Lipid Measurements Research Articles

Expert consensus on fundus photograph-based cardiovascular risk assessment using artificial intelligence technology

Cardiovascular risk assessment is a basic tenet of the prevention of cardiovascular disease. Conventional risk assessment models require measurements of blood pressure, blood lipids, and other health-related information prior to assessment of risk via regression models. Compared with traditional approaches, fundus photograph-based cardiovascular risk assessment using artificial intelligence (AI) technology is novel, and has the advantages of immediacy, non-invasiveness, easy performance, and low cost. The Health Risk Assessment and Control Committee of the Chinese Preventive Medicine Association, in collaboration with the Chinese Society of Cardiology and the Society of Health Examination, invited multi-disciplinary experts to form a panel to develop the present consensus, which includes relevant theories, progress in research, and requirements for AI model development, as well as applicable scenarios, applicable subjects, assessment processes, and other issues associated with applying AI technology to assess cardiovascular risk based on fundus photographs. A consensus was reached after multiple careful discussions on the relevant research, and the needs of the health management industry in China and abroad, in order to guide the development and promotion of this new technology.

Cryptotanshinone promotes brown fat activity by AMPK activation to inhibit obesity.

Activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can protect against obesity and obesity-related metabolic conditions. Cryptotanshinone (CT) regulates lipid metabolism and significantly ameliorates insulin resistance. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a receptor for cellular energy metabolism, is believed to regulate brown fat activity in humans. The in vivo study included high-fat-fed obese mice administered orally 200/400 mg/kg/d CT. They were evaluated through weight measurement, the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), cold stimulation test, serum lipid (total cholesterol, triglycerides, and low-density lipoprotein) measurement, hematoxylin and eosin staining, and immunohistochemistry. Furthermore, the in vitro study investigated primary adipose mesenchymal stem cells (MSCs) with incubation of CT and AMPK agonists (acadesine)/inhibitor (Compound C). Cells were evaluated using Oil Red O staining, Alizarin red staining, flow cytometry, and immunofluorescence staining to identify and observe the osteogenic versus adipogenic differentiation. Quantitative real-time polymerase chain reaction and the Western blot were used to observe related gene expression. In the diet-induced obesity mouse model mice CT suppressed body weight, food intake, glucose levels in the IPGTT and IPTT, serum lipids, the volume of adipose tissue, and increased thermogenesis, uncoupling protein 1, and the AMPK pathway expression. In the in vitro study, CT prevented the formation of lipid droplets from MSCs while activating brown genes and the AMPK pathway. AMPK activator enhanced CT's effects, while the AMPK inhibitor reversed the effects of CT. CT promotes adipose tissue browning to increase body thermogenesis and reduce obesity by activating the AMPK pathway. This study provides an experimental foundation for the use of CT in obesity treatment.

Predictive value of early postoperative blood lipid metabolism for anastomotic leakage after esophageal cancer surgery.

To explore the clinical value of assessing early postoperative blood lipid metabolism levels in predicting anastomotic leakage (AL) after esophageal cancer (EC) surgery. The clinical data of EC patients who underwent surgery at the Northern Jiangsu People's Hospital from May 2021 to May 2023 were retrospectively studied. Totally, 28 patients who developed AL were included in the AL group, while 110 patients who did not develop AL were included in the non-AL group. Outcomes compared between the two groups included clinical baseline data, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Logistic regression analysis was performed to identify independent risk factors for postoperative AL. The predictive value of early postoperative blood lipid metabolism levels for AL was evaluated using Receiver Operating Characteristic (ROC) curves. The AL group exhibited significantly elevated levels of TC and LDL-C but significantly reduced HDL-C levels compared to the non-AL group (all P<0.05). However, there was no significant difference in triglyceride levels between the two groups (P>0.05). Logistic regression analysis revealed that low BMI (P=0.012; OR: 4.409; 95% CI: 1.391-13.976), comorbid hypertension (P=0.011; OR: 5.891; 95% CI: 1.492-23.259), comorbid diabetes (P=0.022; OR: 4.522; 95% CI: 1.238-16.521), low HDL-C (P=0.007; OR: 19.965; 95% CI: 2.293-173.809), and high LDL-C (P=0.012; OR: 4.321; 95% CI: 1.388-13.449) were independent risk factors for developing AL after EC surgery. The combined prediction model using TC, HDL-C, and LDL-C yielded an area under the curve (AUC) of 0.876, with a sensitivity of 79.09%, specificity of 85.71%, and overall accuracy of 80.44%, significantly outperforming individual lipid measurements. The combined assessment of TC, HDL-C, and LDL-C can effectively predict the occurrence of AL after EC surgery. For EC patients with relatively low BMI, hypertension, diabetes, relatively low HDL-C, and relatively high LDL-C, prioritizing weight management, hypertension and diabetes control, and lipid management can significantly reduce the risk of AL post-surgery.

