectomized (OVX) mice. LV ejection fraction (EF) and E/A ratio were analyzed by echocardiography, and the LV and lung weight corrected by tibial length were used as indices of LVH and lung congestion, respectively. On echocardiography, systolic function did not differ between the four groups. LV/tibial length (TL) and Lung/TL significantly increased in all groups. The LV/TL ratio was lower in castrated-ISO vs. Male-Sham-ISO but did not differ between Female-Sham-ISO and OVX-ISO. However, the Lung/TL ratio of OVX-ISO was greater than that of Female-Sham-ISO. Olm prevented LV hypertrophy in all groups. The decrease in E/A and increase in lung weight were improved by Olm in Male-Sham and OVX-ISO but not in the other groups. These sex differences suggest that sex hormones play a pivotal role in modulating cardiac hypertrophy and diastolic dysfunction induced by chronic β-adrenoceptor stimulation, and thus affect the therapeutic potential of angiotensin receptor blockade.

Recent studies have shown that healed plaque at the culprit lesion detected by optical coherence tomography (OCT) is a sign of pan-vascular vulnerability and advanced atherosclerosis. However, the clinical significance of healed plaque is unknown. A total of 265 patients who had OCT imaging of a culprit vessel and 2-year clinical follow-up data were included. Patients were stratified based on the presence or absence of a layered plaque phenotype, defined as layers of different optical density by OCT at either culprit or non-culprit lesions. The association between layered plaque and major adverse cardiac events (MACE), defined as cardiac death, acute coronary syndromes (ACS), or revascularization, was studied. Among 265 patients, 96 (36.2%) had the layered plaque phenotype. Layered plaque was more frequently observed in stable angina pectoris patients than in ACS patients (57.8%vs. 25.1%, p < 0.001). The average clinical follow-up period was 672 ± 172days. Cumulative MACE was significantly higher in patients with layered plaque (p = 0.041), which was primarily driven by the high revascularization rate at 2years (p = 0.002). Multivariate regression analysis showed that presence of layered plaque and low-density lipoprotein cholesterol levels were independently associated with an increased risk of revascularization (p = 0.026, p = 0.008, respectively). Patients with healed plaque in the culprit vessel had a higher incidence of revascularization, as compared to those without healed plaque, at 2years.

Background: Angioscopy was performed in a group of patients in the PRASugrel For Japanese PatIenTs with Coronary Artery Disease Undergoing Elective PCI (PRASFIT-Elective) study to determine the incidence and clinical features of stent thrombosis. Stent thrombosis is an infrequent, but potentially severe event that may require revascularization or lead to other clinically significant events. Its incidence and clinical features in Japanese patients undergoing elective percutaneous coronary intervention (PCI) are poorly understood, especially in those receiving dual antiplatelet therapy with prasugrel or clopidogrel in combination with aspirin.

肥満は心血管イベントの重要なリスク因子であるが、非肥満者でも他のリスク因子を持つとリスク因子を持たない例に比べ心血管イベントが2倍以上発症することが第5回特定健康診査・特定保健指導の在り方に関する検討会で報告され、非肥満者でも生活習慣病に対する取組を積極的に行うことが提唱された。そこで心筋梗塞や脳卒中を発症した人の健康診断結果を調査し、心・脳血管イベントは非肥満者でも発症するか、また、発症年齢についても調査を行った。A社（2015年の健康診断受診者8,813名 男性7,803、女性1,010名 平均年齢40.2歳）において2015年4月1日から2016年6月30日までの1年半の間に発症した心筋梗塞、脳卒中（脳出血、脳梗塞、くも膜下出血）例の健診結果を調査した。心・脳血管イベントは17例発症した。全例男性で平均年齢は49歳であった。内訳は心筋梗塞が8例、脳卒中が9例（脳梗塞4例、くも膜下出血3例、脳出血2例）であった。心筋梗塞、脳卒中は約半数が40歳代で発症していた。特に心筋梗塞例の約3分の2が40歳代で発症していた。心・脳血管イベント発症例でのメタボリックシンドロームの合併は半数（47％）に過ぎなかった。BMI25以上を肥満と定義すると、肥満からの発症は17例中9例（53％）のみで、脳卒中例の多く（67％）が非肥満から発症していた。心・脳血管イベントは非肥満者から約半数発症するので、リスク因子を抱える非肥満者へも生活習慣病予防に関する取り組みを積極的に行っていく必要がある。心・脳血管イベントの半数が40歳代で発症しているので、特定健診の目的が症状の早期発見・早期対応ではなく、症状を来す前に指導を行い、疾患の発症を予防するための取り組みなら、症状を起こす前の30歳代からの特定健診が望まれる。

AimsThe effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events.Methods and resultsWe searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84–0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85–0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80–1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68–1.11) or not (RR 0.91, 95% CI 0.84–0.98).ConclusionIn primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not.

