Shenghan Lai

Background and aimsPeople with HIV (PWH) whose disease is controlled on anti-retroviral regimens remain at an increased risk for coronary artery disease (CAD). Traditional cardiovascular risk factors do not fully explain the residual risk in PWH suggesting contributions from nontraditional factors. Homocysteine (Hcy) may be one of these as prior work in adults without HIV demonstrate that Hcy may impair endothelial function by decreasing the availability of nitric oxide, promoting the development of atherosclerosis. In addition, plasma Hcy levels are higher in PWH than in individuals living without HIV. The aim of this study was to investigate whether Hcy levels influence the association between HIV and coronary stenosis in an inner city African American population.MethodsAfrican Americans from the Heart Study in Baltimore, with and without HIV, recruited from inner-city Baltimore between June 2004 and …

Background: In the antiretroviral therapy (ART) era, HIV-associated neurocognitive disorders (HAND) remain a considerable challenge for people with HIV, yet not all such disorders can be attributed to HIV alone. This study aimed to: (1) identify factors influencing neurocognitive impairment (NCI) utilizing the NIH Toolbox Cognition Battery (NIHTB-CB) as per the revised research criteria for HAND; (2) ascertain the moderating role of high homocysteine levels in the association between NCI and HIV; and (3) assess the mediating effect of elevated homocysteine levels on this association.Methods: We analyzed data from 788 adults (≥45 years) participating in a study on HIV-related comorbidities in underserved Baltimore communities, using NIHTB-CB to gauge neurocognitive performance. Special attention was given to results from the Dimensional Change Card Sort (DCCS) test within the executive function domain …

Aims To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. Materials and Methods We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. Results …

Coronary endothelial dysfunction is an established driver for the development of coronary atherosclerosis, and abnormal coronary endothelial function (CEF) is an independent predictor of adverse cardiovascular events. Advances in magnetic resonance imaging make it possible to quantify CEF by measuring changes in the coronary cross-sectional area in response to isometric handgrip exercise, an endothelial-dependent stressor. Healthy coronaries respond by vasodilatation and thus an increase in cross-sectional area is measured; no change or paradoxical vasoconstriction is seen in the presence of endothelial dysfunction. 1 This noninvasive method allows assessment of the effectiveness of interventions that may improve CEF. Human immunodeficiency virus (HIV) infection is associated with accelerated atherosclerosis. Both elevated LDL-C (LDL-cholesterol) and Lp (a)(lipoprotein [a]) are independently …

BackgroundCocaine use exacerbates human immunodeficiency virus (HIV)–associated subclinical coronary atherosclerosis. We investigated whether cocaine abstinence or reduced use achieved with contingency management (CM) intervention would retard high-risk coronary plaque progression among cocaine users with HIV and subclinical coronary atherosclerosis.MethodsBetween March 2014 and August 2017, 76 cocaine users with HIV and coronary plaques were enrolled in a study designed to decrease cocaine use and determine whether doing so impacted progression of subclinical coronary atherosclerosis as measured by coronary artery computed tomography examinations. Of the 76, 7 did not complete the study, resulting in 69 participants. A 12-month cash-based CM intervention was implemented to promote cocaine abstinence or reduced cocaine use. Generalized estimating equation approach …

