Non-high Density Lipoprotein Research Articles

Estimation of individual lifetime cardiovascular disease risk and treatment benefit in patients with established atherosclerotic cardiovascular disease: the updated SMART-REACH2 model

Abstract Background The 2021 ESC Guidelines on Cardiovascular Disease (CVD) Prevention in Clinical Practice recommend using (lifetime) risk to guide preventive treatment intensification. Purpose Updating and systematically recalibrating the SMART-REACH lifetime prediction model for the estimation of lifetime risk of recurrent CVD in patients with established atherosclerotic CVD (ASCVD) to various European and international risk regions. Methods The updated SMART-REACH (i.e., SMART-REACH2) model was derived using data from 9,477 individuals between 40-90 years with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms included in the UCC-SMART cohort in whom 2,090 ASCVD events were observed during a median follow-up of 8.9 years (interquartile range 4.5–14.1). Coefficients for type of CVD, estimated glomerular filtration rate, non-high density lipoprotein cholesterol, systolic blood pressure, duration of CVD, C-reactive protein, current smoking, and presence of diabetes were derived using sex-stratified cause-specific Cox models with age as the time axis, adjusted for the competing risk of non-CVD mortality. Lifetables were used to estimate 10-year and lifetime CVD-risk and CVD-free life expectancy. The SMART-REACH2 model was externally validated in 121,701 patients from the NOR-COR, Nor-COAST, HUNT3, SWEDEHEART, Bialystok PLUS/Polaspire, REACH-EU, and REACH non-EU (Asia, Japan, Latin America, North America) covering 43 countries. The model was recalibrated to specific risk regions based on the expected-observed ratios from representative cohorts. Performance was assessed by calibration of predicted and observed risk and Harrel’s C-statistic for discrimination. Results 16,689ASCVD events were observed in the external validation cohorts. The model was visually well calibrated for the various risk regions. The pooled C-statistic across risk regions was 0.665 [95% confidence interval 0.640-0.691], with adequate performance in the separate regions (Figure 1). Using SMART-REACH2 to estimate potential gain in CVD-free life expectancy upon treatment initiation showed varying projections. For example, two comparable 55-year-old males from the low-risk region and very high-risk region would gain an estimated 2.2 and 3.9 CVD-free life years as a result of smoking cessation (Figure 2). Conclusion(s) By using larger and more contemporary data sources, considering geographical differences, and extending the age range, the updated SMART-REACH2 model provides an improved algorithm for the estimation of lifetime risk and CVD-free life expectancy for individuals with established ASCVD, facilitating shared decision-making for cardiovascular prevention as recommended by the 2021 ESC Prevention of CVD guidelines.C-statistics across global risk regionsCase vignette

Association of lipid target achievement and cardiovascular outcomes following statin initiation: a population-based cohort study

Abstract Introduction Non-high density lipoprotein cholesterol (non-HDL-C) is increasingly incorporated into clinical practice guidelines along with low density lipoprotein cholesterol (LDL-C) to guide lipid-lowering therapy decisions. We aimed to examine patterns of LDL-C and non-HDL-C levels after statin initiation for primary prevention of cardiovascular disease (CVD), and their association with incident CV events. Methods We conducted a population-based cohort study of Ontario, Canada residents age ≥66 years who initiated a statin for primary prevention between January 1, 2012 and December 31, 2019. For those surviving 1-year after statin initiation, we determined the proportion with a lipid panel in the 1-year period after a statin was started. For those with a lipid panel, we used the lipid panel closest to the end of the 1-year period to categorize individuals based on the LDL-C and non-HDL-C thresholds in the 2021 Canadian Cardiovascular Society dyslipidemia guidelines (Table 1). We stratified by diabetes/chronic kidney disease (CKD) status. We evaluated the association between LDL-C/non-HDL-C category and a composite of all-cause mortality or hospitalization for myocardial infarction, stroke or revascularization (primary outcome). We also investigated the association between each category and each component of the primary outcome. The index date was the 365 days after a statin was initiated and follow-up was until December 31, 2020. We used a cause-specific hazards model for analysis, adjusted for clinical and sociodemographic confounders. Results Our cohort comprised 173,127 people. In the 1-year period after statin initiation, 72% of people had a follow-up lipid panel performed. Median follow-up after that was 2.5 years. Compared with those meeting both LDL-C and non-HDL-C targets, being above both targets was associated with an increased rate of the primary outcome for people without diabetes/CKD (HR 1.10, 95% CI 1.05 to 1.15) and those with diabetes/CKD (HR 1.16, 95% CI 1.09 to 1.23). Being at LDL-C target but above non-HDL-C target was associated with an increased rate of the primary outcome for people with diabetes/CKD (HR 1.16, 95% CI 1.03 to 1.30) but not for those without diabetes/CKD (HR 1.05, 95% CI 0.93 to 1.17). Conclusions In this population-based cohort, having an LDL-C and non-HDL-C above guideline-recommended targets after statin initiation was associated with an increased rate of adverse outcomes. These findings support the residual risk associated with incompletely controlled LDL-C or non-HDL-C levels after initiating statin therapy for primary prevention.Primary outcome associationsComponents of primary outcome

