Are we ready to use oxidative stress in clinical practice?

Authors

  • Marcin Grabowski

    Corresponding author
    1. 1st Department of Cardiology, Medical University of Warsaw, Central University Hospital, Warsaw, Poland
    • 1st Department of Cardiology, Medical University of Warsaw, Central University Hospital, 1a Banacha St., 02 097 Warsaw, Poland Fax: +48 22 599 19 57
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Abstract

See accompanying article http://dx.doi.org/10.1002/ejlt.201200107

The relationship between atherosclerosis, intravascular inflammation, and oxidative stress has fascinated scientists and clinicians for a long time and is still the subject of continuing research. The hypothesis is very attractive, both from the pathophysiological and therapeutic point of view and has perspective for new therapeutic strategies.

Abbreviations:

HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; ox-LDL, oxidized LDL; sd-LDL, small dense LDL; TC, total cholesterol

One unresolved issue is the choice of a method that would allow a reliable assessment of the severity of these conditions, a method which could be applied in clinical practice for early detection of high-risk populations and further to guide the therapy. Existing data in this issue is so inadequate that the current guidelines on dyslipidaemias for cardiovascular screening, characterization of dyslipidaemias, and elevation of treatment effectiveness primarily recommend the use of basic lipid parameters such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglyceride (Table 1). Experts recommend to determine the levels of apolipoprotein B100 (apoB100) and non-HDL cholesterol, but this could be justified mainly in patients with evidence of insulin resistance 1. Thus, the question about the potential lipid parameters for further risk and treatment efficacy assessment, especially in patients with significant atherosclerosis who achieved primary therapeutic targets remains open.

Table 1. Recommendations for lipid analyses for screening for cardiovascular disease risk, characterization of dyslipidaemias before treatment and as treatment target in the prevention of cardiovascular disease 1
 Class of recommendation
Screening for CVD riskCharacterization of dyslipidaemias before treatmentTreatment target in the prevention of CVD
  1. Class of recommendation: I – recommended to be used; IIa – should be considered/recommended; IIb – may be considered; III – not recommended. Apo – apolipoprotein; CVD – cardiovascular disease; HDL-C – high-density lipoprotein-cholesterol; LDL-C – low-density lipoprotein-cholesterol; Lp – lipoprotein; TC – total cholesterol; TG – triglyceride.

TCIIIbIIa
LDL-CIII
TGIIIIa
HDL-CIIIII
Non-HDL-CIIaIIaIIa
Lp(a)IIaIIa
Apo BIIaIIaIIa
Apo B/Apo A1 ratioIIbIII
Non-HDL-C/HDL-C ratioIIbIII

From the perspective of biochemical and clinical practice, applying the TC/apoB100 ratio is an interesting option

The article by Burchardt et al. 2, published in the last issue (114/12) of European Journal of Lipid Science and Technology, is a continuation of previously published results and supports further research on lipids and lipoproteins in an interesting subpopulation of patients already under the treatment with hypolipidemic agents 2, 3. The authors hypothesize that in patients with LDL-C <100 mg/dl, TC/apoB100 ratio might give additional information for cardiovascular risk. According to their assumptions, low TC/apoB100 ratio presumably reflects a greater vulnerability of plasma lipoproteins to oxidative modification. This might characterize patients with significant coronary artery stenosis with LDL-C levels <100 mg/dl on statin treatment contrary to those without significant changes in the vessels with comparable TC and LDL-C. To prove this concept, the authors investigated and finally found a relationship between TC/apoB100 and the level of plasma markers of oxidative stress parameters in most examined subgroups excluding subjects on statins with LDL-C levels >100 mg/dl. The hypothesis is original because TC/apoB100 has not been investigated so far in this particular clinical situation, and the previous publications concern patients with familial hypercholesterolaemia 4, 5. There is lack of reports on the relationship of TC/apoB100 with oxidative stress markers; however, a similar ratio (LDL-C/apoB100) has been previously tested in a similar clinical group with stable coronary heart disease 6.

One issue which needs to be discussed is the selection of the parameters used to evaluate the products of oxidation. The choice of the analyzed parameters is probably based on the authors' own experience and intentions, seeking a cheap biochemical method which would be easy to apply in clinical practice and which could be used to monitor the effects of lipid-lowering therapy in high risk patients. To confirm the authors' hypothesis it might be more effective to evaluate the oxidized LDL (ox-LDL) 7, 8. Ox-LDL and small dense LDL (sd-LDL) might be better parameters to monitor the progress of lipid-lowering therapy among subjects achieving therapeutic LDL levels. On the other hand, they are not widely used in clinical practice due to the lack of validated methods to assess these parameters, which is also mentioned by experts in existing guidelines 1. We also should not forget other, “less sophisticated”, biochemical markers of cardiovascular risk with proved antioxidative role such as HDL-C 9, 10, lipoprotein A, 11, C-reactive protein 12, and other lipid parameters 13, 14, although again in accordance with the guidelines they are of limited importance 1. The interpretation of this study should also take into account relatively small population of patients with most severe coronary artery disease – with multivessel disease – where intense and wider risk profile assessment could be reasonable. Furthermore, the authors divide the study population into subgroups of LDL-C <100 and ≥100 mg/dl, although current guidelines in patients with documented cardiovascular disease recently decreased recommended optimal LDL-C to levels below 70 mg/dl 1.

In summary, from the perspective of biochemical and clinical practice, applying the TC/apoB100 ratio is an interesting option and at the current level of knowledge and technology could be an additional tool in cardiovascular risk assessment especially in people on effective statin treatment, with reduced LDL. It seems that, after all, the main effort would be invested to find effective methods for sd-LDL or ox-LDL assessment which not only express increased cardiovascular risk but are also direct exponents of atherogenicity (sd-LDL and ox-LDL) and lipoprotein oxidation (ox-LDL) 15–18. We can expect that the development and validation of methods for effective sd-LDL or ox-LDL evaluation would allow wider use of these markers in the future.

The author has declared no conflict of interest.

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