OBJECTIVE We describe the prevalence of COVID-19 vaccine uptake, substance use, and other factors associated with vaccine hesitancy among participants from nine North American cohort studies following a diverse group of individuals at risk for or living with HIV. METHODS Between May 2021 and January 2022, participants completed a survey related to COVID-19 vaccination. Participants included those with and without substance use. Those responding as no or undecided to the question Do you plan on getting the COVID-19 vaccine? were categorized as vaccine hesitant. Differences between groups were evaluated using chi-square methods and multivariable log-binomial models were used to calculate prevalence ratios (PR) of COVID-19 vaccine hesitancy with separate models for each substance. RESULTS Among 1,696 participants, COVID-19 vaccination was deferred or declined by 16%. Vaccine hesitant participants were younger, with a greater proportion unstably housed (14.8% vs. 10.0%; p = 0.02), and not living with HIV (48.% vs. 36.6%; p <.01). Vaccine hesitant participants were also more likely to report cannabis (50.0% vs. 42.4%; p = 0.03), methamphetamine (14.0% vs. 8.2%; p <.01), or fentanyl use (5.5% vs. 2.8%; p = 0.03). Based on multivariable analyses methamphetamine or fentanyl use remained associated with COVID-19 vaccine hesitancy (Adjusted PR = 1.4; 95% CI 1.1-1.9 and Adjusted PR = 1.6; 95% CI 1.0-2.6, respectively). CONCLUSION As new COVID-19 vaccines and booster schedules become necessary, people who use drugs (PWUD) may remain vaccine hesitant. Strategies to engage hesitant …

Background:People living with HIV are vulnerable to cardiometabolic diseases. We assessed the prevalence of cardiometabolic risk factors (CMRF) and associations with sexual stigma and depression among sexual and gender minorities (SGM) in Abuja and Lagos, Nigeria.Methods:The TRUST/RV368 study enrolled SGM between March 2013 and February 2020. Participants were assessed for depression, sexual stigma, and CMRF. Robust multinomial logistic regression was used to estimate adjusted odds ratio (aORs) and 95% confidence intervals (CIs) for associations of depression, sexual stigma, and other factors with increasing numbers of CMRF.Results:Among 761 SGM, the mean age was 25.0±6.0 years; 580 (76%) identified as cisgender men, 641 (84%) had≥ 1 CMRF, 355 (47%) had mild–severe depression, and 405 (53%) reported moderate–high sexual stigma. Compared with individuals without …

HIV-associated neurocognitive disorders (HAND) remain a major challenge for people with HIV in the antiretroviral therapy era. Cocaine use may trigger/exacerbate HAND among African American (AA) adults, especially women. Between 2018 and 2019, 922 adults, predominantly AAs, with/without HIV and with/without cocaine use in Baltimore, Maryland, were enrolled in a study investigating the association of HIV and cocaine use with neurocognitive impairment (NCI). Neurocognitive performance was assessed with the NIH Toolbox Cognition Battery (NIHTB-CB). NCI was considered to be present if the fully adjusted standard score for at least two cognitive domains was 1.0 standard deviation below the mean. Although the overall analysis showed HIV and female sex were associated with NCI, the associations were dependent on cocaine use. Neither HIV [adj prevalence ratio (PR): 1.12, confidence interval (95 …

Background:People with HIV (PWH) are at an increased risk of cardiovascular disease, partially believed to be related to chronically elevated systemic inflammation. Abnormal systemic endothelial function (SEF) and coronary endothelial function (CEF) develop early in atherogenesis and predict adverse events. It is unknown whether abnormal CEF is related to systemic inflammation in PWH.Methods:In this substudy of a prior randomized controlled trial in PWH without prior clinical coronary artery disease suppressed on antiretroviral therapy with CEF as a primary end point (N= 82), we investigated the associations between baseline serum markers of inflammation and adhesion and baseline CEF, assessed by noninvasive MRI measures of percentage changes in coronary blood flow and cross-sectional area during isometric handgrip exercise, and SEF using brachial ultrasound for flow-mediated dilation. We also …

Aims Lipoprotein(a) [Lp(a)] levels are generally constant throughout an individual’s lifetime, and current guidelines recommend that a single measurement is sufficient to assess the risk of coronary artery disease (CAD). However, it is unclear whether a single measurement of Lp(a) in individuals with acute myocardial infarction (MI) is indicative of the Lp(a) level six months following the event. Methods and results Lp(a) levels were obtained from individuals with non–ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI) (n = 99) within 24 h of hospital admission and after six months, who were enrolled in two randomized trials of evolocumab and placebo, and in individuals with NSTEMI or STEMI (n = 9) who enrolled in a small observation arm of the two protocols and did not receive study drug, but whose levels were obtained at the same time …