Identifying clinical phenotype clusters for coronary artery disease: a novel approach using clustering by unsupervised machine learning

Abstract Background Guideline recommendations for the prevention of cardiovascular (CV) events in patients with coronary artery disease (CAD) are one-size-fits-all. Clinically identifiable phenotypes needing specific considerations might exist. Purpose To identify phenotypes in patients with CAD based on clinical characteristics and their relationship with the risk of new CV events and treatment benefits. Methods Unsupervised machine learning through latent class analysis (LCA) was performed on patients with CAD included in the UCC-SMART cohort (n = 5,888) and SWEDEHEART registry (n = 67,428), to identify patient clusters (i.e., phenotypes) based on clinical characteristics: age, sex, body-mass-index, diastolic blood pressure, history of diabetes, myocardial infarction, atrial fibrillation, polyvascular disease, current smoking, non-high density lipoprotein cholesterol, estimated glomerular filtration rate, and C-reactive protein. Number of clusters was determined using the Bayesian information criterion. Event free survival and hazard ratios (HR) for major adverse cardiovascular events (MACE) as primary endpoint, including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, were estimated per cluster. The LCA were performed in each respective cohort and cross-validated in the other cohort to assess impact of variations in clustering variables on cluster reproducibility. In UCC-SMART, bootstrapping was performed the assess stability of the LCA model and impact on cluster assignment. Results In UCC-SMART four distinct phenotypes within the CAD population could be distinguished: Phenotype A (16%) of mostly males with isolated CAD, phenotype B (30%) of older patients with polyvascular disease, Phenotype C (28%) of only women with limited traditional risk factors and Phenotype D (27%) young, current smokers with a premature event (Figure 1). Cross-validation in SWEDEHEART identified roughly the same four phenotypes, i.e., phenotype A (39%) with 100% males and 3.8% polyvascular disease, phenotype B (8%) with average age of 71 years and 30% polyvascular disease, phenotype C (19%) with 100% women, and phenotype D (34%) 54 years and 25% current smokers. Notably, although age was comparable between phenotype A and C, MACE-free survival was worse for the female-only cluster. Similarly, although patients where on average 9 years younger in phenotype D when compared to phenotype A, MACE-free survival was worse (Figure 2). No significant changes in clustering models were observed in the bootstrap samples. Conclusion Phenotypes can be distinguished within patients with CAD. These phenotypes are related to differences in the risk of recurrent events. These findings suggest that specific guideline recommendations for these groups could be considered.Cluster interpretation in SMARTSurvival along cluster lines

The association between carbohydrate quality index and conventional risk factors of cardiovascular diseases in an Iranian adult population

ObjectiveCardiovascular diseases (CVDs) are the most common cause of death worldwide. Diet plays an important role among many risk factors for CVDs. The present study aimed to investigate the relationship between carbohydrate quality index (CQI) and conventional risk factors of CVDs in Iranian adults.ResultsA higher CQI was related to a higher intake of energy, fiber, whole grains, fruits, vegetables, nuts, legumes, and dairy products. Additionally, a significant negative association was observed between CQI and triglycerides (TG) (odds ratio (OR) = 0.85; 95% confidence interval (CI): 0.73–0.98, highest versus the lowest tertile, p for trend = 0.026) and non-high density lipoprotein cholesterol (non-HDL-C) (OR = 0.85; 95% CI: 0.75–0.96, highest versus the lowest tertile, p for trend = 0.012). No significant correlation was shown between CQI and other cardiovascular risk factors. The findings indicate that the CQI is inversely associated with TG and non-HDL-C. Further studies are proposed to confirm these findings.

Importance of Dyslipidemias in Very Premature Coronary Artery Disease in India: A Registry-based Study.

