Joint Hypermobility, Autonomic Dysfunction, Gastrointestinal Dysfunction and Autoimmune markers (JAG-A): Clinical Associations and Response to Intravenous Immunoglobulin Therapy.

INTRODUCTION: We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD). METHODS: AIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder (AIDX) with at least one positive seromarker of autoimmunity or at least two positive seromarkers by themselves. Three cohorts were studied: (a) Retrospective (n = 300); (b) Prospective validation cohort (n =133); and (c) Treatment cohort (n=40), administered open-label intravenous immunoglobulin (IVIG). RESULTS: AIM positivity was found in 40% and 29% of the retrospective and prospective cohorts, the majority of whom (71% and 69%, respectively) had AIDX. Significantly more patients with AIM had elevations of C-reactive protein (31% versus 15%, p<0.001) along with an increased proportion of cardiovascular autonomic dysfunction (48% versus 29%; p<.001), small fiber neuropathy (20% versus 9%; p=.002).8) and HLADQ8 positivity (24% versus 13%, p=.01). JH/HSD patients were more likely to have AIM (43% versus 15%, p=.001) along with more severe autonomic and gastrointestinal symptom scores. IVIG treatment was associated with robust improvement in pain, gastrointestinal and autonomic symptoms but adverse events were experienced by 62% patients. CONCLUSIONS: Autoimmune markers and autonomic dysfunction are common in patients with unexplained gastrointestinal symptoms, especially in those with JH/HSD. Many patients seem to respond to IVIG treatment but this needs to be confirmed by controlled trials. These results highlight the need for vigilance for autoimmune and autonomic factors and JH/HSD in patients with neurogastroenterological disorders. Clinicaltrials.gov, NCT04859829.

Myeloid NCOA4 sequesters KEAP1 to reduce ferroptosis for protection against salmonellosis in mice.

Salmonellosis, caused by Salmonella enterica serovar Typhimurium, is a significant global threat. Host immunity limits bacterial replication by inducing hepcidin, which degrades ferroportin, reducing iron transfer. However, this boosts macrophage iron storage, aiding intracellular pathogens like Salmonella. Mice lacking ferritin heavy chain (FTH1) in myeloid cells suffer worsened Salmonella infection. Nuclear receptor co-activator 4 (NCOA4) regulates iron release via FTH1 degradation during low iron, but its role in salmonellosis is unclear. Here, we reveal that myeloid NCOA4 deficiency augments spleen iron levels and increases cellular iron accumulation, oxidative stress, and ferroptosis in bone marrow-derived macrophages. This deficiency also increases susceptibility to Salmonella-induced colitis in mice. Mechanistically, NCOA4 suppresses oxidative stress by directly binding to the E3 ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1) and stabilizing the antioxidant transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2). Activation of NRF2 protects myeloid NCOA4 knockout mice from Salmonella-induced colitis. Antioxidant Tempol and myeloid cell-targeted curcumin offer protection against colitis in myeloid NCOA4-deficient mice. A low iron diet and ferroptosis inhibition also mitigate the heightened colitis in these mice. Overexpression of myeloid cell-specific NCOA4 confers protection against Salmonella-induced colitis via upregulating NRF2 signaling. Serum iron was reduced in myeloid NCOA4-overexpressing mice, but not in NCOA4-deficient mice. Targeted serum metabolomics analysis revealed that many lipids were decreased in myeloid NCOA4-deficient mice, while several of them were increased in myeloid NCOA4-overexpressing mice. Together, this study not only advances our understanding of NCOA4/KEAP1/NRF2/ferroptosis axis but also paves the way for novel myeloid cell-targeted therapies to combat salmonellosis.

Prognostic value of noninvasive combined anatomic/functional assessment by cardiac CT in patients with suspected coronary artery disease - Comparison with invasive coronary angiography and nuclear myocardial perfusion imaging for the five-year-follow up of the CORE320 multicenter study.

