High-density Lipoprotein Cholesterol Research Articles

The association between non-HDL cholesterol and high-grade pancreatic neuroendocrine neoplasms.

High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs). A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis. Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13-1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98-66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04-1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28-19.49). A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs.

Association Between Red Blood Cell Distribution Width in Late Pregnancy and the Incidence of Adverse Perinatal Outcomes: A Retrospective Cohort Study

This study aimed to quantify adverse perinatal outcomes (APO), including small/large for gestational age (SGA/LGA) and preterm birth (PTB), in pregnant women with abnormal red cell distribution width (RDW) and explore the related mechanisms. This study included 11,659 pregnant women who delivered in a specialized hospital. At the time of admission, the lipid profiles and whole blood cell counts were assessed, and APO was analyzed. Women with high RDW (>18.5% [the 97.5th percentile]) in late pregnancy had a higher risk of LGA compared with those with low RDW (<12.3% [the 2.5th percentile]), whereas women with low RDW had a higher risk of SGA and PTB, compared with those with high RDW. A 1% increase in RDW was associated with an increased risk of LGA and a decreased risk of SGA and PTB. Consistent associations were observed in sensitivity analysis among pregnant women of non-advanced age, non-obesity, non-pregnancy complications, and non-PTB (for SGA/LGA only). Increased RDW was significantly associated with increased triglycerides and decreased high-density lipoprotein cholesterol (HDL-C). Triglycerides and HDL-C significantly mediated 10.63 and 15.8% of RDW-associated LGA, 9.51% and 9.40 of RDW-associated SGA, and 8.44 and -8.25% of RDW-associated PTB, respectively. Abnormal RDW was associated with an increased risk of APO, and the RDW-associated APO risk could be partially mediated by triglycerides and HDL-C, suggesting that RDW may be a promising APO predictor.

Volatilome: A Novel Tool for Risk Scoring in Ischemic Heart Disease.

Developing a novel risk score for accurate assessment of cardiovascular disease (CVD) morbidity and mortality is an urgent need in terms of early prevention and diagnosis and, thereafter, management, particularly of ischemic heart disease. The currently used scores for the evaluation of cardiovascular disease based on the classical risk factors suffer from severe limitations, including inaccurate predictive values. Therefore, we suggest adding a novel non-classical risk factor, including the level of specific exhaled volatile organic compounds that are associated with ischemic heart disease, to the SCORE2 and SCORE2-OP algorithms. Adding these nonclassical risk factors can be used together with the classical risk factors (gender, smoking, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, arterial hypertension, ethnicity, etc.) to develop a new algorithm and further program to be used widely.

Associations between adherence to 24-Hour Movement Guidelines with continuous metabolic syndrome score among Chinese children and adolescents

ObjectivesThe objective of this study was to evaluate the associations between adherence to 24-Hour Movement Guidelines (24-HMG) with continuous metabolic syndrome score (cMetS) among Chinese children. Study designCross-sectional study. MethodsWe conducted a cross-sectional study among 4604 children aged 6–17 years from Shenzhen, China. The 24-HMG was constructed using the self-report information on moderate-to-vigorous physical activity (MVPA), screen time (ST), and sleep duration. The cMetS was calculated based on waist circumference, homoeostatic model assessment for insulin resistance, mean arterial blood pressure, high-density lipoprotein cholesterol, and triglyceride. Multivariate linear regression models were used to assess the associations between adherence to recommendations of 24-HMG and cMetS. ResultsAmong the participants, 563 (12.23%) students adhered to 3 recommendations of the 24-HMG. We found that adhering to more recommendations was negatively associated with cMetS (P for trend: <0.001). For specific combinations, meeting the ST + MVPA recommendations was negatively associated with cMetS (coefficients [β]: −0.686; 95% confidence interval [CI]: −1.148, −0.223). Individuals who adhered to all recommendations had a lower cMetS (β: −0.693; 95% CI: −1.147, −0.238) than those who met none of the recommendations. ConclusionsOur study showed that adherence to more recommendations of the 24-HMG was associated with lower levels of cMetS in Chinese children and adolescents.

