Risk factors differ by first manifestation of cardiovascular disease in type 1 diabetes

Aims: We compared risk factors for three CVD manifestations and a composite outcome over 25 years' follow-up in the Pittsburgh Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset (<17 years) type 1 diabetes (n = 658). Methods: First CVD manifestations examined were: (1) major atherosclerotic cardiovascular event (MACE, i.e. CVD death, myocardial infarction, stroke), (2) coronary revascularization, (3) soft coronary artery disease (CAD, i.e. ischemia ECG, angina), and a (4) composite (MACE + revascularization) outcome. Baseline and time-varying mean and current risk factors, including medication use, were assessed, in diabetes duration-adjusted models. Results: MACE (n = 107) was predicted by ln(albumin excretion rate) (AER, HR = 1.3, p < 0.0001), systolic BP (SBP, HR = 1.03, p < 0.0001), white blood cell count (WBC, HR = 1.2, p < 0.0001), HbA1c (HR = 1.2p = 0.03), LDLc (HR = 1.01, p = 0.03). Soft CAD (n = 91) was predicted by ln(AER) (HR = 1.2, p = 0.004), SBP (HR = 1.03, p = 0.0002), WBC (HR = 1.2, p = 0.0003), HbA1c (HR = 1.2, p = 0.005). Revascularization (n = 38) was predicted by LDLc (HR = 1.03, p < 0.0001), eGFR (HR = 0.98, p = 0.002), HbA1c (HR = 1.3, p = 0.03). Adding revascularization to MACE enhanced the role of LDLc, while diminishing that of HbA1c, compared to MACE alone. Conclusions: Important risk factor associations may be affected by examining composite CVD outcomes. More research is needed to determine how to best incorporate revascularization into composite CVD definitions. (C) 2020 Elsevier B.V. All rights reserved.