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Despite current therapies, patients with vascular disease remain at high risk for major adverse cardiovascular events. Low-density lipoprotein cholesterol is a well-established modifiable cardiovascular risk factor. Evolocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 that reduces low-density lipoprotein cholesterol by approximately 60% across various populations. FOURIER is a randomized, placebo-controlled, double-blind, parallel-group, multinational trial testing the hypothesis that adding evolocumab to statin therapy will reduce the incidence of major adverse cardiovascular events in patients with clinically evident vascular disease. The study population consists of 27,564 patients who have had a myocardial infarction (MI), an ischemic stroke, or symptomatic peripheral artery disease and have a low-density lipoprotein ≥70 mg/dL or a non–high-density lipoprotein cholesterol ≥100 mg/dL on an optimized statin regimen. Patients were randomized in a 1:1 ratio to receive either evolocumab (either 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously every month, according to patient preference) or matching placebo injections. The primary end point is major cardiovascular events defined as the composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary end point is the composite of cardiovascular death, MI, or stroke. The trial is planned to continue until at least 1,630 patients experience the secondary end point, thereby providing 90% power to detect a relative reduction of ≥15% in this end point. FOURIER will determine whether the addition of evolocumab to statin therapy reduces cardiovascular morbidity and mortality in patients with vascular disease.

Background Remnant cholesterol (RC) mediates the progression of coronary artery disease, diabetic complications, hypertension, and chronic kidney disease. Limited information is available on the association of RC with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether RC can be used to independently evaluate the risk of NAFLD in the general population and to analyze the predictive value of RC for NAFLD. Methods The study included 14,251 subjects enrolled in a health screening program. NAFLD was diagnosed by ultrasound, and the association of RC with NAFLD was assessed using the receiver operating characteristic (ROC) curve and logistic regression equation. Results Subjects with elevated RC had a significantly higher risk of developing NAFLD after fully adjusting for potential confounding factors (OR 1.77 per SD increase, 95% CI 1.64–1.91, P trend< 0.001). There were significant differences in this association among sex, BMI and age stratification. Compared with men, women were facing a higher risk of RC-related NAFLD. Compared with people with normal BMI, overweight and obesity, the risk of RC-related NAFLD was higher in thin people. In different age stratifications, when RC increased, young people had a higher risk of developing NAFLD than other age groups. Additionally, ROC analysis results showed that among all lipid parameters, the AUC of RC was the largest (women: 0.81; men: 0.74), and the best threshold for predicting NAFLD was 0.54 in women and 0.63 in men. Conclusions The results obtained from this study indicate that (1) in the general population, RC is independently associated with NAFLD but not with other risk factors. (2) Compared with traditional lipid parameters, RC has a better predictive ability for NAFLD in men.

Abstract Background Individuals with obesity have higher concentrations of very low-density lipoprotein (VLDL) cholesterol and increased risk of myocardial infarction. We hypothesized that VLDL cholesterol explains a fraction of the excess myocardial infarction risk in individuals with obesity. Methods We included 29 010 individuals free of myocardial infarction at baseline, nested within 109 751 individuals from the Copenhagen General Population Study. During 10 years of follow-up, 2306 individuals developed myocardial infarction. Cholesterol content in large and small VLDLs, in intermediate-density lipoprotein (IDL), and in LDL was measured directly with nuclear magnetic resonance spectroscopy. Results Median concentrations of cholesterol in large and small VLDLs were 0.12 mmol/L (interquartile range [IQR], 0.07–0.20 mmol/L; 4.5 mg/dL [IQR, 2.6–6.9 mg/dL]) and 0.6 mmol/L (IQR, 0.5–0.8 mmol/L; 25 mg/dL [IQR, 20–30 mg/dL]) in individuals with obesity vs 0.06 mmol/L (IQR, 0.03–0.1 mmol/L; 2.2 mg/dL [IQR, 1.1–3.8 mg/dL]), and 0.5 mmol/L (IQR, 0.4–0.6 mmol/L; 20 mg/dL (IQR, 16–25 mg/dL]) in individuals with normal weight; in contrast, concentrations of IDL and LDL cholesterol were similar across body mass index (BMI) categories. Cholesterol in large and small VLDLs combined explained 40% (95% CI, 27%–53%) of the excess risk of myocardial infarction associated with higher BMI. In contrast, IDL and LDL cholesterol did not explain excess risk of myocardial infarction, whereas systolic blood pressure explained 17% (11%–23%) and diabetes mellitus explained 8.6% (3.2%–14%). Conclusions VLDL cholesterol explains a large fraction of excess myocardial infarction risk in individuals with obesity. These novel findings support a focus on cholesterol in VLDL for prevention of myocardial infarction and atherosclerotic cardiovascular disease in individuals with obesity.

