diabetes contributes strongly to the risk of cvd with a risk that is increased four to six times , both for stroke and myocardial infarction .
the increase in risk for myocardial infarction seem to be more pronounced in women than in men .
the prevalence of igt in the general population is 23 times higher than that of previously unknown diabetes , which , in turn , is as common as known diabetes .
patients with impaired glucose tolerance have an increased risk of cvd that is independent of traditional risk factors such as hypertension , smoking and hypercholesterolemia   and it has been suggested that slightly elevated glucose levels , even in the non - diabetic range , might be associated with increased macrovascular disease .
several publications have focused on the relationship between igt and coronary heart disease ( chd ) .
the results have indicated that ethnicity , sex and age might be factors that modify the strength of the risk of chd with impaired glucose tolerance [ 6 - 11 ] .
the aim of the present investigation was to further evaluate the possible relation between igt and chd .
therefore , we examined ecg 's to identify signs of clinically undiagnosed myocardial infarction together with cardiovascular risk factors in a randomly selected population of men and women from northern sweden , a region with an ethnically homogenous population and a high incidence of cardiovascular disease .
this study was performed within the framework of the northern sweden monica project which , in turn , is a part of the who monica project ( monitoring of trends and determinants in cardiovascular disease ) . during january to april 1986 , a population was screened for cardiovascular risk factors .
a total of 2000 individuals in the 25 to 64 year range were invited . within each age group ( 2534 , 3544 , 4554 , 5564 years )
250 men and 250 women were randomly selected from continuously updated population registers in norrbotten and vsterbotten , the two northernmost provinces of sweden .
people who still did not come , were contacted by telephone to ascertain reasons for reluctance to attend and to get basic information on social background and risk factors .
the participants were asked to complete a questionnaire with items on , inter alia , social background , smoking habits , medical history and intake of drugs .
the questionnaire was returned on the site of the survey , which was performed by two mobile teams in local health centres ( or corresponding ) throughout the monica area .
seven hundred ninety subjects from vsterbotten participated in the study ( 79 % of all invited ) .
six hundred seventeen subjects , without known diabetes , underwent a 75 g oral glucose tolerance test ( ogtt ) with measurement of plasma glucose .
anthropometric measurements and biochemical analyses were as previously described . clinically diagnosed myocardial infarction , or known mi ( kmi ) , was defined by a positive answer to the question " have you ever had a myocardial infarction ? " . clinically diagnosed , or known diabetes , was defined by a positive answer to the question " do you have diabetes ? " .
a validation study of 70 incident diabetes cases in this cohort using clinical case records show these answers to be highly accurate ( unpublished data ) .
hypertension was defined as systolic blood pressure greater than 160 mm hg or diastolic blood pressure greater than 95 mm hg or a positive answer to the question " are you being treated with pharmaceutical drugs for high blood pressure " .
the northern sweden monica study has been approved by the research ethics committee of ume university and the data handling procedures by the national computer data inspection board .
all electrocardiograms ( ecg 's ) were recorded with a cardiovit cs-6 microprocessor - based electrocardiograph ( schiller ag , basel , switzerland ) .
twelve leads were recorded for 10 seconds and used for interpretation by the cs-6 recorder .
original readings were printed on paper ( paper speed 50 mm / s ) together with an averaged ecg and a diagnostic statement made by the computer .
ecg 's were asessed according to the minnesota code by two trained observers and q / qs - wave ; codes 1.11.3 were designated as myocardial infarction .
ecg 's from two subjects were coded differently by the observers and were therefore excluded from the mi group .
students t - test and were used to test for differences between subjects with normal ecg and subjects with ukmi . in a stepwise logistic regression with ukmi as dependent variable , traditional risk factors ( hypertension , smoking , hypercholesterolemia ) and the occurrence of igt were entered as dichotomous independent variables and age as a continuous variable .
all electrocardiograms ( ecg 's ) were recorded with a cardiovit cs-6 microprocessor - based electrocardiograph ( schiller ag , basel , switzerland ) .
twelve leads were recorded for 10 seconds and used for interpretation by the cs-6 recorder .
original readings were printed on paper ( paper speed 50 mm / s ) together with an averaged ecg and a diagnostic statement made by the computer .
ecg 's were asessed according to the minnesota code by two trained observers and q / qs - wave ; codes 1.11.3 were designated as myocardial infarction .
ecg 's from two subjects were coded differently by the observers and were therefore excluded from the mi group .
