Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Reply
  • Published:

Statins for primary prevention: problems with cardiovascular-risk estimation?

Nature Reviews Cardiology volume 10, page 547 (2013)Cite this article

Subjects

I thank Yu-li Huang, Yi Huang, and Yan-xian Wu for their correspondence (Statins for primary prevention: identifying low-risk individuals. Nat. Rev. Cardiol. doi:10.1038/nrcardio.2013.80-c1)1 on my Review (Statins in the primary prevention of cardiovascular disease. Nat. Rev. Cardiol. doi:10.1038/nrcardio.2013.80).2 Huang and colleagues raise some interesting questions. I am glad that they agree that the use of statins for primary prevention in high-risk individuals is undoubtedly beneficial, and that the use of these drugs in low-risk individuals is still controversial. Risk estimation was not the main topic of the Review; nevertheless, in their correspondence, Huang et al. suggest that additional risk-stratification options are needed to guide the use of statins in low-risk individuals. They propose that the level of C-reactive protein measured by high-sensitivity assay (hs-CRP) and the coronary artery calcium (CAC) score might be used to improve risk assessment in these individuals.

Total-cholesterol and LDL-cholesterol levels are associated with cardiovascular disease (CVD) risk in an independent and incremental manner and, therefore, lowering of the LDL-cholesterol level is the primary objective of dyslipidaemia management.3 These parameters also fulfil all the criteria for causality. The HDL-cholesterol level can also contribute substantially to risk estimation,4 whereas other markers of lipid risk, such as the triglyceride and lipoprotein(a) levels, and some other biomarkers of CVD, do not.5,6,7,8 Even less useful for risk estimation is the hs-CRP level, which is associated with CVD risk, but also with death from several types of cancer and lung disease. The pathophysiological relevance of CRP to such a broad range of diseases is unclear.9 The association between the hs-CRP level and CVD has been shown to depend considerably on conventional CVD risk factors and other markers of inflammation. A lack of both specificity and a dose–effect or causality relationship exists between hs-CRP level and CVD risk. Therefore, the authors of the latest European guidelines on CVD prevention recommend that the hs-CRP level can be measured as a part of refined risk assessment only in patients with an unusual or moderate CVD risk profile, and even this recommendation is classified as class IIb, level of evidence B, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) quality of evidence 'weak'.10 Additionally, because of the previously mentioned shortcomings, the authors of the guidelines clearly recommend that the hs-CRP level should not be measured in asymptomatic, low-risk individuals or high-risk patients to assess 10-year risk of CVD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Huang, Y.-l., Huang, Y. & Wu, Y.-x. Statins for primary prevention in individuals at low cardiovascular risk. Nat. Rev. Cardiol. http://dx.doi.org/10.1038/nrcardio.2013.80-c1.

  2. Reiner, Ž. Statins in the primary prevention of cardiovascular disease. Nat. Rev. Cardiol. http://dx.doi.org/10.1038/nrcardio.2013.80.

  3. Graham, I., Cooney, M. T., Bradley, D., Dudina, A. & Reiner, Ž. Dyslipidemias in the prevention of cardiovascular disease: risks and causality. Curr. Cardiol. Rep. 14, 709–720 (2012).

    Article  Google Scholar 

  4. Reiner, Ž. et al. ESC/EAS guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur. Heart J. 32, 1769–1818 (2011).

    Article  Google Scholar 

  5. Chapman, M. J. et al. for the European Atherosclerosis Society Consensus Panel. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur. Heart J. 332, 1345–1361 (2010).

    Google Scholar 

  6. Nordestgaard, B. G. et al. for the European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur. Heart J. 23, 2844–2853 (2010).

    Article  Google Scholar 

  7. Zannad, F. et al. Prevention of cardiovascular disease guided by total risk estimations—challenges and opportunities for practical implementation: highlights of a CardioVascular Clinical Trialists (CVCT) Workshop of the ESC Working Group on CardioVascular Pharmacology and Drug Therapy. Eur. J. Prev. Cardiol. 19, 1454–1464 (2012).

    Article  Google Scholar 

  8. Zannad, F. et al. Risk stratification in cardiovascular disease primary prevention—scoring systems, novel markers, and imaging techniques. Fundam. Clin. Pharmacol. 26, 163–174 (2012).

    Article  CAS  Google Scholar 

  9. Kaptoge, S. et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375, 132–140 (2010).

    Article  Google Scholar 

  10. Perk, J. et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur. Heart J. 33, 1635–1701 (2012).

    Article  CAS  Google Scholar 

  11. Graham, I. et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Eur. Heart J. 28, 2375–2414 (2007).

    Article  Google Scholar 

  12. Grundy, S. M. et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110, 227–239 (2004).

    Article  Google Scholar 

  13. van Werkhoven, J. M. et al. Multislice computed tomography coronary angiography for risk stratification in patients with an intermediate pretest likelihood. Heart 95, 1607–1611 (2009).

    Article  CAS  Google Scholar 

  14. Perrone-Filardi, P. et al. Cardiac computed tomography and myocardial perfusion scintigraphy for risk stratification in asymptomatic individuals without known cardiovascular disease: a position statement of the Working Group on Nuclear Cardiology and Cardiac CT of the European Society of Cardiology. Eur. Heart J. 32, 1986–1993 (2011).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Kispaticeva 12, Zagreb, 10000, Croatia

    Željko Reiner

Authors
  1. Željko Reiner
    View author publications

    Search author on:PubMed Google Scholar

Ethics declarations

Competing interests

The author declares that he has received honoraria from the following companies: Abbot, AstraZeneca, Bayer, and Sanofi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reiner, Ž. Statins for primary prevention: problems with cardiovascular-risk estimation?. Nat Rev Cardiol 10, 547 (2013). https://doi.org/10.1038/nrcardio.2013.80-c2

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/nrcardio.2013.80-c2

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing