Background:HIV and cocaine use (CU) each relate to cognitive deficits and brain abnormalities, yet their combined impact on brain aging remains unclear. This study examined how comorbid HIV and CU relate to brain aging and cognitive impairment. Methods:We trained a morphometry-based brain-age model using harmonized Human Connectome Project-Aging data (HCP-A; n=725) with Gaussian Process Regression. The model was applied to an independent cohort with varying HIV/CU burden (HIV-/CU-, n=34; one disorder [HIV+/CU- or HIV-/CU+], n=72; HIV+/CU+, n=80). Brain age gap (BAG; predicted minus chronological age) was examined in relation to comorbidity burden and neurocognitive impairment (NCI; NIH Toolbox), adjusting for age, sex, education, depression, and image-quality indices. Analyses on SHapley Additive exPlanation (SHAP) values characterized network-wise feature-level contributions to brain age estimates. Results:A dose-dependent effect of comorbidity burden on BAG was observed, with the HIV+/CU+ group showing the highest BAG. Greater BAG was associated with increased likelihood of NCI, and BAG partially mediated the relationship between comorbidity burden and NCI, with a stronger mediation effect in the two-disorder group than in the one-disorder group. Structural contributors to elevated BAG in the HIV/CU cohort included cortical thickness in the visual, ventral attention, and frontoparietal networks, and sulcal depth in the sensorimotor network. Conclusion:Comorbid HIV/CU is linked to accelerated structural brain aging. BAG may reflect brain-level alterations underlying the association between comorbid HIV/CU and cognitive impairment, and may help identify network-specific targets for intervention.

To evaluate the reproducibility of plaque quantification from serial cardiac computed tomography (CCTA) scans by a systematic side-by-side approach using validated AI-enabled software with both scan-specific and fixed attenuation thresholds. Thirty participants from two centers underwent serial CCTA within a short timeframe (median 6 days [IQR 0–30]). Volumes and burden (defined as plaque volume indexed by vessel volume) of total plaque (TP), calcified plaque (CP), non-calcified plaque (NCP), and low-density NCP (LD-NCP) were quantified per-patient while comparing the serial scans side-by-side. Analyses were done by two assessors using consensus readings to reduce individual bias, and inter-scan differences were compared using mean differences and the repeatability coefficient (RC, defined as 1.96 × standard deviation). Mean age was 59 years (70

BACKGROUND:The genetic architecture of circulating amino acids (AAs) and microbiota-related metabolites (MRMs) in relation to cardiometabolic disease remains poorly characterized in East Asian populations, limiting ancestry-specific insights. METHODS:In a prospective cohort of 2953 Chinese individuals, we performed a large-scale genome-wide association study (GWAS) of 28 serum AAs and 22 MRMs. We conducted a cross-ancestry comparison of variant-metabolite associations. Using colocalization and Mendelian randomization (MR), we further investigated causal roles of 50 AAs and MRMs in 25 cardiometabolic diseases from the BioBank Japan. Furthermore, we explored differences in the genetic regulation of these metabolites between incident T2DM cases and healthy controls. RESULTS:We identified 33 metabolite-variant associations, 22 of which were previously unreported, and revealed several loci specific to East Asian ancestry. Integrative colocalization and MR analyses established 49 causal relationships between metabolite levels and cardiometabolic diseases, most notably implicating genetically predicted N-acetyltryptophan to increased risk of type 2 diabetes. Moreover, we observed distinct patterns of genetic regulation between T2DM cases and controls, highlighting substantial heterogeneity of effects and dynamic gene-disease interplay. CONCLUSIONS:These findings offer crucial insights into the ancestry-specific genetic determinants of metabolic traits, and shed new light on their causal roles in the etiology of cardiometabolic diseases in East Asian populations.

Objective: Using an innovative data sharing model, we assessed the impacts of the COVID-19 pandemic on the health of people who inject drugs (PWID). Design: The PWID Data Collaborative was established in 2021 to promote data sharing across PWID studies in North America. Contributing studies submitted aggregate data on 23 standardized indicators during four time periods: prepandemic (March 2019 to February 2020), early-pandemic (March 2020 to February 2021), mid-pandemic (March 2021 to February 2022), and late pandemic (March 2022 to February 2023). Methods: We present study-specific and meta-analyzed estimates for the percentage of PWID who took medications for opioid use disorder, received substance use treatment, shared syringes or injection equipment, had a mental health condition, had been incarcerated, or had experienced houselessness. To examine change over time across indicators, we fit a random effects meta-regression model to prevalence estimates using time as a moderator. Results: Thirteen studies contributed estimates to the Data Collaborative on these indicators, representing 6213 PWID interviews. We observed minimal change across prevalence of the six indicators between the prepandemic (March 2019 to February 2020) and three subsequent time periods, overall or within individual studies. Considerable heterogeneity was observed across study-specific and time-specific estimates. Conclusion: Limited pandemic-related change observed in indicators of PWID health is likely a result of policy and supportive service-related changes and may also reflect resilience among service providers and PWID themselves. The Data Collaborative is an unprecedented data sharing model with potential to greatly improve the quality and timeliness of data on the health of PWID.

