Low-density Lipoprotein Cholesterol Research Articles

Association between estimated cumulative LDL-C exposure and coronary artery disease severity and 2-year prognosis in acute coronary syndrome patients

Objective: To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS). Methods: The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE. Results: The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95%CI 1.08-1.37, P=0.002), 24% (95%CI 1.07-1.43, P=0.004), and 21% (95%CI 1.02-1.43, P=0.025) respectively. Conclusions: A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Clinical characteristics and prognosis of myocardial infarction with nonobstructive coronary arteries evaluated by optical coherence tomography

Myocardial infarction with nonobstructive coronary artery (MINOCA) is a heterogeneous disease with different pathophysiological mechanisms and prognosis. In recent years, it has been found that the incidence of major cardiovascular adverse events in MINOCA is similar to that of myocardial infarction with coronary artery disease (MI-CAD), and it is difficult to clarify the pathogenesis of both through coronary angiography (CAG). Therefore, the aim of this study is to investigate the clinical features, plaque characteristics and prognosis of patients with MINOCA and MI-CAD through optical coherence tomography (OCT). A total of 553 culprit lesions from AMI patients who underwent CAG and OCT were retrospectively analysed. Patients were subsequently divided into two groups: the MINOCA group and the MI-CAD group. The clinical characteristics, plaque characteristics and prognosis of the two groups were compared. The primary endpoint was defined as a composite of major adverse cardiac events (MACE), including cardiac death, non-fatal myocardial infarction, target lesion revascularization, stroke, and rehospitalisation for angina or heart failure. (1) Patients with MINOCA exhibited a lower incidence of ST-segment elevated myocardial infarction (STEMI) and a less frequent history of combined drug-eluting stent (DES) compared to those with MI-CAD. Additionally, they demonstrated lower levels of low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), peak troponin T (peak TnT) and peak creatine kinase (peak CK). The MINOCA group had more lesions in the left anterior descending (LAD) and fewer in the left circumflex (LCX). Additionally, they demonstrated a lower prevalence of multibranch vasculopathy and a diminished post-discharge use of aspirin, P2Y12 receptor inhibitors, beta-blockers, angiotensin converting enzyme inhibitor/angiotensin receptor blockers (ACEI/ARBs), and a higher proportion of conservative treatment compared to DES. The frequency of plaque rupture, calcified plaque, cholesterol crystals, macrophages infiltration, microvessels, thin-cap fibroatheroma (TCFA), and thrombus were found to be lower in the MINOCA group than in the MI-CAD group, with these differences being statistically significant (P < 0.05); (2) No significant difference was observed in the incidence of MACE at 30-days and 1 year between patients in the MINOCA and MI-CAD groups (P > 0.05). Compared with MI-CAD patients, MINOCA patients had fewer high-risk plaques on OCT and were more likely to be treated conservatively, with lower rates of stenting and less post-discharge pharmacological treatment. Both groups had similar rates of MACE at 30-day and 1 year, highlighting the importance of individualising treatment for MINOCA patients. Patients with MINOCA who develop MACE are more likely to exhibit high-risk OCT plaque features, with macrophage infiltration identified as an independent risk factor. OCT plaque features such as plaque rupture, plaque erosion, cholesterol crystals, macrophages, microvessels, TCFA may have played different roles in the progression of the two groups of patients.

Dyslipidaemia among children and adolescents in Pakistan: a five-year retrospective cohort study based on laboratory data

BackgroundDyslipidaemia is a significant risk factor for cardiovascular diseases, which can manifest early in life. Despite its importance, the prevalence of dyslipidaemia in the paediatric population of Pakistan remains poorly understood. This study uses laboratory data to determine the prevalence of dyslipidaemia and lipid testing practices among Pakistani children and adolescents.MethodsThis retrospective cohort study analysed the laboratory data from children and adolescents, aged up to 19 years, who underwent lipid testing. The data was obtained from two centres with collection points all over Pakistan for five years (March 2019–March 2024). Logistic regression models were used to assess relationships between demographic factors (age, sex and regions/provinces) and lipid profile parameters.ResultsOver five years, 9,787 children and adolescents with a mean age of 13.8 ± 5.1 years underwent lipid testing. Boys accounted for 59.7% of those tested compared to 40.3% of girls (p = 0.09). Most tests were conducted in Punjab (81.2%), with minimal representation from Balochistan (0.5%) and Gilgit Baltistan (0.3%). Among tested children and adolescents, 33.3% had elevated total cholesterol, 25.4% high low-density lipoprotein cholesterol, 46.6% low high-density lipoprotein cholesterol, 48.0% abnormal non- high-density lipoprotein cholesterol and 41.7% hypertriglyceridemia. Compared to boys, girls had significantly lower odds of abnormal high-density lipoprotein cholesterol (Odds Ratio 0.556, 95% CI 0.511–0.607, p < 0.001) and triglyceride levels (Odds Ratio 0.702, 95% CI 0.642–0.767, p < 0.001).ConclusionThis study highlights a high prevalence of dyslipidaemia among Pakistani children, with boys more affected than girls. The study also highlights a gender-based inequality in lipid testing where girls appear to be less frequently tested compared to boys.

