The Impact of ApoE and FOXO3 Genotype on the Risk of Intracerebral Hemorrhage Among American Men of Japanese Ancestry

This study assessed the impact of APOE e2, e4 minor alleles and the FOXO3 longevity-associated genotype (carrier of SNP rs2802292 “G” allele) on 34-year incidence of intracerebral hemorrhage (ICH). Cox regression models were performed to assess the impact of the APOE e2, e4 and FOXO3 G alleles on the incidence of ICH. A total of 6483 participants were eligible for the analyses. 213 participants developed ICH. Cox-regression model showed neither APOE minor allele vs. common genotype (APOE e3/e3: RR 0.89, 95% CI: 0.64-1.22, p=0.46) nor FOXO3 G carrier status (RR 0.97, 95% CI: 0.72-1.29, p=0.82) was associated with incident ICH. Conversely, both hypertension (RR: 1.46, 95% CI: 1.07-2.00, p=0.02) and low cholesterol level (RR: 0.99, 95% CI: 0.99-1.00, p=0.001) were associated with incident ICH. Carriage of APOE e2 or E4 alleles and the FOXO3 G allele do not appear to impact risk of ICH over 34 years in this cohort.

Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis

Drosophila’s white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w1118 mutants were resistant to this deficit. The w1118 mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w1118 learning. However, serotonin levels were not lower in the heads of the w1118 mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w1118 brain. We propose that the w1118 learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

Association of low total cholesterol level with clinical outcomes in patients with atrial fibrillation: the Fushimi AF registry

Background Hyperlipidemia is a well-established risk factor for cardiovascular disease. However, low cholesterol is also reported to be associated with poor outcome in patients with chronic disease, which is called “cholesterol paradox”, and the association of cholesterol level with the incidence of clinical outcomes in patients with atrial fibrillation (AF) remains unclear. Methods In the Fushimi AF Registry, a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan, follow-up data and baseline total cholesterol levels were available in 3,054 patients. We excluded 767 patients who were taking statins, and 2,267 patients were included in the analyses. We defined low cholesterol as total cholesterol <150 mg/dl, and examined the incidence of all-cause death, stroke/systemic embolism (SE), heart failure (HF) hospitalization, and major bleeding. Results Patients with low cholesterol (N=464 (20.4%)) were older, more often male, and had higher prevalence of low body weight (<50 kg), permanent/persistent AF, prior stroke/SE, HF, chronic kidney disease, and anemia (hemoglobin <11 g/dl). CHA2DS2-VASc score was higher in patients with low cholesterol (low cholesterol vs others; 3.6±1.6 vs 3.2±1.7: P<0.001). Prescription of oral anti-coagulants was comparable between the groups (50.0% vs 54.5%: P=0.09). During the median follow-up of 1,805 days, the incidence of all-cause death, stroke/SE, HF hospitalization, and major bleeding was significantly higher in patients with low cholesterol (all-cause death, 10.9 vs 3.8 /100 person-years; stroke/SE, 3.4 vs 1.9 /100 person-years; HF hospitalization, 4.7 vs 2.5 /100 person-years; major bleeding, 2.7 vs 1.4 /100 person-years) (Figure 1). After adjustment for the components of CHA2DS2-VASc score, low body weight, permanent/persistent AF, chronic kidney disease, anemia, and prescription of oral anti-coagulants, low cholesterol was significantly associated with the incidence of all-cause death and stroke/SE, but not with that of HF hospitalization or major bleeding (Figure 2, model 3). Total cholesterol levels were still significantly and inversely associated with the incidence of all-cause death (hazard ratio, 0.94; 95% confidence interval, 0.92–0.96 for 10 mg/dl increase) and stroke/SE (hazard ratio, 0.96; 95% confidence interval, 0.92–0.999 for 10 mg/dl increase), when analyzed as continuous variables. Subgroup analysis revealed that the risk of low cholesterol for all-cause death was more pronounced in female (interaction P, 0.049), patient without prior stroke/SE (interaction P, 0.01), those without HF (interaction P, 0.01), and those without vascular disease (interaction P, 0.001). The risk for stroke/SE was more pronounced in patients without vascular disease (interaction P, 0.01). Conclusion Low total cholesterol level was significantly associated with the incidence of all-cause and stroke/SE in AF patients not taking statins, suggesting the existence of cholesterol paradox in AF. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi-Sankyo, Novartis Pharma, MSD, Sanofi-Avent

