TABLE 3.
Observational studies of vitamin K status, CVD, and mortality1
| Participants | Study design | Measurement of vitamin K exposure | Outcome | Results | Reference |
|---|---|---|---|---|---|
| Rotterdam study, 4807 men and women; age 67 ± 8, 60% female | Prospective, 7.2-y follow-up | Phylloquinone and menaquinone intake (µg/d) | Aortic calcification, CHD, mortality | Menaquinone, but not phylloquinone, intake inversely associated with severe aortic calcification, incident CHD, CHD mortality, all-cause mortality | (81) |
| 564 Dutch postmenopausal women; age 67 ± 5 | Cross-sectional | Menaquinone intake (µg/d) | CAC Agatston score | High menaquinone intake associated with less coronary calcification | (79) |
| Prospect-EPIC study, 16,057 Dutch postmenopausal women, mean age 59 ± 6 | Prospective, 8.1-y follow-up | Phylloquinone and menaquinone intake (µg/d) | CVD | Menaquinone, but not phylloquinone, intake inversely associated with CVD risk | (80) |
| 33,289 Men and women from the Dutch EPIC cohort, mean age 48 ± 12, 74% female | Prospective; 16.8-y follow-up | Phylloquinone and menaquinone intake (µg/d) | CVD mortality and all-cause mortality | Neither menaquinone nor phylloquinone intake associated with CVD mortality or all-cause mortality risk | (82) |
| 35,476 Men and women from the Dutch EPIC cohort, mean age 49 ± 12, 74% female | Prospective, 12.1-y follow-up | Phylloquinone and menaquinone intake (µg/d) | Stroke | Neither menaquinone nor phylloquinone intake associated with stroke risk | (93) |
| 7216 Spanish adults from the PREDIMED study, mean age 67 ± 7 | Prospective, 4.8-y follow-up | Phylloquinone and menaquinone intake (µg/d) | All-cause and CVD mortality | Phylloquinone, but not menaquinone, intake inversely associated with all-cause mortality | (86) |
| 72,874 American women from the Nurses’ Health Study, mean age 50 ± 7 y | Prospective, 16-y follow-up | Phylloquinone intake | CHD | Phylloquinone intake not associated with CHD after adjustment for healthy diet and lifestyle | (91) |
| 40,087 American men from the Health Professionals Follow-Up Study, mean age 53 ± 9 y | Prospective, 16-y follow-up | Phylloquinone intake | CHD | Phylloquinone intake not associated with CHD after adjustment for healthy diet and lifestyle | (92) |
| 5296 American men and women from NHANES, age >50 y | Cross-sectional | Phylloquinone intake (µg/d) | Arterial stiffness: pulse pressure | Inadequate dietary phylloquinone intake was associated with higher arterial pulse pressure | (94) |
| 3401 Americans with CKD from NHANES, mean age 61.9 y, 63% female | Prospective, 13.3-y follow-up | Phylloquinone intake (µg/d) | All-cause and CVD mortality | Adequate vitamin K intake associated with reduced risk for all-cause and CVD mortality | (95) |
| 508 Dutch postmenopausal women, age 56 ± 6 y | Cross-sectional | Plasma phylloquinone (nmol/L) | CAC, aortic and mitral valve, aortic artery calcification | Detectable circulating phylloquinone associated with more CAC | (96) |
| 857 American men and women from the MESA, mean age 64 ± 10 y, 45% female | Prospective case-cohort, 2.5-y follow-up | Serum phylloquinone (nmol/L) | CAC progression | Plasma phylloquinone <1.0 nmol/L associated with higher odds of CAC progression in treated hypertensives, but not in those not treated for hypertension | (97) |
| 1061 Older American men and women from Health ABC, mean age 74 ± 5 y, 58% female | Prospective, 12.1-y follow-up | Plasma phylloquinone (nmol/L) | CVD | Plasma phylloquinone <0.2 nmol/L (nondetectable) associated with higher CVD risk in treated hypertensives, but not in those not treated for hypertension | (98) |
| 3891 American men and women from MESA, Health ABC, and the Framingham Offspring, mean age 65 ± 11 y, 55% female | Meta-analysis, prospective, 13.0-y follow-up | Circulating phylloquinone (nmol/L) | CVD and all-cause mortality | Plasma phylloquinone <0.5 nmol/L associated with higher risk of all-cause mortality but not CVD | (99) |
| 200 Dutch postmenopausal women, mean age 67 ± 6 y | Cross-sectional | Plasma dp-ucMGP (pmol/L) | CAC | Borderline positive association between dp-ucMGP and CAC (P = 0.065) | (100) |