BACKGROUND: Few data exist on long-term outcome in patients undergoing combined coronary CT angiography (CTA) and myocardial CT perfusion imaging (CTP) as well as invasive coronary angiography (ICA) and single photon emission tomography (SPECT). METHODS: At 16 centers, 381 patients were followed for major adverse cardiac events (MACE) for the CORE320 study. All patients underwent coronary CTA, CTP, and SPECT before ICA within 60 days. Prognostic performance according binary results (normal/abnormal) was assessed by 5-year major cardiovascular events (MACE) free survival and area under the receiver-operating-characteristic curve (AUC). RESULTS: Follow up beyond 2-years was available in 323 patients. MACE-free survival rate was greater among patients with normal combined CTA-CTP findings compared to ICA-SPECT: 85 vs. 80% (95% confidence interval [CI] for difference 0.1, 11.3) though event-free survival time was similar (4.54 vs. 4.37 years, 95% CI for difference: -0.03, 0.36). Abnormal results by combined CTA-CTP was associated with 3.83 years event-free survival vs. 3.66 years after abnormal combined ICA-SPECT (95% CI for difference: -0.05, 0.39). Predicting MACE by AUC also was similar: 65 vs. 65 (difference 0.1; 95% CI -4.6, 4.9). When MACE was restricted to cardiovascular death, myocardial infarction, or stroke, AUC for CTA-CTP was 71 vs. 60 by ICA-SPECT (difference 11.2; 95% CI -1.0, 19.7). CONCLUSIONS: Combined CTA-CTP evaluation yields at least equal 5-year prognostic information as combined ICA-SPECT assessment in patients presenting with suspected coronary artery disease. Noninvasive cardiac CT assessment may eliminate the need for diagnostic cardiac catheterization in many patients. CLINICAL TRIAL REGISTRATION: NCT00934037.

Acute Kidney Injury After Repeated Exposure to Contrast Material for Coronary Angiography.

OBJECTIVE: To assess the incidence of contrast-associated acute kidney injury (CAAKI) after repeated exposure to contrast material for computed tomography (CT) and conventional coronary angiography within short intervals. METHODS: We studied 651 patients enrolled in the CorE-64 (November 5, 2005-January 30, 2007) and CORE320 (October 21, 2009-August 17, 2011) multicenter studies. Participants with suspected obstructive coronary heart disease were referred for diagnostic cardiac catheterization and underwent coronary CT angiography for research before invasive angiography. Nonionic, low-osmolality iodinated contrast material was used for all imaging. RESULTS: The median age of the patients was 62 years, and 190 (29%) were women. Major risk factors for acute kidney injury were present in 277 of 651 (43%) patients. The median interval between CT imaging and invasive angiography was 3.1 days (interquartile range, 0.9-8.0 days). The median volume of contrast material was 100 mL for each test. In 16 (2.5%) of 651 patients, CAAKI developed. Of these cases, 1 occurred after the CT scan, whereas 6 were documented after invasive angiography (compared with post-CT creatinine concentration assessment). In 9 patients, CAAKI was found in comparing creatinine concentration after completion of both tests with baseline values (but not compared with post-CT imaging). CONCLUSION: Acute kidney injury after repeated exposure to iodinated contrast media within a few days is uncommon even in a population of patients with highly prevalent risk factors. Withholding of clinically indicated contrast-enhanced imaging may therefore not be justified in this setting.

Comparative effectiveness of coronary artery stenosis and atherosclerotic plaque burden assessment for predicting 30-day revascularization and 2-year major adverse cardiac events.

