Long-term Warfarin Treatment may induce Arterial Calcification

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Long-term Warfarin treatment may induce Arterial

calcification

JoAnn Guest

Oct 24, 2004 20:16 PDT

 

Long-term Warfarin treatment may induce Arterial calcification

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1: Clin Invest Med. 2004 Apr;27(2):107-9. Related Articles, Links

Long-term warfarin treatment may induce arterial calcification in

humans: case report.

Schori TR, Stungis GE.

 

Millennium Research, Normal, Ill 61761, USA. tsch-@millennium-

mktg.com

 

 

PURPOSE: To report a case of arterial calcification in a person who

has had long-term treatment with warfarin.

Although the anticoagulant has been shown to induce arterial

calcification in laboratory animals, there have been no previous

reports implicating warfarin as a clinical factor.

CLINICAL FEATURES: On routine annual examination, the coronary

arteries

of a healthy man with no symptoms who has had long-term warfarin

treatment were found to be highly calcified.

 

CONCLUSION: It would be prudent to further evaluate experimentally

the relationship of warfarin and arterial calcification.

 

We suggest that physicians prescribing long-term warfarin treatment

consider arterial calcification as one of its potential

consequences.

 

PMID: 15202830 [PubMed - in process]

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Genetic determinants of arterial calcification associated

with atherosclerosis.

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1: Mayo Clin Proc. 2004 Feb;79(2):197-210. Related Articles, Links

 

Genetic determinants of arterial calcification associated

with atherosclerosis.

 

Doherty TM, Fitzpatrick LA, Shaheen A, Rajavashisth TB, Detrano RC.

Burns and Allen Research Institute, Department of Medicine, Cedars-

Sinai Medical Center, David Geffen School of Medicine at UCLA, Los

Angeles, Calif, USA.

 

Increasing research interest has focused on arterial calcification

in the setting of atherosclerosis. Many features of atherosclerosis-

related

calcification provide useful clinical information.

 

For example, calcium mineral deposits frequently form in

atherosclerotic plaque, and intimal arterial calcification can be

used as a surrogate

marker for atherosclerosis;

 

also, calcium deposits are readily and noninvasively quantified,

which is useful because greater amounts of coronary calcification

predict a

higher risk of myocardial infarction and death.

 

Several mechanisms leading to calcification associated with

atherosclerosis have been proposed; however, no direct testing of

proposed mechanisms has yet been reported.

 

Studies in genetically altered animals and in humans have shed light

on potential genetic determinants, which in turn could form the

basis for a more comprehensive understanding of the factors

affecting calcification

within plaque and the associated pathobiologic implications.

 

We review proposed molecular and cellular mechanisms of

atherosclerosis-associated arterial calcification, summarize genetic

influences, and suggest areas in which further investigation is

needed.

 

Understanding the molecular and genetic determinants of specific

structural plaque components such as calcification can provide a

solid foundation for the development of novel therapeutic approaches

to favorably alter plaque structure and minimize vulnerability to

arterial rupture.

 

Publication Types:

Review

Review, Academic

 

PMID: 14959915 [PubMed - indexed for MEDLINE]

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Vascular influences of calcium supplementation and vitamin D induced

hypercalcemia

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Vascular influences of calcium supplementation and vitamin D-induced

hypercalcemia in NaCl-hypertensive rats.

Kahonen M, Nappi S, Jolma P, Hutri-Kahonen N, Tolvanen JP, Saha H,

Koivisto P, Krogerus L, Kalliovalkama J, Porsti I.

Department of Pharmacological Sciences, Medical School, University

of Tampere, Finland.

 

This 8-week study investigated the effects of increasing dietary

Ca2+ content from 1.0% to 3.0% and hypercalcemia induced by oral

1alpha-OH vitamin D3 (1OH-D3, 1.2 microg/kg), on arterial tone in

NaCl-hypertensive rats. The high-Ca2+ diet completely prevented the

increase in blood pressure induced by the 6.0% NaCl chow, while

plasma total Ca2+ and body weight were not different from controls.

The 1OH-D3 treatment moderately elevated plasma total Ca2+ and

attenuated the

NaCl-induced rise in blood pressure, but also impaired weight gain.

The tone of isolated mesenteric arterial rings was examined at the

end of study.

