Familial hypercholesterolaemia (FH), the commonest and serious but potentially treatable
form of inherited dyslipidaemias, is characterised by severely elevated plasma low-density
lipoprotein-cholesterol (LDL-C) level, which subsequently leads to premature coronary artery
disease (pCAD). Effectiveness of FH early detection and treatment is supported by the
outcome of several international cohort studies. Optimal FH management relies on
prescription of statins either alone or together with other lipid-lowering therapies (LLT).
Intensive lifestyle intervention is required in parallel with LLT, which should be commenced at
diagnosis in adults and childhood. Treatment with high intensity statin should be started as
soon as possible. Combination with ezetimibe and/or bile acid sequestrants is indicated if
target LDL-C is not achieved. For FH patients in the very-high risk category, if their LDL-C
targets are not achieved, despite being on maximally tolerated statin dose and ezetimibe,
proprotein convertase subtilisin/kexin type1 inhibitor (PCSK9i) is recommended. In statin
intolerance, ezetimibe alone, or in combination with PCSK9i may be considered. Clinical
evaluation of response to treatment and safety are recommended to be done about 4-6 weeks
following initiation of treatment. Homozygous FH (HoFH) patients should be treated with
maximally tolerated intensive LLT and, when available, with lipoprotein apheresis. This review
highlights the overall management, and optimal treatment combinations in FH in adults and
children, newer LLT including PCSK9i, microsomal transfer protein inhibitor, allele-specific
oligonucleotide to ApoB100 and PCSK9 mRNA. Family cascade screening and/or screening
of high-risk individuals, is the most cost-effective way of identifying FH cases and initiating
early and adequate LLT.
Tocotrienols have been reported to possess potent cholesterol lowering, anti-hypertensive, antiinflammatory and anti-oxidative properties which are superior to tocopherols. Emerging evidence suggests pure tocotrienols have anti-atherogenic properties. However, optimal doses of oftocotrienolrich fraction (TRF) in progressive atherogenesis remain unclear. This animal model experiment was designed to investigate the effects of a range concentration of TRF supplementation on the extent of atherosclerosis and soluble lipids, inflammatory and oxidative stress biomarkers in high-cholesterol diet (HCD) induced hypercholesterolaemic (HC) rabbits with atherosclerosis. A total of 28 New Zealand white rabbits were given 1% high-cholesterol diet (HCD) for two months and then randomised into five groups: Placebo (n=7), TRF 15 mg/kg (n=5), TRF 30 mg/kg (n=6), TRF 60 mg/kg (n=5) and TRF 90 mg/kg (n=5) daily. The treatment was given for three months and the animals were fed HCD throughout the duration. Aortic vessels were obtained to assess the extent of atherosclerotic lesions at the end of the study. Fasting serum lipids (FSL), C-reactive protein (CRP), malondialdehyde (MDA) and 8-isoprostane levels were measured at baseline, one and two months post-HCD, one, two, and three months postintervention. There were no differences in the extent of the atherosclerotic lesions, percentage changes of FSL, MDA, 8-isoprostane and CRP levels between the placebo and TRF groups. In conclusion, TRF across all doses studied have neutral effects on atherosclerotic lesions, soluble lipids, biomarkers of oxidative stress, coronary risk and inflammation in severely atherosclerotic rabbits with progressive and continuous insult by high cholesterol feeding.
Inflammation and endothelial dysfunction are key components in atherogenesis. Should the status of these pro-atherogenesis factors be enhanced during prolonged confined space travel, specific countermeasures need to be instituted to prevent these processes to ensure safe outcome for astronauts during space expeditions. Six crew members were exposed to prolonged, confined isolation for 520 days. Standard exercise and diet regime were instituted throughout isolation phase. Age and gender-matched healthy, free living controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of inflammation (hsCRP and IL-6) and endothelial activation (sICAM-1, sVCAM-1 and E-selectin). Flow-mediated dilatation (FMD) of the artery was performed following the standard protocols set by the International Brachial Artery Reactivity Task Force by trained personnel. There was decreased sVCAM-1 concentration in crew members compared to baseline. However, there was significant decrease in percentage dilatation from baseline in FMD of the brachial artery in the crew members. Percent change increment was observed in hsCRP while percent change reduction was seen in sVCAM-1. The enhanced inflammation and reduced endothelial function could possibly be attributed to the rigorous exercise instituted throughout the confinement period. Furthermore, possible haemoconcentration as a result of psychosocial stress and/ or exercise-induced physiological response could further explain elevations in hsCRP, and unlikely pathological. Furthermore, endothelial activation was attenuated during isolation, suggesting that the diet and exercise program instated throughout the period improved endothelial function.
Oxidation of low-density lipoprotein (LDL) and activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are critical for the inflammatory response for endothelial dysfunction. The objective of this study is to investigate the effects of various doses of HDL on: (a) LDL susceptibility to oxidation; (b) expression of eNOS; and (c) expression of NF-κB p50 and p65. Different concentrations of HDL were incubated in LDL. The reaction rates of LDL susceptibility to oxidation were obtained by kinetic modeling analysis. For determination of eNOS, NF-κB p50 and p65 expression, different HDL concentrations were incubated in lipo polysacharides (LPS)-stimulated human umbilical vein endothelial cell line for 16 hours. Protein was extracted and analysed by western blot and nuclear transcription factor, for example, Co-incubation of LDL with increasing HDL concentrations showed longer lag time and lower reaction rate in a dose-dependent manner compared to controls (p
The aims of this study are to estimate the equivalent dose to the skin, eyes and thyroid in intra- and extra-oral imaging examination and to compare the dose-area product (DAP) derived from the calculation method with Diagnostic Reference Levels (DRL) that has been provided by the Malaysian Ministry of Health (MOH). Dose equivalent is measured by placing Thermoluminescence Dosimeter (TLD-100H) in the anthropomorphic RANDO phantom. Exposure is performed using intra-oral X-ray machine ActeonSatelec X-Mind® and extra-oral X-ray machine InstrumentariumOP300®, and the value is compared to the equivalent dose of the International Commission on Radiological Protection (ICRP) dose limit. DAP value for both examinations was obtained by using formula and comparing them with the DRL from MOH. The average dose equivalent of intra- and extra-oral radiographic examination is lower than the ICRP dose limit. The doses derived from both examinations did not exceed the prescribed levels when compared with DRL. The doses calculated for intra-oral examination of molar maxillary, molar mandibular and interproximal (bitewing) was 0.880 mGy while periapical examination of the anterior maxillary and mandibular was 0.688 mGy and occlusal examination was 1.100 mGy. For the panoramic examination the dose was 0.011 mGy.m2 while lateral cephalometric examination was 0.0054 mGy.m2. The doses obtained from this study were within the dose limit and predetermined level. This shows that a patient receives the minimum dose for both dental radiographic examinations with the optimum level of safety which meets the ALARA concept.