Treatment Implications of LDL-Cholesterol and Apolipoprotein B Discordance: Insights from the Very Large Database of Lipids (VLDbL) and the National Health and Examination Survey (NHANES)
Abstract Body (Do not enter title and authors here): Background ApoB-containing lipoproteins, including LDL, are well-established causes of atherosclerotic cardiovascular disease (ASCVD). While typically highly correlated, apoB and LDL-C levels can diverge due to differences in lipid composition and response to lipid-lowering therapies (LLT). Furthermore, the definition of cutpoints can influence clinically-relevant discordance between LDL-C and apoB, which may inform guideline-directed treatment. Recent proposals suggest aligning LDL-C and apoB goals using equivalent cutpoints (<55, <70, and <100 mg/dL). Clarifying the prevalence and impact of discordance has important implications for clinical care.
Objectives To quantify the prevalence of LDL-C and apoB discordance among US adults when applying equivalent LDL-C and apoB goals.
Methods We included 298,578 adults (age ≥18) with available apoB and LDL-C measurements from the Very Large Database of Lipids (VLDbL), a population-representative convenience sample with clinical lipid measurements obtained in 2015-2019. We also included 2,707 statin-treated adults from the National Health and Nutrition Examination Survey (NHANES) from 2005-2016 to assess the effects of statin use on discordance. The Martin-Hopkins equation was used to calculate LDL-C. Equivalent goals of <55, <70, and <100 mg/dL for LDL-C and apoB were applied.
Results In VLDbL (mean age 56 years, 57% female), 43.2% had apoB and LDL-C discordance (Table 1). In NHANES statin-treated individuals (mean age 66 years, 47% female), 33.9% had apoB and LDL-C discordance. Among those reaching LDL-C goals of <55, <70, and <100 mg/dL, apoB was discordantly elevated in up to 33%, 12%, and 2%, respectively, for equivalent goals (Figure 1). In contrast, among those reaching apoB goals of <55, <70, and <100 mg/dL, LDL-C was discordantly elevated in up to 61%, 56%, and 49%, respectively, for equivalent goals (Figure 2).
Conclusions LDL-C and apoB discordance was prevalent among US adults, most often due to discordant LDL-C elevation in those reaching equivalent apoB goals, with less discordance in statin-treated adults. These results suggest that using LDL-C and apoB individually as treatment goals could lead to substantially different patient populations eligible for LLT to reduce ASCVD risk, while utilizing both as complementary goals could maximize eligibility for LLT. Taken together, these findings suggest an opportunity for an individualized approach to ASCVD risk optimization.
Peng, Allison
( Johns Hopkins School of Medicine
, Baltimore
, Maryland
, United States
)
Blumenthal, Roger
( Johns Hopkins School of Medicine
, Baltimore
, Maryland
, United States
)
Martin, Seth
( Johns Hopkins School of Medicine
, Baltimore
, Maryland
, United States
)
Zahid, Sohail
( Johns Hopkins
, Baltimore
, Maryland
, United States
)
Gianos, Eugenia
( Lenox Hill- Northwell Health
, New York
, New York
, United States
)
Shapiro, Michael
( Wake Forest Univ School of Medicine
, Winston Salem
, North Carolina
, United States
)
Navar, Ann Marie
( UT Southwestern Medical Center
, Dallas
, Texas
, United States
)
Marvel, Francoise
( Johns Hopkins Hospital
, Baltimore
, Maryland
, United States
)
Rodriguez, Fatima
( STANFORD UNIVERSITY
, Palo Alto
, California
, United States
)
Soffer, Daniel
( University of Pennsylvania
, Philadelphia
, Pennsylvania
, United States
)
Morris, Pamela
( MEDICAL UNIVERSITY OF SC
, Mt Pleasant
, South Carolina
, United States
)
Author Disclosures:
Allison Peng:DO NOT have relevant financial relationships
| Roger Blumenthal:DO NOT have relevant financial relationships
| Seth Martin:DO have relevant financial relationships
;
Consultant:Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Care Access, Chroma, Bristol Myers Squibb, Heartflow, Kaneka, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Premier, Sanofi, Verve Therapeutics, :Past (completed)
; Ownership Interest:Corrie Health, Prevent Medical:Active (exists now)
; Other (please indicate in the box next to the company name):American Heart Association (Immediate Past Chair, EPI Statistics Committee):Active (exists now)
; Other (please indicate in the box next to the company name):National Lipid Association (SELA President):Active (exists now)
; Other (please indicate in the box next to the company name):Editorial Board Member (AJPC, EJPC, JCL):Active (exists now)
; Research Funding (PI or named investigator):National Institutes of Health, Patient-Centered Outcomes Research Institute, American Heart Association, American College of Cardiology:Active (exists now)
; Employee:Johns Hopkins School of Medicine :Active (exists now)
; Other (please indicate in the box next to the company name):National Institutes of Health Data Safety and Monitoring Board:Active (exists now)
| Sohail Zahid:DO NOT have relevant financial relationships
| Eugenia Gianos:DO NOT have relevant financial relationships
| Michael Shapiro:DO have relevant financial relationships
;
Consultant:Ionis:Past (completed)
; Consultant:Arrowhead:Past (completed)
; Consultant:Regeneron:Past (completed)
; Researcher:New Amsterdam:Active (exists now)
; Researcher:Merck:Active (exists now)
; Researcher:Novartis:Active (exists now)
; Researcher:Esperion:Active (exists now)
; Researcher:Cleerly:Active (exists now)
; Researcher:Amgen:Active (exists now)
; Consultant:Novo Nordisk:Active (exists now)
; Consultant:Tourmaline:Active (exists now)
; Consultant:Merck:Active (exists now)
; Consultant:New Amsterdam:Past (completed)
; Consultant:Novartis:Active (exists now)
| Ann Marie Navar:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Amgen:Active (exists now)
; Consultant:Amgen, Arrowhead, Bayer, Esperion, Janssen, Eli Lilly, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Roche, Silence Therapeutics:Active (exists now)
; Research Funding (PI or named investigator):Esperion:Past (completed)
| Francoise Marvel:No Answer
| Fatima Rodriguez:DO have relevant financial relationships
;
Consultant:HealthPals:Past (completed)
; Consultant:Cleerly Health:Active (exists now)
; Consultant:Amgen:Active (exists now)
; Consultant:iRhythm:Active (exists now)
; Consultant:HeartFlow:Active (exists now)
; Consultant:Arrowhead Pharmaceuticals:Active (exists now)
; Consultant:Edwards:Active (exists now)
; Consultant:Inclusive Health:Active (exists now)
; Consultant:Esperion Therapeutics:Past (completed)
; Consultant:Kento Health:Active (exists now)
; Consultant:Movano Health:Active (exists now)
; Consultant:NovoNordisk:Past (completed)
; Consultant:Novartis:Active (exists now)
| Daniel Soffer:DO have relevant financial relationships
;
Consultant:Ionis:Active (exists now)
; Researcher:Arrowhead:Active (exists now)
; Researcher:Heartflow:Active (exists now)
; Researcher:Novartis:Active (exists now)
; Researcher:Ionis:Active (exists now)
; Researcher:Amryt:Active (exists now)
; Researcher:Amgen:Active (exists now)
; Researcher:Akcea:Active (exists now)
; Researcher:PCORI:Active (exists now)
; Consultant:New Amsterdam:Past (completed)
; Advisor:Regeneron:Past (completed)
; Researcher:Lilly:Active (exists now)
; Consultant:Amryt:Past (completed)
; Researcher:NIH:Active (exists now)
| Pamela Morris:DO NOT have relevant financial relationships