Highlights
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This is the first study examining association between mtDNA-CN and incident VTE.
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mtDNA-CN is not associated with incident VTE.
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Low mtDNA-CN is not a major risk factor for VTE among middle-aged women.
Introduction
Materials and methods
Study population
Laboratory measurement of mtDNA-CN
Predictor variables
Baseline measures | Incident VTE | No incident VTE | P |
---|---|---|---|
Age* | 0.34 | ||
Mean | 57.1 | 56.9 | |
Std dev | 2.8 | 2.8 | |
n | 126 | 1991 | |
mtDNA* | 0.49 | ||
Mean | 116.7 | 118.4 | |
Std dev | 28.9 | 27.0 | |
n | 126 | 1991 | |
SBP (mmHg)* | 0.84 | ||
Mean | 132.3 | 132.0 | |
Std dev | 14.9 | 17.2 | |
n | 126 | 1990 | |
DBP (mmHg)* | 0.46 | ||
Mean | 85.7 | 85.1 | |
Std dev | 8.5 | 9.0 | |
n | 126 | 1991 | |
Height mean* (cm) | 165.6 | 165.0 | 0.20 |
Std dev | 5.6 | 5.4 | |
n | 122 | 1948 | |
Weight* (kg) | 0.01 | ||
Mean | 70.8 | 67.9 | |
Std dev | 11.4 | 10.9 | |
n | 114 | 1873 | |
Body mass index | 0.01 | ||
Mean* | 26.3 | 25.5 | |
Std dev | 4.0 | 4.0 | |
n | 126 | 1991 | |
Waist (cm)* | 0.01 | ||
Mean | 84.2 | 81.5 | |
Std dev | 10.1 | 10.3 | |
N | 125 | 1962 | |
Hip (cm)* | 0.02 | ||
Mean | 105.8 | 103.7 | |
Std dev | 7.5 | 8.0 | |
N | 125 | 1962 | |
Waist Hip Ratio | 0.11 | ||
Mean* | 0.79 | 0.78 | |
Std dev | 0.07 | 0.06 | |
n | 126 | 1989 | |
Smoker** | 0.40 | ||
No | 73 (59.4%) | 1161 (59.5%) | |
Current | 28 (22.8%) | 366 (18.7%) | |
Former | 22 (17.9%) | 426 (21.8%) | |
Alcohol** | 0.54 | ||
0 g/w | 27 (23.1%) | 468 (24.8%) | |
> 0–12 g/w | 77 (65.8%) | 1154 (61.1%) | |
> 12 g/w | 13 (11.1%) | 267 (14.1%) | |
Education** | 0.65 | ||
7–9 years | 35 (28.0%) | 489 (25.0%) | |
10–12 years | 51 (40.8%) | 875 (44.7%) | |
> 12 years | 39 (31.2%) | 595 (30.4%) | |
Marital** | 0.90 | ||
Married | 99 (79.2%) | 1538 (77.6%) | |
Unmarried | 6 (4.8%) | 89 (4.5%) | |
Divorced | 15 (12.0%) | 244 (12.3%) | |
Widowed | 5 (4.0%) | 110 (5.6%) | |
Low activity** | 69 (56.1%) | 1093 (55.3%) | 0.97 |
High activity | 54 (43.9%) | 850 (43.7%) | |
Sugar*** | 0.74 | ||
Daily | 8 (6.5%) | 60 (3.1%) | |
Sometimes | 78 (62.9%) | 1326 (67.3%) | |
Avoids | 38 (30.7%) | 584 (29.6%) | |
Fat in food*** | 0.25 | ||
Much | 8 (6.7%) | 125 (6.7%) | |
Careful with | 80 (67.2%) | 1154 (61.5%) | |
Avoids | 31 (26.0%) | 597 (31.8%) | |
Dietary fiber in food*** | 0.29 | ||
Low intake | 1 (0.8%) | 21 (1.1%) | |