Obesity from Clinical Evaluation to Management Local Perspective

For over two millennia, physicians have been aware of the morbidity and mortality linked to overweight and obesity. Various definitions of obesity, as outlined by the World Health Organization (WHO) and the Centers for Disease Control &amp; Prevention (CDC), utilize the Body Mass Index (BMI) to characterize these conditions. Screening for high-risk patients is crucial for guiding lifestyle changes, treatment decisions, and risk reduction strategies.1,2 The assessment involves clinical and laboratory studies to categorize the type and severity of obesity, forming the foundation for effective management. Globally, the prevalence of obesity in 2015 exhibited a rising trend in females compared to males. Between 1980 and 2015, the prevalence surged from 11.1% to 38.3% for males aged 25 to 29 in low to middle-income countries.3 Pakistan ranks tenth among 188 countries, with half of its population classified as overweight or obese. Alarming projections from the World Obese Federation estimate that 5.4 million Pakistani school-aged children will grapple with obesity by 2030, emphasizing the dual challenges of overnutrition and poor nutrition.4,5 World Health Organization data indicates that 58.1% of Pakistanis are overweight, with 43.9% classified as obese. Asian cutoffs, though not globally recognized, suggest that 72.3% of Pakistanis are overweight, with obesity affecting 58.1% of the population. Research by Danielle H. Bodicoat et al. suggests an obesity threshold of 25 kg/m2 for South Asian individuals, coupled with a very high Waist Circumference (WC).6 A WC ≥ 31 inches (80cm) in Asian females and ≥ 35 inches (90cm) in Asian males is considered abnormal. The primary rationale for managing obesity is to mitigate morbidity, including conditions like diabetes, hypertension, dyslipidemia, heart disease, stroke, sleep apnea, and cancer, ultimately reducing mortality. The initial step in managing obesity involves screening to determine the degree of overweight using BMI and waist circumference measurements. However, studies reveal that only 6% of individuals receive ongoing care for weight management, such as prescriptions for obesity medication or referrals to dieticians.7,8 BMI classifications, primarily based on cardiovascular disease (CVD) risk, may underestimate risks for conditions like diabetes in the Asian population. Beyond BMI, measuring waist circumference is essential for identifying adults at increased risk for morbidity and mortality, especially in the BMI range of 25 to 35 kg/m2.9 In addition to physical examinations, measurements of fasting glucose (or glycated hemoglobin [A1C]), thyroid-stimulating hormone (TSH), liver enzymes, and fasting lipids should be conducted.10 Investigating the causes of obesity involves ruling out a sedentary lifestyle, increased caloric intake, and secondary factors. Medical history should include inquiries about medications that cause weight gain and smoking cessation. Weight loss interventions are recommended for those with a BMI exceeding 25 kg/m2, aiming to prevent, treat, or reverse complications associated with obesity. In conclusion, managing obesity in the Pakistani population requires a comprehensive approach involving clinical and laboratory assessments by physicians. This includes evaluating height, weight, BMI, waist circumference, blood pressure, serum triglycerides, serum HDL, cholesterol, fasting blood sugar/HbA1C, history of sleep apnea, medication history, physical activity, and etiological factors. Moreover, physicians should possess knowledge of dietary goals and medications promoting weight loss and consider bariatric surgery if non-responsive to other interventions.

Association between visit-to-visit lipid variability and risk of ischemic heart disease: a cohort study in China.

To explore the associations between visit-to-visit lipid variability and risk of ischemic heart disease (IHD) in a population-based cohort in China. We evaluated lipid variability in 30,217 individuals from the Yinzhou Health Information System who had ≥3 recorded lipid measurements during 2010-2014. We used various indicators including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV) to quantify the variability in triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, a total of 1305 participants with IHD were identified during the follow-up of 194,421 person-years. Subjects in Q4 had a 21% elevated risk of IHD (HR = 1.21, 95% CI: 1.03-1.41) for LDL-C variability (CV) compared with the reference (Q1). The HRs for Q4 vs Q1 were 1.21 (95% CI: 1.04-1.42) for HDL-C variability, and 1.28 (95% CI: 1.10-1.50) for TC variability. However, no association was observed between triglycerides variability and risk of IHD. Higher variability in LDL-C, HDL-C, and TC levels was associated with an elevated risk of IHD, suggesting that lipid variability could be considered as an independent risk factor of IHD.

