A case report of heterozygous familial hypercholesterolaemia with LDLR gene mutation complicated by premature coronary artery disease detected in primary care.

Background: Familial hypercholesterolaemia (FH) is an autosomal dominant genetic condition predominantly caused by the low-density lipoprotein receptor (LDLR) gene mutation. Case summary: This is the case of a 54-year-old Malay woman with genetically confirmed FH complicated by premature coronary artery disease (PCAD). She was clinically diagnosed in primary care at 52 years old, fulfilling the Simon Broome Criteria (possible FH), Dutch Lipid Clinic Criteria (score of 8: probable FH), and Familial Hypercholesterolaemia Case Ascertainment Tool (relative risk score of 9.51). Subsequently, she was confirmed to have a heterozygous LDLR c.190+4A>T intron 2 pathogenic variant at the age of 53 years. She was known to have hypercholesterolaemia and was treated with statin since the age of 25. However, the lipid-lowering agent was not intensified to achieve the recommended treatment target. The delayed FH diagnosis has caused this patient to have PCAD and percutaneous coronary intervention (PCI) at the age of 29 years and a second PCI at the age of 49 years. She also has a very strong family history of hypercholesterolaemia and PCAD, where seven out of eight of her siblings were affected. Despite this, FH was not diagnosed early, and cascade screening of family members was not conducted, resulting in a missed opportunity to prevent PCAD. Discussion: Familial hypercholesterolaemia can be clinically diagnosed in primary care to identify those who may require genetic testing. Multidisciplinary care focuses on improving identification, cascade screening, and management of FH, which is vital to improving prognosis and ultimately preventing PCAD.

Use of thermal drone in detection and assessment of larval mass temperature in decomposed rabbit carcasses.

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.

The effect of post-mortem computed tomography angiography (PMCTA) on biomarkers of coronary artery disease.

Coronary atherosclerosis is due to build-up of plaque within the coronary arteries. Post-mortem computed tomography (PMCT) allows non or minimally invasive visualization of abnormalities prior to an autopsy, however PMCT-angiography (PMCTA) greatly enhances relevant findings, especially in viewing the cardiovascular system which is important in the diagnosis of coronary atherosclerosis. Contrast media used in PMCTA however has been reported to cause distortion of tissue which may interfere with post-mortem investigation outcomes. A cross sectional study to investigate the effect of PMCTA on tissue biomarkers in coronary arteries was performed involving cases brought in dead to the Institute and Accident and Emergency Unit. Sixty-three autopsy cases were included in this study, whereby 18 cases underwent PMCT while 45 cases underwent PMCTA. The subjects subsequently had a conventional autopsy where coronary artery sections were collected for standard histological examination and immunohistochemistry examination for endothelial inflammatory (CD36), prothrombogenic (TPA) and plaque stability (MMP-9) markers. The subjects consisted of 55 males and 8 females with a mean age ±SD of 49 ± 18.11 years. There were no significant differences in the coronary artery endothelial expression of CD36, MMP-9 and TPA between PMCT and PMCTA subjects. PMCTA does not alter CD36, TPA and MMP-9 markers supporting the safe use of PMCTA in post-mortem examinations.

Safety evaluation of saffron extracts in early and established atherosclerotic New Zealand white rabbits.

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.

Correction: Safety evaluation of saffron extracts in early and established atherosclerotic New Zealand white rabbits.

[This corrects the article DOI: 10.1371/journal.pone.0295212.].

International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia.

This contemporary, international, evidence-informed guidance aims to achieve the greatest good for the greatest number of people with familial hypercholesterolaemia (FH) across different countries. FH, a family of monogenic defects in the hepatic LDL clearance pathway, is a preventable cause of premature coronary artery disease and death. Worldwide, 35 million people have FH, but most remain undiagnosed or undertreated. Current FH care is guided by a useful and diverse group of evidence-based guidelines, with some primarily directed at cholesterol management and some that are country-specific. However, none of these guidelines provides a comprehensive overview of FH care that includes both the lifelong components of clinical practice and strategies for implementation. Therefore, a group of international experts systematically developed this guidance to compile clinical strategies from existing evidence-based guidelines for the detection (screening, diagnosis, genetic testing and counselling) and management (risk stratification, treatment of adults or children with heterozygous or homozygous FH, therapy during pregnancy and use of apheresis) of patients with FH, update evidence-informed clinical recommendations, and develop and integrate consensus-based implementation strategies at the patient, provider and health-care system levels, with the aim of maximizing the potential benefit for at-risk patients and their families worldwide.

Design, development, utility and usability testing of the EMPOWER-SUSTAIN Self-Management Mobile App© among primary care physicians and patients with metabolic syndrome.

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.

Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care.

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.

Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study.

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.

In vitro study of Nigella sativa and thymoquinone activity on endothelial activation and monocyte adhesion.

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.

Evaluation on the Effectiveness of High Cholesterol Diet Feeding in Inducing Early and Established Atherosclerotic Lesions in New Zealand White Rabbits.

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.

PCSK9 Inhibitors Reduce PCSK9 and Early Atherogenic Biomarkers in Stimulated Human Coronary Artery Endothelial Cells.

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.

Attainment of Low-Density Lipoprotein Cholesterol Targets and Prescribing Pattern of Lipid-Lowering Medications among Patients with Familial Hypercholesterolemia Attending Specialist Clinics.

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.

Undertreatment and Underachievement of LDL-C Target among Individuals with High and Very High Cardiovascular Risk in the Malaysian Community.

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.

Genetic Spectrum of Familial Hypercholesterolaemia in the Malaysian Community: Identification of Pathogenic Gene Variants Using Targeted Next-Generation Sequencing.

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.

Osteoblast Demineralization Induced by Oxidized High-Density Lipoprotein via the Inflammatory Pathway Is Suppressed by Adiponectin.

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-κß (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.

A Systematic Review on Attenuation of PCSK9 in Relation to Atherogenesis Biomarkers Associated with Natural Products or Plant Bioactive Compounds in In Vitro Studies: A Critique on the Quality and Imprecision of Studies.

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.

Familial hypercholesterolaemia and coronary risk factors among patients with angiogram-proven premature coronary artery disease in an Asian cohort.

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.

A Systematic Review on the Effect of Saffron Extract on Lipid Profile in Hyperlipidaemic Experimental Animal Models.

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.

The Malaysian HEalth and WellBeing AssessmenT (MyHEBAT) Study Protocol: An Initiation of a National Registry for Extended Cardiovascular Risk Evaluation in the Community.

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.