Low Vitamin K Status Is Associated with Increased Elastin Degradation in Chronic Obstructive Pulmonary Disease
Abstract
:1. Introduction
2. Experimental Section
2.1. Study Population and Design
2.2. Assessments and Follow-up
2.3. Quantification of Vitamin K Status
2.4. Quantification of Elastin Degradation
2.5. Statistical Analysis
3. Results
3.1. ICE-Age Cohort
3.1.1. Vitamin K Status in the ICE-Age Cohort
3.1.2. Elastin Degradation in the ICE-Age Cohort
3.2. Leuven COPD Cohort
3.2.1. Vitamin K Status in the Leuven COPD Cohort
3.2.2. Elastin Degradation in the Leuven COPD Cohort
3.2.3. Effects of Vitamin K Status on Mortality in the Leuven COPD Cohort
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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ICE-Age Cohort | COPD | (Former) Smoking Controls | Never-Smoking Controls |
---|---|---|---|
Subjects, n | 192 | 124 | 62 |
Age, years | 61.9 ± 7.1 | 61.3 ± 5.9 | 60.1 ± 7.7 |
Male, n (%) | 113 (58.9) | 63 (50.8) | 23 (37.1) |
Smoking status | |||
Never-smokers, n (%) | 3 (1.6) | 62 (100) | |
Former smokers, n (%) | 124 (64.6) | 105 (84.7) | |
Current smokers, n (%) | 65 (33.9) | 19 (15.3) | |
Smoking pack years | 49.2 ± 29.7 | 18.1 ± 14.9 | 0.0 ± 0.2 |
BMI, kg/m2 | 26.7 ± 5.3 | 27.3 ± 3.4 | 26.0 ± 3.0 |
VKAs | |||
No VKAs, n (%) | 174 (90.6) | 120 (96.8) | 61 (98.4) |
VKA use, n (%) | 14 (7.3) | 3 (2.4) | 0 (0) |
VKA use unknown, n (%) | 4 (2.1) | 1 (0.8) | 1 (1.6) |
COPD stage | |||
COPD GOLD I, n (%) | 1 (0.5) | ||
COPD GOLD II, n (%) | 95 (49.5) | ||
COPD GOLD III, n (%) | 77 (40.1) | ||
COPD GOLD IV, n (%) | 19 (9.9) | ||
MRC, points | 3.0 ± 1.0 | ||
Lung function values | |||
FEV1, L | 1.39 ± 0.52 | 3.36 ± 0.70 | 3.31 ± 0.79 |
Percent of predictive normal value | 49.3 ± 15.7 | 118.3 ± 13.7 | 122.1 ± 16.0 |
FVC, L | 3.41 ± 0.92 | 4.30 ± 0.90 | 4.16 ± 0.98 |
Percent of predictive normal value | 97.5 ± 20.5 | 122.9 ± 14.9 | 126.4 ± 17.1 |
FVC IN, L | 3.48 ± 0.92 | 4.43 ± 0.91 | 4.25 ± 0.99 |
Percent of predictive normal value | 95.4 ± 19.3 | 121.9 ± 14.1 | 124.2 ± 16.0 |
FEV1/FVC, % | 41.0 ± 11.5 | 78.3 ± 4.2 | 79.5 ± 5.2 |
DLCO, mmol/min/kPa | 4.59 ± 1.83 | 8.03 ± 1.89 | 7.82 ± 2.22 |
Percent of predictive normal value | 53.4 ± 19.1 | 92.3 ± 15.9 | 94.0 ± 13.5 |
KCO, mmol/min/kPa | 0.96 ± 0.31 | 1.43 ± 0.24 | 1.50 ± 22 |
Percent of predictive normal value | 67.7 ± 23.1 | 100.8 ± 15.2 | 102.1 ± 16.9 |