Polyphenol-rich Ocimum gratissimum leaf extract attenuates angiotensin-converting enzyme activity and impaired endothelial vascular function in diabetic rats

Endothelial vascular dysfunctions are prevalent among diabetic patients, significantly impacting their quality of life and prognosis. This study examined the effects of polyphenol-rich extracts from Ocimum gratissimum leaves on oxidative stress markers, serum lipid profiles, and angiotensin-converting enzyme activity in diabetic cardiac tissue. Forty Wistar rats (150–220 g) were divided into five groups: normal control, diabetic control, low-dose Ocimum gratissimum (122.46 mg/kg), medium-dose Ocimum gratissimum (244.98 mg/kg), and a positive control (standard diabetic drug). All rats except the normal control group were made diabetic via an intraperitoneal injection of 50 mg/kg streptozotocin, followed by 28 days of extract administration. Diabetes induction led to a significant (p&lt;0.05) disruptions in lipid profiles, oxidative stress markers, and ACE activity. Treatment with Ocimum gratissimum extracts at both doses significantly (p&lt;0.05) decreased triglyceride, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol. Lipid peroxidation marker, malondialdehyde, was significantly (p&lt;0.05) decreased, and antioxidant enzyme activities significantly (p&lt;0.005) improved. ACE activity was significantly (p&lt;0.05) reduced, approaching control levels. These results suggest that the polyphenol-rich extract of Ocimum gratissimum exerts antioxidant and cardio-protective effects, improving vascular functions in diabetic rats by improving lipid profiles, reducing oxidative stress, and suppressing ACE activity.

Associations of Serum Lipid Traits With Fracture and Osteoporosis: A Prospective Cohort Study From the UK Biobank.

Previous studies reveal inconsistent associations between serum lipid traits and the risks of fractures and osteoporosis in the general population. This prospective cohort study analysed data from 414 302 UK Biobank participants (223 060 women and 191 242 men, aged 37-73 years) with serum lipid measurements: apolipoprotein A (Apo A), apolipoprotein B (Apo B), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein A (Lp(a)). Multivariable Cox proportional hazard models with penalized cubic splines were used to explore potential nonlinear associations of each lipid trait with the risks of fractures and osteoporosis. Subgroup analyses by age, sex, BMI categories and pre-existing cardiovascular disease were conducted. Mediation analyses using the g-formula were performed to quantify to which extent bone mineral density (BMD) may mediate the association between serum lipids and fracture risk. Over a median follow-up period of 13.8 years, 25 918 (6.8%) of the 383 530 participants without prior fracture had incident fracture cases, and 7591 (4.1%) of the 184 919 participants with primary care data and without baseline osteoporosis were diagnosed with osteoporosis. TG had nonlinear associations with fractures and osteoporosis, whereas Apo B, TC and LDL-C had linear associations. There were also nonlinear associations of Apo A and HDL-C with fractures. Individuals in the highest quintiles for Apo A (fracture: HR 1.15 [95% CI 1.10, 1.21]; osteoporosis: HR 1.13 [1.02, 1.25]) and HDL-C (fracture: HR 1.27 [1.20, 1.34]; osteoporosis: HR 1.31 [1.18, 1.46]) were associated with higher risks of fractures and osteoporosis. Conversely, those in the highest quintile for Apo B (fracture: HR 0.85 [0.81, 0.89]; osteoporosis: HR 0.86 [0.79, 0.94]), LDL-C (fracture: HR 0.89 [0.85, 0.93]; osteoporosis: HR 0.91 [0.83, 1.00]) and TG (fracture: HR 0.78 [0.74, 0.82]; osteoporosis: HR 0.75 [0.68, 0.82]) were associated with lower risks. The associations of Apo A (ratio of HR [RHR] 1.05 [1.02, 1.09]) and HDL-C (RHR 1.06 [1.03, 1.09]) with fracture risk were more pronounced in men compared to women. Except for TG and Lp(a), the associations between serum lipids and fractures appear to be partially mediated through BMD (mediation proportions: 5.30% to 40.30%), assuming causality. Our study reveals a complex interplay between different lipid markers and skeletal health, potentially partially mediated through BMD. Routine lipid profile assessments, including HDL-C and Apo A among other lipid traits, may be integrated into the strategies for fracture risk stratification.

Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study.

The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Small hepatitis B virus surface antigen (SHBs) induces dyslipidemia by suppressing apolipoprotein-AII expression through ER stress-mediated modulation of HNF4α and C/EBPγ.