PURPOSE: To provide comparative prognostic information of coronary atherosclerotic plaque volume and stenosis assessment in patients with suspected coronary artery disease (CAD). METHODS: We followed 372 patients with suspected or known CAD enrolled in the CORE320 study for 2 years after baseline 320-detector row cardiac CT scanning and invasive quantitative coronary angiography (QCA). CT images were analyzed for coronary calcium scanning (CACS), semi-automatically derived total percent atheroma volume (PAV), segment stenosis score (SSS), in addition to traditional stenosis assessment (≥ 50%) by CT and QCA for (1) 30-day revascularization and (2) major adverse cardiac events (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare accuracy of risk prediction. RESULTS: Sixty percent of patients had obstructive CAD by QCA with 23% undergoing 30-day revascularization and 9% experiencing MACE at 2 years. Most late events (20/32) were revascularization procedures. Prediction of 30-day revascularization was modest (AUC range 0.67-0.78) but improved after excluding patients with known CAD (AUC range 0.73-0.86, p < 0.05 for all). Similarly, prediction of MACE improved after excluding patients with known CAD (AUC range 0.58-0.73 vs. 0.63-0.77). CT metrics of atherosclerosis burden performed overall similarly but stenosis assessment was superior for predicting 30-day revascularization. CONCLUSIONS: Angiographic and coronary atherosclerotic plaque metrics perform only modestly well for predicting 30-day revascularization and 2-year MACE in high risk patients but improve after excluding patients with known CAD. Atherosclerotic plaque metrics did not yield incremental value over stenosis assessment for predicting events that predominantly consisted of revascularization procedures. CLINICAL TRIAL REGISTRATION: NCT00934037.

Intravascular Stem Cell Bioreactor for Prevention of Adverse Remodeling After Myocardial Infarction.

Background Prevention of adverse remodeling after myocardial infarction (MI) is an important goal of stem cell therapy. Clinical trial results vary, however, and poor cell retention and survival after delivery likely limit the opportunity to exert beneficial effects. To overcome these limitations, we built an implantable intravascular bioreactor (IBR) designed to protect contained cells from washout, dilution, and immune attack while allowing sustained release of beneficial paracrine factors. Methods and Results IBRs were constructed using semipermeable membrane adhered to a clinical-grade catheter shaft. Mesenchymal stem cell (MSC) viability in and paracrine factor release from IBRs were assessed in vitro and IBR biocompatibility and immune protection confirmed in vivo. In a porcine anterior MI model, IBRs containing 25 million allogeneic MSCs (IBR-MSCs) were compared with IBRs containing media alone (IBR-Placebo; n=8 per group) with adverse remodeling assessed by magnetic resonance imaging. Four weeks after MI, IBR-MSCs had no significant change in end-diastolic volume (+0.33±4.32 mL; P=0.89), end-systolic volume (+2.14±4.13 mL; P=0.21), and left ventricular ejection fraction (-2.27±2.94; P=0.33) while IBR-Placebo had significant increases in end-diastolic volume (+10.37±3.84 mL; P=0.01) and ESV (+11.35±2.88 mL; P=0.01), and a significant decrease in left ventricular ejection fraction (-5.78±1.70; P=0.025). Eight weeks after MI, adherent pericarditis was present in 0 of 8 IBR-MSCs versus 4 of 8 IBR-Placebo (P=0.02), suggesting an anti-inflammatory effect. In a separate study, 25 million allogeneic pig MSCs directly injected in the peri-infarct zone 3 days after MI (n=6) showed no significant benefit in adverse remodeling at 4 weeks compared with IBR-MSCs. Conclusions MSCs deployed inside an implantable, removable, and potentially rechargeable bioreactor in a large animal model remain viable, are immunoprotected, and attenuate adverse remodeling 4 weeks after MI.

Contemporary Discrepancies of Stenosis Assessment by Computed Tomography and Invasive Coronary Angiography.

