Search

Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV.Associations of HCV with CMV seropositivity and CMV IgG levels we

Background: NASH is considered a contributor to atherosclerotic cardiovascular disease (ASCVD) risk; however, its contribution beyond traditional risk factors for CVD, particularly diabetes, is less clearly understood. This study aimed to quantify the cardiovascular-event risk associated with NASH, independent of diabetes status., Methods: A cross-sectional analysis was conducted using the 2017-2020 NHANES pre-pandemic cycle. NASH was defined based on presence of steatosis without other causes of liver disease, and FibroScan+AST score from vibration-controlled transient elastography (VCTE). Significant fibrosis (stages F2-F4) was identified by liver stiffness measurement from VCTE. Predicted primary CV-event risk was estimated using both the Pooled Cohort Equations (PCE) and the Framingham Risk Score (FRS). NASH patients were matched with non-NASH controls on age, sex, race/ethnicity, and diabetes status. Weighted logistic regression was conducted, modeling elevated predicted CV risk (binary) as the dependent variable and indicators for NASH / fibrosis stages as independent variables., Results: A sample of 125 NASH patients was matched with 2585 controls. NASH with significant fibrosis was associated with elevated predicted 10-year CV risk, although this association was only statistically significant in PCE analyses (odds ratio and 95% CI 2.34 [1.25, 4.36]). Analyses restricting to ages <65 years showed similar results, with associations of greater magnitude., Conclusion: Independent of diabetes, a significant association was observed between NASH with significant liver fibrosis and predicted primary CV-event risk in US adults, particularly for those <65. These findings suggest the importance of accounting for NASH and liver-fibrosis stage in predicting CV-event risk., Competing Interests: “I have read the journal’s policy and the authors of this manuscript have the following competing interests: JJW and TO are employees of Medicus Economics, LLC, a paid consultant of Madrigal Pharmaceuticals. CMP has received consulting fees from Canopy, Clue by Biowink, Collective Acumen, ConcertAI, EQRx, Evidation Health, Flatiron Health, Jazz Pharmaceuticals, Medicus Economics, Omada Health, Plinth and TTi Health Research & Economics. JF was formerly employed by and held stock options in Madrigal Pharmaceuticals. Madrigal Pharmaceuticals paid the publication charges for this piece, via reimbursement to Medicus Economics. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Woolley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease worldwide. Therapies are under development for nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, such that the prevalence of NASH with liver fibrosis, which is likely to require treatment, may be of interest to healthcare decision makers. Noninvasive tests are used in initial screening for NASH, as well as in observational studies of NASH prevalence. However, existing evidence does not address how estimated prevalence varies with different noninvasive tests. This analysis estimated the prevalence of NASH among US adults and assessed variation with different noninvasive tests. Methods: A cross-sectional analysis was conducted using the 2017-March 2020 National Health and Nutrition Examination Survey cycle. Participants with presumed NAFLD (steatosis and without alternative causes of liver disease) were identified, among whom NASH was predicted based on FAST score, Fibrosis-4 (FIB-4), and AST-to-Platelet Ratio Index (APRI) cutoffs across 11 scenarios. Among NASH participants, fibrosis stages were explored based on distribution across the spectrum of liver-stiffness measurements. Results: Among participants with complete data for the analysis (N=6969), prevalence of presumed NAFLD was 25.6%. Within presumed NAFLD, prediction of NASH using imaging-based NIT cutoffs yielded estimated prevalence of 1.3%-4.8% (3.3 million-12.2 million) based on FAST score cutoffs from 0.35-0.67. Using biomarker-based NIT cutoffs yielded estimated prevalence of 0.4%-12.3% (1.0 million-14.5 million) based on FIB-4 cutoffs from 0.90-2.67, and 0.1%-1.9% (0.2-5.0 million) based on APRI cutoffs from 0.50-1.50. Conclusion: Prevalence of NASH among US adults was estimated to range from 1.3% to 4.8% when predicted using imaging-based noninvasive test values for participants with presumed NAFLD, generally aligning with estimates in the literature of prevalence of biopsy-confirmed NASH. Use of biomarker-based noninvasive test values for prediction of NASH yielded a wider range of estimates with FIB-4, and a considerably lower range of estimates with APRI.