students t - test and were used to test for differences between subjects with normal ecg and subjects with ukmi . in a stepwise logistic regression with ukmi as dependent variable , traditional risk factors ( hypertension , smoking , hypercholesterolemia ) and the occurrence of igt were entered as dichotomous independent variables and age as a continuous variable .
table 1 shows baseline characteristics of 790 subjects , 25 to 64 years of age . both sexes were evenly represented .
previously known mi ( kmi ) was present in 2.7 % , hypertension in 18,5 % , hypercholesterolemia in 36.3 % and diabetes in 2.8 % .
characteristics of the total study population , 25 to 64 years of age in the northern sweden monica population survey in 1986 .
cigarette smoking were more common in women but the use of smokeless tobacco was rare compared to men .
characteristics of the study population , men and women , 25 to 64 years of age in the northern sweden monica population survey in 1986 .
an ogtt was carried out in 617 subjects , showing igt in 8.6 % and unknown diabetes in 2.3 % .
a gender - specific analysis of this population did not differ significantly regarding age , anthropometric variables or biochemical markers compared to the total study population shown in table 1 and 2 ( table 3 ) .
characteristics of the glucose tolerance tested subjects , men and women , 25 to 64 years of age in the northern sweden monica population survey in 1986 .
interestingly , there were twice as many subjects with ecg indicating mi ( ukmi ) that had not been clinically diagnosed than with known infarctions ( kmi ) .
comparison of clinically diagnosed myocardial infarctions and ecg indicating myocardial infarction ( n = 771 ) .
mi = myocardial infarction a gender - specific analysis comparing subjects with normal ecg to ukmi subjects are shown in table 5 .
subjects of both sexes with ukmi were older and had a greater burden of previous cvd than did subjects with normal ecg 's .
body mass index and waist - hip ratio were higher in subjects with ukmi , more so in women than in men .
there was a tendency to higher lipid levels in the ukmi group , at least in women .
the number of subjects with igt was significantly higher in the ukmi group in women , but not in men compared to the group with normal ecg .
bmi = body mass index the association between ukmi and sex , age , smoking , hypercholesterolemia , hypertension and igt was analyzed in a multiple logistic regression model .
none of the variables , except for age , showed significant association with ukmi ( table 6 ) .
predictors of ukmi in a multiple logistic stepwise regression analysis ukmi = unknown myocardial infarction . or (= odds ratio )
men and women were analyzed separately and the results are shown in table 7 . in men , no variable was significantly associated with ukmi although the odds ratio for hypercholesterolemia was of borderline significance ; 3.22 ( ci 0.92 ; 11.22 ) . in women ,
the odds ratio of having ukmi was 4.14 ( ci 1.13 ; 15.14 ) in women with igt compared to women with normal glucose tolerance . the odds ratio for hypertension was of borderline significance ; 3.33 ( ci 0.97 ; 11.43 ) .
the results were similar if subjects with st / t changes and left ventricular hypertrophy were excluded from the " normal ecg " group .
if , on the other hand , st / t changes are included in the mi group no significant association between any variable was seen ( data not shown )
. predictors of ukmi in a multiple logistic stepwise regression analysis conditions and abbreviations were as in table 4
our findings indicate that previously unknown q - wave infarction is considerably more common in women 2564 years of age with impaired glucose tolerance than in women with normal glucose tolerance , even after adjustment for traditional risk factors .
the total number of participants was rather small which is a limitation of the study but the attendence rate of 80 % is in accordance with other major population surveys .
cross - sectional studies concerning resting ecg abnormalities indicating ihd in subjects with igt have reported varying results .
in younger south asian men ( 4054 years ) settled overseas , major q - waves were strongly associated with glucose intolerance and hyperinsulinemia .
this association was less strong for european men in the same study . in a chinese population
, igt was associated with ecg abnormalities in both men and women , but the ecg criteria used also included t - wave abnormalities and complete left bundle branch block , which differs from the stricter q - wave criteria used in our study .
data from the rancho bernardo study , an older population of white subjects , showed that ecg abnormalities were more common in subjects with non - insulin dependent diabetes ( niddm ) but not in those with igt . also in this study , ecg criteria were wider than our criteria . in the san luis valley
diabetes study , 2074-year - old hispanics and non - hispanic whites of both sexes were studied .
an association between niddm , but not igt , with mainly q / qs waves was seen .
a study of north american white males , aged 4059 years , could not show any association between blood glucose and major ecg abnormalities indicating mi .
hence , no consistent data concerning association between igt and silent myocardial infarctions have been shown and only few studies have included women . to our knowledge
mi 's were somewhat more common in subjects with igt , although not reaching conventional levels of significance .
this indicates a problem of statistical power and perhaps differing impact of blood glucose abnormalities in different ethnic groups .
