Those infected with the human immunodeficiency virus (HIV) have a greater risk of cardiovascular disease and might undergo computed tomographic (CT) scans for early detection. Incidental findings on cardiac CT imaging are important components of the benefits and costs of testing. We determined the prevalence and factors associated with incidental findings on CT scans performed to screen for coronary artery calcium (CAC) among HIV-infected men. A clinically significant finding was defined as requiring additional workup or a medical referral. A total of 215 HIV-infected men were evaluated. Their median age was 43 years; 17% were current tobacco users; the median CD4 count was 580 cells/mm 3 ; and 83% were receiving antiretroviral medications. Also, 34% had a positive CAC score of >0. An incidental finding was noted among 93 participants (43%), with 36 (17%) having ≥1 clinically significant finding. A total of 139 findings were noted, most commonly pulmonary nodules, followed by granulomas, scarring, and hilar adenopathy. Most of the incidental findings were stable on follow-up, and no malignancies were detected. The factors associated with the presence of an incidental finding in the multivariate model included increasing age (odds ratio 1.6 per 10 years, p <0.01), positive CAC score (odds ratio 2.3, p <0.01), and current tobacco use (odds ratio 2.5, p = 0.02). In conclusion, incidental findings were common among HIV-infected men undergoing screening CT imaging for CAC determination. The incidental findings were more common among older patients and those with detectable CAC.
Although several studies have used coronary artery calcium (CAC) scores to measure subclinical heart disease in human immunodeficiency virus (HIV)-infected persons, no study to date has determined the frequency and types of incidental abnormalities found during these tests. Studies evaluating the incidental findings detected on coronary computed tomographic (CT) imaging (CAC and angiography) in the general population have been published but did not specifically evaluate HIV-infected subjects. HIV-infected persons might be at a greater risk of infectious and malignant conditions, which could have implications for the type and number of incidental findings on imaging studies. Incidental findings are important, because they not only affect the clinical usefulness, but also the cost-effectiveness, of screening CT scans. We report the frequency and clinical significance of incidental findings among HIV-infected persons undergoing CT screening for CAC determination.
Methods
We evaluated HIV-infected men who were screened for CAC using noncontrast CT imaging of the heart from December 9, 2008 to March 1, 2010. The primary study objective was to determine the prevalence of subclinical coronary atherosclerosis using the Agatston scoring method. The objectives of the present substudy were to describe the prevalence and types of incidental findings on CT scans during standard imaging for CAC scores, and to compare the characteristics of HIV-infected men with and without incidental findings.
The inclusion criteria for study participation were a positive HIV test (enzyme-linked immunosorbent assay confirmed by Western blot) and being a military beneficiary, which included active duty members, retirees, and family members. All participants provided written informed consent, and the governing institutional review board approved the study. The study was registered at ClinicalTrials.gov (study identifier NCT00889577 ).
The clinical data collected at the time of the CT scan included demographics, tobacco use history, body mass index, waist circumference, C-reactive protein (lower limit of detection <0.5 mg/dl; particle enhanced immunoturbidimetric Assay, Roche, Indianapolis, Indiana), erythrocyte sedimentation rate (modified Westergren method), CD4 cell counts (flow cytometry), plasma HIV RNA levels (Roche Amplicor, undetectable at <50 copies/ml), and antiretroviral therapy use. The diagnosis of hypercholesterolemia (total cholesterol >200 mg/dl), hypertension, and diabetes (determined by the use of medications for these conditions) and a history of an opportunistic infection were recorded.
Participants underwent noncontrast CT imaging using a multidetector CT machine. Prospectively gated, axial, 3-mm images were obtained at 120 kV on a Siemens Definition Dual Source CT scanner (Siemens Medical Solutions, Forsheim, Germany). The scanning protocol captured images with a 330-ms gantry rotation time, an individual detector width of 0.6 mm with a reconstructed section width of 3 mm and a temporal resolution of 165 ms. Contiguous 3-mm-thick sections were reconstructed during peak inspiration with a 16- to 25-cm field of view, depending on the heart size. The images were processed on an Impax 6.3 workstation (Agfa-Gevaert Group, Mortsel, Belgium). The full field of view reconstructions were performed of the entire lungs at the levels from the carina to just below the cardiac apex. The CT images also included the mediastinum, hilum, and diaphragm. The abdominal organs were not visualized unless the diaphragm had been shifted cranially because of underlying pathology. CAC scoring was performed using an Aquarius workstation (TeraRecon, San Mateo, California) and calculated as the sum of all lesions in each of the coronary arteries using Agatston units, as previously described. A CAC score of >0 was considered positive for detectable calcium.
