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Cardiovascular and Metabolic Risk

Microvascular Disease in Patients With Diabetes With Heart Failure and Reduced Ejection Versus Preserved Ejection Fraction

  1. Jasper Tromp1,2,3,
  2. Shir Lynn Lim4,
  3. Wan Ting Tay1,
  4. Tiew-Hwa Katherine Teng1,
  5. Chanchal Chandramouli1,
  6. Wouter Ouwerkerk1,
  7. Gupreet S. Wander5,
  8. Jitendra P.S. Sawhney6,
  9. Jonathan Yap1,
  10. Michael R. MacDonald7,
  11. Lieng Hsi Ling4,8,
  12. Naveed Sattar9,
  13. John J.V. McMurray9,
  14. A. Mark Richards4,8,10,11,
  15. Inder Anand12 and
  16. Carolyn S.P. Lam1,2,3⇑, on behalf of the ASIAN-HF Investigators*
  1. 1National Heart Centre Singapore, Singapore
  2. 2University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
  3. 3Duke-NUS Medical School, Singapore
  4. 4Department of Cardiology, National University Heart Centre, Singapore
  5. 5Dayanand Medical College and Hospital, Ludhiana, India
  6. 6Department of Cardiology, Sir Ganga Ram Hospital, New Delhi, India
  7. 7Changi General Hospital, Singapore
  8. 8Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore
  9. 9Institute of Cardiovascular and Medical Sciences and School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, U.K.
  10. 10Cardiovascular Research Institute, National University Health System, Singapore
  11. 11Christchurch Heart Institute, University of Otago, Christchurch, New Zealand
  12. 12Veterans Affairs Medical Center, Minneapolis, MN
  1. Corresponding author: Carolyn S.P. Lam, carolyn.lam{at}duke-nus.edu.sg
    Diabetes Care 2019 Sep; 42(9): 1792-1799. https://doi.org/10.2337/dc18-2515
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      Figure 1

      OR adjusted for age, sex, history of CAD, previous stroke, peripheral artery disease, hypertension, atrial fibrillation, ethnicity, NYHA class, duration of HF, BMI, usage of β-blockers, ACEi/ARB, insulin, oral antidiabetes medications, creatinine, hemoglobin. A and B: Forest plot with ORs and 95% CI for having HFpEF stratified according to microvascular complication (A) and number of microvascular complications (B). C: Percentage of participants with cardiac hypertrophy stratified according to number of microvascular complications and HF subtype.

    • Figure 2
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      Figure 2

      A–C: Kaplan-Meier curves according to microvascular status for the combined outcome of all-cause mortality or HF hospitalization for the total population (A), HFrEF only (B), and HFpEF only (C). D: Box plot of quality of life status (KCCQ overall scores) stratified according to HF type and microvascular complication (MC) status.

    Tables

    • Figures
    • Table 1

      Baseline characteristics according to complication status

      DM without microvascular complications (N = 2,199)DM with microvascular complications (N = 601)P value
      Age (years)63.0 (11.4)64.3 (10.8)0.012
      Women586 (26.6)175 (29.1)0.23
      Ethnicity<0.001
       Chinese767 (34.9)180 (30.0)
       Indian673 (30.6)182 (30.3)
       Malaysian415 (18.9)119 (19.8)
       Japanese145 (6.6)73 (12.1)
       Korean103 (4.7)10 (1.7)
       Thai43 (2.0)27 (4.5)
       Filipino12 (0.5)5 (0.8)
       Indigenous SEA34 (1.5)4 (0.7)
       Others6 (0.3)1 (0.2)
      NYHA class<0.001
       I289 (14.9)50 (9.0)
       II1,035 (53.4)286 (51.6)
       III523 (27.0)195 (35.2)
       IV93 (4.8)23 (4.2)
      Systolic BP (mmHg)122.6 (20.9)127.1 (22.6)<0.001
      Diastolic BP (mmHg)72.4 (12.4)71.1 (12.0)0.019
      BMI (kg/m2)26.0 (5.1)26.3 (5.7)0.16
      Heart rate (bpm)80.1 (16.1)78.1 (13.9)<0.001
      eGFR (mL/min/1.73 m2)63.6 (27.4)46.7 (25.5)<0.001
      LVEF (%)33.8 (14.9)35.9 (15.5)0.002
      HFpEF (%)411 (18.7)150 (24.9)0.001
      Ischemic etiology1,202 (58.5)372 (64.4)0.011
      Duration of HF, years0.02
       <1988 (47.1)229 (40.2)
       1–5621 (29.3)196 (34.4)
       >5–10317 (14.9)97 (17.0)
       ≥10185 (8.7)48 (8.4)
      Signs and symptoms
       Shortness of breath on exertion1,531 (69.7)470 (78.2)<0.001
       Angina266 (12.1)56 (9.3)0.058
       Elevated JVP359 (16.3)132 (22.0)0.001
       Peripheral edema636 (28.9)224 (37.3)<0.001
       Pulmonary rales391 (17.8)165 (27.5)<0.001
      Medical history
       Obese380 (18.7)115 (20.6)0.329
       CAD1,263 (57.5)383 (63.7)0.006
       CKD (eGFR <60 mL/min/1.73 m2)877 (48.7)375 (75.0)<0.001
       Prior stroke166 (7.6)67 (11.1)0.005
       Atrial fibrillation/flutter399 (18.2)104 (17.3)0.63
       Hypertension1,532 (69.7)448 (74.5)0.022
       Type of DM0.214
        Type 160 (2.7)11 (1.8)
        Type 22,139 (97.3)590 (98.2)
       Duration of DM (years), median (IQR)7 (3, 12)11 (6, 20)<0.001
       Peripheral arterial disease73 (3.3)63 (10.5)<0.001
      Medication and device use
       ACEi or ARB1,560 (73.2)392 (66.4)0.001
       β-Blockers1,616 (75.8)457 (77.5)0.41
       MRA1,078 (50.6)206 (34.9)<0.001
       Any diuretics1,771 (83.1)489 (82.9)0.9
       Any oral antidiabetes medication1,291 (60.6)320 (54.6)0.008
       Insulin335 (15.7)139 (23.7)<0.001
       Device use0.372
        None1,932 (88.0)539 (89.7)
        ICD/CRT-D177 (8.0)45 (7.5)
        Pacer/pacemaker87 (4.0)17 (2.8)
      Laboratory, median (IQR)
       Potassium (mmol/L)4.2 (3.8, 4.6)4.3 (3.9, 4.6)0.008
       Sodium (mmol/L)138.0 (136.0, 140.0)138.0 (136.0, 141.0)0.88
       Creatinine (mg/dL)1.1 (0.9, 1.5)1.5 (1.2, 2.2)<0.001
      • Data are n (%) or median (interquartile range [IQR]). BP, blood pressure; CKD, chronic kidney disease; CRT-D, cardiac resynchronization therapy defibrillator; HR, heart rate; ICD, implantable cardioverter defibrillator; JVP, jugular venous pressure; MRA, mineralocorticoid receptor antagonist; SEA, Southeast Asia.

