Fructosamine is a risk factor for myocardial infarction and all-cause mortality – Longitudinal experience from the AMORIS cohort

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Highlights

  • Fructosamine measures glycation, an alternative to established diabetes biomarkers.

  • High fructosamine values were strongly associated with risk of MI and death.

  • The association was controlled for major CVD risk factors and remained.

  • Fructosamine was effective above the effects of glucose for the risk of MI.

  • Similar associations as for fructosamine were found by using HbA1c as predictor.

Abstract

Background and aims

Glycation is linked to microvascular complications of diabetes and also to macrovascular events. Fructosamine is a biomarker of glycation but its associations to macrovascular complications are not well documented. The aim of this study was to evaluate fructosamine as a predictor of myocardial infarction and all-cause mortality in a large population based cohort.

Methods and results

Information on glucose and fructosamine was obtained from subjects of the AMORIS cohort (n = 338,443) followed for 19 years on average. Incident cases of myocardial infarction and death from any cause were identified from national patient and cause of death register respectively. The incidence of myocardial infarction (n = 21,526 cases) and all-cause mortality (n = 73,458 deaths) increased at a fructosamine of 2.30 mmol/L or above. For myocardial infarction, the sex-age- fasting- and entry period adjusted hazard ratio in subjects above 2.70 mmol/L vs. reference range subjects was 2.88 (95% CI: 2.70–3.07). The corresponding hazard ratio for all-cause mortality was 2.31 (95% CI: 2.21–2.41). These associations remained basically unchanged after adjustment for total cholesterol, triglycerides, albumin, social class, smoking and hypertension. When additional adjustment for glucose was performed the associations were attenuated but remained. In a sub cohort with simultaneous measurements of fructosamine, HbA1c and fasting glucose respectively similar associations were observed (n = 9746).

Conclusion

There is a strong association between fructosamine and myocardial infarction and death from any cause when major cardiovascular risk factors are accounted for. In addition, this association could only partly be explained by glucose levels.

Introduction

Elevated fasting glucose is associated with an increased risk of myocardial infarction (MI) and cardiovascular death [1], [2], [3], [4]. Fasting plasma glucose and HbA1c are established indicators of glucose status and control while fructosamine is rarely used in clinical or research settings. Fructosamine reflects the average glucose level during the preceding 1–3 weeks [5], [6], [7]. The analytical method is simple, robust and inexpensive and can potentially be useful in risk prediction of micro- and macrovascular diseases either on its own or in combination with glucose and HbA1c. In the AMORIS (Apolipoprotein-related MOrtality RISk) cohort we have recently reported strong associations between fructosamine, glucose and HbA1c both cross-sectionally and longitudinally [8]. Furthermore, in the ARIC study [5] as well as in the KIHD study [9] fructosamine has been shown to predict incident diabetes. In addition, the ARIC study also showed associations of fructosamine and microvascular complications of diabetes [5], [10]. However, little is known about fructosamine as a risk predictor of macrovascular complications in long-term prospective studies with hard endpoints [11], [12]. The aim of this study was to evaluate if levels of fructosamine in the general population are associated with the incidence of MI and all-cause mortality respectively. We also evaluated possible differences between fructosamine, HbA1c and fasting glucose with respect to risk association for these endpoints.

Section snippets

Study population

The study included subjects of the Swedish AMORIS cohort described previously [13], [14], [15]. None of the subjects, 178,947 men and 159,496 women, were inpatient at baseline. Blood samples were obtained during 1985–1996 through routine health check-ups or primary care. Repeated blood sampling was performed in 44% of the subjects, e.g. through annual routine health check-ups. Subjects were 30 years or more at the index examination and had fructosamine, glucose, total cholesterol, triglycerides

General characteristics of the study population

The characteristics for the full cohort are summarized in Table 1. A total of 149,817 subjects (44%), mean age about 50 years, had repeated measurements of the biomarkers. Subjects were followed for up to 26 years with a mean follow-up time of 19 years. There were 21,526 events of MI during the follow-up period of which 18,792 non-fatal and 2734 fatal cases. The total number of deaths during the study period was 73,458. In the subset from 3178 subjects with data on smoking and hypertension

Discussion

Our findings show that elevated fructosamine levels are positively associated with the incidence of myocardial infarction (MI) and all-cause mortality. These associations are similar to those obtained by using the conventional HbA1c as a risk predictor. The new findings for fructosamine are based on a very large unselected study population with a wide range of fructosamine levels followed for a long period of time. Hence, fructosamine can be used to predict not only microvascular diseases as

Acknowledgment

We thank the principal investigators; Professor Lars Alfredsson and Professor Peter Westerholm (WOLF study (Work, Lipids and Fibrinogen)), Professor Alicija Wolk (COSM,SMC cohorts) and Professor Mai-Lis Hellenius (Sollentuna Primary Prevention Study) for generously sharing information regarding smoking, blood pressure and self-reported hypertension for the present study. This work was supported by the Jungner Foundation for Laboratory Medicine, Stockholm, Sweden [Dnr.1118/12-1]. The funder had

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