Persistent infection with hepatitis B virus (HBV) often leads to disruptions in lipid metabolism. Apolipoprotein AII (apoAII) plays a crucial role in lipid metabolism and is implicated in various metabolic disorders. However, whether HBV could regulate apoAII and contribute to HBV-related dyslipidemia and the underlying mechanism remain unclear. This study revealed significant reductions in apoAII expression in HBV-expressing cell lines, the serum, and liver tissues of HBV-transgenic mice. The impact of HBV on apoAII is related to small hepatitis B virus surface antigen (SHBs). Overexpression of SHBs decreased apoAII levels in SHBs-expressing hepatoma cells, transgenic mice, and the serum of HBV-infected patients, whereas suppression of SHBs increased apoAII expression. Mechanistic investigations demonstrated that SHBs repressed the apoAII promoter activity through a HNF4α- and C/EBPγ-dependent manner; SHBs simultaneously upregulated C/EBPγ and downregulated HNF4α by inhibiting the PI3K/AKT signaling pathway through activating endoplasmic reticulum (ER) stress. Serum lipid profile assessments revealed notable decreases in high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) in SHBs-transgenic mice compared to control mice. However, concurrent overexpression of apoAII in these mice effectively counteracted these reductions in lipid levels. In HBV patients, SHBs levels were negatively correlated with serum levels of HDL-C, LDL-C, TC, and TG, whereas apoAII levels positively correlated with lipid content. This study underscores that SHBs contributes to dyslipidemia by suppressing the PI3K/AKT pathway via inducing ER stress, leading to altered expression of HNF4α and C/EBPγ, and subsequently reducing apoAII expression.IMPORTANCEThe significance of this study lies in its comprehensive examination of how the hepatitis B virus (HBV), specifically through its small hepatitis B virus surface antigen (SHBs), impacts lipid metabolism-a key aspect often disrupted by chronic HBV infection. By elucidating the role of SHBs in regulating apolipoprotein AII (apoAII), a critical player in lipid processes and associated metabolic disorders, this research provides insights into the molecular pathways contributing to HBV-related dyslipidemia. Discovering that SHBs downregulates apoAII through mechanisms involving the repression of the apoAII promoter via HNF4α and C/EBPγ, and the modulation of the PI3K/AKT signaling pathway via endoplasmic reticulum (ER) stress, adds critical knowledge to HBV pathogenesis. The research also shows an inverse correlation between SHBs expression and key lipid markers in HBV-infected individuals, suggesting that apoAII overexpression could counteract the lipid-altering effects of SHBs, offering new avenues for understanding and managing the metabolic implications of HBV infection.

Double-sided effect of selenium on blood lipids: A dose-response meta-analysis

Abstract Background Selenium, a trace element with both nutritional and toxicological properties, has been suggested to increase cardiovascular risk, particularly concerning diabetes and blood pressure levels. However, the impact of selenium exposure on the risk of dyslipidemia remains uncertain. This meta-analysis explored the shape of the relation between selenium exposure and its effects on lipid profiles in the most relevant experimental human studies, randomized controlled trials (RCTs). Materials and methods The review was registered in PROSPERO (ID: CRD42022380432). Through a bibliographic search conducted on PubMed, Web of Science, Embase, and the Cochrane Library, we identified RCTs investigating the impact of selenium supplementation on lipid profile. We then compared the results between intervention and control groups and, whenever possible, evaluated the non-linear relationship using a dose-response approach. Results We could include 26 RCTs involving different populations, i.e. healthy individuals, pregnant women, and subjects with health conditions such as cardiovascular diseases and Alzheimer’s dementia. Study endpoints were levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. Our dose-response analysis indicated that selenium supplementation exceeding 200 µg/day adversely affected total cholesterol, HDL, and triglyceride levels. Hence, a threshold for such a detrimental effect of selenium was observed on total and HDL cholesterol and triglycerides, while opposite and inconsistent results emerged for levels below 200 µg/day and for LDL-cholesterol. Blood selenium levels at the end of the studies were positively associated with adverse effects on all endpoints. Conclusions This first dose-response meta-analysis of the effects of selenium on blood lipids highlights the potentially adverse effects of this trace element, in the amount and the chemical forms used in the trials. Key messages • Elevated selenium levels correlated with adverse effects on lipid profile. • Selenium doses exceeding 200 µg/day showed adverse effects on total and HDL cholesterol and triglycerides levels.

