Microvascular endothelial dysfunction in skin is associated with higher risk of heart failure with preserved ejection fraction in women with type 2 diabetes: the Hoorn Diabetes Care System Cohort

Table 3 Associations between log-transformed perfusion response for each substance, the H2FPEF score and the single components of the H2FPEF score in the total study population and in men and women separately

	Total population B (95% CI)	Men B (95% CI)	Women B (95% CI)
Perfusion response to Insulin		N = 75	N = 74
H2FPEF score
Model 1	-42.5 (-66.9; -18.1)**	-19.9 (-55.5; 15.7)	-60.4 (-93.9; -26.9**
Model 2	-38.6 (-62.9; -14.3)**	-14.3 (-49.3; 20.6)	-60.3 (-95.0; -25.6)**
Age	-16.2 (-25.1; -7.2)**	-18.1 (-33.3; -2.8)*	-14.7 (-26.2; -3.2)*
BMI	-11.0 (-18.8; -3.2)**	-6.0 (-17.1; 5.1)	-13.9 (-26.4; -1.3)*
AF	0.1 (-0.1; 0.3)	0.2 (-0.1; 0.5)	0.0 (-0.2; 0.2)
E/E’	-2.0 (-8.0; 4.1)	1.4 (-6.0; 8.8)	-5.7 (-15.6; 4.3)
PASP	-5.5 (-15.3; 4.2)	-6.2 (-23.8; 11.4)	-7.4 (-21.1; 6.3)
Perfusion response to Acetylcholine		N = 74	N = 75
H2FPEF score
Model 1	-26.5 (-50.9; -2.1)*	-14.5 (-50.1; 21.1)	-53.6 (-94.4; -12.8)*
Model 2	-26.3 (-51.5; -1.0)*	-9.0 (-45.9; 27.8)	-57.4 (-100.2; -14.6)**
Age	-11.5 (-20.7; -2.2)*	-24.5 (-39.7; -9.4)**	-6.4 (-20.7; 7.9)
BMI	-6.4 (-14.3; 1.6)	-0.1 (-12.3; 12.1)	-17.5 (-31.2; -3.7)*
AF	-0.0 (-0.2; 0.1)	-0.1 (-0.4; 0.2)	0.1 (-0.1; 0.4)
E/E’	-0.3 (-6.2; 5.6)	2.8 (-5.2; 10.7)	-2.8 (-13.8; 8.1)
PASP	-7.2 (-16.9; 2.6)	-6.1 (-24.6; 12.5)	-12.1 (-26.6; 2.4)
Perfusion response to SNP		N = 74	N = 75
H2FPEF score
Model 1	-7.6 (-14.6; -0.7)*	-38.1 (-78.7; 2.5)	-8.1 (-17.1; 1.0)
Model 2	-6.2 (-13.1; 0.7)	-26.0 (-67.9; 16.0)	-6.4 (-15.7; 2.9)
Age	-3.0 (-5.4; -0.6)*	-16.4 (-35.4; 2.5)	-1.9 (-4.8; 1.0)
BMI	-1.1 (-3.3; 1.1)	-5.5 (-18.8; 7.8)	-1.1 (-4.2; 1.9)
AF	-0.0 (-0.1; 0.0)	0.0 (-0.3; 0.4)	0.0 (-0.0; 0.1)
E/E’	-0.0 (-1.6; 1.6)	4.2 (-4.6; 12.9)	-0.2 (-2.5; 2.1)
PASP	-1.0 (-3.7; 1.8)	-24.2 (-43.9; -4.6)*	-0.8 (-4.3; 2.7)

The determinants (relative change in perfusion from baseline to plateau for each of the substances) were first log-transformed and then added to the model
* P < 0.05 .** p < 0.01. BMI: body mass index. AF: atrial fibrillation. PASP: pulmonary arterial systolic pressure. SNP = sodium nitroprusside
¹The continuous H2FPEF score is an estimation of the probability of developing HFpEF, based on the formula developed by Reddy et al. [24]
Model 1 adjusts for sex, HbA1c, LDL cholesterol, presence of hypertension, serum creatinine, diabetes duration, smoking status, prior CVD, NTproBNP value, and change in perfusion of the skin outside of the measurement area. For the regression analyses with relative change in perfusion due to insulin, model 1 additionally adjusts for change in perfusion due to delivery of NaCl and time since last meal. Model 2 additionally adjusts for metformin use, insulin use, use of anti-hypertensive medication
P-interactions with sex: relative change insulin: 0.296; relative change Acetylcholine: 0.642; relative change SNP: 0.508

ISSN: 1475-2840