The heterogeneous and complex nature of prediabetes presents a major challenge in identifying individuals predisposed to developing incident diabetes and related complications. We aimed to identify phenotypic subgroups of prediabetes at risk and to explore their distinct associations with cardiometabolic outcomes. This study included 79,000 individuals with prediabetes from the three large-scale prospective cohorts in China. Phenotypic heterogeneity was identified using a soft-clustering algorithm based on the proximity network derived from uniform manifold approximation and projection (UMAP), combined with graph-clustering and Gaussian mixture models. Associations between phenotype probabilities and the incidence of type 2 diabetes (T2D), cardiovascular disease (CVD), and kidney events were assessed to evaluate risk differences across the identified profiles. Six phenotypic profiles were identified, including five with distinct metabolic features (representing 70

Background: Sex differences in hippocampal volumes are well-documented, but their interaction with HIV status and omega-3 fatty acids—particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—remains unclear, especially in underserved populations. This study examines how HIV and omega-3 fatty acids influence sex differences in hippocampal volume and explores whether cognitive performance related to episodic memory modifies the association of omega-3 levels with hippocampal volume, considering both HIV status and sex. Methods: We enrolled 166 participants aged over 45 years from a Baltimore, Maryland cohort. Brain MRIs were performed using a 3.0-T Siemens scanner, and volumetric segmentation was conducted with FreeSurfer (version 6.0), adjusting for intracranial volume (ICV). Results: Our study found that: (1) Among HIV-negative participants, females had significantly lower hippocampal volumes than males in 1 of 26 regions, whereas HIV-positive females had lower volumes in 13 of 26 regions (p < 0.006 for HIV-negative vs. HIV-positive females), (2) In HIV-positive individuals with EPA levels ≤0.40 %, females exhibited lower volumes in 11 of 26 regions, compared to no differences in those with EPA levels >0.40 % (p = 0.0003 for ≤0.40 % vs. >0.40 %), (3) Across all participants, lower EPA and DHA levels were associated with greater sex differences in hippocampal volumes, which diminished or disappeared at higher EPA and DHA levels (p < 0.00001 for EPA ≤0.40 % vs. >0.40 %; p = 0.004 for DHA ≤2.0 % vs. >2.0 %), and (4) Among Adults with lower episodic memory, higher log-scaled EPA levels were independently associated with greater hippocampal volume. Conclusions: HIV may amplify sex differences in hippocampal volumes, disproportionately affecting females. Higher EPA and DHA levels may mitigate these effects, suggesting a protective role against hippocampal atrophy. Further studies are warranted to confirm these findings and explore whether the benefits extend to males with HIV or individuals without HIV.

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) (P < 0.05). Interestingly, gender-specific analysis showed that per standard deviation (SD) increment of SCFAs were positively associated with incident T2DM among women, with the odds ratio (95% confidence interval) of 1.16 (1.05–1.29) for total SCFAs and 1.18 (1.07–1.31) for propionate, respectively (P < 0.05, false discovery rate (FDR) < 0.05). No significant associations were observed in men. A significant interaction was detected between men and women for propionate (Pinteraction < 0.001, FDR < 0.01). After further adjustment of insulin measurements, the associations of serum propionate with diabetes remained significant (P < 0.05, FDR < 0.05). Meanwhile, the associations of total BCFAs and isovaleric acid with diabetes were partially mediated by triglycerides, insulin resistance, and β-cell function in mediation analysis. These findings, for the first time in a large prospective cohort, provide evidence for an association between circulating SCFAs and BCFAs with T2DM risk, and support the potential role of circulating propionate with gender disparities in the early pathogenesis of diabetes.

Current obesity classifications may not adequately reflect age- and gender-specific risks in diverse populations. In a prospective cohort study of 166,285 Chinese adults aged ≥40 years without prior cardiovascular disease (CVD) or cancer, we evaluate optimal thresholds of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) for predicting incident CVD and all-cause mortality. We observe monotonically increasing dose-response associations of BMI, WC, and WHR with CVD risk but U-shaped relationships with all-cause mortality. The optimal obesity thresholds based on all-cause mortality risk differ by gender, with the lowest mortality risks occurring at BMI 26.3 kg/m2, WC 88 cm, and WHR 0.90 in men and BMI 25.4 kg/m2, WC 83 cm, and WHR 0.85 in women. Moreover, higher adiposity appears protective in older adults. These findings highlight the need for population-specific obesity criteria to enhance clinical risk assessment and public health strategies.