Premature coronary artery disease (CAD) is an important cause of death in India. To identify risk factors in patients with premature CAD, we performed a registry-based study. Consecutive patients admitted for percutaneous coronary intervention (PCI) from October 2020 to June 2021 were recruited. The patients were classified into three groups-group I (very premature CAD < 40 years), group II (premature CAD 40-59 years), and group III (nonpremature CAD > 60 years). Major risk factors were determined, and intergroup comparison was performed. A total of 627 patients were enrolled (men 541, women 86). Group I had 79 (12.4%), group II had 420 (66.9%), and group III had 128 (20.4%) patients. The prevalence of risk factors in groups I, II, and III, respectively, were-CAD family history in 45.1, 41.1, and 26.6% (p = 0.005), current smoking/tobacco use in 29.1, 21.0, and 10.2% (p = 0.002), hypertension in 31.6, 43.6, and 59.4% (p < 0.001), and diabetes in 22.8, 34.3, and 46.1% (p < 0.001). High total cholesterol (>170 mg/dL) was present in 50.0, 38.0, and 29.9% (p = 0.005), nonhigh-density lipoprotein (HDL) cholesterol (>100 mg/dL) in 76.9, 64.4, and 54.5% (p = 0.001), low-density lipoprotein (LDL) cholesterol (>70 mg/dL) in 85.9, 76.8, and 76.4% (p = 0.167), triglycerides (>150 mg/dL) in 56.4, 45.3, and 33.1% (p = 0.001), and very low density lipoprotein (VLDL) cholesterol (>30 mg/dL) in 24.4, 10.4, and 9.4% (p = 0.005). Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) for smoking/tobacco use in groups I and II compared to group III, respectively, were 3.17 (1.60-6.27) and 2.59 (1.51-4.46); high total cholesterol 2.39 (1.29-4.13) and 1.42 (0.92-2.17); high non-HDL cholesterol 2.70 (1.45-5.03) and 1.48 (0.99-2.20); and high triglycerides 2.57 (1.44-4.58) and 1.64 (1.08-2.49). Important coronary risk factors in very premature and premature CAD in India are a family history of CAD, any tobacco use, and dyslipidemias (raised total, LDL, non-HDL, and VLDL cholesterol and triglycerides).

Abstract P372: Greater Long-Term Non-High Density Lipoprotein Cholesterol Variability From Childhood Is Associated With Higher Risk Of Early-Onset Hypertension: The Bogalusa Heart Study

Background: Early-onset hypertension is associated with greater risk of cardiovascular mortality and hypertension associated organ damage, compared to late-onset hypertension. Non-high-density lipoprotein cholesterol (non-HDL-C) is known to better predict future cardiovascular event risk, compared to low-density lipoprotein cholesterol. Whether higher long-term non-HDL-C variability from childhood is associated with higher risk of early-onset hypertension is unclear. Methods: We included 1271 participants of the Bogalusa Heart Study (age at enrollment: 9.9 ± 4.0 years, follow-up: 38.3 ± 3.8 years, age at last exam: 48.2 ± 5.2 years, 59.5 % women, 34.4 % Black participants) with ≥3 lipid measurements during follow-up. Non-HDL-C was calculated as total cholesterol (mg/dL) - HDL-C (mg/dL). Onset of hypertension was defined as having blood pressure ≥140/90 mmHg or using antihypertensive medications during follow-up. Participants were categorized according to age at hypertension onset (years) into 4 subgroups: &lt;35 (early-onset), 35-44, ≥45, and people without hypertension. Long-term non-HDL-C variability was obtained from the deviation from age predicted values (DEV) and residual SD (RSD). DEV and RSD were calculated from growth curves derived from linear mixed effect models, as the mean and SD of the residuals of observed and predicted non-HDL-C levels. Associations between non-HDL-C variability and hypertension onset subgroups were analyzed using multinomial logistic regression models. Interactions by race and sex were performed. Results: For 1-SD increase in DEV and RSD of non-HDL-C, the odds of hypertension increased for all hypertension onset subgroups compared to people without hypertension, after adjusting for race, sex, diabetes, obesity, and smoking status, education, and non-HDL-C at last exam. The odds of hypertension was highest in the early-onset subgroup (Table). No significant interactions were found between both DEV and RSD and race and sex. Conclusions: Our findings suggest that individuals with higher long-term non-HDL-C variability may be at a greater risk of having early-onset hypertension.

Navigating Cardiovascular Risk and Lipid Management in Indian Patients: Key Messages from the Lipid Association of India 2024 Consensus Statement IV.

