Concordance between LDL-C estimated by various formulas and directly measured LDL-C.

BACKGROUND: Although direct measurement of LDL cholesterol (LDL-C) in blood is possible, there are several formulas for its estimation. The performance and concordance of these formulas have not been evaluated in Colombia. OBJECTIVE: To determine the concordance between LDL-C directly measured using the enzymatic technique and existing methods to calculate it. METHODS: Study of diagnostic tests, and concordance. We analyzed complete lipid profile samples, which included direct measurement of LDL-C, from 2014 to 2022 at Hospital Universitario San Ignacio (Bogotá, Colombia). The direct LDL-C measurements were compared with estimations using the DeLong, Sampson, Friedewald, extended Martin/Hopkins, Anandaraja, and Cordova methods. Lin's concordance correlation coefficient (CCC) and Bland-Altman plots were employed, conducting subgroup analyses based on triglycerides (TG), and LDL-C levels. Kappa coefficients assessed agreement in LDL-C risk categories according to dyslipidemia guidelines. RESULTS: A total of 2144 samples were evaluated. The formulas with the best CCC were DeLong (0.971) and Sampson (0.969), with no relevant differences. The extended Martin/Hopkins formula (0.964) and the Friedewald formula (0.964) also performed well. The Anandaraja (0.921) and Cordova (0.881) equations exhibited inferior performance. For all formulas, a decrease in concordance was observed when triglycerides were ≥400 mg/dL or when LDL-C was <100 mg/dL. Most formulas demonstrated optimal agreement when assessed using risk categories according to dyslipidemia guidelines, except for Anandaraja and Cordova. CONCLUSIONS: The DeLong, Sampson, extended Martin/Hopkins, and Friedewald formulas show the best concordance with directly measured LDL-C, so in most cases the results can be considered interchangeable. However, the Anandaraja and Cordova formulas are not recommended.

Possible Heterozygous Hypercholesterolemia Among Adults in Basrah, Southern Iraq.

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease and is one of the most prevalent genetic disorders. We aimed to determine the prevalence of patients with elevated levels of low-density lipoprotein cholesterol (LDL-C), presumptively indicating possible heterozygous familial hypercholesterolemia (HeFH). Methods Retrospective data analysis was conducted for adult patients aged 18 and above with fasting LDL-C ≥ 190 mg/dL registered in Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) in Basrah for the period from August 2008 to December 2023. The total number of enrolled individuals was 59,026. Results From the data records of the 59,026 individuals enrolled in the study, it was found that 4,093 (6.9 %) had LDL-C levels ≥190 mg/dL and 361 (0.6 %) had very high total cholesterol according to the Make Early Diagnosis to Prevent Early Death (MEDPED) Criteria. Around 30,527 (51.7 %) were aged 40-59 years, representing the peak age group. Women comprised 34,688 (58.8 %), and 42,310 (71.7 %) had diabetes mellitus. Individuals with obesity comprise 27,375 (48.8 %). Out of the 4,093 patients with LDL-C ≥190 mg/dL, 2,422 (59.2 %) were in the 40-59 years age group, and 2,847 (69.6 %) were women. Diabetes was found in 3,442 (84.1 %) patients and obesity in 1,954 (49.9 %) patients. The average blood pressure was higher in the individuals with LDL-C ≥190 (137/83 versus 134/82 respectively, p < 0.001). Conclusions Being one of the largest studies of its kind in the country, the percentage of individuals who might meet the criteria for having possible HeFH in Basrah (Southern Iraq) should raise awareness about the size of the problem in the country, both to encourage family screening programs and to broaden the need for lipid-lowering therapies. Future studies are needed to have further clarifications about the differences in the prevalence between sexes and age groups. These findings need further confirmation by genetic studies including LDL-receptor mutations.

Impact of body mass index on repeat coronary revascularization rates in patients with LDL-C below 55 mg/dL and LDL-C below 70 mg/dL: a 42-month cohort study in Korea.

