ADLM Guidance Document on the Measurement and Reporting of Lipids and Lipoproteins.

BACKGROUND: The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant variations in pre-analytical requirements, methods, nomenclature, and reporting work flows. CONTENT: The guidance document aims to improve standardization of clinical lipid testing work flows. It provides recommendations for the components of the lipid panel, fasting requirements, reporting of results, and specific recommendations for non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (apo B), point-of-care lipid testing, and LDL subfraction testing. SUMMARY: Lipid panels should always report non-HDL-C and LDL-C calculations if possible. Fasting is not routinely required except in specific cases. Modern equations should be utilized for LDL-C calculation. These equations allow for LDL-C reporting at elevated concentrations of triglycerides and obviate the need for direct measured LDL-C in most cases.

Aggressive low-density lipoprotein (LDL) lowering for primary prevention: still an elusive goal.

Cardiovascular disease (CVD) is the leading cause of mortality globally. Low-density lipoprotein (LDL) plays an important role in CVD pathophysiology. Research has shown the safety and efficacy of keeping LDL at very low levels for CVD prevention. Therefore, experts recommend intense LDL-lowering approaches starting at young ages, promoting the mantras "the lower, the better" and "the earlier, the better." This commentary discusses the challenges regarding applying aggressive LDL-lowering approaches in the general population, including pharmacological efficacy and side effects, the cost-effectiveness of interventions, and patient adherence to treatment regimens.

Individualized Nutritional Management Using Dishcook Improves Nutrition Status Markers in Patients with Intellectual Disability.

Dishcook is a new cooking system that allows individual cooking using a dedicated induction heater. This study investigated whether Dishcook use affects the nutritional value of individuals with intellectual disabilities. This study was conducted on users receiving support from a continuous-employment office in Obama City, Fukui Prefecture, in 2022. Of these participants, 18 (seven women and 11 men) who requested the use of the Dishcook were included in the analysis. The study period was from January to August 2023. The mean age was 48.72±16.24 y. A significant increase in the overall phase angles of the limbs was observed. Triglyceride, LDL cholesterol, HbA1c, and serum zinc levels improved in patients who used the Dishcook. The phase angle obtained using Bioelectrical Impedance Analysis also improved, indicating the usefulness of the Dishcook in treating metabolic diseases and the possibility of individualized nutritional management.

Low-Density Lipoprotein Cholesterol, Cardiovascular Risk Factors, and Predicted Risk in Young Adults.

BACKGROUND: Young adults with elevated LDL-C may experience increased burden of additional cardiovascular disease (CVD) risk factors. It is unclear how much LDL-C levels, a modifiable factor, correlate with non-LDL-C CVD risk factors among young adults or how strongly these CVD risk factors are associated with long-term predicted CVD risk. We quantified clustering of non-LDL-C CVD risk factors by LDL-C among young adults to assess the association between non-LDL-C and LDL-C risk factors with predicted CVD risk in young adults. METHODS: The current analysis is a cross-sectional study of adults < 40 years with an LDL-C< 190 mg/dL participating in the National Health and Nutrition Examination Survey (NHANES) between January 2015 and March 2020. We measured the prevalence of non-LDL-C risk factors by LDL-C and association between LDL-C and non-LDL-C risk factors with predicted risk of CVD by the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations. RESULTS: Among 2108 young adults, the prevalence of LDL-C ≥ 130 mg/dL was 15.5%. Compared with young adults with LDL-C < 100 mg/dL, those with LDL-C 100-< 130, 130-< 160, and 160-< 190 mg/dL had greater non-LDL-C risk factors. Both LDL-C and non-LDL-C risk factors were independently associated with a 30-year risk of CVD (OR 1.05, 95% CI 1.03-1.07 and OR 1.17, 95% CI 1.12-1.23, respectively). The association of LDL-C and 30-year risk did not vary by non-LDL-C risk factor burden (pinteraction = 0.43). CONCLUSION: Non-LDL-C risk factors cluster among increasing levels of LDL-C in young adults. Greater guidance on how to manage cardiovascular risk factors in young adults is needed.

Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.