Effective lipid management is crucial for preventing atherosclerotic cardiovascular disease (ASCVD). The Western lipid guidelines may not apply to Indian subjects because of the vast differences in cardiovascular (CV) disease epidemiology. To overcome this challenge, the Lipid Association of India (LAI) in 2016 proposed an ASCVD risk stratification algorithm. The appropriate low-density lipoprotein cholesterol (LDL-C) goals for various risk groups were proposed, with an LDL-C target of <50 mg/dL recommended for the first time globally for patients in the very high-risk group. Subsequently, in 2020, an extreme risk group was added because of observations that patients with more severe or extensive ASCVD, along with multiple risk factors and comorbidities, had increased rates of adverse CV events and could benefit from more intensive LDL-C lowering. The extreme risk group was subdivided into categories A and B, with LDL-C targets as low as 30 mg/dL or lower. The availability of further evidence regarding the significance of novel risk factors and the availability of new LDL-C lowering therapies necessitated refining the ASCVD risk assessment algorithm, defining LDL-C targets for subjects with these risk factors, and incorporating recommendations for attaining very low LDL-C levels in a defined, select group of patients. Accordingly, the LAI expert group recently published the Consensus Statement IV, which is a comprehensive document addressing several key issues about risk stratification and dyslipidemia management in Indian subjects. LDL-C and nonhigh-density lipoprotein cholesterol (non-HDL-C) are not only primary and co-primary targets for lipid-lowering therapy but also risk factors for ASCVD risk stratification. Apolipoprotein B is a secondary target. The risk assessment algorithm has been updated to incorporate several nonconventional yet relevant CV risk factors. Additionally, the role of subclinical atherosclerosis has been highlighted. The CV risk due to subclinical atherosclerosis has been considered equivalent to that of established ASCVD, and hence, similar LDL-C targets have been recommended. Furthermore, a new risk category-extreme risk group category C has been added for the small subgroup of patients who continue to experience ASCVD sequelae despite achieving LDL-C levels of 30 mg/dL or lower. An ultralow LDL-C target (10-15 mg/dL) has been recommended along with optimal control of risk factors and guideline-directed management of comorbidities. Dyslipidemia management should be effective with sustained LDL-C lowering. In high-risk situations (e.g., acute coronary syndrome), the LDL-C target should be achieved as early as possible, preferably within the first 2 weeks. The present document summarizes the key messages from the LAI Consensus Statement IV.

Characteristics of Stroke-related Seizures and their Predictive Factors: A Tertiary Care Center Experience.

Various risk factors have been described in the literature that increase the risk of seizures associated with stroke. This study was aimed to determine the occurrence rate of poststroke seizures (PSSs) and the associated risk factors in Arab population. Study included all stroke patients aged >18 years with a minimum follow-up of 24 months following stroke to identify seizure occurrence. Patient's hospital records for all admissions and clinic visits were reviewed. Seizures were classified into early PSS if they occur within 1 week of stroke, and late PSS if they occur after 1 week of stroke. Out of 594 patients, 380 were males. Seizure occurrence was higher in anterior circulation infarctions (94.8%, P < 0.05), cortical location (80.5%, P < 0.05), large artery atherosclerosis (63.8%, P < 0.05), lower activated partial thromboplastin time (APTT) (P = 0.0007), patients with ischemic heart disease (IHD) (P = 0.01), and those who underwent craniotomy (P = 0.001). Nonhigh-density lipoprotein cholesterol was inversely related to PSS (P = 0.01). Higher stroke severity (89%) and confusion (67%) at the time of presentation were independently related to PSS. Eighty-two (13.8%) patients had PSS. Greater stroke severity at presentation with altered sensorium was independent risk factors for the development of PSS. Patients with underlying IHD, lower APTT, and undergoing neurosurgical intervention require vigilant monitoring for PSS.

Efficacy of Inclisiran in Patients Having Familial Hypercholesterolemia: Heterozygous Compared to Homozygous Trait, a Systematic Review and Meta-analysis.

To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. We conducted the systematic review and meta-analysis of ORION clinical trials. PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atheroscalerotic parameters considered for our objective were low-density lipoprotein cholesterol, total cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B, and nonhigh-density lipoprotein cholesterol. Primary outcomes were the percentage difference in atheroscalerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by the Cochrane risk of bias tool. Meta-analysis was performed when at least 2 studies reported on the same variable. Four ORION clinical trials provided the data related to the mean difference in the atheroscalerotic parameters at follow-up relative to baseline, of HeFH and HoFH patient populations, after administration of 300 mg inclisiran subcutaneously. We pooled together these mean differences for each group and applied a statistical test to analyze if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in low-density lipoprotein cholesterol (HeFH: -48.62%; HoFH: -9.12%; P < 0.05), total cholesterol (HeFH: -30.31%; HoFH: -11.50%; P < 0.05), apolipoprotein (HeFH: -39.97%; HoFH: -14.68%; P < 0.05), and nonhigh-density lipoprotein (HeFH: -44.51%; HoFH: -12.22%; P < 0.05) between HeFH and HoFH groups. However, the difference in pooled mean difference in PCSK9 values (HeFH: -68.41%; HoFH: -56.25%; P = 0.2) between HeFH and HoFH groups was statistically insignificant. Studies were of high quality. There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.

