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INTRODUCTION: Imaging techniques involving optical coherence tomography, computed tomography (CT) and high-resolution magnetic resonance imaging (MRI) are used as tools to identify atherosclerotic plaques. However, the effects of water-based contrast media used in Post Mortem Computed Tomography Angiography (PMCTA) on the histopathology of atherosclerotic plaques have not been widely explored. The objective of this study is to determine the effects of water-based contrast media used in PMCTA on the histopathology of atherosclerotic plaques and biomarkers of atherosclerosis in experimentally induced established atherosclerotic rabbits. MATERIALS AND METHODS: Twenty male New Zealand white rabbits were divided into 2 groups. One group was given a high cholesterol diet (HCD) for 12 weeks to establish atherosclerosis and the control group normal diet (ND). Five rabbits from each group were then given intravenous water-based contrast media before being sacrificed. The entire length of aorta was dissected and submitted for histopathological examination and determination of tissue biomarkers a-SMA and MMP-9. RESULTS: Histopathological examination of the aorta including percentage of area covered by plaque and foam cell formation showed no significant difference in atheromatous plaque formation in both groups of HCD rabbits with or without intravenous contrast media injection (plaque: 55±41 vs. 63±15, p=0.731; foam cells: 124±83 vs. 171±55, p=0.325). Similarly, a-SMA and MMP-9 protein expression also showed no significant difference in both groups (a-SMA: 70±20 vs. 67±26, p=0.807; MMP-9: 60±12 vs. 57±17, p=0.785). CONCLUSION: Water-based contrast media used in PMCTA does not affect the morphology or the immunohistochemistry staining of SMA and MMP-9 in atherosclerotic plaques. [ABSTRACT FROM AUTHOR]

Vitamin E is known to have potent antioxidant activity and plays an important role in reducing oxidative stress, a pivotal step in atherogenesis. However, several randomised clinical trials using α-tocopherol have failed to demonstrate consistent beneficial effects of antioxidants against atherosclerosis and clinical endpoints. Tocotrienol, a vitamin E compound analogue is shown to have more potent antioxidant activity compared to tocopherol. Finding the optimal anti-oxidative dose is crucial and may effectively be applied for cardioprotection in human. The objective of this study was to determine the optimal dose of tocotrienol rich fraction (TRF) with highest antioxidant activity in vitro using the ferric thiocyanate (FTC), 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and 2', 7'- dichlorofluorescein diacetate (DCFHDA) assays. It was found that TRF exhibited potent antioxidant and free radical scavenging activities with an IC50 of 22.10 + 0.01 µg/ml. In all assays, TRF had optimal antioxidant activity at moderate concentrations (10-100 µg/ml). In conclusion, TRF has potent antioxidant activity, which is optimal at moderate concentrations. [ABSTRACT FROM AUTHOR]

Many studies have investigated the coronary risk factors (CRFs) among premature coronary artery disease (PCAD) patients. However, reports on the proportion and CRFs of PCAD according to different age cut-offs for PCAD is globally under-reported. This study aimed to determine the proportion of PCAD patients and analyse the significant CRFs according to different age cut-offs among percutaneous coronary intervention (PCI)-treated patients. Patients who underwent PCI between 2007 and 2018 in two cardiology centres were included (n = 29,241) and were grouped into four age cut-off groups that defines PCAD: (A) Males/females: < 45, (B) Males: < 50; Females: < 55, (C) Males: < 55; Females: < 60 and (D) Males: < 55; Females: < 65 years old. The average proportion of PCAD was 28%; 9.2% for group (A), 21.5% for group (B), 38.6% and 41.9% for group (C) and (D), respectively. The top three CRFs of PCAD were LDL-c level, TC level and hypertension (HTN). Malay ethnicity, smoking, obesity, family history of PCAD, TC level and history of MI were the independent predictors of PCAD across all age groups. The proportion of PCAD in Malaysia is higher compared to other studies. The most significant risk factors of PCAD are LDL-c, TC levels and HTN. Early prevention, detection and management of the modifiable risk factors are highly warranted to prevent PCAD., (© 2024. The Author(s).)

Manual ground searches and cadaver dogs are traditional methods for locating remains, but they can be time- and resource-intensive, resulting in the decomposition of bodies and delay in victim identification. Therefore, thermal imaging has been proposed as a potentially useful tool for detecting remains based on their temperature. This study investigated the potential of a novel search technique of thermal drones to detect surface remains through the detection of maggot mass temperatures. Two trials were carried out at Selangor, Malaysia, each utilizing 12 healthy male Oryctolagus cuniculus European white rabbits and DJI Matrice 300 RTK drone China, equipped with a thermal camera; Zenmuse H20T to record the thermal imaging footage of the carcasses at various heights (15, 30, 60-100 m) for 14 days for each trial. Our results demonstrated that the larval masses and corresponding heat emissions were at their largest during the active decay stage; therefore, all the carcasses were observable in thermal images on day 5 and remained until day 7. Statistical analyses showed that (1) no statistically significant differences in thermal images between clothed and unclothed subjects (p > 0.05); (2) 15 m above ground level was proven to be the optimal height, as it showed the greatest contrast between the carcass heat signature and the background (p < 0.005). Our data suggested the potential window of detection of thermal signatures was detectable up to 7 days post-deposition. This could be an important guideline for the search and recovery teams for operational implementation in this tropical region., (© 2024 The Authors. Journal of Forensic Sciences published by Wiley Periodicals LLC on behalf of American Academy of Forensic Sciences.)

Previous research has shown that natural medications pose health risks, especially in subjects with comorbidities. This study aimed to evaluate the safety of saffron ethanolic extract (SEE) administration in early and established atherosclerotic rabbits. Rabbits were given a high-cholesterol diet (HCD) for 4 and 8 weeks to induce early and established atherosclerosis respectively, and then they were treated with 50 and 100 mg/kg/day SEE. The body weight of the animals was recorded. Blood samples were collected at baseline, pre-treatment, and post-treatment for hematological studies, lipid profiles, and biochemical profiles. Tissue specimens of the vital organs were subjected to histological examination. The above parameters were significantly altered post-intervention with 4 and 8 weeks of HCD. No significant differences in body weight were observed in all the groups post-treatment with 50 and 100mg/kg of SEE compared to pre-treatment. However, low-density lipoprotein cholesterol, total cholesterol, serum urea, and glucose significantly decreased post-treatment with 50 and 100mg/kg/day SEE compared to pre-treatment in early and established atherosclerosis groups. Hematological parameters that were affected post-intervention with HCD returned to their baseline values post-treatment with 50 and 100mg/kg/day SEE. There was a significant improvement in the vital organs post-treatment with 50 and 100mg/kg SEE. SEE can safely be administered without causing harmful effects on the hematological, biochemical profiles, and vital organs. Notably, SEE exerts hypolipidemic and hypoglycemic effects on atherosclerotic conditions. Further clinical trials are warranted to ensure the safety of saffron administration in patients with atherosclerosis-related diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abd Rahim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Patients with familial hypercholesterolemia (FH) are known to have higher exposure to coronary risk than those without FH with similar low-density lipoprotein cholesterol (LDL-C) level. Lipid-lowering medications (LLMs) are the mainstay treatments to lower the risk of premature coronary artery disease in patients with hypercholesterolemia. However, the LLM prescription pattern and its effectiveness among Malaysian patients with FH are not yet reported. The aim of this study was to report the LLM prescribing pattern and its effectiveness in lowering LDL-C level among Malaysian patients with FH treated in specialist hospitals., Methods: Subjects were recruited from lipid and cardiac specialist hospitals. FH was clinically diagnosed using the Dutch Lipid Clinic Network Criteria. Patients' medical history was recorded using a standardized questionnaire. LLM prescription history and baseline LDL-C were acquired from the hospitals' database. Blood samples were acquired for the latest lipid profile assay., Results: A total of 206 patients with FH were recruited. Almost all of them were on LLMs (97.6%). Only 2.9% and 7.8% of the patients achieved the target LDL-C of ＜1.4 and ＜1.8 mmol/L, respectively. The majority of patients who achieved the target LDL-C were prescribed with statin-ezetimibe combination medications and high-intensity or moderate-intensity statins. All patients who were prescribed with ezetimibe monotherapy did not achieve the target LDL-C., Conclusion: The majority of Malaysian patients with FH received LLMs, but only a small fraction achieved the therapeutic target LDL-C level. Further investigation has to be conducted to identify the cause of the suboptimal treatment target attainment, be it the factors of patients or the prescription practice.

