Biomarker Screening for Cardiac Target Organ Damage in Asymptomatic Well-Controlled Patients with Type 2 Diabetes Mellitus

Primary prevention of CV events in people with Type 2 diabetes mellitus (T2DM) needs to improve as they are at risk of CV events. A major problem in T2DM is the high incidence of silent and potentially lethal cardiac disease. Cardiac target organ damage (CTOD) in T2DM, namely myocardial ischaemia (MI), left ventricular hypertrophy (LVH), left ventricular systolic dysfunction (LVSD), left ventricular diastolic dysfunction (LVDD), left atrial enlargement (LAE) all independently predict CV events and mortality. To date there has not been a comprehensive phenotypic assessment of CTOD in patients with T2DM. The aim of my MD project (4P Study, ISCRTN 12700399) was firstly to determine the disease burden in a cohort of patients with well-controlled T2DM and blood pressure (BP) who are asymptomatic, with no known CV disease. Secondly, my MD project was to determine if a simple blood biomarker can be used to predict the presence of CTOD in lieu of complex and expensive cardiac imaging tests. The MD project was a cross-sectional study of randomly selected patients with T2DM with no known CV symptoms or disease, clinic BP or average 24-hour BP ≤140/80mmHg, and HbA1c ≤64mmol/mol. Patients with renal impairment, atrial fibrillation, echocardiographic evidence of moderate to severe valvular disease were excluded. All participants underwent transthoracic echocardiogram, electrocardiogram and dobutamine stress echocardiogram (DSE). Those who did not tolerate DSE or whose DSE was inconclusive, a myocardial perfusion scan or computed tomography coronary angiogram was done. Biomarkers such as BNP, NT-proBNP, high-sensitivity cardiac Troponin I (hs-TnI), high sensitivity cardiac Troponin T (hs-TnT) and Growth Differentiation Factor 15 (GDF-15) were measured. Of the 246 patients (median age 67 years, 36% female) who consented and participated in the 4P Study, 101 (41%) had CTOD. 71 (29%) had 1 CTOD, 21 (9%) with 2 CTOD and 9 (4%) had 3 CTOD. The most prevalent CTOD was LVH, n=71 (29%), followed by LAE, n= 46 (19%); LVDD, n= 11 (4%), MI, n= 8 (3%), LVSD, n=4 (2%). There was statistically significant rise in all biomarker levels corresponding to cumulative number of CTOD, although there was no statistically significant difference in all biomarker levels between presence and absence of both MI and LVSD, owing to the very low prevalence of these 2 CTOD. Both NT-proBNP and hs-TnI performed best in logistic regression testing to detect any out of 5 CTOD. In analysis of NT-proBNP and hs-TnI to detect Stage B cardiomyopathy, i.e. diabetic cardiomyopathy, hs-TnI performed the best in detecting LVH, LAE and LVDD. When classified in tertiles, increasing hs-TnI levels corresponded with increasing prevalence of LVH (p<0.001), LAE (p=0.013) and LVDD (p=0.022). The AUC of hs-TnI in detecting at least 2 of LVH, LAE and LVDD was 0.72 (p<0.001). The findings of my MD project suggest that in a cohort of patients with well-controlled T2DM and hypertension who are asymptomatic, hs-TnI can be used to identify individuals with silent CTOD, especially those associated with diabetic cardiomyopathy. This may be implemented as a screening tool to risk-stratify such patients who may require further specialist investigation and intensification of therapy to reduce future CV risk.