Background

Computed tomography (CT)-based fat and muscle measures are associated with outcome in large populations. We tested if muscle and fat characteristics are associated with long-term outcomes after TAVR.

Methods

We included 403 clinical CTs performed prior to TAVR at our center between 2008 and 2016, measuring area (cm²) and density (Hounsfield units, HU) of both psoas muscles (PM), subcutaneous adipose (SAT), and visceral adipose tissue (VAT). Area measures were indexed to height, log-transformed and both area and density were standardized for analysis. We assessed the association of each measure with all-cause mortality (adjusted for age, sex, body mass index (BMI), and the Society of Thoracic Surgeons (STS) risk score.

Results

Of the 403 individuals (83 ± 8 years; 52% female), 167 (41.4%) died during a median follow-up of 458 days (interquartile range IQR 297-840). Fat measures were feasible and rapid. Fat area was available in 242 (60%) patients with an adequate field of view. Individuals with the lowest PM area, SAT area or VAT area exhibited the highest hazard of mortality. In addition, greater SAT density was associated with a higher mortality hazard (adjusted HR per standard deviation increase in density = 1.35, 95%CI 1.10-1.67, P = 0.005).

Conclusion

Rapid CT-based tissue characterization is feasible in patients referred for TAVR. Decreased PM area and increased SAT density are associated with long-term mortality after TAVR, even after accounting for age, sex, BMI, and STS score. Further studies are necessary to interrogate sex-specific relationships between CT tissue metrics and mortality and whether CT measures are incremental to well-established frailty metrics.

Objectives

The purpose of this study was to compare Coronary Artery Disease Reporting and Data System (CAD-RADS) to traditional stenosis categories and the coronary artery calcium score (CACS) for predicting cardiovascular events in patients with stable chest pain and suspected coronary artery disease (CAD).

Background

The 2016 CAD-RADS has been established to standardize the reporting of CAD on coronary CT angiography (CTA).

Methods

PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial participants' CTAs were assessed by a central CT core laboratory for CACS, traditional stenosis-based categories, and modified CAD-RADS grade including high-risk coronary plaque (HRP) features. Traditional stenosis categories and CAD-RADS grade were compared for the prediction of the composite endpoint of death, myocardial infarction, or hospitalization for unstable angina over a median follow-up of 25 months. Incremental prognostic value over traditional risk factors and CACS was assessed.

Results

In 3,840 eligible patients (mean age: 60.4 ± 8.2 years; 49% men), 3.0% (115) experienced events. CAD-RADS (concordance statistic [C-statistic] 0.747) had significantly higher discriminatory value than traditional stenosis-based assessments (C-statistic 0.698 to 0.717; all p for comparison ≤0.001). With no plaque (CAD-RADS 0) as the baseline, the hazard ratio (HR) for an event increased from 2.43 (95% confidence interval [CI]: 1.16 to 5.08) for CAD-RADS 1 to 21.84 (95% CI: 8.63 to 55.26) for CAD-RADS 4b and 5. In stepwise nested models, CAD-RADS added incremental prognostic value beyond ASCVD risk score and CACS (C-statistic 0.776 vs. 0.682; p < 0.001), and added incremental value persisted in all CACS strata.

Conclusions

These data from a large representative contemporary cohort of patients undergoing coronary CTA for stable chest pain support the prognostic value of CAD-RADS as a standard reporting system for coronary CTA.

Background

People with HIV (PWH) have subclinical coronary artery disease (CAD) despite low traditional atherosclerotic cardiovascular disease (ASCVD) risk scores. Coronary plaque in PWH presents as a unique phenotype, but little is known about the contributions of specific inflammatory pathways to plaque phenotypes in PWH.

Methods

The REPRIEVE Mechanistic Substudy enrolled PWH on ART without known cardiovascular disease. We used a targeted discovery proteomics approach to evaluate 246 unique proteins representing cardiovascular, inflammatory, and immune pathways. Proteomic signatures were determined for presence of coronary artery calcium (CAC > 0) and presence of coronary plaque.

Results

Data were available for 662 participants (aged 51 [SD 6] years, ASCVD risk score 4.9% [SD 3.1%]). Among 12 proteins associated with both CAC and presence of coronary plaque, independent of ASCVD risk score, the odds ratios were highest for NRP1: 5.1 (95% confidence interval [CI], 2.3-11.4) for CAC and 2.9 (95% CI, 1.4-6.1) for presence of plaque. Proteins uniquely related to presence of plaque were CST3, LTBR, MEPE, PLC, SERPINA5, and TNFSF13B; in contrast, DCN, IL-6RA, OSMR, ST2, and VCAM1 were only related to CAC.