    • Table 2

      Crude and adjusted associations of microvascular complications with 1-year outcomes

      Composite outcomeAll-cause mortalityHF hospitalizations
      No. at riskNo. of events (%)No. at riskNo. of events (%)No. at riskNo. of events (%)
      DM without microvascular complications (referent for HR)2,024437 (21.6)2,024209 (10.3)2,024271 (13.4)
      DM with microvascular complications543172 (31.7)54376 (14.0)543114 (21.0)
      HR (95% CI)P valueHR (95% CI)P valueHR (95% CI)P value
      Univariable1.55 (1.32–1.94)<0.0011.39 (1.07–1.81)0.0141.63 (1.31–2.02)<0.001
      Model 11.60 (1.34–1.92)<0.0011.42 (1.08–1.88)0.0121.59 (1.24–2.04)<0.001
      Model 21.52 (1.25–1.86)<0.0011.43 (1.07–1.91)0.0151.46 (1.13–1.90)0.004
      Model 31.34 (1.06–1.69)0.0151.12 (0.78–1.60)0.5361.43 (1.06–1.93)0.019
      Model 41.35 (1.04–1.76)0.0241.16 (0.78–1.73)0.4561.49 (1.06–2.09)0.020
      • Model 1: age, sex, ethnicity, NYHA class, HF subtype (HFrEF/HFpEF), duration of HF. Model 2: model 1 + BMI, history of hypertension, atrial fibrillation, CAD, usage of insulins, and oral DM drugs. Model 3: model 2 + usage of ACEi/ARB, β-blockers, mineralocorticoid receptor antagonist, creatinine levels, hemoglobin levels, type of DM. Model 4: model 3 + duration of DM.

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    Microvascular Disease in Patients With Diabetes With Heart Failure and Reduced Ejection Versus Preserved Ejection Fraction
    Jasper Tromp, Shir Lynn Lim, Wan Ting Tay, Tiew-Hwa Katherine Teng, Chanchal Chandramouli, Wouter Ouwerkerk, Gupreet S. Wander, Jitendra P.S. Sawhney, Jonathan Yap, Michael R. MacDonald, Lieng Hsi Ling, Naveed Sattar, John J.V. McMurray, A. Mark Richards, Inder Anand, Carolyn S.P. Lam
    Diabetes Care Sep 2019, 42 (9) 1792-1799; DOI: 10.2337/dc18-2515

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    Microvascular Disease in Patients With Diabetes With Heart Failure and Reduced Ejection Versus Preserved Ejection Fraction
    Jasper Tromp, Shir Lynn Lim, Wan Ting Tay, Tiew-Hwa Katherine Teng, Chanchal Chandramouli, Wouter Ouwerkerk, Gupreet S. Wander, Jitendra P.S. Sawhney, Jonathan Yap, Michael R. MacDonald, Lieng Hsi Ling, Naveed Sattar, John J.V. McMurray, A. Mark Richards, Inder Anand, Carolyn S.P. Lam
    Diabetes Care Sep 2019, 42 (9) 1792-1799; DOI: 10.2337/dc18-2515
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