Cardiac Autonomic Function Is Associated With Myocardial Flow Reserve in Type 1 Diabetes
Article Figures & Tables
Figures
- Figure 1
Correlations between MFR and measures of cardiac autonomic function: late heart-to-mediastinum ratio (A) and 30-to-15 ratio (B). All correlations were significant, P ≤ 0.001.
- Figure 2
MFR according to CAN status: all participants (A) and participants with known coronary artery disease or reversible and/or irreversible ischemia identified by cardiac PET (B) (n = 10) were excluded. Data are presented as the mean with 95% CI. CAN diagnosis was based on CARTs using the American Diabetes Association criteria; we defined CAN as 1) no CAN when no pathological CART results were detected or if only one abnormal CART result was detected and 2) definite CAN if two or three abnormal CART results were detected. Differences between groups were analyzed with independent-samples t tests.
Tables
- Table 1
Clinical characteristics and measures of cardiac autonomic function
Control subjects (n = 30) Normoalbuminuria (n = 30) Macroalbuminuria (n = 30) P (control subject vs. normoalbuminuria) P (normoalbuminuria vs. macroalbuminuria) Female 12 (40) 12 (40) 13 (43) 1.0 0.79 Age (years) 59.8 ± 9.9 59.8 ± 9.1 58.2 ± 9.9 0.99 0.52 Known diabetes duration (years) 32.6 ± 12.7 41.4 ± 13.3 0.01 BMI (kg/m2) 24.7 ± 3.4 25.6 ± 4.1 27.2 ± 4.2 0.38 0.15 24-h systolic blood pressure (mmHg) 127 ± 13 135 ± 9 138 ± 11 0.009 0.26 24-h diastolic blood pressure (mmHg) 79 ± 8 78 ± 6 77 ± 5 0.88 0.48 Heart rate (bpm) 61 ± 8 69 ± 12 72 ± 12 0.003 0.41 HbA1c (mmol/mol) 35.8 ± 1.9 61.3 ± 8.3 66.3 ± 11.7 <0.0001 0.70 HbA1c (%) 5.4 ± 0.17 7.8 ± 0.76 8.2 ± 1.07 <0.0001 0.70 LDL cholesterol (mmol/L) 3.4 ± 0.7 2.3 ± 0.7 2.1 ± 0.8 <0.0001 0.32 eGFR (mL min−1 1.73 m−2) 82.8 ± 13.1 89.1 ± 10.4 62.5 ± 23.1 0.043 <0.0001 UACR (mg/g)* 6 [5–10.5] 3 (3–5) 121 [53–283] 0.0002 <0.0001 Smokers 4 (13) 4 (14) 4 (14) 0.96 1.0 Alcohol (beverages/week) 8.5 (4–14) 7 (4–18) 6.5 (1–14) 0.87 0.91 Physical activity (hours/week) 5.0 ± 4.2 4.9 ± 5.3 6.1 ± 11.4 0.93 0.61 Treatment Antihypertensive 3 (10) 17 (57) 30 (100) 0.0001 <0.0001 RAAS inhibition 3 (10) 14 (47) 29 (97) 0.002 <0.0001 β-Blocker 0 (0) 1 (3) 8 (27) 1.0 0.03 Aspirin 1 (3) 11 (37) 19 (63) 0.0012 0.04 Lipid-lowering 0 (0) 21 (70) 24 (80) <0.0001 0.37 Amlodipine 0 (0) 4 (13) 10 (33) 0.11 0.07 Known coronary artery disease 0 (0) 0 (0) 7 (23) — 0.01 MFR 3.0 ± 0.79 3.1 ± 0.79 2.1 ± 0.92 0.74 <0.0001 HRV measures Time and frequency domains SDNN intervals (ms) 39.4 [28.6–53.0] 30.0 [20.5–49.6] 18.5 [13.3–34.8] 0.057 0.057 RMSSD (ms) 25 [20.4–39.45] 19.25 [10.1–30.9] 13.0 [6.5–20.1] 0.065 0.21 LF power (ms2) 196.7 [78.3–308.7] 73.1 [24.7–238.3] 21.1 [14.6–92.5] 0.045 0.099 HF power (ms2) 70.9 [45.9–131.5] 43.2 [12.0–87.1]] 22.3 [5.3–66.0] 0.077 0.20 LF/HF (ratio) 