Lipoproteins and Cardiovascular Health

Polygenic prediction of treatment response for precision medicine is vulnerable to collider bias

This paper shows that polygenic risk scores for CAD can create false treatment response patterns due to collider bias, not actual biological effects.

Combined statin probiotic treatment mitigates atherogenic dyslipidemia fueling NAFLD in high-cholesterol-diet fed rats

This study shows that combining statin and probiotic treatments improves lipid profiles and reduces inflammation in rats with high cholesterol diets.

Association of polygenic risk scores with low-density lipoprotein cholesterol levels and control: findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

This study evaluates polygenic risk scores (PRS) for LDL cholesterol in a diverse Hispanic/Latino population, finding that some PRS improve prediction across subgroups but statin effectiveness varies with genetic ancestry.

Proteomic and Kinetic Analyses Reveal Discordant Apolipoprotein Turnover and Support a Revised Model of Human Lipoprotein(a) Metabolism

The paper uses proteomic and kinetic analyses to show that APO(a) and APOB in Lp(a) particles have different turnover rates, suggesting a revised model of Lp(a) metabolism.

Designing to Implement Genomics Informed ASCVD Risk Assessment: Patient and Clinician Perspectives about Identifying and Managing the Underlying Causes of Severe Hypercholesterolemia

The paper explores patient and clinician perspectives on identifying and managing the underlying causes of severe hypercholesterolemia through genomic insights.

Proteomic Insights into Lp(a) Cardiovascular Mechanisms: A Mendelian Randomization Study

This study uses mendelian randomization to identify proteins downstream of Lp(a) and finds they are associated with inflammation and coagulation pathways related to cardiovascular disease.

Gene-drug interactions identify genomic loci that enhance statin effectiveness in lowering LDL cholesterol.

The paper identifies gene-statin interactions that enhance statin effectiveness in lowering LDL cholesterol using genome-wide analyses in the UK Biobank and All of Us.

Phenotypic and genetic sex differences in LDL-C and statin treatment in All of Us

This study examines sex and race differences in LDL-C levels and statin treatment using All of Us data, finding higher LDL-C in women and lower statin use and efficacy in women, especially Black women.

HDL-Triglyceride Index: A Kinetically-Derived Biomarker for Time-Integrated Triglyceride Exposure and Cardiometabolic Risk

The paper develops and validates HDL-Triglyceride Index (HDLTg) as a biomarker for time-integrated triglyceride exposure, showing improved predictive performance for cardiometabolic risk compared to traditional single-point measurements.

Targeted Enzymatic Fragmentation of Lipoprotein(a) via Kringle IV Domains: A Novel Therapeutic Approach for Cardiovascular Disease.

This paper proposes an antibody-drug conjugate targeting KIV domains of Lp(a) to enhance its clearance via enzymatic fragmentation, showing potential for improved therapeutic outcomes in cardiovascular disease.

Functional analysis of LDLR variants reveals that the novel p.(Ser610Tyr) variant in the YMDD motif drastically impacts LDL uptake

The paper functionally analyzes LDLR variants in hypercholesterolemia patients, reclassifying five variants as pathogenic and identifying the novel p.(Ser610Tyr) variant as significantly impacting LDL uptake.

KILDA: identifying KIV-2 repeats from kmers

KILDA identifies KIV-2 repeats and Lp(a)-affecting variants from kmers, achieving results comparable to DRAGEN-LPA on the 1000 Genomes Project.

APOE genotype and the effect of statins: a systematic review and meta-analysis.

This meta-analysis quantifies how APOE genotype affects statin response, showing greater reductions in LDL-C and similar effects on TC and TG in ε2 carriers, and smaller effects in ε4 carriers.

APOE Genotype and Statin Response: Evidence from Electronic Health Records in the UK Biobank and All of Us Research Program

This study examines the relationship between APOE genotype and statin response using electronic health records from UK Biobank and All of Us, finding significant associations with lipid levels and mortality risk.