Background: Previous studies revealed a linear relationship between body mass index (BMI) and repeat coronary revascularization rate in patients who underwent percutaneous coronary intervention (PCI). However, this relationship has not been demonstrated in Korean patients who meet old and new target low-density lipoprotein cholesterol (LDL-C) levels of Korean dyslipidemia guidelines. Therefore, we conducted this study to find out the effect of BMI on repeat coronary revascularization rate in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL. Methods: This cohort study was followed for 42 months in Daegu Catholic Medical Center, Korea. We included 429 patients with LDL-C <70 mg/dL 1 year after PCI. We compared repeat revascularization rates using Kaplan-Meier survival curves between the normal weight group (18.5 kg/m2 ≤ BMI < 23 kg/m2) and the pre-obesity and obesity group (23 kg/m2 ≤ BMI) in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL. Results: During a follow-up period, there was no significant difference in repeat coronary revascularization-free survival between a group with LDL-C <55 mg/dL and a group with LDL-C <70 mg/dL (79.6% vs. 76.2%, P=0.32). In normal weight patients, LDL-C <55 mg/dL group showed higher repeat coronary revascularization-free survival than LDL-C <70 mg/dL group (89.3% vs. 77.1%, P=0.05). There was no significant difference in repeat revascularization-free survival between the normal weight group and the pre-obesity and obesity group in patients with LDL-C <70 mg/dL (77.1% vs. 75.7%, P=0.67). However, the normal weight group showed significantly higher repeat revascularization-free survival compared to the pre-obesity and obesity group in patients with LDL-C <55 mg/dL (89.3% vs. 74.3%, P=0.03). Normal body weight and LDL-C <55 mg/dL [hazard ratio (HR): 0.421, 95% confidence interval (CI): 0.193-0.916, P=0.02] was the only independent predictor for repeat revascularization. Conclusions: In Korean PCI patients with normal body weight whose LDL-C level is less than 70 mg/dL, but more than 55 mg/dL, should be treated with more intensive therapy to lower LDL-C to less than 55 mg/dL. For obese patients who have succeeded in reducing LDL-C below 55 mg/dL, it seems that weight loss should be attempted to a normal body weight level.

Low-Density Lipoprotein Cholesterol, Type 2 Diabetes and Progression of Aortic Stenosis: The RED-CARPET Heart Valve Subgroup Cohort Study.

Background: Low-density lipoprotein cholesterol (LDL-C) and type 2 diabetes (T2DM) are both independent risk factors for aortic stenosis (AS). In AS patients, whether LDL-C or T2DM is associated with fast AS progression (FASP) and their interaction is unknown. This study aims to test the hypothesis that there is a heightened risk of FASP when elevated LDL-C coexists with T2DM. Methods: The Real-world Data of Cardiometabolic Protections (RED-CARPET) study enrolled participants with mild (peak aortic velocity = 2-3 m/s), moderate (3-4 m/s) and severe ( ≥ 4 m/s) AS between January 2015 and December 2020 at a single center. Participants were further stratified by baseline LDL-C joint T2DM, follow-up echocardiography was performed after 6 months, and the primary outcome was FASP, defined as the annual change in aortic peak velocity ( ≥ 0.3 m/s/year). Results: Among the 170 participants included, 45.3% had mild AS, 41.2% had moderate AS, and 13.5% had severe AS. The mean age was 66.84 ± 12.64 years, and 64.1% were women. During the follow-up period of 2.60 ± 1.43 years, 35 (20.6%) cases of FASP were identified. Using non-T2DM with LDL-C < 2.15 mmol/L as reference, FASP risk was 1.30 [odds ratio (OR), 95% CI (0.99-7.78, p = 0.167)] for non-T2DM with LDL-C 2.15-3.14 mmol/L, 1.60 [OR, 95% CI (1.17-3.29, p = 0.040)] for non-T2DM with LDL-C ≥ 3.14 mmol/L, 2.21 [OR, 95% CI (0.49-4.32, p = 0.527)] for T2DM with LDL-C < 2.15 mmol/L, 2.67 [OR, 95% CI (1.65-7.10, p = 0.004)] for T2DM with LDL-C 2.15-3.14 mmol/L, and 3.20 [OR, 95% CI (1.07-5.34, p = 0.022)] for T2DM with LDL-C ≥ 3.14 mmol/L. Conclusions: LDL-C joint T2DM was associated with FASP. This investigation suggests that fast progression of AS may develop if LDL-C is poorly managed in T2DM. Additional research is needed to validate this finding and explore the possible biological mechanism to improve the cardiometabolic management of T2DM and seek possible prevention for AS progression for this population. Clinical Trial Registration: ChiCTR2000039901 (https://www.chictr.org.cn).