Cyp3A4 *1G polymorphism is associated with alcohol drinking: A 5-year retrospective single centered population-based study in China.

We investigated the epidemiology of Cytochrome P450 (CYP) 3A4 genotype and the relationship between CYP3A4 genotype and alcohol drinking habits. A single-centered retrospective study was conducted on 630 patients who underwent CYP3A4*1G genetic testing. Their relevant information on epidemiology and etiology was collected. Laboratory testing, including CYP3A4*1G genotype, liver function tests, and serum lipid measurements were performed. Bi-variate logistic regressions were used to examine the relationship between variables. The relationship between alcohol drinking and CYP3A4*1G genotype was estimated. Demographic and clinical features were analyzed. Participants with drinking history were divided into non-heavy drinking and heavy drinking groups. Liver function and dyslipidemia of participants with drinking histories were compared between CYP3A4*1G mutation (GA+AA) and wild-type (GG) groups. Participants with CYP3A4*1G mutation(GA+AA) had an increased adjusted odds ratio (AOR) of 2.56 (95% CI, 1.4-4.65; P = 0.00) for alcohol abuse when compared with participants without CYP3A4 mutation (GG). In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury levels and serum lipid levels between CYP3A4*1G mutant and wild-type groups. Patients with CYP3A4*1G mutation had an increased AOR of cardiac-vascular diseases and malignant diseases compared with patients without CYP3A4*1G mutation. The epidemiology had no difference between GA and AA group. The study indicated that there was association between alcohol drinking and CYP3A4*1G genetic mutation. In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury and dyslipidemia between CYP3A4*1G mutant and wild-type groups. CYP3A4*1G mutation was also related to cardiac-vascular diseases and malignant diseases.

Association between daily screen time and risk of stroke among middle-aged and elderly people: research based on China health and nutrition survey.

We aimed to explore the independent associations between screen time and the risk of stroke among Chinese adults based on the China Health and Nutrition Survey (CHNS). Data on Chinese adults aged older than 40 years from the CHNS in during 2004-2009 were selected. A total of 4,587 individuals were included in 2009, including screen time and the risk of stroke. Simultaneously, we traced the previous screen time to 2004 for those with outcome measures in 2009 (n = 2,100). Basic information, lifestyle, and screen behavior were obtained through face-to-face interviews and self-completed questionnaires. Anthropometric data collected included blood pressure, body weight, height, hip circumference, and waist circumference. Fasting blood was obtained for measurements of lipid and glucose levels. Cross-sectional analysis and cohort analysis were both performed using multivariate logistic regression. Of all participants, 3,004 (65.49%) participants spent more than 2 h per day on screen time. Taking the men who spent less than 2 h on screen per day as reference, the crude odds ratio (OR) of the high risk of stroke was 1.53 [95% confidence interval (CI), 1.20-1.95] for the men who spent 2-3 h per day on screen and 2.37 (95% CI, 1.78-3.16) for the men who spent more than 3 h per day on screen. This difference remained significant after adjusting for confounding factors. No association was observed among women. However, in the cohort analysis with screen time in 2006 as the independent variable, the association between screen time and stroke risk was found both in men [OR, 1.83 (95% CI, 1.19-2.82)] and women [OR, 1.48 (95% CI, 1.10-1.99)]). We found that the high screen time was associated with an increased stroke risk, which was pronounced in men, warranting a universal need to limit screen time in order to improve health.

Discordance analysis for apolipoprotein and lipid measures for predicting myocardial infarction in statin-treated patients with coronary artery disease: a cohort study.

The optimal apolipoprotein or lipid measures for identifying statin-treated patients with coronary artery disease (CAD) at residual cardiovascular risk remain controversial. This study aimed to compare the predictive powers of apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apoB/apolipoprotein A-1 (apoA-1) and non-HDL-C/HDL-C for myocardial infarction (MI) in CAD patients treated with statins in the setting of secondary prevention. The study included 9191 statin-treated CAD patients with a five-year median follow-up. All measures were analyzed as continuous variables and concordance/discordance groups by medians. The hazard ratio (HR) with 95% CI was estimated by Cox proportional hazards regression. Patients were classified by the clinical presentation of CAD for further analysis. The high-apoB-low-LDL-C and the high-non-HDL-C-low-LDL-C categories yielded HR of 1.40 (95% CI: 1.04-1.88) and 1.51 (95% CI: 1.07-2.13) for MI, respectively, whereas discordant high LDL-C with low apoB or non-HDL-C was not associated with the risk of MI. No association of MI with discordant apoB versus non-HDL-C, apoB/apoA-1 versus apoB, non-HDL-C/HDL-C versus non-HDL-C, or apoB/apoA-1 versus non-HDL-C/HDL-C was observed. Similar patterns were found in patients with acute coronary syndrome. In contrast, no association was observed between any concordance/discordance category and the risk of MI in patients with chronic coronary syndrome. ApoB and non-HDL-C better predict MI in statin-treated CAD patients than LDL-C, especially in patients with acute coronary syndrome. ApoB/apoA-1 and non-HDL-C/HDL-C show no superiority to apoB and non-HDL-C for predicting MI.