Background: Familial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor adaptor protein 1 (LDLRAP1). It is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels leading to premature coronary artery disease. FH can be clinically diagnosed using established clinical criteria, namely, Simon Broome (SB) and Dutch Lipid Clinic Criteria (DLCC), and can be identified using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT), a primary care screening tool., Objective: This study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting., Methods: This is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the "think-aloud" methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool., Results: The recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023., Conclusions: This study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients' perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease., International Registered Report Identifier (irrid): DERR1-10.2196/47911., (©Anis Safura Ramli, Nadeem Qureshi, Hasidah Abdul-Hamid, Aisyah Kamal, Johanes Dedi Kanchau, Nur Syahirah Shahuri, Ralph Kwame Akyea, Luisa Silva, Laura Condon, Suraya Abdul-Razak, Alyaa Al-Khateeb, Yung-An Chua, Mohamed-Syarif Mohamed-Yassin, Noorhida Baharudin, Siti Fatimah Badlishah-Sham, Aznida Firzah Abdul Aziz, Noor Alicezah Mohd Kasim, Siti Hamimah Sheikh Abdul Kadir, Joe Kai, Jo Leonardi-Bee, Hapizah Nawawi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 02.06.2023.)

Introduction: Thymoquinone (TQ) is one of the bioactive compounds in Nigella sativa (NS). Also known as black seeds/cumin, it has been postulated to possess anti-atherogenic properties. However, research on the effects of NS oil (NSO) and TQ on atherogenesis remain scarce. The aim of this study is to determine gene and protein expression of Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Endothelial-eukocyte adhesion molecule (E-selectin) in Human Coronary Artery Endothelial Cells (HCAECs)., Methods: HCAECs were stimulated for 24 hours (h) with 200 µg/ml of Lipopolysaccharides (LPS) and different concentrations of NSO (55, 110, 220, 440 µg/ml) or TQ (4.5, 9.0, 18.0, 36.0 µm). The effects of NSO and TQ on gene and protein expressions were measured using multiplex gene assay and ELISA assay, respectively. Rose Bengal assay was used to analyse monocyte binding activity., Results: NSO and TQ significantly reduced ICAM-1 and VCAM-1 gene and protein expressions. TQ showed significant reduction activity of the biomarkers in dose dependent manner. HCAECs pre-treated with NSO and TQ for 24 h significantly lowered monocytes adherence compared to non-treated HCAECs., Conclusions: NSO and TQ supplementation have anti-atherogenic properties and inhibit monocytes' adherence to HCAECs via down-regulation of ICAM-1 expression. NSO could potentially be incorporated in standard treatment regimens to prevent atherosclerosis and its related complications., Competing Interests: The authors report no conflicts of interest in this work.

Objective: This study aimed to design, develop, assess and refine the EMPOWER-SUSTAIN Self-Management Mobile App © among primary care physicians (PCP) and patients with metabolic syndrome (MetS) in primary care., Methodology: Using the software-development-life-cycle (SDLC) iterative model, storyboard and wireframe were drafted; and a mock prototype was designed to illustrate the content and function graphically. Subsequently, a working prototype was developed. Qualitative studies using the 'think-aloud' and cognitive-task-analysis methods were conducted for the utility and usability testing. Topic guide was based on the 10-Nielsen's-Heuristic-Principles. Utility testing was conducted among PCP in which they 'thought-aloud' while performing tasks using the mobile app. Usability testing was conducted among MetS patients after they were given the app for 3 weeks. They 'thought-aloud' while performing tasks using the app. Interviews were audio- and video-recorded, and transcribed verbatim. Thematic content analysis was performed., Result: Seven PCP and nine patients participated in the utility and usability testing, respectively. Six themes (efficiency of use, user control and freedom, appearance and aesthetic features, clinical content, error prevention, and help and documentation) emerged. PCP found the mobile app attractive and relevant sections were easy to find. They suggested adding 'zoom/swipe' functions and some parts needed bigger fonts. Patients commented that the app was user-friendly, has nice interface, and straightforward language. It helped them understand their health better. Based on these findings, the mobile app was refined., Conclusion: This app was produced using a robust SDLC method to increase users' satisfaction and sustainability of its use. It could potentially improve self-management behaviour among MetS patients in primary care., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2023.)

BACKGROUND In Malaysia, the prevalence of genetically confirmed heterozygous familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care. CASE REPORT In this case series, we report 3 FH cases detected in primary care due to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein-B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest LDL-c level, 8.6 mmol/L, and prominent tendon xanthomas. In case 2, the patient had an LDL-c level of 5.7 mmol/L and premature corneal arcus. In case 3, the patient had an LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with statins and therapeutic lifestyle modifications. They were referred to the lipid specialists for up-titration of lipid lowering medications. First-degree relatives were identified and referred for cascade testing. CONCLUSIONS This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with lipid specialists.