Lifelong prevention of atherosclerotic cardiovascular disease (ASCVD) through LDL-C control - Means and cost/benefit of sustained very low lifetime LDL-C targets.

Central illustration. Coloured bars in the left panel show the impact of age and ethnicity on an individual's lifetime ASCVD risk mediated by cumulative exposure to LDL-C. Even younger individuals with a greater cumulative exposure to LDL-C, despite their age, may have a higher overall risk compared to older individuals with a lower cumulative exposure to LDL-C.Image, graphical abstract.

Rapid achievement of low-density lipoprotein cholesterol goals within 1 month after acute coronary syndrome during combination therapy with rosuvastatin, ezetimibe and bempedoic acid: Initial experience from the LAI-REACT study.

Rapid reduction of low-density lipoprotein cholesterol (LDL-C) to target levels immediately following acute coronary syndrome (ACS) event is critical to prevent future events. High-dose statins alone often fail to achieve LDL-C goals. Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) combined with high-dose statins improves LDL-C goal attainment, but is unaffordable for many patients in India and worldwide. In a real-world open-label study, we demonstrated in a cohort of 122 patients with ACS, concurrent triple therapy with rosuvastatin 40 mg/d, ezetimibe 10 mg/d, and bempedoic acid 180 mg/d (REB) started at the time of hospital admission was associated with 57.7%, 61.7%, 61.9% and 60.6% reductions in LDL-C from 115.6 mg/dL at baseline to 48.9 mg/dL at week 1, 44.3 mg/dL at week 2, 44.1 mg/dL at week 4, and 45.6 mg/dL at week 6, respectively (each p < 0.001 compared to baseline; p < 0.001 across repeated measures). REB provided significant reductions in LDL-C within as early as one week and enabled 76.3% and 92.2% of patients to achieve the Lipid Association of India and American College of Cardiology recommended LDL-C targets of <50 mg/dl and <70 mg/dl within 2-weeks, respectively, which were sustained at 4-6 weeks. REB was generally well tolerated. Our study demonstrates the capacity to rapidly achieve LDL-C goals after ACS with triple REB therapy, an affordable regimen in India.

Assessment of the impact of low-density lipoprotein cholesterol on retinal vessels using optical coherence tomography angiography.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is acknowledged as an independent risk factor (IRF) for atherosclerotic cardiovascular disease. Nevertheless, studies on the impact of LDL-C on microvasculature are still scarce. The retina, abundant in microvasculature, can now be examined for microvascular alterations through the novel, non-invasive, and quantitative optical coherence tomography angiography (OCTA) technique. METHODS: In this cross-sectional study, 243 patients from the geriatric department were recruited (between December 2022 and December 2023). Individuals were classified into four groups based on their LDL-C levels: Group 1 (≤ 1.8 mmol/L), Group 2 (> 1.8 mmol/L to ≤ 2.6 mmol/L), Group 3 (> 2.6 mmol/L to ≤ 3.4 mmol/L), and Group 4 (> 3.4 mmol/L). The OCTA results including retinal vessel density (VD), foveal avascular zone (FAZ) area, macula thickness, and retinal nerve fiber layer (RNFL) thickness were contrasted across these groups. T-tests, analysis of variance, Welch's tests, or rank-sum tests were employed for statistical comparisons. In cases where significant differences between groups were found, post-hoc multiple comparisons or rank-sum tests were performed for pairwise group comparisons. Spearman's correlation coefficient was employed to perform bivariate correlation analysis to evaluate the relationship between LDL-C levels and various OCTA measurements. Multivariable regression analysis was used to evaluate the association between LDL-C levels and various OCTA measurements. Linear regression analysis or mixed-effects linear models were applied. RESULTS: It was discovered that individuals with LDL-C levels exceeding 2.6 mmol/L (Groups 3 and 4) exhibited reduced VD in the retina, encompassing both the optic disc and macular regions, compared to those with LDL-C levels at or below 2.6 mmol/L (Groups 1 and 2). A negative correlation among LDL-C levels and retinal VD was identified, with r values spanning from - 0.228 to -0.385. Further regression analysis presented ß values between - 0.954 and - 2.378. Additionally, no notable disparities were detected among the groups regarding FAZ area, macular thickness, and RNFL thickness. CONCLUSIONS: The outcomes of this study suggest that elevated LDL-C levels constitute an IRF for decreased VD across the entire retina. TRIAL REGISTRATION: NCT05644548, December 1, 2022.