[Low and very low cholesterol levels: what we need to know]. / Livelli di colesterolo bassi e molto bassi: cosa è necessario sapere.

Due to the growing evidence of clinical benefits conferred by the reduction of low-density lipoprotein cholesterol (LDL-C) levels, the availability of multiple effective lipid-lowering agents, and guideline recommendations, clinicians not infrequently have to manage patients with low or very low LDL-C levels. In clinical practice it is essential to consider that, when LDL-C plasma concentrations are low, the Friedewald formula commonly used for LDL-C level calculation is less accurate, hence risk assessment should be integrated by using different methods for LDL-C level quantification and other parameters, such as non-high-density lipoprotein cholesterol and, where possible, apolipoprotein B, should be measured. As regards the clinical impact of low LDL-C levels, genetically determined hypocholesterolemia forms provide reassuring data on the effects of this condition in the long term, except for the forms with extremely low or undetectable LDL-C levels. Evidence from clinical studies that used highly effective lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 inhibitors, goes in the same direction. In these studies, the incidence of non-cardiovascular adverse events in patients who reached very low LDL-C levels was similar to that in the placebo arm. Overall, the fear of adverse effects should not deter intensive lipid-lowering treatment when indicated to reduce the risk of cardiovascular events.

Prediction of Cumulative Exposure to Atherogenic Lipids During Early Adulthood.

BACKGROUND: The ability of a 1-time measurement of non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood (age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear. OBJECTIVES: The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years. METHODS: We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had ≥3 measurements of LDL-C and non-HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non-HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40 years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years. RESULTS: Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995 participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non-HDL-C and LDL-C had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC: 0.93 for the 4 models). The absolute values of non-HDL-C and LDL-C that predicted membership in the top quartiles with the highest simultaneous sensitivity and specificity (highest Youden's Index) were >135 mg/dL for non-HDL-C and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for non-HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non-HDL-C and LDL-C exposure had demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years, respectively, when compared with each bottom quartile. CONCLUSIONS: Single measures of non-HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events.

Sex specific analysis of patients with and without reported statin intolerance referred to a specialized outpatient lipid clinic.

BACKGROUND: Lowering LDL-cholesterol is a fundamental goal for both primary and secondary prevention of atherosclerotic cardiovascular diseases. Our study aims to analyse potential sex disparities regarding the tolerability and effectiveness of lipid-lowering therapy in patients with and without reported statin intolerance who are being treated at a lipid-outpatient clinic. METHODS: From 2017 to 2022, n = 1062 patients (n = 612 men, n = 450 women) at high-risk were referred to our lipid-outpatient clinic because of difficulties in lipid control by primary healthcare providers. The main therapeutic objective was to optimize lipid-lowering therapy according to current treatment guidelines. RESULTS: Patients presented with high LDL-C baseline levels (4.97 ± 1.81 mmol/l (192 ± 70 mg/dL) in men and 5.46 ± 2.04 mmol/l (211 ± 79 mg/dL) in women). Intolerance towards statins was reported more frequently by women (48.2%) than by men (38.9%, p = 0.004). LDL-C continuously decreased with individual treatment adjustments across follow-up visits. In total, treatment goals (LDL < 1.4 mmol/l (< 55 mg/dl) or < 1.8 mmol/l (< 70 mg/dl)) were accomplished in 75.8% of men and 55.5% of women after the last follow-up visit (p < 0.0001). In men, these data are almost identical in subjects with statin intolerance. In contrast, treatment goals were reached less frequently in women with statin intolerance compared to women tolerant to statin therapy. CONCLUSION: Even if treated in a specialized lipid clinic, women are less likely to reach their target LDL-C than men, particularly when statin intolerant. Nevertheless, many patients with statin intolerance can be successfully treated using oral combination and PCSK9 inhibitor therapy. However, ongoing follow-up care to monitor progress and to adjust treatment plans is necessary to reach this goal.