Background: Various methods were used to induce atherosclerosis in rabbits. One of the most common methods used is high-cholesterol diet (HCD) feeding. However, the exact amount and duration of HCD feeding to induce early and established atherosclerosis in New Zealand white rabbits (NZWR) continue to be debated among researchers. Therefore, this study aims to evaluate the effectiveness of 1% HCD feeding in inducing early and established atherosclerosis lesions in NZWR., Methods: A total of 50 g/kg/day of 1% HCD was fed to three to four months old male rabbits weighing 1.8 to 2.0 kg for four and eight weeks to induce early and established atherosclerosis respectively. The body weight and lipid profile were measured at baseline and post-HCD intervention. Following euthanasia, the aorta was excised and prepared for histology and immunohistochemical analysis to confirm the stages of atherosclerosis., Results: The mean body weight of the rabbits in early and established atherosclerosis groups increased significantly up to 17.5% ( p = 0.026) and 19.75% ( p = 0.019) respectively compared to baseline. The total cholesterol level dramatically elevated up to 13-fold ( p = 0.005) and 38-fold ( p = 0.013) compared to baseline, after four and eight weeks of 1% HCD feeding respectively. The low-density lipoprotein level significantly increased up to 42-fold ( p = 0.006) and 128-fold ( p = 0.011) compared to baseline, after four and eight weeks of 1% HCD feeding respectively. Rabbits fed with four and eight weeks 1% HCD significantly developed 5.79% ( p = 0.008) and 21.52% ( p = 0.008) aortic lesion areas compared to the control group. Histological evaluation in the aorta showed accumulation of foam cells in early atherosclerosis group and formation of fibrous plaque and lipid core in the established atherosclerosis group. Rabbits fed with eight weeks HCD showed higher tissue expressions of ICAM-1, VCAM-1, e-selectin, IL-6, IL-8, NF-κBp65, and MMP-12 compared to four weeks of HCD intervention., Conclusions: A total of 50 g/kg/day of 1% HCD for four and eight weeks is sufficient to induce early and established atherosclerosis in NZWR respectively. The consistent results through this method could facilitate researchers in inducing early and established atherosclerosis in NZWR., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Despite reports on the efficacy of proprotein convertase subtilisin-Kexin type 9 (PCSK9) inhibitors as a potent lipid-lowering agent in various large-scale clinical trials, the anti-atherogenic properties of PCSK9 inhibitors in reducing PCSK9 and atherogenesis biomarkers via the NF-ĸB and eNOS pathway has yet to be established. This study aimed to investigate the effects of PCSK9 inhibitors on PCSK9, targeted early atherogenesis biomarkers, and monocyte binding in stimulated human coronary artery endothelial cells (HCAEC). HCAEC were stimulated with lipopolysaccharides (LPS) and incubated with evolocumab and alirocumab. The protein and gene expression of PCSK9, interleukin-6 (IL-6), E-selectin, intercellular adhesion molecule 1 (ICAM-1), nuclear factor kappa B (NF-ĸB) p65, and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. The binding of U937 monocytes to endothelial cell capacity was measured by the Rose Bengal method. The anti-atherogenic effects of evolocumab and alirocumab were contributed to by the downregulation of PCSK9, early atherogenesis biomarkers, and the significant inhibition of monocyte adhesion to the endothelial cells via the NF-ĸB and eNOS pathways. These suggest the beyond cholesterol-lowering beneficial effects of PCSK9 inhibitors in impeding atherogenesis during the initial phase of atherosclerotic plaque development, hence their potential role in preventing atherosclerosis-related complications.

Dyslipidaemia is a major cause of morbidity and mortality. The aims of this study are to determine the prevalence of dyslipidaemia subtypes, the proportions of lipid-lowering therapy (LLT) use, and the achievement of low-density lipoprotein cholesterol (LDL-C) treatment targets for high-risk (HR) and very high-risk (VHR) Malaysians. This cross-sectional study involves 5279 participants across 11 states in Malaysia. The data were obtained through a standardised questionnaire, anthropometric measurements, venous glucose and lipid profile. The participants with existing cardiovascular disease (CVD) or diabetes with at least one of the other major risk factors (smoking, hypertension or dyslipidaemia) were grouped into the VHR category. Other participants were risk-categorised using the Framingham General CVD Risk Score (FRS-CVD). The prevalence of elevated LDL-C, LLT use and LDL-C target were set according to respective risk categories. Pearson's chi-squared test was used to test the difference in the proportions. The mean ± standard deviation (SD) age was 41.1 ± 14.8 years, and 62.2% (3283/5279) of the group were females. Within the participant group, 51.5% were found to have elevated total cholesterol, 28.8% had low HDL-C, and 33.8% had high triglyceride. As for elevated LDL-C, 9.8% were in VHR, 8.6% in HR, 5.8% in MR and 34.9% in LR categories. Among the VHR group, 75.8% were not on LLT, and only 15.9% achieved the LDL-C target. As for the HR category, 87.7% were not on LLT, and only 16.1% achieved the LDL-C target. Dyslipidaemia is highly prevalent among Malaysians. The majority of VHR and HR participants were not on LLT and did not achieve LDL-C treatment targets. Proactive programs are warranted to combat dyslipidaemia-associated CVD events in these groups.

Familial hypercholesterolaemia (FH) is caused by mutations in lipid metabolism genes, predominantly in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin-type 9 (PCSK9) and LDL receptor adaptor protein 1 (LDLRAP1). The prevalence of genetically confirmed FH and the detection rate of pathogenic variants (PV) amongst clinically diagnosed patients is not well established. Targeted next-generation sequencing of LDLR, APOB, PCSK9 and LDLRAP1 was performed on 372 clinically diagnosed Malaysian FH subjects. Out of 361 variants identified, 40 of them were PV (18 = LDLR, 15 = APOB, 5 = PCSK9 and 2 = LDLRAP1). The majority of the PV were LDLR and APOB, where the frequency of both PV were almost similar. About 39% of clinically diagnosed FH have PV in PCSK9 alone and two novel variants of PCSK9 were identified in this study, which have not been described in Malaysia and globally. The prevalence of genetically confirmed potential FH in the community was 1:427, with a detection rate of PV at 0.2% (12/5130). About one-fourth of clinically diagnosed FH in the Malaysian community can be genetically confirmed. The detection rate of genetic confirmation is similar between potential and possible FH groups, suggesting a need for genetic confirmation in index cases from both groups. Clinical and genetic confirmation of FH index cases in the community may enhance the early detection of affected family members through family cascade screening.

Low mineralization activity by human osteoblast cells (HOBs) indicates abnormal bone remodeling that potentially leads to osteoporosis. Oxidation, the most prominent form of high-density lipoprotein (HDL) modification, is suggested to affect bone mineralization through the inflammatory pathway. Adiponectin, which possesses anti-inflammatory activity, is postulated to have the ability to suppress the detrimental effects of oxidized HDL (oxHDL). This study aimed to investigate the effects of HDL before and after oxidation on markers of mineralization and inflammation. The protective effects of adiponectin on demineralization and inflammation induced by oxHDL were also investigated. OxHDL at 100 µg/mL protein had the highest inhibitory effect on mineralization, followed by lower calcium incorporation. OxHDL also had significantly lower expression of a mineralization marker (COL1A2) and higher expression of inflammatory markers (IL-6, TNF-α, and RELA proto-oncogene, NF-κβ (p65)) compared to the unstimulated control group. These findings suggest that oxHDL reduces the mineralization activity of HOBs by increasing the expression of inflammatory markers. Interestingly, co-incubation of adiponectin and oxHDL in HOBs resulted in higher expression of mineralization markers (ALPL, COL1A2, BGLAP, and RUNX2) and significantly reduced all targeted inflammatory markers compared to the oxHDL groups. On the contrary, HDL increased the expression of mineralization markers (COL1A2 and STAT-3) and exhibited lower expression of inflammatory cytokines (IL-6 and TNF-α), proving the protective effect of HDL beyond the reverse cholesterol transport activity., Competing Interests: The authors declare no conflict of interest.

A systematic review was performed to identify all the related publications describing PCSK9 and atherogenesis biomarkers attenuation associated with a natural product and plant bioactive compounds in in vitro studies. This review emphasized the imprecision and quality of the included research rather than the detailed reporting of the results. Literature searches were conducted in Scopus, PubMed, and Science Direct from 2003 until 2021, following the Cochrane handbook. The screening of titles, abstracts, and full papers was performed by two independent reviewers, followed by data extraction and validity. Study quality and validity were assessed using the Imprecision Tool, Model, and Marker Validity Assessment that has been developed for basic science studies. A total of 403 articles were identified and 31 of those that met the inclusion criteria were selected. 13 different atherogenesis biomarkers in relation to PCSK9 were found, and the most studied biomarkers are LDLR, SREBP, and HNF1α. In terms of quality, our review suggests that the basic science study in investigating atherogenesis biomarkers is deficient in terms of imprecision and validity.