Alternating current electromagnetic field exposure lessens intramyocellular lipid accumulation due to high-fat feeding via enhanced lipid metabolism in mice.

Long-term high-fat feeding results in intramyocellular lipid accumulation, leading to insulin resistance. Intramyocellular lipid accumulation is related to an energy imbalance between excess fat intake and fatty acid consumption. Alternating current electromagnetic field exposure has been shown to enhance mitochondrial metabolism in the liver and sperm. Therefore, we hypothesized that alternating current electromagnetic field exposure would ameliorate high-fat diet-induced intramyocellular lipid accumulation via activation of fatty acid consumption. C57BL/6J mice were either fed a normal diet (ND), a normal diet and exposed to an alternating current electromagnetic field (ND+EMF), a high-fat diet (HFD), or a high-fat diet and exposed to an alternating current electromagnetic field (HFD+EMF). Electromagnetic field exposure was administered 8 hrs/day for 16 weeks using an alternating current electromagnetic field device (max.180 mT, Hokoen, Utatsu, Japan). Tibialis anterior muscles were collected for measurement of intramyocellular lipids, AMPK phosphorylation, FAT/CD-36, and carnitine palmitoyltransferase (CPT)-1b protein expression levels. Intramyocellular lipid levels were lower in the HFD + EMF than in the HFD group. The levels of AMPK phosphorylation, FAT/CD-36, and CPT-1b protein levels were higher in the HFD + EMF than in the HFD group. These results indicate that alternating current electromagnetic field exposure decreases intramyocellular lipid accumulation via increased fat consumption.

Cardiac and Metabolic Effects of Bariatric Surgery Among Obese Patients in a Malaysian Tertiary Hospital: A 6-month Prospective Cohort Study.

Obesity is known to be associated with left ventricular diastolic dysfunction due to its effect on blood pressure and glucose tolerance. We aimed to investigate whether weight loss after bariatric surgery might improve diastolic dysfunction through in-depth echocardiographic examination. We recruited twenty-eight patients who were about to undergo bariatric surgery by purposive sampling. They underwent echocardiography at baseline and 6 months after surgery with a focus on diastolic function measurements and global longitudinal strain (GLS). They also had fasting serum lipid and glucose measurements pre- and post-surgery. The mean weight loss after surgery was 24.1 kg. Out of the 28 subjects, fifteen (54%) initially had diastolic dysfunction before surgery. Only two had persistent diastolic dysfunction 6 months after surgery. The mean indexed left atrial volume 6 months post-surgery was 27.1 from 32 ml/m2 prior to surgery. The average E/e' is 11.78 post-surgery from 13.43 pre-surgery. The left ventricular GLS became (-)25.7% after surgery from (-)21.2% prior to surgery. Their post-surgery fasting serum lipid and glucose levels also showed significant improvement. Our study reinforced the existing evidence that bariatric surgery significantly improved echocardiographic parameters of diastolic function and left ventricular global longitudinal strain, along with various metabolic profiles.

Metabolic association of serum prolactin in polycystic ovary syndrome: A retrospective analysis of 840 patients in Bangladesh

AimsTo explore the metabolic influence of prolactin in subjects with polycystic ovary syndrome (PCOS). MethodsThis retrospective cross-sectional study analyzed data of women newly diagnosed with PCOS attending the Endocrinology outpatient department of a tertiary hospital in Mymensingh, Bangladesh, during 2017–2022. Clinical, anthropometric, and laboratory data, including results of oral glucose tolerance test, measurements of serum lipids, total testosterone (TT), thyroid-stimulating hormone (TSH), and prolactin, were extracted and analyzed. Cases of high prolactin (≥100 ng/mL) were excluded. Results840 cases [median age 21.5 (18.0–25.7) years] were considered for final analysis; 17.1 % had hyperprolactinemia. Serum prolactin had significant negative correlations (P < 0.05) with age (rs = − 0.153), body mass index (rs = − 0.172), waist circumference (rs = − 0.193), triglyceride (rs = − 0.174), and TT (rs = − 0.133) levels, and the presence of metabolic syndrome (rs = − 0.073) and positive correlations with TSH (rs = 0.090). In multiple regression analysis, prolactin was inversely associated with fasting plasma glucose (FPG) and positively associated with TSH after correcting for age and BMI. ConclusionAn inverse association exists between serum prolactin levels and some metabolic risk factors, such as FPG, in women with PCOS.