We investigated patients at high cardiovascular risk who were referred to our specialized lipid outpatient clinic because of elevated lipid levels and difficulties in lipid-lowering treatment in the primary care setting. The primary goal of such a clinic is to help patients to achieve optimal lipid levels through personalized treatment plans. We focused on prescription behavior and differences in treatment tolerability and effectiveness between men and women.A large proportion of patients (more frequently women (48.2%) than men (38.9%)) reported intolerance towards statins and most patients' LDL-cholesterol levels were far away from treatment goals. However, when treated at a specialized lipid clinic providing ongoing follow-up care to monitor progress and to adjust treatment plans if necessary, many of those patients were able to tolerate lipid lowering medication to achieve better lipid control and to maintain their lipid levels within target ranges.However, women were less likely to reach LDL-cholesterol treatment targets compared to men, especially if they reported intolerance towards statins. Ongoing follow-up care to monitor progress and to adjust treatment plans is necessary to reach treatment goals.

Associations between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and hyperuricemia: a cross-sectional study.

BACKGROUND AND OBJECTIVE: The value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) assessment in the context of metabolic abnormalities is growing in importance. Nevertheless, the relationship between NHHR and hyperuricemia (HUA) is unknown. This study seeks to investigate the relationship between NHHR and HUA. METHODS: The data derived from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) included 7,876 adult participants. The multivariable logistic regression model, subgroup analysis and smooth fitting curve were utilized in order to investigate the association between NHHR and HUA. RESULTS: In the fully adjusted model 3, NHHR was significantly associated with HUA. Specifically, participants in the highest quartile of NHHR had 1.95 times higher odds of HUA prevalence compared to those in the lowest quartile [2.95 (2.39, 3.64), P < 0.0001]. Although the overall trend suggested a positive association, further analysis using smooth fitting curves and threshold effect analysis indicated that this association was nonlinear, with an inflection point at 5.8. The positive association persisted across different HUA definitions and after removing outliers. Subgroup analysis showed significant interactions between NHHR and HUA in different races and diabetes statuses. The odds of HUA prevalence were higher among non-diabetic participants [1.40 (1.32, 1.49), P < 0.0001] compared to diabetic participants [1.18 (1.06, 1.32), P = 0.0031]. Mexican Americans had the lowest odds of HUA prevalence [1.09 (0.92, 1.27), P = 0.2413] compared to other races. CONCLUSIONS: There is a significant positive association between NHHR and HUA, indicating that NHHR may serve as a potential risk assessment maker for HUA, although further prospective studies are needed for validation.

Role of gut microbiota and metabolomics in the lipid-lowering efficacy of statins among Chinese patients with coronary heart disease and hypercholesterolemia.

Background: Statins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy. Methods: A quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the "Up to standard" (US) group and the "Below standard" (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites. Results: A total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-ß-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism. Conclusions: The findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.

Genetically predicted small dense low-density lipoprotein cholesterol and ischemic stroke subtype: multivariable Mendelian randomization study.

Purpose: Small dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design. Methods: We identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis. Results: In univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117-1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106-1.597, P = 0.002). Conclusions: Findings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C.

Discover QTLs for the level of blood components in Shaoxing duck using GWAS and haplotype sharing analysis.

Blood composition is indicative of health-related traits such as immunity and metabolism. The use of molecular genetics to investigate alterations in these attributes in laying ducks is a novel approach. Our objective was to employ genome - wide association studies (GWAS) and haplotype - sharing analysis to identify genomic regions and potential genes associated with 11 blood components in Shaoxing ducks. Our findings revealed 35 SNPs and 1 SNP associated with low-density lipoprotein cholesterol (LDL) and globulin (GLB), respectively. We identified 36 putative candidate genes for the LDL trait in close proximity to major QTLs and key loci. Based on their biochemical and physiological properties, TRA2A, NPY, ARHGEF26, DHX36, and AADAC are the strongest putative candidate genes. Through linkage disequilibrium analysis and haplotype sharing analysis, we identified three haplotypes and one haplotype, respectively, that were significantly linked with LDL and GLB. These haplotypes could be selected as potential candidate haplotypes for molecular breeding of Shaoxing ducks. Additionally, we utilized a bootstrap test to verify the reliability of GWAS with small experimental samples. The test can be accessed at https://github.com/xuwenwu24/Bootstrap-test.

The Effect of Curcumin on Reducing Atherogenic Risks in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial.