Effect and mechanism of EtOAc extract of Draconis Sanguis onimproving atherosclerosis in ApoE~(-/-) mice

This study aims to investigate the effect and mechanism of the EtO Ac extract of Draconis Sanguis(DSE) on improving athero sclerosis in ApoE gene knockout(ApoE~(-/-)) mice. The ApoE~(-/-) mice were randomly divided into five groups: control group, mo delgroup, positive group treated with ezetimibe of 5 mg·kg~(-1)(EG), and low(100 mg·kg~(-1)) and high dose(200 mg·kg~(-1)) groups ofDSE. xcept for the control group, all other groups were fed a high-fat diet and administered drugs for 16 successive weeks. After 16 weeks of Eadministration, the body weight, liver, and epididymal fat mass of the mice were measured; the level of blood lipid and the plaquearea of the aortic outflow tract were detected to evaluate the efficacy of DSE in vivo. In addition, in vitro cultures of human umbilical v ein endothelial cell(HUVEC) were conducted. Oxidative stress of endothelial cells was induced by oxidized low-density lipoprot ein(ox-LDL), and the effects of DSE on oxidative stress-related proteins in endothelial cells were examined. The results sho wedthat both doses of DSE significantly improved the epididymal fat mass and index of ApoE~(-/-) mice with atherosclerosis, lowered thelevels of plasma cholesterol, triglyceride, and non-high density lipoprotein cholesterol, and reduced the plaque area of the aortic ou tflow tract. totIn alvitro experiments confirmed that ox-LDL significantly increased the level of lipid peroxidation marker 4-HNE in HUVECcells, confirming that DSE improved the degree of atherosclerotic lesions in ApoE~(-/-) mice by inhibiting ox-LDL-induced oxidative stress in vascular endothelial cells.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Effect of a Dietary Supplement Containing Dry Artichoke and Bergamot Extracts on Metabolic and Vascular Risk Factors in Individuals with Suboptimal Cholesterol Levels.

The aim of this study was to assess whether dietary supplementation with a nutraceutical blend comprising extracts of bergamot and artichoke-both standardized in their characteristic polyphenolic fractions-could positively affect serum lipid concentration and insulin sensitivity, high-sensitivity C-reactive protein (hs-CRP), and indexes of non-alcoholic fatty liver disease (NAFLD) in 90 healthy individuals with suboptimal cholesterol levels. Participants were randomly allocated to treatment with a pill of either active treatment or placebo. After 6 weeks, the active-treated group experienced significant improvements in levels of triglycerides (TG), apolipoprotein B-100 (Apo B-100), and apolipoprotein AI (Apo AI) versus baseline. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (Non-HDL-C), and hs-CRP also significantly decreased in the active-treated group compared to both baseline and placebo. At the 12-week follow-up, individuals allocated to the combined nutraceutical experienced a significant improvement in TC, LDL-C, Non-HDL-C, TG, Apo B-100, Apo AI, glucose, alanine transaminase (ALT), gamma-glutamyl transferase (gGT), hs-CRP, several indexes of NAFLD, and brachial pulse volume (PV) in comparison with baseline. Improvements in TC, LDL-C, Non-HDL-C, TG, fatty liver index (FLI), hs-CRP, and endothelial reactivity were also detected compared to placebo (p < 0.05 for all). Overall, these findings support the use of the tested dietary supplement containing dry extracts of bergamot and artichoke as a safe and effective approach for the prevention and management of a broad spectrum of cardiometabolic disorders.

Gut microbial metabolism is linked to variations in circulating non-high density lipoprotein cholesterol

Non-high-density lipoprotein cholesterol (non-HDL-c) was a strong risk factor for incident cardiovascular diseases and proved to be a better target of lipid-lowering therapies. Recently, gut microbiota has been implicated in the regulation of host metabolism. However, its causal role in the variation of non-HDL-c remains unclear. Microbial species and metabolic capacities were assessed with fecal metagenomics, and their associations with non-HDL-c were evaluated by Spearman correlation, followed by LASSO and linear regression adjusted for established cardiovascular risk factors. Moreover, integrative analysis with plasma metabolomics were performed to determine the key molecules linking microbial metabolism and variation of non-HDL-c. Furthermore, bi-directional mendelian randomization analysis was performed to determine the potential causal associations of selected species and metabolites with non-HDL-c. Decreased Eubacterium rectale but increased Clostridium sp CAG_299 were causally linked to a higher level of non-HDL-c. A total of 16 microbial capacities were found to be independently associated with non-HDL-c after correcting for age, sex, demographics, lifestyles and comorbidities, with the strongest association observed for tricarboxylic acid (TCA) cycle. Furthermore, decreased 3-indolepropionic acid and N-methyltryptamine, resulting from suppressed capacities for microbial reductive TCA cycle, functioned as major microbial effectors to the elevation of circulating non-HDL-c. Overall, our findings provided insight into the causal effects of gut microbes on non-HDL-c and uncovered a novel link between non-HDL-c and microbial metabolism, highlighting the possibility of regulating non-HDL-c by microbiota-modifying interventions. A full list of funding bodies can be found in the Sources of funding section.

