HOW VITAMIN K2-MK7 CAN PERMANENTLY REVERSE ARTERIAL CALCIFICATION (PART TWO)

Atherosclerosis and arteriosclerosis devastate our arteries with age due to calcium infiltrations, contributing to degenerative diseases. Recent studies demonstrate that a deficiency in a relatively unknown vitamin, Vitamin K, leads to greater vascular calcification than initially thought.

Which forms of this Vitamin K are most effective, why pasture-raised meat is important, and how osteoporosis can also be countered with this vitamin.

In the first part of this article, I illustrated the peculiarities of Vitamin K in the context of overall health and specifically in relation to atherosclerosis and arteriosclerosis. In this second part, I delve into the technical aspect concerning the relationship between calcium and Vitamin K, particularly K2.

Calcium Inhibitors Need Vitamin K

Matrix Gla-protein is a Vitamin K-dependent protein and must be carboxylated to function properly.

But what exactly is Matrix Gla-protein, and what does carboxylated mean?

The earliest forms of life came from calcium-rich oceans, and because of this, primitive organisms developed mechanisms to prevent widespread calcium crystallization in living soft tissues (77).

An important calcium-blocking mechanism is through the activation of a protein called gamma-carboxyglutamic acid, more commonly known as Matrix Gla-protein or Matrix Gla (78).

The key to how Matrix Gla-protein functions lies in its “carboxyl” group. For Matrix Gla to function correctly, it must be carboxylated (74). In the following illustrations, there is a technical explanation of the biochemical mechanism, but it is enough to know that Vitamin K essentially activates a process that prevents calcium infiltration and thus prevents atherosclerosis, or the calcification of the arteries.

Vitamin K is a cofactor for the enzyme gamma-glutamyl carboxylase (GGCX). Together, they are necessary for the post-translational modifications of proteins (carboxylation). Protein carboxylation is achieved by converting glutamic acid residues in the protein structure into gamma-carboxyglutamic acid (Gla) residues (Figure above). These Gla residues express a strong binding affinity with calcium. This modification allows the proteins to perform their desired function.

In the presence of vitamin K2, the Matrix Gla-protein becomes “carboxylated,” which means it has been turned “on” to repel calcium infiltration. (74)

An insufficient amount of vitamin K2 means that the Matrix Gla-protein cannot be adequately carboxylated and therefore cannot inhibit calcium infiltration in soft tissues.

This means that to keep our Matrix Gla, our fundamental natural calcium inhibitor, continuously carboxylated (i.e., “on” and active), we need a constant supply of vitamin K2.

It is evident and proven that low levels of vitamin K lead to an inactive and non-carboxylated Matrix Gla-protein, which allows calcium to accumulate in soft tissues. (67-69).

The failure to optimize the carboxylation of the Matrix Gla-protein is also a risk factor (in addition to atherosclerosis) for coronary infarction and kidney diseases. (70-74).

As early as 2008, a study examining the impact of cardiovascular calcification had a title that said it all:

“Matrix Gla-protein: a calcification inhibitor that requires vitamin K.” (75-76).

The Matrix Gla-protein lines our vascular system, and its function is regulated by the amount of vitamin K in our blood.

As shown in Figure 3, when vitamin K levels are not optimal, the Matrix Gla-protein allows calcium to infiltrate our soft tissues in a manner similar to how calcium is absorbed in the bone.

When you hear the term “hardening of the arteries,” it can literally mean that previously flexible blood vessels are turning into rigid (calcified) bone-like structures.

With optimal levels of vitamin K, the Matrix Gla-protein is activated to protect calcium from arteries, heart valves, and other soft tissues.

Put differently, vitamin K functions as a control switch.

When the Matrix Gla-protein is “activated” by vitamin K, it blocks calcium from entering the soft tissues.

In the absence of adequate vitamin K, the Matrix Gla-protein switch is “deactivated,” and calcium rapidly infiltrates the soft tissues.

What happens when vitamin K is chronically low?

As I mentioned in the first part of the article, Warfarin (commercial name “Coumadin”) is an anticoagulant drug that works by antagonizing the effects of vitamin K in the body. (79)

Scientists have long been aware that patients treated with Warfarin accelerated arterial calcification, but until recently, there was no alternative to protect high-risk patients from a thrombotic event (arterial clotting), such as an ischemic stroke.

A study published in 2015 evaluated 451 women using mammography to measure arterial calcification.

After just a month or more of Warfarin therapy, the prevalence of arterial calcification increased by a staggering 50% compared to untreated women.

These women were re-evaluated five years later, and the prevalence of arterial calcification had increased by almost three times. (1)

This new study provides strong evidence of rapid calcification occurring in response to the reduction of vitamin K caused by Warfarin, which is a vitamin K antagonist drug.

What happens when vitamin K is introduced in patients with deficiency?

Patients with kidney failure are kept alive by an artificial filtration treatment called dialysis, three times a week.

This hemodialysis has undoubtedly added countless years to human life, but it produces devastating side effects in the long term.

In fact, over 50% of hemodialysis patients have vascular calcification, which, as we have seen, is one of the main causes of cardiovascular diseases.

Heart and vascular diseases account for about 50% of all deaths in these patients (80-82).

A very interesting study was conducted to evaluate the effects of different doses of the MK-7 form of vitamin K2 on markers of arterial calcification, including the carboxylation (activation) of matrix Gla-proteins (83).

MK-7 (menaquinone-7) is a unique form of vitamin K2 because it remains active in the body for 24 hours and longer (84).

Hemodialysis patients, without any kind of supplementation, have 4.5 times higher levels of non-carboxylated (thus inactive) matrix Gla-protein compared to a control group of healthy patients (83).

The dialysis patients were divided into three groups, each with different daily dosages of Vitamin K2 – MK-7 form: 45 mcg, 135 mcg, and 360 mcg, which were administered for a period of six weeks.

The results were measured based on the reduction of non-carboxylated matrix Gla-protein and other parameters of systemic calcification.

Remember that when matrix Gla is under-carboxylated, it allows calcification of the surrounding tissue.

Supplementation with the MK-7 form of vitamin K2 reduced non-carboxylated matrix Gla-protein by:

• 36.7% in the 135 mcg dosage group
• 61.1% in the 360 mcg dosage group

In the group treated with 360 mcg per day of Vitamin K2/MK-7, the favorable response rate was a remarkable 93% (83).

When vitamin K2 supplementation was stopped in these dialysis patients, plasma levels of non-carboxylated matrix Gla-protein increased significantly, indicating that these high-risk individuals were again vulnerable to severe vascular calcifications.

WHY VITAMIN K2-MK7 IS THE MOST EFFECTIVE OF THE THREE FORMS OF VITAMIN K

The three most applicable forms of vitamin K for human health are:

– Vitamin K1. Vitamin K1, also known as phylloquinone, is found in plants, and some of it converts to vitamin K2 in the body (85).