The change of paradigm: high HDL-c levels could not mean a long lifespan

Abstract Background It is known that a low HDL-c level is associated with a high risk of overall mortality. Consequently, it was presumed that achieving higher levels of high-density lipoprotein cholesterol (HDL-c) would reduce the risk or even extend the lifespan. However, clinical trials with medical intervention failed to find clinical benefits. Aim We aimed to investigate the association between (HDL-c) levels and overall mortality using a prospective cohort from Portugal. Methods A prospective sub-study (2001-2022) was performed in a cohort of 1718 participants without coronary artery disease (CAD) of the control arm of the ongoing GENEMACOR study. The participants &amp;lt;65 years were followed during a mean follow-up of 7.0±5.7 years. All demographic, biochemical, and clinical data were collected. Participants were stratified into six levels of HDL-c. Kaplan-Meier estimated differences in the survival probability of each HDL-c level. Cox proportional analysis models (unadjusted and adjusted) were used to assess the association between HDL-c levels and overall mortality. Results The HDL-c levels with the lowest overall mortality rate were 60 to 70 mg/dl, set as the reference level. Total HDL-c strata were associated with overall mortality with a U-shaped relationship: in the control group, the first level (&amp;lt;40 mg/dl) was independently associated with increased risk of overall mortality (HR of 3.533; 95% CI: 1.738-7.178; p&amp;lt;0.0001). This risk drops and falls to the reference level (the lower risk) and rises again to an HR of 3.875 (95% CI: 1.472-10.201; p=0.006) in the very high HDL-c levels (≥80 mg/dl). Conclusions Our results, based on a large Portuguese cohort, suggest that very high HDL-c levels in the normal population may not represent a good prognosis, especially in women. Future research may confirm these findings and investigate the underlying mechanisms.

Impaired high-density lipoprotein-associated cholesterol efflux capacity predicts coronary rapid plaque progression

Abstract Background Rapid progression of coronary atherosclerotic plaques is recognized as a surrogate endpoint of cardiac ischemic events. Low high-density lipoprotein (HDL)-associated cholesterol efflux capacity (CEC) has been associated with atherosclerotic cardiovascular disease independent of HDL cholesterol (HDL-C) level. In this study, we aim to investigate the predictive role of CEC in rapid plaque progression (RPP). Methods We consecutively enrolled patients with stable angina from January 2017 to August 2019 in our hospital who underwent elective coronary angiography with at least one untreated coronary lesion. A follow-up angiography was performed at around 12 months. Afterwards, these patients were followed-up for every 3 months to June 2021. The primary endpoint was RPP during the 12-month angiography follow-up. The second endpoint was defined as a composite endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or unplanned coronary revascularization. Fluorescence-labeled cholesterol and J774 macrophages were used to measure CEC of ApoB-depleted serum samples. Results A total of 430 patients with 586 coronary lesions were included in the final analysis. During a mean follow-up of 12.7 ± 2.0 months, 120 lesions (20.5%) in 80 patients (18.6%) exhibited RPP. CEC, rather than HDL-C, was inversely associated with the extent of plaque progression (net luminal loss from the lowest to highest CEC quartile: 0.22±0.42 vs. 0.20±0.41 vs. 0.13±0.36 vs. 0.11±0.34 mm, P = 0.035). In multivariate analysis, baseline CEC was inversely associated with RPP independent of conventional risk and protective factors including HDL-C or apolipoprotein A-I. Subgroup analysis demonstrated that the association between CEC and RPP was more prominent in patients with high (≥4.02 mmol/L) than low (&amp;lt;4.02 mmol/L) total cholesterol. Finally, although patients with RPP had higher risk of the composite endpoint than those without RPP (P=0.012), no significant difference was observed between patients in different quartiles of CEC (P=0.720). Conclusions HDL-associated CEC is inversely associated with RPP in patients with coronary artery disease. HDL function assessment behaves as a better diagnostic biomarker than HDL-C for predicting RPP.

Lipids as the link between central obesity and diabetes: perspectives from mediation analysis

BackgroundCentral obesity is a well-recognized risk factor for diabetes, yet the potential role of lipids in the diabetes risk associated with central obesity remains unclear. This study aimed to explore the possible mediating role of 11 lipid parameters [high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein cholesterol (Non-HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), remnant cholesterol (RC), and ratios of Non-HDL-C/HDL-C, RC/HDL-C, LDL/HDL-C, TG/HDL-C, TC/HDL-C] in the association of central obesity with diabetes risk.MethodsWe utilized data from 15,453 participants in the NAGALA longitudinal cohort to assess the association of baseline central obesity indicators [waist-height ratio (WHtR), waist circumference (WC)] and the 11 lipid parameters with diabetes risk. Mediation analysis models were constructed to explore the mediating role of lipid parameters in the association of WC/WHtR with diabetes.ResultsConfirmatory associative analysis using multivariable Cox regression showed that, except for Non-HDL-C, TC and LD-C, the remaining eight lipid parameters were significantly associated with WC/WHtR and diabetes risk. Mediation analysis indicated that TG, RC, HDL-C, and lipid ratios such as Non-HDL-C/HDL-C ratio, RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio and LDL/HDL-C ratio are potential lipids affecting the diabetes risk related to central obesity. Among these, the RC/HDL-C ratio seemed to contribute the most in the WC/WHtR-related diabetes risk association, with a mediation percentage of about 37%. Additionally, lipid ratio parameters appeared to play a more mediating role in the association of central obesity-related diabetes risk than individual lipids.ConclusionsIn central obesity-related diabetes risk, most lipids, especially lipid ratio parameters, play a significant mediating role. Given these findings, we advocate for increased efforts in multifactorial risk monitoring and joint management of diabetes. The evaluation of lipids, particularly lipid ratio parameters, may be holds substantial value in the prevention and management of diabetes risk under close monitoring of central obesity.