Estimating the effect of inclisiran on hypercholesterolemia and primary prevention of cardiovascular disease: the NHANES 1999-2018 study.

BACKGROUND: Hypercholesterolemia has been identified as an independent predictor of cardiovascular disease (CVD). Inclisiran, an innovative small interfering RNA agent, is anticipated to result in a notable reduction of approximately 50% in low-density lipoprotein cholesterol (LDL-C) levels. Given its transformative impact, this study scrutinized the eligibility of the US population for inclisiran treatment and evaluated its potential effects on hypercholesterolemia and the primary prevention of CVD. METHODS: This study applied the eligibility criteria from the ORION 10 and 11 trials to the 1999-2018 National Health and Nutrition Examination Survey (NHANES) dataset to estimate the size of the eligible population for atherosclerotic cardiovascular disease (ASCVD) and ASCVD-risk equivalents. Utilizing the reduction in LDL-C levels from ORION 10, this study predicted the impact of inclisiran on LDL-C levels among ASCVD patients. Similarly, leveraging the changes in lipid levels from ORION 11, this study predicted inclisiran's effect on the 10-year change in CVD risk and preventable CVD events in the ASCVD-risk equivalents population, employing the Framingham CVD Risk Score. RESULTS: The study identified 579 ASCVD patients (5 million) and 382 ASCVD-risk equivalents (2.66 million) who met the eligibility criteria from ORION 10 and 11. Among the ASCVD population, 3.5 million (70.2%) would achieve a ≥ 50% reduction in LDL-C levels after treatment. Furthermore, 4.6 million (91.3%) would achieve LDL-C levels < 70 mg/dL, and 3.8 million (75%) would achieve LDL-C levels < 55 mg/dL after treatment. For the ASCVD-risk equivalents population, the estimated 10-year CVD risk would decrease from 25.3 to 17.7%, an absolute reduction of 7.6% and a relative reduction of 30% following inclisiran treatment, potentially preventing 202,353 CVD events over a decade, including 138,084 coronary heart disease cases, 37,351 strokes, and 23,894 congestive heart failure cases. CONCLUSIONS: Inclisiran has the potential to substantially reduce the prevalence of hypercholesterolemia and prevent nearly 200,000 CVD events in eligible US adults.

Quantifying the 'distance to LDC-goal' in patients at very high cardiovascular risk with hyperlipidaemia in Germany: a retrospective claims database analysis.

BACKGROUND AND OBJECTIVES: This study quantified the 'distance to LDL-C goal' in patients at very high cardiovascular risk with uncontrolled hyperlipidaemia. 'Distance to LDL-C goal' was defined as the percentage by which low-density lipoprotein cholesterol (LDL-C) levels needed to be reduced to achieve the LDL-C goals specified in the 2016 or 2019 European Society of Cardiology/European Atherosclerosis Society guidelines. DESIGN AND METHODS: This retrospective analysis using data from the IQVIA Disease Analyzer database included patients who were predominantly treated by a primary care physician, diabetologist or cardiologist between 2014 and 2018, with a diagnosis of hyperlipidaemia and an initial LDL-C measurement (index event) and one or more cardiovascular risk factors. The primary outcome was to assess the proportion of patients with uncontrolled hyperlipidaemia and to classify the 'distance to LDL-C goal' in these patients. RESULTS: Data from 32,963 patients were analysed (n = 27,159, n = 3873 and n = 1931 patients in the primary care physician, diabetology and cardiology cohorts, respectively). Most patients had uncontrolled LDL-C levels (⩾70 mg/dL; ⩾1.8 mmol/L) at index (91.0%, 86.4% and 94.0% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). Analysis of the 'distance to LDL-C goal' indicated that approximately one-third of patients in each cohort required an LDL-C level reduction of up to 50% relative to index to achieve their LDL-C goal (35.8%, 43.7% and 28.4% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). LDL-C control was not achieved at 36 months post-index in most patients with uncontrolled LDL-C levels (86.8%, 81.7% and 90.2% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). CONCLUSION: LDL-C levels were uncontrolled in most patients with hyperlipidaemia. Analysis of the 'distance to LDL-C goal' showed that most patients required a substantial LDL-C level reduction to achieve their LDL-C goal.

