Addressing residual risk begins with LDL-C and goes beyond
Even at LDL-C targets with statins, residual ASCVD risk can remain2,3,5
Uncovering residual risk means assessing LDL-C—and beyond1-4
Uncovering residual risk means assessing LDL-C—and beyond1-4
LDL-C isn’t the whole picture—other lipid markers (e.g., Lp(a), apoB, non-HDL-C, HDL-C, sdLDL-P) can contribute to residual ASCVD risk.1-4,6
ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a); apoB, apolipoprotein B; non-HDL-C, non–high-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; sdLDL-P, small dense low-density lipoprotein particles.
The multi-biomarker link to ASCVD
Higher Lp(a), higher risk
Elevated Lp(a) is a risk-enhancing factor associated with increased ASCVD risk; higher levels indicate greater lifetime risk.1
Low HDL-C highlights unmet cardiovascular concerns
Low HDL-C—particularly <40 mg/dL—is associated with increased risk of coronary arterial disease (CAD) and peripheral arterial disease (PAD). It is also commonly observed in metabolic disease, including diabetes.1,4,7
Non-HDL-C adds information beyond LDL-C
In patients with metabolic disorders (including type 2 diabetes/obesity) and atherogenic dyslipidemia, non-HDL-C is associated with improved risk prediction vs LDL-C.1,3,8
ApoB helps capture the full spectrum of atherogenic lipoproteins
In addition to its link with residual risk, apoB reflects the total burden of atherogenic lipoprotein particles—and may predict some ASCVD risks more effectively than LDL-C.3,4,9
sdLDL-P helps complete the lipid profile picture
sdLDL-P is associated with ASCVD and coronary heart disease (CHD), and may help refine cardiovascular risk stratification beyond traditional markers. Elevated sdLDL-P numbers characterize dyslipidemia in type 2 diabetes.10-12
ACC & AHA: Treat to LDL-C, then use risk-enhancers to refine ASCVD risk1,13
ACC, American College of Cardiology; AHA, American Heart Association.
European guidelines highlight Lp(a) as a CV risk factor
American College of Cardiology (ACC) 2022 expert recommendations
See how lipid-lowering therapies differ in their impact
References: 1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143. doi:10.1161/CIR.0000000000000625 2. Reijnders E, van der Laarse A, Jukema JW, Cobbaert CM. High residual cardiovascular risk after lipid-lowering: prime time for predictive, preventive, personalized, participatory, and psycho-cognitive medicine. Front Cardiovasc Med. 2023;10:1264319. doi:10.3389/fcvm.2023.1264319 3. Raja V, Aguiar C, Alsayed N, et al. Non–HDL-cholesterol in dyslipidemia: review of the state-of-the-art literature and outlook. Atherosclerosis. 2023;383:117312. doi:10.1016/j.atherosclerosis.2023.117312 4. Catapano AL, Tokgözoğlu L, Mello e Silva A, Bruckert E. Atherogenic markers in predicting cardiovascular risk and targeting residual cardiovascular risk. Atheroscler Suppl. 2019;39S:100001. doi:10.1016/j.athx.2019.100001 5. Matsuura Y, Kanter JE, Bornfeldt KE. Highlighting residual atherosclerotic cardiovascular disease risk. Arterioscler Thromb Vasc Biol. 2019;39(1):e1-e9. doi:10.1161/ATVBAHA.118.311999 6. Doherty S, Hernandez S, Rikhi R, et al. Lipoprotein(a) as a causal risk factor for cardiovascular disease. Curr Cardiovasc Risk Rep. 2025;19(8):8. doi:10.1007/s12170-025-00760-1 7. Rohatgi A, Westerterp M, von Eckardstein A, Remaley A, Rye KA. HDL in the 21st century: a multifunctional roadmap for future HDL research. Circulation. 2021;143(23):2293-2309. doi:10.1161/CIRCULATIONAHA.120.044221 8. Brunner FJ, Waldeyer C, Ojeda F, et al. Multinational Cardiovascular Risk Consortium. Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium. Lancet. 2019;394(10215):2173-2183. doi:10.1016/S0140-6736(19)32519-X 9. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4(3):337-345. doi:10.1161/CIRCOUTCOMES.110.959247 10. Schaefer EJ, Ikezaki H, Diffenderfer MR, et al. Atherosclerotic cardiovascular disease risk and small dense low-density lipoprotein cholesterol in men, women, African Americans and non-African Americans: the pooling project. Atherosclerosis. 2023;367:15-23. doi:10.1016/j.atherosclerosis.2023.01.015 11. Newman CB, Blaha MJ, Boord JB, et al. Lipid management in patients with endocrine disorders: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2020;105(12):3613-3682. doi:10.1210/clinem/dgaa674 12. Hirano T. Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb. 2018;25(9):771-782. doi:10.5551/jat.RV17023 13. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022;80(14):1366-1418. doi:10.1016/j.jacc.2022.07.006 14. Mach F, Koskinas KC, Roeters van Lennep JE, et al; ESC/EAS Scientific Document Group. 2025 focused update of the 2019 ESC/EAS guidelines for the management of dyslipidaemias. Atherosclerosis. 2025;389:120479. doi:10.1016/j.atherosclerosis.2025.120479