Background Ongoing advancements of coronary computed tomographic angiography (CTA) continue to challenge the role of invasive coronary angiography (ICA) as the gold standard for the evaluation of coronary artery disease (CAD). We sought to investigate the diagnostic accuracy of 320-slice CTA for detecting obstructive CAD in reference to ICA and nuclear myocardial perfusion imaging using single-photon emission computed tomography. Methods For the CORE320 study (Coronary Artery Evaluation Using 320-Row Multidetector Computed Tomography Angiography and Myocardial Perfusion), 381 patients at 16 centers underwent CTA, nuclear myocardial perfusion imaging by single-photon emission computed tomography, and ICA for the evaluation of CAD. Imaging studies were analyzed in blinded core laboratories, and a stenosis of ≥50% by quantitative coronary angiography was considered obstructive, whereas a stress difference score of ≥1 indicated inducible myocardial ischemia. The area under the receiver operating characteristic curve was used to evaluate diagnostic accuracy. Results Of 381 patients, 229 (60%) had obstructive CAD by quantitative coronary angiography. Diagnostic accuracy of CTA on a per-patient analysis revealed an area under the receiver operating characteristic curve of 0.90 (95% CI, 0.87-0.93). Per-vessel and per-segment analysis revealed lower area under the receiver operating characteristic curve of 0.87 (0.84-0.90) and 0.81 (0.78-0.83), respectively. Median radiation dose was lower for CTA versus ICA: 3.16 (interquartile range, 2.82-3.59) versus 11.97 (interquartile range, 7.60-17.8) mSv ( P<0.001). Accuracy for identifying patients with inducible myocardial ischemia by SPECT-MPI was similar for CTA and ICA (area under the receiver operating characteristic curve, 0.68 versus 0.71 by quantitative coronary angiography and 0.68 by visual angiographic assessment; P>0.05). Furthermore, accuracy for identifying patients who subsequently underwent clinically driven coronary revascularization also was similar for CTA (0.76 [0.71-0.81]) and ICA (0.78 [0.74-0.83]; P=0.20). Conclusions Contemporary CTA accurately identifies patients with obstructive CAD by ICA at lower radiation exposure; however, agreement is lower in vessel- and segment-level analyses. Both CTA and ICA perform similarly for predicting clinically driven revascularization and for detecting myocardial ischemia by myocardial perfusion imaging using single-photon emission computed tomography, suggesting that limitations by both CTA and ICA contribute to variability of stenosis quantification. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00934037.

Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging versus Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events: The CORE320 Multicenter Study.

Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study. All images were analyzed in blinded independent core laboratories, and a panel of physicians adjudicated all adverse events. MACE was defined as revascularization (>30 days after index ICA), myocardial infarction, or cardiac death; hospitalization for chest pain or congestive heart failure; or arrhythmia. Late MACE was defined similarly, except for patients who underwent revascularization within the first 182 days after ICA, who were excluded. Comparisons of 2-year survival (time to MACE) used standard Kaplan-Meier curves and restricted mean survival times bootstrapped with 2000 replicates. Results An MACE (49 revascularizations, five myocardial infarctions, one cardiac death, nine hospitalizations for chest pain or congestive heart failure, and one arrhythmia) occurred in 51 of 379 patients (13.5%). The 2-year MACE-free rates for combined CT angiography and CT perfusion findings were 94% negative for coronary artery disease (CAD) versus 82% positive for CAD and were similar to combined ICA and single photon emission CT findings (93% negative for CAD vs 77% positive for CAD, P < .001 for both). Event-free rates for CT angiography and CT perfusion versus ICA and single photon emission CT for either positive or negative results were not significantly different for MACE or late MACE (P > .05 for all). The area under the receiver operating characteristic curve (AUC) for combined CT angiography and CT perfusion (AUC = 68; 95% confidence interval [CI]: 62, 75) was similar (P = .36) to that for combined ICA and single photon emission CT (AUC = 71; 95% CI: 65, 79) in the identification of MACE at 2-year follow-up. Conclusion Combined CT angiography and CT perfusion enables similar prediction of 2-year MACE, late MACE, and event-free survival similar to that enabled by ICA and single photon emission CT. © RSNA, 2017 Online supplemental material is available for this article.

Coronary Plaque Progression and Regression in Asymptomatic African American Chronic Cocaine Users With Obstructive Coronary Stenoses: A Preliminary Study.

