Physicians' Academy for Cardiovascular Education

Higher LDL-C and non-HDL-C related to increased risk of MACE in patients with arterial disease

van den Berg MJ et al., Am J Cardiol 2016

Low-Density Lipoprotein Cholesterol, None High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease

van den Berg MJ, van der Graaf Y, de Borst GJ, et al.
Am J Cardiol 2016;118:804-810


Studies assessing which lipid parameters are related to the risk of CV events have shown that apoB and non-HDL-C are more powerful markers compared with LDL-C, and that triglyceride-rich remnants can also be a good marker in this context [1]. However, most of these studies were either done in a primary prevention setting, or they were randomised controlled statin trials in the secondary prevention setting [2]. Moreover, the type or extent of atherosclerosis appears to influence the link between lipids and risk of recurrent CV events [3].
In this study, the relation between LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality was evaluated in 7,216 patients with clinically manifest arterial disease. Data were used from patients enrolled in the prospective ongoing Second Manifestation of Arterial Disease (SMART) cohort. It was also assessed whether the location of vascular disease influences this relation.

Main results

  • During a median follow-up of 6.5 years, a higher MACE risk was found with 1 SD higher LDL-C (HR: 1.15; 95% CI: 1.09-1.22), non-HDL-C (HR: 1.17; 95% CI: 1.11-1.23), triglycerides (HR: 1.12; 95% CI: 1.06-1.19), and apoB (HR: 1.12; 95% CI: 0.99-1.27).
  • The relation between levels of triglycerides and risk of MACE was dependent of the location of vascular disease at inclusion (P = 0.04 for interaction between triglycerides and type of vascular disease).
  • For LDL-C and non-HDL-C, the interaction was not statistically significant (P=0.66 and 0.58, respectively). After adjustment, 1 SD higher LDL-C and non-HDL-C were related to an increased risk of MACE in patients with a history of cerebrovascular disease, CAD, or poly-vascular disease.
  • As compared with the lowest quartile for risk of vascular mortality, patients in the top quartile of non-HDL-C had HR: 2.09; 95% CI: 1.62-2.69 for risk of vascular mortality, HR: 1.60; 95% CI: 1.34-1.91 for risk of future MACE and HR: 1.54; 95% CI: 1.29-1.83 for risk of all-cause mortality.
  • The relationships between LDL-C or triglycerides and future MACE were less strong (highest vs. lowest quartile: LDL: HR: 1.47, 95%CI: 1.24-1.75; triglycerides HR: 1.32, 95%CI: 111 – 1.57), as were the relationships with risk of all-cause mortality (LDL: HR: 1.38, 95%CI: 1.16-1.63, triglycerides: HR: 1.19, 95%CI: 1.00-1.40).
    Risk of stroke was higher in the top (>3.53 mmol/L) vs. the lowest quartile (<2.12 mmol/L) of LDL-C (HR: 1.88, 95%CI: 1.22-2.64). Risk of future myocardial infarction was higher for the top quartile of triglycerides (>2.00 mmol/L, HR: 1.63, 95%CI: 1.20-2.21) and for patients in the top quartile of non-HDL-C (HR: 1.55, 95%CI: 1.15-2.08).
    None of the apoB quartiles were associated with any of the end points compared with the lowest quartile.


In a large prospective secondary prevention cohort study, higher levels of LDL-C and non-HDL-C were related to an increased risk of MACE in patients with cerebrovascular, coronary artery, or poly-vascular disease. This relationship was not seen in patients with abdominal aortic aneurysm or peripheral artery disease. Higher triglyceride levels were also related to a higher risk of MACE in patients with cerebrovascular disease or coronary artery disease.
Find this article online at Am J Cardiol


1. Arsenault BJ, Rana JS, Stroes ES, et al. Beyond low-density lipoprotein cholesterol: respective contributions of non-high-density lipoprotein cholesterol levels, triglycerides, and the total cholesterol/high-density lipoprotein cholesterol ratio to coronary heart disease risk in apparently healthy men and women. J Am Coll Cardiol 2009;55:35-41.
2. Barter PJ, Ballantyne CM, Carmena R, et al. Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel. J Intern Med 2006;259:247-258.
3. Achterberg S, Cramer MJ, Kappelle LJ, et al. Patients with coronary, cerebrovascular or peripheral arterial obstructive disease differ in risk for new vascular events and mortality: the SMART study. Eur J Cardiovasc Prev Rehabil 2010;17:424-430.