Cardiovascular Risk Prediction in Type 2 Diabetes Before and After Widespread Screening: A Derivation and Validation Study

Background: Most patients with diabetes are diagnosed when symptomatic, most have high cardiovascular risk, and most should be prescribed cardiovascular preventive medications. However, approximately 90% of adult New Zealanders have now been screened for diabetes, identifying many asymptomatic patients with recent-onset diabetes. We hypothesised that cardiovascular risk prediction equations derived prior to widespread screening will overestimate risk in screen-detected patients. Methods: New Zealanders aged 30-74 years with type 2 diabetes, were identified from the 400,000 person PREDICT primary care cohort study between 2004 and 2016. Sex-specific equations estimating 5-year risk of cardiovascular disease were developed using Cox regression models, with 18 pre-specified predictors, including diabetes-related and renal function measures. Equation performance was compared with an equivalent equation derived in the New Zealand Diabetes Cohort Study (NZDCS), recruited between 2000 and 2006, before widespread screening. Findings: The 46,652 participant PREDICT Diabetes subcohort experienced 4,114 first cardiovascular events during follow-up (median 5·2 years). One-third were not taking hypoglycaemic medications at baseline. Median 5-year cardiovascular risk estimated by the new equations was 4·0% in women and 7·1% in men. The older NZDCS equations, overestimated median cardiovascular risk by threefold in women and twofold in men. Model and discrimination performance measures for PREDICT equations (e.g. women: R2 =32% [95% CI:29, 34], Harrell’s C =0·73 [0·72, 0·74]) were significantly better than for NZDC equations (women: R2=24% [95% CI:21, 26], Harrell’s C =0·69 [0·67, 0·7]). Interpretation: Widespread diabetes screening has radically changed the cardiovascular risk profile of New Zealanders with diabetes. Many have normal renal function, are not dispensed glucose-lowering medications, and have low cardiovascular risk. These findings provide a window to the future as diabetes screening increases worldwide. Equations derived from contemporary diabetes populations, with multiple diabetes-related and renal function predictors, will be required to accurately predict cardiovascular risk in this increasingly heterogeneous population. Funding Statement: Health Research Council of New Zealand, Heart Foundation of New Zealand and Healthier Lives national Science Challenge. Declaration of Interests: I declare no competing interests. Ethics Approval Statement: The PREDICT study was approved by the Northern Region Ethics Committee Y in 2003 (AKY/03/12/314), with annual approval by the National Multi Region Ethics Committee since 2007 (MEC07/19/EXP).