This form is considered the least effective because it depends on conversion to the more active K2 form to provide significant protection against calcification, although there are some published studies showing a reduced risk of disease in response to vitamin K1 ingestion (86-90).

– Vitamin K2 (MK-4). MK-4 is found in meat, eggs, and dairy products (91).

It is the most studied form of vitamin K for preserving bone health and is rapidly absorbed and metabolized by the body (92-96).

– Vitamin K2 (MK-7). MK-7 is found in fermented soybeans and fermented cheeses (97-98).

What makes this form so special is that it remains active in the body for more than 24 hours (84). This is crucial for protection against calcification by matrix Gla-protein, which inactivates quickly in the absence of vitamin K2 (99).

So it is evident that for an adequate intake of vitamin K2, one should consume meat and eggs and also take a daily MK-7 supplement.

Of course, some (the usual naysayers…) might argue that in the Paleolithic era, no one took vitamin K2 supplements…

Indeed, that was the case, but our ancestors did not need them because K2 was found in more than sufficient quantities in grass-fed meat, as all wild game naturally was back then.

Today, 95% of the meat we consume is grain-fed, meaning raised on cereals, so oral supplementation is necessary.

This absurd situation for our health began in the 1940s when farmers realized that livestock could be cheaply raised on a diet of cereals enriched with synthetic vitamins A and D, allowing cattle to survive without ever seeing sunlight.

Since then, these poor animals have been raised in large commercial buildings, increasing production and revenue.

The problem is that vitamin K2 is synthesized from the chlorophyll ingested by cows, chickens, or pigs when they graze on grass, which means they need to be in the sun to do so!

When animals were confined to dark spaces, without movement, and fed cereal mixtures, the ability to provide this precious vitamin K2 in their meat ended forever.

Not to mention the unnecessary suffering these poor creatures endure, which could instead live happily outdoors while providing us with high-quality meat rich in triple the omega-3 of regular meat.

And to think that homo sapiens, meaning us, consider ourselves intelligent beings…

Also, because to ingest just 45 mcg of vitamin K2, one would need to consume 4 kg of grain-fed meat.

In Italy, the health ministry’s guidelines recommend a daily intake of 70 mcg of vitamin K (with a maximum of 105 mcg in dietary supplements), while the U.S. federal government advises that adults consume 90 to 120 mcg of vitamin K per day. (100-102)

These doses are certainly sufficient to ensure proper blood coagulation, but in light of all the scientific research data I have presented above, it is clear that these dosages actually fall below the levels necessary for protection against vascular calcification. (99, 103-106)

The importance of adequate calcium intake

Calcium serves numerous vital support processes, the most important of which is maintaining the electrolyte balance necessary for proper rhythmic heartbeats. (107)

If the bloodstream were to run out of calcium, one could die from a heart attack caused by an acute arrhythmia disorder.

In a healthy body, 99% of all calcium is stored in the bones, where it provides structural support. (108)

The amount of calcium allowed in the blood is strictly controlled by the parathyroid glands. (109)

In the bones, vitamin K2 activates the proteins that bind calcium (110), and populations with high intake of this vitamin have lower rates of osteoporosis. (111-114)

The human body needs about 1,200 mg of calcium per day from the diet to maintain bone density.

Most people can rely on their diet to balance their calcium needs (115), and even (and especially) without dairy products, supplementing with moderate daily doses of calcium will not accelerate arterial calcification (116-117).

One reason is that blood calcium levels are strictly regulated in the body, and any extra ingested calcium will be stored in the bones.

Cheese is not necessary: among populations with a high rate of hip fractures (138), there is also a high intake of dairy products. On the contrary, in nations where dairy is not consumed, the incidence of osteoporosis is very low.

Your blood has the highest priority when it comes to obtaining the calcium it needs, which means that if you intentionally deprive yourself of dietary calcium, the parathyroid glands will have to steal calcium from your bones to maintain a constant blood calcium level to ensure electrolyte balance (118).

Vitamin K is a nutrient involved in calcium regulation.

When properly supplemented, vitamin K2 activates the matrix Gla-proteins in soft tissues to keep calcium out. Conversely, vitamin K2 activates calcium-binding proteins in the bones to maintain skeletal density.

In the absence of vitamin K, bone structures form in soft tissues.

Pathologists were the first to be puzzled by finding arteries that should have been soft and flexible, instead literally turning into stone.

In 1863, Rudolf Virchow, known as the “father of pathology,” described the vascular changes he observed as “ossification, not just calcification, occurring by the same mechanism by which an osteophyte forms on the surface of bone.” (119)

These observations have been confirmed by modern findings that clearly demonstrate the power of vitamin K (or its lack) to control the maintenance of strong bone density and flexible soft tissues, or to develop osteoporosis with vascular calcification.

BIBLIOGRAPHY:

1. TANTISATTAMO E, HAN KH, O’NEILL WC. INCREASED VASCULAR CALCIFICATION IN PATIENTS RECEIVING WARFARIN.ARTERIOSCLER THROMB VASC BIOL. 2015 JAN;35(1):237-42.

2. SALUSKY IB, GOODMAN WG. CARDIOVASCULAR CALCIFICATION IN END-STAGE RENAL DISEASE. NEPHROL DIAL TRANSPLANT. 2002 FEB;17(2):336-9.

3. PILKEY RM, MORTON AR, BOFFA MB, ET AL. SUBCLINICAL VITAMIN K DEFICIENCY IN HEMODIALYSIS PATIENTS. AM J KIDNEY DIS. 2007 MAR;49(3):432-9.

4. ALLISON MA, CRIQUI MH, WRIGHT CM. PATTERNS AND RISK FACTORS FOR SYSTEMIC CALCIFIED ATHEROSCLEROSIS.ARTERIOSCLER THROMB VASC BIOL. 2004 FEB;24(2):331-6.

5. DEMER LL. CHOLESTEROL IN VASCULAR AND VALVULAR CALCIFICATION. CIRCULATION. 2001 OCT 16;104(16):1881-3.

6. WAYHS R, ZELINGER A, RAGGI P. HIGH CORONARY ARTERY CALCIUM SCORES POSE AN EXTREMELY ELEVATED RISK FOR HARD EVENTS. J AM COLL CARDIOL. 2002 JAN 16;39(2):225-30.

7. ARAD Y, SPADARO LA, GOODMAN K, NEWSTEIN D, GUERCI AD. PREDICTION OF CORONARY EVENTS WITH ELECTRON BEAM COMPUTED TOMOGRAPHY. J AM COLL CARDIOL. 2000 OCT;36(4):1253-60.