Importance: Individually, cardiac, renal, and metabolic (CRM) conditions are common and leading causes of death, disability, and health care-associated costs. However, the frequency with which CRM conditions coexist has not been comprehensively characterized to date., Objective: To examine the prevalence and overlap of CRM conditions among US adults currently and over time., Design, Setting, and Participants: To establish prevalence of CRM conditions, nationally representative, serial cross-sectional data included in the January 2015 through March 2020 National Health and Nutrition Examination Survey (NHANES) were evaluated in this cohort study. To assess temporal trends in CRM overlap, NHANES data between 1999-2002 and 2015-2020 were compared. Data on 11 607 nonpregnant US adults (≥20 years) were included. Data analysis occurred between November 10, 2020, and November 23, 2022., Main Outcomes and Measures: Proportion of participants with CRM conditions, overall and stratified by age, defined as cardiovascular disease (CVD), chronic kidney disease (CKD), type 2 diabetes (T2D), or all 3., Results: From 2015 through March 2020, of 11 607 US adults included in the analysis (mean [SE] age, 48.5 [0.4] years; 51.0% women), 26.3% had at least 1 CRM condition, 8.0% had at least 2 CRM conditions, and 1.5% had 3 CRM conditions. Overall, CKD plus T2D was the most common CRM dyad (3.2%), followed by CVD plus T2D (1.7%) and CVD plus CKD (1.6%). Participants with higher CRM comorbidity burden were more likely to be older and male. Among participants aged 65 years or older, 33.6% had 1 CRM condition, 17.1% had 2 CRM conditions, and 5.0% had 3 CRM conditions. Within this subset, CKD plus T2D (7.3%) was most common, followed by CVD plus CKD (6.0%) and CVD plus T2D (3.8%). The CRM comorbidity burden was disproportionately high among participants reporting non-Hispanic Black race or ethnicity, unemployment, low socioeconomic status, and no high school degree. Among participants with 3 CRM conditions, nearly one-third (30.5%) did not report statin use, and only 4.8% and 3.0% used glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, respectively. Between 1999 and 2020, the proportion of US adults with multiple CRM conditions increased significantly (from 5.3% to 8.0%; P < .001 for trend), as did the proportion having all 3 CRM conditions (0.7% to 1.5%; P < .001 for trend)., Conclusions and Relevance: This cohort study found that CRM multimorbidity is increasingly common and undertreated among US adults, highlighting the importance of collaborative and comprehensive management strategies.

Background: Clinical trials suggest α-fetoprotein (AFP) reduction may be prognostic among patients with advanced hepatocellular carcinoma. However, the association of AFP reduction with outcomes in real-world settings is unclear., Methods: Patients with advanced hepatocellular carcinoma between January 1, 2011, and June 30, 2021, first-line tyrosine kinase inhibitor, and baseline and posttreatment AFP values (closest to 8 ± 2 weeks after first-line initiation) were included. AFP reduction was defined as ≥20% decrease from baseline vs <20% or no decrease. Real-world overall survival and progression-free survival (rwPFS) were defined as time from posttreatment AFP measurement to death, and the first progression event or death, respectively. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models adjusted for potential confounders and baseline AFP. Effect modification by baseline AFP and hepatocellular carcinoma risk factors was assessed., Results: Among 533 patients, median baseline AFP was higher in those with AFP reduction than those without (N = 166, 210 µg/L vs N = 367, 150 µg/L). There was a 35% decrease in hazard of death for patients with reduction vs without (aHR = 0.65; 95% CI, 0.52-0.81; median, 10.3 vs 5.9 months). Results were similar for rwPFS (aHR = 0.66; 95% CI, 0.54-0.81; median, 4.6 vs 2.6 months). AFP reduction was associated with better outcomes among patients with baseline AFP ≥400 µg/L or with history of hepatitis B virus, hepatitis C virus, or alcohol use. Only the interaction between baseline AFP and reduction in association with rwPFS was statistically significant., Conclusions: For certain etiologies, posttreatment AFP change may be more important than baseline AFP for prognosis. Further work should characterize the prognostic implications of longitudinal AFP changes during treatment., Plain Language Summary: The prognostic value of the change in α-fetoprotein (AFP) concentration after treatment initiation is less established, particularly in real-world settings. Longitudinal data from a large nationwide cohort of patients with advanced hepatocellular carcinoma (HCC) treated with first-line tyrosine kinase inhibitor in routine practice revealed that ≥20% reduction in posttreatment AFP levels was associated with better real-world overall survival and progression-free survival after adjusting for baseline AFP levels and other factors. The results also suggested that the associations may be stronger among patients with a history of HCC risk factors (e.g., hepatitis C virus, alcohol) or with higher baseline AFP levels., (© 2023 Flatiron Health Inc and The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: The use of digital symptom monitoring with patient-reported outcomes (PROs) has been shown to improve patient outcomes. The evidence of benefit has been largely derived from research studies. The feasibility of adopting this technology in the real-world setting is unknown., Methods: We report on the clinical implementation of a proprietary electronic patient-reported outcome (ePRO)-based digital symptom monitoring platform at the Highlands Oncology Group practice, a large community oncology practice. We present here our experience with patient enrollment, engagement, and retention; reasons for discontinued use; proportion of reports generating alerts and containing severe symptoms; and the responses to alerts including nursing telephone consultations and urgent office visits., Results: Over an approximately 17-month period, 923 patients were successfully enrolled. Patients enrolled from June 20, 2020, through November 30, 2021, with follow-up through February 28, 2022. Retention rates at 3, 6, 9, and 12 months were 94%, 88%, 73%, and 67%, respectively, with greater retention at 12 months in patients age 65 years or older. Few patients discontinued use for reasons related to the platform (n = 47; 5%). Of the 25,311 ePRO reports submitted, 49% (n = 12,334) exceeded the predefined alert thresholds and 8% (n = 1,920) included severe symptoms. The nursing team responded within 24 hours by telephone to 31.2% (n = 3,910) of all reports with alerts. Of reports with severe symptoms, 72.7% (n = 1,395) received a call. Only 6.4% (n = 249) of phone calls required an office evaluation within 72 hours of the report., Conclusion: This single-center experience indicates that an ePRO-based digital symptom monitoring platform can be effectively implemented at a large scale with a high level of long-term patient engagement. Most reports could be effectively resolved by nurses, and physician intervention was infrequently required.

