Anurag Mehta1, Salim S Virani2, Colby R Ayers3, Wensheng Sun4, Ron C Hoogeveen4, Anand Rohatgi5, Jarett D Berry5, Parag H Joshi5, Christie M Ballantyne6, Amit Khera7. 1. Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. Electronic address: https://twitter.com/amehta_09. 2. Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas; Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. Electronic address: https://twitter.com/virani_md. 3. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas. 4. Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas. 5. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. 6. Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas. Electronic address: https://twitter.com/CBallantyneMD. 7. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: amit.khera@utsouthwestern.edu.
Abstract
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.
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.
Authors: Nathan D Wong; Matthew J Budoff; Keith Ferdinand; Ian M Graham; Erin D Michos; Tina Reddy; Michael D Shapiro; Peter P Toth Journal: Am J Prev Cardiol Date: 2022-03-15