LDL-c/ApoB ratio is a predictor of MACE in patients with atherosclerosis

The LDL-C/ApoB ratio predicts major cardiovascular events in patients with established atherosclerotic cardiovascular disease

Literature - Drexel H, Larcher B, Mader A, et al., - Atherosclerosis 2021, doi.org/10.1016/j.atherosclerosis.2021.05.010

Introduction and methods

LDL particles vary in size, density and atherogenicity and they can be divided into subclasses [1]. Small dense LDL (sdLDL) particles are more atherogenic than large LDL particles [2-4]. A high proportion of sdLDL was reported in individuals with insulin resistance, including those with obesity, metabolic syndrome, and T2DM [4]. Measuring LDL particle size is time-consuming and expensive. Determining the LDL-c/ApoB ratio overcomes this limitation and is an easy and valid proxy of LDL particle size [5,6,7].

In this prospective cohort study, it was examined whether LDL-c/ApoB is a predictor of MACE in a high-risk cohort of patients with established atherosclerotic CVD.

Patients with established or suspected CAD or PAD were recruited between 1999 and 2008 in a hospital in Austria. Those with previous MI or ACS 3 months prior were excluded. 1389 Patients with CAD and 298 with PAD were included. Follow-up was 9.9 years (SD: 4.6). Primary endpoint was MACE, a composite of CV death, non-fatal MI and non-fatal stroke. Patients were divided into tertiles based on LDL-c/ApoB ratio using cut-off points of 1.23 and 1.46. Low to normal LDL-c/ApoB was ≤1.46 and high LDL-c/ApoB ratio was considered >1.46.

Main results

  • Strongest predictors of LDL-c/ApoB ratio were T2DM and age, followed by gender, smoking and hypertension.
  • Patients in the highest tertile of LDL-c/ApoB ratio had significant better outcome than those in the lower tertiles (log rank p=0.005).
  • In a fully adjusted model, high LDL-c/ApoB ratio was associated with lower MACE (HR 0.87, 95%IC: 0.78-0.97, P=0.013).
  • High LDL-c/ApoB ratio was also associated with lower all-cause mortality and total CV events (HR 0.88, ,95%CI: 0.80-0.97, P=0.012 and HR 0.88, 95%CI: 0.80-0.95, P=0.0003, respectively).

Conclusion

In this prospective cohort study, high LDL-c/ApoB ratio predicted MACE. LDL-c/ApoB ratio may therefore be used as a parameter to optimize risk estimation in patients with manifest atherosclerosis.

References

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2. J. Bor´en, M.J. Chapman, R.M. Krauss, C.J. Packard, J.F. Bentzon, C.J. Binder, et al., Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel, Eur. Heart J. 41 (24) (2020) 2313–2330.

3. A.V. Grechko, E.A. Ivanova, A.N. Orekhov, A.A. Melnichenko, V.A. Myasoedova, Small dense low-density lipoprotein as biomarker for atherosclerotic diseases, Oxid Med Cell Longev (2017) 1–10, 2017.

4. D. Nikolic, N. Katsiki, G. Montalto, E.R. Isenovic, D.P. Mikhailidis, M. Rizzo, Lipoprotein subfractisons in metabolic syndrome and obesity: clinical significance and therapeutic approaches, Nutrients 5 (3) (2013) 928–948.

5. S. Tani, T. Yagi, W. Atsumi, K. Kawauchi, R. Matsuo, A. Hirayama, Relation between low-density lipoprotein cholesterol/apolipoprotein B ratio and triglyceride-rich lipoproteins in patients with coronary artery disease and type 2 diabetes mellitus: a cross-sectional study, Cardiovasc.Diabetol. 16 (1) (2017) 1–13.

6. T. Hirano, Y. Ito, G. Yoshino, Measurement of small dense low-density lipoprotein particles, J. Atherosclerosis Thromb. 12 (2) (2005) 67–72.

7. C.H. Kwon, B.J. Kim, B.S. Kim, J.H. Kang, Low-density lipoprotein cholesterol to apolipoprotein B ratio is independently associated with metabolic syndrome in Korean men, Metabolism 60 (8) (2011) 1136–1141.

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