Comprehensive evaluation of siRNA therapeutics on Lp(a): A network meta-analysis.

To evaluate the efficacy and safety of siRNA drugs that lower Lp(a) in patients with dyslipidaemia. A network meta-analysis and systematic review were conducted to compare siRNA drugs targeting Lp(a), based on relevant randomized controlled trials (RCTs). A comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library (up to October 24, 2024). RCTs with an intervention duration of at least 12 weeks were included. Eligible studies compared siRNA drugs that reduce Lp(a), including both Lp(a)-targeted and non-targeted agents, with placebo or other siRNA drugs that reduce Lp(a). The primary outcomes were the percentage reduction and absolute reduction in Lp(a), percentage reduction in low-density lipoprotein cholesterol (LDL-C), percentage reduction in apolipoprotein B (apo(B)), adverse events and serious adverse events, including injection-site reactions. The risk of bias was assessed using the Cochrane Risk of Bias Tool (ROB2), and a random-effects network meta-analysis was performed using the frequentist approach. Confidence in effect estimates was evaluated using the Confidence In Network Meta-Analysis (CINeMA) framework. A total of 14 trials involving 5646 participants were included. Lp(a)-targeted siRNA agents, particularly Olpasiran, demonstrated strong efficacy in significantly reducing Lp(a) levels, with the greatest percentage reduction in Lp(a) (mean difference [MD]: -92.06%; 95% CI: -102.43% to -81.69%; P-score: 0.98). Olpasiran also showed the greatest absolute reduction in Lp(a) (MD: -250.70 nmol/L; 95% confidence interval [CI]: -279.89 to -221.50; P-score: 0.99). Certain non-Lp(a)-targeted siRNA agents, such as inclisiran and zodasiran, also showed modest reductions in Lp(a) levels, reducing Lp(a) by approximately 15%. Lp(a)-targeted siRNA agents reduced LDL-C by more than 20% and decreased apo(B) by approximately 15%. In terms of safety, most drugs exhibited favourable safety profiles with no significant differences compared to placebo. However, zerlasiran raised concerns regarding injection-site reactions and other adverse events when compared to placebo. Lp(a)-targeted siRNA agents have shown robust effectiveness in substantially reducing Lp(a) levels, including both percentage and absolute reductions, with moderate improvements in LDL-C and apo(B) concentrations. Non-Lp(a)-targeted siRNA agents also demonstrate modest reductions in Lp(a) levels. The safety profile is generally favourable, but zerlasiran and inclisiran may increase the incidence of injection-site reactions.

Predictive value of the triglyceride-glucose index for coronary artery bypass grafting-acute kidney injury patients

BackgroundAcute kidney injury (AKI) is a common and serious complication after coronary artery bypass grafting (CABG), significantly affecting patient outcomes. The triglyceride-glucose (TyG) index, a marker of insulin resistance, has shown potential in predicting various metabolic and cardiovascular conditions. This study aimed to evaluate the predictive value of the TyG index for AKI occurrence following CABG.MethodsThis retrospective, single-center study included 3,260 patients who underwent CABG. Patients were categorized into AKI and non-AKI groups based on postoperative renal function. The preoperative TyG index was calculated from fasting blood glucose and triglyceride levels. Patients were further divided into quartiles based on the TyG index. Logistic regression analysis was used to assess the relationship between TyG index and AKI risk. Subgroup analyses and spline regression were employed to explore potential interactions and non-linear relationships.ResultsOf the 3,260 patients, 514 (15.8%) developed AKI. Baseline characteristics showed that AKI patients had significantly higher levels of hemoglobin (Hb), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose, while brain natriuretic peptide (BNP) levels were lower compared to non-AKI patients. Logistic regression analysis confirmed that the TyG index was an independent risk factor for AKI following CABG, both as a continuous variable (OR 1.034 [95% CI 1.017–1.050], p < 0.001) and when grouped by quartiles. A non-linear relationship between TyG index and AKI risk was observed, with a significant increase in AKI risk when the TyG index exceeded 5.4. Subgroup analyses revealed that this association was consistent across multiple patient groups, including those stratified by age, sex, BMI, extracorporeal circulation use, and comorbidities such as hypertension, diabetes, and hyperlipidemia.ConclusionsThe preoperative TyG index is a significant independent predictor of AKI after CABG, with a dose-response relationship observed across various subgroups. Monitoring the TyG index can help identify high-risk patients, potentially guiding early intervention and improving postoperative outcomes. These findings underscore the potential of the TyG index as a valuable tool for predicting AKI in clinical practice, warranting further validation in prospective studies.