Examining a decade-long trend in exposure to per- and polyfluoroalkyl substances and their correlation with lipid profiles: Insights from a prospective cohort study on the young Taiwanese population.

Per- and polyfluoroalkyl substances (PFAS) are artificial chemicals extensively utilized in everyday products, and numerous cross-sectional epidemiological studies consistently link PFAS exposure with lipid profiles across diverse populations and age groups. In longitudinal studies, the findings also indicate a positive correlation between PFAS and lipid profiles; however, this association remains unexplored in adolescents and young adults. Notably, previous research has predominantly focused on conventional lipid biomarkers, with limited exploration of the relationship between PFAS and diverse lipoprotein subfractions. Furthermore, there is a lack of comprehensive investigation into the temporal trends in PFAS concentrations in Taiwan. To address this research gap, we conducted a prospective study following 592 adolescents and young adults (12-30 years old at enrollment) from the YOung TAiwanese Cohort (YOTA) over a duration of 10 years. During the follow-up period, we measured 11 types of PFAS and various lipid profile biomarkers (low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), low-density lipoprotein triglyceride (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, lipoprotein(a), triglyceride). Our results revealed a general decline in PFAS concentrations in the study population. Regarding the correlation between the average levels (averaged across the initial and second tracking periods) of PFAS and lipid profiles (during the second tracking period), we observed positive correlations with total cholesterol and LDL-C for perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), N-methylperfluorooctane sulfonamide acetic acid (N-MeFOSAA), and the sum of PFAS (sum of the 11 kinds of PFAS). Additionally, average levels of PFUdA, N-MeFOSAA, and the sum of PFAS exhibited positive associations with sdLDL-C. This study unveiled an overall decrease in PFAS concentrations and underscores a potential link between PFAS exposure and adverse changes in lipid profiles among young populations, emphasizing the need for further exploration into the mechanisms of PFAS on lipid metabolism and atherosclerosis.

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.

Clinical Impact of Lipoprotein (a) and Cumulative Low-Density Lipoprotein Cholesterol Exposure on Coronary Artery Disease in Patients with Heterozygous Familial Hypercholesterolemia.

AIMS: Elevated lipoprotein (a) (Lp[a]), predominantly determined by genetic variability, causes atherosclerotic cardiovascular disease (ASCVD), particularly in patients with familial hypercholesterolemia (FH). We aimed to elucidate the clinical impact of Lp(a) and cumulative exposure to low-density lipoprotein cholesterol (LDL-C) on CAD in patients with FH. METHODS: One hundred forty-seven patients clinically diagnosed with heterozygous familial hypercholesterolemia (HeFH) were retrospectively investigated. Patients were divided into 2 groups according to the presence of CAD. Their clinical characteristics and lipid profiles were evaluated. RESULTS: There were no significant differences in untreated LDL-C levels between the 2 groups (p=0.4), whereas the cumulative exposure to LDL-C and Lp(a) concentration were significantly higher in patients with CAD (11956 vs. 8824 mg-year/dL, p＜0.01; 40 vs. 14 mg/dL, p＜0.001, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated that the cutoff values of Lp(a) and cumulative LDL-C exposure to predict CAD in patients with FH were 28 mg/dL (AUC 0.71) and 10600 mg-year/dL (AUC 0.77), respectively. A multivariate analysis revealed that cumulative LDL-C exposure ≥ 10600 mg-year/dL (p＜0.0001) and Lp(a) level ≥ 28 mg/dL (p＜0.001) were independent predictors of CAD. Notably, the risk of CAD remarkably increased to 85.7% with smoking, Lp(a) ≥ 28 mg/dL, and cumulative LDL-C exposure ≥ 10600 mg-year/dL (odds ratio: 46.5, 95%CI: 5.3-411.4, p＜0.001). CONCLUSIONS: This study demonstrated an additive effect of Lp(a) and cumulative LDL-C exposure on CAD in patients with HeFH. Interaction with traditional risk factors, particularly smoking and cumulative LDL-C exposure, enormously enhances the cardiovascular risk in this population.

