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.

  • Original Article
  • Published:

Impact of the metabolic syndrome on the predictive values of new risk markers in the general population

Journal of Human Hypertension volume 22, pages 634–640 (2008)Cite this article

Abstract

Although the metabolic syndrome (MetS) is positively associated with high-sensitivity C-reactive protein (hsCRP), negatively associated with N-terminal pro-brain natriuretic peptide (Nt-proBNP) and inconsequently related to urine albumin/creatinine ratio (UACR) they are all associated with cardiovascular events. Therefore, we wanted to determine the influence of MetS on the predictive values of UACR, hsCRP and Nt-proBNP. On the basis of the definition of MetS by the International Diabetes Federation, a Danish population sample of 1983 apparently healthy subjects was divided into three groups: 530 subjects without any elements of MetS, 1093 subjects with some elements of MetS and 360 subjects with MetS. During the following 9.5 years the composite end point of cardiovascular death, non-fatal myocardial infarction or stroke (composite cardiovascular end point, CEP) occurred in 204 subjects. In Cox-regression analyses adjusting for age, gender and smoking, all three cardiovascular risk markers predicted CEP independently of MetS. Despite no significant interaction with MetS, high log(hsCRP) was associated with CEP primarily in subjects without any elements of MetS (hazard ratio (HR)=4.5 (1.5–14.0), P<0.01), log(Nt-proBNP) primarily in subjects with some elements of MetS (HR=3.0 (1.6–5.6), P<0.01), and logUACR independently of elements of MetS. Pre-specified gender-adjusted (men/women) cutoff values of hsCRP⩾6.0/7.3 mg l−1 predicted CEP in subjects without elements of MetS with positive and predictive values of 11.5 and 98%, respectively. UACR⩾0.73/1.06 mg mmol−1 predicted CEP in subjects with MetS with positive and predictive values of 23.5 and 93%, respectively. In apparently healthy subjects, high hsCRP was associated with CEP primarily in subjects without MetS, high Nt-proBNP in subjects with elements of MetS and UACR independently of MetS.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Olsen MH, Christensen MK, Hansen TW, Gustafsson F, Rasmussen S, Wachtell K et al. High-sensitivity C-reactive protein is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors. J Hypertens 2006; 24: 655–661.

    Article  CAS  Google Scholar 

  2. Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K et al. N-terminal pro brain natriuretic peptide is inversely related to metabolic cardiovascular risk factors and the metabolic syndrome. Hypertension 2005; 46: 660–666.

    Article  CAS  Google Scholar 

  3. Ingelsson E, Sullivan LM, Murabito JM, Fox CS, Benjamin EJ, Polak JF et al. Prevalence and prognostic impact of subclinical cardiovascular disease in individuals with the metabolic syndrome and diabetes. Diabetes 2007; 56: 1718–1726.

    Article  CAS  Google Scholar 

  4. Pedrinelli R, Dell'Omo G, Penno G, Di BV, Giorgi D, Pellegrini G et al. Microalbuminuria, a parameter independent of metabolic influences in hypertensive men. J Hypertens 2003; 21: 1163–1169.

    Article  CAS  Google Scholar 

  5. Ridker PM, Hennekens CH, Buring JE, Rifai N . C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836–843.

    Article  CAS  Google Scholar 

  6. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR . Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347: 1557–1565.

    Article  CAS  Google Scholar 

  7. Kistorp C, Raymond I, Pedersen F, Gustafsson F, Faber J, Hildebrandt P . N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA 2005; 293: 1609–1616.

    Article  CAS  Google Scholar 

  8. Borch-Johnsen K, Feldt-Rasmussen B, Strandgaard S, Schroll M, Jensen JS . Urinary albumin excretion. An independent predictor of ischemic heart disease. Arterioscler Thromb Vasc Biol 1999; 19: 1992–1997.

    Article  CAS  Google Scholar 

  9. de SG, Olsen MH, Wachtell K, Hille DA, Dahlof B, Ibsen H et al. Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study. J Hum Hypertens 2007; 21: 625–632.

    Article  Google Scholar 

  10. Aguilar D, Fisher MR, O'Connor CM, Dunne MW, Muhlestein JB, Yao L et al. Metabolic syndrome, C-reactive protein, and prognosis in patients with established coronary artery disease. Am Heart J 2006; 152: 298–304.

    Article  CAS  Google Scholar 

  11. Pickup JC, Mattock MB, Chusney GD, Burt D . NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997; 40: 1286–1292.

    Article  CAS  Google Scholar 

  12. Hak AE, Pols HA, Stehouwer CD, Meijer J, Kiliaan AJ, Hofman A et al. Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam Study. J Clin Endocrinol Metab 2001; 86: 4398–4405.

    Article  CAS  Google Scholar 

  13. Festa A, D'Agostino Jr R, Tracy RP, Haffner SM . Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 2002; 51: 1131–1137.

    Article  CAS  Google Scholar 

  14. Festa A, D'Agostino R, Howard G, Mykkanen L, Tracy RP, Haffner SM . Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study. Kidney Int 2000; 58: 1703–1710.

