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Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study

BMJ 2009; 338 doi: https://doi.org/10.1136/bmj.a3083 (Published 09 January 2009) Cite this as: BMJ 2009;338:a3083
  1. Wouter de Ruijter, general practitioner and clinical researcher1,
  2. Rudi G J Westendorp, professor2,
  3. Willem J J Assendelft, professor1,
  4. Wendy P J den Elzen, clinical researcher1,
  5. Anton J M de Craen, senior epidemiologist2,
  6. Saskia le Cessie, statistician3,
  7. Jacobijn Gussekloo, professor1
  1. 1Leiden University Medical Center, Department of Public Health and Primary Care (V0-P), PO Box 9600, 2300 RC Leiden, Netherlands
  2. 2Leiden University Medical Center, Department of Gerontology and Geriatrics (C2-R), PO Box 9600, 2300 RC Leiden, Netherlands
  3. 3Leiden University Medical Center, Department of Medical Statistics (S5-P), PO Box 9600, 2300 RC Leiden, Netherlands
  1. Correspondence to: W de Ruijter w.de_ruijter{at}lumc.nl
  • Accepted 20 October 2008

Abstract

Objectives To investigate the performance of classic risk factors, and of some new biomarkers, in predicting cardiovascular mortality in very old people from the general population with no history of cardiovascular disease.

Design The Leiden 85-plus Study (1997-2004) is an observational prospective cohort study with 5 years of follow-up.

Setting General population of the city of Leiden, the Netherlands.

Participants Population based sample of participants aged 85 years (215 women and 87 men) with no history of cardiovascular disease; no other exclusion criteria.

Main measurements Cause specific mortality was registered during follow-up. All classic risk factors included in the Framingham risk score (sex, systolic blood pressure, total and high density lipoprotein cholesterol, diabetes mellitus, smoking and electrocardiogram based left ventricular hypertrophy), as well as plasma concentrations of the new biomarkers homocysteine, folic acid, C reactive protein, and interleukin 6, were assessed at baseline.

Results During follow-up, 108 of the 302 participants died; 32% (35/108) of deaths were from cardiovascular causes. Classic risk factors did not predict cardiovascular mortality when used in the Framingham risk score (area under receiver operating characteristic curve 0.53, 95% confidence interval 0.42 to 0.63) or in a newly calibrated model (0.53, 0.43 to 0.64). Of the new biomarkers studied, homocysteine had most predictive power (0.65, 0.55 to 0.75). Entering any additional risk factor or combination of factors into the homocysteine prediction model did not increase its discriminative power.

Conclusions In very old people from the general population with no history of cardiovascular disease, concentrations of homocysteine alone can accurately identify those at high risk of cardiovascular mortality, whereas classic risk factors included in the Framingham risk score do not. These preliminary findings warrant validation in a separate cohort.

Footnotes

  • Contributors: WDR analysed and interpreted data, drafted the manuscript, and did statistical analysis. RGJW was responsible for study concept and design, acquisition of data, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, and obtaining funding. WJJA analysed and interpreted data and critically revised the manuscript for important intellectual content. WPJDE acquired, analysed, and interpreted data, drafted the manuscript, and analysed statistics. AJMDC was responsible for study concept and design, acquisition of data, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. SLC analysed and interpreted data, critically revised the manuscript for important intellectual content, and did statistical analysis. JG was responsible for study concept and design, acquisition of data, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, and obtaining funding. JG is guarantor.

  • Funding: The Leiden 85-plus Study was partly funded by an unrestricted grant from the Dutch Ministry of Health, Welfare and Sports. The funder played no role in study design, collection, analysis and interpretation of data, writing of the report, nor in the decision to submit the article for publication.

  • Independence of researchers: All researchers were independent from the funder.

  • Competing interests: None declared.

  • Ethical approval: The medical ethical committee of Leiden University Medical Center approved the study.

  • Provenance and peer review: Not commissioned, externally peer reviewed.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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