On-treatment lipoprotein components and risk of cerebrovascular events in the Treating to New Targets study
Abstract
BACKGROUND: The Treating to New Targets (TNT) study has recently provided evidence that reduction in LDL-C levels below 2·6 mmol L⁻¹ lowers the risk of cerebrovascular events by an additional 20% to 25%, thereby confirming the value of statin therapy in preventing transient ischaemic attacks and stroke. Despite the protective effects of statin therapy, the epidemiological association between lipid components and cerebrovascular events is less clear. We therefore assessed the strength of association between in-trial lipoprotein components and cerebrovascular disease in patients receiving intensive lipid-lowering therapy. METHODS: In 9247 patients (mean age 61·0 years, 81·2% males), the association between lipoprotein components and the risk of cerebrovascular events after the first year into the TNT trial was assessed after stratification of lipoprotein components into approximate quartiles. Cox proportional hazards models were used to explore the association between lipoprotein components and time to first cerebrovascular event after adjustment for potential confounding variables. RESULTS: All lipoprotein components, except LDL-C, showed a significant gradient for incidence of cerebrovascular events with increasing quartiles of the lipoprotein component. If the lipoprotein components were treated as continuous variables, the adjusted hazard ratios (95% CI) for cerebrovascular events for 1 SD difference in 1-year lipoprotein components were 1·13 (1·02-1·25) for LDL-C, 0·86 (0·76-0·97) for HDL-C, 1·17 (1·04-1·28) for apoB, 0·83 (0·74-0·94) for apoA-1, 1·22 (1·10-1·34) for TC/HDL-C and 1·24 (1·12-1·37) for apoB/apoA-1. CONCLUSIONS: In coronary heart disease patients receiving intensive lipid-lowering treatment, the on-treatment apoB/apoA-1 ratio provides the strongest association with incidence of cerebrovascular events followed by TC/HDL-C.
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Emerging evidence suggested the apoB:apoA1 ratio to be the best overall predictor of CVD risk compared with other lipid markers.
“Emerging evidence suggested the apoB:apoA1 ratio to be the best overall predictor of CVD risk compared with other lipid markers (44, 47, 48).”
Cites
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972) · Clinical Chemistry · doi:10.1093/clinchem/18.6.499 · Cited by 32,423 · see citing works
Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease
LaRosa, J. C., Grundy, S. M., Waters, D. D., Shear, C., Barter, P., Fruchart, J.-C., Gotto, A. M., Greten, H., Kastelein, J. J. P., Shepherd, J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050461 · Cited by 3,489 · see citing works
Lorenz, M. W., Markus, H. S., Bots, M. L., Rosvall, M., & Sitzer, M. (2007) · Circulation · doi:10.1161/circulationaha.106.628875 · Cited by 2,977 · see citing works
High-Dose Atorvastatin after Stroke or Transient Ischemic Attack
The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061894 · Cited by 2,887 · see citing works
Gotto, A. M., Whitney, E. J., Stein, E. A., Shapiro, D. R., Clearfield, M. B., Weis, S. E., Jou, J. Y., Langendörfer, A., Beere, P. A., Watson, D. J., et al. (2000) · Circulation · doi:10.1161/01.cir.101.5.477 · Cited by 562 · see citing works
Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment
Kastelein, J. J. P., van der Steeg, W. A., Holme, I., Gaffney, M., Cater, N. B., Barter, P., Deedwania, P., Olsson, A. G., Boekholdt, S. M., Demicco, D. A., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.713438 · Cited by 478 · see citing works