Management of children with heterozygous familial hypercholesterolemia worldwide: a meta-analysis

Abstract Background HeFH is one of the most frequent monogenic disorders in the world, leading to premature ASCVD. Purpose The aim of this meta-analysis was to evaluate the efficacy and safety of lipid lowering therapy (LLT) and achievement of LDL-C goal in heFH children. Methods The main endpoint was efficacy of goal achievement for LDL-C and other lipid parameters: total cholesterol [TC], triglycerides [TG], high density lipoprotein cholesterol [HDL-C], apolipoprotein B [apo B] and lipoprotein(a) [Lp(a)]), and the LLT safety (adverse events [AEs], including endocrine function, and growth indices). The secondary endpoint was an effect of LLT on attainment of LDL-C goal treatment (&amp;lt;3.5 mmol/L/130 mg/dL). Results A total of 41 studies with 4667 pediatric patients at mean age 12.08±2.4 years were included. At median follow-up of 18.8 months, the group on LLT had significantly higher mean reductions of TC, LDL-C, TG, and increased HDL-C compared to control (-1.75 [-67,7 mg/dl], -1.84 [-71.2 mg/dl], -0.11 [-9.74 mg/dl], 0.08 mmol/L [3.1 mg/dl], respectively, p&amp;lt;0.001 for all). In the subgroup analysis according to different types of LLT we observed a significantly higher mean reduction of LDL-C by statin combined with ezetimibe treatment, followed by PCSK9 inhibitors, statins in monotherapy, and monotherapy with ezetimibe (-2.48 [-95.9 mg/dl], -2.16 [-83.5 mg/dl], -2.03 [-78.5 mg/dl], and -1.50 mmol/L [-58 mg/dl], respectively, test for overall effect: p&amp;lt;0.001). The pooled LDL-C was reduced by 33.44% (-2.14 mmol/L [-82.8 mg/dl], p&amp;lt;0.001) and failed to reach the goal treatment (&amp;lt;3.5 mmol/L) by 12.6% (95%CI, 12.4 – 12.9%). 38.7% of children achieved the LDL-C goal, 23.9% fell short by up to 10%, 10.7% experienced moderate failure (were over the LDL-C target between &amp;gt;10-20%), and 26.7% failed by more than 20% to reach the LDL-C target. When comparing different regions, only Sweden and Greece achieved the LDL-C goal &amp;lt;3.5 mmol/L in the follow-up, followed by the Netherlands, Norway, Poland, USA, UK, France, Spain, Belgium, and Austria (with the following additional required LDL-C reduction to be on the goal: 2.2%, 3.4%, 3.5%, 8.9%, 10.2%, 11.2%, 11.2%, 15%, 19.4%, respectively). For other investigated countries over 20% mean LDL-C reduction was required. All parameters related to endocrine function and demographic indices were unaffected by LLT therapy (p&amp;gt;0.05). The adverse events were not reported significantly higher when compared to the control and the prevalence of therapy discontinuation was only 0.8%. Conclusions Despite the efficacy of LLT in children with HeFH and the low occurrence of discontinuation-related adverse events, achieving LDL-C treatment goals was relatively rare, with large differences between the investigated countries. These results underscore the importance of considering early combination therapy of statins and ezetimibe, and PCSK9 inhibitors (if available) to attain LDL-C goals effectively.Lipoproteins reduction with LLT.Goal achievement and therapy safety.