Conclusions

Distinct immune and inflammatory pathways are differentially associated with subclinical CAD phenotypes among PWH. This comprehensive set of targets should be further investigated to reduce atherosclerosis and ASCVD in PWH.

Clinical trials registration

NCT02344290.

Background

Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque.

Methods

The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40-75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk. Among a subset of US REPRIEVE participants, coronary plaque was assessed by coronary computed tomography angiography. Here, we assessed the relationship between CMV immunoglobulin G (IgG) titer and (1) levels of immune activation, (2) inflammatory biomarkers, and (3) coronary plaque phenotypes at study entry.

Results

Of 672 participants, mean age was 51 years, 83% were men, median ASCVD risk score was 4.5%, and 66% had current CD4+ T-cell count ≥500 cells/mm3. Higher CMV IgG quartile group was associated with older age and lower current and nadir CD4+ T-cell counts. CMV IgG titer was associated with specific inflammatory biomarkers (sCD163, MCP-1, interleukin [IL]-6, hsCRP) in univariate analysis, but not after controlling for HIV-specific factors. In contrast, CMV IgG titer was not associated with coronary artery disease indexes, including presence of plaque, coronary artery calcium (CAC) score >0, vulnerable plaque presence, or Leaman score >5.

Conclusions

No meaningful association was seen between CMV IgG titer and coronary artery disease indexes among ART-treated PWH at study enrollment. Longitudinal assessments in REPRIEVE will determine the relationship of CMV IgG titer to plaque progression and cardiovascular events.

Clinical trials registration

NCT02344290.

Background

Pericoronary adipose tissue (PCAT) may influence plaque development through inflammatory mechanisms. We assessed PCAT density, as a measure of pericoronary inflammation, in relationship to coronary plaque among people with human immunodeficiency virus (HIV [PWH]) and to a matched control population.

Methods

In this baseline analysis of 727 participants of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) Mechanistic Substudy, we related computed tomography-derived PCAT density to presence and extent (Leaman score) of coronary artery disease (CAD), noncalcified plaque, coronary artery calcium (CAC), and vulnerable plaque features using multivariable logistic regression analyses. We further compared the PCAT density between PWH and age, sex, body mass index, CAC score, and statin use-matched controls from the community-based Framingham Heart Study (N = 464), adjusting for relevant clinical covariates.

Results

Among 727 REPRIEVE participants (age 50.8 ± 5.8 years; 83.6% [608/727] male), PCAT density was higher in those with (vs without) coronary plaque, noncalcified plaque, CAC >0, vulnerable plaque, and high CAD burden (Leaman score >5) (P < .001 for each comparison). PCAT density related to prevalent coronary plaque (adjusted odds ratio [per 10 HU]: 1.44; 95% confidence interval, 1.22-1.70; P < .001), adjusted for clinical cardiovascular risk factors, body mass index, and systemic immune/inflammatory biomarkers. Similarly, PCAT density related to CAC >0, noncalcified plaque, vulnerable plaque, and Leaman score >5 (all P ≤ .002). PCAT density was greater among REPRIEVE participants versus Framingham Heart Study (-88.2 ± 0.5 HU versus -90.6 ± 0.4 HU; P < .001).

Conclusions

Among PWH in REPRIEVE, a large primary cardiovascular disease prevention cohort, increased PCAT density independently associated with prevalence and severity of coronary plaque, linking increased coronary inflammation to CAD in PWH.

Background

Among people with HIV (PWH), sex differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein.

Methods

REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of US participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (n = 755 CTA; n = 725 CTA + immune). We characterized sex differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score.

Results

The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median: 4.9% vs 2.1%), while obesity rates were higher among females (48% vs 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors (RR [95% CI] for any plaque: .67 [.50, .92]; RR for NC/V-P: .71 [.51, 1.00] [adjusted for ASCVD risk score and body mass index]). Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P < .001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P < .02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = .055).

Conclusions

Among US PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer but not other tested parameters. Clinical Trial Registration. ClinicalTrials.gov; identifier: NCT0234429 (date of initial registration: 22 January 2015).