Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk.
Open accessAbstract
OBJECTIVE: Whereas epidemiological studies show that levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) predict incident cardiovascular disease (CVD), there is limited evidence relating lipoprotein subfractions and composite measures of subfractions to risk for CVD in prospective cohort studies. METHODS AND RESULTS: We tested whether combinations of lipoprotein subfractions independently predict CVD in a prospective cohort of 4594 initially healthy men and women (the Malmö Diet and Cancer Study, mean follow-up 12.2 years, 377 incident cardiovascular events). Plasma lipoproteins and lipoprotein subfractions were measured at baseline with a novel high-resolution ion mobility technique. Principal component analysis (PCA) of subfraction concentrations identified 3 major independent (ie, zero correlation) components of CVD risk, one representing LDL-associated risk, a second representing HDL-associated protection, and the third representing a pattern of decreased large HDL, increased small/medium LDL, and increased triglycerides. The last corresponds to the previously described "atherogenic lipoprotein phenotype." Several genes that may underlie this phenotype-CETP, LIPC, GALNT2, MLXIPL, APOA1/A5, LPL-are suggested by SNPs associated with the combination of small/medium LDL and large HDL. CONCLUSIONS: PCA on lipoprotein subfractions yielded three independent components of CVD risk. Genetic analyses suggest these components represent independent mechanistic pathways for development of CVD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several prospective studies suggest that circulating levels of small, dense LDL particles are better predictors of coronary atherosclerosis, carotid atherosclerosis, and response to therapy than are levels of large, buoyant LDL particles.
“Several prospective studies suggest that circulating levels of small, dense LDL particles are better predictors of coronary atherosclerosis, carotid atherosclerosis, and response to therapy than are levels of large, buoyant LDL particles (28,(31)(32)(33).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [33]
The Discussion (page unavailable) reports that small and medium LDL particle levels were associated with cardiovascular disease, whereas large LDL particle levels were not significantly related; it also says this pattern agrees with prospective cohorts including a study of carotid atherosclerosis. It does not establish that small, dense LDL levels predict response to therapy better than large LDL levels. Instead, the Discussion proposes evaluating lipoprotein measures in treatment studies as future work. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 42 · Cited by 168
Research works printed but not linked: 1
- [10]Caulfield MP Li S Lee G Blanche PJ Salameh WA Benner WH Reitz RE Krauss RM Concerns regarding lipoprotein particle measurement by ion mobility analysis. In reply Clin Chem 2008 54 2088 2089 18515257
- Authors
- Musunuru, K., Orho-Melander, M., Caulfield, M. P., Li, S., Salameh, W. A., Reitz, R. E., Berglund, G., Hedblad, B., Engström, G., Williams, P. T., Kathiresan, S., Melander, O., & Krauss, R. M.
- Affiliations
- Broad Institute (US)
- From the Center for Human Genetic Research and Cardiovascular Research Center, Cardiology Division (K.M., S.K.), Massachusetts General Hospital, Boston, and Broad Institute of MIT and Harvard (K.M., S.K.), Cambridge, Mass; University Hospital Malmö (M.O.-M., G.B., B.H., G.E., O.M.), Lund University, Malmö, Sweden; Quest Diagnostics Nichols Institute (M.P.C., S.L., W.A.S., R.E.R.), San Juan Capistrano, Calif; Life Sciences Division (P.T.W.), Ernest Orlando Lawrence Berkeley National Laboratory,...
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2009-11
- Volume
- 29
- Issue
- 11
- Pages
- 1975-1980
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC2772123
- OpenAlex
- W2101573428
- Cited by
- 168
- References
- 42
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 8 · 2023: 11 · 2022: 12 · 2021: 6 · 2020: 14 · 2019: 9 · 2018: 13 · 2017: 11 · 2016: 8 · 2015: 14 · 2014: 10 · 2013: 12 · 2012: 9
- FWCI
- 11.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U01HL069757)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- lipoprotein subfractions, cardiovascular risk, ion mobility spectrometry, atherogenic lipoprotein phenotype, LDL cholesterol, HDL cholesterol, triglycerides, principal component analysis, cholesteryl ester transfer protein, hepatic lipase, GALNT2, MLXIPL, lipoprotein lipase, genetic susceptibility, Malmö Diet and Cancer Study
- MeSH terms
- Adult, Aged, Cardiovascular Diseases, Chromatography, High Pressure Liquid, Chromatography, Ion Exchange, Female, Humans, Cholesterol, HDL, Cholesterol, LDL, Lipoproteins, VLDL, Male, Middle Aged, Predictive Value of Tests, Probability, Prognosis, Prospective Studies, Cohort Studies, Biomarkers, Multivariate Analysis, Logistic Models, Ion Transport, Risk Assessment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
