Risk Factors Differ by First Manifestation of Cardiovascular Disease (CVD) in Type 1 Diabetes (T1D)

Abstract

CVD is a major contributor to T1D morbidity and mortality but presents in a variety of first manifestations. Thus we aimed to assess risk factors for 3 CVD manifestations in a T1D cohort: 1) major atherosclerotic cardiovascular event (MACE, i.e., CVD death, myocardial infarction (MI), stroke), 2) coronary revascularization, no prior MI (REV), 3) soft CVD (SOFT, i.e., ischemic ECG or angina). Data are from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, an ongoing, prospective cohort study of childhood-onset (<17 years) T1D diagnosed 1950-80 with 25 years of follow-up (n=658, 49% women, mean age 27, T1D duration 18 years at 1986-88 baseline). Follow-up exams occurred biennially for the first 10 years and at 18 and 25 years. MACE and REV were ascertained by death certificate adjudication or self-report, confirmed with medical records. Angina was determined by EDC physician history and ischemia by Minnesota coded ECGs. Prevalent CVD cases (n=54) were excluded. Those experiencing each manifestation were compared to participants not developing any CVD over follow-up. Baseline (BL), time varying updated mean (UM) and time varying most recent (MR) risk factors were assessed in Cox models (HRs per unit). CVD first manifested as n=107 MACE, n=38 REV, and n=91 SOFT. In T1D duration-adjusted multivariable models, MACE was predicted by MR ln (albumin excretion rate (AER)) (HR 1.3 p<.0001), UM systolic blood pressure (SBP) (HR 1.03 p<.0001), BL smoking (HR 1.9 p=0.003), UM LDLc (HR 1.01 p=0.03) and UM HbA1c (HR 1.2 p=0.03). REV was predicted by BL LDLc (HR 1.03, p<.0001), BL estimated glomerular filtration rate (HR 0.98 p=0.002) and MR HbA1c (HR 1.3 p=0.03). SOFT was predicted by MR SBP (HR 1.03 p<.0001), UM ln(triglycerides) (HR 1.8 p=0.01), MR HbA1c (HR 1.2 p=0.01) and MR ln(AER) (HR 1.2 p=0.02). HbA1c was consistently, but modestly, associated with all CVD manifestations. Additionally, BP and AER are important predictors of MACE and SOFT, while REV is most strongly predicted by BL LDLc. Disclosure R.G. Miller: None. T.J. Orchard: None.