Cardiovascular disease (CVD) has been a burden to many developing countries for decades, including Malaysia. Although various steps have been taken to prevent and manage CVD, it remains the leading cause of morbidity and mortality. The rising prevalence of CVD risk factors such as hypertension, hypercholesterolaemia, diabetes, overweight and obesity is the main driving force behind the CVD epidemic. Therefore, a nationwide health study coined as the Malaysian Health and Wellbeing Assessment (MyHEBAT) was designed. It aimed to investigate the prevalence of CVD and the associated risk factors in the community across Malaysia. The MyHEBAT study recruited participants (18-75 years old) through community health screening programmes from 11 states in Malaysia. The MyHEBAT study was further divided into two sub-studies, namely, the Cardiovascular Risk Epidemiological Study (MyHEBAT-CRES) and the MyHEBAT Familial Hypercholesterolaemia Study (MyHEBAT-FH). These studies assessed the prevalence of CVD risk factors and the prevalence of FH in the community, respectively. The data garnered from the MyHEBAT study will provide information for healthcare providers to devise better prevention and clinical practice guidelines for managing CVD in Malaysia.

Background: Familial hypercholesterolaemia (FH) patients have elevated levels of low-density lipoprotein cholesterol, rendering them at high risk of premature coronary artery disease (PCAD). However, the FH prevalence among angiogram-proven PCAD (AP-PCAD) patients and their status of coronary risk factors (CRFs) have not been reported in the Asian population., Objectives: This study aimed to (1) determine the prevalence of clinically diagnosed FH among AP-PCAD patients, (2) compare CRFs between AP-PCAD patients with control groups, and (3) identify the independent predictors of PCAD., Methods: AP-PCAD patients and FH patients without PCAD were recruited from Cardiology and Specialist Lipid Clinics. Subjects were divided into AP-PCAD with FH (G1), AP-PCAD without FH (G2), FH without PCAD (G3) and normal controls (G4). Medical records were collected from the clinic database and standardised questionnaires. FH was clinically diagnosed using Dutch Lipid Clinic Network Criteria., Results: A total of 572 subjects were recruited (males:86.4%; mean±SD age: 55.6±8.5years). The prevalence of Definite, Potential and All FH among AP-PCAD patients were 6%(19/319), 16% (51/319) and 45.5% (145/319) respectively. G1 had higher central obesity, family history of PCAD and family history of hypercholesterolaemia compared to other groups. Among all subjects, diabetes [OR(95% CI): 4.7(2.9,7.7)], hypertension [OR(95% CI): 14.1(7.8,25.6)], FH [OR(95% CI): 2.9(1.5,5.5)] and Potential (Definite and Probable) FH [OR(95% CI): 4.5(2.1,9.6)] were independent predictors for PCAD. Among FH patients, family history of PCAD [OR(95% CI): 3.0(1.4,6.3)] and Definite FH [OR(95% CI): 7.1(1.9,27.4)] were independent predictors for PCAD., Conclusion: Potential FH is common among AP-PCAD patients and contributes greatly to the AP-PCAD. FH-PCAD subjects have greater proportions of various risk factors compared to other groups. Presence of FH, diabetes, hypertension, obesity and family history of PCAD are independent predictors of PCAD. FH with PCAD is in very-high-risk category, hence, early management of modifiable CRFs in these patients are warranted., Competing Interests: The authors have declared that no competing interests exist.

Saffron is widely used in traditional medicine to treat various medical disorders, including hyperlipidaemia. This study aims to systematically review the effects of saffron extract (SE) on lipid profile in in vivo studies. A strategic literature search was done following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Scopus, PubMed (MEDLINE) and Web of Science databases and hand-searching methods were utilised to identify studies published up to January 2020 that reported the effects of SE on lipid profile in a hyperlipidaemic experimental animal model. A total of six articles met the inclusion criteria. The methods of extraction were aqueous ( n = 4), ethanolic ( n = 1) and hydroalcoholic ( n = 1) extracts. Five doses of SE ranging from 10 mg/kg to 100 mg/kg were administered to rats and hamsters, with a duration ranging from 10 days to 8 weeks. SE at doses of 40 mg/kg/day and 80 mg/kg/day significantly decreased the levels of total cholesterol (21.4%-35.4%), low-density lipoproteins (38.7%-50.0%) and triglycerides (TGs) (29.1%-45.0%) and markedly increased the level of high-density lipoproteins (36.6%-65%) in the treated group compared to the untreated group with a minimum 3-week intervention duration ( P < 0.05). This systematic review demonstrated that SE exhibits hypolipidaemic effects compared to a placebo. SE has almost the same ability to reduce cholesterol levels as the standard therapy., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2022.)

Background: Despite being a preventable disease, the prevalence of obesity is rising progressively worldwide. However, the prevalence of obesity and its associated factors among older adults remains unclear in Malaysia. The aim of this study was to determine the prevalence of obesity and its associated factors among older adults who voluntarily attended the health screening programs, which were part of the Malaysian HEalth and Well-Being AssessmenT (My-HEBAT) Study., Methods: Cross-sectional study was conducted among Malaysian adults, aged ≥60 years. A standardized self-administered questionnaire was used to gather information regarding socio-demographic status, personal, family and medical history. Anthropometric indices, blood pressure and physical examinations were conducted on site. Venous blood samples were collected for lipid profile and blood glucose analysis. Participants with BMI of ≥30 kg/m 2 or < 30kg/m 2 were classified as obese or non-obese respectively. Age was categorized into three subgroups: 60-69, 70-79, and ≥80 years old. The factors associated with obesity among older adults were then identified using multiple logistic regression., Results: A total of 716 older adults aged ≥60 years (mean ± SD: 66.6 ± 6.0 years) were recruited. The prevalence of obesity among older adults was 15.8%, while higher prevalence was found among females (42.9%) compared to males (38.3%). The prevalence of obesity decreased with increasing age (48.5% in 60-69 years, 20.8% in 70-79 years, and 11.8% in ≥80 years)., Conclusion: The prevalence of obesity among Malaysian population is higher than that of worldwide prevalence. Current national health promotion and educational programs should focus on identifying factors associated with obesity, and promotion of healthy lifestyle with obesity should be improved and modified, particularly for older adults in Malaysia., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: Coronary artery disease (CAD) is one of the major causes of morbidity and mortality worldwide. Early identification of the cardiovascular risk factors (CRF) among youths assists in determining the high-risk group to develop CAD in later life. In view of the modernised lifestyle, both urban and rural residing youths are thought to be equally exposed to various CRF. This study aimed to describe the common CRF including obesity, dyslipidaemia, hypertension, smoking and family history of hypercholesterolaemia and premature CAD in youths residing in urban and rural areas in Malaysia., Methods: We recruited 942 Malaysian subjects aged 15-24 years old [(males = 257, and urban = 555 vs. rural = 387, (mean age ± SD = 20.5 ± 2.1 years)] from the community health screening programmes organised in both rural and urban regions throughout Malaysia. Medical history and standardised anthropometric measurements were recorded. Laboratory investigations were obtained for fasting serum lipid profiles and plasma glucose levels., Results: A total of 43.7% from the total study population was either obese or overweight. Youths in the rural were more overweight and obese (49.4% vs. 42.7%, p < 0.044) and have higher family history of hypercholesterolaemia (16.3% vs. 11.3%, p < 0.036) than youths in the urban areas. Low-density lipoprotein (LDL-c) (2.8 vs. 2.7 mmol/L) and total cholesterol (TC) (4.7 vs. 4.5 mmol/L) were significantly higher in urban compared to rural youths (p < 0.019 and p < 0.012). Overall, more youth in this study has CRF rather than not (Has ≥ 1 CRF = 69.9%). Significantly more rural youths have at least one CRF compared to urban youths (rural = 74.2% vs. urban = 66.8%, p = 0.016)., Conclusion: In conclusion, our study showed that a large number of youths had at least one or more CRF. Rural youths have significantly higher BMI with higher family history of hypercholesterolaemia compared to urban youths. However, urban youths have higher LDL-c and TC levels. Other coronary risk factors are not significantly different between urban and rural youths. Rural youths have more CRF compared to urban youths. A larger longitudinal study focusing on this population is important to better understand the effect of the area of residence on CRF in youth., (© 2022. The Author(s).)

