As a result of an epidemiological transition from communicable to non-communicable diseases for last few decades, cardiovascular diseases (CVD) are being considered as an important cause of mortality and morbidity in many developing countries including Bangladesh. Performing an extensive literature search, we compiled, summarized, and categorized the existing information about CVD mortality and morbidity among different clusters of Bangladeshi population. The present review reports that the burden of CVD in terms of mortality and morbidity is on the rise in Bangladesh. Despite a few non-communicable disease prevention and control programs currently running in Bangladesh, there is an urgent need for well-coordinated national intervention strategies and public health actions to minimize the CVD burden in Bangladesh. As the main challenge for CVD control in a developing country is unavailability of adequate epidemiological data related to various CVD events, the present review attempted to accumulate such data in the current context of Bangladesh. This may be of interest to all stakeholder groups working for CVD prevention and control across the country and globe.
Long noncoding RNAs (lncRNAs) were a group of non-protein-coding RNAs ＞200 nucleotides and participated in biological processes and pathophysiological conditions in vivo or in vitro. Recently, more and more lncRNAs interfering with the progress of atherosclerosis were identified and characterized in the atherogenic cells such as vascular smooth muscle cells (VSMCs), endothelial cells (ECs), and monocytes/macrophages showing that lncRNAs play an important role in the occurrence of atherosclerosis. In this review, we summarized and highlighted the lncRNAs that play a role in the process of atherosclerosis. This study may provide helpful insights regarding further study of lncRNAs associated with atherosclerosis.
Clinical trials and epidemiological studies have revealed a negative correlation between serum high-density lipoprotein (HDL) cholesterol levels and the risk of cardiovascular events. Currently, statin treatment is the standard therapy for cardiovascular diseases, reducing plasma low-density lipoprotein (LDL) cholesterol levels. However, more than half of the patients have not been able to receive the beneficial effects of this treatment. The reverse cholesterol transport pathway has several potential anti-atherogenic properties. An important approach to HDL-targeted therapy is the optimization of HDL cholesterol levels and function in the blood to enhance the removal of circulating cholesterol and to prevent or mitigate inflammation that causes atherosclerosis. Cholesteryl ester transfer protein inhibitors increase HDL cholesterol levels in humans, but whether they reduce the risk of atherosclerotic diseases is unknown. HDL therapies using HDL mimetics, including reconstituted HDL, apolipoprotein (Apo) A-IMilano, ApoA-I mimetic peptides, or full-length ApoA-I, are highly effective in animal models. In particular, the Fukuoka University ApoA-I-mimetic peptide (FAMP) effectively removes cholesterol via the ABCA1 transporter and acts as an anti-atherosclerotic agent by enhancing the biological functions of HDL without elevating HDL cholesterol levels. Our literature review suggests that HDL mimetics have significant atheroprotective potential and are a therapeutic tool for atherosclerotic diseases.
Aim: Regular exercise habits are well-known to exert a favorable effect on the metabolic syndrome, which may cause proteinuria and chronic kidney disease (CKD). However, it remains unknown if exercise exerts a favorable effect on proteinuria and kidney dysfunction. The aim of this study was to reveal the association between exercise and the prevalence of proteinuria and kidney dysfunction and the attenuation by obesity. Methods: This study was a cross-sectional cohort study that included 292,013 participants who underwent the Specific Health Check and Guidance in Japan. The exercise score (range 0-3) was based on the number of positive answers to three questions regarding exercise habits. The outcome was defined as urinary protein detected by a dipstick test and kidney dysfunction [estimated glomerular filtration rate (GFR) less than 45 ml/min/1.73 m2]. Results: The exercise score was significantly associated with the prevalence of proteinuria in both males [vs. exercise score 0; exercise score 1, multivariate-adjusted odds ratio 0.86 (95% confidence interval 0.81-0.92), P＜0.001; exercise score 2, 0.84 (0.79-0.90), P＜0.001; exercise score 3, 0.77 (0.72-0.82), P＜0.001] and females (same as in males). After the male subjects were divided into quintiles according to body mass index (BMI) in more than three groups (22.9＜BMI＜24.1), there was no significant association between the exercise score and the prevalence of proteinuria. In females, a higher exercise score was associated with a lower prevalence of proteinuria, regardless of BMI. The association between the exercise score and kidney dysfunction was as similar as that between the exercise score and proteinuria, except the attenuation of BMI. Conclusion: Exercise may associate with a lower prevalence of proteinuria and kidney dysfunction, and a high BMI may attenuate this association between exercise and proteinuria in male subjects.