Sex sifferences in lifes essential eight and its association with mortality among adults without known CVD

Abstract Background The American Heart Association’s Life’s Essential 8 (LE8) score is a helpful tool to quantify cardiovascular health (CVH) metrics. Sex differences in relation to LE8 and its association with mortality are not known. Methods The National Health and Nutrition Examination Survey (NHANES) between 2009 and 2018 was utilized to evaluate the prevalence of health metrics included in LE8 among adult patients, stratified by sex. Health metrics were further subdivided into health behaviors (diet, physical activity, nicotine exposure, and sleep) and health factors (body mass index, non–high density lipoprotein cholesterol, blood glucose, and blood pressure). LE8 scores were also evaluated based on age, race/ethnicity, and socioeconomic status. Cox proportional hazard models were used to evaluate the association between the levels of CVH and risk of all-cause and cardiovascular mortality. Results Among 22,761 participants, 52% were female. Overall CVH score was similar in both females and males (65.8 vs. 65.9). Females had higher health factors score (64.3 vs. 63.1, p &amp;lt;0.001) and lower health behaviors score (67.2 vs 68.6, p &amp;lt;0.001). Amongst individual metrics, blood pressure score was higher in females (73.2 vs. 67.7, p &amp;lt;0.001) while males had higher physical activity score (70.6 vs. 54.9, p &amp;lt;0.001). For individuals under 65 years of age, overall CVH and health factors scores were higher in females while in those age 65 or older, males had higher scores. The most prominent sex differences were noted in non-Hispanic Black females who had significantly lower CVH scores than Black males. High or moderate LE8 scores vs. low LE8 scores demonstrated lower all-cause and CV mortality in both sexes (p-interaction 0.98 and 0.9). High or moderate health behaviors scores also demonstrated a significant association with lower all-cause and CV mortality, with the reduction in mortality being more prominent in females (p-interaction 0.01 and 0.03). Conclusions We demonstrate important sex differences in CVH metrics along with notable variations based on age and race/ethnicity. Furthermore, we highlight sex differences in the association of CVH metrics with mortality. These findings underscore the importance of designing and implementing effective strategies for both sexes, aimed at targeting these specific factors.

Interaction of polychlorinated biphenyls exposure, lifestyle and genetic risk in dyslipidemia

Abstract Background Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals that have been associated with various adverse health conditions. However, the interaction effects between PCBs, lifestyle, and/or genetic susceptibility on dyslipidemias are still unknown. Methods Six serum PCBs including PCB-28, 101, 118, 138, 153, and 180 were determined in 3,845 participants from the Wuhan-Zhuhai cohort. Dyslipidemias, including hyper-total cholesterol (HyperTC), hyper-triglyceride (HyperTG), hyper-low density lipoprotein cholesterol (HyperLDL-C), and hypo-high density lipoprotein cholesterol (HypoHDL-C) were classified based on serum lipids levels, which were examined by an automatic biochemical analyzer. Besides, we constructed lipid-specific polygenic risk scores (PRS) and healthy lifestyle scores, and used Logistic regression models to explore the relationships of serum PCBs, lifestyle, and PRS with dyslipidemias. Results We observed that all six PCB congeners were positively associated with the prevalence of dyslipidemias to varying degrees. In particular, dose-response manners were observed between ΣPCB levels and odds ratios (ORs) of HyperTC, HyperTG, and HyperLDL-C, respectively. Besides, we found that PRSs and unhealthy lifestyles were both positively associated with dyslipidemias. For the combined effect of ΣPCB, lifestyle, and PRS, participants with high ΣPCB, unfavorable lifestyle, and high genetic risk had the highest odds of HyperTC (2.285; 1.533, 3.417), HyperTG (7.944; 5.169, 12.329), and HyperLDL-C (3.523; 2.311, 5.394) when compared with those with low ΣPCB, healthy lifestyle, and low genetic risk. Conclusions Our study provided evidence that PCB exposure potentially increases the prevalence of dyslipidemias, which may be exacerbated by genetic susceptibility and unhealthy lifestyles. Key messages • Our results highlighted the importance of reducing PCB exposure, adopting healthy lifestyles for the prevention of dyslipidemia. • Our work might facilitate the emergence of reducing or regulating PCB pollution to control blood lipids and the resultant dyslipidemia epidemic.

Associations of smoking status with long-term cardiovascular events in different arterial territories: the EPIC Norfolk prospective population cohort