Life Course Approach for Managing Familial Hypercholesterolemia.

Treatment of familial hypercholesterolemia is directed toward the moment of the medical encounter. However, risk for heart disease as a consequence of having familial hypercholesterolemia is related to lifelong exposure to elevated low-density lipoprotein cholesterol, rather than low-density lipoprotein cholesterol level at a specific time point. The purpose of this review is to reassess contemporary research on treatment of familial hypercholesterolemia and current evidence-based guidelines, to present an approach that emphasizes treatment across the life course, and to recognize the importance of family experiences to care. To accomplish this, we review the changing treatment needs that emerge across the life course, from birth through childhood, adolescence, young adulthood, peripregnancy, middle age, and late in life. Special attention is paid to improving adherence to treatment, the potential role of monitoring atherosclerosis in a lifelong model of care, and medical issues related to care transitions: from pediatric to internal medicine care, peripregnancy, after a cardiac event, and care after age 70 years in the absence of a cardiac event. Novel considerations related to treatment of homozygous familial hypercholesterolemia are discussed. The summary identifies research gaps that need to be closed to move from the current point-of-care model to one that considers treatment over the life course.

Association of dyslipidemia with intervertebral disc degeneration: a case–control study

PurposeTo investigate the relationship between dyslipidemia and intervertebral disc degeneration (IVDD). MethodsA total of 269 patients with lumbar disc herniation (Grade III–VIII using the modified Pfirrmann Grading Systems and Total End Plate Damage Score (TEPS) III–VI grade) and 269 patients with lumbar vertebral fracture (LVF, Grade I–II using the modified Pfirrmann Grading Systems and TEPS I–II grade) were enrolled in this study. The total cholesterol level (TC), low-density lipoprotein-cholesterol level (LDL-C), triglyceride level (TG), high-density lipoprotein-cholesterol level (HDL-C), nonHDL-C, ApoB level, ApoB A1 level and arteriosclerosis index (AI) were measured. The 269 patients with single-level LDH who underwent surgery were assigned to the disc herniation group (DH) and 269 patients who underwent surgical treatment for lumbar vertebral fracture during the same period were enrolled as the control group. The participants in the control group were selected randomly and matched for sex.ResultsThe analysis revealed that the levels of TC, TG, LDL, nonHDL-C, APOB, and APOA1 in patients with LDH were significantly higher compared with those in the controls. The proportion of high-TC, borderline high-total cholesterol, high LDL-C, high-TG, borderline high LDL-C, high APO B, high arteriosclerosis index (AI), and high-ApoB/ApoA1 in the LDH group was significantly higher relative to that of the control group. The ratio of TC/HDL-C, TG/HDL-C, LDL-C/HDL-C, nonHDL-C/HDL-C, and ApoB/ApoA1 in the LDH group was significantly higher compared with that of the control group. Multivariate logistic regression analysis showed that the levels of serum TG, Apo B/ApoA1 ratio, atherogenic index(AI), labour intensity, and age were positively associated with the risk of LDH and were independent risk factors predicting IVDD development.ConclusionOverall, this study indicates that age, labour intensity, TG, ApoB/ApoA1 ratio and atherogenic index (AI) may increase the risk of IVDD. The levels of TC, TG, LDL-C, nonHDL-C, Apo B, and atherogenic index (AI) may be related to the degree of cartilage endplate (CEP) and intervertebral disc degeneration (IVDD). Moreover, dyslipidemia may be a useful predictor of IVDD.

A meta-analysis of adverse offspring health outcomes in patients with gestational diabetes mellitus.

