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Original Research

n-3 Fatty Acids, Ventricular Arrhythmia–Related Events, and Fatal Myocardial Infarction in Postmyocardial Infarction Patients With Diabetes

  1. Daan Kromhout, MPH, PHD1⇓,
  2. Johanna M. Geleijnse, PHD, FAHA1,
  3. Janette de Goede, MSC1,
  4. Linda M. Oude Griep, MSC1,
  5. Barbara J.M. Mulder, MD, PHD2,
  6. Menko-Jan de Boer, MD, PHD3,
  7. Jaap W. Deckers, MD, PHD4,
  8. Eric Boersma, PHD4,
  9. Peter L. Zock, PHD5 and
  10. Erik J. Giltay, MD, PHD6
  1. 1Division of Human Nutrition, Wageningen University, Wageningen, Netherlands
  2. 2Department of Cardiology, Academic Medical Center, Amsterdam, Netherlands
  3. 3Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands
  4. 4Department of Cardiology, Erasmus University Medical Center, Rotterdam, Netherlands
  5. 5Unilever Research and Development, Vlaardingen, Netherlands
  6. 6Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands
  1. Corresponding author: Daan Kromhout, daan.kromhout{at}wur.nl.
Diabetes Care 2011 Dec; 34(12): 2515-2520. https://doi.org/10.2337/dc11-0896
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    Figure 1

    Kaplan-Meier curves of ventricular arrhythmia–related events (A), death from MI (B), or both end points combined (C). The cumulative incidence of end points is shown in 1,014 patients with an MI and diabetes. Patients were randomly assigned to receive a margarine containing supplemental EPA combined with DHA, a margarine containing supplemental ALA, a margarine containing both EPA-DHA and ALA, or a placebo margarine. P value by log-rank (Mantel-Cox) test.

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  • Table 1

    Baseline characteristics of the 1,014 patients with an MI and diabetes,* according to n-3 fatty acid supplementation group

    VariablesPlacebo (N = 249)ALA (N = 258)EPA-DHA (N = 262)EPA-DHA plus ALA (N = 245)P value
    Age (years)69.1 ± 5.869.4 ± 5.769.3 ± 5.770.0 ± 5.50.31
    Male sex (%)197 (79.1)176 (68.2)197 (75.2)177 (72.2)0.04
    Diabetes*
     Diagnosis from a physician (%)202 (81.5)215 (84.0)212 (80.9)198 (81.8)0.81
     Use of antidiabetic drugs (%)184 (73.9)192 (74.4)184 (70.2)180 (73.5)0.70
     Elevated plasma glucose level (%)115 (46.2)100 (38.8)118 (45.0)108 (44.1)0.34
    Time since MI (years)4.7 ± 3.24.5 ± 3.34.4 ± 3.04.5 ± 3.10.77
    Self-reported history of stroke (%)13 (5.2)23 (8.9)18 (6.9)24 (9.8)0.22
    Use of cardiovascular medication (%)
     Antithrombotic drugs241 (96.8)250 (96.9)256 (97.7)234 (95.5)0.58
     Blood pressure–lowering drugs232 (93.2)238 (92.2)247 (94.3)227 (92.7)0.82
     Lipid-lowering drugs213 (85.5)217 (84.1)223 (85.1)205 (83.7)0.93
     Antiarrhythmic drugs11 (4.4)11 (4.3)9 (3.4)9 (3.7)0.93
    Systolic blood pressure (mmHg)142.1 ± 20.3143.4 ± 22.5143.5 ± 21.1142.6 ± 23.20.88
    Serum lipids (mmol/L)†
     Total cholesterol4.65 ± 0.954.65 ± 0.974.63 ± 0.924.65 ± 1.011.00
     LDL cholesterol2.49 ± 0.822.40 ± 0.822.47 ± 0.782.41 ± 0.840.63
     HDL cholesterol1.18 ± 0.311.22 ± 0.331.22 ± 0.361.22 ± 0.330.51
     Triglycerides2.25 ± 1.352.34 ± 1.272.13 ± 1.122.21 ± 1.200.31
    BMI‡
     Mean29.2 ± 4.629.3 ± 4.328.9 ± 4.329.4 ± 4.80.58
     ≥30 (%)93 (37.5)97 (37.7)93 (35.8)96 (39.2)0.89
    Current smoker (%)54 (21.7)44 (17.1)41 (15.6)30 (12.2)0.04
    Consumption of ≥1 glass of alcohol/week (%)165 (66.3)165 (64.2)181 (69.1)155 (63.3)0.52
    Physically active (%)**40 (16.2)36 (14.2)53 (20.4)47 (19.3)0.24
    • Data are means ± SD unless otherwise indicated. As data for a number of patients were missing from several variables (BMI, 4 patients; alcohol use, 1 patient; and physical activity, 9 patients), some percentages are based on a smaller number than the column total.