Regularly | 79 (64.8%) | 1164 (59.5%) | |
High intake | 42 (34.4%) | 773 (39.5%) | |
Fruit*** | 0.38 | ||
Much fruit | 83 (66.4%) | 1229 (62.2%) | |
Eats regularly | 39 (31.2%) | 708 (35.8%) | |
Eats rarely | 3 (2.4%) | 39 (21.97%) | |
Overall diet*** | 0.35 | ||
Less healthy | 16 (12.8%) | 202 (10.2%) | |
Healthy | 109 (87.2%) | 1779 (89.8%) | |
Self-rated health*** | 0.49 | ||
1. Very poor | 1 (0.8%) | 8 (0.4%) | |
2 | 0 (0.0%) | 30 (1.5%) | |
3 | 5 (4.0%) | 101 (5.2%) | |
4 | 19 (15.3%) | 271 (13.8%) | |
5 | 37 (28.8%) | 496 (25.3%) | |
6 | 38 (30.7%) | 5589 (30.1%) | |
7. Excellent | 24 (19.4%) | 463 (23.7%) | |
Self-rated health group*** | 0.84 | ||
Poor | 25 (20.2%) | 410 (20.1%) | |
Good | 99 (79.8%) | 1548 (79.1%) | |
Amount of food*** | 0.60 | ||
Big portions | 5 (4.4%) | 129 (7.0%) | |
Regularly | 81 (71.7%) | 1186 (64.5%) | |
Small portions | 27 (23.9%) | 525 (28.5%) | |
Diabetes before baseline*** | 0.59 | ||
Yes | 1 (0.8%) | 27 (1.4%) | |
No | 124 (99.2%) | 1941 (98.6%) | |
Hypertension** | 0.75 | ||
Yes | 23 (18.4%) | 343 (17.3%) | |
No | 102 (81.6%) | 1639 (82%) | |
Varicose veins*** | 0.15 | ||
Yes | 5 (4.0%) | 41 (2.1%) | |
No | 121 (96.0%) | 1950 (98.0%) | |
Acetylsalicylic treatment*** | 0.99 | ||
Yes | 1 (0.8%) | 16 (0.8%) | |
No | 125 (99.2%) | 1975 (99.2%) | |
Knowledge about family history** | 0.23 | ||
Yes | 16 (12.9%) | 180 (9.3%) | |
No | 96 (77.4%) | 1622 (83.4%) | |
Do not know | 12 (9.7%) | 144 (7.4%) |
Outcome variable (VTE)
Statistical analysis
Result
Incident VTE and mtDNA-CN
Hazard ratio | 95% CI | p | n | Failures | |
---|---|---|---|---|---|
mtDNA-CN | 0.99 | 0.99–1.00 | 0.013 | 2117 | 87 |
mtDNA-CN median* | 0.76 | 0.50–1.17 | 0.21 | 2117 | 87 |
Age | 1.05 | 0.97–1.13 | 0.23 | 2117 | 87 |
Height | 1.02 | 0.99–1.06 | 0.20 | 2070 | 85 |
Weight | 1.02 | 1.00–1.04 | 0.01 | 1987 | 79 |
BMI | 1.18 | 0.93–1.49 | 0.18 | 2117 | 87 |
Waist circumference | 1.02 | 1.00–1.04 | 0.01 | 2087 | 86 |
Hip circumference | 1.03 | 1.00–1.05 | 0.02 | 2087 | 86 |
WHR | 1.29 | 0.51–3.15 | 0.59 | 2115 | 87 |
Diastolic blood pressure | 1.01 | 0.99–1.04 | 0.30 | 2117 | 87 |
Systolic blood pressure | 1.00 | 0.99–1.02 | 0.62 | 2116 | 87 |
Education | 2084 | 87 | |||
7–9 years | 1.39 | 0.84–2.28 | 0.20 | ||
10–12 years | Ref | ||||
> 12 years | 1.00 | 0.60–1.67 | 1.00 | ||
Marital | 2106 | 87 | |||
Married | Ref | ||||
Unmarried | 1.32 | 0.53–3.29 | 0.54 | ||
Divorced | 1.07 | 0.57–2.03 | 0.83 | ||
Widowed | 0.89 | 0.32–2.44 | 0.82 | ||