Angiopoietin-like protein (ANGPTL)8 (alternatively called TD26, RIFL, Lipasin, and Betatrophin) is a newly recognized ANGPTL family member that has been implicated in both triglyceride (TG) and glucose metabolism. Hepatic overexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inactivating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8 ⁻/⁻) mice gained weight more slowly than wild-type littermates due to a selective reduction in adipose tissue accretion. Plasma levels of TGs of the Angptl8 ⁻/⁻ mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG levels were associated with both a reduction in very low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity. Despite the increase in LPL activity, the uptake of very low density lipoprotein-TG is markedly reduced in adipose tissue but preserved in hearts of fed Angptl8 ⁻/⁻ mice. Taken together, these data indicate that ANGPTL8 plays a key role in the metabolic transition between fasting and refeeding; it is required to direct fatty acids to adipose tissue for storage in the fed state. Finally, glucose and insulin tolerance testing revealed no alterations in glucose homeostasis in mice fed either a chow or high fat diet. Thus, although absence of ANGPTL8 profoundly disrupts TG metabolism, we found no evidence that it is required for maintenance of glucose homeostasis.

Some studies have reported the association between maternal serum lipid profile abnormalities and pre-eclampsia. However, many studies have reported controversial results. Hence, this systematic review and meta-analysis was planned to generate summarized evidence on the association between maternal serum lipid profiles and pre-eclampsia in African women. Four electronic databases such as; PubMed, Hinari, Google Scholar, and African Journals Online were searched for studies published in English. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument and Newcastle-Ottawa Scale were used for data extraction and quality assessment of the included studies. The meta- regression analysis was performed by Stata 14 software. The standardized mean difference (SMD) values of lipid profiles were computed to assess their association with pre-eclampsia at 95% CI. In this review a total of 15 observational studies were included. The mean values of triglyceride (TG), total cholesterol (TC), low density lipoprotein- cholesterol (LDL-c) and very low density lipoprotein- cholesterol (VLDL-c) were significantly higher in pre-eclamptic women as compared with normotensive pregnant women (TG = 229.61±88.27 and 147.00 ± 40.47, TC = 221.46 ± 45.90 and 189.67 ± 39.18, LDL = 133.92 ± 38.77 and 112.41 ± 36.08, VLDL = 41.44 ± 19.68 and 26.64 ± 7.87), respectively. The serum high density lipoprotein cholesterol (HDL-c) level was lower, but it is not statistically significant (HDL-c = 51.02 ± 16.01 and 61.80 ± 25.63) in pre-eclamptic women as compared with controls. The pooled standardized mean difference (SMD) of TG, TC, LDL-C and VLDL-C were significantly increased in pre-eclamptic women as compared with normotensive pregnant women with the SMD of (TG = 1.65 (1.10, 2.21), TC = 0.84 (0.40, 1.29), LDL-C = 0.95 (0.46, 1.45) and VLDL-C = 1.27 (0.72, 1.81)) at 95% CI, respectively, but the pooled SMD of HDL-cholesterol was decreased in pre-eclamptic women as compared with normotensive pregnant women (SMD = -0.91 (95% CI: -1.43, -0.39). In this review, the maternal serum levels of TG, TC, LDL-c and VLDL-c were significantly associated with the risk of preeclampsia. However, HDL- cholesterol was not significantly associated but it was lower in pre-eclamptic women. Further, large scale prospective studies should verify these outcomes and it is recommended that lipid profiles should be included as a routine diagnostic test for pre-eclamptic women.

