An epidemiological study of Greenlandic Inuit suggested that fish oil, or omega-3 polyunsaturated fatty acids (PUFA), was important in preventing atherosclerotic disease. After this landmark study, many large-scale epidemiological studies and meta-analyses have examined the health benefits of omega-3 PUFA as part of a fatty acid-rich diet to demonstrate its beneficial roles in the prevention of cardiovascular diseases. Recent research has also focused attention on the anti-inflammatory effects of omega-3 PUFA and on specialized pro-resolving mediators. Findings of these studies have led to the development of omega-3 PUFA preparations for the treatment of dyslipidemia, including a highly purified eicosapentaenoic acid (EPA)-ethyl ester product (Epadel^®) in Japan and an EPA/docosahexaenoic acid (DHA) preparation (Lotriga^®) in the United States and Europe. Although various large-scale clinical trials on the cardiovascular preventive effect of omega-3 PUFA were conducted and reported, the results were not always consistent. The issues of not targeting subjects with hypertriglyceridemia and using low dose of omega-3 PUFA have been suggested to contribute to the failure of demonstrating the preventive effect of omega-3 PUFA in these clinical trials. Taking into account the above issues, the REDUCE-IT trial evaluated a highly purified EPA preparation at a high dose of 4 g/day in patients with hypertriglyceridemia and high cardiovascular risk, and demonstrated an extraordinary outcome of 25% relative reduction in cardiovascular events. This article reviews studies on omega-3 fatty acids during the last 50 years, including the progress in elucidating molecular mechanisms and recent large-scale clinical studies.

Aim: To investigate the relationship between perinatal condition around birth and cardiovascular risk in later life.

Methods: Retrospective data were examined from 1241 city dwellers (521 men, 720 women; age 41–69 years) who had undergone medical examination at a single institution including blood tests and physical measurements from 2007 to 2008. The questionnaire was conducted to determine how perinatal factors affect their lives later. We also selected and studied a total of 28 individuals (12 men and 16 women) specifically about the conformity rate of the breastfeeding method between participants' memories and what was written in the maternal and child health handbooks.

Results: The conformity rate of the breastfeeding method between a self-questionnaire and his/her maternal and child health handbook was well correlated (r=0.73; p＜0.025). Among the data in women who were born at home, HbA1C levels (5.36±0.03 vs. 5.25±0.05 mg/dL, p=0.03) and low-density lipoprotein cholesterol (136.0±1.4 vs. 129.3±2.5 mg/dL, p=0.04) were higher than women who were born at the hospital. Women raised by formula showed higher low-density lipoprotein cholesterol levels than women fed breast milk or a mixture of breast milk and formula (150.2±4.8 vs. 138.7±3.7, 142.5±2.6 mg/dL, p=0.04). Fasting blood glucose levels at an adult time in men and women born through breech presentation were higher than those by the cephalic presentation (123.2±7.8 vs. 106.8±1.2 mg/dL, p=0.03).

Conclusion: The study proposed that some perinatal conditions around birth such as delivery place, presenting part, and lactation affected especially Japanese women's cardiovascular risks between ages 41 and 69 years.

Aims: The assessment of bleeding risk in patients with coronary artery disease (CAD) is clinically important. We recently developed the Total Thrombus-Formation Analysis System (T-TAS) for the quantitative analysis of thrombus formation using microchips with thrombogenic surfaces. Here, we assessed the utility of T-TAS parameters in predicting 1-year bleeding events in patients with CAD.

Methods: The study subjects were 561 consecutive patients who underwent coronary angiography (CAG) between August 2013 and September 2016 for suspected CAD. Blood samples collected at the time of CAG were used for T-TAS to compute the area under the curve (AUC) (AR₁₀-AUC₃₀) in the AR chip. Patients were divided into three groups according to AR₁₀-AUC₃₀ (low: ≤ 1603, intermediate, and high: ＞1765, n=187 each). One-year bleeding events were defined by the Platelet Inhibition and Patient Outcomes criteria.

Results: Bleeding occurred in 21 (3.7%) patients and was classified as major (8 [1.4%]) and minor (13 [2.3%]). The AR₁₀-AUC₃₀ levels were significantly lower in the bleeding group than the non-bleeding group (median [interquartile range] 1590 [1442–1734] vs. 1687 [1546–1797], p=0.04). Univariate Cox regression analysis demonstrated that low AR₁₀-AUC₃₀ , high prothrombin time-international normalized ratio levels, and diabetes correlated with bleeding events. Multivariate Cox regression analysis identified low AR₁₀-AUC₃₀ levels as a significant determinant of bleeding events. Kaplan-Meier survival curves showed a higher rate of bleeding events in the low than the high AR₁₀-AUC₃₀ group (p=0.007).

Conclusions: The results highlight the potential usefulness of the AR₁₀-AUC₃₀ levels in the prediction of 1-year bleeding events in patients with CAD treated with various antithrombotic therapies.

Aim: β-actin (ACTB) participates in the vascular remodeling and contributes to the cardiovascular diseases. Herein, we investigated the associations of ACTB with hypertension and stroke.

Methods: Three single-nucleotide polymorphisms in ACTB were selected for genotyping in 2,012 hypertension cases and 2,210 controls. The associations of ACTB with hypertension and stroke were examined in another follow-up study. Logistic and Cox regression were performed in a case-control study and a follow-up study, respectively. Additive scale interaction was examined by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI). The multiplicative interaction hazard ratio was calculated by fitting the Cox regression model. ACTB mRNA in peripheral blood mononuclear cells was measured in ischemic stroke (IS) cases and in controls.