Amarenco, P., Goldstein, L. B., Szarek, M. J., Sillesen, H. H., Rudolph, A. E., Callahan, A. S., III, Hennerici, M. G., Simunovic, L., Zivin, J. A., & Welch, K. M. A. (2007) · Stroke · doi:10.1161/strokeaha.107.493106 · Cited by 342 · see citing works
Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups
Tirschwell, D., Smith, N. L., Heckbert, S. R., Lemaître, R. N., Longstreth, W. T., Jr., & Psaty, B. M. (2004) · Neurology · doi:10.1212/01.wnl.0000144282.42222.da · Cited by 336 · see citing works
Sacco, R. L., Benson, R. T., Kargman, D. E., Boden-Albala, B., Tuck, C., Lin, I.-F., Cheng, J. F., Paik, M. C., Shea, S., & Berglund, L. (2001) · JAMA · doi:10.1001/jama.285.21.2729 · Cited by 311 · see citing works
Simes, R. J., Marschner, I. C., Hunt, D. U., Colquhoun, D., SULLIVAN, D. R., Stewart, R., Hague, W. E., KEECH, A. C., Thompson, P., White, H. D., et al. (2002) · Circulation · doi:10.1161/hc1002.105136 · Cited by 250 · see citing works
Amarenco, P., Labreuche, J., & Touboul, P. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.07.033 · Cited by 232 · see citing works
Waters, D. D., Guyton, J. R., Herrington, D. M., McGowan, M. P., WENGER, N. K., & Shear, C. L. (2004) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2003.09.031 · Cited by 200 · see citing works
van der Steeg, W. A., Boekholdt, S. M., Stein, E. A., El-Harchaoui, K., Stroes, E. S. G., Sandhu, M. S., Wareham, N. J., Jukema, J. W., Luben, R., Zwinderman, A. H., et al. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-9-200705010-00007 · Cited by 165 · see citing works
LaRosa, J. C., Grundy, S. M., Kastelein, J. J. P., Kostis, J. B., & Greten, H. (2007) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2007.03.102 · Cited by 148 · see citing works
Juonala, M., Viikari, J. S. A., Kähönen, M. A. P., Solakivi, T., Helenius, H. Y. M., Jula, A., Marniemi, J., Taittonen, L. M., Laitinen, T. P., Nikkari, T., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.03.054 · Cited by 146 · see citing works
The Friedewald Formula Underestimates LDL Cholesterol at low Concentrations
Scharnagl, H., Nauck, M. A., Wieland, H., & März, W. (2001) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2001.068 · Cited by 140 · see citing works
Stroke mortality and the apoB/apoA‐I ratio: results of the AMORIS prospective study
Walldius, G., AASTVEIT, A. H., & Jungner, I. (2006) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2005.01610.x · Cited by 122 · see citing works
Albers, J. J., Marcovina, S. M., & Kennedy, H. (1992) · Clinical Chemistry · doi:10.1093/clinchem/38.5.658 · Cited by 103 · see citing works
Holme, I., AASTVEIT, A. H., Hammar, N., Jungner, I., & Walldius, G. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2008.02016.x · Cited by 100 · see citing works
Amarenco, P., Goldstein, L. B., Callahan, A. S., III, Sillesen, H. H., Hennerici, M. G., O’Neill, B. J., Rudolph, A. E., Simunovic, L., Zivin, J. A., & Welch, K. M. A. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.09.008 · Cited by 97 · see citing works
Waters, D. D., LaRosa, J. C., Barter, P. J., Fruchart, J., Gotto, A. M., Carter, R., Breazna, A., Kastelein, J. J. P., & Grundy, S. M. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.07.041 · Cited by 75 · see citing works
Charlton-Menys, V., Betteridge, D. J., Colhoun, H. M., Fuller, J., France, M. W., Hitman, G. A., Livingstone, S. J., Neil, H. A. W., Newman, C. B., Szarek, M. J., et al. (2008) · Diabetologia · doi:10.1007/s00125-008-1176-8 · Cited by 41 · see citing works
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Updated Society for Vascular Surgery guidelines for management of extracranial carotid disease
Ricotta, J. J., AbuRahma, A. F., Ascher, E., Eskandari, M. K., Faries, P. L., & Lal, B. K. (2011) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2011.07.031 · Cited by 611 · see citing works