Aim: Current Japanese guidelines state the target level of low-density lipoprotein cholesterol (LDL-C) of ＜100mg/dL for secondary prevention of coronary artery disease (CAD). However, this level was set considering the results of trials mainly conducted in Western countries. In addition, the effect of achieving target LDL-C on secondary prevention is unknown. Methods: We examined the effects of achieving target LDL-C on clinical outcomes. Patients who underwent percutaneous coronary intervention at Juntendo University Hospital (Tokyo, Japan) from 2004 to 2010 and received follow-up coronary angiography (CAG) were analyzed. The study population was divided into two groups based on the follow-up LDL-C. The incidence of major adverse cardiovascular events within 3 years after the follow-up CAG was examined. Results: A total of 1321 consecutive patients were enrolled. Sixty-three percent of the patients achieved the target LDL-C. The rate of 3-year events was lower in the group that achieved the target LDL-C (achieved group). The adjusted relative risk reduction in the achieved group was 26% (p=0.02). In the sub-analysis among the four groups stratified by baseline LDL-C of 140 and follow-up LDL-C of 100, the adjusted hazard ratio for 3-year events was 1.84 (95% confidence interval; 1.10-3.24)in Group 3 (baseline ＜140, follow-up ≥100) and 2.05 (1.18-3.74) Group 4 (baseline ≥140, follow-up ≥100) [Group 2 (baseline ≥140, follow-up ＜100) as reference]. Conclusions: Our data suggested that follow-up LDL-C ＜100mg/dL was appropriate for secondary prevention of CAD in Japanese population.
Aim: The Japan Atherosclerosis Society Guidelines for the Diagnosis and Prevention of Atherosclerotic Cardiovascular Diseases 2012 (JAS Guidelines 2012) indicate that the management target for serum non-high-density lipoprotein cholesterol (non-HDLC) level is 30 mg/dL higher than that for low-density lipoprotein cholesterol (LDLC) level. However, it remains unclear whether this value is applicable to subjects at a low risk of cardiovascular disease. This study aimed to propose the optimal management target for serum non-HDLC level in low-risk Japanese subjects. Methods: Among 20,909 subjects who underwent annual medical checkup at a Japanese company in 2008, we analyzed the data of 17,023 subjects (14,352 men, mean age 37.8±8.6 years) in risk category I according to the JAS Guidelines 2012. The correlation between LDLC and non-HDLC levels was examined. Results: A strong correlation was found between LDLC and non-HDLC levels (r=0.95, p＜0.001). The following regression equation for calculation of non-HDLC was obtained from linear regression analysis: non-HDLC (mg/dL)=1.09×LDLC (mg/dL)＋7.79. According to this equation, the optimal management target for non-HDLC level corresponding to that for LDLC level (160 mg/dL) was 180 mg/dL. A multiple logistic regression analysis revealed that age, obesity, habitual alcohol intake, and current smoking were significantly associated with non-HDLC ≥180 mg/dL. Conclusions: The management target for non-HDLC level is recommended to be set at 20 mg/dL higher than that for the LDLC level (i.e., 180 mg/dL) in low-risk Japanese subjects.
Aim: We report the study of a familial rare disease with recurrent venous thromboembolic events that remained undiagnosed for many years using standard coagulation and hemostasis techniques. Methods: Exome sequencing was performed in three familial cases with venous thromboembolic disease and one familial control using NimbleGen exome array. Clot lysis experiments were performed to analyze the reasons of the altered fibrinolytic activity caused by the mutation found. Results: We found a mutation that consists of a R458C substitution on the fibrinogen alpha chain (FGA) gene confirmed in 13 new familial subjects that causes a rare subtype of dysfibrinogenemia characterized by venous thromboembolic events. The mutation was already reported to be associated with a fibrinogen variant called fibrinogen Bordeaux. Clot-lysis experiments showed a decreased and slower fibrinolytic activity in carriers of this mutation as compared to normal subjects, thus demonstrating an impaired fibrinolysis of fibrinogen Bordeaux. Conclusions: The exome sequencing and clot-lysis experiments might be powerful tools to diagnose idiopathic thrombophilias after an unsuccessful set of biochemical laboratory tests. Fibrinogen Bordeaux is associated with impaired fibrinolysis in this family with idiopathic thrombophilia.
Aim: The main pathophysiology of abdominal aortic aneurysm (AAA) considerably overlaps with that of atherosclerosis. We reported that incretins [glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP)] or a dipeptidyl peptidase-4 inhibitor (DPP-4I) suppressed atherosclerosis in apolipoprotein E-null (Apoe－/－) mice. Here we investigated the effects of incretin-related agents on AAA in a mouse model. Methods: Apoe－/－ mice maintained on an atherogenic diet were subcutaneously infused with saline, Ang II (2000 ng/kg/min), Ang II, and native GLP-1 (2.16 nmol/kg/day) or Ang II and native GIP (25 nmol/kg/day) for 4 weeks. DPP-4I (MK0626, 6 mg/kg/day) was provided in the diet to the Ang II-infused mice with or without incretin receptor antagonists [(Pro3) GIP and exendin (9-39)]. Results: AAA occurred in 70% of the animals receiving Ang II. DPP-4I reduced this rate to 40% and significantly suppressed AAA dilatation, fibrosis, and thrombosis. In contrast, incretins failed to attenuate AAA. Incretin receptor blockers did not reverse the suppressive effects of DPP-4I on AAA. In the aorta, DPP-4I significantly reduced the expression of Interleukin-1β and increased that of tissue inhibitor of metalloproteinase (TIMP)-2. In addition, DPP-4I increased the ratio of TIMP-2 to matrix metalloproteinases-9. Conclusions: DPP-4I, MK0626, but not native incretins has protective effects against AAA in Ang II-infused Apoe－/－ mice via suppression of inflammation, proteolysis, and fibrosis in the aortic wall.
