ArticleInternational journal of epidemiology2025
Factorial Mendelian randomization of lipoprotein (a) lowering, low-density lipoprotein cholesterol lowering, and lifestyle improvements: joint associations with cardiovascular risk.
Article in International journal of epidemiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Genetic evidence supports the combined targeting of lipoprotein(a) and LDL cholesterol to reduce coronary artery disease risk.Nature cardiovascular research · 2026Article
- Estimating the indirect economic burden of elevated lipoprotein(a): A 5-year simulation of cardiovascular events and associated patient and caregiver costs.American journal of preventive cardiology · 2026Article
- The Lipoprotein(a) Implementation Gap: Bridging Evidence and Clinical Practice.Reviews in cardiovascular medicine · 2026Review
- Lipoprotein(a) and High-Risk Coronary Plaques: Mechanisms, Characteristics, and Emerging Therapeutic Strategies.Reviews in cardiovascular medicine · 2025Review
- Impact of smoking and alcohol consumption on telomere length: A univariable and multivariable Mendelian randomization study.Medicine · 2025Article
- Age-Dependent Clinical Relevance of Lipoprotein(a): A Comprehensive Review from Childhood to Adulthood.Journal of clinical medicine · 2025Review
- Burden and trends of cardiovascular diseases attributable to high LDL-C in China, 1990-2021: an age-period-cohort analysis with projectioans to 2050.Frontiers in cardiovascular medicine · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundHigh levels of lipoprotein(a) [Lp(a)] have been associated with an increased risk of cardiovascular disease (CVD); however, the effects of Lp(a)-lowering therapy in combination with low-density lipoprotein cholesterol (LDL-C)-lowering treatment or lifestyle improvements on CVD risk remain unexplored.
methodsWe conducted a factorial Mendelian randomization study among 385 917 participants in the UK Biobank. Separate genetic scores were constructed to proxy the effects of Lp(a) lowering, LDL-C lowering through different targets [HMG-CoA reductase, NPC1-like intracellular cholesterol transporter 1, proprotein convertase subtilisin/kexin Type 9, and low-density lipoprotein receptor (LDLR)], as well as improvements in body mass index (BMI), systolic blood pressure (SBP), and lifestyle factors (cigarette smoking, alcohol consumption, and physical activity).
resultsGenetically predicted lower Lp(a) levels were associated with a decreased risk of CVD and CVD-specific mortality. Per 50-mg/dl, the hazard ratio ranged from 0.73 [95% confidence interval (CI): 0.73, 0.73] for peripheral artery disease (PAD) to 0.95 (95% CI: 0.92, 0.99) for venous thromboembolism. In factorial analyses exploring combined exposure to low-level Lp(a) and low-level LDL-C, there was no consistent evidence for departure from an additive model for any outcome (Pinteraction > .05), with the exception of the analysis using the LDLR score and PAD (Pinteraction = .006). In factorial analyses exploring combination therapies integrating Lp(a) lowering with interventions on BMI, SBP, and lifestyle factors, there was no evidence for departure from an additive model in any analysis (Pinteraction > .05).
conclusionsOur study suggests that Lp(a) lowering will have a similar magnitude for reducing cardiovascular events whether it is considered alone, or in conjunction with LDL-C reduction or lifestyle improvements.
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