Chronic inflammation of the native vessel wall with infiltration of lipid-laden foamy macrophages through impaired endothelium results in atherosclerosis. Percutaneous coronary intervention, including metallic stent implantation, is now widely utilized for the treatment of atherosclerotic lesions of the coronary artery. Bare-metal stents and the subsequently developed drug-eluting stents seal the atherosclerosis and resolve lumen stenosis or obstruction of the epicardial coronary artery and myocardial ischemia. After stent implantation, neointima proliferates within the stented segment. Chronic inflammation caused by a foreign body reaction to the implanted stent and subsequent neovascularization, which is characterized by the continuous recruitment of macrophages into the vessel, result in the transformation of the usual neointima into an atheromatous neointima. Neointima with an atherosclerotic appearance, such as that caused by thin-cap fibroatheromas, is now recognized as neoatherosclerosis, which can sometimes cause in-stent restenosis and acute thrombotic occlusion originating from the stent segment following disruption of the atheroma. Neoatherosclerosis is emerging as a new coronary stent-associated problem that has not yet been resolved. In this review article, we will discuss possible mechanisms, clinical challenges, and the future outlook of neoatherosclerosis.

The composition of plaque and thrombus can be determined from their appearance. Plaque is classified into yellow and white according to color and smooth or complex according to shape. Complex plaque is subdivided to three categories: ulceration (erosion), intimal flap, and intimal cleft. Yellow plaque seems to have thin fibrous cap or superficial or diffuse lipid deposition with or without lipid core. Tiny calcium particle, macrophage foam cells, or degenerated collagen fiber may glisten yellow. White plaque is histologically composed of dense collagen fiber (fibrous) or thick fibrous or calcified cap covered with lipid and macrophage foam cell-free endothelia with lipid pool below. Yellow plaque is likely to be vulnerable, whereas white plaque seems to be stable.

Increased mean corpuscular volume (MCV) is common in alcohol abusers and alcoholics. MCV is higher in Japanese heavy drinkers with inactive aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/2*2 than among those with active ALDH2 encoded by ALDH2*1/2*1. Inactive ALDH2 dramatically increases blood acetaldehyde levels after alcohol intake. Because moderate and heavy drinkers with ALDH2*1/2*2 have very high risks for esophageal cancer, MCV might serve as an indicator of these high-risk drinkers. In this investigation of the association of red cell values with the ALDH2 genotype and possible confounding factors, the drinking, smoking, and dietary habits reported on a structured questionnaire by 163 Japanese working men were subjected to multivariate analyses. Aging, lower body mass index (BMI), more alcohol consumption, and more smoking were positively associated with increased MCV. Among moderate to heavy drinkers (>or=9 units/week; 1 unit = 22 g of ethanol), both MCV and mean corpuscular hemoglobin were higher and the red cell count was lower in those with ADLH2*1/2*2 than in those with ALDH2*1/2*1. Multiple linear regression analysis after adjustment for age, BMI, and smoking revealed that a positive relationship between the amount of drinking and MCV but inverse relationships for drinking and red cell count, as well as hemoglobin and hematocrit values, were significantly stronger for men with ALDH2*1/2*2 than for those with ALDH2*1/2*1, demonstrating a gene-environment interaction. Drinking accounted for 19.9% of interindividual MCV variance among men with ALDH2*1/*2*2 but for only 1.3% of variance among those with ALDH2*1/2*1. Age, BMI, drinking, and smoking accounted for 52.1 and 34.7% of the variation among those with ALDH2*1/2*2 and ALDH2*1/2*1, respectively. Macrocytosis (MCV >or=100.0 fl) was observed in 18 subjects (11.0%), and use of macrocytosis as a biomarker of moderate to heavy drinkers with ALDH2*1/2*2 had a sensitivity of 54.5% (6 of 11) and a specificity of 92.1% (140 of 152). Alcohol-related red cell value changes associated with inactive ALDH2 in Japanese men suggest the importance of acetaldehyde's role in increasing MCV and the potential for using MCV as a marker for high-risk drinkers for esophageal cancer.

Abundant clinical trial evidence supports the importance of LDL cholesterol-lowering in decreasing coronary artery disease (CAD) risk. Even in trials of statin therapy in which substantial reductions of LDL have been obtained, statin decrease by 24-37%, but do not entirely eliminate events. This is suggesting that other lipid parameters such as HDL, triglyceride, Lp(a), LDL particle size and susceptibility of LDL to oxidation should be considered. Furthermore, fibrinolytic activity, hyperinsulinemia, hyperhomocysteinemia and alcohol consumption should be also included as parameters to obtain significant benefit.