Can cholesterol be too low? A retrospective correlation of cholesterol lab values to other markers of cardiovascular disease risk

Introduction/Objective Most recommendations for lipid panel reference ranges are one-sided (desirable total cholesterol is <200 mg/dL, optimal LDL cholesterol [LDL-C] is <100 mg/dL). However, recent studies suggest risks for cardiovascular diseases or mortality at very low cholesterol values. In this retrospective study, we investigated the association between lipid panel results and surrogate markers of cardiovascular disease to test the hypothesis that very low cholesterol levels are associated with increases in cardiovascular risk. Methods/Case Report Patients with lipid panels reported from April 2020-March 2021 at LAC+USC Medical Center were included. Lipid panels (total cholesterol, LDL-C, HDL-C, triglycerides) and laboratory results representing risk factors for cardiovascular disease (troponin T (TnT), NT-pro brain natriuretic peptide (BNP), hemoglobin A1c (HbA1c), high sensitivity C-reactive protein (CRP)) were collated. Lipid panel values were compared against the percentage of patients with non-optimal laboratory results for the cardiovascular risk markers. Results (if a Case Study enter NA) Decreasing total cholesterol levels vs. the percentage of patients with high TnT or BNP showed a U-curve with a nadir at 200-240 mg/dL (elevated TnT: 15%, BNP: 49%) and further increased with lower cholesterol levels <60 mg/dL (TnT: 56%, BNP: 92%); HbA1c (U-curve, nadir: 160-180 mg/dL); and CRP (90% at cholesterol <60 mg/dL; 43% at 220-240 mg/dL). Decreasing HDL-C against all markers of cardiovascular disease demonstrated a continued downtrend below optimal HDL-C levels. Decreasing LDL-C vs. the percentage of high TnT showed a U-curve with a nadir at 120-140 mg/dL; BNP (uptrends in the optimal range of LDL-C); HbA1c (U-curve, nadir: 90-100 mg/dL); and CRP (uptrends with decreasing LDL-C). TnT and BNP decreased with increasing triglycerides, while HbA1c increased with increasing triglycerides. Data points (TnT: n > 5,000; BNP: n > 3,000; HbA1c: n > 29,000; CRP: n > 4,500). Conclusion Very low concentrations of total cholesterol and LDL-cholesterol are associated with elevated markers of cardiovascular risk. Laboratories may wish to consider incorporating low ends to total cholesterol and LDL-cholesterol reference ranges.

Hypocholesterolemia and Statins in Multiple Myeloma

Statins are lipid-lowering agents. They also have immunomodulatory, anti-inflammatory, anti-angiogenic, and anti-proliferative functions. In this context, they are demonstrated to have beneficial effects on mortality in several malignancies including esophageal, breast, lung, liver, pancreatic, endometrial, and colorectal cancers. Multiple myeloma is considered as an incurable plasma cell disorder with current therapy; however due to the current knowledge about the correlation between cholesterol-lowering agents and myeloma; it’s suggested to have lower mortality rates for patients using statins. Patients with multiple myeloma usually have a low cholesterol level which is often underestimated by clinicians. Hereby we aimed to summarize the myeloma-hypocholesterolemia relationship and emphasize the importance of statins as an inexpensive and beneficial approach for these patients.

