The Prospective Army Coronary Calcium Project is evaluating the predictive value of coronary artery calcium (CAC) in unselected, healthy, lower-risk, 40- to 50-year-old men. Although this study has found that coronary calcium is predictive of future coronary heart disease (CHD), criteria are needed to narrow the screening population to those in whom CAC measurement is most efficient (vs unselected screening of low-risk men). In 1,634 unselected volunteer men (mean age 42 years, mean 10-year CHD Framingham risk score [FRS] 4.6%, CAC prevalence 22.4%), we evaluated the independent relation between CAC and incident CHD over 5.6 years including hard events (hospitalized unstable angina, myocardial infarction, and CHD death) and coronary revascularization. The cohort was analyzed in tertiles of FRS for the relation between CAC and CHD outcomes. FRS tertile cutpoints were 0% to 3% (n = 547), >3% to 5% (n = 547), and >5% (n = 540) 10-year CHD risk. Over a mean follow-up of 5.6 ± 1.5 years (range 1.0 to 8.3), there were 22 total CHD events, including 14 hard events and 8 revascularizations. Most events occurred in the highest FRS tertile (n = 14) versus the middle (n = 6) and lowest (n = 2) risk tertiles (p = 0.005). CAC and CHD events increased across FRS tertiles. Only in the highest FRS tertile was there a significant relation between CAC and CHD outcomes (hazard ratio 9.3). In conclusion, CAC screening could be of benefit in refining risk assessment of low-risk men, but only when the FRS exceeds approximately 5%.
Scientific statements of the American College of Cardiology and the American Heart Association each identify coronary calcium testing as a potentially reasonable strategy to refine cardiovascular risk in patients at intermediate risk for coronary heart disease (CHD). However, such a risk level, defined as a 10-year absolute risk assessment using the Framingham risk score (FRS) of 10% to 20%, is uncommon in younger patients, even when multiple CHD risk factors are present, due to the significant weight given to age within the FRS. The Prospective Army Coronary Calcium (PACC) Project previously reported that, in asymptomatic men 40 to 50 years of age, coronary artery calcium (CAC) independently predicted risk of future CHD with an odds ratio of 11.8. However, screening lower-risk patients is generally not considered appropriate due to a perceived imbalance between costs and benefits. Nonetheless, a threshold of CHD risk may exist in younger patients above which CAC testing most effectively predicts CHD risk. Accordingly, we explored the relation among the FRS, CAC, and incident CHD in PACC Project participants.
Methods
The methods of the PACC Project have been previously published. Briefly, all active duty army personnel 40 to 50 years old and stationed within the National Capital Area of the Walter Reed Health Care System were recruited at the time of a periodic, army-mandated physical examination. Subjects with a history of coronary CHD or who indicated a history of angina pectoris by the Rose questionnaire were ineligible. From October 26, 1998, to February 19, 2003, 2,259 eligible subjects were screened and 2,000 men and women provided written informed consent to undergo electron beam computed tomography and the cardiovascular risk-screening program. Of enrolled subjects, 1,640 were men and form the basis of this report.
Each participant provided details of his medical history, lifestyle behaviors, and psychosocial history. Ethnicity was self-reported. Medical history included a history of hypertension, diabetes mellitus, hypercholesterolemia, and current medications. Smoking was self-reported as current, recent (within 6 months), or remote (>6 months) and included the use of any inhaled tobacco products with the exception of intermittent cigar consumption. A family history of CHD included a history of sudden death, myocardial infarction, or coronary revascularization in a relative before the age of 55 years (men) or 65 years (women). Family history data were collected separately for first-degree (parents, siblings, children) or second-degree (grandparents, aunts, uncles) relatives.
Blood pressure at rest was measured using an automated sphygmomanometer and was recorded as the average of 3 seated measurements taken 5 minutes apart. Hypertension was defined as a systolic blood pressure >135 mm Hg, a diastolic blood pressure >85 mm Hg, or a history of hypertension (treated or untreated). Height and weight were measured, and body mass index was calculated as weight (kilograms) divided by height (meters) squared. Waist girth was measured as the maximum abdominal circumference between the iliac crest and umbilicus. Metabolic syndrome was classified according to the recommendations of the National Cholesterol Education Program. Fasting blood was collected for the measurement of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, serum glucose, and hemoglobin A 1C . The predicted 10-year FRS for incident CHD was calculated using measured risk factor variables as specified within regression equations from the Framingham Heart Study. For the measurement of CAC, electron beam computed tomography was performed using an Imatron C-150 LXP scanner (Imatron Corp., South San Francisco, California) as previously described.