This study aims to comprehensively evaluate the association between gestational diabetes mellitus (GDM) and the risk of chronic diseases, including obesity, glycolipid metabolic disorders, neurodevelopmental conditions and cardiovascular diseases, in offspring through a systematic meta-analysis. By searching PubMed, Web of Science and Cochrane systematic review databases, relevant observational studies published from January 2010 to February 2024 were comprehensively retrieved, and the Newcastle-Ottawa Scale was used to assess the quality of the studies. Subgroup analyses were performed based on the country status, offspring age, screening method and diagnostic criteria of GDM. A meta-regression model was used to assess the potential impact of study characteristics on the combined effect odds ratio (OR). Sensitivity analysis was conducted to examine the impact of individual studies on the overall results. Additionally, Egger's test and funnel plot analysis were utilized to assess potential publication bias. This meta-analysis included 32 studies, encompassing a total of 3 310 217 participants (90 304 women with GDM and 3 219 913 controls). Offspring exposed to GDM exhibited significantly elevated risks of obesity and overweight (OR = 1.57, 95% confidence interval [CI] [1.35, 1.82]), diabetes (OR = 4.50, 95% CI [2.87, 7.70]), autism spectrum disorder (OR = 1.38, 95% CI [1.20, 1.59]) and intellectual disabilities (OR = 1.70, 95% CI [1.52, 1.90]). Furthermore, offspring of mothers with GDM demonstrated higher systolic blood pressure (mean difference [MD] = 2.33, 95% CI [0.92, 3.75]), diastolic blood pressure (MD = 0.53, 95% CI [0.09, 0.96]), body mass index (BMI) (MD = 0.62, 95% CI [0.45, 0.80]), z-BMI score (MD = 0.27, 95% CI [0.15, 0.39]), triglyceride levels (MD = 0.04, 95% CI [0.04, 0.04]) and LDL cholesterol levels (MD = 0.02, 95% CI [0.02, 0.02]) compared to controls. In conclusion, maternal GDM is significantly associated with an increased risk of obesity, neurodevelopmental disorders, diabetes and cardiovascular diseases in offspring. Subgroup and regression analyses revealed that this association was largely unaffected by factors such as country status, offspring age, GDM screening methods or diagnostic criteria. Sensitivity analysis and bias assessment indicated that the findings were robust, with no significant publication bias detected among the included studies. GDM is a significant risk factor for offspring developing glycolipid metabolic disorders, neurodevelopmental conditions and cardiovascular diseases. This study provides a comprehensive understanding of the long-term health implications for offspring exposed to GDM, highlighting the elevated risk of chronic diseases in this population. These findings underscore the importance of implementing early preventive measures post-birth to mitigate the burden of associated chronic diseases.

Analysis of ABCG2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemia

The relationship between the single nucleotide polymorphism (SNP) at the rs2231142 locus of the Adenosine triphosphate-binding cassette transporter G subfamily member 2 (ABCG2) gene and susceptibility to hyperuricemia (HUA) is to be investigated, alongside an analysis of the associated risk factors for HUA. Venous blood samples were obtained from 1612 patients diagnosed with HUA and 1770 individuals exhibiting normal uric acid (UA) levels. Deoxyribonucleic acid was isolated, followed by amplification of the target gene via polymerase chain reaction. The genotype at the ABCG2 gene rs2231142 locus were determined using the enhanced multiplex ligation detection reaction method. Serum concentrations of UA, glucose, blood urea nitrogen (BUN), creatinine (CREA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) were assessed in both groups. Clinical data were compiled. LASSO regression and multivariate logistic regression analyses were conducted to identify independent risk factors for HUA. A predictive model for HUA that integrates the SNP at the ABCG2 gene rs2231142 locus was developed. The model’s accuracy in predicting HUA was evaluated through the receiver operating characteristic (ROC) curve. The frequencies of the GG, GT, and TT genotypes at the rs2231142 locus of the ABCG2 gene in the male control and HUA groups were 66.2% and 60.3%, 29.2% and 35.5%, 4.6% and 4.3% (P = 0.012). These frequencies were markedly different from those of the female control and HUA groups, which exhibited 68.5% and 58.2%, 29.2% and 36.0%, 2.3% and 5.8% (P < 0.001). Regression analysis revealed seven independent risk factors for HUA: waist-to-hip ratio (WHR), BUN, TG, TC, LDL-C, and the rs2231142 G/T and T/T genotypes. For every unit increase in WHR, BUN, TG, and LDL-C, the odds of developing HUA increased by 1.794, 1.166, 1.421, and 1.286 times, respectively. A significant association was found between HUA risk and the rs2231142 G/T and T/T genotypes. Individuals harboring the rs2231142 G/T mutation exhibited a 1.192 times greater likelihood of developing HUA compared to those without the mutation, while those with the T/T genotype had a risk increase of 2.557 times. A diagnostic model for HUA was developed utilizing these risk factors, with performance assessed through the ROC curve. The area under the curve was measured at 74.8%, indicating that the model incorporating the ABCG2 gene rs2231142 locus possesses diagnostic efficacy for early prediction of HUA. Male HUA patients with the TT genotype at the ABCG2 gene rs2231142 locus displayed markedly elevated CREA levels (87.051 ± 36.378 μmol/L) in comparison to homozygous G/G (82.128 ± 39.482 μmol/L) and heterozygous G/T carriers (81.733 ± 35.926 μmol/L). A higher frequency of the T allele mutation at the rs2231142 locus of the ABCG2 gene is observed in HUA patients. Individuals possessing the rs2231142 T allele demonstrate an increased probability of developing HUA, potentially more pronounced in females. The model integrating the rs2231142 T allele locus with associated clinical risk factors exhibits diagnostic efficacy for the early prediction of HUA occurrence. Additionally, the mutation at the ABCG2 gene rs2231142 locus may influence serum CREA levels.

