The role of coronary artery calcification testing in incident coronary artery disease risk prediction in type 1 diabetes

OBJECTIVE Individuals with type 1 diabetes are at a high lifetime risk of coronary artery disease (CAD), calling for early interventions. This study explores the use of a genetic risk score (GRS) for CAD risk prediction, compares it to established clinical markers, and investigates its performance according to the age and pharmacological treatment. RESEARCH DESIGN AND METHODS This study in 3,295 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study (467 incident CAD, 14.8 years follow-up) used three risk scores: a GRS, a validated clinical score, and their combined score. Hazard ratios (HR) were calculated with Cox regression, and model performances were compared with the Harrell C-index (C-index). RESULTS A HR of 6.7 for CAD was observed between the highest and the lowest 5th percentile of the GRS (P = 1.8 × 10−6). The performance of GRS (C-index = 0.562) was similar to HbA1c (C-index = 0.563, P = 0.96 for difference), HDL (C-index = 0.571, P = 0.6), and total cholesterol (C-index = 0.594, P = 0.1). The GRS was not correlated with the clinical score (r = −0.013, P = 0.5). The combined score outperformed the clinical score (C-index = 0.813 vs. C-index = 0.820, P = 0.003). The GRS performed better in individuals below the median age (38.6 years) compared with those above (C-index = 0.637 vs. C-index = 0.546). CONCLUSIONS A GRS identified individuals at high risk of CAD and worked better in younger individuals. GRS was also an independent risk factor for CAD, with a predictive power comparable to that of HbA1c and HDL and total cholesterol, and when incorporated into a clinical model, modestly improved the predictions. The GRS promises early risk stratification in clinical practice by enhancing the prediction of CAD.

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The Association of Coronary Artery Calcification and Carotid Artery Intima-Media Thickness With Distinct, Traditional Coronary Artery Disease Risk Factors in Asymptomatic Adults

American Journal of Epidemiology ◽

10.1093/aje/kwn211 ◽

2008 ◽

Vol 168 (9) ◽

pp. 1016-1023 ◽

Cited By ~ 28

Author(s):

E. Rampersaud ◽

L. F. Bielak ◽

A. Parsa ◽

H. Shen ◽

W. Post ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Carotid Artery ◽

Coronary Artery Calcification ◽

Disease Risk ◽

Intima Media Thickness ◽

Coronary Artery Disease Risk ◽

Media Thickness ◽

Artery Disease

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Abstract 3126: Coronary Artery Calcification as a Predictor of Subsequent Coronary Artery Disease Events

Circulation ◽

10.1161/circ.118.suppl_18.s_1097-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Tina Costacou ◽

Trevor J Orchard

Keyword(s):

Coronary Artery Disease ◽

Type 1 Diabetes ◽

Coronary Artery ◽

Coronary Artery Calcification ◽

Diabetes Duration ◽

Glucose Disposal ◽

Agatston Score ◽

Cross Sectional ◽

Artery Disease

Coronary artery calcification (CAC) as measured by electron beam computed tomography (EBCT) can be used as an indicator of atherosclerotic burden. We have previously reported a cross sectional association between the presence of CAC and history of clinical coronary artery disease (CAD) in type 1 diabetes. In this analysis, we assessed the ability of CAC to predict the incidence of CAD events. Participants from the Pittsburgh Epidemiology of Diabetes Complications Study of childhood onset type 1 diabetes who underwent an EBCT screening (1996–98) and were free of clinical CAD were selected for study (n=236). Mean age at EBCT screening was 36.6 years and diabetes duration 28 years. CAC was calculated using the Agatston score and was used both as a continuous variable (after log transformation) and as a categorical variable. CAD was defined as non-fatal MI (n=4), ischemic ECG changes (Minnesota codes 1.3, 4.1, 4.2, 4.3, 5.1, 5.2, 5.3, 7.1) (n=9), hospitalized unstable angina (n=1), new onset angina leading to revascularization (n=2) or fatal CAD (n=4). Glucose disposal rate (eGDR-insulin sensitivity) was estimated by a regression equation derived from hyperinsulinemic euglycemic clamp studies with terms for waist to hip ratio, HbA 1c , and hypertension. During a mean follow-up of 7.4 years, 20 (8.5%) individuals had an incident event. Individuals who had an event were older, with a greater diabetes duration, systolic blood pressure, HbA 1c , and WBC count, a lower eGDR (all p-values <0.05), and a higher CAC score (p<0.0001). Thus, approximately 24% of persons with CAC ≥200 had a subsequent CAD event compared to only 3% of those with a zero score. In multivariable Cox proportional hazard models with backward elimination, a CAC score greater than zero was a significant predictor of CAD incidence (HR=4.07, 95% CI=1.38–11.96). Other significant predictors comprised diabetes duration (HR=1.07, 95% CI=1.01–1.14) and HbA 1c (HR=1.39, 95% CI=1.10–1.76). The area under the ROC curve increased from 0.720 to 0.784 with the inclusion of CAC score. In this cohort of individuals with type 1 diabetes, CAC is a significant predictor of subsequent CAD status and adds to the prediction beyond standard risk factors. Thus, CAC may be used as a screening tool for CAD risk in type 1 diabetes.

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