The vital status of the cohort was tracked through annual telephonic contacts during which a structured interview was conducted. Detailed interview data on a reported possible CHD event was conducted by experience nurse co-ordinators who obtained details and requested source documents (hospital records) for review. Records of the CHD event were independently reviewed by 2 researchers and a third independent cardiologist to confirm the nature of the CHD event. These reviews were conducted blinded to all cardiovascular risk factor and CAC data. This analysis report adjudicated acute CHD events defined as sudden cardiac death (sudden, unexpected death within 1 hour of onset of symptoms), myocardial infarction (documented by increased cardiac biomarkers and a clinical course of care consistent with this diagnosis), and unstable angina pectoris (acute-care hospitalization for new-onset or rapidly progressive chest pain or another ischemic equivalent symptom with demonstrated inducible ischemia or obstructive coronary artery disease and a course of care consistent with this diagnosis). Stable chest-pain syndromes and asymptomatic revascularization procedures were not included.
Of the original PACC cohort of 1,640 men, 6 were lost to follow-up. None were identified in a search of the Social Security Death Index or were known to have accessed the military or civilian health care network (ascertained through military administrative health care databases) under a cardiovascular diagnosis or procedure code. These subjects were not included in the present analysis. Mean follow-up was 5.6 ± 1.5 years (range 1 to 8.3) and included ≥2 follow-up contacts for all subjects. The time-dependent relation between CAC and CHD outcomes was analyzed using multivariate Cox proportional hazards modeling and stepwise methods to assess for the independent predictive value of CAC for CHD events. The cohort was then analyzed in tertiles based on FRS for the relation between CAC and CHD outcomes. All analyses were performed using SPSS 16.0 for Windows (SPSS, Inc., Chicago, Illinois). Data are presented as mean ± SD. A 2-tailed p value ≤0.05 was considered statistically significant.
Results
Demographic and descriptive characteristics of the 1,634 participants included in this analysis are listed in Table 1 . The most prevalent cardiac risk factors included a family history of CHD in a first- or second-degree relative (31.7%) and hypertension (14.5%). Current tobacco use was present in 6.9% of participants, and 6.6% of participants had metabolic syndrome. Mean 10-year FRS for CHD was 4.6% ± 2.6% (range 0.5 to 22). Coronary artery calcification was detected in 22.4% of participants, with a mean CAC score of 20 ± 111.
| Variable | Men |
|---|---|
| (n = 1,634) | |
| Age (years) | 42.9 ± 2.8 |
| White | 71.8% |
| Black | 17.8% |
| College-educated | 82.6% |
| Hypertension | 14.5% |
| Family history of coronary heart disease (first- or second-degree relative) | 31.7% |
| Metabolic syndrome | 6.6% |
| Current tobacco use | 6.9% |
| Diabetes mellitus | 0.8% |
| 10-year Framingham risk index | |
| Coronary heart disease | 4.6 ± 2.6 |
| Cardiovascular disease | 7.3 ± 3.9 |
| Coronary artery calcification score | |
| Mean | 19.5 ± 110.7 |
| Median | 0 |
| 0 | 1,263 (77.6%) |
| 1–9 | 120 (7.4%) |
| 10–44 | 120 (7.4%) |
| ≥45 | 124 (7.6%) |
| Baecke Sports Index ⁎ | 3.0 ± 1.0 |
| Body mass index (kg/m 2 ) | 27.8 ± 3.5 |
| Waist girth (cm) | 95.8 ± 24.9 |
| Systolic blood pressure (mm Hg) | 124.3 ± 12.0 |
| Diastolic blood pressure (mm Hg) | 77.6 ± 8.8 |
| Total cholesterol (mg/dl) | 204.2 ± 36.1 |
| Low-density lipoprotein cholesterol (mg/dl) | 128.5 ± 31.4 |
| High-density lipoprotein cholesterol (mg/dl) | 50.4 ± 12.62 |
| Triglycerides (mg/dl) | 129.8 ± 86.5 |
| Fasting glucose (mg/dl) | 92.7 ± 11.1 |
| Hemoglobin A 1C (%) (n = 1,581) | 5.4 ± 0.6 |
| Lipoprotein(a) (mg/dl) | 30.1 ± 33.5 |
| Homocysteine (μmol/L) | 9.6 ± 2.5 |
| Fibrinogen (mg/dl) | 315.2 ± 58.9 |
| Insulin (μU/ml) | 8.0 ± 6.0 |
| C-reactive protein (mg/L) (n = 832 men) | 1.9 ± 2.2 |
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