The aim of this study is to evaluate Breast Imaging Reporting and Data Systems (BI-RADS) 4A/B subcategory risk estimates for ductal carcinoma in situ (DCIS) and invasive cancer (IC), determining whether changing the proposed cutoffs to a higher biopsy threshold could safely increase cancer-to-biopsy yields while minimizing false-positive biopsies. A prospective clinical trial was performed to evaluate BI-RADS 4 lesions from women seen in clinic between January 2006 and March 2007. An experienced radiologist prospectively estimated a percent risk-estimate for DCIS and IC. Truth was determined by histopathology or 4-year follow-up negative for malignancy. Risk estimates were used to generate receiver-operating characteristic (ROC) curves. Biopsy rates, cancer-to-biopsy yields, and type of malignancies missed were then calculated across postulated risk thresholds. A total of 124 breast lesions were evaluated from 213 women. An experienced radiologist gave highly accurate risk estimates for IC, DCIS alone, or the combination with an area under ROC curve of 0.91 (95 % CI 0.84-0.99) (p < 0.001), 0.81 (95 % CI 0.69-0.93) (p = 0.011), and 0.89 (95 % CI 0.83-0.95) (p < 0.001), respectively. The cancer-to-biopsy yield was 30 %. Three hypothetical thresholds for intervention were analyzed: (1) DCIS or IC ≥ 10 %; (2) DCIS ≥ 50 % or IC ≥ 10 %; and (3) IC ≥ 10 %, which translated to 22, 48, and 56 % of biopsies avoided; cancer-to-biopsy yields of 36, 47, and 46 %; and associated chance of missing an IC of 0, 1, and 2 %, respectively. Expert radiologists estimate risk of IC and DCIS with a high degree of accuracy. Increasing the cut off point for recommending biopsy, substituting with a short-term follow-up protocol with biopsy if any change, may safely reduce the number of false-positive biopsies.

Background

The utility and validity of cardiovascular diseases (CVD) risk scores are not well studied in sub-Saharan Africa. We compared and correlated CVD risk scores with carotid intima media thickness (c-IMT) among HIV-infected and uninfected people in Uganda.

Methods

We first calculated CVD risk using the (1) Framingham laboratory-based score; (2) Framingham nonlaboratory score (FRS-BMI); (3) Reynolds risk score; (4) American College of Cardiology and American Heart Association score; and (5) the Data collection on Adverse Effects of Anti-HIV Drugs score. We then compared absolute risk scores and risk categories across each score using Pearson correlation and kappa statistics, respectively. Finally, we fit linear regression models to estimate the strength of association between each risk score and c-IMT.

Results

Of 205 participants, half were females and median age was 49 years [interquartile range (IQR) 46-53]. Median CD4 count was 430 cells/mm (IQR 334-546), with median 7 years of antiretroviral therapy exposure (IQR 6.4-7.5). HIV-uninfected participants had a higher median systolic blood pressure (121 vs. 110 mm Hg), prevalent current smokers (18% vs. 4%, P = 0.001), higher median CVD risk scores (P < 0.003), and greater c-IMT (0.68 vs. 0.63, P = 0.003). Overall, FRS-BMI was highly correlated with other risk scores (all rho >0.80). In linear regression models, we found significant correlations between increasing CVD risk and higher c-IMT (P < 0.01 in all models).

Conclusions

In this cross-sectional study from Uganda, the FRS-BMI correlated well with standard risk scores and c-IMT. HIV-uninfected individuals had higher risk scores than HIV-infected individuals, and the difference seemed to be driven by modifiable factors.

Preventable cardiovascular disease (CVD) risk factors are responsible for the majority of CVD-related deaths, and are increasingly recognized as a cause of morbidity and mortality for HIV-infected persons taking antiretroviral therapy (ART). Simplified tools such as the American Heart Association's ideal cardiovascular health (iCVH) construct may identify and prognosticate CVD risk in resource-limited settings. No studies have evaluated iCVH metrics in sub-Saharan Africa or among HIV-infected adults. Thus, the central aim of this study was to compare levels of iCVH metrics and their correlations with carotid atherosclerosis for HIV-infected adults versus uninfected controls in a well-phenotyped Ugandan cohort. We analyzed the prevalence of iCVH metrics in a mixed cohort of HIV-infected persons on stable ART and uninfected, population-based comparators in Mbarara, Uganda. We also assessed the validity of iCVH by correlating iCVH values with common carotid intima media thickness (CCIMT). HIV-infected persons had a mean of 4.9 (SD 1.1) iCVH metrics at ideal levels versus 4.3 (SD 1.2) for uninfected controls (p = .002). This difference was largely driven by differences in blood pressure, blood glucose, and diet. In multivariable-adjusted linear regression models, each additional iCVH metric at an ideal level was associated with a significant 0.024 mm decrease in CCIMT (p < .001).HIV-infected persons on ART in rural Uganda had more iCVH metrics at ideal levels than uninfected persons. The difference appeared driven by factors that are putatively influenced by access to routine medical care. Composite scores of iCVH metrics were associated with subclinical atherosclerosis and more predictive of atherosclerosis for uninfected persons.

HIV infection is associated with arterial stiffness, but no studies have assessed this relationship in sub-Saharan Africa. We enrolled 205 participants over 40 years old in Uganda: 105 on antiretroviral therapy for a median of 7 years, and a random sample of 100 age and sex-matched HIV-uninfected controls from the clinic catchment area. The prevalence of arterial stiffness (ankle brachial index  > 1.2) was 33%, 18%, 19% and 2% in HIV+ men, HIV- men, HIV+ women, and HIV- women. In multivariable models adjusted for cardiovascular risk factors, HIV+ individuals had over double the prevalence of arterial stiffness (adjusted prevalence ratio 2.86, 95% confidence interval 1.41-5.79, P = 0.003).

Background Although ≈70% of the world's population of people living with HIV reside in sub-Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population-based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3-4, range 1-5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non-high-density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001-0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003-0.008 mm], HIV×time interaction P=0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub-Saharan Africa. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02445079.

Background

Human immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa.

Methods

Beginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT).

Results

A total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01).

Conclusions

Persistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region.