The images were read by a board-certified radiologist (G.B.) for incidental noncoronary findings at CAC scoring. Any finding requiring additional clarification was reread by the same radiologist. Incidental findings were captured only if the finding was not solely age-related (e.g., calcification of the aorta), due to trauma (e.g., old rib fractures), or postoperative. The incidental findings were classified as clinically significant by the need for additional workup, including imaging or medical referral. The need for additional radiologic imaging was determined using available evidence-based criteria; for example, the management of pulmonary nodules was determined using the Fleischner guidelines. A pulmonary nodule was defined as a ≤3-cm lesion in the lung parenchyma and a granuloma as a calcified opacity. The patients with emphysema or bronchiectasis were recommended for referral to pulmonary medicine. The medical records of the participants with a clinically significant incidental finding were reviewed in August 2010 for clinical outcomes, including data on follow-up imaging.
The statistical analysis included descriptive statistics of the prevalence of incidental findings. Categorical variables are described as numbers with proportions and continuous variables as medians with interquartile ranges. The incidental findings were divided into “clinically significant” and “not clinically significant,” as defined. The comparisons of participants with and without incidental findings were performed using Fisher’s exact and rank-sum tests for categorical and continuous variables, respectively. A multivariate logistic regression model was performed to evaluate the factors associated with the incidental findings on cardiac CT scanning. The variables with p <0.10 on univariate testing were placed in the full multivariate model, and a backward stepwise approach was used to derive the final model. p-values <0.05 were considered statistically significant. All analyses were performed using Stata, version 10 (StataCorp, College Station, Texas).
Results
The study population consisted of 215 HIV-infected men ( Table 1 ). An incidental finding was noted for 93 patients (43%), with 36 (17%) having a clinically significant finding that required follow-up or medical referral. The range of incidental findings per person was 0 to 5. Of those with an incidental finding, 62 patients had 1 finding, 19 had 2 findings, 10 had 3 findings, 1 had 4 findings, and 1 had 5 findings.
| Characteristic ⁎ | Total Cohort (n = 215) | Incidental Findings | p-value | |
|---|---|---|---|---|
| Yes (n = 93) | No (n = 122) | |||
| Age (years) | 43 (36–50) | 48 (39–52) | 41 (34–47) | <0.01 |
| Ethnicity | ||||
| White | 110 (51%) | 50 (54%) | 60 (49%) | 0.69 |
| Black | 48 (22%) | 21 (22%) | 27 (22%) | |
| Other | 57 (27%) | 22 (24%) | 35 (29%) | |
| Tobacco use | ||||
| Current | 37 (17%) | 22 (23%) | 15 (12%) | 0.04 |
| Ever | 109 (51%) | 54 (58%) | 55 (45%) | 0.07 |
| Years of use † | 12 (5–20) | 17 (8–26) | 10 (5–18) | <0.01 |
| Diabetes mellitus | 13 (6%) | 10 (11%) | 3 (2%) | 0.02 |
| Hypertension | 64 (30%) | 34 (37%) | 30 (25%) | 0.07 |
| Hypercholesteremia ‡ | 66 (31%) | 27 (29%) | 39 (32%) | 0.66 |
| Body mass index (kg/m 2 ) | 26.7 (24.1–29.5) | 26.8 (23.8–29.6) | 26.5 (24.4–29.1) | 0.86 |
| Waist circumference (cm) | 94 (85–100) | 94 (87–103) | 93 (85–98) | 0.31 |
| C-reactive protein >0.5 mg/dl | 30 (14%) | 14 (15%) | 16 (13%) | 0.70 |
| Erythrocyte sedimentation rate (mm/hour) | 10 (7–18) | 13 (9–23) | 10 (7–15) | <0.01 |
| Erythrocyte sedimentation rate >20 mm/hour | 47 (22%) | 26 (28%) | 21 (17%) | 0.07 |
| Presence of coronary atherosclerosis (coronary artery calcium >0) | 74 (34%) | 43 (46%) | 31 (25%) | <0.01 |
| Human immunodeficiency virus duration (years) | 12 (5 to 19) | 13 (7 to 21) | 9 (5 to 19) | 0.08 |
| Current CD4 cell count (cells/mm 3 ) | 580 (386–729) | 563 (334–682) | 600 (457–754) | 0.02 |
| Nadir CD4 cell count (cells/mm 3 ) | 260 (138–366) | 230 (100–360) | 278 (184–367) | 0.06 |
| Undetectable human immunodeficiency virus RNA level (<50 copies/ml) | 150 (70%) | 59 (63%) | 91 (75%) | 0.10 |
| Current antiretroviral therapy | 178 (83%) | 74 (80%) | 104 (85%) | 0.28 |
| History of opportunistic infection | 16 (7%) | 9 (10%) | 7 (6%) | 0.30 |
⁎ Categorical variables expressed as n (%) and continuous variables as median (interquartile range).
