BMJ 2003;326:681 ( 29 March )

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Increase in blood glucose concentration during antihypertensive treatment as a predictor of myocardial infarction: population based cohort study

Kristina Dunder, medical doctor, ^a Lars Lind, professor, ^b Björn Zethelius, medical doctor, ^a Lars Berglund, statistician, ^a Hans Lithell, professor. ^a

^a Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, PO Box 609, SE-751 25 Uppsala, Sweden, ^b Department of Medical Sciences, Uppsala University, Akademiska sjukhuset, SE-751 85 Uppsala, Sweden

Correspondence to: K Dunder kristina.dunder{at}pubcare.uu.se

Objective: To investigate the impact of an increase in blood glucose on the risk of developing myocardial infarction, with particular emphasis on people taking antihypertensive drugs.
Design: Prospective population based cohort study.
Setting: Uppsala, Sweden.
Participants: 1860 men who had participated in 1970-3 at age 50 in a health survey aimed at identifying risk factors for cardiovascular disease and were re-examined at age 60 and then followed for 17.4 years.
Main outcome measure: Myocardial infarction after age 60.
Results: The incidence of myocardial infarction was significantly higher in men treated for hypertension than in those without such treatment (23% v 13.5%, P<0.0001). Participants who developed myocardial infarction after the age of 60 (n=253) showed a significantly larger increase in blood glucose between age 50 and 60 than did those without myocardial infarction. In multivariate Cox proportional hazard models increase in blood glucose was an independent risk factor for myocardial infarction (P=0.0001) in men receiving antihypertensive treatment at age 60 (n=291, mainly  blockers and thiazide diuretics) but not in those without such treatment. The impact of increase in blood glucose declined after inclusion of serum proinsulin concentrations at baseline but was still significant. A significant interaction existed between proinsulin concentration (a marker of insulin resistance) at baseline and antihypertensive treatment on increase in blood glucose.
Conclusions: Increase in blood glucose between the ages of 50 and 60 and baseline proinsulin concentration were important risk factors for myocardial infarction in men receiving antihypertensive treatment, indicating that both an insulin resistant state and the metabolic impact of  blockers and diuretics increase the risk of myocardial infarction.

What is already known on this topic Patients with hypertension are resistant to insulin stimulated glucose uptake and are hyperinsulinaemic compared with normotensive controls Treatment with  blockers and thiazide diuretics further increases insulin resistance, thereby increasing the risk of developing type 2 diabetes mellitus or impaired glucose tolerance The influence of metabolic changes induced by antihypertensive treatment on the risk of myocardial infarction has been questioned What this study adds Men who received antihypertensive treatment showed a larger increase in blood glucose during a 10 year period than those without such treatment Increase in blood glucose during antihypertensive treatment was a significant, independent risk factor for myocardial infarction in men with an insulin resistant state at baseline

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© 2003 BMJ Publishing Group Ltd
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