OBJECTIVE: 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.

UNASSIGNED: In this study, we investigated whether the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is associated with the development of acute ST-segment elevation myocardial infarction (STEMI).
UNASSIGNED: 889 STEMI patients who had not previously received lipid-lowering therapy were selected as the test group and 120 patients with less than 50% coronary stenosis were selected as the control group. All patients completed the related blood tests the morning after admission, and Gensini scores were based on coronary angiography results. The differences were compared using a t-test, rank sum test, chi-square test and logistic regression analysis. Linear regression analysis was used to study the correlation between variables. Receiver Operating Characteristic (ROC) curves were used to validate the predictive value of NHHR for STEMI.
UNASSIGNED: NHHR was shown to be a significant independent risk factor for STEMI according to binary logistic regression analysis (OR = 0.163, 95% CI: 0.065-0.411, p < 0.05). There were shown to be differences in the NHHR depending on the gender of the STEMI patients (z = -1.663, p < 0.1). Linear regression analysis revealed a stronger correlation between NHHR and Gensini score (r = 0.394, p < 0.05) in the test group. Finally, we demonstrated that NHHR has a good predictive effect on STEMI, using an ROC curve (Area Under Curve (AUC): 0.818, 95% CI: 0.777-0.859, p < 0.05).
UNASSIGNED: NHHR is a good predictor of coronary artery disease severity in STEMI patients and an important independent risk factor for STEMI, especially for patients who have not received lipid-lowering treatment in the past, and male STEMI patients need more stringent lipids management than female STEMI patients.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD.

BACKGROUND: The association of low-density lipoprotein cholesterol (LDL-C) and lymphocyte counts with the development of deep vein thrombosis (DVT) has been demonstrated in many fields but remains lacking in open wedge high tibial osteotomy (OWHTO). This study aimed to assess the predictive value of LDL-C to lymphocyte count ratio (LLR) in screening for postoperative new-onset DVT.
METHODS: Clinical data were retrospectively collected from patients who underwent OWHTO between June 2018 and May 2023. The limited restricted cubic spline (RCS) was conducted to evaluate the nonlinear relationship between LLR and the risk of postoperative new-onset DVT. The receiver operating characteristic (ROC) curves were plotted and the predictive value of biomarkers was assessed. After adjusting for intergroup confounders by propensity score matching, the univariate logistic regression was applied to assess the association between LLR and DVT.
RESULTS: 1293 eligible patients were included. RCS analysis showed a linear positive correlation between LLR and the risk of DVT (P for overall = 0.008). We identified LLR had an area under the curve of 0.607, accuracy of 74.3%, sensitivity of 38.5%, and specificity of 80.7%, and LLR > 1.75 was independently associated with a 1.45-fold risk of DVT (95% CI: 1.01-2.08, P = 0.045). Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, diabetes mellitus, hypertension, Kellgren-Lawrence grade, the American Society of Anesthesiologists (ASA) score, and intraoperative osteotomy correction size.
CONCLUSIONS: LLR is a valuable biomarker for predicting postoperative new-onset DVT in patients with OWHTO, and routine screening is expected to yield positive benefits.

Emerging evidence suggests that personalized dietary supplement regimens can significantly influence lipid metabolism and cardiovascular risk. The efficacy of AI-guided dietary supplement prescriptions, compared with standard physician-guided prescriptions, remains underexplored. In a randomized, parallel-group pilot study, 70 patients aged 40-75 years with LDL-C levels between 70 and 190 mg/dL were enrolled. Participants were randomized to receive either AI-guided dietary supplement prescriptions or standard physician-guided prescriptions for 90 days. The primary endpoint was the percent change in LDL-C levels. Secondary endpoints included changes in total cholesterol, HDL-C, triglycerides, and hsCRP. Supplement adherence and side effects were monitored. Sixty-seven participants completed the study. The AI-guided group experienced a 25.3% reduction in LDL-C levels (95% CI: -28.7% to -21.9%), significantly greater than the 15.2% reduction in the physician-guided group (95% CI: -18.5% to -11.9%; p < 0.01). Total cholesterol decreased by 15.4% (95% CI: -19.1% to -11.7%) in the AI-guided group compared with 8.1% (95% CI: -11.5% to -4.7%) in the physician-guided group (p < 0.05). Triglycerides were reduced by 22.1% (95% CI: -27.2% to -17.0%) in the AI-guided group versus 12.3% (95% CI: -16.7% to -7.9%) in the physician-guided group (p < 0.01). HDL-C and hsCRP changes were not significantly different between groups. The AI-guided group received a broader variety of supplements, including plant sterols, omega-3 fatty acids, red yeast rice, coenzyme Q10, niacin, and fiber supplements. Side effects were minimal and comparable between groups. AI-guided dietary supplement prescriptions significantly reduce LDL-C and triglycerides more effectively than standard physician-guided prescriptions, highlighting the potential for AI-driven personalization in managing hypercholesterolemia.