Aims Platelet activation and endothelial dysfunction contribute to adverse outcomes in patients with acute coronary syndromes (ACS). The goals of this study were to assess the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on markers of platelet activation and endothelial dysfunction in ACS patients and the interaction among PCSK9, platelets, and endothelial cells (ECs) on left internal mammary artery (LIMA) vascular endothelium using specimens obtained during coronary artery bypass surgery (CABG). Methods and Results Acute coronary syndromes patients enrolled in the Evolocumab in ACS trials were randomized to placebo or a single dose of 420 mg evolocumab within 24 h of hospitalization. Serum samples for analysis of platelet factor 4 (PF4) and P-selectin, markers of platelet activation, and von Willebrand factor (vWF), a marker of …

AimWe aimed to examine risks of major cardiovascular events (MACEs), renal outcomes, and all-cause mortality in type 2 diabetes mellitus (T2DM) patients with different diabetic kidney disease (DKD) subtypes.MethodsA total of 36,509 participants with T2DM recruited from 20 community sites across mainland China were followed up during 2011-2016. DKD subtypes were categorized based on albuminuria (urinary albumin-to-creatinine ratio, UACR ≥ 30 mg/g) and reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) as Alb−/eGFR−, Alb+/eGFR−, Alb−/eGFR+, and Alb+/eGFR+. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of developing clinical outcomes in DKD subtypes.ResultsMore than half (53.5%) of participants with diabetes and reduced eGFR had normal UACR levels (Alb−/eGFR+), termed as non-albuminuria …

Lipoprotein(a), or Lp(a), levels and the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on Lp(a) during the peri-infarction and early postinfarction period are not well characterized. This study aimed to describe the trajectory of Lp(a), as well as the effect of PCSK9 inhibition on that trajectory during the peri-infarction and early postinfarction period. Lp(a) levels were obtained within 24 hours of hospital admission as well as within 24 hours of hospital discharge and at 30 days from 74 participants who presented with a NSTEMI (troponin I >5 ng/ml) or with a STEMI and were enrolled in 2 randomized, double-blind trials of evolocumab and placebo (Evolocumab in Acute Coronary Syndrome [EVACS I]; ClinicalTrials.gov, NCT03515304 and Evolocumab in Patients With STEMI [EVACS II]; ClinicalTrials.gov Identifier: NCT04082442). There was a significant increase from the pretreatment level in the …

Objective Determine if cocaine use impacts gut permeability, promotes microbial translocation and immune activation in people living with HIV (PLWH) using effective antiretroviral therapy (ART). Methods Cross-sectional analysis of 100 PLWH (ART ≥6 months, HIV-RNA <200 copies/mL) from the Miami Adult Studies on HIV (MASH) cohort. Cocaine use was assessed by self-report, urine screen, and blood benzoylecgonine (BE). Blood samples were collected to assess gut permeability (intestinal fatty acid-binding protein, I-FABP), microbial translocation (lipopolysaccharide, LPS), immune activation (sCD14, sCD27, and sCD163) and markers of inflammation (hs-CRP, TNF-α and IL-6). Multiple linear regression models were used to analyze the relationships of cocaine use. Results A total of 37 cocaine users and 63 cocaine non-users were evaluated. Cocaine users had higher levels of I-FABP (7.92±0.35 vs. 7.69±0.56 pg/mL, P = 0.029) and LPS (0.76±0.24 vs. 0.54±0.27 EU/mL, P<0.001) than cocaine non-users. Cocaine use was also associated with the levels of LPS (P<0.001), I-FABP (P = 0.033), and sCD163 (P = 0.010) after adjusting for covariates. Cocaine users had 5.15 times higher odds to exhibit higher LPS levels than non-users (OR: 5.15 95% CI: 1.89–13.9; P<0.001). Blood levels of BE were directly correlated with LPS (rho = 0.276, P = 0.028), sCD14 (rho = 0.274, P = 0.031), and sCD163 (rho = 0.250, P = 0.049). Conclusions Cocaine use was associated with markers of gut permeability, microbial translocation, and immune activation in virally suppressed PLWH. Mitigation of cocaine use may prevent further gastrointestinal …