OBJECTIVE: Although rapid progression of coronary atherosclerosis was observed in chronic cocaine users, it is unknown whether reduced cocaine use retards the progression of atherosclerosis. We investigated whether reduced cocaine use over a 12-month period was associated with coronary plaque regression in cocaine users. METHODS: Fifteen African American chronic cocaine users with previously coronary computed tomography angiography (CCTA)-confirmed >50% coronary stenosis in Baltimore, Maryland, were enrolled in a study to investigate whether reduced cocaine use is associated with changes in coronary plaque burden over a 12-month period of cash-based incentive intervention, which was implemented to systematically reinforce cocaine abstinence. In addition to previous CCTA (preintervention), CCTA was performed at the intervention baseline and at postintervention. Plaque analyses were performed to determine the trajectory of plaque changes in the absence of intervention by comparing the preintervention with the intervention baseline studies; the trajectory of plaque changes associated with the intervention by comparing the intervention baseline with the postintervention studies; and (3) whether reduced cocaine use was independently associated with changes in coronary plaque burden. RESULTS: During the 12-month cash-based incentive intervention period, cocaine use in participants was lower. The medians of noncalcified plaque indices were 37.8 (interquartile range [IQR] 29.3-44.0), 43.1 (IQR 38.3-49.0), and 38.7 (IQR 31.2-46.8) mm at preintervention, intervention baseline, and postintervention, respectively. Multivariable generalized estimating equation analysis showed that both total plaque and noncalcified plaque indices at preintervention were significantly lowered as compared with intervention baseline levels; both total plaque and noncalcified plaque indices after intervention were significantly lowered as compared with intervention baseline levels; and reduced cocaine use was independently associated with lower total plaque volume index (P < 0.0001) and noncalcified plaque volume index (P = 0.010). CONCLUSIONS: Our findings suggest that continued cocaine use may be associated with noncalcified plaque progression, whereas reduced cocaine use may be associated with noncalcified plaque regression. Larger studies are needed to confirm these findings.

Total coronary atherosclerotic plaque burden assessment by CT angiography for detecting obstructive coronary artery disease associated with myocardial perfusion abnormalities.

BACKGROUND: Total atherosclerotic plaque burden assessment by CT angiography (CTA) is a promising tool for diagnosis and prognosis of coronary artery disease (CAD) but its validation is restricted to small clinical studies. We tested the feasibility of semi-automatically derived coronary atheroma burden assessment for identifying patients with hemodynamically significant CAD in a large cohort of patients with heterogenous characteristics. METHODS: This study focused on the CTA component of the CORE320 study population. A semi-automated contour detection algorithm quantified total coronary atheroma volume defined as the difference between vessel and lumen volume. Percent atheroma volume (PAV = [total atheroma volume/total vessel volume] × 100) was the primary metric for assessment (n = 374). The area under the receiver operating characteristic curve (AUC) determined the diagnostic accuracy for identifying patients with hemodynamically significant CAD defined as ≥50% stenosis by quantitative coronary angiography and associated myocardial perfusion abnormality by SPECT. RESULTS: Of 374 patients, 139 (37%) had hemodynamically significant CAD. The AUC for PAV was 0.78 (95% confidence interval [CI] 0.73-0.83) compared with 0.84 [0.79-0.88] by standard expert CTA interpretation (p = 0.02). Accuracy for both CTA (0.91 [0.87, 0.96]) and PAV (0.86 [0.81-0.91]) increased after excluding patients with history of CAD (p < 0.01 for both). Bland-Altman analysis revealed good agreement between two observers (bias of 280.2 mm(3) [161.8, 398.7]). CONCLUSIONS: A semi-automatically derived index of total coronary atheroma volume yields good accuracy for identifying patients with hemodynamically significant CAD, though marginally inferior to CTA expert reading. These results convey promise for rapid, reliable evaluation of clinically relevant CAD.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry.

BACKGROUND: Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. PATIENTS AND METHODS: Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. RESULTS: PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. CONCLUSIONS: PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

Successful extraction of right ventricular lead remnants using the FlexCath® steerable sheath.

In patients undergoing laser lead extraction, incomplete or failed lead removal occur in over 3 % of leads. Because the current available tools have limitations in reaching the right ventricle (RV), the procedure becomes challenging when the lead breaks and its fragments remain lodged in the RV. We describe two cases in which the FlexCath® steerable sheath, normally used in cryoballoon catheter ablation for atrial fibrillation, was useful in directing a bioptome to right ventricular lead fragments and thus allowing for complete lead extraction.

