Author + information
- Received December 4, 2017
- Revision received March 21, 2018
- Accepted April 16, 2018
- Published online July 9, 2018.
- Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Nancy R. Cook, Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, Massachusetts 02215-1204.
Background Although lipoprotein(a) [Lp(a)] is associated with incident cardiovascular disease (CVD), its contribution to prediction remains controversial.
Objectives This study examined the association and clinical utility of Lp(a) with incident CVD in women.
Methods A turbidimetric assay assessed Lp(a) in 3 cohorts of women (the WHS [Women’s Health Study] [N = 24,558], a case-cohort sample from the WHI [Women’s Health Initiative] Observational Study [n = 1,815 cases, subcohort n = 1,989], and the JUPITER [Justification for Use of Statins in Prevention] trial [n = 2,569]) and in men from JUPITER (n = 5,161). A WHS derivation sample (n = 16,400) determined the form of association with incident CVD. This was tested in WHS validation data (n = 8,158) and the other study samples. Models including traditional CV risk factors but with and without Lp(a) were compared using risk reclassification.
Results In the WHS, there was a curvilinear association, with increased CVD risk among those with Lp(a) >50 mg/dl, but only among women with total cholesterol (TC) >220 mg/dl. In the WHS test sample, there was a small but significant change in the C-statistic (0.790 to 0.797; p = 0.035) but no improvement in measures of reclassification. This pattern was replicated among women in the WHI and JUPITER trial. In contrast, there was a strong association of Lp(a) with CVD among men with low TC levels in JUPITER.
Conclusions In 3 cohorts of women, Lp(a) was associated with CVD only among those with high TC, and improvement in prediction was minimal. These data have implications for Lp(a) in clinical practice among women and for trials of Lp(a)-lowering agents.
The WHS (Women’s Health Study) was supported by grants HL043851 from the National Heart, Lung, and Blood Institute (NHLBI) and CA047988 from the National Cancer Institute. The WHS blood analysis was supported by the Donald W. Reynolds Foundation and the Leducq Foundation. The WHI (Women’s Health Initiative) program is funded by the NHLBI, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The WHI blood analysis was supported by BAA award HHSN268200960011C and grant HL113080 from the NHLBI. The JUPITER (Justification for Use of Statins in Prevention) trial was supported by AstraZeneca, which had no role in the design or conduct of the present study. Quest Diagnostics Nichols Institute performed the Lp(a) measurements in JUPITER at no additional cost to the study. The study was also funded by grants HL117861, HL136852, and K134811 from the NHLBI. Dr. Mora has received institutional research grant support from Atherotech Diagnostics and the National Institute of Diabetes and Digestive and Kidney Diseases (DK112940); and has served as consultant to Amgen, Pfizer, and Quest Diagnostics. Dr. Ridker has received research funding support from multiple not-for-profit entities including the NHLBI, the National Cancer Institute, the American Heart Association, the Doris Duke Charitable Foundation, the Leducq Foundation, and the Donald W. Reynolds Foundation; has received investigator-initiated research support from AstraZeneca, Novartis, Pfizer, and Kowa; has received nonfinancial research support from Amgen; is listed as a coinventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to Siemens and AstraZeneca; and has served as a research consultant to Sanofi, Quintiles, AstraZeneca, and Teva. Dr. Cook has reported that she has no relationships relevant to the contents of this paper to disclose.
- Received December 4, 2017.
- Revision received March 21, 2018.
- Accepted April 16, 2018.
- 2018 American College of Cardiology Foundation
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