Evidence map›Paper›PMID 39492722›Full record

SynthesisCirculation2025

Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol-Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis.

Harpreet S Bhatia, Simon Wandel, Peter Willeit, Anastasia Lesogor, Keith Bailey, Paul M Ridker, Paul Nestel, John Simes, Andrew Tonkin, Gregory G Schwartz and 3 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 3 pooled it
–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

57 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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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

13 authors.

Harpreet S BhatiaDivision of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (H.S.B., S.T.).ORCID 0000-0002-3964-2989
Simon WandelNovartis Pharma AG, Basel, Switzerland (S.W., A.L., K.B.).ORCID 0000-0002-1442-597X
Peter WilleitDepartment of Medical Statistics, Informatics and Health Economics at the Medical University of Innsbruck, Austria (P.W.).ORCID 0000-0002-1866-7159
Anastasia LesogorNovartis Pharma AG, Basel, Switzerland (S.W., A.L., K.B.).
Keith BaileyNovartis Pharma AG, Basel, Switzerland (S.W., A.L., K.B.).
Paul M RidkerBrigham and Women's Hospital, Harvard Medical School, Boston, MA (P.M.R.).ORCID 0000-0003-1249-4522
Paul NestelBaker Heart and Diabetes Institute, Melbourne, Victoria, Australia (P.N.).ORCID 0000-0001-5180-2132
John SimesNHMRC Clinical Trials Centre, University of Sydney, NSW, Australia (J.S.).ORCID 0000-0002-3740-7563
Andrew TonkinSchool of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (A.T.).ORCID 0000-0001-5291-0610
Gregory G SchwartzDivision of Cardiology, Rocky Mountain Regional VA Medical Center and University of Colorado School of Medicine, Aurora (G.G.S.).ORCID 0000-0003-2954-0695
Helen ColhounMRC Human Genetics Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, Edinburgh, UK (H.C.).
Christoph WannerDivision of Nephrology, Department of Internal Medicine and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Germany (C.W.).ORCID 0000-0001-9507-5301
Sotirios TsimikasDivision of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (H.S.B., S.T.).ORCID 0000-0001-9834-9494

Funding

Aspirin for Primary Prevention of Cardiovascular Disease in Patients with Elevated Lipoprotein(a)K08HL166962 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Harpreet Singh Bhatia · 2023 to 2026
$676k
NHLBI NIH HHS K08 HL166962
6 · The paper itself

Abstract

backgroundLow-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) levels are independently associated with atherosclerotic cardiovascular disease (ASCVD). However, the relationship between Lp(a) level, LDL-C level, and ASCVD risk at different thresholds is not well defined.

methodsA participant-level meta-analysis of 27 658 participants enrolled in 6 placebo-controlled statin trials was performed to assess the association of LDL-C and Lp(a) levels with risk of fatal or nonfatal coronary heart disease events, stroke, or any coronary or carotid revascularization (ASCVD). The multivariable-adjusted association between baseline Lp(a) level and ASCVD risk was modeled continuously using generalized additive models, and the association between baseline LDL-C level and ASCVD risk by baseline Lp(a) level by Cox proportional hazards models with random effects. The joint association between Lp(a) level and statin-achieved LDL-C level with ASCVD risk was evaluated using Cox proportional hazards models.

resultsCompared with an Lp(a) level of 5 mg/dL, increasing levels of Lp(a) were log-linearly associated with ASCVD risk in statin- and placebo-treated patients. Among statin-treated individuals, those with Lp(a) level >50 mg/dL (≈125 nmol/L) had increased risk across all quartiles of achieved LDL-C level and absolute change in LDL-C level. Even among those with the lowest quartile of achieved LDL-C level (3.1-77.0 mg/dL), those with Lp(a) level >50 mg/dL had greater ASCVD risk (hazard ratio, 1.38 [95% CI, 1.06-1.79]) than those with Lp(a) level ≤50 mg/dL. The greatest risk was observed with both Lp(a) level >50 mg/dL and LDL-C level in the fourth quartile (hazard ratio, 1.90 [95% CI, 1.46-2.48]).

conclusionsThese findings demonstrate the independent and additive nature of Lp(a) and LDL-C levels for ASCVD risk, and that LDL-C lowering does not fully offset Lp(a)-mediated risk.

Indexed as

Cardiovascular DiseasesCholesterol, LDLLipoprotein(a)AgedFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMiddle AgedRandomized Controlled Trials as TopicRisk FactorsCholesterol, LDLHydroxymethylglutaryl-CoA Reductase InhibitorsLipoprotein(a)cholesterolheart disease risk factorslipoprotein(a)lipoproteins, LDL

Identifiers

PMID39492722
PMCPMC11771346

What Socratic holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.