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study

BackgroundRemnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited.MethodsThis prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment.ResultsAmong all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45–0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34–0.75; P < 0.001), without a significant increase of adverse reactions.ConclusionCurrent levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

Abstract PO5-02-08: Prognostic value of serum lipid levels in breast cancer patients who received neoadjuvant chemotherapy: A retrospective exploratory analysis of the prospective cohort

Abstract 【Background】 Lipid metabolism is one of the most conspicuous metabolic changes in malignant tumors. Previous studies confirmed that higher levels of “adverse lipids” might lead to poor outcomes and lipid-lowering drugs could act as a protective role in improving the prognosis of breast cancer patients. Nevertheless, few studies have clarified the impact of serum lipid levels and their changes on the tumor prognosis. Particularly for breast cancer patients treated with neoadjuvant chemotherapy, little has been studied whether their lipid levels or changes during neoadjuvant chemotherapy can serve as a valid prognostic factor. 【Methods】This study enrolled patients who received surgical treatment after neoadjuvant chemotherapy in Renji Hospital from March 2016 to December 2020. Patients were included if they were female aged 18 years or older; had pathologically confirmed unilateral invasive breast cancer; had tumor of at least 2cm in size without distant metastasis (T1-4, N0-3, M0); and underwent radical surgery for breast cancer successfully after neoadjuvant chemotherapy. We retrospectively gathered the baseline clinicopathological information and lipid metabolism-related biomarkers from electronic medical records. The study endpoints were disease free survival (DFS), overall survival (OS), relapse free survival (RFS), distance recurrence free survival (DRFS), and local recurrence free survival (LRFS). The prognostic value of each lipid levels and their variation levels were systematically evaluated and the importance of lipid biomarkers were ranked by Random Forest. 【Results】 The baseline clinicopathological information and lipid metabolism biomarkers were available from 200 eligible patients. As of the last follow-up in March 2023, 11 patients died, 24 experienced DFS events and 20 underwent RFS events. It showed no significant correlations of lipid levels before (baseline) and after (preoperative) neoadjuvant chemotherapy with any survival outcome. However, we found that the relative increase of low-density lipoprotein (LDL) led to poorer DFS (P=0.003), RFS (P=0.01), DRFS (P=0.01), and LRFS (P=0.0039), meanwhile the relative increase of total cholesterol (TC) and non-high-density lipoprotein (NHDL) during neoadjuvant period was significantly related to the worse prognosis (TC, DFS P=0.0084; NHDL, DFS P=0.031, RFS P=0.009) as well. After adjusted by multiple factors, the adverse impacts of increasing TC (DFS P=0.005; RFS P=0.026), LDL (DFS P=0.004; RFS P=0.006) and NHDL (DFS P=0.032; RFS P=0.014) on DFS or RFS were still maintained. The results of Random Forest revealed that LDL changes and Body Mass Index (BMI) ranked higher in terms of predicting survival outcomes. Based on these data, BMI &amp;gt;25.4 kg/m2 or LDL elevation &amp;gt;0.54 mmol/L were defined as High-risk Lipid Metabolism (HLM), while BMI ≤ 25.4 kg/m2 and LDL elevation ≤ 0.54 mmol/L were regarded as Low-risk Lipid Metabolism (LLM). Compared to LLM, HLM had a worse OS (P=0.026), DFS (P=0.0011) and RFS (P=0.0011). 【Conclusion】Our study demonstrated that the relative elevation of LDL, TC and NHDL levels during neoadjuvant chemotherapy is an independent prognostic risk factor for breast cancer patients. It was also the first time to propose the concept of high-risk lipid metabolism (HLM). 【keywords】Breast cancer, Lipid metabolism, Low-density lipoprotein (LDL), Body Mass Index (BMI), Prognosis. Citation Format: Xinru Chen, Wenjin Yin, Yingying Zhao, Jinsong Lu. Prognostic value of serum lipid levels in breast cancer patients who received neoadjuvant chemotherapy: A retrospective exploratory analysis of the prospective cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-08.

Plasma oxysterols are associated with serum lipids and dementia risk in older women.

Apolipoprotein E4 (APOE4) carriers' tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood-brain barrier. Relationships between baseline plasma oxysterols, APOE status, serum lipids, and cognitive impairment risk were examined in 328 postmenopausal women from the Women's Health Initiative Memory Study. Women were followed for 25 years or until incident dementia or cognitive impairment. Levels of 24(S)-hydroxycholesterol (24-OHC), 27-hydroxycholesterol (27-OHC), and 24-OHC/27-OHC ratio did not differ by APOE status (p's>0.05). Higher 24-OHC and 27-OHC were associated with higher total, low density lipoprotein (LDL), non-high density lipoprotein (HDL), remnant, LDL/HDL, and total/HDL cholesterol and triglycerides (p's<0.05). Higher 24-OHC/27-OHC was associated with greater dementia risk (hazard ratio=1.51, 95% confidence interval:1.02-2.22), which interaction analyses revealed as significant for APOE3 and APOE4+, but not APOE2+ carriers. Less favorable lipid profiles were associated with higher oxysterol levels. A higher ratio of 24-OHC/27-OHC may contribute to dementia risk in APOE3 and APOE4+ carriers.