    • ↵*Diabetes was considered to be present if a patient reported having received the diagnosis from a physician, was taking antidiabetic drugs, or had an elevated plasma glucose level (≥7.0 mmol/L [126 mg/dL] in the case of patients who had fasted more than 4 h or ≥11.1 mmol/L [200.0 mg/dL] in the case of nonfasting patients).

    • ↵†To convert the values for cholesterol to milligrams per deciliter, divide by 0.02586. To convert the values for triglycerides to milligrams per deciliter, divide by 0.01129.

    • ↵‡The BMI is the weight in kilograms divided by the square of the height in meters.

    • ↵**Greater than or equal to three metabolic equivalent of task (indicating at least moderate intensity for at least 30 min/day) during 6 or 7 days/week.

  • Table 2

    Unadjusted and adjusted HRs of n-3 fatty acid supplementation on end points in 1,014 patients with diabetes, according to n-3 fatty acid supplementation group

    VariablesPlacebo (N = 249)ALA (N = 258)EPA-DHA (N = 262)EPA-DHA plus ALA (N = 245)
    Ventricular arrhythmia–related events (N = 29)
     No./total no. (%)13/249 (5.2%)6/258 (2.3%)8/262 (3.1%)2/245 (0.8%)
     Crude*1.0 (ref.)0.45 (0.17–1.18); 0.100.57 (0.24–1.38); 0.210.15 (0.04–0.68); 0.01
     Adjusted*†1.0 (ref.)0.47 (0.18–1.24); 0.130.58 (0.24–1.39); 0.220.16 (0.04–0.69); 0.01
    Death from MI (N = 27)
     No./total no. (%)7/249 (2.8%)11/258 (4.3%)5/262 (1.9%)4/245 (1.6%)
     Crude*1.0 (ref.)1.52 (0.59–3.93); 0.390.67 (0.21–2.10); 0.490.57 (0.17–1.96); 0.38
     Adjusted*†1.0 (ref.)1.45 (0.56–3.75); 0.450.66 (0.21–2.07); 0.470.53 (0.15–1.81); 0.31
    Ventricular arrhythmia–related events or death from MI (N = 56)
     No./total no. (%)20/249 (8.0%)17/258 (6.6%)13/262 (5.0%)6/245 (2.4%)
     Crude*1.0 (ref.)0.82 (0.43–1.57); 0.560.60 (0.30–1.21); 0.150.30 (0.12–0.74); 0.009
     Adjusted*†1.0 (ref.)0.81 (0.43–1.56); 0.540.60 (0.30–1.20); 0.150.28 (0.11–0.71); 0.007
    All-cause mortality (N = 110)
     No./total no. (%)31/249 (12.4%)28/258 (10.9%)26/262 (9.9%)25/245 (10.2%)
     Crude*1.0 (ref.)0.88 (0.53–1.47); 0.620.78 (0.47–1.32); 0.360.81 (0.48–1.37); 0.43
     Adjusted*†1.0 (ref.)0.87 (0.52–1.46); 0.600.80 (0.47–1.34); 0.390.78 (0.46–1.33); 0.37
    • ↵*Data are HRs with 95% CIs and P values, with the use of Cox proportional hazards models.

    • ↵†Adjusted for age, sex, and smoking status.

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n-3 Fatty Acids, Ventricular Arrhythmia–Related Events, and Fatal Myocardial Infarction in Postmyocardial Infarction Patients With Diabetes
Daan Kromhout, Johanna M. Geleijnse, Janette de Goede, Linda M. Oude Griep, Barbara J.M. Mulder, Menko-Jan de Boer, Jaap W. Deckers, Eric Boersma, Peter L. Zock, Erik J. Giltay
Diabetes Care Dec 2011, 34 (12) 2515-2520; DOI: 10.2337/dc11-0896

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n-3 Fatty Acids, Ventricular Arrhythmia–Related Events, and Fatal Myocardial Infarction in Postmyocardial Infarction Patients With Diabetes
Daan Kromhout, Johanna M. Geleijnse, Janette de Goede, Linda M. Oude Griep, Barbara J.M. Mulder, Menko-Jan de Boer, Jaap W. Deckers, Eric Boersma, Peter L. Zock, Erik J. Giltay
Diabetes Care Dec 2011, 34 (12) 2515-2520; DOI: 10.2337/dc11-0896
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