Low-density lipoprotein cholesterol (LDL-C), a major modifiable risk factor for cardiovascular diseases, is typically calculated using the Friedewald formula when triglyceride (TG) levels are below 400 mg/dL. Recent studies have demonstrated the superior accuracy of the Martin-Hopkins method across diverse populations. While this method estimates very-low-density lipoprotein cholesterol (VLDL-C) using strata-specific median TG/VLDL-C ratios, its reliance on median statistics raises questions about whether these ratios are truly optimal. This study evaluated the performance of the Martin-Hopkins method compared to the Friedewald formula, focusing on its potential for improvement by applying optimal TG/VLDL-C ratios. Using data from 18,322 individuals in the Korea National Health and Nutrition Examination Survey (KNHANES), we derived strata-specific optimal TG/VLDL-C ratios designed to maximize concordance with directly measured LDL-C values, based on LDL-C categories defined by clinical guidelines. We compared the performance of four LDL-C estimation models: the Friedewald formula (LDL-CF), the original Martin-Hopkins method (LDL-CM-N), and two alternative models that applied TG/VLDL-C ratios derived from our data-one using median values (LDL-CKM-N) and the other using optimal values tailored to each stratum (LDL-CKO-N). The Martin-Hopkins method showed significantly higher concordance than the Friedewald formula for TG levels < 400 mg/dL (79.6% for LDL-CF vs. 83.2% for LDL-CM-180, p < 0.001). Concordance improved by less than 2% for TG levels < 150 mg/dL (83.3% vs. 84.9%), but by approximately 10% for TG levels of 150-399 mg/dL (68.8% vs. 78.0%). The largest discrepancy was observed in classifying LDL-C levels < 70 mg/dL among individuals with TG levels of 150-399 mg/dL (47.5% for LDL-CF vs. 90.3% for LDL-CM-180). However, the overall concordance differed only modestly between the 10-cell and 180-cell Martin-Hopkins equations (82.8% for LDL-CM-10 vs. 83.2% for LDL-CM-180, a difference of 0.4%), indicating only a marginal benefit despite the substantial increase in the number of strata. Using optimal TG/VLDL-C ratios increased overall concordance compared to median ratios within the same stratification, with LDL-CKO-N estimates outperforming their LDL-CKM-N counterparts. However, this improvement was not statistically significant in LDL-C estimates derived from TG-only stratification. Applying optimal TG/VLDL-C ratios within the Martin-Hopkins method improves accuracy compared to median ratios, particularly when stratifications incorporate both TG and non-high-density lipoprotein cholesterol (non-HDL-C) levels. This enhancement can be achieved without increasing the number of strata, offering a practical pathway to refine LDL-C estimation while avoiding excessive stratification. Our findings suggest that while median statistics may be sufficient for TG-only stratifications, they do not fully capture optimal TG/VLDL-C ratios for combined TG and non-HDL-C stratifications.

Background and aims Lipoprotein particle (p) size and count beyond lipoprotein lipid content [triglycerides (tg) and cholesterol (c)] are critical for their atherogenicity. This study characterized lipoprotein profiles in metabolically healthy individuals with overweight or obesity and assessed the impact of sex, obesity, and lipid background. Methods Proton-nuclear magnetic resonance (¹H-NMR) was used to assess the composition of very low-, low-, intermediate-, and high-density lipoproteins (VLDL, LDL, IDL, HDL), and particle number and size of VLDL, LDL, and HDL in 101 healthy subjects with overweight and obesity. Results Men showed significantly higher VLDLc and VLDLtg levels, counts of VLDLp (all subfractions) and LDLp (total and small), and smaller LDLp size, compared to women. Men had lower HDLc and HDLp (total and medium). In Obesity (Ob) compared to overweight (Ov), VLDLp number, VLDLtg and remnant cholesterol (RC) levels were significantly increased [Fold changes (FC) Ob.vs.Ov: 1.45, 1.39, and 1.26, respectively]. When stratified by sex, obesity-related VLDL and IDL profile deterioration was evident only in women. Individuals with LDLc ≥ 130 mg/dL showed increased RC compared to those with LDLc < 130 mg/dL (FC:1.26). The median 10-year cardiovascular disease (CVD) risk REGICOR was low (2%), but higher in men and in obesity. Individuals with higher CVD risk showed increased VLDLc, VLDLtg, VLDLp, and RC levels. Conclusion Men had a higher 10-year CVD risk and a less favorable triglyceride-rich lipoprotein and RC profile, while obesity aggravated these patterns, particularly in women. These findings support considering high-risk lipoprotein patterns in targeted CVD prevention for overweight and obese populations.