The use of drones has rapidly evolved over the past decade involving a variety of fields ranging from agriculture, commercial and becoming increasingly used in disaster management or humanitarian aid. Unfortunately, the evidence of its use in mass disasters is still unclear and scarce. This article aims to evaluate the current drone feasibility projects and to discuss a number of challenges related to the deployment of drones in mass disasters in the hopes of empowering and inspiring possible future work. This research follows Arksey and O'Malley framework and updated by Joanna Briggs Institute Framework for Scoping Reviews methodology to summarise the results of 52 research papers over the past ten years, from 2009 to 2020, outlining the research trend of drone application in disaster. A literature search was performed in Medline, CINAHL, Scopus, individual journals, grey literature and google search with assessment based on their content and significance. Potential application of drones in disaster are broad. Based on articles identified, drone application in disasters are classified into four categories; (1) mapping or disaster management which has shown the highest contribution, (2) search and rescue, (3) transportation and (4) training. Although there is a significant increase in the number of publications on use of drone in disaster within the last five years, there is however limited discussion to address post-disaster healthcare situation especially with regards to disaster victim identification. It is evident that drone applications need to be further explored; to focus more on drone assistance to humans especially in victim identification. It is envisaged that with sufficient development, the application of drones appears to be promising and will improve their effectiveness especially in disaster management., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: Familial hypercholesterolaemia (FH) is the most common autosomal dominant lipid disorder, leading to severe hypercholesterolaemia. Early detection and treatment with lipid-lowering medications may reduce the risk of premature coronary artery disease in FH patients. However, there is scarcity of data on FH prevalence, detection rate, treatment and control with lipid-lowering therapy in the Malaysian community., Methods: Community participants (n=5130) were recruited from all states in Malaysia. Blood samples were collected for lipid profiles and glucose analyses. Personal and family medical histories were collected by means of assisted questionnaire. Physical examination for tendon xanthomata and premature corneal arcus were conducted on-site. FH were clinically screened using Dutch Lipid Clinic Network Criteria., Results: Out of 5130 recruited community participants, 55 patients were clinically categorised as potential (Definite and Probable) FH, making the prevalence FH among the community as 1:100. Based on current total population of Malaysia (32 million), the estimated number of FH patients in Malaysia is 320,000, while the detection rates are estimated as 0.5%. Lipid-lowering medications were prescribed to 54.5% and 30.5% of potential and possible FH patients, respectively, but none of them achieved the therapeutic LDL-c target., Conclusion: Clinically diagnosed FH prevalence in Malaysian population is much higher than most of the populations in the world. At community level, FH patients are clinically under-detected, with majority of them not achieving target LDL-c level for high-risk patients. Therefore, public health measures are warranted for early detection and treatment, to enhance opportunities for premature CAD prevention.

Experiencing good quality of life (QOL) among university staff is extremely crucial to ensuring academic excellence; however, there are limited data on factors that contribute to QOL among university staff. This study aims to determine the level and the predictors for good QOL among university staff. The consenting participants were selected using a stratified sampling method. Participants who had fulfilled the selection criteria were provided with socio-demographic, medical illness, job factor, and family background questionnaires. QOL and psychological well-being (depression, anxiety, and stress) were assessed using the World Health Organization Quality of Life brief version (WHOQOL-BREF) and Depression, Anxiety, and Stress Scale (DASS-21) questionnaires, respectively. A total of 278 staff (mean ± SD age: 38.84 ± 7.85 years, 44.2% males, 82.7% married) had participated in this study. This study found that participants had low QOL in the domains of physical health [P-QOL] (11.2%), psychological health [PSY-QOL] (9.7%), social relationships [SR-QOL] (19.1%), and environment [E-QOL] (14.4%). The predictors of P-QOL were depression, medical illness, and number of dependents, while those of PSY-QOL were work promotion, depression, medical illness, and number of dependents. Additionally, the predictors of SR-QOL were campus location, depression, and work promotion, while those of E-QOL were age, level of education, depression, work promotion, and medical illness. Depression significantly affected all domains of QOL. Younger participants without medical illness and those with tertiary level of education had increased odds of having good QOL. Participants having dependents without work promotion and employed in suburban areas had decreased odds of having good QOL. The relevant authority should be identified and then assist staff with difficulties to ensure the staff benefited from having a good QOL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nazali, Razali, Ariaratnam, Ahmad and Nawawi.)

Background: Primary care physicians (PCP) play an important role in detecting Familial Hypercholesterolaemia (FH) early. However, knowledge, awareness and practice (KAP) regarding FH among Malaysian PCP are not well established, and there was no validated tool to assess their FH KAP. Thus, the aim of this study was to adapt an FH KAP questionnaire and determine its validity and reliability among Malaysian PCP., Methods: This cross-sectional validation study involved Malaysian PCP with ≥ 1-year work experience in the primary care settings. In Phase 1, the original 19-item FH KAP questionnaire underwent content validation and adaptation by 7 experts. The questionnaire was then converted into an online survey instrument and was face validated by 10 PCP. In Phase 2, the adapted questionnaire was disseminated through e-mail to 1500 PCP. Data were collected on their KAP, demography, qualification and work experience. The construct validity was tested using known-groups validation method. The hypothesis was PCP holding postgraduate qualification (PCP-PG-Qual) would have better FH KAP compared with PCP without postgraduate qualification (PCP-noPG-Qual). Internal consistency reliability was calculated using Kuder Richardson formula-20 (KR-20) and test-retest reliability was tested on 26 PCP using kappa statistics., Results: During content validation and adaptation, 10 items remained unchanged, 8 items were modified, 1 item was moved to demography and 7 items were added. The adapted questionnaire consisted of 25 items (11 knowledge, 5 awareness and 9 practice items). A total of 130 out of 1500 PCP (response rate: 8.7%) completed the questionnaire. The mean percentage knowledge score was found to be significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (53.5, SD ± 13.9 vs. 35.9, SD ± 11.79), t(128) = 6.90, p < 0.001. The median percentage awareness score was found to be significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (15.4, IqR ± 23.08 vs. 7.7, IqR ± 15.38), p = 0.030. The mean percentage practice score was significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (69.2, SD ± 17.62 vs. 54.4, SD ± 19.28), t(128) = 3.79, p < 0.001. KR-20 value was 0.79 (moderate reliability) and average Kappa was 0.796 (substantial agreement)., Conclusion: This study has proven that the 25-item adapted FH KAP questionnaire is valid and reliable. It can be used to measure and establish FH KAP among PCP in Malaysia.

