Cardiovascular disease risk prediction in type 1 diabetes: Accounting for the differences

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Abstract

Present analyses used data from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective study of subjects with childhood type 1 diabetes (T1D), diagnosed between 1950 and 1980. Baseline exams took place 1986–1988 with biennial exams since. The Framingham risk equation was applied to generate the probability of risk for coronary heart disease (CHD) (MI, CHD death, or Q-waves) in 552 CHD free subjects who experienced 42 events over the 10-year follow-up period. Probabilities were split in to deciles. Expected and observed events were compared and demonstrated poor prediction. Risk factors previously found to be associated with CHD in T1D other than those in the Framingham risk function (age, smoking, cholesterol/HDLc, systolic blood pressure) were compared within the highest risk deciles. In men, elevated fibrinogen (p = 0.007), white blood cell count (WBC) (p = 0.037), albumin excretion rate (AER) (p = 0.0001), and lower HDLc (p = 0.048) were predictive. In females, higher Beck Depression Inventory (p = 0.008), HbA1 (p = 0.008), AER (p = 0.01), LDLc (p = 0.007), fibrinogen (p = 0.006), WBC (p = 0.005), non-HDLc (p = 0.0005), WHR (p = 0.003), and estimated glucose disposal rate (p = 0.002) were associated. Risk factors not considered by the Framingham risk equation may account for the lack of fit and should be examined further.

Introduction

Cardiovascular disease is the leading cause of death for people with diabetes [1]. Because many of the risk factors for heart disease are modifiable, predicting an individual's risk for a coronary heart disease event at some point in the future provides an opportunity for targeting interventions. Prediction models already exist for this purpose. The most commonly used for the general population is from the Framingham Heart Study (in which only 4% of the study population had diabetes) [2] and the UKPDS Risk Engine specifically for type 2 diabetes [3]. Both of these models significantly underestimate the risk of coronary heart disease (CHD) in patients with type 1 diabetes (T1D) [4].

The limitation of these models is particularly concerning since people with T1D suffer a disproportionate burden of CHD exhibiting at least a 10-fold increased risk compared to those similarly aged in the general population [5], [6] Although prediction by the Framingham and UKPDS risk functions in this population is significantly inaccurate [4], the specific factors related to this inaccuracy are not well understood. Therefore our objective was to determine if specific risk factors account for this significant underestimation of events using data from an epidemiologically representative cohort of T1D subjects.

Section snippets

Methods

These analyses used data from the Epidemiology of Diabetes Complications Study, which includes subjects with childhood (<17 years old) onset T1D diagnosed between 1950 and 1980. All subjects were seen within 1 year of diagnosis at Children's Hospital of Pittsburgh. Although this population is clinic based, it has been shown to be epidemiologically representative of type 1 diabetes cases in Allegheny County, Pennsylvania [7]. The 658 subjects participating in baseline exams were followed

Definitions

The CHD outcome of interest was defined by a fatal CAD or non-fatal myocardial infarction (MI) confirmed by medical records, or Q-waves according to Minnesota codes 1.1 or 1.2 [8]. This endpoint is the same used in the Framingham model [2].

At the baseline exam, information was collected by questionnaire concerning demographic characteristics, medical history, and health care behaviors. Both a standardized medical history and clinical examination were performed by a trained internist to document

Results

Of the 552 eligible subjects, 49% were male, 98% were Caucasian, mean age at entry into the study was 27 years old, and duration of diabetes prior to study entry was 18 years. There were 42 (7%) subjects who had their first hard CHD event by the end of their 10th year of follow-up. Those that had an event were older (32.4 years versus 25.8 years; p < 0.0001) and had longer diabetes duration (24.4 years versus 17.3 years; p < 0.0001). Race, gender and age at onset of diabetes were not significantly

Discussion

This study sought to determine factors associated with the underestimation of CHD events when using the Framingham model in T1D subjects. These results are important as the Framingham risk score is commonly used in clinical practices for all T1D. Using this model to provide risk information to patients with type 1 diabetes may not only underestimate risk, but may mis-specify the importance of various risk factors and the potential effects of risk factor modification. In the analysis of males in

Conflict of interest

There are no conflicts of interest.

Acknowledgements

This study was funded by National Institutes of Health DK34818, DK070725, and the American Diabetes Association Junior Faculty Award 1-05-JF-59. The authors have no conflicts of interest and had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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This was presented as a poster at the Society for Medical Decision Making Meeting, San Francisco, CA, in October 2005.

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