Trajectories of Blood Lipids Profile in Midlife Women: Does Menopause Matter?

It remains controversial whether changes of lipids over menopause transition (MT) are more age-related or more menopause-related. We aimed to classify women into different trajectory groups based on pattern and level of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C), triglyceride, and apolipoprotein A-I over the MT, as well as examine the effect of MT-related factors on lipid trajectory groups and levels. The cohort included 2582 subjects from the Study of Women's Health Across the Nation. Different trajectory patterns of lipids during the MT were determined using the latent class growth mixture model. The predictors of distinct blood lipids trajectory groups were determined by multiple linear regression models and multinomial logistic regression models. Women were categorized into either inverse U-shape or progressing trajectory group in each blood lipids measurement. The inverse U-shape total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, high-density lipoprotein cholesterol, log(TG), and apolipoprotein A-I trajectories showed an increasing trend before menopause but a decreasing trend after menopause. The U-shape total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B trajectories started to rise 5 years before menopause. Age at menopause, follicle-stimulating hormone, vasomotor symptoms, and estradiol predicted the shape and level of the women's lipids over the MT. Distinct lipid trajectories were identified during the MT, and the existence of at least 1 trajectory in each lipid parameters suggested a contribution of menopause. Our study highlights the need for earlier and continuous surveillance of lipids during the MT.

Large-scale lipidomics profiling reveals characteristic lipid signatures associated with an increased cardiovascular risk

Abstract Background Patients with cardiovascular disease (CVD) are at high risk to develop adverse events.1 The distinct risk of developing recurring adverse cardiovascular events is not solely explained by traditional risk factors.2-4 Platelets are essentially involved in progression of CVD including coronary artery disease (CAD) and platelet hyperreactivity leads to development of adverse cardiovascular (CV) events.5-7 Alterations in the platelet lipidome are associated with disease severity in CAD and lead to platelet hyperresponsiveness and thus might alter the individual risk profile.8,9 Objective In this study we investigate the platelet lipidome of CAD patients by untargeted lipidomics and elucidate alterations in the lipid composition of patients with recurring adverse cardiovascular events. Methods We characterized the platelet lipidome in a large consecutive CAD cohort (n=1057) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. Results The platelet lipidome in this study covered 767 lipids and characteristic changes occurred in patients with adverse cardiovascular events. The most prominent upregulated lipids in patients with cardiovascular events primarily belong to the class of phospholipids (lysophosphatidylethanolamines (LPE)) and fatty acyls (acylcarnitines (CAR) and unsaturated fatty acids (FA)). It was striking that patients with ischemic events exclusively showed upregulation of LPE whereas mainly CAR and FA were upregulated in patients with major bleeding events in contrast to patients without CV events (Figure 1 A, B). PCA revealed a major separation of patients with adverse CV events when compared to patients free from any events during follow-up indicating a substantial change in the platelet lipidome of patients with adverse CV events (Figure 1C). Further, upregulated platelet lipids are associated with an increased cardiovascular or bleeding risk and independently predict upcoming adverse events (Figure 2 A, B). Stratification of an increased CV risk in patients with CAD including platelet lipids outperformed conventional risk assessment utilizing conventional lipids measurements (e.g. plasma lipoproteins) (Figure 2 C). In addition, specific alterations of the platelet lipidome, including LPE and CAR are associated with modulation of in vitro platelet functions and thus, might contribute to the development of adverse CV events by promotion or inhibition of platelet functions (Figure 2D, E). Conclusions Our results reveal that the composition of the platelet lipidome is altered in CVD patients with an increased cardiovascular risk and distinct platelet lipids may indicate adverse events. Results of this study may contribute to improved risk discrimination and classification for cardiovascular events in patients with CVD. Further, altered lipid signatures might modulate platelet function and contribute to disease progression and development of adverse CV events in patients with CVD.Figure 1Figure 2

6 Exercise Induced Growth Factor Increases Directly and Indirectly Reduce Systemic Vascular Risk Parameters: Translational Project Amongst Midlife Human and Animal Models of Preclinical Alzheimer’s disease and Vascular Dementia