Genetically predicted lipoprotein(a) associates with coronary artery plaque severity independent of low-density lipoprotein cholesterol.

AIMS: Elevated Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease, but the mechanisms of risk are debated. Studies have found inconsistent associations between Lp(a) and measurements of atherosclerosis. We aimed to assess the relationship between Lp(a), low-density lipoprotein cholesterol (LDL-C) and coronary artery plaque severity. METHODS: The study population consisted of participants of the Million Veteran Program who have undergone an invasive angiogram. The primary exposure was genetically predicted Lp(a), estimated by a polygenic score. Genetically predicted LDL-C was also assessed for comparison. The primary outcome was coronary artery plaque severity, categorized as normal, non-obstructive disease, 1-vessel disease, 2-vessel disease, and 3-vessel or left main disease. RESULTS: Among 18,927 adults of genetically inferred European ancestry and 4,039 adults of genetically inferred African ancestry, we observed consistent associations between genetically predicted Lp(a) and obstructive coronary plaque, with effect sizes trending upward for increasingly severe categories of disease. Associations were independent of risk factors, clinically measured LDL-C and genetically predicted LDL-C. However, we did not find strong or consistent evidence for an association between genetically predicted Lp(a) and risk for non-obstructive plaque. CONCLUSIONS: Genetically predicted Lp(a) is positively associated with coronary plaque severity independent of LDL-C, consistent with Lp(a) promoting atherogenesis. However, the effects of Lp(a) may be greater for progression of plaque to obstructive disease than for the initial development of non-obstructive plaque. A limitation of this study is that Lp(a) was estimated using genetic markers and could not be directly assayed, nor could apo(a) isoform size.

This study assessed the association between genetic propensity towards higher lipoprotein(a) [Lp(a)] in the blood and the severity of coronary artery plaque seen on clinical angiograms, independent of other factors, including low-density lipoprotein cholesterol (LDL-C). The study was conducted in a large U.S. population using data from the Million Veteran Program. Genetically predicted high Lp(a) was associated with obstructive coronary plaque, but it was not associated with non-obstructive coronary plaque. This association was independent of LDL-C, and the association was greater for more severe forms of disease.The mechanisms of association between Lp(a) and cardiovascular events are debated. Prior studies have shown that Lp(a) does not associate with early markers of atherosclerosis. Our analyses support the idea that Lp(a) plays less of a role in early plaque initiation but plays a significant role in the progression of plaque towards more severe disease, independent of LDL-C.

The clinical relevance of the reversal of coronary atherosclerotic plaque.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death globally despite advances in preventive therapies. Understanding of the initiation and progression of atherosclerosis, the interplay between lipoproteins, endothelial dysfunction, inflammation, and immune responses is critical to treating this disease. The development of vulnerable coronary plaques prone to thrombosis, can lead to acute coronary syndromes, for these reasons, the potential plaque stabilization and regression through pharmacological interventions, particularly lipid-lowering agents like statins and PCSK9 inhibitors is crucial. The imaging techniques such as intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT) play a key role in assessing plaque composition and guiding interventional therapeutic strategies. Clinical evidence supports the efficacy of intensive lipid-lowering therapy in inducing plaque regression, with studies demonstrating reductions in plaque volume and improvements in plaque morphology assessed by IVUS, OCT and NIRS. While pharmacological interventions show promise in promoting plaque regression and stabilization, their impact on long-term cardiovascular events requires further investigation. Multimodality imaging and comprehensive outcome trials are proposed as essential tools for elucidating the relationship between plaque modification and clinical benefit in coronary atherosclerosis. The stabilization or regression of atherosclerotic plaque might serve as the phenomenon linking the reduction in LDL-C levels to the decrease in cardiovascular events. Overall, this review emphasizes the ongoing efforts to advance our understanding of ASCVD pathophysiology and optimize therapeutic approaches for improving patient outcomes.

Causal effects of omega-6 and LDL-C on androgenetic alopecia: A Mendelian randomization study.