some of these studies found that increases in risk were attenuated by adjustement for other known risk factors .
our population - based study is thus the first to show that in middle - aged european women , there is a strong and independent relationship between igt and previously unknown mi , defined by strict criteria .
major q - waves were shown to occur in only 43 % of subjects in whom old myocardial infarcts were detected at autopsy , and q / qs abnormalities were found to be rather common in non q - wave infarctions as well .
twenty to thirty percent of major q / qs infarctions are known to be silent .
moreover , q / qs abnormalities often disappear during recovery from an acute myocardial infarction .
this was also evident in our study where only a minority of reported previous mi were classified as mi on ecg .
interestingly , it was recently shown that left ventricular hypertrophy ( lvh ) mass and wall thickness increased with worsening glucose intolerance , an effect that was more striking in women compared with men . hence , since lvh can mimic mi this might lead to misclassification bias in the ecg interpretation . in the present investigation
many kmi 's were seen in the group with normal ecg , a not surprising observation considering the findings mentioned .
specificity for q / qs - infarctions was high but sensitivity was low when ecg was compared to autopsy - verified infarctions .
thus , some infarctions might be undetected in our material which could lead to misclassification bias and a dilution of effect .
an increased ihd mortality has been described in subjects with igt , particularly in women . in the decode study , which included monica data from our survey , igt predicted mortality from all causes , cvd and chd .
previous studies indicate that the risk of cvd is increased at the time of diabetes diagnosis .
the risk seem to be independent of the duration of diabetes suggesting that factors operating before the development of overt diabetes contribute to the risk of cvd .
this was recently shown in women where the risk for mi or stroke was substantially increased before diagnosis of type 2 diabetes .
hyperglycemia has also been suggested to be a direct cause of some of the changes associated with atherosclerosis , but several other factors could act as casual links in this association such as impaired fibrinolysis and high fibrinogen levels , high levels of leptin   as well as others which have not been assessed in population studies .
these factors could link igt to atherosclerosis and thereby to the q / qs abnormalities found in the present investigation although the diverging results in men and women are difficult to explain . in conclusion
, we found that igt was associated with ecg findings indicating silent myocardial infarction in women in a middle - aged general population in northern sweden .
as encouraging results have recently been published on the effect of life - style modification to prevent high risk individuals from developing diabetes , our study underlines that such efforts may also lead to decreased cardiovascular risks . also , more research is needed to improve our understanding of the pathogenesis of coronary artery disease in subjects with early glucose dysregulation
dl participated in the design of the study , performed the statistical analyses and drafted the manuscript .
me participated in the design of the study and in the final preparation of the manuscript .
we are grateful to dr per bjerle for participating in the sampling and coding of the ecg 's .
this study was supported by grants from the swedish medical research council , ( grant no .
27x-07192 to ka ) , the council for worklife and social research , the heart and chest fund , the foundation for strategic research , king gustaf v 's and queen victoria 's foundation and vsterbotten and norrbotten county councils .
 backgroundpatients with impaired glucose tolerance ( igt ) have an increased risk of cardiovascular disease ( cvd ) that is independent of traditional risk factors . hence , slightly elevated glucose levels , even in the non - diabetic range , might be associated with increased macrovascular disease.methodswithin the northern sweden monica project a population survey was performed in 1986 . 
 electrocardiograms ( ecg 's ) were recorded for half of the survey ( n = 790 ) and oral glucose test was carried out in 78 % of those . 
 the association between subjects with ecg 's indicating previously unknown myocardial infarction ( ukmi ) , igt and conventional risk factors were analyzed by logistic regression for men and women separately , adjusting for age , smoking , hypercholesterolemia and hypertension.resultsimpaired glucose tolerance was significantly more common among women with ukmi , but not in men , compared to the group with normal ecg . in men , 
 no variable was significantly associated with ukmi although the odds ratio ( or ) for hypercholesterolemia was of borderline significance , 3.2 ( 95% confidence interval ( ci ) 0.9 to 11 ) . 
 the or of having ukmi was 4.1 ( ci 1.1 to 15 ) in women with igt compared to women with normal glucose tolerance after multiple adjustment . 
 the or for hypertension was of borderline significance ; 3.3 ( ci 0.97 to 11).conclusionwe found that igt was associated with ecg findings indicating silent myocardial infarction in women in a middle - aged general population in northern sweden . 
 the results persisted even after adjusting for known risk factors . 
Background
Methods
Electrocardiography
Statistical analysis
Results
Discussion
Competing interests
Authors' contributions
Acknowledgements