Objective:Using a humanized APOE3/4 (Alzheimer’s disease genetic risk allele) mouse model we investigated the potential modulating effects of exercise on systemic risk factors and the ability of this mouse model to translate to active or sedentary, midlife, human participants. We present preliminary results of an ongoing, translational pilot study.Participants and Methods:26 Midlife individuals, ages 40-65, were recruited from the community and dichotomized into active or sedentary groups following health screening and cognitive assessment. Blood samples were drawn from human participants for lipid assessment and other general health measures as well as peripheral growth factors concentrations (VEGF, BDNF and FGF21). Traditional, transgenic mouse models have helped the scientific community to understand biological mechanisms of Alzheimer’s disease (AD), but they do not develop significant neuronal loss, a hallmark of AD pathology. The MODEL-AD consortium has created a new “humanized” APOE4 model that has the human APOE4 allelic sequence in place of the mouse APOE gene; the model has shown known human phenotypes including deficits in cholesterol trafficking, amyloid clearance and BBB integrity. Of upmost importance, this model does not develop a full AD phenotype indicating that additional genetics and/or environmental factors are required as would be seen in human populations. We used males and females of this model to complete identical sedentary and active measures of each APOE genotype.Results:Lipid and general health marker assessment between mouse and human were similar and reproduced published literature. In both humans and mice we saw increased total cholesterol and HDL in active females and decreased total cholesterol and HDL in active males. We also saw similar relationships between APOE genotype, sex, and activity with regards to triglycerides. Although total cholesterol, HDL and LDL measures are the primary lipids needed to confirm or deny translation, other lipid measurements were not equivalent between the two models. Growth factor assessment in both species are also similar and reproduce published literature with regards to VEGF and BDNF as we see trending elevated levels in the active group. Less published on is the finding seen between active females and these elevated growth factors levels; our results indicates that although elevated as a result of exercise, this increase may be more prominent in females.Conclusions:Based on the results found here we conclude that The Jackson Laboratory’s humanized APOE3/4 mouse model is a translatable model of vascular dysfunction, dementia and Alzheimer’s disease. We also conclude that exercise modulates these aspects by growth factor activation and increases resulting in downstream effects that reduce peripheral vascular risk factors and therefore reduce the risk of Alzheimer’s disease as a result of neuroinflammation. Complete, APOE genotype results from human participants are still ongoing. Descriptive analysis is limited by human samples size.

Association of LDL-cholesterol subfractions with cardiovascular disorders: a systematic review

BackgroundCardiovascular disorders (CVDs) are the leading cause of death worldwide. This study aimed to evaluate the association between low-density lipoprotein (LDL) subfractions and cardiovascular disorders.MethodsTo ensure the rigor of the systematic review, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. For this systematic review, a comprehensive search strategy was performed in important databases including PubMed, Scopus, Embase, International Statistical Institute (ISI) Web of Science, and google scholar from 2009 to February 2021. The following terms were used for systematic search: low-density lipoprotein, LDL, subfractions, subclasses, nuclear magnetic resonance, NMR, chromatography, high-pressure liquid, HPLC, cardiovascular disease, cerebrovascular, and peripheral vascular disease. Also, for evaluating the risk of bias, the Newcastle-Ottawa scale was employed.ResultsAt the end of the search process, 33 articles were included in this study. The results of most of the evaluated studies revealed that a higher LDL particle number was consistently associated with increased risk for cardiovascular disease, independent of other lipid measurements. Also, small dense LDL was associated with an increased risk of CVDs. There was no association between LDL subfraction and CVDs in a small number of studies.ConclusionsOverall, it seems that the evaluation of LDL subclasses can be used as a very suitable biomarker for the assessment and diagnosis of cardiovascular diseases. However, further studies are required to identify the mechanisms involved.

Variations in the Relative Abundance of Gut Bacteria Correlate with Lipid Profiles in Healthy Adults.

The gut microbiome is a versatile system regulating numerous aspects of host metabolism. Among other traits, variations in the composition of gut microbial communities are related to blood lipid patterns and hyperlipidaemia, yet inconsistent association patterns exist. This study aims to assess the relationships between the composition of the gut microbiome and variations in lipid profiles among healthy adults. This study used data and samples from 23 adult participants of a previously conducted dietary intervention study. Circulating lipid measurements and whole-metagenome sequences of the gut microbiome were derived from 180 blood and faecal samples collected from eight visits distributed across an 11-week study. Lipid-related variables explained approximately 4.5% of the variation in gut microbiome compositions, with higher effects observed for total cholesterol and high-density lipoproteins. Species from the genera Odoribacter, Anaerostipes, and Parabacteroides correlated with increased serum lipid levels, whereas probiotic species like Akkermansia muciniphila were more abundant among participants with healthier blood lipid profiles. An inverse correlation with serum cholesterol was also observed for Massilistercora timonensis, a player in regulating lipid turnover. The observed correlation patterns add to the growing evidence supporting the role of the gut microbiome as an essential regulator of host lipid metabolism.