Objective We aimed to examine the effects of “5:2 regimens” diet (2-day/week of energy restriction by formula diet) or exercise (2-day/week of high-intensity interval training and resistance training) intervention compared with routine lifestyle education (control) on glycemic control and cardiometabolic health among adults with overweight/obesity and type 2 diabetes. Research Design and Methods This two-center, open-label, three-arm, parallel-group, randomized controlled trial recruited 326 participants with overweight/obesity and type 2 diabetes, and randomized them into a 12-week of diet intervention (N=109), exercise intervention (N=108), or lifestyle education (control) (N=109). The primary outcome was the change of glycemic control measured as glycated hemoglobin (HbA1c) between the diet or exercise intervention groups and the control group after a 12-week intervention. Results The diet intervention significantly reduced HbA1c level (%) after the 12-week intervention (−0.72, 95% confidence interval (CI) −0.95 to −0.48), compared with the control group (−0.37, 95% CI −0.60 to −0.15) (diet vs. control: −0.34, 95% CI −0.58 to −0.11, p=0.007). The reduction in HbA1c level in the exercise intervention group (−0.46, 95% CI −0.70 to −0.23) did not significantly differ from the control group (exercise vs. control: −0.09, 95% CI −0.32 to 0.15, p=0.47). The exercise intervention group was superior in maintaining lean body mass. Both diet and exercise interventions induced improvements in adiposity and hepatic steatosis. Conclusions These findings suggested that the medically supervised 5:2 energy-restricted diet could provide an alternative strategy for improving glycemic control, and the exercise regimen improved body composition, although inadequate to improve glycemic control.

Understanding sex disparities in modifiable risk factors across the lifespan is essential for crafting individualized intervention strategies. We aim to investigate age-related sex disparity in cardiometabolic phenotypes in a large nationwide Chinese cohort. A total of 254,670 adults aged 40 years or older were selected from a population-based cohort in China. Substantial sex disparities in the prevalence of metabolic diseases were observed across different age strata, particularly for dyslipidemia and its components. Generalized additive models were employed to characterize phenotype features, elucidating how gender differences evolve with advancing age. Half of the 16 phenotypes consistently exhibited no sex differences, while four (high-density lipoprotein [HDL] cholesterol, apolipoprotein A1, diastolic blood pressure, and fasting insulin) displayed significant sex differences across all age groups. Triglycerides, apolipoprotein B, non-HDL cholesterol, and total cholesterol demonstrated significant age-dependent sex disparities. Notably, premenopausal females exhibited significant age-related differences in lipid levels around the age of 40-50 years, contrasting with the relatively stable associations observed in males and postmenopausal females. Menopause played an important but not sole role in age-related sex differences in blood lipids. Sleep duration also had an age- and sex-dependent impact on lipids. Lipidomic analysis and K-means clustering further revealed that 58.6% of the 263 measured lipids varied with sex and age, with sphingomyelins, cholesteryl esters, and triacylglycerols being the most profoundly influenced lipid species by the combined effects of age, sex, and their interaction. These findings underscore the importance of age consideration when addressing gender disparities in metabolic diseases and advocate for personalized, age-specific prevention and management.

Abstract: Lipoprotein(a) [Lp(a)] is a risk factor for coronary disease. Although levels are primarily genetically determined, data from patients with inflammatory diseases indicate that the inflammatory milieu is associated with increased Lp(a) levels. Lp(a) is synthesized in the liver and the LPA gene promoter contains an interleukin-6 (IL-6) responsive binding site, but the regulatory steps linking inflammation with hepatic Lp(a) synthesis are not well clarified. We explored the interplay between IL-6, peroxisome proliferator-activated receptor gamma (PPARγ), and Lp(a) synthesis in HepG2 cells. Through genetic mapping, a regulatory variant within the LPA promoter overlapping with a PPARγ binding site was identified. In in vitro experiments, IL-6-mediated LPA gene transcription was heightened with PPARγ knock-down and suppressed with pioglitazone, a PPARγ agonist. These results demonstrate an important role of PPARγ as a negative regulator of IL-6-induced hepatic Lp(a) production and may represent a new therapeutic target for patients with inflammatory conditions characterized by elevated Lp(a).