Prognostic impact of residual inflammatory and triglyceride risk in statin-treated patients with well-controlled LDL cholesterol and atherosclerotic cardiovascular disease.

Identifying alternative contributors to the residual risk of atherosclerotic cardiovascular disease (ASCVD) beyond LDL cholesterol (LDL-C) levels is crucial. We investigated the relative impact of triglycerides (TGs) and high-sensitivity C-reactive protein (hs-CRP) on outcomes in statin-treated patients with well-controlled LDL-C undergoing percutaneous coronary intervention (PCI) for established ASCVD. We included 9446 statin-treated patients with LDL-C < 70 mg/dL undergoing PCI between 2012 and 2022, stratified into four groups: (i) no residual risk (TG <150 mg/dL + hs-CRP <2 mg/L); (ii) residual TG risk (TG ≥150 mg/dL + hs-CRP <2 mg/L); (iii) residual inflammatory risk (TG <150 mg/dL + hs-CRP ≥2 mg/L); and (iv) residual TG and inflammatory risk (TG ≥150 mg/dL + hs-CRP ≥2 mg/L). The primary endpoint was major adverse cardiovascular events (MACE) at 1 year, consisting of all-cause mortality, myocardial infarction, or stroke. Cox regression analysis was performed, using the no residual risk group as a reference. Of the total population, 5339 (56.5%) had no residual risk, 555 (5.9%) presented residual TG risk, 3009 (31.9%) had residual inflammatory risk, and 543 (5.7%) exhibited residual combined risk. After multivariable adjustment, patients with residual inflammatory or combined risk showed a significantly higher hazard of MACE, mainly driven by all-cause mortality. No significant difference was observed between patients with residual TG risk and those with no residual risk. In statin-treated patients with well-controlled LDL-C undergoing PCI, residual inflammatory risk-alone or in combination with residual TG risk-was associated with a higher incidence of MACE, highlighting the need for targeted preventive strategies beyond LDL-C lowering.

Biomechanical impact of hyperlipidemia on blood flow and vascular pressure: A computational and in vivo analysis

Hyperlipidemia is a major contributor to cardiovascular diseases, impacting vascular function by altering hemodynamic parameters such as blood flow velocity and vascular pressure. This study investigated these effects using Doppler ultrasound, vascular pressure sensors, and computational fluid dynamics (CFD) modeling in a cohort of 100 participants, divided into 50 hyperlipidemic individuals (total cholesterol: 250.4 ± 15.2 mg/dL, triglycerides: 180.3 ± 20.5 mg/dL, low-density lipoprotein (LDL) cholesterol: 170.1 ± 10.3 mg/dL) and 50 controls (total cholesterol: 190.7 ± 10.4 mg/dL, triglycerides: 130.2 ± 15.7 mg/dL, LDL cholesterol: 120.5 ± 9.8 mg/dL). Future research could explore the differential effects of LDL and HDL on blood flow velocity and vascular pressure, as LDL is known to increase blood viscosity and contribute to endothelial dysfunction, while HDL may have a protective effect by improving endothelial function and reducing vascular resistance. Results showed a significant reduction in blood flow velocity in the hyperlipidemic group (28.1 ± 3.1 cm/s) compared to controls (32.5 ± 2.3 cm/s, p &lt; 0.001) and an increase in vascular pressure (98.6 ± 5.4 mmHg vs. 85.2 ± 4.1 mmHg, p &lt; 0.001). CFD analysis revealed increased turbulence and shear stress variability, contributing to endothelial dysfunction and vascular resistance. Statistical correlations indicated a strong negative association between LDL cholesterol and blood flow velocity (r = −0.624, p &lt; 0.001) and a positive association between total cholesterol and vascular pressure (r = 0.583, p &lt; 0.001). These findings highlight the biomechanical consequences of hyperlipidemia, emphasizing the need for early intervention through lipid-lowering therapies and lifestyle modifications to improve vascular health. The integration of CFD modeling into clinical practice may enhance risk assessment and personalized treatment strategies for hyperlipidemic individuals.

