Mendelian Randomization review links Lp(a) to inflammatory protein pathways
Photo by Navy Medicine / Unsplash
Key Takeaway
Consider that Lp(a) may influence cardiovascular risk through inflammatory pathways, based on genetic association evidence.
This is a Mendelian Randomization analysis, not a primary clinical trial. The scope was to use genetic instruments for Lp(a) blood concentrations to identify associated proteins and pathways relevant to major adverse cardiovascular events (MACE).
The authors identified a total of 521 proteins associated with Lp(a). Pathway enrichment analysis then highlighted 91 Lp(a) downstream proteins comprising MACE-relevant pathways. These pathways include oxidized phospholipid-related processes, chemotaxis of immune cells, endothelial cell activation, pro-inflammatory monocyte activation, neutrophil activity, coagulation, and lipid metabolism.
The analysis is observational in nature, using genetic proxies to infer associations. The authors note that the results suggest the influence of Lp(a) may be primarily through modifying inflammation rather than lipid-lowering, providing a mechanistic framework. However, the study does not report effect sizes, p-values, confidence intervals, or a specific study population.
Limitations include the inferential nature of Mendelian Randomization and the lack of reported statistical measures for the protein associations. Practice relevance is restrained; the findings offer insight into potential biological mechanisms but do not provide direct evidence for clinical interventions or trial outcomes.
More on Cardiovascular Disease
Reversion of Prediabetes to Normoglycemia Linked to 68% Lower Diabetes Risk
Reversing prediabetes cuts diabetes risk by 68 percent in a massive study
A meta-analysis of 535,066 participants with prediabetes found that reversion to normoglycemia was associated with a 68% lower risk of incid…
Reversing prediabetes to normal blood sugar levels lowers the risk of developing diabetes by 68 percent in people with the condition.
Lipid lowering therapy patterns in patients with ASCVD and familial hypercholesterolemia in Israel
Lipid lowering therapy patterns observed in Israeli patients
This retrospective database study examined lipid lowering therapy patterns among patients with atherosclerotic cardiovascular disease, ASCVD…
A look at how patients with high cholesterol and heart disease manage their lipid lowering therapy and treatment adherence in Israel.
Systematic review of observational data shows wide variation in primary care discontinuation of lipid-lowering and antihypertensive therapies
Millions of heart patients stop or restart key medicines at alarming rates in primary care
This systematic review of observational data analyzed 9,146,252 patients in primary care regarding discontinuation and restarting of lipid-l…
Nearly one million patients in primary care stopped or restarted heart medicines within a year, with rates varying widely by age and backgro…
Retrospective cohort study links ABSI and TyG index to incident cardiovascular disease in Chinese adults
Combining Body Shape And Blood Sugar Predicts Heart Risk Better
This retrospective cohort study evaluated 920 overweight or obese Chinese adults aged 40 to 80 years free of cardiovascular disease at basel…
Overweight adults face higher heart risks than weight alone suggests since new measures combining body shape and blood sugar offer better cl…
View Original Abstract ↓
Background: Elevated lipoprotein(a) [Lp(a)] is a known risk factor for several cardiovascular-related diseases established from multiple genetic and observational studies. However, the underlying mechanisms mediating the effects of Lp(a) levels on cardiovascular disease risk and major adverse cardiovascular events (MACE) are unclear. The aim of this study was to identify proteins downstream of Lp(a) using mendelian randomization (MR) - a genetic causal inference approach. Methods: A two-sample MR was performed by initially identifying Lp(a) genetic instruments based on data from genome wide association studies (GWAS) of Lp(a) blood concentrations. These instruments were then tested for association with proteins from proteomic pQTL data (Olink from UK Biobank, 2940 proteins and SomaScan from deCODE, 4907 proteins). Results: A total of 521 proteins associated with Lp(a) were identified. Using pathway enrichment analysis, the following MACE-relevant pathways were identified comprising a total of 91 Lp(a) downstream proteins: oxidized phospholipid-related, chemotaxis of immune cells and endothelial cell activation, pro-inflammatory monocyte activation, neutrophil activity, coagulation, and lipid metabolism. Conclusion: The results suggest that the influence of Lp(a) treatments is primarily through modifying inflammation rather than lipid-lowering, thus providing insight into the mechanistic framework which mediates the effects of elevated Lp(a) on atherosclerotic cardiovascular disease.
Regional motif diversity score in cfDNA predicts pembrolizumab response in head and neck cancer
Can a DNA pattern predict who will heal from head and neck cancer immunotherapy?
Related in Genetics & Precision Medicine
Protocol outlines feasibility study of genomic newborn screening for 100,000 births in England
Newborn Screening Could Catch Rare Diseases Earlier
This study protocol describes a planned investigation into the feasibility and acceptability of offering genomic newborn screening in routin…
A huge new study will test if DNA screening can safely find rare diseases in newborns before symptoms appear.
Sex differences in genetic correlation between ischaemic heart disease and depression found in 1.14 million European ancestry individuals
Genetic links between heart disease and depression are twice as strong in women
This review analysis of summary statistics from a sex-stratified genome-wide association study involving 1.14 million European ancestry indi…
Genetic links between heart disease and depression are twice as strong in women. This analysis of 1.14 million people shows why sex matters …
Proof of concept study uses preSCRIPT framework to annotate prescriptions in UK Biobank
preSCRIPT framework identifies genetic links to drug response in UK Biobank
This proof of concept study utilized the preSCRIPT framework to filter and annotate raw prescription data from the UK Biobank, which include…
A proof of concept study in the UK Biobank used preSCRIPT to find genetic links to how people respond to common medications like warfarin an…
GWAS and Mendelian randomization link aging, rheumatoid arthritis, and herpes zoster via shared MHC signals
Shared genetic link found for aging, arthritis, and shingles
This genomic analysis integrates genome-wide association studies, multi-omics quantitative trait loci, linkage disequilibrium-aware colocali…
A shared genetic signal may explain why aging, rheumatoid arthritis, and shingles often overlap.
From Other Specialties
Phase 1 study traces ainuovirine metabolism and excretion in healthy men
A single dose of oral ainuovirine clears the body within two days in healthy men
This phase 1 open-label study in 6 healthy men examined the pharmacokinetics and mass balance of a single dose of radiolabelled ainuovirine.…
A single dose of oral ainuovirine clears the body within two days in healthy men, with most of the drug leaving unchanged through urine and …
Nirmatrelvir/Ritonavir in Breast Milk: Low Infant Exposure in Lactating Women
Paxlovid levels low in breast milk, early study finds
This Phase 1 open-label study in 8 healthy lactating women found that nirmatrelvir/ritonavir concentrations in breast milk were consistently…
A small study finds that nirmatrelvir/ritonavir (Paxlovid) passes into breast milk at low levels, suggesting minimal infant exposure.
Islatravir and lenacapavir fixed-dose combination shows similar bioavailability to single agents in healthy volunteers
New HIV pill works with or without food in early safety tests
This open-label phase 1 study enrolled 93 people without HIV to assess the oral relative bioavailability and safety of a fixed-dose combinat…
A new HIV pill containing islatravir and lenacapavir showed similar drug levels whether taken with food or on an empty stomach, supporting f…
Digital chest radiography with CAD shows variable sensitivity for asymptomatic tuberculosis in South African adults
Digital scans miss many silent tuberculosis cases in South Africa adults
This cohort study evaluated digital chest radiography (dCXR) read by blinded human readers and qXR CAD in 1353 adults in South Africa. The s…
New data from South Africa shows digital scans and computer tools miss many silent tuberculosis cases, raising questions about current scree…