Time Course of LDL Cholesterol Exposure and Cardiovascular Disease Event Risk
Open accessAbstract
Background Incident cardiovascular disease (CVD) increases with increasing low-density lipoprotein cholesterol (LDL-C) concentration and exposure duration. Area under the LDL-C versus age curve is a possible risk parameter. Data-based demonstration of this metric is unavailable and whether the time course of area accumulation modulates risk is unknown. Objectives Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we assessed the relationship of area under LDL-C versus age curve to incident CVD event risk and modulation of risk by time course of area accumulation-whether risk increase for the same area increment is different at different ages. Methods This prospective study included 4,958 asymptomatic adults age 18 to 30 years enrolled from 1985 to 1986. The outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death. Results During a median 16-year follow-up after age 40 years, 275 participants had an incident CVD event. After adjustment for sex, race, and traditional risk factors, both area under LDL-C versus age curve and time course of area accumulation (slope of LDL-C curve) were significantly associated with CVD event risk (hazard ratio: 1.053; p < 0.0001 per 100 mg/dl × years; hazard ratio: 0.797 per mg/dl/year; p = 0.045, respectively). Conclusions Incident CVD event risk depends on cumulative prior exposure to LDL-C and, independently, time course of area accumulation. The same area accumulated at a younger age, compared with older age, resulted in a greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Multiple epidemiological, clinical, and experimental investigations have underscored the critical importance of LDL cholesterol, including its oxidized variant, as primary catalysts in the advancement of atherosclerosis.
“Multiple epidemiological, clinical, and experimental investigations have underscored the critical importance of LDL cholesterol, including its oxidized variant, as primary catalysts in the advancement of atherosclerosis [5].”
From Residual Cardiovascular Risk: Role of Remnants Cholesterol, Monocyte/HDL Ratio and Lipoprotein Ratios on Personalized Cardiovascular Prevention (2024) · cites this paper as [5]
Cites
A New Equation to Estimate Glomerular Filtration Rate
Levey, A. S., Stevens, L. A., Schmid, C. H., Zhang, Y. (., Castro, A. F., Feldman, H. I., Kusek, J. W., Eggers, P., Van Lente, F., Greene, T., et al. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-9-200905050-00006 · Cited by 25,603 · see citing works
A Proportional Hazards Model for the Subdistribution of a Competing Risk
Fine, J. P., & Gray, R. J. (1999) · Journal of the American Statistical Association · doi:10.1080/01621459.1999.10474144 · Cited by 14,290 · see citing works
General Cardiovascular Risk Profile for Use in Primary Care: The Framingham Heart Study
D’Agostino, R. B., Vasan, R. S., Pencina, M. J., Wolf, P. A., Cobain, M., Massaro, J. M., & Kannel, W. B. (2008) · Circulation · doi:10.1161/circulationaha.107.699579 · Cited by 7,491 · see citing works
Lloyd-Jones, D. M., Hong, Y., Labarthe, D., Mozaffarian, D., Appel, L. J., Van Horn, L., Greenlund, K., Daniels, S., Nichol, G., Tomaselli, G. F., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.192703 · Cited by 4,750 · see citing works
Self-citationFerence, B. A., Yoo, W., Alesh, I., Mahajan, N., Mirowska, K. K., Mewada, A., Kahn, J., Afonso, L., Williams, K. A., & Flack, J. M. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.09.017 · Cited by 898 · see citing works
Variation in<i>PCSK9</i>and<i>HMGCR</i>and Risk of Cardiovascular Disease and Diabetes
Ference, B. A., Robinson, J. G., Brook, R. D., Catapano, A. L., Chapman, M. J., Neff, D. R., Voros, S., Giugliano, R. P., Davey Smith, G., Fazio, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1604304 · Cited by 743 · see citing works
Impact of Lipids on Cardiovascular Health
Ference, B. A., Graham, I., Tokgozoglu, L., & Catapano, A. L. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.06.046 · Cited by 511 · see citing works
