RESEARCH - Long-term anticoagulant users show elevated coronary, aortic calcium

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Long-term anticoagulant users show elevated coronary, aortic calcium

12/2/2005

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CHICAGO - Patients who take oral anticoagulants may risk developing

significant coronary and aortic calcification. In a study that casts a wary

eye on the routine use of the vitamin K antagonists such as warfarin,

researchers from Aachen, Germany, found that long-term oral anticoagulant

therapy was independently associated with increased calcium scores and

valvular calcium deposits.

To date the evidence linking oral anticoagulation (OAC) therapy with

increased calcification has been insufficient, said Dr. s Mahnken in a

presentation Friday at the 2005 RSNA meeting.

Vitamin K antagonists are known to affect the synthesis of the matrix Gla

protein, which inhibits calcification in tissues, said Mahnken, who is from

the Aachen University of Technology.

" We know there might be a correlation between the severity of coronary

artery calcium and the presence of matrix Gla protein, reported about a year

ago, " he said (Jono S. Journal of Thrombosis and Haemostasis, 2004, Vol. 91,

pp. 790; Schurges LJ. Blood, 2004, Vol. 104, pp. 323). " We also know that

calcification is usually greater in patients who use oral anticoagulants for

a long time, but we don't know what's going on in patients who have aortic

stenosis. "

The researchers sought to determine if there is an association between the

use of oral anticoagulants and Agatston calcium scores, as well as aortic

calcification.

Their prospective study examined 86 patients with aortic stenosis (53 men,

33 women; mean age 71 ± eight years) including 23 on long-term oral

anticoagulant therapy (OAC) for six to 384 months (mean 88 months ± 113).

Those with diseases associated with increased coronary calcification, such

as Paget's disease, hyperthyroidism, and elevated serum calcium were

excluded.

Most patients were on anticoagulant therapy for chronic atrial fibrillation

(n = 16, 70%); other indications included low ejection fraction due to

nonischemic cardiomyopathy (n = 3, 13%), recurrent deep venous thrombosis (n

= 2, 9%), and recurrent PE or stroke (for each indication n = 1, 4%).

All patients underwent MDCT imaging on a 16-row scanner (Sensation 16,

Siemens Medical Solutions, Erlangen, Germany) at 12 x 0.75 mm, 120 kVp, 133

effective mAs, and 3-mm slice thickness with 2-mm overlapping

reconstructions. The images were evaluated for Agatston coronary calcium

score and same scoring method was used for aortic calcification, Mahnken

said. Echocardiography was also performed to assess the presence of

stenosis.

The results showed significant differences in coronary calcium burden

between the two patient groups. The mean coronary calcium score in patients

without OAC was 738 ± 978 versus 1,561 ± 1,141 in patients with long-term

OAC (p = 0.024). Similarly, the mean aortic calcium score was 1,070 ± 1,085

in patients without OAC versus 2,410 ± 1,759 in patients with long-term OAC

(p = 0.002).

" There was no correlation between the duration of the oral anticoagulation

therapy and the coronary (p=0.35) or aortic calcification score (p=0.31),

but it's important to note that we only included patients . with at least 6

months of anticoagulation therapy, " Mahnken said.

Multiple linear regression analysis found that OAC was an independent

predictor of coronary calcium score (p = 0.011 for OAC, compared to p =

0.045 for male gender, p = 0.049 for hypertension).

" We conclude from our findings that oral anticoagulation is associated with

increasing levels of calcium in the coronary arteries as well as aortic

valve, " Mahnken said. " This is due to the decreased protection against

tissue calcification which is caused by the decreased vitamin K activation

of the matrix Gla protein, " he said. " This will be of clinical interest in

patients who have aortic stenosis, and we expect them to have a faster

increase in the calcification level. "

The effect will need to be confirmed in larger trials; the group has

initiated a five-year study that is already under way, he said.

" We are sure that we are also exposing young patients to a higher risk of

developing vascular calcification, " Mahnken said in response to an audience

member who asked about the age distribution of increased calcification. The

department of nephrology at his institution has come to the same conclusion,

he said.

" Everywhere in Europe there is heavy discussion of this issue, because all

patients undergoing dialysis, for example, have problems with oral

anticoagulation, " he said, adding that warfarin is strongly implicated in

the development of calcification that is independent of the calcification

risk of dialysis alone.

Internal medicine doctors and pathologists really became aware of the

problem with OAC about a year ago, and the interest has intensified since

that time, Mahnken told AuntMinnie.com. " But it takes a long time before

radiologists become aware of it because we are farther away from the

patient, " he said.

By

AuntMinnie.com staff writer

December 2, 2005

http://www.auntminnie.com/index.asp?Sec=sup & Sub=cto & Pag=dis & ItemId=69054 & wf=525

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Mayo Clinic in Rochester

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