8. KEELAN PC, BIELAK LF, ASHAI K, ET AL. LONG-TERM PROGNOSTIC VALUE OF CORONARY CALCIFICATION DETECTED BY ELECTRON-BEAM COMPUTED TOMOGRAPHY IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY. CIRCULATION. 2001 JUL 24;104(4):412-7.

9. KELLY RP, TUNIN R, KASS DA. EFFECT OF REDUCED AORTIC COMPLIANCE ON CARDIAC EFFICIENCY AND CONTRACTILE FUNCTION OF IN SITU CANINE LEFT VENTRICLE. CIRC RES.1992 SEP;71(3):490-502.

10. OHTSUKA S, KAKIHANA M, WATANABE H, SUGISHITA Y. CHRONICALLY DECREASED AORTIC DISTENSIBILITY CAUSES DETERIORATION OF CORONARY PERFUSION DURING INCREASED LEFT VENTRICULAR CONTRACTION. J AM COLL CARDIOL. 1994 NOV 1;24(5):1406-14.

11. WATANABE H, OHTSUKA S, KAKIHANA M, SUGISHITA Y. DECREASED AORTIC COMPLIANCE AGGRAVATES SUBENDOCARDIAL ISCHAEMIA IN DOGS WITH STENOSED CORONARY ARTERY. CARDIOVASC RES. 1992 DEC;26(12):1212-8.

12. SANGIORGI G, RUMBERGER JA, SEVERSON A, ET AL. ARTERIAL CALCIFICATION AND NOT LUMEN STENOSIS IS HIGHLY CORRELATED WITH ATHEROSCLEROTIC PLAQUE BURDEN IN HUMANS: A HISTOLOGIC STUDY OF 723 CORONARY ARTERY SEGMENTS USING NONDECALCIFYING METHODOLOGY. J AM COLL CARDIOL. 1998 JAN;31(1):126-33.

13. VLIEGENTHART R, OUDKERK M, HOFMAN A, OEI HH, VAN DIJCK W, VAN ROOIJ FJ, WITTEMAN JC. CORONARY CALCIFICATION IMPROVES CARDIOVASCULAR RISK PREDICTION IN THE ELDERLY. CIRCULATION. 2005 JUL 26;112(4):572-7.

14. KALRA SS, SHANAHAN CM. VASCULAR CALCIFICATION AND HYPERTENSION: CAUSE AND EFFECT. ANN MED. 2012 JUN;44 SUPPL 1:S85-92.

15. MESSERLI FH, AEPFELBACHER FC. HYPERTENSION AND LEFT-VENTRICULAR HYPERTROPHY. CARDIOL CLIN. 1995 NOV;13(4):549-57.

16. LEENING MJ, ELIAS-SMALE SE, KAVOUSI M, ET AL. CORONARY CALCIFICATION AND THE RISK OF HEART FAILURE IN THE ELDERLY: THE ROTTERDAM STUDY. JACC CARDIOVASC IMAGING. 2012 SEP;5(9):874-80.

17. AVAILABLE AT: HTTP://WWW.CDC.GOV/DHDSP/DATA_STATISTICS/FACT_SHEETS/FS_HEART_FAILURE.HTM. ACCESSED FEBRUARY 12, 2015.

18. AVAILABLE AT: HTTP://WWW.NCBI.NLM.NIH.GOV/PUBMEDHEALTH/PMH0062945/. ACCESSED APRIL 17, 2015.

19. BEKEREDJIAN R, GRAYBURN PA. VALVULAR HEART DISEASE: AORTIC REGURGITATION. CIRCULATION. 2005 JUL 5;112(1):125-34. REVIEW. ERRATUM IN: CIRCULATION. 2005 AUG 30;112(9):E124.

20. DUJARDIN KS, ENRIQUEZ-SARANO M, SCHAFF HV, BAILEY KR, SEWARD JB, TAJIK AJ. MORTALITY AND MORBIDITY OF AORTIC REGURGITATION IN CLINICAL PRACTICE. A LONG-TERM FOLLOW-UP STUDY. CIRCULATION. 1999 APR 13;99(14):1851-7.

21. WEBB JG, PASUPATI S, HUMPHRIES K, ET AL. PERCUTANEOUS TRANSARTERIAL AORTIC VALVE REPLACEMENT IN SELECTED HIGH-RISK PATIENTS WITH AORTIC STENOSIS. CIRCULATION. 2007 AUG 14;116(7):755-63.

22. WILLIAMS JW JR, COEYTAUX R, WANG A, ET AL. PERCUTANEOUS HEART VALVE REPLACEMENT. COMPARATIVE EFFECTIVENESS TECHNICAL BRIEFS, NO. 2. ROCKVILLE (MD): AGENCY FOR HEALTHCARE RESEARCH AND QUALITY (US); 2010 AUG. INTRODUCTION.

23. NOVARO GM, GRIFFIN BP. CALCIFIC AORTIC STENOSIS: ANOTHER FACE OF ATHEROSCLEROSIS? CLEVE CLIN J MED. 2003 MAY;70(5):471-7.

24. DWECK MR, JONES C, JOSHI NV, ET AL. ASSESSMENT OF VALVULAR CALCIFICATION AND INFLAMMATION BY POSITRON EMISSION TOMOGRAPHY IN PATIENTS WITH AORTIC STENOSIS. CIRCULATION. 2012 JAN 3;125(1):76-86.

25. MOHTY D, PIBAROT P, DESPRÉS JP, ET AL. ASSOCIATION BETWEEN PLASMA LDL PARTICLE SIZE, VALVULAR ACCUMULATION OF OXIDIZED LDL, AND INFLAMMATION IN PATIENTS WITH AORTIC STENOSIS. ARTERIOSCLER THROMB VASC BIOL. 2008 JAN;28(1):187-93.

26. LATSIOS G, TOUSOULIS D, ANDROULAKIS E, ET AL. MONITORING CALCIFIC AORTIC VALVE DISEASE: THE ROLE OF BIOMARKERS.CURR MED CHEM. 2012;19(16):2548-54.

27. PAOLISSO G, TAGLIAMONTE MR, RIZZO MR, ET AL. PROGNOSTIC IMPORTANCE OF INSULIN-MEDIATED GLUCOSE UPTAKE IN AGED PATIENTS WITH CONGESTIVE HEART FAILURE SECONDARY TO MITRAL AND/OR AORTIC VALVE DISEASE. AM J CARDIOL. 1999 MAY 1;83(9):1338-44.

28. KATZ R, WONG ND, KRONMAL R, ET AL. FEATURES OF THE METABOLIC SYNDROME AND DIABETES MELLITUS AS PREDICTORS OF AORTIC VALVE CALCIFICATION IN THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS. CIRCULATION. 2006 MAY 2;113(17):2113-9.

