Coronary Calcification
Conditions
Keywords
coronary calcification, vitamin K dependent proteins, warfarin
Brief summary
The purpose of the study is to assess whether the use of warfarin, a commonly used anticoagulation drug, is associated with increased amounts of coronary artery calcification. Studies in animals and preliminary but small retrospective studies in humans have suggested a possible link to increased tissue calcification with use of this drug. The researchers will investigate this by assessing the amount of calcification seen in the coronary arteries using a specialized computed tomography (CT) scan (electron-beam CT) and assessing to see if the amount is influenced by the amount of time a patient has been taking warfarin. The researchers will exclude patients with known coronary artery disease, chronic kidney disease or hyperparathyroidism.
Interventions
None listed
Sponsors
Walter Reed Army Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years of age or older * Patients referred to begin or already treated with warfarin anticoagulation therapy.
Exclusion criteria
* Known prior myocardial infarction or coronary heart disease * History of advanced chronic kidney disease manifested by serum creatinine\>2 or calculated glomerular filtration rate (GFR)\<30 * History of hyperparathyroidism * Current hypercalcemia * Current hyperphosphatemia * Uncertain duration of warfarin therapy * Lack of records documenting international normalized ratio (INR) during therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Calcification (Presence and Degree as Measured by Agatston Score) Attributed to Duration of Warfarin Use in Months After Controlling for Standard Cardiovascular Risk Factors to Include the Framingham Risk Score | EBCT scan is done at time of enrollment of patient into 1 of 3 groups based on warfarin use duration: <6 months; 6-24 months; >24 mos. | The Agatston score is calculated using a non-contrast computed tomography (CT) scan to measure for the presence and severity of coronary artery disease through identification of calcification in the coronary arteries. Scores can range from 0 to several thousands. The measure is without units. Score categories are as follows: 0 = no coronary disease; 1-100 = low amount of coronary artery disease; 101-400 = moderately elevated score / moderate coronary artery disease; 401-1000 = severely elevated score; \>1000 very severely elevated score. Higher Agatston scores corelate with more coronary artery disease and predict a higher risk of coronary heart disease events and mortality. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| International Normalized Ratio | EBCT scan is done at time of enrollment of patient into 1 of 3 groups based on warfarin use duration: <6 months; 6-24 months; >24 mos. | The International Normalized Ratio (INR) is a standardized lab value that measures the intensity of anticogulation using warfarin. It is used to monitor patients taking warfarin. |
Countries
United States
Participant flow
Recruitment details
Recruitment is complete. All patients were recruited from within the Walter Reed Anticoagulation Clinic, as specified in the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Warfarin Use Short Duration Warfarin use for less than 6 months | 31 |
| 2 - Warfarin Use Intermediate Warfarin use for 6 to 24 months in duration | 11 |
| 3 - Warfarin Use Chronic Warfarin use \>24 months | 28 |
| Total | 70 |
Baseline characteristics
| Characteristic | 2 - Warfarin Use Intermediate | 3 - Warfarin Use Chronic | Warfarin Use Short Duration | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 19 Participants | 10 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 9 Participants | 21 Participants | 34 Participants |
| Age Continuous | 68 years STANDARD_DEVIATION 11 | 73 years STANDARD_DEVIATION 12 | 64 years STANDARD_DEVIATION 13 | 68 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 11 participants | 28 participants | 31 participants | 70 participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 10 Participants | 24 Participants |
| Sex: Female, Male Male | 6 Participants | 19 Participants | 21 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 31 | 0 / 11 | 0 / 28 |
| serious Total, serious adverse events | 0 / 31 | 0 / 11 | 0 / 28 |
Outcome results
Primary
Coronary Calcification (Presence and Degree as Measured by Agatston Score) Attributed to Duration of Warfarin Use in Months After Controlling for Standard Cardiovascular Risk Factors to Include the Framingham Risk Score
The Agatston score is calculated using a non-contrast computed tomography (CT) scan to measure for the presence and severity of coronary artery disease through identification of calcification in the coronary arteries. Scores can range from 0 to several thousands. The measure is without units. Score categories are as follows: 0 = no coronary disease; 1-100 = low amount of coronary artery disease; 101-400 = moderately elevated score / moderate coronary artery disease; 401-1000 = severely elevated score; \>1000 very severely elevated score. Higher Agatston scores corelate with more coronary artery disease and predict a higher risk of coronary heart disease events and mortality.
Time frame: EBCT scan is done at time of enrollment of patient into 1 of 3 groups based on warfarin use duration: <6 months; 6-24 months; >24 mos.
Population: After interim analysis following n=70 showed no effect, further enrollment was halted.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Warfarin Use Short Duration | Coronary Calcification (Presence and Degree as Measured by Agatston Score) Attributed to Duration of Warfarin Use in Months After Controlling for Standard Cardiovascular Risk Factors to Include the Framingham Risk Score | 175 Agatston Score | Standard Deviation 285 |
| 2 - Warfarin Use Intermediate | Coronary Calcification (Presence and Degree as Measured by Agatston Score) Attributed to Duration of Warfarin Use in Months After Controlling for Standard Cardiovascular Risk Factors to Include the Framingham Risk Score | 289 Agatston Score | Standard Deviation 382 |
| 3 - Warfarin Use Chronic | Coronary Calcification (Presence and Degree as Measured by Agatston Score) Attributed to Duration of Warfarin Use in Months After Controlling for Standard Cardiovascular Risk Factors to Include the Framingham Risk Score | 426 Agatston Score | Standard Deviation 789 |
Secondary
International Normalized Ratio
The International Normalized Ratio (INR) is a standardized lab value that measures the intensity of anticogulation using warfarin. It is used to monitor patients taking warfarin.
Time frame: EBCT scan is done at time of enrollment of patient into 1 of 3 groups based on warfarin use duration: <6 months; 6-24 months; >24 mos.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Warfarin Use Short Duration | International Normalized Ratio | 1.8 ratio | Standard Deviation 0.9 |
| 2 - Warfarin Use Intermediate | International Normalized Ratio | 2.4 ratio | Standard Deviation 0.4 |
| 3 - Warfarin Use Chronic | International Normalized Ratio | 2.5 ratio | Standard Deviation 0.4 |