Infective endocarditis (IE) is a relatively uncommon disease, but has been challenging to diagnose over the years. With the increasing incidence, variety of causative agents and the resistance of microorganisms towards antibiotics, there is still an occurrence of sudden death due to undiagnosed IE. The most common microorganism causing IE is Staphylococcus aureus. However, there is increasing prevalence of other microorganisms causing IE. This case report highlights a case of sudden death due to IE caused by a rare pathogen, Streptococcus constellatus which belongs to the Streptococcus anginosus group (Milleri group). A study noted the crude incidence of IE in 6 world regions ranged between 1.5 and 11.6 cases per 100,000 people. To date, there has been no previous report on sudden death due to IE caused by Streptococcus constellatus in Malaysia, neither in the forensic nor clinical setting. This case report underlined the characteristics and pathological features of this microorganism. The increasing incidence and variety of causative organisms in IE are important public health issues. It is vital for future studies to examine the risk factors of IE related to Streptococcus constellatus, to enhance better understanding, insight and awareness regarding the course of this disease. This in turn may facilitate preventive measures to avoid morbidity and mortality from this condition.

Introduction: Apart from inflammation and endothelial dysfunction, other key components in the development of atherogenesis include prothrombogenesis and oxidative stress. The effects of long-term confinement and isolation, exposure to radiation and different gravity forces during space travel could potentially increase the long-term risk of atherosclerosis. To the best of our knowledge, this is the first study determining the status of prothrombogenesis and oxidative stress in six cosmonauts subjected to the longest duration of confined isolation period of 520 days in preparation for prospective undetermined manned space travel to Mars., Materials and Methods: This collaborative research between the National Space Agency (ANGKASA), Universiti Teknologi MARA, Malaysia and Institute of Biomedical Problems (IBMP), Russia was conducted at the Russian Academy of Sciences IBMP, Moscow, Russia. Six multi-national cosmonauts were assigned to live in a ground-based confined module for 520 days. Standard exercise and diet regime were instituted throughout the isolation phase. Six age, ethnic and gender-matched healthy, free-living ground controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of prothrombogenesis [plasminogen activator inhibitor-1 (PAI-1) and homocysteine] and oxidative stress [oxidised low-density lipoprotein (ox-LDL) and malondialdehyde (MDA)]., Results: There were significantly lower concentrations of PAI-1 and homocysteine in cosmonauts during confinement compared to the controls. There were no significant differences seen in the concentrations of biomarkers of oxidative stress during confinement but there was a significant percentage change increment for serum MDA in cosmonauts., Conclusion: Long-term confinement decreased the risk of prothrombogenesis and this could be attributed to the exercise and diet regime which includes omega-3 fatty acids supplementation given to the crew members during their confinement period. However, oxidative damage could not be excluded and may be attributed to the influence of psychological stress during this prolonged confinement.

Introduction: Coronary artery disease (CAD) is a known cause of major cardiovascular events and calcium score (CS) has been developed as a marker of coronary atherosclerosis. Yet, the relationship between post mortem computed tomography (PMCT) CS with histologically observed calcification and the severity of coronary artery stenosis has not been widely explored and is still unclear. This study aims to determine the association between coronary artery PMCT CS with histologically observed calcification and degree of stenosis of coronary arteries in post-mortem cases., Materials & Methods: This was a cross-sectional study involving 101 subjects recruited from the National Institute of Forensic Medicine (IPFN) Hospital Kuala Lumpur (HKL) over a period of 15 months, from December 2012 until April 2014. PMCT CS of the coronary arteries was calculated using Agatston-Janowitz score. Histological presence of calcification was observed and the degree of stenosis was calculated using an image analysis technique., Results: PMCT CS increased with increasing severity of stenosis (p<0.001). PMCT CS showed a positive correlation with the presence of calcification (r=-0.82, p<0.001)., Conclusion: Calcium score is strongly associated with coronary artery calcification and the degree of luminal stenosis in post mortem subjects. Thus, PMCT may be useful as a non-invasive tool in diagnosing CAD in the event that an autopsy is not possible.

Objectives: To determine the prevalence of metabolic syndrome (MS), ascertain the status of coronary risk biomarkers and establish the independent predictors of these biomarkers among the Negritos., Settings: Health screening programme conducted in three inland settlements in the east coast of Malaysia and Peninsular Malaysia., Subjects: 150 Negritos who were still living in three inland settlements in the east coast of Malaysia and 1227 Malays in Peninsular Malaysia. These subjects were then categorised into MS and non-MS groups based on the International Diabetes Federation (IDF) consensus worldwide definition of MS and were recruited between 2010 and 2015. The subjects were randomly selected and on a voluntary basis., Primary and Secondary Outcome Measures: This study was a cross-sectional study. Serum samples were collected for analysis of inflammatory (hsCRP), endothelial activation (sICAM-1) and prothrombogenesis [lp(a)] biomarkers., Results: MS was significantly higher among the Malays compared with Negritos (27.7%vs12.0%). Among the Malays, MS subjects had higher hsCRP (p=0.01) and sICAM-1 (p<0.05) than their non-MS counterpart. There were no significant differences in all the biomarkers between MS and the non-MS Negritos. However, when compared between ethnicity, all biomarkers were higher in Negritos compared with Malays (p<0.001). Binary logistic regression analysis affirmed that Negritos were an independent predictor for Lp(a) concentration (p<0.001)., Conclusions: This study suggests that there may possibly be a genetic influence other than lifestyle, which could explain the lack of difference in biomarkers concentration between MS and non-MS Negritos and for Negritos predicting Lp(a)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: This study aimed to determine knowledge, awareness and practice (KAP) regarding familial hypercholesterolaemia (FH) among Malaysian primary care physicians (PCP), and to compare KAP between PCP with postgraduate qualification (PCP-PG-Qual) and PCP without PG qualification (PCP-noPG-Qual)., Methods: This was a cross-sectional study involving PCP with ≥1-year working experience in Malaysian primary care settings. An adapted and validated 25-item FH-KAP questionnaire was disseminated during primary care courses. Total score for each domain was calculated by summing-up the correct responses, converted into percentage scores. Normality distribution was examined and comparisons of mean/median percentage scores were made between the two groups of PCP., Results: A total of 372 PCP completed the questionnaire. Regarding knowledge, 77.7% correctly defined FH. However, only 8.3% correctly identified coronary artery disease risk in untreated FH. The mean percentage knowledge score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (48.9, SD ± 13.92 vs. 35.2, SD ± 14.13), t(370) = 8.66, p < 0.001. Regarding awareness, 39% were aware of the NICE FH guideline and only 27.2% were aware of FH diagnostic criteria. The median percentage awareness score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (15.4, IqR ± 23.08 vs. 7.7, IqR ± 11.54), p = 0.013. Regarding practice, only 19.1% stratified FH patients as high risk irrespective of other risk factors. The mean percentage practice score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (52.4, SD ± 12.92 vs. 42.7, SD ± 16.63), t(370) = 9.65, p < 0.001., Conclusions: Substantial gaps in FH-KAP among Malaysian PCP were identified, with PCP-PG-Qual having better knowledge, awareness and practice than PCP-noPG-Qual, emphasising the importance of professional training and certification., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Cardiovascular disease (CVD) has been the main cause of mortality and an important cause of morbidity in Malaysia for several years. To reduce global cardiovascular (CV) risk in the population, primary preventive strategies need to be implemented. Hypercholesterolaemia is one of the major risk factors for CVD. This paper is an expert review on the management of hypercholesterolemia focusing on high and very high risk individuals. In low and Intermediate risk individuals, therapeutic lifestyle changes (TLC) and a healthy lifestyle alone may suffice. In high and very high risk individuals, drug therapy in conjunction with TLC are necessary to achieve the target LDL-C levels which have been shown to slow down progression and sometimes even result in regression of atherosclerotic plaques. Statins are first-line drugs because they have been shown in numerous randomized controlled trials to be effective in reducing CV events and to be safe. In some high risk individuals, despite maximally tolerated statin therapy, target Low Density Lipoprotein Cholesterol (LDL-C) levels are not achieved. These include those with familial hypercholesterolaemia and statin intolerance. This paper discusses non-statin therapies, such as ezetimibe and the newer Proprotein convertase subtilisin/kexin type 9 Inhibitors (PCSK9-i).