Background Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic remodeling is much less established. CK (creatine kinase), the primary muscle energy reserve reaction which rapidly provides ATP at the myofibrils and regenerates mitochondrial ADP, is down-regulated in experimental and human HF. We tested the hypotheses that pathologic remodeling in human HF is related to impaired cardiac CK energy metabolism and that rescuing CK attenuates maladaptive hypertrophy in experimental HF. Methods First, in 27 HF patients and 14 healthy subjects, we measured cardiac energetics and left ventricular remodeling using noninvasive magnetic resonance 31P spectroscopy and magnetic resonance imaging, respectively. Second, we tested the impact of metabolic rescue with cardiac-specific overexpression …

ObjectivesVolumetric evaluation of coronary artery disease (CAD) allows better prediction of cardiac events. However, CAD segmentation is labor intensive. Our objective was to create an open-source deep learning (DL) model to segment coronary plaques on coronary CT angiography (CCTA).MethodsThree hundred eight individuals’ 894 CCTA scans with 3035 manually segmented plaques by an expert reader (considered as ground truth) were used to train (186/308, 60%), validate (tune, 61/308, 20%), and test (61/308, 20%) a 3D U-net model. We also evaluated the model on an external test set of 50 individuals with vulnerable plaques acquired at a different site. Furthermore, we applied transfer learning on 77 individuals’ data and re-evaluated the model’s performance using intra-class correlation coefficient (ICC).ResultsOn the test set, DL outperformed the currently used minimum cost approach method to …

BackgroundThe simultaneous consumption of cocaine and alcohol results in the production of cocaethylene (CE) in the liver, a highly toxic metabolite. Prior research suggests that cocaine use contributes to liver disease and its concomitant use with alcohol may increase its hepatotoxicity, but studies in humans are lacking. We evaluated the role of cocaine, its simultaneous use with alcohol, and CE on liver fibrosis.MethodsWe performed a cross-sectional analysis of the Miami Adult Studies on HIV (MASH) cohort. Cocaine use was determined via self-report, urine screen, and blood metabolites, using liquid chromatography with tandem mass spectrometry. Hazardous drinking was determined with the AUDIT-C and liver fibrosis with the Fibrosis-4 Index (FIB-4).ResultsOut of 649 participants included in this analysis, 281 (43.3%) used cocaine; of those, 78 (27.8%) had CE in blood. Cocaine users with CE had higher …

Although previous studies suggest that amino acids (AAs) and microbiota-related metabolites (MRMs) are associated with type 2 diabetes mellitus (T2DM), the results remain unclear among normoglycemic populations. We test 28 serum AAs and 22 MRMs in 3,414 subjects with incident diabetes and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. In fully adjusted logistic regression models, per SD increment of branched-chain AAs, aromatic AAs, asparagine, alanine, glutamic acid, homoserine, 2-aminoadipic acid, histidine, methionine, and proline are positively associated with incident T2DM. In the MRM panel, serum carnitines, N-acetyltryptophan, and uric acid are positively associated with incident T2DM. Causal mediation analyses indicate 34 significant causal mediation linkages, with 88.2% through obesity and lipids. Variances explained in the serum …

Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR …

Methods: People living with human immunodeficiency virus (PLWH) were prospectively enrolled between March 2014 and August 2016 to undergo cash-based contingency management to achieve cocaine abstinence. Participants underwent coronary CT angiography (CTA) at baseline, 6-and 12-months following recruitment. We segmented coronary plaques and extracted 1103 radiomic features. We implemented weighted correlation network analysis to derive consensus eigen radiomic features and used linear mixed models and mediation analysis to assess whether cocaine abstinence affects plaque morphology correcting for clinical variables and plaque volumes. Furthermore, we used a Bayesian hidden Markov network changepoint to assess potential rewiring of the radiomic network in result to cocaine abstinence.Results: Altogether, 69 PLWH (median age 55 years, 19% female) completed the study, of …