2.05 [1.38–4.25] 2.07 [1.34–3.52] 2.06 [0.89–3.46] 0.64 0.44 Total power (ms2) 606.1 [253.6–1,106.2] 291.7 [118.6–644.5] 101.9 [54.6–447.4] 0.03 0.08 CARTs 30-to-15 ratio (response to standing) 1.24 ± 0.17 1.12 ± 0.11 1.03 ± 0.25 0.0002 0.12 E-to-I ratio (deep breathing) 1.24 ± 0.15 1.15 ± 0.12 1.12 ± 0.0 0.02 0.28 Valsalva test ratio 1.77 ± 0.41 1.48 ± 0.19 1.39 ± 0.34 0.0045 0.33 CAN No CAN 28 (100) 22 (85) 13 (43) 0.047 0.03 CAN 0 (0) 4 (15) 10 (57) 123I-MIBG imaging n = 14 n = 30 n = 30 Late heart-to-mediastinum ratio 2.9 ± 0.39 2.6 ± 0.38 2.3 ± 0.50 0.01 0.05 Sudomotor function Feet (µS) 69.9 ± 14.4 55.2 ± 24.4 0.008 Sudomotor dysfunction** 11 (38) 18 (62) 0.006 Hands (µS) 58.6 ± 17.0 47.5 ± 18.7 0.02 Sudomotor dysfunction** 8 (27) 18 (62) 0.006 Data represent total number (%), mean ± SD, or median [IQR]. CAN was defined as no CAN when no pathological CART results were detected or if only one abnormal CART result was detected and as definite if two or three abnormal CART results were detected, according to the American Diabetes Association criteria. RAAS, renin-angiotensin-aldosterone system.
*UAER for control subjects.
**We applied age- and sex-stratified electrochemical skin conduction thresholds when evaluating sudomotor dysfunction in hands and feet.
- Table 2
Unadjusted and stepwise adjusted associations between measures of cardiac autonomic function and MFR
Model 1 unadjusted Model 2 adjusted for age Model 3 adjusted for age and heart rate Model 4 adjusted for age, heart rate, and other risk factors** Model 5 adjusted as model 4 + physical activity and medication*** β P β P β P β P β P 123I-MIBG imaging (n = 74) Late heart-to-mediastinum ratio 0.39 0.0004 0.38 0.0005 0.32 0.0027 0.24 0.03 0.28 0.01 HRV measures (n = 84) Time and frequency domains* SDNN intervals (ms) 0.34 0.0006 0.32 0.001 0.19 0.10 0.14 0.29 0.12 0.37 RMSSD (ms) 0.33 0.0009 0.30 0.002 0.16 0.20 0.14 0.30 0.12 0.39 LF power (ms2) 0.34 0.0007 0.31 0.001 0.20 0.07 0.14 0.25 0.11 0.38 HF power (ms2) 0.29 0.004 0.25 0.01 0.09 0.46 0.05 0.71 0.06 0.65 LF/HF (ratio) 0.10 0.32 0.13 0.18 0.15 0.10 0.09 0.30 0.06 0.55 Total power (ms2) 0.32 0.001 0.30 0.002 0.18 0.14 0.12 0.36 0.10 0.47 CARTs 30-to-15 ratio (response to standing, n = 83) 0.30 0.001 0.27 0.004 0.25 0.04 0.30 0.01 E-to-I ratio (deep breathing, n = 84) 0.30 0.002 0.26 0.006 0.15 0.11 0.19 0.05 Valsalva test ratio (n = 60) 0.14 0.19 0.14 0.19 −0.01 0.92 −0.002 0.99 *Log2 transformed for analyses.
**Not included in adjustment for the CARTs. The β-estimates represent standardized effect. Other risk factors included sex, 24-h systolic blood pressure, BMI, HbA1c, UACR (UAER in control subjects), and smoking.
***Treatment with β-blockers, amlodipine, tramadol, tricyclic antidepressants, or chlorpromazine.
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