BACKGROUND: Increasing studies have reported a causal relationship between androgenetic alopecia (AGA) and lipid-related metabolites. However, the relationships between HDL-C, LDL-C, Omega-6, and Omega-3 with AGA remain unclear. Some research findings are even contradictory. Therefore, we designed this study to explore this issue. METHODS: In this study, we selected seven exposure factors, screened SNPs with significant associations, removed linkage disequilibrium and weak instrumental variables, and conducted bidirectional MR analysis. RESULTS: The study found that omega-6 and LDL-C, especially total cholesterol in medium LDL and total cholesterol in small LDL, are risk factors for the occurrence of androgenetic alopecia. CONCLUSION: In summary, we found that various lipid-related metabolites have a causal relationship with the occurrence of androgenetic alopecia, providing new insights into the pathogenesis of androgenetic alopecia and offering references for clinical treatment of androgenetic alopecia.

The role of neutrophil and LDL-C levels in predicting intracranial hemorrhage following endovascular thrombectomy in patients with acute ischemic stroke.

OBJECTIVES: To investigate the association between intracranial hemorrhage (ICH) and preoperative levels of neutrophils and low-density lipoprotein-cholesterol (LDL-C) in acute ischemic stroke (AIS) patients following endovascular thrombectomy (EVT), and to assess the predictive value of preoperative levels of neutrophils and LDL-C. METHODS: A retrospective analysis was performed on the clinical records of patients diagnosed with AIS who underwent EVT at Nanchong Central Hospital between 2019 and 2023. Multivariate regression analysis was employed to examine the association of preoperative levels of neutrophils and LDL-C with the occurrence of ICH. Furthermore, a receiver operating characteristic curve was constructed to assess the predictive efficacy of these parameters. RESULTS: A total of 300 patients with a mean age of 68.0 years (standard deviation, 11.1 years) and a median baseline National Institutes of Health Stroke scale (NIHSS) score of 15.5 (interquartile range, 12.0-19.75) were identified in this cohort. Of these, 28 (9.3%) patients experienced ICH. Multivariate regression analysis revealed that elevated preoperative neutrophil (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.10-1.38, P < 0.001) and LDL-C (OR 2.64, 95% CI 1.52-4.58, P < 0.001) levels were independently associated with ICH. The combined indicator demonstrated a higher area under the curve (AUC 0.759, 95% CI 0.654-0.865) compared with preoperative neutrophil (AUC 0.647, 95% CI 0.532-0.763) and LDL-C (AUC 0.711, 95% CI 0.607-0.814) levels individually.The specificity and sensitivity of the combined indicator were 67.9% and 83.1%, respectively. CONCLUSIONS: Preoperative levels of neutrophils and LDL-C may serve as predictive indicators for ICH in patients with AIS who have undergone EVT; moreover, the combination of preoperative neutrophil and LDL-C levels demonstrates enhanced predictive efficacy.

Association Between Calculated Small Dense Low-Density Lipoprotein Cholesterol (sdLDL-C) and Soft Carotid Plaques on CT Angiogram of the Head and Neck.

BACKGROUND: Cerebrovascular accident (CVA), also commonly known as stroke, is an acute condition characterized by jeopardized perfusion of the brain tissue. Atherosclerosis is a common converging point for the various risk factors for CVA. It is a chronic, evolving condition of the vessel wall characterized by peculiar lesions known as atheromas. Low-density lipoprotein cholesterol (LDL-C) has been one of the established and traditional risk factors for the development of plaques in atherosclerosis. Small dense LDL-C (sdLDL-C) is a subclass of LDL-C that is considered more atherogenic, and its role in atherosclerotic plaque formation has been very well established. Hence, in this study, we aimed to find the association between calculated sdLDL-C and atherosclerotic carotid plaque (including various plaque characteristics). MATERIALS AND METHODS: This retrospective cross-sectional study was conducted at Sri Ramachandra Medical College and Research Institute between December 2022 and December 2023 after getting ethics approval from the Institutional Ethics Committee. Patients who underwent CT angiogram (312) were included in the study, and their lipid profile data were collected from the Laboratory Information System. Participants were divided into groups depending on the presence or absence of carotid plaque, the characteristics of the plaque, and the narrowing caused by the plaque. sdLDL-C was calculated using Sampson formula from the lipid parameters in these groups. Statistical analysis was done using SPSS Statistics version 16.0 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.). A p-value of <0.05 was considered significant. RESULTS: sdLDL-C was significantly higher in the plaque group (37.25 ± 13.69 mg/dL) when compared to the group without plaques on CT angiogram (34.09 ± 11.64 mg/dL) (p<0.05), wherein the LDL-C wasn't significantly different between the two groups. sdLDL-C was also elevated in the soft plaque sub-group (39.46 ± 13.63 mg/dL) when compared to the calcific plaque sub-group (35.41 ± 13.05 mg/dL), which was statistically significant (p<0.05). CONCLUSION: sdLDL-C is associated with atherosclerotic carotid plaques, especially the soft plaques on CT angiogram, which are considered to be vulnerable plaques. Thus, calculated sdLDL-C can be utilized as a cost-effective tool to assess plaque vulnerability and monitor hypolipidemic treatment in addition to LDL-C.