AbuRahma, A. F., Avgerinos, E. D., Chang, R. W., Darling, R. C., Duncan, A. A., Forbes, T. L., Malas, M. B., Perler, B. A., Powell, R. J., Rockman, C. R., et al. (2021) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2021.04.074 · Cited by 198 · see citing works
The apoB/apoA-I Ratio is a Strong Predictor of Cardiovascular Risk
Walldius, G. (2012) · InTech eBooks · doi:10.5772/47869 · Cited by 36 · see citing works
N-Glycosylation Profiles of Immunoglobulin G and Future Cardiovascular Events
Hoshi, R. A., Plavša, B., Liu, Y., Trbojević‐Akmačić, I., Glynn, R. J., Ridker, P. M., Cummings, R. D., Gudelj, I., Lauc, G., Demler, O., et al. (2024) · Circulation Research · doi:10.1161/circresaha.123.323623 · Cited by 36 · see citing works
Avocado Consumption and Cardiometabolic Health: A Systematic Review and Meta-Analysis
James‐Martin, G., Brooker, P. G., Hendrie, G. A., & Stonehouse, W. (2022) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2022.12.008 · Cited by 25 · see citing works
Stonehouse, W., Sergi, D., Benassi-Evans, B., James-Martin, G., Johnson, N., Thompson, C. H., & Abeywardena, M. (2021) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa347 · Cited by 16 · see citing works
Sawant, S., Tucker, B., Senanayake, P., Waters, D. D., Patel, S., Rye, K., Ong, K. L., & Cochran, B. J. (2021) · American Heart Journal Plus Cardiology Research and Practice · doi:10.1016/j.ahjo.2021.100024 · Cited by 12 · see citing works
Walldius, G. (2025) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2025.2543537 · Cited by 4 · see citing works
Interventions in Carotid Artery Surgery
Banks, C. A., & Pearce, B. J. (2023) · Surgical Clinics of North America · doi:10.1016/j.suc.2023.05.003 · Cited by 1 · see citing works
Optimizing care for patients with symptomatic carotid disease
Kolkert, J. L. (2017) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Kontush, A., & Chapman, M. J. (2011) · Wiley eBooks · doi:10.1002/9781118158678.ch5
Statin effects on immunoglobulin-G glycomic architecture and the link to cardiovascular diseasePreprint
Yazdani, A., Hoshi, R. A., Ammar, M., Li, C., Cummings, R. D., Akmačić-Trbojević, I., Cindrić, A., Šimunić-Briški, N., Gudelj, I., Glynn, R. J., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-6112380/v1
- Authors
- van den Bogaard, B., van den Born, B.-J. H., Fayyad, R., Waters, D. D., DeMicco, D. A., LaRosa, J. C., Kastelein, J. J. P., Holme, I., & On behalf of the Treating to New Targets investigators
- Affiliations
- Pfizer (United States) (US)
- University of California, San Francisco (US)
- State University of New York (US)
- Amsterdam UMC Location University of Amsterdam (NL)
- Oslo University Hospital (NO)
- Venue
- European Journal of Clinical Investigation
- Publisher
- Wiley
- Published
- 2010-09-27
- Volume
- 41
- Issue
- 2
- Pages
- 134-142
- ISSN
- 0014-2972 (ISSN-L)
- OpenAlex
- W1588172340
- Cited by
- 12
- References
- 24
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2017: 1 · 2012: 1
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- cerebrovascular events, LDL cholesterol, HDL cholesterol, apolipoprotein B, apolipoprotein A-I, TC/HDL-C ratio, ApoB/ApoA1 ratio, intensive lipid-lowering therapy, statin therapy, coronary artery disease, stroke, transient ischemic attack, risk factors
- MeSH terms
- Aged, Anticholesteremic Agents, Ischemic Attack, Transient, Coronary Disease, Female, Follow-Up Studies, Humans, Lipoproteins, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Risk Factors, Time Factors, Proportional Hazards Models, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Stroke
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