Abstract
BackgroundAssociations 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 FindingsFasting 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 ≥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 (HbA1c) levels. In this combined analysis, in which participants with a self-reported history of diabetes and/or fasting blood glucose ≥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 HbA1c (9 cohorts, 1639 cases, 49,099 participants).ConclusionsIn 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 HbA1c levels and CHD risk. Please see later in the article for the Editors' Summary
Highlights
Diabetes is an established risk factor for coronary heart disease (CHD)
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
In people who had no history of diabetes at baseline, hazard ratio (HR) for CHD—adjusted for age, sex, recruitment period, smoking status, systolic blood pressure, total cholesterol, and body mass index (BMI) (‘‘adjusted HR’’)—was 2.37 (1.79–3.14) in those with fasting glucose $7.0 mmol/l compared with those,7.0 mmol/l. (HR was 1.67 [1.36–2.02] with fasting glucose $6.1 mmol/l compared with those,6.1 mmol/l, a definition of diabetes proposed for studies involving capillary whole blood samples [39].) In analyses across tenths of fasting glucose values, adjusted HRs for CHD were generally weak and nonsignificant at levels below 7 mmol/l (Figure 1)
Summary
Diabetes is an established risk factor for coronary heart disease (CHD). There is considerable interest in whether circulating markers of glucose metabolism are associated with risk of CHD in people without diabetes. A major goal of diabetes treatment is to keep glucose control as normal as possible through diet, weight control, exercise, and pharmacological treatments It is unclear whether the link between high blood sugar and macrovascular disease (principally heart disease and strokes) holds for people who have slightly higher than normal blood sugar levels, but in whom this level does not reach the diabetic threshold. Some previous research studies have suggested that a continuous relationship exists between blood sugar level and the risk of heart disease across the spectrum, i.e., below the diabetic threshold as well as above it If such a relationship were confirmed this might have important implications for the management of high blood sugar levels even among people who would not normally meet the usual definition for a diagnosis of diabetes (the ‘‘diabetic threshold’’)
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