ITGV, L | 4.61 ± 1.28 | 3.12 ± 0.72 | 3.06 ± 0.76 |
Percent of predictive normal value | 144.1 ± 34.0 | 99.4 ± 17.0 | 100.7 ± 20.4 |
RV, L | 3.51 ± 1.12 | 2.11 ± 0.44 | 1.95 ± 0.41 |
Percent of predictive normal value | 159.2 ± 46.8 | 96.5 ± 17.1 | 91.6 ± 18.8 |
Leuven COPD Cohort | COPD Stage | |||
---|---|---|---|---|
GOLD I | GOLD II | GOLD III | GOLD IV | |
Subjects, n | 69 | 74 | 75 | 72 |
Age, years | 64.1 ± 7.1 | 67.0 ± 71 | 67.6 ± 8.6 | 64.1 ± 8.1 |
Male, n (%) | 52 (75.4) | 55 (74.3) | 59 (78.7) | 56 (77.8) |
Smoking pack years | 44.3 ± 22.7 | 51.0 ± 24.4 | 50.2 ± 25.7 | 51.5 ± 28.3 |
BMI, kg/m2 | 25.9 ± 3.5 | 26.1 ± 4.8 | 25.2 ± 5.5 | 23.4 ± 5.6 |
VKA use, n (%) | 5 (7.2) | 10 (13.5) | 7 (9.3) | 5 (6.9) |
MRC, points | 1.6 ± 0.8 | 2.5 ± 1.0 | 3.1 ± 1.1 | 3.4 ± 1.2 |
Aortic calcification score, points | 0.79 ± 0.87 | 1.20 ± 0.88 | 1.45 ± 0.98 | 1.50 ± 1.05 |
Lung function values | ||||
FEV1, L | 2.68 ± 0.57 | 1.72 ± 0.41 | 1.13 ± 0.22 | 0.69 ± 0.14 |
Percent of predictive normal value | 90.4 ± 8.6 | 61.4 ± 7.5 | 39.9 ± 5.2 | 24.3 ± 4.1 |
FVC, L | 4.26 ± 0.91 | 3.35 ± 0.77 | 2.91 ± 0.65 | 2.31 ± 0.71 |
Percent of predictive normal value | 114.3 ± 13.3 | 94.1 ± 16.2 | 81.5 ± 14.0 | 64.4 ± 15.0 |
FEV1/FVC, % | 63.2 ± 5.1 | 52.0 ± 8.1 | 39.6 ± 7.4 | 31.4 ± 6.5 |
VC, L | 4.24 ± 0.90 | 3.38 ± 0.80 | 2.99 ± 0.65 | 2.41 ± 0.70 |
Percent of predictive normal value | 109.5 ± 13.1 | 91.7 ± 15.7 | 81.0 ± 13.8 | 64.4 ± 14.6 |
DLCO, mmol/min/kPa | 6.63 ± 2.22 | 4.89 ± 1.57 | 3.89 ± 1.40 | 3.04 ± 0.88 |
Percent of predictive normal value | 74.6 ± 20.5 | 57.4 ± 15.7 | 46.1 ± 15.6 | 35.8 ± 9.8 |
KCO, mmol/min/kPa | 1.12 ± 0.30 | 1.04 ± 0.30 | 0.91 ± 0.30 | 0.88 ± 0.28 |
Percent of predictive normal value | 81.3 ± 21.2 | 76.0 ± 22.1 | 67.1 ± 21.4 | 63.9 ± 20.0 |
ITGV, L | 4.09 ± 0.81 | 4.41 ± 1.07 | 5.22 ± 1.21 | 6.10 ± 1.45 |
Percent of predictive normal value | 121.5 ± 19.3 | 132.4 ± 28.8 | 156.2 ± 33.5 | 183.1 ± 36.9 |
RV, L | 2.72 ± 0.67 | 3.17 ± 0.80 | 3.89 ± 1.00 | 4.95 ± 1.29 |
Percent of predictive normal value | 115.6 ± 23.1 | 134.7 ± 31.7 | 166.0 ± 41.7 | 212.7 ± 50.3 |
TLC, L | 6.95 ± 1.26 | 6.55 ± 1.31 | 6.88 ± 1.32 | 7.36 ± 1.56 |
Percent of predictive normal value | 108.0 ± 11.0 | 104.8 ± 16.6 | 110.4 ± 18.1 | 118.3 ± 20.2 |
Airway resistance, kPa/L/sec | 0.34 ± 0.12 | 0.47 ± 0.14 | 0.57 ± 0.14 | 0.77 ± 0.20 |