APOE Genotype and Statin Response: Evidence from the UK Biobank Baseline Assessment and Linked Mortality Data

This study examines how APOE genotype interacts with statin use to affect lipid biomarkers and mortality using UK Biobank data, finding significant genotype-specific responses and increased mortality risk for APOE ε4ε4 carriers.

A novel method for predicting Lp(a) levels from routine outpatient genomic testing identifies those at risk of cardiovascular disease across a diverse cohort

This paper develops a method to predict Lp(a) levels from genomic data, combining SNV risk scores and KIV-2 repeat counts, and shows it improves risk prediction for cardiovascular disease in diverse populations.

Unraveling the Potential of Hypericin: A Novel Approach to Targeting PCSK9 Mutations in Cholesterol Management

This study evaluates the binding of natural compounds to PCSK9 mutants using molecular docking and in silico analysis, identifying Hypericin as a promising candidate for cholesterol management.

A plasma proteomic signature for atherosclerotic cardiovascular disease risk prediction in the UK Biobank cohort

This paper develops a plasma proteomic signature for predicting atherosclerotic cardiovascular disease risk using UK Biobank data and finds it modestly improves prediction over clinical and genetic factors.

Systemic inflammation is a minor contributor to remnant cholesterol atherogenicity

This study examines the relationship between remnant cholesterol, systemic inflammation, and cardiovascular risk in a cohort, finding that remnant cholesterol is more strongly associated with MACE than LDL-C, with some mediation by inflammation.

Weighted burden analysis of rare coding variants in 470,000 exome-sequenced UK Biobank subject characterises effects on hyperlipidaemia risk

The paper extends a previous study by analyzing 270,000 additional UK Biobank exomes, confirming six genes' association with hyperlipidaemia risk and identifying protective and risk-increasing variant effects.

LPA and APOE are associated with statin selection in the UK Biobank

This study identifies genetic variants in APOE and LPA associated with statin selection and higher intensity statin doses in the UK Biobank.

Use of polygenic risk scores and other molecular markers to enhance cardiovascular risk prediction: Prospective cohort study and modelling analysis

This study evaluates how adding polygenic risk scores and clinical biochemistry markers to conventional CVD risk models improves prediction accuracy and informs statin therapy decisions in a UK primary care setting.

A prostaglandin F2 alpha analog protects from statin-induced myopathic changes in primary human muscle cells

This study shows statins alter gene and protein expression in human muscle cells, with a prostaglandin F2 alpha analog potentially mitigating these effects.

Long-Term Exposure to Elevated Lipoprotein(a) Levels, Parental Lifespan and Risk of Mortality

This study investigates the association between elevated Lp(a) levels, parental lifespan, and long-term mortality risk using genetic and observational data.

Genetic inhibition of PCSK9, atherogenic lipoprotein concentrations, and calcific aortic valve stenosis

This study shows genetic inhibition of PCSK9 lowers lipoprotein levels and reduces risk of CAD and CAVS, with PCSK9 present in calcified aortic valves and induced by oxidative stress.

Molecular Screening of Familial Hypercholesterolemia in the Icelandic Population

The paper develops an NGS panel to identify pathogenic LDLR mutations in Icelandic FH families and population-based samples with high cholesterol.

CETP inhibition and ADCY9 genotype: evidence of a qualitative pharmacogenetic interaction in cardiovascular disease?

This paper meta-analyzes two RCTs to assess if ADCY9 genotype modifies CETP inhibitor response on cardiovascular risk, finding heterogeneity and a trend across genotypes.

Exploring repositioning opportunities and side-effects of statins: a Mendelian randomization study of HMG-CoA reductase inhibition with 55 complex traits

This study uses Mendelian randomization to investigate statin repositioning opportunities and side-effects across 55 traits, finding associations between LDL-C reduction and various outcomes.

Moving Beyond Clinical Risk Scores with a Mobile App for the Genomic Risk of Coronary Artery Disease

The paper introduces a mobile app, MyGeneRank, that provides individuals with their genomic risk of coronary artery disease to inform lifestyle and medication decisions.