Author + information
- Received June 10, 2020
- Accepted June 12, 2020
- Published online August 10, 2020.
- Anurag Mehta, MDa@amehta_09,
- Salim S. Virani, MD, PhDb,c@virani_md,
- Colby R. Ayers, MSd,e,
- Wensheng Sun, MPH, MSb,
- Ron C. Hoogeveen, PhDb,
- Anand Rohatgi, MD, MHScd,
- Jarett D. Berry, MD, MSd,
- Parag H. Joshi, MD, MHSd,
- Christie M. Ballantyne, MDb@CBallantyneMD and
- Amit Khera, MD, MScd,∗ (, )@dramitkhera
- aEmory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
- bSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas
- cSection of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- dDivision of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
- eDepartment of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas
- ↵∗Address for correspondence:
Dr. Amit Khera, Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8830.
Background Elevated lipoprotein(a) (Lp[a]) and family history (FHx) of coronary heart disease (CHD) are individually associated with cardiovascular risk, and Lp(a) is commonly measured in those with FHx.
Objectives The aim of this study was to determine independent and joint associations of Lp(a) and FHx with atherosclerotic cardiovascular disease (ASCVD) and CHD among asymptomatic subjects.
Methods Plasma Lp(a) was measured and FHx was ascertained in 2 cohorts. Elevated Lp(a) was defined as the highest race-specific quintile. Independent and joint associations of Lp(a) and FHx with cardiovascular risk were determined using Cox regression models adjusted for cardiovascular risk factors.
Results Among 12,149 ARIC (Atherosclerosis Risk In Communities) participants (54 years, 56% women, 23% black, 44% with FHx), 3,114 ASCVD events were observed during 21 years of follow-up. FHx and elevated Lp(a) were independently associated with ASCVD (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.09 to 1.26, and HR: 1.25; 95% CI: 1.12 to 1.40, respectively), and no Lp(a)-by-FHx interaction was noted (p = 0.75). Compared with subjects without FHx and nonelevated Lp(a), those with either elevated Lp(a) or FHx were at a higher ASCVD risk, while those with both had the highest risk (HR: 1.43; 95% CI: 1.27 to 1.62). Similar findings were observed for CHD risk in ARIC, in analyses stratified by premature FHx, and in an independent cohort, the DHS (Dallas Heart Study). Presence of both elevated Lp(a) and FHx resulted in greater improvement in ASCVD and CHD risk reclassification and discrimination indexes than either marker alone.
Conclusions Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions.
- atherosclerotic cardiovascular disease
- cardiovascular risk
- family history
- primary CVD prevention
The ARIC study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I). The Dallas Heart Study was funded by the Donald W. Reynolds Foundation and partially supported by the National Center for Advancing Translational Sciences of the NIH (UL1TR001105). Dr. Mehta has received grants from the American Heart Association (outside the submitted work). Dr. Virani has received grants from the U.S. Department of Veterans Affairs, the World Heart Federation, and the Tahir and Jooma Family; has received honorarium from the American College of Cardiology; and is on the steering committee of the PALM (Patient and Provider Assessment of Lipid Management) registry at Duke Clinical Research Institute (outside the submitted work). Dr. Ayers has received personal fees from the NIH (outside the submitted work). Dr. Hoogeveen has received grants and personal fees from Denka Seiken (during the conduct of the study). Dr. Rohatgi has received grants from the NIH/NHLBI, the American Heart Association, and Merck; and has received personal fees from HDL Diagnostics and CSL Limited (outside the submitted work). Dr. Berry has received personal fees from AstraZeneca and Roche; and has received grants from the NHBLI and Abbott (outside the submitted work). Dr. Joshi has received grants from the American Heart Association and Novo Nordisk; has received personal fees and nonfinancial support from Regeneron; has received personal fees from Bayer; has equity in the Global Genomic Group; and has received nonfinancial support from GlaxoSmithKline, Sanofi, AstraZeneca, and Pfizer (outside the submitted work). Dr. Ballantyne has received grants from the NIH (during the conduct of the study); has received grants and personal fees from Abbott Diagnostic, Amgen, Esperion, Novartis, Regeneron, Roche Diagnostic, and Akcea; has received personal fees from AstraZeneca, Amarin, Matinas BioPharma, Merck, Sanofi-Synthelabo, Boehringer Ingelheim, Novo Nordisk, Denka Seiken, Intercept, Janssen, Corvidia, and Arrowhead; has received grants from the NIH, the American Heart Association, and the American Diabetes Association (outside the submitted work); and has a provisional patent (61721475), “Biomarkers to Improve Prediction of Heart Failure Risk,” filed by Baylor College of Medicine and Roche (pending). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received June 10, 2020.
- Accepted June 12, 2020.
- 2020 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.