29. NOVARO GM, ARONOW HD, MAYER-SABIK E, GRIFFIN BP. PLASMA HOMOCYSTEINE AND CALCIFIC AORTIC VALVE DISEASE.HEART. 2004 JUL;90(7):802-3.

30. GUNDUZ H, ARINC H, TAMER A, ET AL. THE RELATION BETWEEN HOMOCYSTEINE AND CALCIFIC AORTIC VALVE STENOSIS.CARDIOLOGY. 2005 103(4):207-11.

31. HRUBY A, O’DONNELL CJ, JACQUES PF, MEIGS JB, HOFFMANN U, MCKEOWN NM. MAGNESIUM INTAKE IS INVERSELY ASSOCIATED WITH CORONARY ARTERY CALCIFICATION: THE FRAMINGHAM HEART STUDY. JACC CARDIOVASC IMAGING. 2014 JAN;7(1):59-69.

32. KOBAYASHI KJ, WILLIAMS JA, NWAKANMA L, GOTT VL, BAUMGARTNER WA, CONTE JV. AORTIC VALVE REPLACEMENT AND CONCOMITANT CORONARY ARTERY BYPASS: ASSESSING THE IMPACT OF MULTIPLE GRAFTS. ANN THORAC SURG. 2007 MAR;83(3):969-78.

33. SAINANI GS, SAINANI R. HOMOCYSTEINE AND ITS ROLE IN THE PATHOGENESIS OF ATHEROSCLEROTIC VASCULAR DISEASE. J ASSOC PHYSICIANS INDIA. 2002 MAY;50 SUPPL:16-23.

34. WILSON PW. EVIDENCE OF SYSTEMIC INFLAMMATION AND ESTIMATION OF CORONARY ARTERY DISEASE RISK: A POPULATION PERSPECTIVE. AM J MED. 2008 OCT;121(10 SUPPL 1):S15-20.

35. BUDOFF MJ. ATHEROSCLEROSIS IMAGING AND CALCIFIED PLAQUE: CORONARY ARTERY DISEASE RISK ASSESSMENT. PROG CARDIOVASC DIS. 2003 SEP-OCT;46(2):135-48.

36. AVAILABLE AT: HTTP://WWW.NHLBI.NIH.GOV/HEALTH/HEALTH-TOPICS/TOPICS/HS/TYPES. ACCESSED APRIL 18, 2015.

37. LIU YC, SUN Z, TSAY PK, CHAN T, HSIEH IC, CHEN CC, WEN MS, WAN YL. SIGNIFICANCE OF CORONARY CALCIFICATION FOR PREDICTION OF CORONARY ARTERY DISEASE AND CARDIAC EVENTS BASED ON 64-SLICE CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY. BIOMED RES INT. 2013;2013:472347.

38. EISEN A, TENENBAUM A, KOREN-MORAG N, ET AL. CORONARY AND AORTIC CALCIFICATIONS INTER-RELATIONSHIP IN STABLE ANGINA PECTORIS: A CORONARY DISEASE TRIAL INVESTIGATING OUTCOME WITH NIFEDIPINE GITS (ACTION)–ISRAELI SPIRAL COMPUTED TOMOGRAPHY SUBSTUDY. ISR MED ASSOC J. 2007 APR;9(4):277-80.

39. GREENLAND P, BONOW RO, BRUNDAGE BH, ET AL. ACCF/AHA 2007 CLINICAL EXPERT CONSENSUS DOCUMENT ON CORONARY ARTERY CALCIUM SCORING BY COMPUTED TOMOGRAPHY IN GLOBAL CARDIOVASCULAR RISK ASSESSMENT AND IN EVALUATION OF PATIENTS WITH CHEST PAIN: A REPORT OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION CLINICAL EXPERT CONSENSUS TASK FORCE. CIRCULATION. 2007 115:402-26.

40. FERNANDEZ-FRIERA L, GARCIA-ALVAREZ A, BAGHERIANNEJAD-ESFAHANI F, ET AL. DIAGNOSTIC VALUE OF CORONARY ARTERY CALCIUM SCORING IN LOW-INTERMEDIATE RISK PATIENTS EVALUATED IN THE EMERGENCY DEPARTMENT FOR ACUTE CORONARY SYNDROME. AM J CARDIOL. 2011 JAN;107(1):17-23.

41. VAN CAMPENHOUT A, MORAN CS, PARR A, ET AL. ROLE OF HOMOCYSTEINE IN AORTIC CALCIFICATION AND OSTEOGENIC CELL DIFFERENTIATION. ATHEROSCLEROSIS. 2009 FEB;202(2):557-66.

42. ALLISON MA, WRIGHT M, TIEFENBRUN J. THE PREDICTIVE POWER OF LOW-DENSITY LIPOPROTEIN CHOLESTEROL FOR CORONARY CALCIFICATION. INT J CARDIOL. 2003 AUG;90(2-3):281-9.

43. KROON PA. CHOLESTEROL AND ATHEROSCLEROSIS. AUST N Z J MED. 1997. AUG;27(4):492-6.

44. JIALAL I, DEVARAJ S. LOW-DENSITY LIPOPROTEIN OXIDATION, ANTIOXIDANTS, AND ATHEROSCLEROSIS: A CLINICAL BIOCHEMISTRY PERSPECTIVE. CLIN CHEM. 1996 APR;42(4):498-506.

45. WILSON PW, D’AGOSTINO RB, LEVY D, BELANGER AM, SILBERSHATZ H, KANNEL WB. PREDICTION OF CORONARY HEART DISEASE USING RISK FACTOR CATEGORIES. CIRCULATION. 1998 MAY 12;97(18):1837-47.

46. LIABEUF S, OLIVIER B, VEMEER C, ET AL. VASCULAR CALCIFICATION IN PATIENTS WITH TYPE 2 DIABETES: THE INVOLVEMENT OF MATRIX GLA-PROTEIN. CARDIOVASC DIABETOL. 2014 APR 24;13:85.

47. CHEN NX, MOE SM. ARTERIAL CALCIFICATION IN DIABETES. CURR DIAB REP. 2003 FEB;3(1):28-32.

48. REAVEN PD, SACKS J. CORONARY ARTERY AND ABDOMINAL AORTIC CALCIFICATION ARE ASSOCIATED WITH CARDIOVASCULAR DISEASE IN TYPE 2 DIABETES. DIABETOLOGIA . 2005 FEB;48(2):379-85.

49. NISKANEN LK, SUHONEN M, SIITONEN O, LEHTINEN JM, UUSITUPA MI. AORTIC AND LOWER LIMB ARTERY CALCIFICATION IN TYPE 2 (NON-INSULIN-DEPENDENT) DIABETIC PATIENTS AND NON-DIABETIC CONTROL SUBJECTS. A FIVE YEAR FOLLOW-UP STUDY. ATHEROSCLEROSIS. 1990 SEP;84(1):61-71.

