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  • Clinical Research
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Relationships between leptin and C-reactive protein with cardiovascular disease in the adult general population

Nature Clinical Practice Cardiovascular Medicine volume 5, pages 418–425 (2008)Cite this article

Abstract

Background Leptin could be a key regulator of C-reactive protein (CRP) levels, which serve as a marker of systemic inflammation. Both leptin and CRP are predictors of cardiovascular disease (CVD). However, the interactions between leptin and CRP, and their association with CVD, remain unclear. We therefore studied them in a large, multiethnic population.

Methods We analyzed leptin and CRP levels, anthropometric variables and cardiovascular risk factor data from 6,251 participants from the Third National Health and Nutrition Examination Survey (NHANES III). Logistic regression was used to estimate the association between leptin, CRP and CVD (defined as history of myocardial infarction or stroke). Receiver operating characteristic curves were created to study the additional value of leptin and CRP for the association with CVD.

Results The mean age was 44.4 ± 0.21 years (52.5% women). After adjustment for age, race, dyslipidemia, hypertension, diabetes, smoking, obesity and CRP, high levels of leptin were significantly associated with CVD in men (odds ratio 2.47, 95% CI 1.19–5.19) and in women (odds ratio 3.30, 95% CI 1.47–7.99). After adjustment for leptin, CRP was not associated with CVD. There was a significant correlation between levels of leptin and CRP (Spearman correlation ρ = 0.22 in men and ρ = 0.32 in women, both P < 0.0001). The area under the curve, representing the association between cardiovascular risk factors and CVD, increased after the addition of high levels of both leptin and CRP together.

Conclusion High leptin levels are independently associated with CVD even after adjustment for CRP; elevated CRP levels are not associated with CVD after adjustment for leptin. However, increased concentrations of both leptin and CRP confer the highest risk for CVD.

Key Points

  • High leptin levels were independently associated with risk of developing CVD, even after adjustment for raised CRP levels

  • Elevated CRP levels were no longer significantly associated with CVD after adjustment for raised leptin levels

  • Individuals with raised concentrations of both leptin and CRP were at the highest risk of developing CVD

  • Women with high levels of leptin might have a higher risk of developing CVD than men, possibly because they have a higher proportion of body fat

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Figure 1: Sex-specific odds ratios for the association between cardiovascular disease with CRP and leptin levels.
Figure 2: Sex-specific receiver operating characteristic curves for the association between cardiovascular risk factors.

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Acknowledgements

A Romero-Corral is supported by a Postdoctoral Fellowship from the American Heart Association. J Sierra-Johnson is supported by faculty funds from the Board of Post-Graduate Education of the Karolinska Institute (KID Award), the Swedish Heart and Lung Foundation and by the European Foundation for the Study of Diabetes through a Research Fellowship. F Lopez-Jimenez is the recipient of a Clinical Scientist Development Award from the American Heart Association. P Singh is supported by a Postdoctoral Fellowship from the American Heart Association. M Hoffman is supported by a Pickwick grant from the National Sleep Foundation. A Okcay is supported by NIH grant DK07897-08. VK Somers is supported by NIH grants HL-65176, HL-70302, HL-73211 and M01-RR00585.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Mayo Foundation, 200 First Street SW, Rochester, 55905, MN, USA

    Abel Romero-Corral, Justo Sierra-Johnson, Francisco Lopez-Jimenez, Randal J Thomas, Prachi Singh, Michal Hoffmann, Aynur Okcay, Josef Korinek, Robert Wolk & Virend K Somers

  2. Department of Medicine, Atherosclerosis Research Unit, Karolinska Institutet, SE-171 77, Stockholm, Sweden

    Justo Sierra-Johnson

  3. Cardiovascular/Metabolic Diseases Division, Pfizer Global Research & Development, Pfizer Inc., 558 Eastern Point Road, Groton, 06340-5109, CT, USA

    Robert Wolk

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Correspondence to Virend K Somers.

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Competing interests

A Romero-Corral is funded by Select Research Ltd. He is also a consultant for this company

VK Somers is funded by Select Research Ltd.

F Lopez-Jimenez is funded by Select Research Ltd.

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Romero-Corral, A., Sierra-Johnson, J., Lopez-Jimenez, F. et al. Relationships between leptin and C-reactive protein with cardiovascular disease in the adult general population. Nat Rev Cardiol 5, 418–425 (2008). https://doi.org/10.1038/ncpcardio1218

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