Author + information
- Received July 2, 2020
- Revision received July 30, 2020
- Accepted July 30, 2020
- Published online September 21, 2020.
- Michael J. Domanski, MDa,∗ (, )@MDomanskiMD,
- Xin Tian, PhDb,
- Colin O. Wu, PhDb,
- Jared P. Reis, PhDc,
- Amit K. Dey, MDd,
- Yuan Gu, PhDe,
- Lihui Zhao, PhDf,
- Sejong Bae, PhDg,
- Kiang Liu, PhDf,
- Ahmed A. Hasan, MD, PhDc,
- David Zimrin, MDa,
- Michael E. Farkouh, MD, MSch,
- Charles C. Hong, MDa,
- Donald M. Lloyd-Jones, MD, ScMf and
- Valentin Fuster, MD, PhDi
- aDivision of Cardiovascular Medicine and Data Science Initiative, University of Maryland School of Medicine, Baltimore, Maryland
- bOffice of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
- cDivision of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland
- dCardiovascular Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland
- eDepartment of Statistics, George Washington University, Washington, DC
- fDepartment of Preventive Medicine, Northwestern Feinberg School of Medicine, Chicago, Illinois
- gDivision of Preventive Medicine, University of Alabama School of Medicine, Birmingham, Alabama
- hDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada
- iCardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- ↵∗Address for correspondence:
Dr. Michael J. Domanski, University of Maryland School of Medicine, 110 South Paca Street, Baltimore, Maryland 21201.
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.
- cardiovascular disease
- cholesterol lowering
- coronary heart disease
- low-density lipoprotein
- preventive cardiology
The CARDIA (Coronary Artery Risk Development in Young Adults) study is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). The views expressed in this paper are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the U.S. Department of Health and Human Services. This paper has been reviewed by CARDIA for scientific content. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Michael David Shapiro, DO, served as Guest Associate Editor for this paper. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper.
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 July 2, 2020.
- Revision received July 30, 2020.
- Accepted July 30, 2020.
- 2020 American College of Cardiology Foundation
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