50. GOODMAN WG, LONDON G, AMANN K, ET AL. VASCULAR CALCIFICATION IN CHRONIC KIDNEY DISEASE. AM J KIDNEY DIS. 2004 MAR;43(3):572-9. REVIEW.

51. SHARON M. MOE, NEAL X. CHEN. MECHANISMS OF VASCULAR CALCIFICATION IN CHRONIC KIDNEY DISEASE. JASN. 2008 FEB;(19)2:213-6.

52. QUNIBI WY. REDUCING THE BURDEN OF CARDIOVASCULAR CALCIFICATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE. J AM SOC NEPHROL. 2005 16(SUPPL 2):S95-S102.

53. DOHERTY TM, ASOTRA K, FITZPATRICK LA, ET AL. CALCIFICATION IN ATHEROSCLEROSIS: BONE BIOLOGY AND CHRONIC INFLAMMATION AT THE ARTERIAL CROSSROADS. PROC NATL ACAD SCI U S A. 2003 SEP 30;100(20):11201-6

54. NADRA I, MASON JC, PHILIPPIDIS P, ET AL. PROINFLAMMATORY ACTIVATION OF MACROPHAGES BY BASIC CALCIUM PHOSPHATE CRYSTALS VIA PROTEIN KINASE C AND MAP KINASE PATHWAYS: A VICIOUS CYCLE OF INFLAMMATION AND ARTERIAL CALCIFICATION? CIRC RES. 2005 JUN 24;96(12):1248-56.

55. BYON CH, JAVED A, DAI Q, ET AL. OXIDATIVE STRESS INDUCES VASCULAR CALCIFICATION THROUGH MODULATION OF THE OSTEOGENIC TRANSCRIPTION FACTOR RUNX2 BY AKT SIGNALING. J BIOL CHEM. 2008 MAY 30;283(22):15319-27.

56. DEL GOBBO LC, IMAMURA F, WU JH, DE OLIVEIRA OTTO MC, CHIUVE SE, MOZAFFARIAN D. CIRCULATING AND DIETARY MAGNESIUM AND RISK OF CARDIOVASCULAR DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF PROSPECTIVE STUDIES. AM J CLIN NUTR. 2013 JUL;98(1):160-73.

57. GORGELS TG, WAARSING JH, DE WOLF A, TEN BRINK JB, LOVES WJ, BERGEN AA. DIETARY MAGNESIUM, NOT CALCIUM, PREVENTS VASCULAR CALCIFICATION IN A MOUSE MODEL FOR PSEUDOXANTHOMA ELASTICUM. J MOL MED (BERL). 2010 MAY;88(5):467-75.

58. VAN DEN BROEK FA, BEYNEN AC. THE INFLUENCE OF DIETARY PHOSPHORUS AND MAGNESIUM CONCENTRATIONS ON THE CALCIUM CONTENT OF HEART AND KIDNEYS OF DBA/2 AND NMRI MICE. LAB ANIM. 1998 OCT;32(4):483-91.

59. MICHOS ED, VAIDYA D, GAPSTUR SM, ET AL. SEX HORMONES, SEX HORMONE BINDING GLOBULIN, AND ABDOMINAL AORTIC CALCIFICATION IN WOMEN AND MEN IN THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA). ATHEROSCLEROSIS. 2008 OCT;200(2):432-8.

60. JOFFE HV, RIDKER PM, MANSON JE, COOK NR, BURING JE, REXRODE KM. SEX HORMONE-BINDING GLOBULIN AND SERUM TESTOSTERONE ARE INVERSELY ASSOCIATED WITH C-REACTIVE PROTEIN LEVELS IN POSTMENOPAUSAL WOMEN AT HIGH RISK FOR CARDIOVASCULAR DISEASE. ANN EPIDEMIOL. 2006 FEB;16(2):105-12.

61. SARKAR NN. HORMONAL PROFILES BEHIND THE HEART OF A MAN. CARDIOL J. 2009 16(4):300-6.

62. CALDERON-MARGALIT R, SCHWARTZ SM, WELLONS MF, ET AL. PROSPECTIVE ASSOCIATION OF SERUM ANDROGENS AND SEX HORMONE-BINDING GLOBULIN WITH SUBCLINICAL CARDIOVASCULAR DISEASE IN YOUNG ADULT WOMEN: THE CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS WOMEN’S STUDY. J CLIN ENDOCRINOL METAB. 2010 SEP;95(9):4424-31.

63. TORDJMAN KM, YARON M, IZKHAKOV E, ET AL. CARDIOVASCULAR RISK FACTORS AND ARTERIAL RIGIDITY ARE SIMILAR IN ASYMPTOMATIC NORMOCALCEMIC AND HYPERCALCEMIC PRIMARY HYPERPARATHYROIDISM. EUR J ENDOCRINOL. 2010 MAY;162(5):925-33.

64. HAN D, TROOSKIN S, WANG X. PREVALENCE OF CARDIOVASCULAR RISK FACTORS IN MALE AND FEMALE PATIENTS WITH PRIMARY HYPERPARATHYROIDISM. J ENDOCRINOL INVEST. 2012 JUN;35(6):548-52.

65. REYNOLDS JL, JOANNIDES AJ, SKEPPER JN, ET AL. HUMAN VASCULAR SMOOTH MUSCLE CELLS UNDERGO VESICLE-MEDIATED CALCIFICATION IN RESPONSE TO CHANGES IN EXTRACELLULAR CALCIUM AND PHOSPHATE CONCENTRATIONS: A POTENTIAL MECHANISM FOR ACCELERATED VASCULAR CALCIFICATION IN ESRD. J AM SOC NEPHROL. 2004 NOV;15(11):2857-67.

66. ROBERTS WC, WALLER BF. EFFECT OF CHRONIC HYPERCALCEMIA ON THE HEART. AN ANALYSIS OF 18 NECROPSY PATIENTS.AM J MED. 1981 SEP;71(3):371-84.

67. LUO G, DUCY P, MCKEE MD ET AL. SPONTANEOUS CALCIFICATION OF ARTERIES AND CARTILAGE IN MICE LACKING MATRIX GLA-PROTEIN. NATURE. 1997 MAR 6;386(6620):78-81.

68. ZEBBOUDJ AF, SHIN V, BOSTRÖM K. MATRIX GLA-PROTEIN AND BMP-2 REGULATE OSTEOINDUCTION IN CALCIFYING VASCULAR CELLS. J CELL BIOCHEM. 2003 NOV 1;90(4):756-65.

69. CRANENBURG EC, VERMEER C, KOOS R, ET AL. THE CIRCULATING INACTIVE FORM OF MATRIX GLA-PROTEIN (UCMGP) AS A BIOMARKER FOR CARDIOVASCULAR CALCIFICATION. J VASC RES. 2008 45(5):427-36.