Ference, B. A., Kastelein, J. J. P., Ginsberg, H. N., Chapman, M. J., Nicholls, S. J., Ray, K. K., Packard, C. J., Laufs, U., Brook, R. D., Oliver-Williams, C., et al. (2017) · JAMA · doi:10.1001/jama.2017.11467 · Cited by 304 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association
Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Anderson, C. A. M., Arora, P., Avery, C. L., Baker-Smith, C. M., Beaton, A. Z., Boehme, A. K., Buxton, A. E., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001123 · Cited by 8,300 · see citing works
Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association
Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Alonso, A., Beaton, A. Z., Bittencourt, M. S., Boehme, A. K., Buxton, A. E., Carson, A. P., Commodore-Mensah, Y., et al. (2022) · Circulation · doi:10.1161/cir.0000000000001052 · Cited by 5,987 · see citing works
The changing landscape of atherosclerosis
Libby, P. (2021) · Nature · doi:10.1038/s41586-021-03392-8 · Cited by 2,873 · see citing works
Zhang, Y., Pletcher, M. J., Vittinghoff, E., Clemons, A. M., Jacobs, D. R., Allen, N. B., Alonso, A., Bellows, B. K., Oelsner, E. C., Zeki Al Hazzouri, A., et al. (2021) · JAMA Cardiology · doi:10.1001/jamacardio.2021.3508 · Cited by 257 · see citing works
2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia
Blumenthal, R. S., Morris, P. B., Gaudino, M., Johnson, H. M., Anderson, T. S., Bittner, V. A., Blankstein, R., Brewer, L. C., Cho, L., de Ferranti, S. D., et al. (2026) · JACC · doi:10.1016/j.jacc.2025.11.016 · Cited by 304 · see citing works
Self-citationWriting Committee Members, Blumenthal, R. S., Morris, P. B., Gaudino, M., Johnson, H. M., Anderson, T. S., Bittner, V. A., Blankstein, R., Brewer, L. C., Cho, L., et al. (2026) · Circulation · doi:10.1161/cir.0000000000001423 · Cited by 122 · see citing works
Self-citationNdumele, C. E., Rodriguez, F., Dixon, D. L., Khan, S. S., Mukherjee, D., Bajaj, M., Bangalore, S., Bozkurt, B., Breathett, K., Clarke, S. L., et al. (2026) · JACC · doi:10.1016/j.jacc.2026.03.056 · Cited by 90 · see citing works
New Approaches for Targeting PCSK9: Small-Interfering Ribonucleic Acid and Genome Editing
Oostveen, R. F., Khera, A. V., Kathiresan, S., Stroes, E. S. G., Fitzgerald, K., Harms, M. J., Oakes, B. L., & Kastelein, J. J. P. (2023) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.122.317963 · Cited by 31 · see citing works
Sucato, V., Comparato, F., Ortello, A., Galassi, A. R., & Novo, G. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14050460 · Cited by 12 · see citing works
- Authors
- Domanski, M. J., Tian, X., Wu, C. O., Reis, J. P., Dey, A. K., Gu, Y., Zhao, L., Bae, S., Liu, K., Hasan, A. A., Zimrin, D., Farkouh, M. E., Hong, C. C., Lloyd-Jones, D. M., & Fuster, V.
- Affiliations
- University of Maryland, Baltimore (US)
- National Institutes of Health (US)
- National Heart, Lung, and Blood Institute (US)
- George Washington University (US)
- Northwestern University (US)
- University of Alabama at Birmingham (US)
- University of Toronto (CA)
- Corresponding author
- Domanski, Michael J.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 76
- Issue
- 13
- Pages
- 1507-1516
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W3087016701
- Cited by
- 411
- References
- 8
- Citations by year
- 2026: 81 · 2025: 79 · 2024: 90 · 2023: 75 · 2022: 44 · 2021: 37 · 2020: 5
- FWCI
- 36.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Maryland
- 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 › Cardiovascular Health and Risk Factors
- Keywords
- LDL cholesterol, cardiovascular risk, young adults, coronary artery disease, stroke, heart failure hospitalization, peripheral arterial disease, cardiovascular mortality
- MeSH terms
- Age Factors, Cardiovascular Diseases, Female, Humans, Cholesterol, LDL, Longitudinal Studies, Male, Prospective Studies, United States, Incidence, Young Adult
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