Background: Familial hypercholesterolaemia (FH) is a genetic disorder with a high risk of developing premature coronary artery disease that should be diagnosed as early as possible. Several clinical diagnostic criteria for FH are available, with the Dutch Lipid Clinic Criteria (DLCC) being widely used. Information regarding diagnostic performances of the other criteria against the DLCC is scarce. We aimed to examine the diagnostic performance of the Simon-Broom (SB) Register criteria, the US Make Early Diagnosis to Prevent Early Deaths (US MEDPED) and the Japanese FH Management Criteria (JFHMC) compared to the DLCC., Methods: Seven hundered fifty five individuals from specialist clinics and community health screenings with LDL-c level ≥ 4.0 mmol/L were selected and diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive values of individuals screened with the SB register criteria, US MEDPED and JFHMC were assessed against the DLCC., Results: We found the SB register criteria identified more individuals with FH compared to the US MEDPED and the JFHMC (212 vs. 105 vs. 195; p < 0.001) when assessed against the DLCC. The SB Register criteria, the US MEDPED and the JFHMC had low sensitivity (51.1% vs. 25.3% vs. 47.0% respectively). The SB Register criteria showed better diagnostic performance than the other criteria with 98.8% specificity, 28.6% efficiency value, 98.1% and 62.3% for positive and negative predictive values respectively., Conclusion: The SB Register criteria appears to be more useful in identifying positive cases leading to genetic testing compared to the JFHMC and US MEDPED in this Asian population. However, further research looking into a suitable diagnosis criterion with high likelihood of positive genetic findings is required in the Asian population including in Malaysia.

Background: Familial hypercholesterolaemia (FH) leads to premature coronary artery diseases (CAD) which pathophysiologically can be measured by inflammation, endothelial activation and oxidative stress status. However, the status of these biomarkers among related unaffected relatives of FH cases and whether FH is an independent predictor of these biomarkers have not been well established. Thus, this study aims to (1) compare the biomarkers of inflammation, endothelial activation and oxidative stress between patients with FH, their related unaffected relatives (RUC) and normolipaemic subjects (NC) (2)determine whether FH is an independent predictor of these biomarkers., Methods: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis., Results: hsCRP was higher in FH and RUC compared to NC (mean ± SD = 1.53 ± 1.24 mg/L and mean ± SD = 2.54 ± 2.30 vs 1.10 ± 0.89 mg/L, p < 0.05). sICAM-1 and E-selectin were higher in FH compared to NC (mean ± SD = 947 ± 742 vs 655 ± 191 ng/mL, p < 0.001 and 175 ± 131 vs 21.6 ± 10.7 ng/mL, p < 0.001 respectively) while sICAM-1 concentration was higher in RUC compared to NC (mean ± SD = 945 ± 379 vs 655 ± 191 ng/mL, p < 0.01). Biomarkers of oxidation (ox-LDL, MDA and ISP) were elevated in FH compared to NC [mean ± SD = (48.2 ± 26.8 vs 27.3 ± 13.2 mU/L, p < 0.001), (2.57 ± 1.3 vs 1.20 ± 0.30 nmol/mL, p < 0.001) and (645 ± 396 vs 398 ± 20.5 pg/L, p < 0.001) respectively], but no significant differences were observed between RUC and NC (p > 0.05). FH was an independent predictor for sICAM-1 (p = 0.007), ox-LDL (p < 0.001) and MDA (p < 0.001) while RUC independently predicted for sICAM-1 (p < 0.001)., Conclusion: The screening for FH is vital as all biomarkers associated with atherogenesis are higher in these subjects and FH also independently predict biomarkers of endothelial activation and oxidative stress. Furthermore, despite not fulfilling the diagnostic criteria for FH, related unaffected family members that may not phenotypically express the mutation may still be at risk of developing CAD as reflected from the enhanced inflammatory and endothelial activation status observed in this group. This highlights the need to not only conduct family tracing in indexed FH cases, but also assess the coronary risk among family members that do not fulfil the FH diagnostic criteria.

Background: The potential for global collaborations to better inform public health policy regarding major non-communicable diseases has been successfully demonstrated by several large-scale international consortia. However, the true public health impact of familial hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide., Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects., Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Atherosclerosis is the main cause of coronary artery disease -related deaths worldwide. The atheroprotective properties of pure tocotrienols (T3) in the absence of alpha-tocopherol (α-TCP) in vitamin E has not been extensively examined., Aim: To determine the atheroprotective properties of T3 in early and established atherosclerosis rabbits., Methods: Thirty New Zealand white rabbits were divided into two groups, B1 and B2 which represent early [fed 1% high cholesterol diet (HCD) for 2 weeks] and established (fed 1% HCD for 8 weeks) atherosclerosis. Each group was subdivided into three intervention arms: 1) T3-4 mg/kg, 2) T3-15 mg/kg and 3) vehicle without T3 (T3 negative) for 8 weeks. Serial fasting blood samples were obtained for lipid profile, and whole lengths of aorta were used to determine tissue markers of endothelial activation, inflammation and plaque stability., Results: In B1, atherosclerotic lesion in T3-4 mg/kg group was significantly reduced ( p =0.008), while aortic tissue expression of vascular cellular adhesion molecule 1 (VCAM-1), interleukin-6 (IL-6) and matrix metalloproteinase (MMP-12) was reduced in T3-4 mg/kg compared to T3-negative rabbits group (0.2±0.1 vs. 28.5±3.1%; 3.0±1.6 vs. 14.0±1.7%; and 5.2±2.2 vs. 27.7±0.8%, respectively, p< 0.05). T3-15 mg/kg group showed reduction in VCAM-1, E-selectin, IL-6 and MMP-12 (3.9±1.9 vs. 28.5±3.1%; 10.3±0.5 vs. 59.8±8.5%; 2.6±1.7 vs. 14.0±1.7%; and 16.2±3.2 vs. 27.7 0.8%, respectively, p< 0.05). In B2, T3-4 mg/kg group reduced aortic tissue expression of intercellular adhesion molecule 1 (ICAM-1), E-selectin, IL-6, MMP-12 and MMP-9 compared to T3-negative rabbits group (29.9±2.4 vs. 55.3±1.3%; 26.7±1.5 vs. 60.5±7.6%; 15.7±0.7 vs. 27.7±4.8%; 34.8±2.7 vs. 46.5±3.4%; and 25.89±3.9 vs. 45.9±1.7%, respectively, p< 0.05). T3-15 mg/kg group showed reduced VCAM-1, ICAM-1, E-selectin, IL-6, MMP-12 and MMP-9 (20.5±3.3 vs. 35.6±2.5%; 24.9±1.3 vs. 55.3±1.3%; 29.9±6.7 vs. 60.5±7.6; 11.3±2.2 vs. 27.7±4.8%; 23.0±1.7 vs. 46.5±3.4%; and 17.6±1.9 vs. 45.9±1.7%, respectively, p< 0.05., Conclusion: These findings suggest the possible atheroprotective role T3 plays as an adjunct supplementation to standard treatment in the prevention of CAD., Competing Interests: and funding The authors have not received any funding or benefits from industry or elsewhere to conduct this study.