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 μm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Background and aims People 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. Methods African Americans from the Heart Study in Baltimore, with and without HIV, recruited from inner-city Baltimore between June 2004 and February 2015, were included in this analysis. Participants underwent coronary CT angiography to evaluate the presence of coronary stenosis, defined as luminal stenosis >10%. Hcy was measured from stored serum samples. Results In this analysis, the median [IQR] age of the 664 participants was 56 [50–66] years; 68.1% were living with HIV and 43.1% were women. Elevated Hcy (>15 µmol/L) was more prevalent in those with coronary stenosis (23.3%, 95% CI: 18.4%–28.2%) than in those without coronary stenosis (13.1%, 95% CI: 9.7%–16.5%) ( p = 0.0007), and HIV was associated with coronary stenosis in those participants with an elevated Hcy (Prevalence Ratio: 1.94, 95% CI: 1.04-3.64, p = 0.0038) and not in those with a Hcy ≤15 µmol/L (Prevalence Ratio: 1.02, 95% CI: 0.83-1.25, p = 0.87). Conclusions Our data suggest an association between elevated Hcy levels (>15 µmol/L) and the prevalence of coronary stenosis in PWH from this inner city African American population.

BACKGROUND:Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES:Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS:This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS:The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS:These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

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:During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS:This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

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 evaluated whether baseline marker levels were associated with CEF after 8 weeks in the placebo group (N = 40).RESULTS:CEF measures were abnormal at baseline, based on trial entry criteria. A higher value of CEF was directly associated with levels of interleukin 10, whereas CEF at baseline was inversely associated with E-selectin. Worse CEF at 8 weeks was directly associated with baseline tumor necrosis factor alpha, intercellular adhesion molecule 1, C-reactive protein, interferon gamma and sICAM-3. SEF at baseline or 8 weeks was not associated with any baseline markers.CONCLUSION:Coronary but not systemic endothelial dysfunction was significantly associated with select markers of inflammation and adhesion in PWH. Furthermore, CEF but not SEF at 8 weeks was associated with baseline levels of inflammation. Our findings suggest that abnormal CEF and systemic markers of inflammation are linked in PWH.

Background Cocaine 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. Methods Between 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 was used to perform longitudinal data analyses. Findings During the 12-month CM, all 69 participants reduced cocaine use, and of these, 25 (36%; 95% confidence interval, 25%–49%) achieved cocaine abstinence. After adjusting for potential confounding factors, generalized estimating equation analyses showed that (1) endothelin-1 (ET-1) levels, a proinflammatory biomarker for endothelial dysfunction, at the 6-month and 12-month visits were significantly lower compared with baseline ET-1 (P = 0.001 and P < 0.001, respectively), and (2) low-attenuation noncalcified coronary plaque volume, a predictor for myocardial infarction, at 12-month visit was significantly lower compared with baseline low-attenuation noncalcified coronary plaque volume (P < 0.05). Conclusions The findings of this study have not only demonstrated that CM is effective in achieving a sustained reduction in cocaine use, but also provided compelling evidence that reduction in cocaine use leads to quantifiable cardiovascular health benefits, including concurrent decrease in high-risk plaque burden and ET-1, among cocaine users with HIV-associated coronary atherosclerosis.

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% CI): 0.77-1.64] nor female sex (adj PR: 1.07, 95% CI: 0.71-1.61) was associated with NCI among cocaine nonusers, while both HIV (adj PR: 1.39, 95% CI: 1.06-1.81) and female sex (adj PR: 1.53, 95% CI: 1.18-1.98) were associated with NCI in cocaine users. HIV was associated with two NIHTB-CB measures overall. In addition, HIV was associated with a lower dimensional change card sort score (an executive function measure) in cocaine users and not in nonusers. Cognitive performance was poorer in female than in male cocaine users. The adverse effect of HIV on cognitive performance predominantly affected cocaine users. However, cocaine use may moderate the impact of HIV and female sex on cognitive performance, highlighting the importance of reducing cocaine use in NCI prevention among the AA population.

