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Longitudinal Plasma Kallikrein Levels and their Association with the Risk of Cardiovascular Disease Outcomes in Type 1 Diabetes in DCCT/EDIC

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posted on 21.08.2020 by Ada Admin, Miran A Jaffa, Ionut Bebu, Deirdre Luttrell, Barbara H Braffett, John M Lachin, Kelly Hunt, Maria Lopes-Virella, Louis Luttrell, Timothy J Lyons, Ayad A Jaffa
We determined the relationship between plasma kallikrein and cardiovascular disease (CVD) outcomes as well as major adverse cardiovascular events (MACE) in the DCCT/EDIC-cohort of type 1 diabetes (T1D). Plasma kallikrein levels were measured longitudinally in 693 subjects at DCCT baseline (1983-1989), mid-point of DCCT (1988-1991), end of DCCT (1993), and EDIC years 4-6 (1997-1999), 8-10 (2001-2003), and 11-13 (2004-2006). Cox proportional hazards regression models assessed the association between plasma kallikrein levels and the risk of CVD. In unadjusted models, higher plasma kallikrein levels were associated with higher risk of any CVD during DCCT/EDIC (HR=1.16 per 20 nM higher levels of plasma kallikrein; p=0.0177) as well as over the EDIC-only period (HR=1.22; p=0.0024). The association between plasma kallikrein levels and the risk of any CVD remained significant during the EDIC follow-up after adjustment for age and mean HbA1c (HR=1.20; p=0.0082) and in the fully adjusted model for other CVD risk factors (HR=1.17; p=0.0330). For MACE, higher plasma kallikrein levels were associated with higher risk in unadjusted (HR=1.25; p=0.0145), minimally adjusted (HR=1.23; p=0.0417, and fully adjusted (HR=1.27; p=0.0328) models during EDIC-only. These novel findings indicate that plasma kallikrein level associates with the risk of any CVD and MACE in T1D individuals.

Funding

This work was supported by National Institutes of Health Grants HL077192, HL087986 (AAJ), and HL-055782 (MLV). The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2017, 2017-2022), and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland, USA.

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