Joint Associations of APOC3 and LDL-C–Lowering Variants With the Risk of Coronary Heart Disease

Despite substantial progress in low-density lipoprotein cholesterol (LDL-C)-lowering strategies, residual cardiovascular risk remains. Apolipoprotein C3 (APOC3) has emerged as a novel target for lowering triglycerides. Multiple clinical trials of small-interfering RNA therapeutics targeting APOC3 are currently underway. To investigate whether genetically predicted lower APOC3 is associated with a reduction in cardiovascular risk and if the combined exposure to APOC3 and LDL-C-lowering variants is associated with a reduction in the risk of coronary heart disease (CHD). This was a population-based genetic association study with 2 × 2 factorial mendelian randomization. Included were participants of European ancestry in the UK Biobank. Data were analyzed from November 2023 to July 2024. Genetic scores were constructed to mimic the effects of APOC3, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors. Plasma lipid and lipoprotein levels, CHD, and type 2 diabetes (T2D). This study included 401 548 UK Biobank participants (mean [SD] age, 56.9 [8.0] years; 216 901 female [54.0%]). Genetically predicted lower APOC3 was associated with a lower risk of CHD (odds ratio [OR], 0.96; 95% CI, 0.93-0.98) and T2D (0.97; 95% CI, 0.95-0.99). Genetically lower APOC3 and PCSK9 were associated with a similar magnitude of risk reduction in CHD per 10-mg/dL decrease in apolipoprotein B (ApoB) level (APOC3: 0.70; 95% CI, 0.59-0.83; PCSK9: 0.71; 95% CI, 0.65-0.77). Combined exposure to genetically lower APOC3 and PCSK9 was associated with an additive lower risk of CHD (APOC3: 0.96; 95% CI, 0.92-0.99; PCSK9: 0.93; 95% CI, 0.90-0.97; combined: 0.90; 95% CI, 0.86-0.93). Genetically lower HMGCR was also associated with a lower risk of CHD, and the risk was further reduced when combined with APOC3 (0.93; 95% CI, 0.90-0.97). Genetically predicted lower APOC3 was associated with a reduced risk of CHD that is comparable with that associated with lower PCSK9 per unit decrease in ApoB. Combined exposure to APOC3 and LDL-C-lowering variants was associated with an additive reduction in CHD risk. Future studies are warranted to investigate the therapeutic potential of these combined therapies, particularly among high-risk patients who cannot achieve therapeutic targets with existing lipid-lowering therapies.

Renal Safety Assessment of Lipid-Lowering Drugs: Between Old Certainties and New Questions.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Quantitative and qualitative changes in plasma lipoprotein profiles are frequently associated with CKD and represent a significant risk factor for CVD in patients with CKD. Guidelines from the European Society of Cardiology and the European Atherosclerosis Society classify CKD as a condition with high or very high cardiovascular risk and set specific low-density lipoprotein cholesterol targets. Conventional lipid-lowering therapies (LLTs), such as statins, ezetimibe, and fibrates, can control CKD-associated dyslipidemia and, to some extent, prevent major atherosclerotic events in patients with CKD, but their use in clinical practice presents challenges because of the potential renal safety concerns. In recent years, novel therapies with the ability to lower both low-density lipoprotein cholesterol and triglycerides have been introduced to the market (e.g., proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, lomitapide, volanesorsen) to improve our ability to control lipid abnormalities. However, their impact on kidney functionality has not been fully elucidated. The aim of this review was to examine the renal safety profiles of various LLTs, with special reference to novel medications, and to highlight important considerations and guidance for the use of these medications in overt CKD or in patients with some degree of renal function impairment. We underscore the lack of a comprehensive understanding of kidney safety, particularly for novel LLT therapies, and strongly emphasize the importance of future dedicated research to fully assess the safety and efficacy of these agents in patients with kidney abnormalities.

Potential for the use of nutraceuticals for hyperlipidemia correction

Lipid storage disorders are one of the risk factors for systemic atherosclerotic process development. One of important aspects of hyperlipidemia treatment is non-drug methods, including lifestyle changes and the use of nutraceuticals. Objective. To analyze current data on the efficacy and safety of the dietary food supplements use for hyperlipidemia correction. Materials and methods. Search and analysis of literature reviews and original articles from PubMed and eLibrary databases published between 2016 and May 2024 were performed. The following keywords were used: nutraceuticals, hyperlipidemia. A number of full-text publications equal 47 was selected. The review also presents primary sources covering studies of dietary food supplements dated earlier than 2016, as they contain valuable information. Results. Red yeast rice (monacolin), phytosterols, omega-3 fatty acids, dietary fibers were used as functional food ingredients widely studied in hyperlipidemia. Efficacy of a given nutraceutical varies and is in the range of minus 5% to 25% of the baseline low-density lipoprotein cholesterol level. Data on side effects, related to both the action of biologically active agent itself and the lack of standardization and presence of undesirable impurities in the composition were obtained. Conclusion. Change in dietary pattern for primary prevention can be used in persons with low/moderate or high cardiovascular risk in low-density lipoprotein cholesterol level ranging from 1.8 to 2.6 mmol/L in the absence of indications for taking statins and/or at doctor’s discretion. Despite the positive effects of nutraceuticals administration, it is important to remember that they cannot replace lipid-lowering therapy, but have the potential to reduce residual cardiovascular risk.