Two Cases of Congenital Chylethorax: A Successful Story of Medical Management

Congenital chylothorax (CC) is one of the most common causes of pleural effusions in neonates. Associated ipsilateral pulmonary aplasia in CC results in neonatal respiratory distress. Here, we report 2 cases of CC who were managed in the Teaching Hospital Karapitiya, Sri Lanka, between 2017 and 2019. Both babies were males who presented with respiratory distress within a few hours of birth. Their antenatal ultrasound scans failed to detect CC. Chest radiographs showed left-sided pleural effusions. Pleural fluid was milky yellowish suggestive of chylothorax, and the analysis revealed elevated triglycerides, high lymphocyte counts, and low cholesterol levels compatible with CC. They were managed in the neonatal intensive care unit and kept nil by mouth for initial 48 hours. Intravenous octeotride infusion was started on day one and was continued for 7 and 10 days, respectively. The maximum dose of octeotride was 2 μg/kg/hour. Both babies needed intercostal tube placement for 5 and 6 days, respectively. None of them required invasive ventilation. They were started on a medium-chain fatty acid formula, which was continued for about one week. Both babies were commenced on breast milk by day 7 of life and continued with exclusive breastfeeding. Within two weeks, they were discharged home and followed up in the paediatric respiratory clinic for another year. None of them was found to have long-term respiratory complications during the follow-up.

Effect of feeding goat meat containing low cholesterol and rich omega-6 fatty acid on blood lipid status of white rat (Rattus norvegicus)

Background and Aim: Healthy goat meat is an essential aspect in increasing consumer acceptance for this livestock product. The research aimed to examine the effect of goat meat containing low cholesterol and rich omega-6 fatty acid on the performance and blood lipid status of white rats (Rattus norvegicus). Materials and Methods: Thirty 2-month-old male white rats (R. norvegicus) weighing 195-230 g were randomly divided into three groups, with each group consisting of 10 rats. Group I was treated with a control feed (T0; BR I concentrate). Group II (T1) was treated with a mixed feed containing 50% control feed and 50% goat meat. Group III (T2) was treated with a mixed feed comprising 50% control feed and 50% goat meat with low cholesterol and rich omega-6 fatty acids. Each treatment was given ad libitum for 30 days. The variables measured were dry matter and organic matter consumption, daily body weight gain, feed conversion, triglyceride levels, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and atherogenic index (AI). The data were analyzed statistically using analysis of variance in a completely randomized design. Results: The total, HDL, and LDL cholesterol levels at T0, T1, and T2 were as follows: 99.97, 35.97, and 50.43 mg/dL (total cholesterol); 108.35, 33.92, and 58.17 mg/dL (HDL cholesterol); and 101.43, 38.09, and 48.65 mg/dL (LDL cholesterol). The highest HDL and the lowest LDL cholesterol levels (p<0.05) were observed in the T2 treatment group, which had the lowest AI (1.69 vs. 1.77 and 2.19). Conclusion: The consumption of goat with low cholesterol and rich omega-6 fatty acids reduces the total cholesterol and LDL cholesterol, raises the HDL cholesterol levels, and decreases the AI.

Pendampingan Pengolahan Lele Menjadi Abon Lele Tanpa Minyak di Desa Sampora, Tangerang

The community of Sampora village, located in Tangerang, has been able to cultivate catfish. In general, the catfish that is produced is directly sold without being processed. In order to increase the economic value of catfish, it is better if catfish is processed into ready-to-eat food products whose selling price can be higher than the price of raw catfish. One of the catfish processed products that can be made is catfish shredded. Shredded catfish has high protein and low cholesterol levels. In addition, shredded catfish is a durable food, can be processed in various flavors so that it is of great interest to the public. Therefore, through community service activities, the Faculty of Engineering collaborates with Village-Owned Enterprises (BUMDES), Sampora Village to provide counseling / assistance for mothers to process catfish into catfish floss without using oil. During this pandemic, assistance was provided in the form of online tutorials. With this assistance, it is hoped that the women of Sampora village can produce shredded catfish products that can be sold in food stalls prepared by BumDes.