 

The endothelium-independent relaxations to nitroprusside,

isoproterenol,

and cromakalim were impaired in NaCl-hypertension. Experiments with

NG-nitro-l-arginine methyl ester and tetraethylammonium in vitro

suggested that both the nitric oxide- and hyperpolarization-mediated

components of endothelium-dependent relaxation to acetylcholine were

reduced in NaCl-hypertensive rats. All of the impaired relaxations

in NaCl hypertension were normalized by concomitant Ca2+

supplementation.

The 1OH-D3 treatment did not affect vascular relaxation, but it

attenuated maximal contractile responses induced by norepinephrine

and KCl by more than 50%.

 

The reduced vasoconstrictor responses could not be explained by

increased apoptosis in the vessel wall, but calcification may have

played a role, since moderate signs of medial or adventitial

calcification were observed in the aortic preparations after the 1OH-

D3 treatment.In conclusion, a high-Ca2+ diet, which did not cause

hypercalcemia,

normalized blood pressure and endothelium-dependent and

endothelium-independent vasorelaxation in NaCl-hypertensive rats.

In contrast, chronic hypercalcemia induced by 1OH-D3 was associated

with moderately lowered blood pressure, possibly because of reduced

vasoconstrictor responses in arterial smooth muscle.

 

PMID: 12960676 [PubMed - indexed for MEDLINE

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Media calcification, low erythrocyte magnesium,

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Biomed Pharmacother. 2003 Mar;57(2):88-97. Related Articles, Links

 

 

Media calcification, low erythrocyte magnesium, altered plasma

magnesium, and calcium homeostasis following grafting of the

thoracic aorta to the infrarenal aorta in the rat--

 

differential preventive effects of long-term oral magnesium

supplementation alone and in combination with alkali.

 

Schwille PO, Schmiedl A, Schwille R, Brunner P, Kissler H, Cesnjevar

R, Gepp H.

Mineral Metabolism and Endocrine Research Laboratory, University of

Erlangen, Erlangen, Germany. schw-

 

Calcifications in arterial media are clinically well documented, but

the role played by magnesium in pathophysiology and therapy is

uncertain.

To clarify this, an animal model in which the juxtacardial aorta was

grafted to the infrarenal aorta, and the subsequent calcifications

in the media of the graft and their response to oral supplementation

with three magnesium-containing and alkalinizing preparations was

investigated.

Groups of highly inbred rats were formed as follows: sham-operation

(Sham, n = 12), aorta transplantation (ATx, n = 12), ATx + magnesium

citrate (MgC, n = 12), ATx + MgC + potassium citrate (MgCPC, n =

12), ATx + MgC + MgCPC (MgCPCSB, n = 12). At 84 (+/-2) days after

ATx with or without treatment the following observations were made:

(1) weight gain and general status were normal; (2) ATx rats

developed massive media calcification, mineral accumulation in the

graft, decreased erythrocyte

magnesium and plasma parathyroid hormone, and increased plasma

ionized magnesium and calcium, and uric acid;

 

(3) Mg-treated rats developed variable degrees of metabolic

alkalosis, but only MgCPCSB

supplementation prevented calcifications.

 

Additional findings after ATx alone were: imbalance in endothelin

and nitric oxide production, the mineral deposited in media was

poorly crystallized

" calcium phosphate " , calcium exchange between plasma and graft, and

bone resorption were unchanged.

 

The superior anti-calcification effect of MgCPCSB was characterized

by complete restoration of normal extracellular mineral homeostasis

and uric acid, but sub-optimal normalization of erythrocyte

magnesium.

 

It was concluded that in the rat:

(1) ATx causes loss of cellular magnesium, excess of extracellular

magnesium and calcium in the presence of apparently unchanged bone

resorption, and increased uricemia;

(2) ATx facilitates enhanced influx of calcium into vascular tissue,

leading to calcium phosphate deposition in the media;

(3) ATx-induced calcification is prevented by dietary

supplementation

with a combination of magnesium, alkali citrate and bases.

 

Although the described circulatory model of media calcification in

the rat requires further investigation,

 

the data allow ascribing a fundamental role to magnesium and acid-

base metabolism.

 

PMID: 12842494 [PubMed - indexed for MEDLINE

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