Cardiovascular disease and stroke prevention educational-behavioural programs for culturally and/or linguistically diverse communities: a systematic review and meta-analysis.

To identify the types of cardiovascular disease (CVD) and stroke prevention educational-behavioural programs for people from culturally and/or linguistically diverse (CALD) backgrounds and investigate their effect on CVD risk factors and disease knowledge. Four electronic databases were searched from inception to September 2023. Mean difference (MD) and standardised MD was calculated using random-effects model, and heterogeneity was assessed using the I2 statistic. Studies that were not included in the meta-analysis were narratively described. The Cochrane Risk of Bias tool and Joana Briggs Institute Critical Appraisal checklist were used to assess the quality of the included studies. Sixteen studies originating from USA and UK (4 RCTs and 12 quasi-experimental pre-post studies) with n=2331 participants (mean age 57.2 years, 50% women) were included. The programs were multi-component, 15 of which were culturally adapted and 1 was co-designed. Most were delivered face-to-face in groups. In contrast to the results among the pre-post studies, the pooled analysis showed that educational-behavioural programs may have little to no effect on SBP (MD 1.18 mmHg, 95% CI -2.42-4.79) and HbA1c (MD -0.29%, 95% CI -0.89-0.32). The results for LDL cholesterol, BMI, physical activity and dietary intake were also mixed except for CVD or stroke knowledge which demonstrated statistically significant improvements after the intervention. The effect of educational-behavioural programs on CVD risk factors is inconclusive but may improve CVD or stroke knowledge. Co-designing programs underpinned by behaviour change theories/techniques with stakeholders and target CALD communities may enhance their potential impact. Future studies should use more rigorous study design i.e., RCTs, valid and reliable outcome measures to reduce inherent bias and strengthen the evidence base for the effectiveness of these programs.

Impact of Sex Differences on Lipids and Statin Utilization.

Hypercholesterolemia is a significant and modifiable risk factor for cardiovascular disease (CVD), with Low-Density Lipoprotein Cholesterol (LDL-C) being the primary target for lipid-lowering therapies in both primary and secondary prevention. This review aims to explore the efficacy of statin therapy in women, its safety and application during pregnancy, and treatment disparities that contribute to undertreatment of dyslipidemia in women. Statins has demonstrated efficacy in reducing LDL-C and CVD risk in women. However, women are less likely to achieve LDL-C targets compared to men, largely due to undertreatment and delays in initiating therapy, often influenced by sex-specific factors. The unique considerations of lipid management during pregnancy, including suspension of statin therapy, present additional challenges in achieving optimal lipid control in high-risk women. Evidence also points to systemic disparities in healthcare delivery and treatment allocation, further exacerbating undertreatment of dyslipidemia among women. While LDL-C lowering remains a cornerstone of CVD prevention, women face distinct challenges in achieving lipid goals due to biological, clinical, and healthcare disparities. Addressing these barriers, including improving timely initiation of statins and addressing gaps in care during pregnancy, is essential to enhance the dyslipidemia management and reduce CVD risk in women.

Upfront lipid-lowering combination therapy in high cardiovascular risk patients: a route to effective atherosclerotic cardiovascular disease prevention.

Despite three decades of using statin therapy, 20 years of experience with ezetimbe, and availability of innovative non-statin lipid lowering therapies (LLT), there are still about 70% patients over the low-density lipoprotein cholesterol (LDL-C) goal, with every 5-6th being over the target from the group of very high and extremely high cardiovascular disease (CVD) risk patients. Adding another even every 5th patient at very high CVD risk without any LLT, makes this situation highly frustrating, especially lipid disorders are the most common CVD risk factor with the prevalence of over 60%, with the worst awareness within all cardiovascular risk factors (only about 15% people knows their LDL-C level). To answer this since 2021 there is an approach to apply upfront (immediate) lipid lowering combination therapy of statin and ezetimibe in very high and extremely high-risk patients to be on the LDL-C target as low as possible, but especially as early as possible, enabling to introduce the third line therapy (i.e., bempedoic acid and/or PCSK9 targeted therapy) already after 4-6 weeks. This review discusses the current stage of knowledge and recent data on the group of patients that might benefit the most from the upfront combination LLT, when it should be optimally implemented, and the recent data on its role on LDL-C reduction, cardiovascular and mortality outcomes as well as safety issues.