Aim: The molecular mechanism of the unique interaction between platelet membrane glycoprotein Ibα (GPIbα) and von Willebrand Factor (VWF), necessary for platelet adhesion under high shear stress, is yet to be clarified. Methods: The molecular dynamics simulation using NAMD (Nanoscale Molecular Dynamics) package with the CHARMM 22 (Chemistry at Harvard Macromolecular Mechanics) force field were used to predict dynamic structural changes occurring in the binding site of A1 domain of VWF and N terminus domain of GPIbα under water soluble condition. Results: The mean distance between the mass center of A1 domain of VWF and GPIbα in the stable form was predicted as 27.3 Å. The potential of mean force between the A1 domain of VWF and GPIbα were calculated in conditions of various distances of the mass center between them. All the calculated values were fitted to the Morse potential energy function curve. The maximum adhesive force between A1 domain of VWF and GPIbα was predicted as 62.3 pN by differentiating the potential of mean force with respect to the molecular distance. Conclusions: The molecular dynamics simulation is useful for predicting the dynamic structure changes of protein bonds involved in platelet adhesion and for predicting the adhesive forces generated between their interactions.
Aim: To compare the outcomes of intracoronary (IC) and intravenous (IV) administration of eptifibatide during primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction (STEMI). Methods: In this prospective double-blind randomized clinical trial, 76 patients with STEMI selected for PPCI were randomly assigned in two groups to receive either IC or IV bolus of eptifibatide. The primary end point was coronary perfusion assessment by thrombolysis in myocardial infarction (TIMI) flow grade (TFG), TIMI perfusion grade (TPG), and corrected TIMI frame count (cTFC). Secondary end points were left ventricular ejection fraction (LVEF) restoration, ST-segment elevation resolution, and in-hospital major cardiovascular adverse events (MACEs) (including recurrent MI, need for target vessel revascularization (TVR), stroke, and death resulting from any cause) until discharge. Results: Assessment revealed significantly better TFG (95% CI: 1.01-10.26, OR=3.224, P=0.042), more TFG 3 (65.79% vs. 86.11% in IV and IC groups, respectively), better TPG (P=0.024), more achieved TPG 3 and TPG 2＋3 (TPG 3: 44.74% vs. 72.22% and TPG 2＋3: 78.95% vs. 94.44% in the IV and IC groups, respectively) with better cTFC in the IC group (37.33±15.84 vs. 32.53± 20.71 in the IV and IC groups, respectively; P=0.034). LVEF was better restored in the IC group (6.21±8.61% vs. 14.72±5.34% in the IV and IC groups, respectively; P＜0.001) and the ST-segment elevation resolution was better achieved in the IC administration (95% CI: -22.55 to -6.23, P=0.001). There were no recurrent MI, stroke, or need for TVR among patients during the in-hospital stay. Conclusions: IC administration of eptifibatide during PPCI in patients with STEMI in comparison with IV administration of eptifibatide is associated with significantly better coronary reperfusion and improved clinical outcomes (IRCT2012090510751N1).
Aim: The Japan Atherosclerosis Society (JAS) Guidelines for Diagnosis and Prevention of Atherosclerotic Cardiovascular Diseases for Japanese 2012 version have set a non-high-density lipoprotein cholesterol (non-HDL-C)-management target of low-density lipoprotein cholesterol (LDL-C) ＋30 mg/dL. However, the actual difference between non-HDL-C and LDL-C is not clear. Therefore, we evaluated its joint distribution and assessed the validity of this criterion in the general Japanese population. Methods: We used baseline cross-sectional data of 4,110 participants from two studies; the KOBE Study (n=1,108) and the Tsuruoka Metabolomic Cohort Study (n=3,002). To evaluate whether the difference between LDL-C and non-HDL-C in the general population match that of the current guidelines, we classified LDL-C levels into four groups according to the JAS Guideline and evaluated its agreement with the corresponding non-HDL-C group. Analysis was also done using six groups (the previous four groups plus the upper and lower cut-off values). Results: The mean difference (mg/dL) between the non-HDL-C and LDL-C (for the KOBE Study and Tsuruoka Metabolomic Cohort Study, respectively) was 19.6 and 24.1 (p＜0.001) for men and 15.9 and 18.3 (p＜0.001) for women. In both the cohort studies, the difference was lower than 30 mg/dL. It was especially small among individuals with normal triglyceride levels. Conclusions: In the general Japanese population, the difference between non-HDL-C and LDL-C was lower than the expected difference of 30 mg/dL. Changes to the criteria for non-HDL-C target levels may be considered in the future.