Percent of predictive normal value | 152.4 ± 54.8 | 214.5 ± 64.2 | 260.8 ± 63.7 | 349.4 ± 91.7 |
Specific airway conductance, 1/kPa*sec | 0.78 ± 0.24 | 0.51 ± 0.16 | 0.35 ± 0.11 | 0.23 ± 0.07 |
Percent of predictive normal value | 91.2 ± 28.4 | 60.0 ± 19.1 | 41.1 ± 13.1 | 26.7 ± 8.2 |
Mortality | ||||
Died during follow-up, n (%) | 16 (23.2) | 27 (36.5) | 44 (58.7) | 47 (65.3) |
Mortality unknown, n (%) | 4 (5.8) | 0 (0) | 2 (2.7) | 1 (1.4) |
Follow-up, years | 5.9 ± 2.0 | 6.1 ± 2.1 | 4.9 ± 2.7 | 4.3 ± 2.8 |
dp-ucMGP | pDES | |||||
ICE-Age Cohort | Ratio | 95% CI | p-Value | Ratio | 95% CI | p-Value |
VKA use, yes | 198.6% | 138.7 to 274.0% | p < 0.0005 | 4.2% | −8.1 to 18.1% | p = 0.522 |
Presence of COPD, yes | 36.8% | 21.5 to 53.7% | p < 0.0005 | 15.6% | 8.3 to 23.4% | p < 0.0005 |
Gender, female | −8.9% | −17.4 to 0.5% | p = 0.064 | 5.3% | −0.3 to 11.2% | p = 0.064 |
Age, per year | 2.3% | 1.6 to 3.0% | p < 0.0005 | 2.1% | 1.7 to 2.5% | p < 0.0005 |
BMI, per kg/m2 | 3.6% | 2.5 to 4.7% | p < 0.0005 | −0.1% | −0.7 to 0.5% | p = 0.794 |
Smoking packyears, per year | 0.1% | −0.1 to 0.3% | p = 0.489 | 0.1% | 0.0 to 0.2% | p = 0.132 |
Dp−ucMGP, per 10% | - | - | - | 1.0% | 0.4 to 1.5% | p = 0.001 |
Lung function parameters | ||||||
FEV1, per 10 pp | −3.0% | −6.8 to 1.0% | p = 0.173 | 1.0% | −1.0 to 4.1% | p = 0.323 |
FVC, per 10 pp | −1.0% | −3.9 to 2.0% | p = 0.533 | 1.0% | −2.0 to 3.0% | p = 0.585 |
FVC IN, per 10 pp | −1.0% | −3.9 to 2.0% | p = 0.547 | 0.0% | −2.0 to 3.0% | p = 0.667 |
FEV1/FVC, per 10 pp | −1.0% | −1.0 to 6.6% | p = 0.199 | 1.0% | −3.0 to 5.0% | p = 0.607 |
DLCO, per 10 pp | −4.9% | −8.6 to −2.0% | p = 0.005 | −3.9% | −5.8 to −1.0% | p = 0.004 |
KCO, per 10 pp | −3.0% | −5.8 to 2.0% | p = 0.076 | −3.0% | −4.9 to −1.0% | p = 0.004 |
RV, per 10 pp | 0.1% | −1.0 to 2.0% | p = 0.430 | 0.0% | −1.0 to 1.0% | p = 0.428 |
ITGV, per 10 pp | 0.0% | −2.0 to 2.0% | p = 0.850 | 0.0% | −2.0 to 1.0% | p = 0.723 |
dp-ucMGP | pDES | |||||
Leuven COPD Cohort | Ratio | 95% CI | p-Value | Ratio | 95% CI | p-Value |
VKA use, yes | 141.1% | 62.9 to 256.4% | p < 0.0005 | 5.4% | −9.3 to 22.5% | p = 0.485 |
Gender, female | 14.3% | −13.1 to 50.4% | p = 0.336 | 5.0% | −5.4 to 16.6% | p = 0.360 |
Age, per year | 1.3% | −0.2 to 2.8% | p = 0.079 | 3.0% | 2.5 to 3.7% | p < 0.0005 |
