European Heart Journal Advance Access originally published online on May 17, 2007
European Heart Journal 2007 28(20):2491-2497; doi:10.1093/eurheartj/ehm115
Circulating concentrations of insulin markers and coronary heart disease: a quantitative review of 19 Western prospective studies
1 Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK
2 University Department of Vascular Biochemistry, Glasgow, Scotland
3 The Icelandic Heart Association, Kopavogur, Iceland
Received 10 October 2006; revised 2 March 2007; accepted 22 March 2007; online publish-ahead-of-print 17 May 2007.
* Corresponding author. Tel: +44 1223 741 302; fax: +44 1223 741 339. E-mail address: karina.prasad{at}phpc.cam.ac.uk
Aims: It is uncertain whether there are associations between circulating levels of insulin markers and coronary heart disease (CHD) risk. We report an updated meta-analysis of studies of circulating levels of three insulin markers (fasting insulin, non-fasting insulin, and pro-insulin) and CHD risk.
Methods and results: Prospective studies based in Western populations that reported on associations between levels of fasting insulin, non-fasting insulin, and pro-insulin and incident CHD [defined as non-fatal myocardial infarction (MI) or coronary death] were identified by computer-based searches and by manual searches of the relevant literature. Nineteen relevant population-based studies were identified, of which 14 reported on fasting insulin levels involving 2649 CHD cases, eight reported on non-fasting insulin levels involving 1980 CHD cases and three reported on pro-insulin levels involving 413 CHD cases. In a comparison of individuals who had circulating levels of each of these markers in the top third with those in the bottom third of the population, the odds ratio for CHD was 1.12 [95% confidence interval (CI): 0.98–1.28] for raised fasting insulin, 1.35 (1.14–1.60) for raised non-fasting insulin, and 2.23 (1.65–3.00) for raised pro-insulin. There was no good evidence of heterogeneity in these estimates attributable to the several study characteristics recorded, including sex, assay methods used, or degree of adjustment of risk estimates, but the available data in many of these subgroups, particularly by sex, are sparse.
Conclusion: Associations between CHD risk and fasting or non-fasting insulin levels are likely to be more modest than previously suspected. Preliminary data suggest that pro-insulin levels may be more strongly associated with CHD risk than are insulin levels, and this possibility should be evaluated in larger and more rigorous studies.
Key Words: Insulin • Pro-insulin • Coronary disease • Meta-analysis
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