† Among those with a history of tobacco use.
‡ Hypercholesteremia defined as total cholesterol >200 mg/dl.
The number and type of incidental findings are listed in Table 2 . A total of 139 incidental findings were noted, with some participants having multiple findings. The most common findings were pulmonary nodules, followed by granulomas and scars. A total of 15 patients (7% of the cohort) had findings consistent with emphysema or bronchiectasis. Several extrapulmonary findings were noted, including gynecomastia, hiatal hernia, pathologic aortic dilation, and a large (15 × 13 cm) asymptomatic splenic cyst.
| Finding | Incidental Findings (n) | Findings With Clinical Significance (n) |
|---|---|---|
| Lung | 78 | 37 |
| Parenchymal/bronchi | ||
| Nodule | 23 | 18 |
| Granuloma | 19 | 0 |
| Scar | 13 | 0 |
| Emphysema | 9 | 9 † |
| Bronchiectasis | 6 | 6 † |
| Parenchymal opacity/consolidation | 4 | 3 |
| Bronchial opacity | 2 | 1 |
| Bullae | 1 | 0 |
| Pleura | ||
| Pleural thickening | 1 | 0 |
| Heart | 4 | 2 |
| Cardiac valves with significant calcification | 2 | 2 |
| Papillary muscle fat/calcification | 2 | 0 |
| Mediastinum | 9 | 1 |
| Lymph nodes | 7 | 0 |
| Mass | 2 | 1 |
| Hilum/subcarina | 18 | 0 |
| Lymph node | 17 | 0 |
| Granuloma | 1 | 0 |
| Pericardiac | 1 | 1 |
| Lymph node | 1 | 1 |
| Other | 29 | 5 |
| Gynecomastia | 8 | 0 |
| Hiatal hernia | 7 | 0 |
| Axillary adenopathy | 7 | 0 |
| Aortic dilation/aneurysm | 1 | 1 |
| Thymus mass | 1 | 1 |
| Paralyzed hemidiaphragm | 1 | 1 |
| Diaphragm eventration | 1 | 0 |
| Pectus excavatum | 1 | 0 |
| Enlarged pulmonary artery | 1 | 1 |
| Large splenic cyst ‡ | 1 | 1 |
| Total | 139 | 46 |
⁎ Some patients had multiple incidental findings.
† Medical referral recommended.
Of the incidental findings, 46 (33%) were deemed clinically significant. Most often, these were pulmonary nodules ( Table 2 ). On the follow-up evaluation at a median of 15 months (range 6 to 21) after the initial CT scan for CAC scoring, 15 of 18 of the pulmonary nodules were reimaged. Of the 15 pulmonary nodules, 13 were unchanged; 1 had increased in size (from 7 to 20 mm) but the workup findings, including bronchoscopy with cultures and cytology, have been negative; and 1 was determined not to be a nodule on reimaging. The remaining 3 participants with pulmonary nodules failed to undergo the scheduled follow-up imaging. The patients with pneumonia/opacities received antibiotics, and the cases had resolved or were improving for 4 of the 5 who underwent repeat imaging. The subjects with emphysema or bronchiectasis had no changes in management, except for 1, for whom bronchodilators were prescribed. The aortic dilation detected on imaging remained stable. The single patient with the large splenic cyst underwent splenectomy because of the high risk of rupture. Only 1 participant died during the follow-up period; the cause of death was not associated with the incidental finding (i.e., nodule) on CT imaging.
The HIV-infected persons with an incidental finding were older (48 vs 41 years, p <0.01), were current tobacco users (23% vs 12%, p = 0.04), were diabetic (11% vs 2%, p = 0.02), had a greater erythrocyte sedimentation rate (13 vs 10 mm/hour, p <0.01), had a positive CAC score (46% vs 25%, p <0.01), and had a lower current CD4 cell count (563 vs 600 cells/mm 3 , p = 0.02) compared to those without an incidental finding ( Table 1 ). Of the tobacco users, a longer duration of use was also associated with an incidental finding (p <0.01).
In the final multivariate model, increasing age (odds ratio 1.6 per 10 years, p <0.01), the presence of CAC (odds ratio 2.3, p <0.01), and current tobacco use (odds ratio 2.5, p = 0.02) were associated with the presence of an incidental finding ( Table 3 ). No HIV-specific factor was significant in the final model. The final model had a good fit (likelihood-ratio test, 26.7, p <0.01).