High activity /low activity | 0.87 | 0.56–1.34 | 0.52 | 2066 | 85 |
Smoking | 2076 | 85 | |||
Non smoker | Ref | ||||
Current smoker | 1.30 | 0.78–2.18 | 0.32 | ||
Former smoker | 0.74 | 0.41–1.33 | 0.31 | ||
Alcohol | 2006 | 81 | |||
0 g/w | 0.98 | 0.59–1.64 | 0.94 | ||
0–12 g/w | Ref | ||||
> 12 g/w < 130 g/w | 0.67 | 0.32–1.40 | 0.28 | ||
Sugar | 2094 | 87 | |||
Daily | 2.87 | 1.30–6.33 | < 0.01 | ||
Sometimes | Ref | ||||
Avoids | 1.32 | 0.84–2.08 | 0.23 | ||
Fat in food | 1995 | 81 | |||
Much | 1.08 | 0.47–2.52 | 0.85 | ||
Careful with | Ref | ||||
Avoids | 0.84 | 0.51–1.38 | 0.49 | ||
Fiber | 2080 | 84 | |||
Low intake | 1.23 | 0.17–8.88 | 0.84 | ||
Regularly | Ref | ||||
Much | 0.96 | 0.62–1.49 | 0.85 | ||
Fruit | 2101 | 87 | |||
Much fruit | 0.96 | 0.61–1.48 | 0.84 | ||
Eats regularly | Ref | ||||
Eats rarely | 1.16 | 0.28–4.84 | 0.84 | ||
Overall diet Less healthy/healthy | 1.56 | 861–2.98 | 0.14 | 2106 | 87 |
Amount of food | 1953 | 77 | |||
Big portions | 0.64 | 0.23–1.77 | 0.39 | ||
Regularly | Ref | ||||
Small portions | 0.64 | 0.37–1.12 | 0.12 | ||
Acetylsalicylic | 1.83 | 0.25–13.13 | 0.55 | 2117 | 87 |
Knowledge about FH** VTE | 2070 | 86 | |||
Yes | 1.58 | 0.86–2.92 | 0.14 | ||
No | Ref | ||||
Do not know | 1.17 | 0.54–2.55 | 0.69 | ||
Diabetes | 0.89 | 0.12–6.39 | 0.91 | 2093 | 87 |
Hypertension | 1.30 | 0.78–2.19 | 0.32 | 2107 | 87 |
Prevalent varicose veins | 2.89 | 1.17–7.13 | 0.02 | 2117 | 87 |
Self-rated health Poor/good | 1.74 | 0.24–12.49 | 0.58 | 2117 | 87 |
Model | 1 | 2 | 3 |
---|---|---|---|
Total n | 2117 | 2117 | 2003 |
Failures n | 87 | 87 | 82 |
mtDNA median* | |||
HR | 0.76 | 0.76 | 0.89 |
CI | 0.49–1.17 | 0.50–1.17 | 0.57–1.38 |
P | 0.21 | 0.22 | 0.60 |
mtDNA (continuous) | |||
HR | 0.99 | 0.99 | 1.00 |
CI | 0.98–1.00 | 0.98–1.00 | 0.99–1.00 |
p | 0.13 | 0.14 | 0.34 |
Model 1 mtDNA-CN | Model 2 mtDNA-CN and age | Model 3 mtDNA-CN, age, smoking, waist circumference physical activity and prevalent varicose veins |
Sensitivity analysis
Model | 1 | 2 | 3 |
---|---|---|---|
Total n | 2401 | 2401 | 2277 |
Failures n | 142 | 142 | 136 |
mtDNA median* | |||
HR | 0.87 | 0.87 | 0.94 |
CI | 0.63–1.21 | 0.63–1.22 | 0.67–1.31 |
p | 0.41 | 0.42 | 0.74 |
mtDNA (continuous) | |||
HR | 1.00 | 1.00 | 1.00 |
CI | 0.99–1.00 | 0.99–1.00 | 0.99–1.01 |
p | 0.40 | 0.41 | 0.66 |
Model 1 mtDNA-CN | Model 2 mtDNA-CN and age | Model 3 mtDNA-CN, age, smoking, waist circumference physical activity and prevalent varicose veins |