Background: Hypertension is the leading cardiovascular risk factor globally as well as in Malaysia. This study aimed to estimate the prevalence, awareness, treatment, control and the socio demographic determinants of hypertension among Malaysian adults., Method: The analytic sample consisted of 11,288 adults aged ≥ 30 years recruited at baseline in 2007-2011 from the REDISCOVER Study which is an ongoing, prospective cohort study involving 18 urban and 22 rural communities in Malaysia. Socio-demographics, anti-hypertensive treatment details and an average of at least two blood pressure measurements were obtained., Results: The age-adjusted prevalence was 42.0 % (CI: 40.9-43.2) and was higher in men [43.5 % (CI: 41.2-45.0)] than women [41.0 % (CI: 39.8-42.3)]. Participants from rural areas (APR: 1.12, CI: 1.04-1.20); aged at least 40-49 years (APR: 1.86, CI: 1.62-2.14); who were overweight (APR: 1.24, CI: 1.15-1.34) and obese (APR: 1.54, CI: 1.43-1.6) were more likely to have hypertension. The Indigenous ethnic group was less likely to be aware (APR: 0.81, CI: 0.69-0.92) and to be on treatment (APR: 0.66, CI: 0.55-0.79). Those in rural areas were less likely to have their hypertension controlled (APR: 0.61, CI: 0.49-0.75). On the other hand, control was more likely in females (APR: 1.25, CI: 1.01-1.54) and Indigenous group (APR: 1.64, CI: 1.19-2.25)., Conclusion: Hypertension is common in the Malaysian adults. The control of hypertension has increased over the years but is still quite low. Public health measures, as well as individual interventions in primary care are crucial to reduce their risk of developing complications.

Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Inflammation, endothelial activation and oxidative stress have been established as key events in the initiation and progression of atherosclerosis. High-density lipoprotein cholesterol (HDL-c) is protective against atherosclerosis and coronary heart disease, but its association with inflammation, endothelial activation and oxidative stress is not well established., Objectives: (1) To compare the concentrations of biomarkers of inflammation, endothelial activation and oxidative stress in subjects with low HDL-c compared to normal HDL-c; (2) To examine the association and correlation between HDL-c and these biomarkers and (3) To determine whether HDL-c is an independent predictor of these biomarkers., Methods: 422 subjects (mean age±SD = 43.2±11.9 years) of whom 207 had low HDL-c concentrations (HDL-c <1.0 mmol/L and <1.3 mmol/L for males and females respectively) and 215 normal controls (HDL-c ≥1.0 and ≥1.3 mmol/L for males and females respectively) were recruited in this study. The groups were matched for age, gender, ethnicity, smoking status, diabetes mellitus and hypertension. Fasting blood samples were collected for analysis of biomarkers of inflammation [high-sensitivity C-reactive protein (hsCRP) and Interleukin-6 (IL-6)], endothelial activation [soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and E-selectin)] and oxidative stress [F2-Isoprostanes, oxidized Low Density Lipoprotein (ox-LDL) and Malondialdehyde (MDA)]., Results: Subjects with low HDL-c had greater concentrations of inflammation, endothelial activation and oxidative stress biomarkers compared to controls. There were negative correlations between HDL-c concentration and biomarkers of inflammation (IL-6, p = 0.02), endothelial activation (sVCAM-1 and E-selectin, p = 0.029 and 0.002, respectively), and oxidative stress (MDA and F2-isoprostane, p = 0.036 and <0.0001, respectively). Multiple linear regression analysis showed HDL-c as an independent predictor of IL-6 (p = 0.02) and sVCAM-1 (p<0.03) after correcting for various confounding factors., Conclusion: Low serum HDL-c concentration is strongly correlated with enhanced status of inflammation, endothelial activation and oxidative stress. It is also an independent predictor for enhanced inflammation and endothelial activation, which are pivotal in the pathogenesis of atherosclerosis and atherosclerosis-related complications.

The effects of spaceflight on cardiovascular health are not necessarily seen immediately after astronauts have returned but can be delayed. It is important to investigate the long term effects of spaceflight on protein and gene expression of inflammation and endothelial activation as a predictor for the development of atherosclerosis and potential cardiovascular problems. The objectives of this study were to investigate the (a) protein and gene expression of inflammation and endothelial activation, (b) expression of nuclear factor kappa B (NFκB), signal transducer and activator of transcription-3 (STAT-3) and endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC) 3 months post-space flight travel compared to ground controls. HUVEC cultured on microcarriers in fluid processing apparatus were flown to the International Space Station (ISS) by the Soyuz TMA-11 rocket. After landing, the cells were detached from microcarriers and recultured in T-25 cm(2) culture flasks (Revived HUVEC). Soluble protein expression of IL-6, TNF-α, ICAM-1, VCAM-1 and e-selectin were measured by ELISA. Gene expression of these markers and in addition NFκB, STAT-3 and eNOS were measured. Spaceflight induced IL-6 and ICAM-1 remain elevated even after 3 months post spaceflight travel and this is mediated via STAT-3 pathway. The downregulation of eNOS expression in revived HUVEC cells suggests a reduced protection of the cells and the surrounding vessels against future insults that may lead to atherosclerosis. It would be crucial to explore preventive measures, in relation to atherosclerosis and its related complications.

The structure and functions of endothelial cells after space mission were studied by electron and laser confocal microscopy, image analysis, and MTT test. The endothelial cells changed significantly (proliferative activity, size, contours, shape, distribution of mitochondria and microtubules) in comparison with controls on the Earth. These changes indicated injuries in the cytoskeleton and impairment of the barrier function of the cells, which presumably contributed to the development of endothelial dysfunction.

Metabolic syndrome (MetS) is a steering force for the cardiovascular diseases epidemic in Asia. This study aimed to compare the prevalence of MetS in Malaysian adults using NCEP-ATP III, IDF, and JIS definitions, identify the demographic factors associated with MetS, and determine the level of agreement between these definitions. The analytic sample consisted of 8,836 adults aged ≥30 years recruited at baseline in 2007-2011 from the Cardiovascular Risk Prevention Study (CRisPS), an ongoing, prospective cohort study involving 18 urban and 22 rural communities in Malaysia. JIS definition gave the highest overall prevalence (43.4%) compared to NCEP-ATP III (26.5%) and IDF (37.4%), P < 0.001. Indians had significantly higher age-adjusted prevalence compared to other ethnic groups across all MetS definitions (30.1% by NCEP-ATP III, 50.8% by IDF, and 56.5% by JIS). The likelihood of having MetS amongst the rural and urban populations was similar across all definitions. A high level of agreement between the IDF and JIS was observed (Kappa index = 0.867), while there was a lower level of agreement between the IDF and NCEP-ATP III (Kappa index = 0.580). JIS definition identified more Malaysian adults with MetS and therefore should be recommended as the preferred diagnostic criterion.