Gut permeability is associated with lower insulin sensitivity in youth with perinatally acquired HIV.

The relationships between alterations in the intestinal barrier, and bacterial translocation with the development of metabolic complications in youth with perinatally acquired HIV (YPHIV) have not been investigated. The PHACS Adolescent Master Protocol enrolled YPHIV across 15 U.S. sites, including Puerto Rico, from 2007 to 2009. For this analysis, we included YPHIV with HIV viral load 1000 c/ml or less, with at least one measurement of homeostatic assessment of insulin resistance (HOMA-IR) or nonhigh density lipoprotein (non-HDLc) between baseline and year 3 and plasma levels of intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide-binding protein (LBP), and zonulin levels at baseline. We fit linear regression models using generalized estimating equations to assess the association of baseline log 10 gut markers with log 10 HOMA-IR and non-HDLc at all timepoints. HOMA-IR or non-HDLc was measured in 237, 189, and 170 PHIV at baseline, Yr2, and Yr3, respectively. At baseline, median age (Q1, Q3) was 12 years (10, 14), CD4 + cell count was 762 cells/μl (574, 984); 90% had HIV RNA less than 400 c/ml. For every 10-fold higher baseline I-FABP, HOMA-IR dropped 0.85-fold at baseline and Yr2. For a 10-fold higher baseline zonulin, there was a 1.35-fold increase in HOMA-IR at baseline, 1.23-fold increase in HOMA-IR at Yr2, and 1.20-fold increase in HOMA-IR at Yr3 in adjusted models. For a 10-fold higher baseline LBP, there was a 1.23-fold increase in HOMA-IR at baseline in the unadjusted model, but this was slightly attenuated in the adjusted model. Zonulin was associated with non-HDLc at baseline, but not for the other time points. Despite viral suppression, intestinal damage may influence downstream insulin sensitivity in YPHIV.

Abstract P271: Greater Long-Term Non-High Density Lipoprotein Cholesterol Variability From Childhood is Associated With Poorer Midlife Cognitive Function: The Bogalusa Heart Study

Background: Exposure to elevated plasma non-high density lipoprotein cholesterol (non-HDL-C) levels during adulthood has been associated with higher risk of cardiovascular events. However, whether long term non-HDL-C variability from childhood impacts midlife cognitive function (CF) is unclear. Hypothesis: We hypothesized that higher long-term non-HDL-C variability from childhood would be associated with worse midlife CF measures. Aim: We aimed to identify the effect of long term lipid variability from childhood on midlife CF. Methods: We studied 1,249 midlife participants of the Bogalusa Heart Study (age at baseline: mean 9.5 years+/- standard deviation(SD)3.5 years; age at midlife: mean 48.2 years+/- SD 5.2 years; 59.8 % women(747 of 1249), 34.3% Black(428 of 1249)) with ≥3 lipid measurements across follow up. Non-HDL-C levels were obtained as total cholesterol - HDL cholesterol. Visit-to visit non-HDL-C variability from childhood was estimated by the deviation from age predicted values (DEV), and residual SD (RSD). Non-HDL-C measurements were fitted in random-effects models stratified by race and sex, to produce individual growth curves. DEV and RSD were measured as the mean and SD of the residuals of observed and predicted non-HDL levels. Midlife CF was measured by 10 neuropsychological (NP) tests. NP test results were categorized into 3 distinct NP profiles (optimal, average, and mixed-low) using cluster analysis. Associations between non-HDL-C and NP profiles were analyzed using multinomial logistic regression models, adjusting for education status and the mean of non-HDL-C measurements from childhood to midlife. DEV and RSD were standardized to z-scores before conducting regression analysis. Interactions according to race and sex were performed. Results: The odds of having a mixed-low CF compared to optimal increased by 31.1% (95% CI 1.075, 1.599) for every 1 SD increase in DEV, and by 30.5% (95% CI 1.069, 1.591) for every 1 SD increase in RSD, respectively, adjusted for education status and mean non-HDL-C levels. Neither race or sex were found to modify the associations of DEV nor RSD on CF. Conclusions: Higher long-term non-HDL-C variability was linked to poorer midlife CF. Further studies are needed to identify the impact of long-term non-HDL-C variability in the association of cardiometabolic risk factors and midlife CF.