Effect of oral resveratrol-loaded nanoliposomes on hyperlipidemia via toll-like receptor 3 and TIR domain-containing adaptor inducing interferon-β protein expression in an animal model

Hyperlipidemia, a critical risk factor for various health conditions, necessitates innovative therapeutic strategies. Investigating the effectiveness of liposomal formulations in managing hyperlipidemia is essential. Resveratrol (RES)-loaded nanoliposomes present a promising new approach for hyperlipidemia treatment. In this study, we investigated the anti-hyperlipidemic potential of RES-loaded nanoliposomes in high-fat diet (HFD)-fed rats. The nanoliposomes were prepared using a thin-film hydration method. According to transmission electron microscopy (TEM) and dynamic light scattering (DLS) results, the mean size of prepared RES-loaded nanoliposomes were about 42 nm and 68 nm, respectively, with a zeta potential of −65.6 mV. The entrapment efficiency and loading content were 83.78% and 14.25%, respectively. Additionally, the RES-loaded nanoliposomes exhibited controlled release kinetics compared to the free RES form. Moreover, in a hyperlipidemic rat model induced by an HFD, orally administered RES-loaded nanoliposomes significantly reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG), while concurrently increasing high-density lipoprotein cholesterol (HDL-C) levels. Additionally, liver damage induced by HFD was alleviated by RES-loaded nanoliposomes. The expression levels of Toll-like receptor 3 (TLR3) and TIR domain-containing adaptor-inducing interferon-β (TRIF) were assessed using fluorescence immunohistochemistry. Notably, RES-loaded nanoliposomes significantly reduced the expression of these protein. The effect of RES-loaded nanoliposomes was measured on body weight of HFD rats, demonstrting RES-loaded nanoliposomes hold promise for weight management. These findings underscore the potential of RES-loaded nanoliposomes as a safe and effective therapeutic option for hyperlipidemia.

Comparative Analyses Between Vulnerability Biomarkers of Aging and Health Biomarkers in Middle-Aged and Older Female Adults

Biological aging is normally associated with greater physiological changes which predispose individuals to adverse outcomes. In this way, the evaluation of vulnerability biomarkers and their relationships with other health biomarkers could contribute to the promotion of interventions and the improvement of older adults’ quality of life. Thereby, this study aimed to compare vulnerability biomarkers (Growth Differentiation Factor 15 (GDF-15), General Functional Fitness Index (GFFI), and frailty phenotype) and their influence on health markers (blood biochemistry, body composition, and hemodynamic variables) in middle-aged and older female adults. Methods: A cross-sectional observational study was conducted with community-dwelling females aged 54–84 with at least 6 months of experience with physical training. The participants were categorized based on functional fitness, frailty phenotype, and GDF-15 quartiles. The General Functional Fitness Index (GFFI) was assessed using the AAHPERD test battery, while frailty phenotype was determined using Fried’s criteria. GDF-15 levels were measured through ELISA. Results: A higher training status (TS) showed better functional fitness and favorable biochemical profiles, including lower total cholesterol (p = 0.006, η2p = 0.253), LDL cholesterol (p = 0.001, η2p = 0.346), triglycerides (p = 0.048, η2p = 0.195), and systolic blood pressure (p = 0.001, η2p = 0.333). Individuals classified as robust (non-frail) had better physical performance and lower total cholesterol (p = 0.002, η2p = 0.306) and LDL cholesterol (p = 0.014, η2p = 0.216) compared to those classified as frail and pre-frail. The GDF-15 quartile did not present differences in health markers between groups. Conclusions: These findings suggest that GFFI may be considered a health biomarker for middle-aged and female older adults while highlighting the need for further research on the role of biomarkers of vulnerability and healthy aging.

Association between hyperlipidemia and postoperative delirium risk: a systematic review and meta-analysis

IntroductionThe association between hyperlipidemia and its potential role as a risk factor for postoperative delirium (POD) remains unclear.MethodsWe systematically searched PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov to identify studies meeting the inclusion criteria. Outcomes of interest included comparisons of blood lipid levels between POD and non-POD (NPOD) patients, the association between hyperlipidemia and POD risk, and the predictive value of hyperlipidemia for POD.ResultsA total of nine studies involving 4,686 patients were included in the meta-analysis. Pooled analysis revealed that hyperlipidemia was significantly associated with an increased risk of POD (OR = 1.47; 95% CI 1.13–1.91; P = 0.004;) compared to patients without hyperlipidemia. Patients with POD exhibited significantly higher levels of total cholesterol (TC) (weighted mean difference [WMD] = 0.31; 95% CI 0.03–0.59; P = 0.030), triglycerides (TG) (WMD = 0.37; 95% CI 0.03–0.71; P = 0.033), and low-density lipoprotein cholesterol (LDL-C) (WMD = 0.09; 95% CI 0.01–0.17; P = 0.023) compared to NPOD patients. In contrast, high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in POD patients (WMD = −0.07; 95% CI −0.12 to −0.01; P = 0.026). Insufficient evidence was available to summarize the area under the curve (AUC) results.ConclusionsBlood lipid levels were significantly elevated in POD patients compared to NPOD patients. Hyperlipidemia was significantly associated with an increased risk of POD, highlighting its potential role as a risk factor.