BMI, per kg/m2 | 1.9% | −0.4 to 4.3% | p = 0.109 | −0.5% | −1.3 to 0.4% | p = 0.294 |
Smoking packyears, per year | 0.0% | −0.4 to 0.5% | p = 0.845 | 0.2% | 0.0 to 0.3% | p = 0.065 |
Dp-ucMGP, per 10% | - | - | - | 0.6% | 0.2 to 1.1% | p = 0.004 |
Lung function parameters | ||||||
FEV1, per 10 pp | 2.0% | −3.0 to 6.2% | p = 0.472 | 2.0%, | 0.0 to 4.1%, | p = 0.027 |
FVC, per 10 pp | 0.0% | −4.9 to 5.1% | p = 0.925 | 1.0% | −1.0 to 3.0% | p = 0.296 |
FEV1/FVC, per 10 pp | 5.1% | −3.9 to 13.9% | p = 0.272 | 5.1%, | 2.0 to 9.4% | p = 0.001 |
VC, per 10 pp | 0.0% | −4.9 to 5.1% | p = 0.989 | 1.0% | −1.0 to 3.0% | p = 0.441 |
DLCO, per 10 pp | −4.9% | −10.4 to 1.0% | p = 0.075 | −2.0% | −3.9 to 0.0% | p = 0.084 |
KCO, per 10 pp | −4.9% | −10.4 to 1.0% | p = 0.075 | −2.0% | −3.9 to −0.02% | p = 0.048 |
ITGV, per 10 pp | −3.9% | −6.8 to −1.0% | p = 0.023 | −2.0% | −3.0 to −1.0% | p = 0.002 |
RV, per 10 pp | −3.0% | −4.9 to −1.0% | p = 0.012 | −1.0% | −2.0 to −1.0% | p = 0.001 |
TLC, per 10 pp | −9.5% | −15.6 to −3.0 % | p = 0.004 | −4.9% | −6.8 to −2.0% | p = 0.001 |
Airway resistance, per 10 pp | 0.0% | −2.0 to 1.0% | p = 0.472 | 0.0% | −1.0 to 0.1% | p = 0.114 |
Specific airway conductance, per 10 pp | 3.0% | −1.0 to 7.3% | p = 0.139 | 2.0% | 0.0 to 3.0% | p = 0.009 |
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Piscaer, I.; van den Ouweland, J.M.W.; Vermeersch, K.; Reynaert, N.L.; Franssen, F.M.E.; Keene, S.; Wouters, E.F.M.; Janssens, W.; Vermeer, C.; Janssen, R. Low Vitamin K Status Is Associated with Increased Elastin Degradation in Chronic Obstructive Pulmonary Disease. J. Clin. Med. 2019, 8, 1116. https://doi.org/10.3390/jcm8081116
Piscaer I, van den Ouweland JMW, Vermeersch K, Reynaert NL, Franssen FME, Keene S, Wouters EFM, Janssens W, Vermeer C, Janssen R. Low Vitamin K Status Is Associated with Increased Elastin Degradation in Chronic Obstructive Pulmonary Disease. Journal of Clinical Medicine. 2019; 8(8):1116. https://doi.org/10.3390/jcm8081116
Chicago/Turabian StylePiscaer, Ianthe, Jody M. W. van den Ouweland, Kristina Vermeersch, Niki L. Reynaert, Frits M. E. Franssen, Spencer Keene, Emiel F. M. Wouters, Wim Janssens, Cees Vermeer, and Rob Janssen. 2019. "Low Vitamin K Status Is Associated with Increased Elastin Degradation in Chronic Obstructive Pulmonary Disease" Journal of Clinical Medicine 8, no. 8: 1116. https://doi.org/10.3390/jcm8081116