    Article  CAS  Google Scholar 

  15. Pannacciulli N, Cantatore FP, Minenna A, Bellacicco M, Giorgino R, De Pergola G . Urinary albumin excretion is independently associated with C-reactive protein levels in overweight and obese nondiabetic premenopausal women. J Intern Med 2001; 250: 502–507.

    Article  CAS  Google Scholar 

  16. Olsen MH, Wachtell K, Tuxen C, Fossum E, Bang LE, Hall C et al. N-terminal pro-brain natriuretic peptide predicts cardiovascular events in patients with hypertension and left ventricular hypertrophy: a LIFE study. J Hypertens 2004; 22: 1597–1604.

    Article  CAS  Google Scholar 

  17. Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K et al. N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population. Eur Heart J 2007; 28: 1374–1381.

    Article  CAS  Google Scholar 

  18. Drivsholm T, Ibsen H, Schroll M, Davidsen M, Borch-Johnsen K . Increasing prevalence of diabetes mellitus and impaired glucose tolerance among 60-year-old Danes. Diabet Med 2001; 18: 126–132.

    Article  CAS  Google Scholar 

  19. Guerrero-Romero F, Rodriguez-Moran M . Concordance between the 2005 International Diabetes Federation definition for diagnosing metabolic syndrome with the National Cholesterol Education Program Adult Treatment Panel III and the World Health Organization definitions. Diabetes Care 2005; 28: 2588–2589.

    Article  Google Scholar 

  20. Madsen M, Davidsen M, Rasmussen S, Abildstrom SZ, Osler M . The validity of the diagnosis of acute myocardial infarction in routine statistics: a comparison of mortality and hospital discharge data with the Danish MONICA registry. J Clin Epidemiol 2003; 56: 124–130.

    Article  Google Scholar 

  21. Yeo KT, Wu AH, Apple FS, Kroll MH, Christenson RH, Lewandrowski KB et al. Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite Triage BNP assay. Clin Chim Acta 2003; 338: 107–115.

    Article  CAS  Google Scholar 

  22. Rowe DJ, Dawnay A, Watts GF . Microalbuminuria in diabetes mellitus: review and recommendations for the measurement of albumin in urine. Ann Clin Biochem 1990; 27: 297–312.

    Article  CAS  Google Scholar 

  23. Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K et al. Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex. J Hypertens 2008; 26: 26–34.

    Article  CAS  Google Scholar 

  24. Tamura K, Takahashi N, Nakatani Y, Onishi S, Iwasaka T . Prognostic impact of plasma brain natriuretic peptide for cardiac events in elderly patients with congestive heart failure. Gerontology 2001; 47: 46–51.

    Article  CAS  Google Scholar 

  25. de Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001; 345: 1014–1021.

    Article  CAS  Google Scholar 

  26. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 2004; 350: 655–663.

    Article  CAS  Google Scholar 

  27. Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH . Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes 2002; 51: 1157–1165.

    Article  CAS  Google Scholar 

  28. McLenachan JM, Williams JK, Fish RD, Ganz P, Selwyn AP . Loss of flow-mediated endothelium-dependent dilation occurs early in the development of atherosclerosis. Circulation 1991; 84: 1273–1278.

    Article  CAS  Google Scholar 

  29. Mykkanen L, Zaccaro DJ, O'Leary DH, Howard G, Robbins DC, Haffner SM . Microalbuminuria and carotid artery intima-media thickness in nondiabetic and NIDDM subjects. The Insulin Resistance Atherosclerosis Study (IRAS). Stroke 1997; 28: 1710–1716.

    Article  CAS  Google Scholar 

  30. Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE et al. Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study. Diabetes Care 2006; 29: 595–600.

    Article  CAS  Google Scholar 

  31. Ridker PM, Cook N . Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores. Circulation 2004; 109: 1955–1959.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Center for Prevention and Health, Glostrup University Hospital, Copenhagen, Denmark

    M H Olsen, T W Hansen & S Rasmussen

  2. Department of Internal Medicine, Glostrup University Hospital, Copenhagen, Denmark

    M H Olsen

  3. Department of Clinical Physiology and Nuclear Medicine, Glostrup University Hospital, Copenhagen, Denmark

    M K Christensen

  4. Department of Cardiology, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark

    F Gustafsson & K Wachtell

  5. Department of Internal Medicine, Holbæk Hospital, Holbæk, Denmark

    H Ibsen

  6. Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark

    C Torp-Pedersen

  7. Department of Cardiology, Roskilde University Hospital, Roskilde, Denmark

    P R Hildebrandt

Authors
  1. M H Olsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T W Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M K Christensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F Gustafsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Rasmussen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K Wachtell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Ibsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Torp-Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P R Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M H Olsen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Olsen, M., Hansen, T., Christensen, M. et al. Impact of the metabolic syndrome on the predictive values of new risk markers in the general population. J Hum Hypertens 22, 634–640 (2008). https://doi.org/10.1038/jhh.2008.40

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2008.40

Keywords

Search

Advanced search

Quick links