Cardiac computed tomography (CCT) coronary artery calcium scoring (CACS) is a noninvasive method of detecting subclinical atherosclerosis that has emerged as a reliable tool to predict the risk of major cardiac events in people living with HIV (PLWH) [1–4]. Several studies have reported the prevalence of incidental findings on CCT in the general population; however, there are limited data available on their prevalence and clinical impact in PLWH over 50 years of age [5–7]. Prevalence of incidental findings in the general population range from 8 to 53% [8–12], whereas in PLWH vary from 43 to 57% [5,6]. In a comparison study, the percentage of incidental findings was higher in the general population compared with PLWH (60 vs. 48%), but clinical significance of these were similar between the two groups (10 vs. 9%) . Whilst most incidental findings on imaging are benign, older age, smoking and chronic inflammation are established risk factors of malignancy and these are highly prevalent in PLWH. It is, therefore, important to understand the clinical relevance of such incidental findings to better define clear management pathways in order to improve diagnosis while avoiding unnecessary follow-up examinations.
To the best of our knowledge, this is the largest study performed in PLWH over 50 years of age to determine the prevalence and clinical outcomes of noncardiac incidental findings identified by CCT CACS. We conducted a retrospective service evaluation of patients reviewed in a London clinic dedicated to PLWH at least 50 years who underwent CCT CACS for assessment of subclinical coronary atherosclerosis between 1 January 2009 and 31 December 2018. Demographic data, incidental extracardiac findings on CCT CACS and recommended follow-up were collected. Univariate and multivariate logistic regression models were used for statistical analysis.
A total of 744 patients performed CCT CACS, 92% were men, mean (±SD) age was 56 ± 5 years, 84% were white British, 87% were MSM. Mean (±SD) CD4+ cell count was 660 ± 258 cells/μl, 97% were on antiretroviral treatment and 94% had an undetectable HIV viral load. Median duration of HIV infection was 16 years (interquartile range, IQR, 12). Median CD4+/CD8+ ratio was 0.8 (IQR 0.6). Current smoking was reported in 42% of patients.
Incidental findings were found in 30.4% (226/744) and 9.5% (71/744) of patients presented more than one incidental finding (Table 1). Most incidental findings were pulmonary (263/315, 83.5%) or mediastinal (17/315, 5.4%). The commonest lung abnormalities were atelectasis (76/263, 28.9%), nodules less than 10 mm requiring (42/263, 15.9%) or not requiring (37/263, 14.1%) follow-up, and emphysema (32/263, 12.2%).
Among the 226 patients with at least one incidental finding, 63 (27.9%) were clinically relevant requiring further radiological follow-up or onwards referral. Follow-up was completed in 36/63 (57.2%). At follow-up, 24/36 patients were stable whereas in 8/36 (22.2%) abnormalities had resolved (three cases received antibiotic treatment for pneumonia). In three out of 63 patients with clinically relevant findings, a diagnosis of malignancy was subsequently established (two lung cancers and one Kaposi sarcoma).
Incidental findings were higher but, not statistically significant in males vs females (30.5 vs. 22.6%), MSM vs. heterosexuals (31 vs. 24.2%), and current or ex-smokers vs. nonsmokers (72.7 vs. 27.3%). Other explored variables [age, ethnicity, CD4+ count, neutrophil : lymphocyte ratio, undetectable viral load, years living with HIV, CACS, alcohol excess, polypharmacy (≥5 medications) and BMI] were not significantly associated with the presence of incidental findings. At multivariable logistic regression analysis, CD4+/CD8+ ratio 0.9 or less and multimorbidity (≥2 noncommunicable diseases) were significantly associated with the presence of incidental findings (P = 0.001 and P > 0.05, respectively). A low CD4+/CD8+ ratio was also a strong predictor of clinically relevant findings requiring follow-up (P = 0.013).
Our study indicates that the prevalence of incidental findings in PLWH over 50 years of age with well controlled HIV infection is not higher than the prevalence previously reported for general population [5–7]; however, we found a higher prevalence of clinically relevant findings compared with previous reports in PLWH. Having low or inverted CD4+/CD8+ ratio indicating an impaired immune response and chronic inflammation despite a suppressed viral load was significantly associated with the presence of clinically relevant incidental lung findings. Also patients with multimorbidity were more likely to present with extra-cardiac incidental findings on CCT CACS. We conclude that CCT CACS determination has added value of identifying clinically significant abnormalities in PLWH over 50 years of age; however, at the expense of increased costs and increased anxiety for the patient [13–15]. Our results suggest that older age, multimorbidity and low CD4+/CD8+ ratio should be incorporated as risk factors for determining follow-up pathways of incidental imaging findings in PLWH.
M.C., M.M. and M.B. were involved in the study design. M.C., M.M., A.M., T.M., B.P., A.M., A.P., S.R. and T.K. contributed to data collection. M.C. and M.M. did the literature review. S.M. performed statistical analysis. M.C. and M.M. drafted the manuscript. All authors were involved in manuscript revision.
Results of this article were presented in part at EACS conference (6–9 November 2019), in Basel (Switzerland).
Conflicts of interest
There are no conflicts of interest.
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