Impact of 24-week dapagliflozin treatment on body weight, body composition, and cardiac risk indicators of patients with type-2 diabetes mellitus.

To reveal the impacts of dapagliflozin, a sodium glucose transporter-2 inhibitor (SGLT-2i), on body weight and body composition, cardiovascular risk indices, and carotid intima-media thickness (CIMT). The data of patients with type-2 diabetes mellitus (T2DM) who applied to Department of Endocrinology and Metabolic Disorders between September 2019 and 2020, and had started dapagliflozin treatment along with their current medications were recorded retrospectively. Body weights, body compositions measured through bioelectrical impedance, and CIMT with T2DM receiving SGLT-2i treatment and medication were measured at weeks 1, 12, and 24 of 42. The visceral adiposity index (VAI), lipid accumulation product (LAP), and atherogenic index of plasma (AIP) were used to determine the lipid measurements and anthropometric values. The mean change in the total body weight and total fat mass was -2.96 and -1.97 kg, respectively (p < 0.001). There was a reduction in total fat mass of 1.23 kg (from 31.4 to 29.3 kg, p < 0.001) and in body fat percentage of 2.5% (from 35.8% to 34.4%, p < 0.001) in the first 12 weeks. A mild increase was observed in both the total fat mass and body fat percentage between weeks 12 and 24, which was not statistically significant (p = 0.783 and p = 0.925, respectively), whereas there was a statistically significant reduction in high-sensitive C-reactive protein (hsCRP), AIP, and CIMT values (p = 0.006, p = 0.035, and p = 0.007, respectively). No changes were observed in the VAI and LAP values (p = 0.985 and p = 0.636, respectively). It was observed that dapagliflozin not only contributes to weight and fat loss but also has positive impacts on cardiovascular and atherosclerotic indicators.

FRI660 Serum Lipids And Inflammatory Markers Reveal Race-associated Differences Between Diabetics And Non-diabetics

Abstract Disclosure: G. Pacheco Sanchez: None. M.L. Lopez: None. C. Jang: None. M.K. Evans: None. A.B. Zonderman: None. R. Kapadia: None. D.A. Nicholas: None. Health disparities (HD) disproportionately affect racial groups. One of the fastest growing HD worldwide with severe health consequences and high mortality rates is Type 2 Diabetes (T2D). T2D is an inflammatory disease associated with an increase in body mass index (BMI), a common obesity measurement, and clinically characterized by dysregulation of lipids or dyslipidemia. Reports suggest that compromised lipid metabolism can exacerbate chronic inflammation seen in T2D. Importantly, lipid metabolism can be impacted by systemic overabundance of lipids, a condition that has been reported to impact some racial groups, like African Americans (AA), in a disproportionate manner. Further, literature supports that elevated levels of inflammatory molecules correlate with excess of systemic lipids and impact the risk to develop T2D in AA women. Despite previous efforts, comprehensive biological information is still needed to determine the relationship of lipids and inflammation to the onset and/or progression of T2D. Here we show results from identified metabolic, and immunological features of serum and plasma samples derived from a cohort of AA and White individuals with and without T2D.Evaluation of clinical parameters related to metabolic state indicate that lipids measurements, such as blood concentrations of low-density cholesterol (LDL), high-density cholesterol (HDL), total cholesterol to HDL ratio, and triglycerides, are the main drivers of biological variability in our cohort, irrespective of diabetes status and race. Counterintuitively, Hemoglobin A1C and other glucose-related clinical standardized T2D measurements were not beneficial at addressing cohort variability. Based on results from our cytokine and chemokine analysis performed using a comprehensive 53-analytes Luminex panel we conclude that: : 1) Significant inflammatory molecules differences at a univariate level are seen when comparing AA and white in our total cohort, differences maintained irrespective of diabetes status; and 2) In a multivariate analysis, differential expression of a distinctive inflammatory cluster of cytokines and chemokines, composed of Eotaxin, IL6, IL18, IL27, IP10, MCP1, MDC and CXCL9, was identified between AA and whites, once again irrespective of diabetes status. Importantly, BMI had no major biological effect on any of the parameters we measured. Our results demonstrate a relation between lipids, not glucose, and the differential expression of inflammatory molecules, not conventionally reported for T2D, in a race-dependent manner. We anticipate this work to be the starting point for mechanistic studies addressing modulation of inflammatory responses by race-specific lipids profiles and components, for a better understanding of the immunometabolic contributors to HD. Presentation: Friday, June 16, 2023

Association between exposure to air pollution and blood lipids in the general population of Spain.