Abstract Background Smoking cessation is associated with a reduced risk of cardiovascular disease (CVD) events, mainly in ischemic heart disease (IHD) and stroke. However, the impact of smoking status (never, former or current smoking) on long-term CVD events across different arterial territories remains understudied. Knowledge of such associations is important, as it may assist in risk communication and smoking cessation motivation. We therefore investigated associations between smoking status and territory-specific CVD events in a large cohort with ≥20 years follow-up. Methods We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between smoking, former smoking and never smoking with the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisation or death due to IHD, ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, systolic blood pressure, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), diabetes, renal function and body mass index. We compared former and current smoking (at baseline) with never smoking. Results We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. Current (vs. never) smoking was associated with IHD [adjusted hazard rate (aHR) 1.53, 95% confidence interval (CI) 1.36-1.72], PAD (aHR 1.29, 95%CI 1.07-1.56) and AA (aHR 4.81, 95%CI 3.54-6.54). Current smoking was not significantly associated with ischemic stroke (aHR 1.20, 95% CI 0.95-1.52) and haemorrhagic stroke (aHR 1.18, 95% CI 0.81-1.70). In former (vs. never) smoking individuals, the association with AA remained statistically significant but less pronounced [aHR 1.69, 95%CI 1.29-2.23]. Conversely, former smoking was not associated with IHD (aHR 1.07, 95%CI 0.99-1.16) or PAD (aHR 1.09, 95%CI 0.95-1.26) (Figure 1). Conclusion After 20-years of follow-up, former smokers, compared to never-smokers, remain at considerably higher risk for CVD events, particularly for aortic aneurysm. This knowledge may assist in treatment decisions and risk communication.

Regulating lipid metabolism in osteoarthritis: a complex area with important future therapeutic potential

Background Osteoarthritis (OA), which is characterized by pain, inflammation and pathological changes, is associated with abnormal lipid metabolism. Extensive studies have been conducted on the potential functions of lipids including cholesterol, fatty acids (FAs) and adipokines. Materials and Methods By searching and screening the literature included in the PubMed and Web of Science databases from 1 January 2019 to 1 January 2024, providing an overview of research conducted on lipid metabolism and OA in the last 5 years. Results In addition to adiponectin, several studies on the effects of lipid metabolism on OA have been consistent and complementary. Total cholesterol, triglycerides, low-density lipoprotein cholesterol, adipsin, leptin, resistin, saturated FAs, monounsaturated FAs, FA-binding protein 4 and the ratios of the FAs hexadecenoylcarnitine (C16:1) to dodecanoylcarnitine and C16:1 to tetradecanoylcarnitine induced mostly deleterious effects, whereas high-density lipoprotein cholesterol and apolipoprotein A/B/D had a positive impact on the health of joints. The situation for polyunsaturated FAs may be more complicated, as omega-3 increases the genetic susceptibility to OA, whereas omega-6 does the opposite. Conclusion: Alterations in lipid or adipokine levels and the resulting pathological changes in cartilage and other tissues (such as bone and synovium) ultimately affect joint pain, inflammation and cartilage degradation. Lipid or adipokine regulation has potential as a future direction for the treatment of OA, this potential avenue of OA treatment requires high-quality randomized controlled trials of combined lipid regulation therapy, and more in-depth in vivo and in vitro studies to confirm the underlying mechanism.

Fat mass mediating effect on the association of worsening insulin resistance with increased left ventricular mass in 1595 adolescents: a 7-Year Longitudinal and Mediation Study

Abstract Background Fat mass-insulin resistance vicious cycle has been established in the young population and late adolescence has been identified as the critical time when the pathologic cycle begins. However, the independent and synergistic effect of fat mass in the relationship of insulin resistance with cardiac structure remains unexamined in a large cohort of adolescents, possibly due to the scarcity of repeated echocardiography measures. Mounting effective prevention strategies relies on strong evidence of the timing of the earliest cardiovascular alteration induced by insulin resistance. Purpose To investigate the longitudinal association of insulin resistance with left ventricular mass (LVM) and the mediating effect of fat mass in adolescents. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting glucose and insulin measured at 17- and 24-year clinic visits were included. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated from fasting insulin x fasting glucose/22.5 at ages 17 and 24 years. Repeated echocardiography measured LVM indexed for height2.7 (LVMI2.7) was available at baseline and follow-up. Fat mass was repeatedly measured with dual-energy Xray absorptiometry at both time points. Multivariable adjusted association was examined using generalized linear mixed-effect models and adjusted for sex, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, and time-varying covariates measured at both baseline and follow-up such as age, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, fat mass, lean mass, smoking status, sedentary time, light physical activity, moderate-to-vigorous physical activity, low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol. Mediation analysis was conducted with a structural equation model adjusting for same covariates, except fat mass. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) median insulin resistance increased from 1.46 to 1.74, median fat mass increased from 15.6kg to 19.2kg and the mean LVMI increased from 35.4g/m2.7 to 38.1g/m2.7, over 7 years. In a fully adjusted model, increased insulin resistance from adolescence through young adulthood was significantly associated with increased LVMI (effect estimate 1.01g/m2.7 [95% CI, 0.63 – 1.57], p&amp;lt;0.001) across the 7-year observation period. Increased fat mass mediated (62.3% mediation effect) the longitudinal association between insulin resistance and LVMI from ages 17 – 24 years. Conclusion Worsening insulin resistance from adolescence through young adulthood was associated with increased cardiac mass, contributing 37% to the total increase in LVMI between ages 17 to 24 years but increased fat mass explained two-thirds of the relationship.