| 1087 Czech men and women from the MONICA study, mean age 55 ± 13 y, 53% female | Cross-sectional | Plasma dp-ucMGP (pmol/L) | Arterial stiffness by aortic and distal PWV | Individuals with highest circulating dp-ucMGP (≥641 pmol/L) more likely to elevated aortic PWV; dp-ucMGP was not associated with femoral artery PWV | (56) |
| 1001 Swiss men and women from Kidney Project on Genes in Hypertension (SKIPOGH), mean age 47 ± 17 y, 52% female | Cross-sectional | Plasma dp-ucMGP (pmol/L) | Aortic PWV | Plasma dp-ucMGP positively associated with aortic PWV | (54) |
| 66 American type 2 diabetics, mean age 62 ± 12 y, 9% female | Cross-sectional | Plasma dp-ucMGP (pmol/L) | Carotid-femoral PWV | Plasma dp-ucMGP positively associated with carotid-femoral PWV | (101) |
| 489 Danish adults, mean age 51 ± 13 y, 46% female | Cross-sectional | Plasma dp-ucMGP (pmol/L) | Estimated PWV (ePWV, from mean arterial pressure and age) | Plasma dp-ucMGP positively associated with ePWV | (55) |
| 147 Norwegian patients with symptomatic aortic stenosis, mean age 74 ± 10 y | Prospective, 1.9-y follow-up | Plasma dp-ucMGP (pmol/L) | All-cause mortality | Increased mortality risk in patients with >950 pmol/L dp-ucMGP | (102) |
| 107 Dutch patients with CKD, mean age 67 ± 13 y, 40% female | Prospective, 2.0-y follow-up | Plasma dp-ucMGP (pmol/L) | All-cause mortality | Increased mortality risk in patients with >921 pmol/L dp-ucMGP | (103) |
| 518 Dutch type 2 diabetics in the EPIC cohort, mean age 51 ± 7 y, 82% female | Prospective, 11.2-y follow-up | Plasma dp-ucMGP (pmol/L) | CHD, CVD, peripheral artery disease, heart failure | dp-ucMGP positively associated with CHD, CVD, peripheral artery disease, heart failure risk | (104) |
| 2940 Dutch men and women from the EPIC cohort, mean age 50 ± 12 y, 75% female | Prospective case-cohort, 11.5-y follow-up | Plasma dp-ucMGP (pmol/L) | CVD and stroke | No association between circulating dp-ucMGP and stroke risk or CVD risk | (105) |
| 577 older Dutch men and women from the Longitudinal Aging Study Amsterdam, mean age 59.9 ± 2.9 y, 55% female | Prospective, 5.6-y follow-up | Plasma dp-ucMGP (pmol/L) | CVD | Increased risk of CVD in highest tertile of dp-ucMGP (>400 pmol/L) | (58) |
| 799 Czech patients with stable vascular disease, 65 ± 9 y, 29% female | Prospective, 5.6-y follow-up | Plasma dp-ucMGP (pmol/L) | Mortality | Increased risk of mortality in highest quartile of dp-ucMGP (≥977 pmol/L) | (106) |
| 518 Dutch stable kidney transplant recipients, mean age, 51 ± 12 y, 44% female | Prospective, 9.8-y follow-up | Plasma dp-ucMGP (pmol/L) | Mortality | Increased risk of mortality in highest quartile of dp-ucMGP (≥1535 pmol/L) compared with lowest (<735 pmol/L) | (107) |
| 2318 Flemish adults, mean age 44 ± 18 y, 51% female | Prospective, 14.1-y follow-up | Plasma dp-ucMGP (pmol/L) | Total mortality, CVD mortality, noncancer mortality, coronary events | Total, CVD, and noncancer mortality risk increased in curvilinear manner as dp-ucMGP increased; coronary event risk decreased in curvilinear manner as dp-ucMGP increased | (108) |
| 1061 Older American men and women from Health ABC, mean age 74 ± 5 y, 58% female | Prospective, 12.1-y follow-up | Plasma dp-ucMGP (pmol/L) | CVD | Plasma dp-ucMGP not associated with CVD risk | (98) |
| 4275 Dutch men and women in the Prevention of Renal and Vascular End-Stage Disease Study, mean age 53 ± 12 y, 54% female | Prospective, 10-y follow-up | Plasma dp-ucMGP (pmol/L) | CVD mortality, all-cause mortality | Positive J-shape association between plasma dp-ucMGP and CVD mortality and all-cause mortality; cutoff for all-cause mortality was 414 pmol/L and for CVD mortality was 557 pmol/L | (59) |
| Meta-analysis | 7 prospective studies | Plasma dp-ucMGP (pmol/L) | CVD, CVD mortality, all-cause mortality | Plasma dp-ucMGP positively associated with all-cause mortality and cardiovascular mortality risk, but not with CVD risk | (109) |
1CAC, coronary artery calcification; CHD, coronary heart disease; CKD, chronic kidney disease; CVD, cardiovascular disease; dp-ucMGP dephosphorylated uncarboxylated matrix Gla protein; EPIC, European Prospective Investigation into Cancer and Nutrition; MESA, Multi-Ethnic Study of Atherosclerosis; MONICA MonItoring Trends and Determinants in Cardiovascular Disease, PREDIMED Prevention with Mediterranean Diet, PWV, pulse-wave velocity.