Curcumin, derived from turmeric root, exhibits notable anti-inflammatory effects. These anti-inflammatory properties might also provide advantages in reducing cardiovascular complications, such as atherosclerosis. This study aimed to evaluate the efficacy of curcumin in reducing the risk of atherogenesis in obese patients with type 2 diabetes. The study employed a randomized, double-blind, placebo-controlled trial design with 227 participants diagnosed with type 2 diabetes. The parameters used to assess atherogenic risk reduction included pulse wave velocity and metabolic profiles, including low-density lipoprotein cholesterol and small dense low-density lipoprotein cholesterol. Measurements were recorded at baseline and at 3-, 6-, 9-, and 12-month intervals. After 12 months, participants receiving curcumin exhibited a significant reduction in pulse wave velocity (p < 0.001). This group showed significantly reduced levels of cardiometabolic risk biomarkers, including low-density lipoprotein cholesterol and small dense low-density lipoprotein cholesterol, all with p values less than 0.001. High-sensitivity C-reactive protein, interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha were also significantly lower in the curcumin group, with p values less than 0.001. The curcumin intervention significantly reduced pulse wave velocity and improved cardiometabolic risk profiles. These findings suggest that curcumin treatment may effectively reduce atherogenic risks in type 2 diabetes patients with obesity.

Influence of Varied Dietary Cholesterol Levels on Lipid Metabolism in Hamsters.

Syrian hamsters are valuable models for studying lipid metabolism due to their sensitivity to dietary cholesterol, yet the precise impact of varying cholesterol levels has not been comprehensively assessed. This study examined the impact of varying dietary cholesterol levels on lipid metabolism in Syrian hamsters. Diets ranging from 0% to 1% cholesterol were administered to assess lipid profiles and oxidative stress markers. Key findings indicate specific cholesterol thresholds for inducing distinct lipid profiles: below 0.13% for normal lipids, 0.97% for elevated LDL-C, 0.43% for increased VLDL-C, and above 0.85% for heightened hepatic lipid accumulation. A cholesterol supplementation of 0.43% induced hypercholesterolemia without adverse liver effects or abnormal lipoprotein expression. Furthermore, cholesterol supplementation significantly increased liver weight, plasma total cholesterol, LDL-C, and VLDL-C levels while reducing the HDL-C/LDL-C ratio. Fecal cholesterol excretion increased, with stable bile acid levels. High cholesterol diets correlated with elevated plasma ALT activities, reduced hepatic lipid peroxidation, and altered leptin and CETP levels. These findings underscore Syrian hamsters as robust models for hyperlipidemia research, offering insights into experimental methodologies. The identified cholesterol thresholds facilitate precise lipid profile manipulation, enhancing the hamster's utility in lipid metabolism studies and potentially informing clinical approaches to managing lipid disorders.

Association between atherogenic dyslipidemia and muscle quality defined by myosteatosis.

Background: Myosteatosis, ectopic fat accumulation in skeletal muscle, is a crucial component of sarcopenia, linked to various cardiometabolic diseases. This study aimed to analyze the association between dyslipidemia and myosteatosis using abdominal computed tomography (CT) in a large population. Methods: This study included 11,823 patients not taking lipid-lowering medications with abdominal CT taken between 2012 and 2013. Total abdominal muscle area (TAMA), measured at the L3 level, was segmented into skeletal muscle area (SMA) and intramuscular adipose tissue. SMA was further classified into normal attenuation muscle area (NAMA: good quality muscle) and low attenuation muscle area (poor quality muscle). NAMA divided by TAMA (NAMA/TAMA) represents good quality muscle. Atherosclerotic dyslipidemia was defined as high-density lipoprotein cholesterol (HDL-C) less than 40 mg/dL in men and 50 mg/dL in women, low-density lipoprotein cholesterol (LDL-C) greater than 160 mg/dL, triglycerides (TG) greater than 150 mg/dL, small dense LDL-C (sdLDL-C) greater than 50.0 mg/dL, or apolipoprotein B/A1 (apoB/A1) greater than 0.08. Results: The adjusted odds ratios (ORs) of dyslipidemia according to the HDL-C and sdLDL definitions were greater in both sexes in the lower quartiles (Q1~3) of NAMA/TAMA compared with Q4. As per other definitions, the ORs were significantly increased in only women for LDL-C and only men for TG and ApoB/A1. In men, all lipid parameters were significantly associated with NAMA/TAMA, while TG and ApoB/A1 did not show significant association in women. Conclusion: Myosteatosis measured in abdominal CT was significantly associated with a higher risk of dyslipidemia. Myosteatosis may be an important risk factor for dyslipidemia and ensuing cardiometabolic diseases.

