Evidence map›Paper›PMID 40064167›Full record

ArticleInternational journal of epidemiology2025

Factorial Mendelian randomization of lipoprotein (a) lowering, low-density lipoprotein cholesterol lowering, and lifestyle improvements: joint associations with cardiovascular risk.

Lijuan Wang, Fangyuan Jiang, Jing Sun, Jianhui Zhao, Yazhou He, Dipender Gill, Stephen Burgess, Susanna C Larsson, Shuai Yuan, Xue Li

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Lijuan WangThe Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.ORCID 0000-0002-9797-0753
Fangyuan JiangThe Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
Jing SunThe Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.ORCID 0000-0003-0046-6663
Jianhui ZhaoThe Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
Yazhou HeDepartment of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Dipender GillDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.ORCID 0000-0001-7312-7078
Stephen BurgessMRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-5365-8760
Susanna C LarssonUnit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0003-0118-0341
Shuai YuanUnit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0001-5055-5627
Xue LiThe Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.

Funding

American Heart Association Postdoctoral FellowshipNational Nature Science Foundation of China 82204019Wellcome Trust 225790
6 · The paper itself

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.

Indexed as

Cardiovascular DiseasesCholesterol, LDLLife StyleLipoprotein(a)AdultAgedBody Mass IndexFemaleHeart Disease Risk FactorsHumansMaleMendelian Randomization AnalysisMiddle AgedPolymorphism, Single NucleotideUnited KingdomCholesterol, LDLLipoprotein(a)cardiovascular diseasecardiovascular mortalityfactorial Mendelian randomizationlifestyle factorlipoprotein(a)

Identifiers

PMID40064167
PMCPMC11893152

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.