Based on a recent study of an 'apparently healthy' and non-metabolic syndrome population, the following cut-offs have been defined for
- A cut-off of <60 U/L defines a population with a low relative risk of developing metabolic syndrome,
- A range of 60 to 69 U/L defines a population with a moderate relative risk (2.8 fold) and
- Levels equal or greater than 70 U/L defines a population with a high relative risk (3.5-fold).
Metabolic syndrome (MetS) represents a cluster of risk factors for cardiovascular disease (CVD), defined by the presence of ≥3 of the following 5 physiological risk factors:
- increased waist circumference,
- elevated blood pressure,
- low HDL cholesterol,
- elevated triglycerides,
- and elevated glucose.
Despite established diagnostic and treatment guidelines for MetS, the clinical evidence guiding the use of markers to predict MetS onset is still evolving.
One potential marker of MetS risk is oxidized LDL (oxLDL), which is formed when oxidative stress leads to modification of the apoB subunit on LDL cholesterol (LDL). Conversion of LDL to oxLDL appears to be an important event that helps initiate and accelerate the development of early atherosclerotic lesions, or fatty streaks. Cardiovascular sequelae of elevated oxLDL include coronary artery disease, acute myocardial infarction, stable and unstable angina, and untreated overt hypothyroidism. In a cross-sectional study of 3,987 non-diabetic individuals without symptoms of atherosclerosis, elevated oxLDL was strongly associated with prevalent MetS: odds ratios for the highest quartile ranged from 2.57 (95% CI 1.66-4.04) to 3.36 (95% CI 2.33-4.91), depending on which variables were adjusted for.
Measurement of oxLDL can also help in assessing the risk of MetS. A prospective, longitudinal study looked at oxLDL levels in 1,367 initially healthy adults in Finland. Individuals with elevated baseline oxLDL levels were more likely to develop MetS at 6-year follow-up, after adjusting for age, sex, smoking status, insulin resistance, body mass index, and C-reactive protein; however, the trend was not significant after also adjusting for apoB.
Similar findings were reported in another prospective, longitudinal study of 1,889 initially healthy adults in the United States. At 5-year follow-up, individuals in the highest quintile of oxLDL at baseline had 3.5 times the risk of developing MetS compared to those in the lowest quintile; individuals in the fourth quintile were at moderate risk (OR=2.8) for MetS.
- Holvoet et al. JAMA. 2008; 299: 2287-2293 [L]
- Moore JX, Chaudhary N, Akinyemiju T. Metabolic syndrome prevalence by race/ethnicity and sex in the United States, National Health and Nutrition Examination Survey, 1988-2012. Prev Chronic Dis. 2017;14:4-5.
- 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. 2018:25709.
- Srikanthan K, Feyh A, Visweshwar H, et al. Systematic review of metabolic syndrome biomarkers: a panel for early detection, management, and risk stratification in the West Virginian population. Int J Med Sci. 2016;13:25-38.
- Gruzdeva O, Uchasova E, Dyleva Y, et al. Multivessel coronary artery disease, free fatty acids, oxidized LDL and its antibody in myocardial infarction. Lipids Health Dis. 2014;13:111.
- Salvayre R, Negre-Salvayre A, Camaré C. Oxidative theory of atherosclerosis and antioxidants. Biochimie. 2016;125:281-296.
- Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272:20963-20966.
- Oge A, Sozmen E, Karaoglu AO. Effect of thyroid function on LDL oxidation in hypothyroidism and hyperthyroidism. Endocr Res. 2004;30:481-489.
- Hurtado-Roca Y, Bueno H, Fernandez-Ortiz A, et al. Oxidized LDL is associated with metabolic syndrome traits independently of central obesity and insulin resistance. Diabetes. 2017;66:474-482.
- Koskinen J, Magnussen CG, Würtz P, et al. Apolipoprotein B, oxidized low-density lipoprotein, and LDL particle size in predicting the incidence of metabolic syndrome: the Cardiovascular Risk in Young Finns study. Eur J Prev Cardiol. 2012;19:1296-1303.
- Holvoet P, Lee DH, Steffes M, et al. Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA. 2008;299:2287-2293.
- Harmon ME, Campen MJ, Miller C, et al. Associations of circulating oxidized LDL and conventional biomarkers of cardiovascular disease in a cross-sectional study of the Navajo population. PLoS One. 2016;11:e0143102.
Researchers have found that individuals with high levels of oxidized LDL are 4x more likely to develop metabolic syndrome up to five years following testing. In particular, increased oxidized LDL levels were associated with abdominal obesity and high triglyceride levels, as well as high blood glucose. The oxidized LDL test can also help your medical provider decide if you may be at a higher risk for heart attack or heart disease than by looking at traditional risk factors alone. Oxidized LDL may be twice as good at helping your medical provider know your risk for heart disease as any one of the traditional risk factors.
What can you do to help lower your oxidized LDL levels?
- Lifestyle changes are the best option to help lower your oxidized LDL levels.
- If you smoke, ask your medical provider to help you quit. It is not easy but there are programs and strategies (including over-thecounter and prescription medications) that can improve your chance of success.
- Adjust your diet to include foods low in saturated fat and those with zero trans-fat. Fruits and vegetables are also great options as they contain anti-oxidants.
- Talk with your medical provider about over-thecounter supplements containing anti-oxidants.
- Increase your amount of physical activity as approved by your medical provider.
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