Safety and Effectiveness of High-Intensity Statins Versus Low/Moderate-Intensity Statins Plus Ezetimibe in Patients With Atherosclerotic Cardiovascular Disease for Reaching LDL-C Goals: A Systematic Review and Meta-Analysis.

BACKGROUND: It remains controversial whether adding ezetimibe to low/moderate-intensity statins has a more beneficial impact on the treatment efficacy and safety of patients with existing atherosclerotic cardiovascular disease (ASCVD) compared to high-intensity statin regimens. HYPOTHESIS: A combination of low/moderate-intensity statins plus ezetimibe might be more effective and safer than high-intensity statin monotherapy. METHODS: We searched databases for randomized controlled trials comparing lipid profile alterations, drug-related adverse events, and MACE components between high-intensity statin monotherapy and low/moderate-intensity statin plus ezetimibe combination therapy. Pooled risk ratios (RR), mean differences (MD), and 95% confidence intervals (95% CI) were estimated using a random-effects model. RESULTS: Our comprehensive search resulted in 32 studies comprising 6162 patients treated with monotherapy against 5880 patients on combination therapy. Combination therapy was more effective in reducing low-density lipoprotein cholesterol (LDL-C) levels compared to monotherapy (MD = -6.6, 95% CI: -10.6 to -2.5); however, no significant differences were observed in other lipid parameters. Furthermore, the combination therapy group experienced a lower risk of myalgia (RR = 0.27, 95% CI: 0.13-0.57) and discontinuation due to adverse events (RR = 0.61, 95% CI: 0.51-0.74). The occurrence of MACE was similar between the two treatment groups. CONCLUSIONS: Adding ezetimibe to low/moderate-intensity statins resulted in a greater reduction in LDL-C levels, a lower rate of myalgia, and less drug discontinuation compared to high-intensity statin monotherapy in patients with existing cardiovascular disease. However, according to our meta-analysis, the observed reduction in LDL-C levels in the combination group did not correlate with a reduction in MACE compared to the high-intensity statin group.

Spurious dyslipidemia due to paraprotein in a patient with Waldenström macroglobulinemia.

INTRODUCTION: Serum lipid profiles play a crucial role in diagnosing and evaluating cardiovascular diseases. However, the presence of paraprotein can lead to inaccurate dyslipidemia results on automated analyzers. CASE REPORT: A 65-year-old woman whose combined concentrations of HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) consistently surpassed her total serum cholesterol levels over a period of three months presented with unusual lipid component detection. Further analysis revealed the presence of a monoclonal paraprotein, identified as an IgMλ band, with a concentration of 28.0 g/L. The patient was subsequently diagnosed with Waldenström macroglobulinemia. The use of abnormal reaction kinetic curves and the ß quantification method, along with an alternative method that did not suffer from interference, revealed that the monoclonal paraprotein interfered with the measurements of HDL-C, LDL-C, apolipoprotein A-I (apoA-I), and apolipoprotein B (apoB) when using the Roche detection system. This interference led to spurious elevated HDL-C concentrations and falsely decreased apoA-I and apoB concentrations, while the LDL-C results were minimally affected. Although diluting the sample normalized the HDL-C and LDL-C measurements, the interference with the apoA-I and apoB assays persisted. No other common biochemical tests were interfered with this paraprotein. CONCLUSION: Caution is advised when using a homogenous method for direct measurement of HDL-C and LDL-C in patients with monoclonal paraprotein. Techniques to recognize and eliminate this interference are available. However, immunoturbidimetric detection of apoA-I and apoB levels is also susceptible to this interference, which is not readily removable.

