A. Baseline characteristics of patients with SH and without SH
We matched our case and control cohort accordingly to minimize confounding factors for CAD such as age, gender, race, BMI, duration of diabetes, smoking status, family history of CAD in first degree relatives, history of cerebrovascular accidents, medication usage, and creatinine clearance, as shown in
Despite matching baseline characteristics, patients with history of SH had a higher median ACC/AHA CVD risk score and Framingham risk score of more than 30%.
For laboratory investigation, T2DM patients with SH had higher total cholesterol and LDL-C, but lower HDL-C and HbA1c levels. This might accounted why these patients had higher clinical risk scores and were more susceptible to SH as a result of having a lower Hba1c level.
Hs-CRP level was significantly higher among patients with history of SH as compared with patients without history of SH (P = 0.029). This indicated that patients with a history of SH had a higher degree of pro-inflammatory state, with subsequent greater risk of plaque rupture and destabilization.
(Table 1)
B. Comparison of CCTA and CACS between group with SH and no SH
We performed CACS for every patient, where 12 (21%) patients (10 from SH group, 2 from non-SH group) did not proceed with CCTA mostly due to extremely high CACS (≥800) which affects the objective interpretation of the CCTA, or technical issues such as suboptimal images, or uncontrolled heart rate.
Median CACS was statistically significantly higher in the SH group as compared with the non-SH group. For CACS subgroup analysis, SH group had fewer patients with CACS 0 and CACS<100, but more patients in the CACS≥100, CACS 100-399, and CACS ≥400 categories.
In terms of CCTA features, SH group has fewer patients with no significant stenosis. Patients in the SH group had more prevalent obstructive CAD in each of the epicardial coronary arteries, with statistical significant finding for the right coronary artery. Both scores that we created to compare the severity of coronary artery disease were also higher in the SH group, mean percentage of segments involved and mean percentage of segment severity.
The SH group had more patients with significant CAD, based on CACS ≥400, and/or presence of at least one epicardial coronary artery stenosis ≥50%, with OR 4.231, CI 1.314-13.617, P = 0.026. The prevalence of significant ACAD in the control T2DM patients, 46.4% correlated with previous studies which employed CCTA for detection of significant CAD.28-29
(Table 2)
C. Subgroup analysis within SH group
i. Recurrent SH vs single episode of SH
There were 5 (18%) patients with recurrent episodes of SH. Comparison between patients with recurrent SH and single episode of SH, showed these patients to be older, and had lower creatinine clearance which might had explained the higher risk of recurrent severe hypoglycemia. All the patients with recurrent SH had significant CAD. Their hs-CRP and MMP-9 values were also higher signifying greater risk of CV events. Their CACS values were also statistically more significant, however due to most patients having extremely high CACS values of more than 800, CCTA were not performed in this group of patients.
(Table 3)
ii. Onset of SH within the first month vs more than 1 month
There were 10 (36%) patients who were investigated within the first month of the occurrence of SH. Hs-CRP and MMP-9 levels were higher in this group as compared to those who had SH more than a month ago, signifying possible temporal association of SH with the process of inflammation and risk of plaque rupture.
(Table 4)