Background Sampson et al. developed a novel method to estimate very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) in the setting of hypertriglyceridemia. Familial Combined Hyperlipidemia (FCHL) is a common primary dyslipidemia in which lipoprotein composition interferes with LDL-C estimation. This study aimed to evaluate performance of LDL-C using this new method (LDL-S) compared with LDL-C estimated by Friedewald’s and Martin eq. (LDL-F, LDL-M) in FCHL. Methods Data were collected from 340 subjects with confirmed FCHL. Concordance for VLDL-C measured by ultracentrifugation and LDL-C estimated using these measures compared to Sampson’s, Martin’s and Friedewald’s equations was performed using correlation coefficients, root mean squared error (RMSE) and bias. Also, concordance of misclassified metrics according to LDL-C (< 70 and < 100 mg/dL) and Apo B (< 80 and < 65 mg/dL) thresholds were assessed. Results Sampson’s equation was more accurate (RMSE 11.21 mg/dL; R 2  = 0.88) compared to Martin’s (RMSE 13.15 mg/dL; R 2  = 0.875) and the Friedewald’s equation (RMSE 13.7 mg/dL; R 2  = 0.869). When assessing performance according to LDL-C, Sampson’s had highest correlation and lowest RMSE compared to other equations (RMSE 19.99 mg/dL; R 2  = 0.840). Comparing performance strength across triglyceride levels, Sampson’s showed consistently improved correlations compared to Martin’s and Friedewald’s formulas for increasing triglycerides and for the FCHL phenotype of mixed dyslipidemia. Sampson’s also had improved concordance with treatment goals. Conclusions In FCHL, VLDL-C and LDL-C estimation using Sampson’s formula showed higher concordance with lipid targets assessed using VLDL-C obtained by ultracentrifugation compared with Friedewald’s and Martin’s equations. Implementation of Sampson’s formula could improve treatment monitoring in FCHL.

The ratio of non-high-density lipoprotein cholesterol (NHDL-C) to high-density lipoprotein cholesterol (HDL-C), referred to as NHHR, is an emerging lipid parameter. The relationship between NHHR and the urinary albumin-creatinine ratio (ACR) remains unclear. Therefore, our aim is to explore the potential correlation between NHHR and ACR. Data for this study were sourced from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). Participants under 20 years, pregnant individuals, and those missing NHHR or ACR data were excluded. NHHR, calculated as the difference between total cholesterol (TC) and HDL-C divided by HDL-C, was assessed. Our analysis of the NHHR-ACR association involved multivariable linear regression, smoothed curve fitting, and subgroup analysis. A total of 34,734 participants were included, with a mean age of 49.81 ± 17.66 years. The prevalence of albuminuria was 12.66%. Multivariable regression analysis indicated a significant and independent positive association between NHHR and ACR after fully adjustment [β (95% CI): 7.19 (4.54, 9.85), p < 0.0001], particularly among female participants, individuals aged 60 or older, those of Mexican American or Non-Hispanic Black ethnicity, individuals with obesity, hypertension or diabetes. Our findings demonstrate a positive correlation between NHHR and elevated ACR in US adults, implying that lowering NHHR may serve as a preventive and palliative strategy for albuminuria.

The aim of this trial is to assess the effect of Almega®PL on improving the Omega-3 Index, cardio-metabolic parameters, and other biomarkers in generally healthy individuals. The benefits of long-chain omega-3 fatty acids for cardiovascular health are primarily built upon mixtures of docosahexaenoic (DHA) and eicosapentaenoic acids (EPA). Highly purified EPA therapy has proven to be particularly effective in the treatment of cardiovascular disease, but less is known about the benefits of EPA-only supplementation for the general healthy population. Almega®PL is a polar rich oil (>15%) derived from the microalga Nannochloropsis that contains EPA (>25%) with no DHA. Participants (n = 120) were given a capsule of 1 g/day of either Almega®PL or placebo for 12 weeks. Differences in the Omega-3 Index, cardiometabolic markers, and other general health indicators were measured at the baseline, six, and 12 weeks. Compared to the placebo group, Almega®PL supplementation significantly increased the Omega-3 Index and EPA concentration from 4.96 ± 0.90 and 0.82 ± 0.37% at the baseline to 5.75 ± 0.90 and 1.27 ± 0.36 at week 12, respectively. Very-low-density lipoprotein cholesterol (VLDL) decreased by 25%, which resulted in a significant decrease in total cholesterol compared to the placebo. Interestingly, the decrease in VLDL was not associated with an increase in LDL, which seems to be a benefit associated with EPA-only based formulations. Collectively, these results show that Almega®PL provides a natural EPA-only option to increase EPA and manage cholesterol levels in the general population.