Exploring the Relationship between Lipid Profile, Inflammatory State and 25-OH Vitamin D Serum Levels in Hospitalized Patients.

Anomalies in lipid metabolism involve multifactorial pathogenesis, among other factors, being associated with an inflammatory state and disturbances in vitamin D status. The literature has focused on the binary relationships between inflammation and dyslipidemia, vitamin D and dyslipidemia, or vitamin D and inflammation. Our study aimed to explore the link between all these three factors: 25-OH vitamin D serum levels, the presence of inflammation assessed through serum C-reactive protein (CRP), and serum lipid profile in 2747 hospitalized patients. Our results showed a positive correlation of HDL-C with 25 (OH) vitamin D and a negative correlation of HDL-C with CRP. This relationship had different patterns in the statistical network analysis. The network analysis patterns are preserved for males and females, except for the relationship between CRP and vitamin D, which is present in male cases and absent in females. The same triangular relationship between all three-CRP, vitamin D, and HDL-C was found with different strengths of partial correlation in obese and non-obese patients. This pattern was similar in patients with and without fatty liver. A shifted pattern was found in the network analysis of hypertensive patients. The CRP was negatively correlated with vitamin D and HDL-C, and vitamin D was positively correlated with HDL-C in non-hypertensive patients. Castelli's Risk indexes I and II were positively associated with CRP, suggesting that increased cardiovascular risk is proportional to an inflammatory state. The triad formed by altered serum lipid levels, inflammation, and vitamin D represents a complex relationship marked by specific dynamics between lipidic fractions such as HDL-C and C-reactive protein and vitamin D.

Ebronucimab in Chinese patients with hypercholesterolemia---A randomized double-blind placebo-controlled phase 3 trial to evaluate the efficacy and safety of ebronucimab.

Randomized clinical trials (RCTs) of PCSK9 monoclonal antibody(mAb) specifically for Chinese patients have been limited. This multi-center RCT is to clarify the efficacy and safety of a novel mAb, Ebronucimab, in Chinese patients. Patients diagnosed with primary hypercholesterolemia, including Heterozygous Familial Hypercholesterolemia, or mixed dyslipidemia, were categorized by ASCVD risk and randomly assigned at a ratio of 2:1:2:1 to receive Ebronucimab 450 mg or matching placebo every 4 weeks (Q4W), or Ebronucimab 150 mg or matching placebo every 2 weeks (Q2W). The primary outcome was the percentage change of LDL-C from baseline to week 12 for all groups. The least squares mean reduction difference (95 %CI) in LDL-C from baseline to week 12 of Ebronucimab 450 mg Q4W and Ebronucimab 150 mg Q2W groups versus the placebo group was -59.13 (-64.103, -54.153) (Adjusted p<0.0001) and -60.43 (-65.450, -55.416) (Adjusted p<0.0001), respectively. Meanwhile, the Ebronucimab group exhibited notably high rates in reaching LDL-C goals of each cardiovascular risk stratification. In addition, Ebronucimab effectively improved other lipid panel. During the double-blind treatment period, relatively frequently reported adverse events (AEs) were injection site reactions (ISR), urinary tract infection, and hyperuricemia (Incidence rate are 6.9 %, 4.8 % and 3.5 %). Among treatment-associated AEs, only injection site reactions (ISR) occurred more in the dose groups. In conclusion, Ebronucimab, with either 450 mg Q4W or 150 mg Q2W doses, demonstrated significant efficacy in lowering serum LDL-C level with a favorable safety and immunogenicity profile among hypercholesterolemic patients.