70. O’DONNELL CJ, SHEA MK, PRICE PA, ET AL. MATRIX GLA-PROTEIN IS ASSOCIATED WITH RISK FACTORS FOR ATHEROSCLEROSIS BUT NOT WITH CORONARY ARTERY CALCIFICATION. ARTERIOSCLER THROMB VASC BIOL. 2006 DEC;26(12):2769-74.

71. SCHURGERS LJ, TEUNISSEN KJ, KNAPEN MH, ET AL. NOVEL CONFORMATION-SPECIFIC ANTIBODIES AGAINST MATRIX GAMMA-CARBOXYGLUTAMIC ACID (GLA) PROTEIN: UNDERCARBOXYLATED MATRIX GLA-PROTEIN AS MARKER FOR VASCULAR CALCIFICATION. ARTERIOSCLER THROMB VASC BIOL. 2005 AUG;25(8):1629-33.

72. UELAND T, DAHL CP, GULLESTAD L, ET AL. CIRCULATING LEVELS OF NON-PHOSPHORYLATED UNDERCARBOXYLATED MATRIX GLA-PROTEIN ARE ASSOCIATED WITH DISEASE SEVERITY IN PATIENTS WITH CHRONIC HEART FAILURE. CLIN SCI (LOND). 2011 AUG;121(3):119-27.

73. SCHLIEPER G, WESTENFELD R, KRÜGER T, ET AL. CIRCULATING NONPHOSPHORYLATED CARBOXYLATED MATRIX GLA-PROTEIN PREDICTS SURVIVAL IN ESRD. J AM SOC NEPHROL. 2011 FEB;22(2):387-95.

74. SCHURGERS LJ, BARRETO DV, BARRETO FC, ET AL. THE CIRCULATING INACTIVE FORM OF MATRIX GLA PROTEIN IS A SURROGATE MARKER FOR VASCULAR CALCIFICATION IN CHRONIC KIDNEY DISEASE: A PRELIMINARY REPORT. CLIN J AM SOC NEPHROL. 2010 APR;5(4):568-75.

75. SCHURGERS LJ, CRANENBURG EC, VERMEER C. MATRIX GLA-PROTEIN: THE CALCIFICATION INHIBITOR IN NEED OF VITAMIN K.THROMB HAEMOST. 2008 OCT;100(4):593-603.

76. THEUWISSEN E, SMIT E, VERMEER C. THE ROLE OF VITAMIN K IN SOFT-TISSUE CALCIFICATION. ADV NUTR. 2012 MAR 1;3(2):166-73.

77. DEMER LL, TINTUT Y. VASCULAR CALCIFICATION: PATHOBIOLOGY OF A MULTIFACETED DISEASE. CIRCULATION. 2008 JUN 3;117(22):2938-48.

78. GOPALAKRISHNAN R, OUYANG H, SOMERMAN MJ, MCCAULEY LK, FRANCESCHI RT. MATRIX GAMMA-CARBOXYGLUTAMIC ACID PROTEIN IS A KEY REGULATOR OF PTH-MEDIATED INHIBITION OF MINERALIZATION IN MC3T3-E1 OSTEOBLAST-LIKE CELLS. ENDOCRINOLOGY. 2001 OCT;142(10):4379-88.

79. MCCABE KM, BOOTH SL, FU X, ET AL DIETARY VITAMIN K AND THERAPEUTIC WARFARIN ALTER THE SUSCEPTIBILITY TO VASCULAR CALCIFICATION IN EXPERIMENTAL CHRONIC KIDNEY DISEASE. KIDNEY INT. 2013 MAY;83(5):835-44.

80. FOLEY RN, PARFREY PS, SARNAK MJ. CLINICAL EPIDEMIOLOGY OF CARDIOVASCULAR DISEASE IN CHRONIC RENAL DISEASE.AM J KIDNEY DIS. 1998 NOV;32(5 SUPPL 3):S112-9. REVIEW.

81. HUJAIRI NM, AFZALI B, GOLDSMITH DJ. CARDIAC CALCIFICATION IN RENAL PATIENTS: WHAT WE DO AND DON’T KNOW. AM J KIDNEY DIS 2004;43:234–43.

82. NEVEN E, D’HAESE PC. VASCULAR CALCIFICATION IN CHRONIC RENAL FAILURE: WHAT HAVE WE LEARNED FROM ANIMAL STUDIES? CIRC RES. 2011 JAN 21;108(2):249-64.

83. WESTENFELD R, KRUEGER T, SCHLIEPER G, ET AL. EFFECT OF VITAMIN K2 SUPPLEMENTATION ON FUNCTIONAL VITAMIN K DEFICIENCY IN HEMODIALYSIS PATIENTS: A RANDOMIZED TRIAL. AM J KIDNEY DIS. 2012 FEB;59(2):186-95.

84. SCHURGERS LJ, TEUNISSEN KJ, HAMULYÁK K, KNAPEN MH, VIK H, VERMEER C. VITAMIN K-CONTAINING DIETARY SUPPLEMENTS: COMPARISON OF SYNTHETIC VITAMIN K1 AND NATTO-DERIVED MENAQUINONE-7. BLOOD. 2007 APR 15;109(8):3279-83.

85. BOOTH SL. VITAMIN K: FOOD COMPOSITION AND DIETARY INTAKES. FOOD NUTR RES. 2012;56.

86. VILLINES TC, HATZIGEORGIOU C, FEUERSTEIN IM, O’MALLEY PG, TAYLOR AJ. VITAMIN K1 INTAKE AND CORONARY CALCIFICATION. CORON ARTERY DIS. 2005 MAY;16(3):199-203.

87. POLI D, ANTONUCCI E, LOMBARDI A, ET AL. SAFETY AND EFFECTIVENESS OF LOW DOSE ORAL VITAMIN K1 ADMINISTRATION IN ASYMPTOMATIC OUT-PATIENTS ON WARFARIN OR ACENOCOUMAROL WITH EXCESSIVE ANTICOAGULATION. HAEMATOLOGICA. 2003 FEB;88(2):237-8.

88. SHETTY HG, BACKHOUSE G, BENTLEY DP, ROUTLEDGE PA. EFFECTIVE REVERSAL OF WARFARIN-INDUCED EXCESSIVE ANTICOAGULATION WITH LOW DOSE VITAMIN K1. THROMB HAEMOST. 1992 JAN 23;67(1):13-5.

89. BOLTON-SMITH C, MCMURDO ME, PATERSON CR, ET AL. TWO-YEAR RANDOMIZED CONTROLLED TRIAL OF VITAMIN K(1) (PHYLLOQUINONE) AND VITAMIN D(3) PLUS CALCIUM ON THE BONE HEALTH OF OLDER WOMEN. J BONE MINER RES. 2007 APR;22(4):509-19.

