Female sex and systolic blood pressure are independently associated with coronary microvascular dysfunction in asymptomatic adults with type 2 diabetes

Abstract

Abstract Introduction Coronary microvascular dysfunction is frequently reported in people with type 2 diabetes (T2D), is associated with reduced exercise capacity, and is a prognostic marker. Identifying modifiable risk factors associated with microvascular dysfunction may facilitate early intervention to improve outcomes in these patients. Purpose To identify independent determinants of myocardial perfusion reserve (MPR) in asymptomatic adults with T2D and no prevalent cardiovascular disease. Methods Prospective cross-sectional study. People with and without T2D and no signs, symptoms or evidence of cardiovascular disease underwent comprehensive phenotyping with echocardiography, coronary artery calcium scoring, and multiparametric cardiac MRI including adenosine stress and rest perfusion with automated pixel-wise myocardial blood flow (MBF) mapping. Participants with regional perfusion defects indicating obstructive coronary disease or silent myocardial infarct on late-gadolinium enhancement were excluded from analysis. Univariable and multivariable linear regression was performed to identify independent determinants of MPR. Results Two-hundred people with T2D (diabetes duration 11±8 years) were compared with 39 sex- and ethnicity-matched non-diabetic controls (Table 1). People with T2D had higher body mass index (BMI) and ambulatory 24-hour systolic blood pressure (SBP). There was evidence of concentric left ventricular (LV) remodelling (higher LV mass/volume), extracellular matrix expansion (higher ECV fraction), and both systolic and diastolic dysfunction (lower global longitudinal systolic strain and E/A ratio, respectively) in those with T2D. Resting MBF was similar between groups, but stress MBF tended to be lower in T2D compared to controls with significantly reduced MPR in T2Ds (2.87±0.86 vs 3.18±0.82, p=0.043). In univariable analysis, MPR correlated with sex, 24-hour SBP, and E/e' ratio. In a multivariable model adjusting for clinical (age, sex, smoking status, BMI, ambulatory SBP, diabetes duration, HbA1c, low-density lipoprotein, albuminuria) and imaging variables (E/e' ratio, LV mass/volume, global longitudinal strain, myocardial ECV, coronary calcium score) known to affect coronary perfusion, female sex (β=−0.227, p=0.013) and 24-hour SBP (β=−0.275, p=0.001) were the only variables independently associated with MPR. Conclusion Female sex is associated with coronary microvascular dysfunction in asymptomatic people with T2D but not LV mass or myocardial extracellular volume. Systolic BP is the only modifiable independent determinant of MPR and may be an early target for intervention to prevent heart failure development in these patients. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health Research (NIHR) United Kingdom through a Research Professorship award (RP-2017-08-ST2-007).British Heart Foundation through a Clinical Research Training Fellowship award (FS/16/47/32190).