Sex-specific associations between remnant cholesterol and cardiovascular risk in patients undergoing percutaneous coronary intervention: a 5-year large-sample study from the real world

Abstract Background Differences in the pathophysiological characteristics and cardiovascular risk between female and male patients with coronary artery disease (CAD) are well-established. Recent studies on the relationship between remnant cholesterol (RC) and cardiovascular risk in coronary artery disease patients have gained popularity. To date, little is known about the RC-related cardiovascular risk disparities between males and females. Purpose The aim is to investigate sex-specific differences in the association between RC and cardiovascular risk among CAD patients undergoing percutaneous coronary intervention (PCI). Methods A prospective cohort study was conducted among 10,724 CAD patients undergoing PCI from January to December in 2013. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE, including cardiac mortality, revascularization and ischemic stroke) and the secondary outcomes were each component of MACCE. Results Among 9,587 PCI patients included (the average age was 58.43 ± 10.26 years and 2,181 (22.70%) were female), 1,864 (19.4%) MACCEs were recorded during the 5-year follow-up. For primary outcome, a significant interaction was observed between RC levels and sex (P for interaction = 0.007 and 0.011, for continuous and categorical RC variables, respectively). Specifically, in male patients, no significant MACCE risk was observed at any RC level (both P &amp;gt; 0.05) (Figure 1). However, in female patients, both continuous RC levels (hazard ratio [HR] 1.412, 95% confidence interval [CI] 1.103-1.807) and the upper two quartiles of RC relative to the lowest quartile (Q3: HR 1.458, 95% CI 1.062-2.001; Q4: HR 1.496, 95% CI 1.081-2.070) were associated with higher MACCE risk. For secondary outcomes, higher RC levels were linked to an increased risk of cardiac mortality and revascularization in female patients but not in males (Table 1). Conclusions In a large-scale 5-year follow-up study from the real world, we are the first to demonstrate that RC-related cardiovascular risk is specifically observed in female CAD patients undergoing PCI, suggesting that female patients merit closer surveillance and more aggressive RC management to reduce cardiovascular risk.

Impact of glucose metabolism status on the relationship between remnant cholesterol and ischemic risk after percutaneous coronary intervention: a large-scale long-term cohort study from real-world

Abstract Background Elevated remnant cholesterol (RC) is considered a risk factor for ischemic events in patients with coronary artery disease (CAD). Recently evidence demonstrates a close connection between RC and cardiometabolic disorders, particularly diabetes mellitus (DM). However, it remains unclear whether different glucose metabolism statuses modify the association between RC and ischemic risk after percutaneous coronary intervention (PCI). Purpose This study aims to explore whether glucose metabolism statuses alter the relationship between RC and ischemic risk in CAD patients undergoing PCI. Methods This prospective study enrolled consecutive 10,724 CAD patients undergoing PCI throughout 2013. Patients were categorized into three groups: DM, pre-DM, and normal glucose regulation (NGR) group. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, and was analyzed based on tertile levels (low, middle, and high). The clinical endpoint was major adverse cardiovascular and cerebrovascular events (MACCE, including cardiac mortality, revascularization and stroke). Results A total of 9,406 PCI patients were ultimately included, among whom the average age was 58.44 ± 10.26 years and 2,142 (22.80%) were female. During 5-year follow-up, 1,876 (19.9%) patients experienced MACCE. In the overall cohort, the highest RC tertile was associated with a higher risk of MACCE (hazard ratio [HR]: 1.129, 95% confidence interval [CI]: 1.006-1.267) compared to those in the lowest tertile (Figure 1). Importantly, a significant interaction was observed between RC levels and glucose metabolism statuses (P for interaction = 0.032). In the DM group, multivariate Cox regression analysis revealed that the highest tertile of RC significantly increased a 1.172-fold risk of MACCE (HR:1.172, 95% CI:1.004-1.369). However, neither the pre-DM nor NGR groups showed any significant association between RC and MACCE (both P &amp;gt; 0.05). Further subgroup analysis found that the correlation between the highest tertile of RC and an increased MACCE risk was only in the DM group, which was prominent among females (Figure 2). Conclusions In a large-scale 5-year follow-up study, we are the first to demonstrate that RC-related ischemic risk may be exacerbated by diabetes in CAD patients undergoing PCI, highlighting the potential benefits of intensifying RC-lowering treatments for PCI patients combined with DM.