90. OKANO T, SHIMOMURA Y, ET AL. CONVERSION OF PHYLLOQUINONE (VITAMIN K1) INTO MENAQUINONE-4 (VITAMIN K2) IN MICE: TWO POSSIBLE ROUTES FOR MENAQUINONE-4 ACCUMULATION IN CEREBRA OF MICE. J BIOL CHEM. 2008 APR 25;283(17):11270-9.

91. ELDER SJ, HAYTOWITZ DB, HOWE J, PETERSON JW, BOOTH SL. VITAMIN K CONTENTS OF MEAT, DAIRY, AND FAST FOOD IN THE U.S. DIET. J AGRIC FOOD CHEM. 2006 JAN 25;54(2):463-7.

92. KOMAI M, SHIRAKAWA H. VITAMIN K METABOLISM. MENAQUINONE-4 (MK-4) FORMATION FROM INGESTED VK ANALOGUES AND ITS POTENT RELATION TO BONE FUNCTION. CLIN CALCIUM. 2007 NOV;17(11):1663-72.

93. MIKI T, NAKATSUKA K, NAKA H, ET AL. VITAMIN K(2) (MENAQUINONE 4) REDUCES SERUM UNDERCARBOXYLATED OSTEOCALCIN LEVEL AS EARLY AS 2 WEEKS IN ELDERLY WOMEN WITH ESTABLISHED OSTEOPOROSIS. J BONE MINER METAB. 2003 21(3):161-5.

94. KAWASHIMA H, NAKAJIMA Y, MATUBARA Y, ET AL. EFFECTS OF VITAMIN K2 (MENATETRENONE) ON ATHEROSCLEROSIS AND BLOOD COAGULATION IN HYPERCHOLESTEROLEMIC RABBITS. JPN J PHARMACOL. 1997 OCT;75(2):135-43.

95. SHEARER MJ, NEWMAN P. METABOLISM AND CELL BIOLOGY OF VITAMIN K. THROMB HAEMOST. 2008 OCT;100(4):530-47.

96. SUHARA Y, MURAKAMI A, NAKAGAWA K, MIZUGUCHI Y, OKANO T. COMPARATIVE UPTAKE, METABOLISM, AND UTILIZATION OF MENAQUINONE-4 AND PHYLLOQUINONE IN HUMAN CULTURED CELL LINES. BIOORG MED CHEM. 2006 OCT 1;14(19):6601-7.

97. CHOW CK. DIETARY INTAKE OF MENAQUINONES AND RISK OF CANCER INCIDENCE AND MORTALITY. AM J CLIN NUTR. 2010 DEC;92(6):1533-4; AUTHOR REPLY 1534-5.

98. SATO T, SCHURGERS LJ, UENISHI K. COMPARISON OF MENAQUINONE-4 AND MENAQUINONE-7 BIOAVAILABILITY IN HEALTHY WOMEN. NUTR J. 2012 NOV 12;11:93.

99. SCHURGERS LJ, SPRONK HM, SOUTE BA, SCHIFFERS PM, DEMEY JG, VERMEER C. REGRESSION OF WARFARIN-INDUCED MEDIAL ELASTOCALCINOSIS BY HIGH INTAKE OF VITAMIN K IN RATS. BLOOD. 2007 APR 1;109(7):2823-31.

100. AVAILABLE AT: HTTP://WWW.WEBMD.COM/VITAMINS-AND-SUPPLEMENTS/LIFESTYLE-GUIDE-11/SUPPLEMENT-GUIDE-VITAMIN-K?PAGE=2. ACCESSED APRIL 17, 2015.

101. MEETA, DIGUMARTI L, AGARWAL N, VAZE N, SHAH R, MALIK S. CLINICAL PRACTICE GUIDELINES ON MENOPAUSE: AN EXECUTIVE SUMMARY AND RECOMMENDATIONS. J MIDLIFE HEALTH. 2013 APR;4(2):77-106

102. AVAILABLE AT: HTTP://WWW.NLM.NIH.GOV/MEDLINEPLUS/ENCY/ARTICLE/002407.HTM. ACCESSED APRIL 17, 2015.

103. VERMEER C. VITAMIN K: THE EFFECT ON HEALTH BEYOND COAGULATION – AN OVERVIEW. FOOD NUTR RES. 2012 56.

104. ADAMS, J, PEPPING J. VITAMIN K IN THE TREATMENT AND PREVENTION OF OSTEOPOROSIS AND ARTERIAL CALCIFICATION. AM J HEALTH SYST PHARM. 2005 62(15):1574-81.

105. BERKNER KL, RUNGE KW. THE PHYSIOLOGY OF VITAMIN K NUTRITURE AND VITAMIN K-DEPENDENT PROTEIN FUNCTION IN ATHEROSCLEROSIS. J THROMB HAEMOST. 2004 DEC;2(12):2118-32.

106. AVAILABLE AT:HTTP://WWW.FDA.GOV/FOOD/GUIDANCEREGULATION/GUIDANCEDOCUMENTSREGULATORYINFORMATION/LABELINGNUTRITION/UCM064928.HTM. ACCESSED APRIL 17, 2015.

107. MARKS AR. CALCIUM AND THE HEART: A QUESTION OF LIFE AND DEATH. J CLIN INVEST. 2003 MAR;111(5):597-600.

108. BONJOUR JP. CALCIUM AND PHOSPHATE: A DUET OF IONS PLAYING FOR BONE HEALTH. J AM COLL NUTR. 2011 OCT;30(5 SUPPL 1):438S-48S. REVIEW.

109. AVAILABLE AT: HTTP://PARATHYROID.COM/PARATHYROID-FUNCTION.HTM. ACCESSED FEBRUARY 12, 2015.

110. HAUSCHKA PV. OSTEOCALCIN: THE VITAMIN K-DEPENDENT CA2+-BINDING PROTEIN OF BONE MATRIX. HAEMOSTASIS. 1986;16(3-4):258-72.

111. TSUKAMOTO Y. STUDIES ON ACTION OF MENAQUINONE-7 IN REGULATION OF BONE METABOLISM AND ITS PREVENTIVE ROLE OF OSTEOPOROSIS. BIOFACTORS. 2004 22(1-4):5-19.

112. YAMAGUCHI M. REGULATORY MECHANISM OF FOOD FACTORS IN BONE METABOLISM AND PREVENTION OF OSTEOPOROSIS.YAKUGAKU ZASSHI. 2006 NOV;126(11):1117-37.

113. IWAMOTO J. VITAMIN K₂ THERAPY FOR POSTMENOPAUSAL OSTEOPOROSIS. NUTRIENTS. 2014 MAY 16;6(5):1971-80.

114. PLAZA SM, LAMSON DW. VITAMIN K2 IN BONE METABOLISM AND OSTEOPOROSIS. ALTERN MED REV. 2005 MAR;10(1):24-35.

115. AVAILABLE AT: HTTP://WWW.NLM.NIH.GOV/MEDLINEPLUS/MAGAZINE/ISSUES/WINTER11/ARTICLES/WINTER11PG12.HTML. ACCESSED APRIL 17, 2015.