Results: The associations of rs852426 with hypertension and stroke had statistical significance in drinkers but not after Bonferroni correction. An additive interaction of rs852426 and drinking was observed for stroke incidence, the adjusted RERI was −0.907 (p=4.108×10^－4), and the multiplicative interaction was still sound (HR=0.541, p=0.048). Furthermore, the significant interaction was further replicated in a nested case-control study. In the drinking population, the relative expression of ACTB mRNA in IS was lower (0.99±0.26) than that in controls (1.13±0.20), with a p value of 0.026.

Conclusions: ACTB rs852426 was significantly associated with alcohol consumption on stroke risk, and the expression of ACTB mRNA in IS who had a drinking habit was significantly down-regulated. This finding will provide a novel insight into the prevention of stroke.

Aims: To investigate the association of chronic kidney disease (CKD) and intracranial artery stenosis (ICAS), as well as its effects on ICAS distribution in the middle-aged and elderly population.

Methods: Data from the China Hypertension Survey in Beijing was analyzed. Estimated glomerular filtration rate (eGFR) was used to evaluate CKD, and ICAS was assessed by transcranial doppler. Clinical and biochemical variables were compared between the ICAS group and the non-ICAS group, as well as in different vascular distribution groups. Univariable and multivariable logistic regression analyses were introduced to demonstrate the association between CKD and ICAS.

Results: A total of 3678 subjects were included in this study, with a mean age of 62 years old. Of which, 19.2% presented with decreased eGFR (eGFR ＜60 ml/min/1.73 m²) and 17.4% for ICAS. The percentage of anterior circulation ICAS was 3.5 times than that of posterior circulation (10.9% vs. 3.1%). In multivariable regression analysis, eGFR ＜45 ml/min/1.73 m² was independently associated with ICAS after correction for covariates, odds ratio (OR)=1.69, 95% confidence interval (CI) (1.08, 2.65); in particular, this association had a preference for posterior circulation but not anterior circulation ICAS with OR=2.29, 95% CI (1.28, 4.07) and OR=1.44, 95%CI (0.89, 2.33), respectively.

Conclusion: Severe eGFR decline is associated with ICAS in the middle-aged and elderly population, and this correlation is more related to posterior circulation ICAS.

Aim: Inflammation plays a significant role in the pathogenesis of human abdominal aortic aneurysm (AAA). AEBP1 can promote activation of the NF-κB pathway, subsequently affecting the expression of NF-κB target genes, including inflammatory cytokines and matrix metalloproteinases (MMPs). Our objective was to examine the role of AEBP1 in the development of AAA and characterize the underlying mechanism.

Methods: ITRAQ, RT-PCR, western blot, immunohistochemistry, and ELISA were used to compare different experimental groups with the controls and to determine the differentially expressed genes. We generated an AAA model using porcine pancreatic elastase in Sprague–Dawley rats and silenced their AEBP1 in vivo by adenoviruses injected intra-adventitially. We also silenced or overexpressed AEBP1 in human vascular smooth muscle cells in vitro in the presence and in the absence of NF-κB inhibitor BAY 11-7082.

Results: Proteome iTRAQ revealed a high expression of AEBP1 in AAA patients, which was verified by qRT-PCR, western blot, immunohistochemistry, and ELISA. The mean expression level of AEBP1 in AAA patients was higher than that in controls. Along with AEBP1 upregulation, we also verified mis-activation of NF-κB in human AAA samples. The in vivo studies indicated that AEBP1 knockdown suppressed AAA progression. Finally, the in vitro studies illustrated that AEBP1 promotes activation of the NF-κB pathway, subsequently upregulating pro-inflammatory factors and MMPs.

Conclusions: Our results indicate a role of AEBP1 in the pathogenesis of AAA and provide a novel insight into how AEBP1 causes the development of AAA by activating the NF-κB pathway.

An 83-year-old woman with severe aortic stenosis was admitted to our hospital due to heart failure with refractory anemia requiring blood transfusions. She had repetitive bleeding episodes from endoscopically proven angiodysplasia in the stomach. Moreover, she repeatedly underwent endoscopic argon plasma coagulation for hemostasis. Importantly, she had a deficiency of the high-molecular-weight (HMW) multimers of von Willebrand factor (VWF), and she was diagnosed with Heyde's syndrome.

After she underwent transcatheter aortic valve implantation (TAVI), aortic valve area and mean left ventricular aorta pressure gradient improved. Notably, endoscopy showed cessation of bleeding at 10 days after TAVI and the disappearance of angiodysplasia at 4 months after TAVI. Even at 2 years after TAVI, follow-up endoscopy showed remaining free of angiodysplasia in the stomach. She experienced no episodes of anemia since TAVI procedure. Additionally, analysis of HMW multimers demonstrated immediate and lasting recovery after TAVI.

Recovery of HMW multimers of VWF with cessation of gastrointestinal bleeding following aortic valve replacement has been previously reported in a patient diagnosed with Heyde's syndrome. To the best our knowledge, this is the first case to demonstrate that angiodysplasia disappears after TAVI for a long term with endoscopic images in a patient with Heyde's syndrome. Here, we summarized case reports of patients with Heyde's syndrome that required aortic valve intervention. Cessation of gastrointestinal bleeding and anemia after aortic valve intervention for severe aortic stenosis may be attributed not only to recovery of HMW multimers of VWF but also to the disappearance of angiodysplasia.