Using biomarkers to identify diabetic patients with multiple silent cardiac abnormalities
Authors: Chong V.H , Singh J.S.S , Dow E , McCrimmon R.J , Lang C.C , Struthers A.D 
Published: November 2020

Abstract

Background
Primary prevention of cardiovascular events in people with Type 2 diabetes mellitus (T2DM) needs to improve due to risk of cardiovascular events. A major problem in T2DM is the high incidence of silent yet potentially lethal cardiac abnormalities, namely myocardial ischaemia (MI), left ventricular hypertrophy (LVH), left ventricular systolic dysfunction (LVSD), left ventricular diastolic dysfunction (LVDD), and left atrial enlargement (LAE). All these independently predict cardiovascular events and mortality. There is not a single study with comprehensive enough cardiac phenotyping to document the prevalence of all the aforementioned 5 cardiac abnormalities. To improve primary prevention of cardiovascular disease in diabetes, we need to first identify the type of silent cardiac abnormality and treat accordingly. However cardiac phenotyping in all people with T2DM would be prohibitively expensive.

Purpose
Our study examines the prevalence of all 5 cardiac abnormalities, and the accuracy of biomarkers in identifying them in a cohort of patients with well-controlled T2DM and blood pressure (BP) with no known cardiovascular symptom or disease.

Methods
This is a cross-sectional study of randomly selected patients with T2DM with no known cardiovascular symptom or disease, clinic BP or average 24-hour BP ≤140/80mmHg, and HbA1c ≤64mmol/mol. Patients with renal impairment, atrial fibrillation, moderate to severe valvular heart 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-cTnI), and high sensitivity cardiac Troponin T (hs-cTnT) were measured.

Results
Of 246 participants (mean age 66 years, 63% male), 141 (57.3%) had silent cardiac abnormalities. 90 (36.6%) had 1 cardiac abnormality, 44 (17.9%) had 2 cardiac abnormalities and 7 (2.8%) had 3 cardiac abnormalities. The most prevalent abnormality was LAE, n=106 (43.1%); followed by LVH, n=71 (28.9%); LVDD, n=13 (5.3%); MI, n=8 (3.3%); LVSD, n=1 (0.4%). Both NT-proBNP and hs-cTnI performed best in detecting silent cardiac abnormalities with p-values of 0.02 and 0.0004, and AUC 0.66 and 0.68 respectively. Increasing NT-proBNP (p=0.002) and hs-cTnI (p=0.002) levels correlated to increasing number of concomitant cardiac abnormalities. Our key new finding is that biomarkers identify those with multiple silent cardiac abnormalities.

Conclusion
BNP and high-sensitivity cardiac Troponin appear to identify those with multiple silent cardiac abnormalities which may make them useful screening tests so that cardiac investigations are focused on this high-risk subset, with a view to intensifying potential therapies on this subset to reduce the cardiotoxic effect of diabetes.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Chief Scientist Office