Better understanding the disparity in heart failure risk between the females and males with type 2 diabetes (RF_FR_365)

Background: Type 2 diabetes(T2D) carries an increased risk of heart failure(HF) with both reduced and preserved ejection fraction¹. The incidence of HF is higher for women with T2D compared to men(5- vs 2.4-fold respectively) after adjustment for risk factors, such as age, coronary heart disease, and hypertension². We aimed to determine the effect of sex on the phenotypic expression of diabetic heart disease in patients with T2D. 


Methods:

A total of 59females mean age 60years[95%CI 57,62], body mass index [BMI] 31.2[29.6,32.8]kg/m², mean HBA1c of 54mmol/mol) [49,66], and 94males mean age 61years[59,63], BMI 29.6[28.6,30.6]kg/m², mean HBA1c 61mmol/mol) [49,72] T2D patients on oral glucose lowering treatment were prospectively recruited at a single centre. Left ventricular (LV) volumes, mass, concentricity (LV-mass/LV-end-diastolic-volume), function, T1 mapping, perfusion parameters (rest and dobutamine-stress myocardial blood flow(MBF), myocardial perfusion reserve(MPR) and scarring were assessed using cardiovascular magnetic resonance imaging. Electronic healthcare records were reviewed at an average of 24months for major adverse cardiovascular events(MACE)- heart failure admissions, cardiovascular death, non-fatal myocardial infarction and non-fatal stroke.



Results:

There were no significant differences in age or BMI between females and males with T2D(Table 1). In this asymptomatic participant cohort, while within the normal range, females with T2D had higher NTproBNP levels (70[36,128]ng/l). Although patients were matched for treatment and HbA1c, insulin levels were higher and fasting glucose levels were lower in females(Table-1). All functional parameters of the LV were significantly higher in female T2D patients compared to their male counterparts including LV ejection fraction(63[62,65] vs 60[59,62]%;P=0.0084), rest global longitudinal shortening(18.9[18.0,19.9] vs 17.1[16.4,17.8]%;P=0.0012)(Table-2). Compared to females with T2D, males with T2D showed greater concentric hypertrophic remodeling(0.59(0.54,0.64) vs 0.72(0.67,0.76) g/mL;P=0.0007) with higher LV mass and wall thickness. There was no difference in native T1, extracellular volume fraction or non-ischemic scar between the sexes. Among the perfusion parameters, significant differences were observed in endocardial to epicardial stress MBF ratio(1.10(1.05,1.15)vs1.02(1.00, 1.05);P=0.0032) and rest MBF(0.77(0.73,0.81)vs0.68(0.65,0.71)ml/min/g;P=0.0004) with higher values detected in females with T2D compared to males. In this asymptomatic, T2D patient cohort, over a 24month period there was a total of 2 MACE events (1HF admission and 1 cardiovascular death).  



Conclusion:

In this homogenous, well controlled, uncomplicated T2D patient cohort, males show lower LV function and greater concentric remodelling compared to females (while within the normal range). Paradoxically females show higher NTproBNP levels. While in the general population females show higher perfusion parameters compared to males, in this study, females with T2D show subtle differences in myocardial perfusion with higher rest MBF and endocardial to epicardial stress-MBF ratio in females and no differences in global stress-MBF, MPR, despite males showing greater concentric hypertrophy. This potential attenuation of the otherwise protective effect of female sex in myocardial perfusion may be an important factor for the disparity in HF risk for females with T2D. Larger longitudinal studies are needed to explore this.