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Association of High-Density Lipoprotein Cholesterol With Incident Cardiovascular Events in Women, by Low-Density Lipoprotein Cholesterol and Apolipoprotein B100 Levels: A Cohort Study

Samia Mora, MD, MHS; Julie E. Buring, ScD; Paul M Ridker, MD, MPH; and Yadong Cui, MD, PhD
[+] Article, Author, and Disclosure Information

From the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts, and Merck & Co., North Wales, Pennsylvania.

Grant Support: The research for this article was supported by an investigator-initiated research grant to Dr. Mora from Merck & Co. The study was also supported by grants K08 HL094375 (Dr. Mora) and HL 43851, HL 080467, and CA 47988 from the National Heart, Lung, and Blood Institute and the National Cancer Institute, National Institutes of Health.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-1677.

Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Mora (e-mail, smora@partners.org).

Requests for Single Reprints: Samia Mora, MD, MHS, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Third Floor, Boston, MA 02215; e-mail, smora@partners.org.

Current Author Addresses: Drs. Mora, Buring, and Ridker: Brigham and Women's Hospital, 900 Commonwealth Avenue East, Third Floor, Boston, MA 02215.

Dr. Cui: Merck & Co., 351 North Sumneytown Pike, North Wales, PA 19454.

Author Contributions: Conception and design: S. Mora, Y. Cui.

Analysis and interpretation of the data: S. Mora, Y. Cui.

Drafting of the article: S. Mora, Y. Cui.

Critical revision of the article for important intellectual content: S. Mora, J.E. Buring, P.M Ridker, Y. Cui.

Final approval of the article: S. Mora, J.E. Buring, P.M Ridker, Y. Cui.

Statistical expertise: S. Mora, Y. Cui.

Obtaining of funding: S. Mora, J.E. Buring, P.M Ridker.

Administrative, technical, or logistic support: S. Mora, P.M Ridker.

Collection and assembly of data: J.E. Buring, P.M Ridker.

Ann Intern Med. 2011;155(11):742-750. doi:10.7326/0003-4819-155-11-201112060-00006
Text Size: A A A

Background: Prior studies have found inverse associations between high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I levels and cardiovascular disease (CVD). Whether this observation is consistent across low-density lipoprotein cholesterol (LDL-C) levels or total atherogenic particle burden (apolipoprotein B100) is less well-studied, particularly in women.

Objective: To determine the association between HDL-C or apolipoprotein A-I level and CVD across a range of LDL-C and apolipoprotein B100 values.

Design: Prospective cohort study.

Setting: The Women's Health Study, a cohort of U.S. female health professionals.

Participants: 26 861 initially healthy women, aged 45 years or older at study entry (1992–1995), who were followed for a mean of approximately 11 years.

Measurements: Baseline lipids were measured directly, and apolipoproteins were measured with immunoassays. Outcomes were incident total CVD (n = 929), coronary events (n = 602), and stroke (n = 319).

Results: In multivariable analyses, HDL-C and apolipoprotein A-I levels were inversely associated with CVD and coronary events but not stroke. Adjusted coronary hazard ratios for decreasing quintiles of HDL-C were 1.00 (reference), 1.23 (95% CI, 0.85 to 1.78), 1.42 (CI, 0.98 to 2.06), 1.90 (CI, 1.33 to 2.71), and 2.19 (CI, 1.51 to 3.19) (P for linear trend < 0.001); corresponding hazard ratios for apolipoprotein A-I were 1.00 (reference), 0.98 (CI, 0.71 to 1.35), 1.02 (CI, 0.72 to 1.44), 1.37 (CI, 0.98 to 1.90), and 1.58 (CI, 1.14 to 2.20) (P for linear trend = 0.005). Consistent inverse associations were found for HDL-C with coronary events across a range of LDL-C values, including among women with low LDL-C levels. No associations were noted for HDL-C or apolipoprotein A-I among women with low apolipoprotein B100 values (<0.90 g/L).

Limitation: Participants were at low risk for CVD, the number of events in the lowest apolipoprotein B100 stratum was small, only a single baseline measurement was obtained, and residual confounding may have occurred.

Conclusion: Consistent inverse associations were found for HDL-C with incident coronary events among women with a range of LDL-C values. Among women with low total atherogenic particle burden (apolipoprotein B100 level <0.90 g/L), few events occurred and no associations were seen.

Primary Funding Source: Merck & Co. and the National Heart, Lung, and Blood Institute and National Cancer Institute, National Institutes of Health.


Grahic Jump Location
Study flow diagram.

CHD = coronary heart disease; CVD = cardiovascular disease.

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Appendix Figure.
Age-adjusted hazard ratios (95% CIs) for coronary events by decile of HDL-C and apolipoprotein A-I.

The bottom decile is the reference group. HDL-C = high-density lipoprotein cholesterol.

Grahic Jump Location




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Summary for Patients

Does Low-Density Lipoprotein Cholesterol Influence the Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular Risk in Women?

The full report is titled “Association of High-Density Lipoprotein Cholesterol With Incident Cardiovascular Events in Women, by Low-Density Lipoprotein Cholesterol and Apolipoprotein B100 Levels. A Cohort Study.” It is in the 6 December 2011 issue of Annals of Internal Medicine (volume 155, pages 742-750). The authors are S. Mora, J.E. Buring, P.M Ridker, and Y. Cui.


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