The Causal Effect of Serum Lipid Levels Mediated by Neuregulin 4 on the Risk of Four Atherosclerosis Subtypes: Evidence from Mendelian Randomization Analysis.

Background: Neuregulin 4 (NRG4) was known to be associated with serum lipid levels and atherosclerosis. However, it is unknown whether the role of NRG4 in lipid homeostasis is causal to atherosclerosis and whether the effect is beneficial across different atherosclerosis subtypes. Methods: We investigated the causal role of the levels of serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides regulated by NRG4 in subtypes of atherosclerosis through two sample Mendelian randomization. Aggregated genome-wide association study (GWAS) summary data for serum lipid level of 1.32 million individuals with European ancestry were obtained from the Global Lipids Genetics Consortium. GWAS summary data for four atherosclerosis subtypes (peripheral, coronary, cerebral and the other atherosclerosis) were obtained from FinnGen Consortium. Generalized inverse-variance-weighted Mendelian randomization and several sensitivity analyses were used to obtain the causal estimates. Results: A 1-SD genetically elevated LDL-C level mediated by NRG4 was validated to be nominally associated with the risk of peripheral atherosclerosis (log (odds ratio)= 4.14, 95% confidence interval 0.11 to 8.17, P = 0.04), and the other associations were not significant or could not be validated by sensitivity analyses. Conclusion: LDL-C lowering mediated by NRG4 is likely to prevent peripheral atherosclerosis.

What Guidelines Say About Risk Reduction: Major Data on the Link Between Lipid Lowering and Outcomes.

Atherosclerotic cardiovascular disease (ASCVD) is a significant health challenge, and apolipoprotein B (ApoB)-containing lipoproteins are increasingly recognized as central to its progression. Initially labelled as the "low-density lipoprotein hypothesis," our understanding of the etiology of ASCVD has evolved into the "ApoB principle," which highlights the causal and consistent role of all ApoB lipoproteins in ASCVD development. We review the large body of data from genetic studies, to epidemiologic studies, to clinical trials that support this foundational principle. We also provide an overview of the recommendations from guideline committees across the globe on dyslipidemia management and compare these with recent Canadian guidelines. With a few key differences, recent guidelines worldwide provide largely concordant recommendations for diagnosing and managing dyslipidemia with general consensus regarding the need for optimal control of low-density lipoprotein cholesterol and ApoB-containing lipoproteins to prevent cardiovascular events and improve patient care.

Traditional and Novel Markers: Target of Treatment vs Marker of Risk.

In this article we discuss lipid-related markers associated with cardiovascular (CV) risk, and emphasize the significance of low-density lipoprotein (LDL) cholesterol (LDL-C), non-high-density lipoprotein cholesterol, and apolipoprotein B100. LDL-C, a traditional CV risk factor, correlates directly with atherosclerotic CV disease. However, LDL-C alone, usually estimated using the Friedewald equation, might not capture the entire risk profile. Therefore, triglycerides (TGs) and lipoprotein(a) [Lp(a)] should be measured as part of a complete CV risk assessment. Although TGs represent potential markers of increased CV risk, their role as direct causal agents remains inconclusive. Elevated TG levels suggest a greater cholesterol presence in non-LDL particles, necessitating the use of non-high-density lipoprotein cholesterol or apolipoprotein B100, rather than solely LDL-C, to ensure an accurate CV risk assessment. Lp(a), however, is a genetically determined particle resembling LDL, linked with various significant CV diseases. Its role in CV risk is potentially because of its added inflammatory and prothrombotic properties. Certain medications (most notably proprotein convertase subtilisin/kexin type 9 inhibitors and novel small interfering RNA molecules) can reduce Lp(a) levels. Whether this confers a benefit in preventing CV outcomes requires validation from ongoing trials. Although LDL-C remains a crucial metric, health care professionals must acknowledge its limitations and understand the emerging significance of TGs and Lp(a) in CV risk assessment. This article underscores the need to reevaluate traditional lipid markers in light of emerging evidence on TGs and Lp(a) to promote a more comprehensive approach to CV risk assessment.