116. BHAKTA M, BRUCE C, MESSIKA-ZEITOUN D, ET AL. ORAL CALCIUM SUPPLEMENTS DO NOT AFFECT THE PROGRESSION OF AORTIC VALVE CALCIFICATION OR CORONARY ARTERY CALCIFICATION. J AM BOARD FAM MED. 2009 NOV-DEC;22(6):610-6.

117. MANSON JE, ALLISON MA, CARR JJ, ET AL. CALCIUM/VITAMIN D SUPPLEMENTATION AND CORONARY ARTERY CALCIFICATION IN THE WOMEN’S HEALTH INITIATIVE. MENOPAUSE. 2010 JUL;17(4):683-91.

118. OFFICE OF THE SURGEON GENERAL (US). BONE HEALTH AND OSTEOPOROSIS: A REPORT OF THE SURGEON GENERAL. ROCKVILLE (MD): OFFICE OF THE SURGEON GENERAL (US); 2004:3.

119. VIRCHOW R. CELLULAR PATHOLOGY: AS BASED UPON PHYSIOLOGICAL AND PATHOLOGICAL HISTOLOGY. NEW YORK, NY: DOVER;1971.

120. IWAMOTO J, TAKEDA T, ICHIMURA S. COMBINED TREATMENT WITH VITAMIN K2 AND BISPHOSPHONATE IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS. YONSEI MED J. 2003 OCT 30;44(5):751-6.

121. KANEKI M, HODGES SJ, HOSOI T, ET AL. JAPANESE FERMENTED SOYBEAN FOOD AS THE MAJOR DETERMINANT OF THE LARGE GEOGRAPHIC DIFFERENCE IN CIRCULATING LEVELS OF VITAMIN K2: POSSIBLE IMPLICATIONS FOR HIP-FRACTURE RISK.NUTRITION. 2001 APR;17(4):315-21.

122. TANAKA S, MIYAZAKI T, UEMURA Y, ET AL. DESIGN OF A RANDOMIZED CLINICAL TRIAL OF CONCURRENT TREATMENT WITH VITAMIN K2 AND RISEDRONATE COMPARED TO RISEDRONATE ALONE IN OSTEOPOROTIC PATIENTS: JAPANESE OSTEOPOROSIS INTERVENTION TRIAL-03 (JOINT-03). J BONE MINER METAB. 2014 MAY;32(3):298-304.

123. IWAMOTO J. VITAMIN K₂ THERAPY FOR POSTMENOPAUSAL OSTEOPOROSIS. NUTRIENTS. 2014 MAY 16;6(5):1971-80.

124. STEWART VL, HERLING P, DALINKA MK. CALCIFICATION IN SOFT TISSUES. JAMA. 1983 JUL 1;250(1):78-81.

125. RATTAZZI M, BERTACCO E, DEL VECCHIO A, PUATO M, FAGGIN E, PAULETTO P. AORTIC VALVE CALCIFICATION IN CHRONIC KIDNEY DISEASE. NEPHROL DIAL TRANSPLANT. 2013 DEC;28(12):2968-76.

126. RAGGI P, BOULAY A, CHASAN-TABER S, ET AL. CARDIAC CALCIFICATION IN ADULT HEMODIALYSIS PATIENTS. A LINK BETWEEN END-STAGE RENAL DISEASE AND CARDIOVASCULAR DISEASE? J AM COLL CARDIOL. 2002 FEB 20;39(4):695-701.

127. GOHR CM, FAHEY M, ROSENTHAL AK. CALCIFIC TENDONITIS : A MODEL. CONNECT TISSUE RES. 2007 48(6):286-91.

128. SATO T, HORI N, NAKAMOTO N, AKITA M, YODA T. MASTICATORY MUSCLE TENDON-APONEUROSIS HYPERPLASIA EXHIBITS HETEROTOPIC CALCIFICATION IN TENDONS. ORAL DIS. 2014 MAY;20(4):404-8.

129. GIACHELLI CM. ECTOPIC CALCIFICATION: GATHERING HARD FACTS ABOUT SOFT TISSUE MINERALIZATION. AM J PATHOL. 1999 MAR;154(3):671-5

130. SEIFERT G. HETEROTOPIC (EXTRAOSSEOUS) CALCIFICATION (CALCINOSIS). ETIOLOGY, PATHOGENESIS AND CLINICAL IMPORTANCE. PATHOLOGE. 1997 NOV;18(6):430-8.

131. ANDERSON HC, MORRIS DC. MINERALIZATION. MUNDY GR MARTIN TJ EDS. PHYSIOLOGY AND PHARMACOLOGY OF BONE.NEW YORK:SPRINGER-VERLAG.1993:267-98.

132. GIACHELLI CM. Z ECTOPIC CALCIFICATION: NEW CONCEPTS IN CELLULAR REGULATION. KARDIOL. 2001 90 SUPPL 3:31-7.

133. MACKMAN N. NEW INSIGHTS INTO THE MECHANISMS OF VENOUS THROMBOSIS. J CLIN INVEST. 2012 JUL;122(7):2331-6. DOI: 10.1172/JCI60229. EPUB 2012 JUL 2. ERRATUM IN: J CLIN INVEST. 2012 SEP 4;122(9):3368.

134. SILVERSTEIN MD, HEIT JA, MOHR DN, PETTERSON TM, O’FALLON WM, MELTON LJ 3RD. TRENDS IN THE INCIDENCE OF DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM: A 25 YEAR POPULATION-BASED STUDY. ARCH INTERN MED. 1998 MAR 23;158(6):585-93.

135. FRINK RJ, ROONEY PA JR, TROWBRIDGE JO, ROSE JP. CORONARY THROMBOSIS AND PLATELET/FIBRIN MICROEMBOLI IN DEATH ASSOCIATED WITH ACUTE MYOCARDIAL INFARCTION. BR HEART J. 1988 FEB;59(2):196-200.

136. NIESWANDT B, PLEINES I, BENDER M. PLATELET ADHESION AND ACTIVATION MECHANISMS IN ARTERIAL THROMBOSIS AND ISCHAEMIC STROKE. J THROMB HAEMOST. 2011 JUL;9 SUPPL 1:92-104.

137. BEULENS JW, BOOTH SL, VAN DEN HEUVEL EG, STOECKLIN E, BAKA A, VERMEER C. THE ROLE OF MENAQUINONES (VITAMIN K₂) IN HUMAN HEALTH. BR J NUTR. 2013 OCT;110(8):1357-68.