Serum endocan, asymmetric dimethylarginine and lipid profile in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a chronic inflammatory disease, and it is thought that subclinical inflammation persists even when there are no attacks, eventually causing endothelial dysfunction (ED) and atherosclerosis. Limited data are available about serum endocan, asymmetric dimethylarginine (ADMA) and lipid profile in children with FMF, so we aimed to evaluate these markers in children with FMF during the attack-free period. A total of 50 patients diagnosed with FMF and 50 age and sex-matched healthy children were recruited. Serum endocan, ADMA and lipid profiles were measured. Also, atherogenic indices (Castelli's risk indices I and II [CRI I and II], atherogenic index of plasma [AIP] and atherogenic coefficient [AC]) were calculated. Serum endocan, ADMA levels, low-density lipoprotein cholesterol, triglycerides, CRI II and AIP of the FMF patients were significantly higher than controls (p < 0.001). Unlike serum endocan, serum ADMA showed a positive significant correlation with total cholesterol, non-high density lipoprotein cholesterol, CRI I, AIP and AC (p < 0.001, p < 0.001, p = 0.004, p = 0.028, p = 0.004 respectively). Serum ADMA and lipid profile might be used as potential markers for endothelial dysfunction and increased cardiovascular risk in FMF patients. Theoretically, serum ADMA may affect lipid profiles and serum endocan represents an intriguing biomarker related to inflammation. Coexistence of dyslipidemia represents an additional risk factor that contributes to the onset of early atherosclerosis. A few studies investigated the role of changes in lipid profile and lipid ratios in accelerated atherosclerosis pathogenesis in FMF patients. The relationship between colchicine and lipid profile is contradictory. Although colchicine can cause dyslipidemia, it also has anti-atherosclerosis effects. Elevated ADMA level and atherogenic indices in FMF children reflect their potential role in the early detection of cardiovascular affection in FMF patients.

Chronic Real-Ambient PM2.5 Exposure Exacerbates Cardiovascular Risk via Amplifying Liver Injury in Mice Fed with a High-Fat and High-Cholesterol Diet.

Epidemiology has associated fine particulate matter (PM2.5) exposure with an increased cardiovascular risk. However, the underlying mechanism, particularly from the liver perspective, remains unclear. Here, the influence of chronic PM2.5 exposure on cardiovascular risk in mice fed a high-fat and high-cholesterol diet (HFCD) was studied by using a real-world PM2.5 exposure system. Results showed that PM2.5 exposure elevated the serum levels of nonhigh-density lipoprotein cholesterol (non-HDL-C) and oxidized low-density lipoprotein (oxLDL) in HFCD-fed mice, demonstrating increased cardiovascular risk. To investigate the molecular mechanism, lipidomics and metabolomics analyses were conducted and revealed that PM2.5 exposure enhanced lipid accumulation and disturbed purine metabolism and glutathione metabolism in the liver of HFCD-fed mice, contributing to the elevated non-HDL-C levels and intensified oxidative stress. Moreover, PM2.5 exposure increased total cholesterol levels by upregulating Hmgcr expression and downregulating Cyp7a1 expression in the livers of HFCD-fed mice. The HDL-C level was reduced by inhibiting the hepatic Abca1 and Abcg1 expression and decreasing the levels of ApoA-I and LCAT. Additionally, the PM2.5-induced pro-oxidative environment impeded the oxLDL clearance and further triggered inflammation, in turn exacerbating oxidative stress and oxLDL production. This study demonstrated a synergy of PM2.5 and HFCD on cardiovascular risk and illuminated the molecular mechanism in PM2.5-susceptible populations.

Novel Synthesis of Phytosterol Ferulate Using Acidic Ionic Liquids as a Catalyst and Its Hypolipidemic Activity.

Phytosterol ferulate (PF) is quantitively low in rice, corn, wheat, oats, barley, and millet, but it is potentially effective in reducing plasma lipids. In this study, PF was synthesized for the first time using acidic ionic liquids as a catalyst. The product was purified, characterized using Fourier transform infrared, mass spectroscopy, and nuclear magnetic resonance, and ultimately confirmed as the desired PF compound. The conversion of phytosterol surpassed an impressive 99% within just 2 h, with a selectivity for PF exceeding 83%. Plasma lipid-lowering activity of PF was further investigated by using C57BL/6J mice fed a high-fat diet as a model. Supplementation of 0.5% PF into diet resulted in significant reductions in plasma total cholesterol, triacylglycerols, and nonhigh-density lipoprotein cholesterol by 13.7, 16.9, and 46.3%, respectively. This was accompanied by 55.8 and 36.3% reductions in hepatic cholesterol and total lipids, respectively, and a 22.9% increase in fecal cholesterol excretion. Interestingly, PF demonstrated a higher lipid-lowering activity than that of its substrates, a physical mixture of phytosterols and ferulic acid. In conclusion, an efficient synthesis of PF was achieved for the first time, and PF had the great potential to be developed as a lipid-lowering dietary supplement.