We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain. We included 4647 adults (>18 years), participants in the national, cross-sectional, population-based di@bet.es study, conducted in 2008-2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1 H-NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter <10 μm (PM10 ), <2.5 μm (PM2.5 ) and nitrogen dioxide (NO2 ), corresponding to the health examination year, obtained by modelling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). In multivariate linear regression models, each IQR increase in PM10 , PM2.5 and NO2 was associated with 3.3%, 3.3% and 3% lower levels of HDL-c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL-p) concentrations (p < .001 for all associations). In multivariate logistic regression, there was a significant association between PM10 , PM2.5 and NO2 concentrations and the odds of presenting low HDL-c (<40 mg/dL), low HDL-p (<p25) and higher LDL particle (LDL-p) concentrations (≥p75). In subgroup analyses there were stronger associations between PM10 and NO2 and low HDL-p in men (p for interaction .008 and .034), and between NO2 and low HDL-p in individuals with obesity (p for interaction .015). Our study shows an association between the exposure to air pollutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosis.

FRI181 Increased LDL Particle And Apolipoprotein B Concentrations In Patients With Nonfunctioning And Cortisol Secreting Adrenal Adenomas

Abstract Disclosure: R. Sandooja: None. A. Kittithaworn: None. P. Dogra: None. D. Gruppen: None. E. Atkinson: None. S. Achenbach: None. K. Yu: None. M. Connelly: None. V. Simha: None. R.P. Dullaart: None. I. Bancos: None. INTRODUCTION: Based on the spectrum of cortisol excess, adrenal adenomas are classified as adenomas with Cushing syndrome (CS), adenomas with mild autonomous cortisol secretion (MACS), and non-functioning adenomas (NFA). Patients with adrenal adenomas demonstrate a high prevalence of cardiovascular morbidity and mortality proportional to the degree of hypercortisolism. Evidence on whether dyslipidemia is a contributing cardiovascular risk factor in patients with NFA and MACS is discrepant. We aimed to characterize (apo) lipoprotein abnormalities across the spectrum of cortisol excess in patients with adenomas as compared to referent subjects. METHODS: Study Design: Single center cross sectional study between 01/2015 - 05/2021.Patients: Adults with NFA, MACS, or CS were consecutively enrolled. MACS was diagnosed based on post-dexamethasone cortisol &amp;gt;1.8 mcg/dL. Referent subjects were recruited from local population of patients with available abdominal imaging and no adrenal disorders. All subjects provided fasting ethylenediaminetetraacetic acid (EDTA) venous samples. Measurements: Nuclear magnetic resonance (NMR) spectroscopy measurements included total cholesterol (TC), low-density lipoprotein (LDL) and LDL particle concentrations, high-density lipoprotein (HDL) subclasses, apolipoprotein B (apo B), triglycerides (TG) and TG-rich lipoprotein concentrations. RESULTS: Participants included 101 patients with CS (median age 44 years, IQR 31-58, 85% women), 158 patients with MACS (median age 62 years, IQR 51-70, 62% women), 166 patients with NFA (median age 60 years, IQR 53--66, 63% women) and 136 referent subjects (median age 68 years, IQR 57-77, 52% women). Patients had higher BMI (32 vs 27 kg/m2), higher prevalence of hypertension (72% vs 46%) and diabetes mellitus (27% vs 9%) as compared to reference subjects. Statin therapy was used in 32% of patients and referent subjects. After adjusting for age, sex, BMI, smoking, diabetes, hypertension, and statin therapy, as compared to referent subjects, we found inconsistent increase in TC, LDL cholesterol and TG across CS, MACS and NFA and no consistent differences in LDL size, HDL variables, TG and TG-rich lipoproteins. However, when compared to referent subjects, LDL particle concentrations- CS(OR 1.78, 95% CI 1.33-2.39), MACS (OR 1.31, 95% CI 1.03-1.67), and NFA (OR 1.43, 95% CI 1.12-1.82) and Apo B levels were higher in all patient categories: CS (OR 2.26, 95% CI 1.57-3.24), MACS (OR 1.36 95% CI 1.00-1.85 ), and NFA (OR 1.54 95% CI 1.13-2.09). These differences were particularly evident in patients not on statin therapy. CONCLUSIONS: We found that LDL particle and Apo B concentrations were elevated in all patient groups, including those with MACS and NFA. In comparison to conventional lipid measurements, LDL particle and Apo B may serve as a better biomarker of the future cardiovascular risk in patients with adrenal adenomas. Presentation: Friday, June 16, 2023