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Meta-Analysis
. 2010 May 25;7(5):e1000278.
doi: 10.1371/journal.pmed.1000278.

Markers of dysglycaemia and risk of coronary heart disease in people without diabetes: Reykjavik prospective study and systematic review

Nadeem Sarwar  1 , Thor Aspelund, Gudny Eiriksdottir, Reeta Gobin, Sreenivasa Rao Kondapally Seshasai, Nita G Forouhi, Gunnar Sigurdsson, John Danesh, Vilmundur Gudnason
Affiliations
Meta-Analysis

Markers of dysglycaemia and risk of coronary heart disease in people without diabetes: Reykjavik prospective study and systematic review

Nadeem Sarwar et al. PLoS Med. .

Abstract

Background: Associations between circulating markers of dysglycaemia and coronary heart disease (CHD) risk in people without diabetes have not been reliably characterised. We report new data from a prospective study and a systematic review to help quantify these associations.

Methods and findings: Fasting and post-load glucose levels were measured in 18,569 participants in the population-based Reykjavik study, yielding 4,664 incident CHD outcomes during 23.5 y of mean follow-up. In people with no known history of diabetes at the baseline survey, the hazard ratio (HR) for CHD, adjusted for several conventional risk factors, was 2.37 (95% CI 1.79-3.14) in individuals with fasting glucose > or = 7.0 mmol/l compared to those < 7 mmol/l. At fasting glucose values below 7 mmol/l, adjusted HRs were 0.95 (0.89-1.01) per 1 mmol/l higher fasting glucose and 1.03 (1.01-1.05) per 1 mmol/l higher post-load glucose. HRs for CHD risk were generally modest and nonsignificant across tenths of glucose values below 7 mmol/l. We did a meta-analysis of 26 additional relevant prospective studies identified in a systematic review of Western cohort studies that recorded fasting glucose, post-load glucose, or glycated haemoglobin (HbA(1c)) levels. In this combined analysis, in which participants with a self-reported history of diabetes and/or fasting blood glucose > or = 7 mmol/l at baseline were excluded, relative risks for CHD, adjusted for several conventional risk factors, were: 1.06 (1.00-1.12) per 1 mmol/l higher fasting glucose (23 cohorts, 10,808 cases, 255,171 participants); 1.05 (1.03-1.07) per 1 mmol/l higher post-load glucose (15 cohorts, 12,652 cases, 102,382 participants); and 1.20 (1.10-1.31) per 1% higher HbA(1c) (9 cohorts, 1639 cases, 49,099 participants).

Conclusions: In the Reykjavik Study and a meta-analysis of other Western prospective studies, fasting and post-load glucose levels were modestly associated with CHD risk in people without diabetes. The meta-analysis suggested a somewhat stronger association between HbA(1c) levels and CHD risk.

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Conflict of interest statement

JD has received research funding from the British Heart Foundation, BUPA Foundation, Denka, diaDexus, European Union, Evelyn Trust, GlaxoSmithKline MRC, Merck, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, Novartis, Pfizer, Roche, Wellcome Trust and UK Biobank. John Danesh is on the Editorial Board of </emph type="italic">PLoS Medicine</emph>.

Figures

Figure 1
Figure 1. Risk of CHD across tenths of baseline fasting glucose levels in the Reykjavik Study.
All hazard ratios are adjusted for age, sex, recruitment period, smoking status, systolic blood pressure, total cholesterol, and BMI, and all are compared to individuals in the middle tenth of the distribution. The grey area denotes the 95% CI of the reference group. Analyses involved the full range of glucose values (i.e., including individuals with glucose levels in the diabetic range). To limit any bias related to having a diagnosis of diabetes (e.g., medication use, lifestyle changes), however, individuals with a known history of diabetes at the baseline survey were excluded.
Figure 2
Figure 2. Risk of CHD across tenths of baseline 1 h post-load glucose levels in the Reykjavik Study.
All hazard ratios are adjusted for age, sex, recruitment period, smoking status, systolic blood pressure, total cholesterol, and BMI, and all are compared to individuals in the middle tenth of the distribution. The grey area denotes the 95% CI of the reference group. Analyses involved the full range of glucose values (i.e., including individuals with glucose levels in the diabetic range). To limit any bias related to having a diagnosis of diabetes (e.g., medication use, lifestyle changes), however, individuals with a known history of diabetes at the baseline survey were excluded.
Figure 3
Figure 3. Prospective studies of markers of dysglycaemia and CHD risk in individuals without diabetes in Western populations.
Analyses were restricted to individuals who did not have a self-reported history of type 2 diabetes or had a fasting blood glucose <7.0 mmol/l at baseline. Risk estimates are presented per 1 mmol/l higher fasting and post-load glucose, and per 1% higher HbA1c. Abbreviations as listed in Table S2.
Figure 4
Figure 4. Prospective studies of fasting and post-load glucose and CHD risk in individuals without diabetes in Western population, grouped by study characteristics.
Meta-regression analyses separately considered each characteristic presented. *Assessed as continuous factors.
See this image and copyright information in PMC

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