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Incremental Prognostic Value of a Coronary Heart Disease Polygenic Risk Score in Type 2 Diabetes

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posted on 2024-10-16, 20:36 authored by Ify R Mordi, Ivy Li, Gittu George, Rory J McCrimmon, Colin N Palmer, Ewan R Pearson, Chim C Lang, Alex S Doney

Objective The recent availability of cardiovascular risk-reducing type 2 diabetes (T2D) therapies makes it imperative to optimally identify individuals who could derive benefit. Current clinical risk prediction may misclassify individuals as low-risk and could be improved. Our aim was to determine the incremental prognostic value of a coronary heart disease genome-wide polygenic risk score (CHD PRS) to a clinical risk score in prediction of major adverse cardiovascular events (MACE) in patients with T2D. Research Design and Methods We evaluated 10,556 individuals with T2D aged 40-79 without a prior cardiovascular hospitalisation. We calculated 10-year clinical cardiovascular risk at the date of recruitment using the Pooled Cohort Equation (PCE Risk) and constructed a CHD PRS. The primary outcome was time to first MACE incidence and we assessed the additional incremental predictive value of the CHD PRS to the PCE risk. Results At 10 years there were 1,477 MACE events. After adjustment for clinical risk the CHD PRS was significantly associated with MACE (HR 1.69 per SD increase, 95% CI 1.60-1.79). Individuals with PCE risk <7.5% but in the top quintile of CHD PRS had a significantly increased likelihood of MACE (HR 10.69, 95% CI 5.07-22.55) compared to those in the lowest. The addition of the PRS to the clinical risk score led to significant improvements in risk prediction, particularly in those at low clinical risk. Conclusion The addition of a CHD PRS to clinical assessment improved MACE prediction in T2D individuals without prior cardiovascular disease, particularly in those at low clinical risk.

Funding

This work was supported by the National Institute of Health Research Global Health Programme (16/136/102). iDiabetes is supported by a Chief Scientist Office Precision Medicine Alliance Scotland Award (PMAS/21//01). Dr Mordi is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/ICRF/24/26101).

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