HomeCirculation: Cardiovascular ImagingVol. 16, No. 10Rapid Improvement of Coronary Endothelial Function With PCSK9 Inhibition in People With HIV Is Associated With Reduced Lipoprotein (a) and Not LDL-cholesterol No AccessResearch ArticleRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessResearch ArticleRequest AccessFull TextRapid Improvement of Coronary Endothelial Function With PCSK9 Inhibition in People With HIV Is Associated With Reduced Lipoprotein (a) and Not LDL-cholesterol Tarek Harb, Efthymios Ziogos, Michael Schär, Todd T. Brown, Shenghan Lai, Gary Gerstenblith, Allison G. Hays and Thorsten M. Leucker Tarek HarbTarek Harb https://orcid.org/0000-0002-2573-5260 Division of Cardiology, Department of Medicine (T.H., E.Z., G.G., A.G.H., T.M.L.), Johns Hopkins University School of Medicine, Baltimore, MD. , Efthymios ZiogosEfthymios Ziogos https://orcid.org/0000-0002-5343-8714 Division of Cardiology, Department of Medicine (T.H., E.Z., G.G., A.G.H., T.M.L.), Johns Hopkins University School of Medicine, Baltimore, MD. , Michael SchärMichael Schär https://orcid.org/0000-0002-7044-9941 Division of Magnetic Resonance Research, Department of Radiology (M.S.), Johns Hopkins University School of Medicine, Baltimore, MD. , Todd T. BrownTodd T. Brown Division of Endocrinology, Diabetes and Metabolism, Department of Medicine (T.T.B.), Johns Hopkins University School of Medicine, Baltimore, MD. , Shenghan LaiShenghan Lai https://orcid.org/0000-0003-1340-9609 Department of Epidemiology and Public Health, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD (S.L.). , Gary GerstenblithGary Gerstenblith https://orcid.org/0000-0001-6046-6812 Division of Cardiology, Department of Medicine (T.H., E.Z., G.G., A.G.H., T.M.L.), Johns Hopkins University School of Medicine, Baltimore, MD. , Allison G. HaysAllison G. Hays https://orcid.org/0000-0003-2138-1589 Division of Cardiology, Department of Medicine (T.H., E.Z., G.G., A.G.H., T.M.L.), Johns Hopkins University School of Medicine, Baltimore, MD. and Thorsten M. LeuckerThorsten M. Leucker Correspondence to: Thorsten M. Leucker, MD, PhD, 600 N. Wolfe St. Johns Hopkins Hospital- Halsted 500, Baltimore, MD 21287. Email E-mail Address: [email protected] https://orcid.org/0000-0003-2569-6617 Division of Cardiology, Department of Medicine (T.H., E.Z., G.G., A.G.H., T.M.L.), Johns Hopkins University School of Medicine, Baltimore, MD. Originally published29 Sep 2023https://doi.org/10.1161/CIRCIMAGING.123.015693Circulation: Cardiovascular Imaging. 2023;16Footnotes*A.G. Hays and T.M. Leucker contributed equally.This manuscript was sent to Linda D. Gillam, Senior Guest Editor, for review by expert referees, editorial decision, and final disposition.For Sources of Funding and Disclosures, see page 841 & 842.Correspondence to: Thorsten M. Leucker, MD, PhD, 600 N. Wolfe St. Johns Hopkins Hospital- Halsted 500, Baltimore, MD 21287. Email tleucke1@jhmi.eduREFERENCES1. Leucker TM, Weiss RG, Schär M, Bonanno G, Mathews L, Jones SR, Brown TT, Moore R, Afework Y, Gerstenblith G, et al. Coronary endothelial dysfunction is associated with elevated serum PCSK9 levels in people with HIV independent of low-density lipoprotein cholesterol.J Am Heart Assoc. 2018; 7:e009996. doi: 10.1161/JAHA.118.009996LinkGoogle Scholar2. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease.N Engl J Med. 2017; 376:1713–1722. doi: 10.1056/NEJMoa1615664CrossrefMedlineGoogle Scholar3. Leucker TM, Gerstenblith G, Schär M, Brown TT, Jones SR, Afework Y, Weiss RG, Hays AG. Evolocumab, a PCSK9-monoclonal antibody, rapidly reverses coronary artery endothelial dysfunction in people living with HIV and people with dyslipidemia.J Am Heart Assoc. 2020; 9:e016263. doi: 10.1161/JAHA.120.016263LinkGoogle Scholar4. O'Donnell VB, Freeman BA. Interactions between nitric oxide and lipid oxidation pathways.Circ Res. 2001; 88:12–21. doi: 10.1161/01.res.88.1.12LinkGoogle Scholar5. Bhatia HS, Yeang C, Baruch A, Yang X, Stroes ESG, Tsimikas S. PCSK9 inhibition and oxidized phospholipids.J Am Coll Cardiol. 2021; 78:1288–1289. doi: 10.1016/j.jacc.2021.07.031CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails October 2023Vol 16, Issue 10 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.123.015693PMID: 37772401 Originally publishedSeptember 29, 2023 Keywordscholesterol, LDLcoronary vesselsHIVhumanlipoprotein(a)magnetic resonance imagingproprotein convertase 9PDF download Advertisement SubjectsMagnetic Resonance Imaging (MRI)