Accuracy of Computed Tomographic Angiography and Single-Photon Emission Computed Tomography-Acquired Myocardial Perfusion Imaging for the Diagnosis of Coronary Artery Disease.

BACKGROUND: Establishing the diagnosis of coronary artery disease (CAD) in symptomatic patients allows appropriately allocating preventative measures. Single-photon emission computed tomography (CT)-acquired myocardial perfusion imaging (SPECT-MPI) is frequently used for the evaluation of CAD, but coronary CT angiography (CTA) has emerged as a valid alternative. METHODS AND RESULTS: We compared the accuracy of SPECT-MPI and CTA for the diagnosis of CAD in 391 symptomatic patients who were prospectively enrolled in a multicenter study after clinical referral for cardiac catheterization. The area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of CTA and SPECT-MPI for identifying patients with CAD defined as the presence of ≥1 coronary artery with ≥50% lumen stenosis by quantitative coronary angiography. Sensitivity to identify patients with CAD was greater for CTA than SPECT-MPI (0.92 versus 0.62, respectively; P<0.001), resulting in greater overall accuracy (area under the receiver operating characteristic curve, 0.91 [95% confidence interval, 0.88-0.94] versus 0.69 [0.64-0.74]; P<0.001). Results were similar in patients without previous history of CAD (area under the receiver operating characteristic curve, 0.92 [0.89-0.96] versus 0.67 [0.61-0.73]; P<0.001) and also for the secondary end points of ≥70% stenosis and multivessel disease, as well as subgroups, except for patients with a calcium score of ≥400 and those with high-risk anatomy in whom the overall accuracy was similar because CTA's superior sensitivity was offset by lower specificity in these settings. Radiation doses were 3.9 mSv for CTA and 9.8 for SPECT-MPI (P<0.001). CONCLUSIONS: CTA is more accurate than SPECT-MPI for the diagnosis of CAD as defined by conventional angiography and may be underused for this purpose in symptomatic patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00934037.

Cocaine Abstinence and Reduced Use Associated With Lowered Marker of Endothelial Dysfunction in African Americans: A Preliminary Study.

OBJECTIVES: Clinical and epidemiological evidence suggests that cocaine use is associated with an increased risk of premature atherosclerosis. The objectives of this study were to explore (1) whether cocaine abstinence is associated with a reduced marker of endothelial dysfunction, (2) whether cocaine abstinence is associated with a slower coronary plaque progression, and (3) whether reduction in cocaine use is associated with a reduced marker of endothelial dysfunction in African American chronic cocaine users with contrast-enhanced coronary CT angiography-confirmed less than 50% coronary stenosis. METHODS: Between March and June 2014, a total of 57 African American cocaine users with contrast-enhanced CT angiography-confirmed less than 50% coronary stenosis in Baltimore, Maryland, were enrolled in a 6-month follow-up study to investigate whether cocaine abstinence or reduction in cocaine use is associated with decreased endothelin-1 (ET-1) levels and coronary plaque progression at the 6-month follow-up. A voucher-based incentive approach was used to systematically reinforce cocaine abstinence, and urine benzoylecgonine test was implemented to confirm cocaine use. RESULTS: Among the 57 participants, 44 were HIV-infected. The median of duration of cocaine use was 18 (interquartile range, 7-30) years. According to generalized estimating equation analyses, both cocaine abstinence and reduction in cocaine use in the 6 months were independently associated with decreased ET-1. The incidence of coronary plaque progression was 7.4/100 person-years and 23.1/100 person-years in those who were totally abstinent from cocaine and those who continued to use cocaine, respectively. However, the difference in the incidence between these 2 groups was not significant (exact P = 0.30). CONCLUSIONS: The findings of this study revealed a possible association of cocaine abstinence/reduction with lowered ET levels, which suggests that such changes in cocaine use might be beneficial for preventing endothelial damage. Further studies should be conducted to investigate whether ET-1 could be used as a marker for cocaine abstinence and reduction in cocaine use.