UNASSIGNED: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease triggered by a novel bunyavirus (SFTSV). Characterized by fever, thrombocytopenia, leukocytopenia, and multiple organ dysfunction manifestations, its primary mode of transmission is through tick bites. Despite the critical role of lipid metabolism in viral infections, the role of lipids in SFTS remains unclear.
UNASSIGNED: This retrospective study analyzed 602 patients with SFTS treated at the Shandong Public Health Clinical Center from January 2021 to December 2023. Based on the endpoint events, patients were classified into survival (S) and death (D) groups. The S group was further classified into non-critical (non-C) and critical (C) groups based on symptoms. All patients were followed up for at least 28 days after admission. Propensity score matching, multivariable logistic regression, survival analysis, time trend analysis, and mediation analysis were conducted to assess the association between LDL-C levels and prognosis in SFTS.
UNASSIGNED: The serum LDL-C levels on admission were significantly lower in the D and C groups than in the S and non-C groups. The logistic regression models indicated a potential association between LDL-C levels and a poor prognosis in SFTS. The restricted cubic spline showed a unidirectional trend between LDL-C levels and mortality, with a cutoff value of 1.59 mmol/L. The survival analysis revealed higher and earlier mortality in the low-LDL-C group than in the high-LDL-C group. The trends over 28 days post-admission showed that the serum LDL-C levels gradually increased in SFTS, with a favorable prognosis. Finally, the mediation analysis indicated that low LDL-C levels are associated with mortality through poor hepatic, cardiac, and coagulation functions.
UNASSIGNED: Low LDL-C levels are potentially associated with a poor prognosis in SFTS.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 μM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.

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Hypercholesterolemia is an independent risk factor for cardiovascular disease and lowering circulating levels of low-density lipoprotein cholesterol (LDL-C) can prevent and reduce cardiovascular events. MicroRNA-181d (miR-181d) can reduce the levels of triglycerides and cholesterol esters in cells. However, it is not known whether miR-181d-5p can lower levels of circulating LDL-C. Here, we generated two animal models of hypercholesterolemia to analyze the potential relationship between miR-181d-5p and LDL-C. In hypercholesterolemia model mice, adeno-associated virus (AAV)-mediated liver-directed overexpression of miR-181d-5p decreased the serum levels of cholesterol and LDL-C and the levels of cholesterol and triglyceride in the liver compared with control mice. Target Scan 8.0 indicated Proprotein convertase subtilisin/kexin type 9 (PCSK9) to be a possible target gene of miR-181d-5p, which was confirmed by in vitro experiments. miR-181d-5p could directly interact with both the PCSK9 3\'-UTR and promoter to inhibit PCSK9 translation and transcription. Furthermore, Dil-LDL uptake assays in PCSK9 knockdown Huh7 cells demonstrated that miR-181d-5p promotion of LDL-C absorption was dependent on PCSK9. Collectively, our findings show that miR-181d-5p targets the PCSK9 3\'-UTR to inhibit PCSK9 expression and to reduce serum LDL-C. miR-181d-5p is therefore a new therapeutic target for the development of anti-hypercholesterolemia drugs.

暂无摘要。