Introduction: We previously demonstrated that real-world progression (rwP) can be ascertained from unstructured electronic health record (EHR)-derived documents using a novel abstraction approach for patients with advanced non-small cell lung cancer (base case). The objective of this methodological study was to assess the reliability, clinical relevance, and the need for disease-specific adjustments of this abstraction approach in five additional solid tumor types., Methods: Patients with metastatic breast cancer (mBC), advanced melanoma (aMel), small cell lung cancer (SCLC), metastatic renal cell carcinoma (mRCC), and advanced gastric/esophageal cancer (aGEC) were selected from a real-world database. Disease-specific additions to the base case were implemented as needed. The resulting abstraction approach was applied to each disease cohort to capture rwP events and dates. To provide comprehensive clinical context, real-world progression-free survival (rwPFS) and time to progression (rwTTP) were compared to real-world overall survival (rwOS), time to next treatment (rwTTNT), and time to treatment discontinuation (rwTTD). Endpoint estimates were assessed using the Kaplan-Meier method. Correlations between real-world endpoints and rwOS were calculated using Spearman's ρ., Results: Additions to the base-case rwP abstraction approach were required for mBC, aMel, and SCLC. Inter-abstractor agreement for rwP occurrence, irrespective of date, ranged from 88% to 97%. Occurrence of clinically relevant downstream events (new antineoplastic systemic therapy start, antineoplastic systemic therapy end, or death relative to the rwP event) ranged from 59% (aMel) to 72% (mBC). Median rwPFS ranged from 3.7 (aMel) to 7.7 (mBC) months, and median rwTTP ranged from 4.6 (aMel) to 8.3 (mRCC) months. Correlations between rwOS and rwPFS ranged from 0.52 (aMel) to 0.82 (SCLC). The correlation between rwOS and rwTTD was often lower relative to other comparisons (range 0.40-0.62)., Conclusion: Derivation of a rwP variable from EHR documentation is feasible and reliable across the five solid tumors. Endpoint analyses show that rwP produces clinically meaningful information., (© 2022. The Author(s).)

Objective: We expanded the previous assessment of a mortality variable suited for real-world evidence-focused oncology research., Data Source: We used a nationwide electronic health record (EHR)-derived de-identified database., Data Collection: We included patients with at least 1 of 18 cancer types between January 1, 2011 and December 31, 2017. Patient-level structured data (EHRs, obituaries, and Social Security Death Index) and unstructured EHR data (abstracted) were linked to generate a composite mortality variable., Study Design: We benchmarked sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ±15-day agreement against the National Death Index (NDI). Real-world overall survival (rwOS) was estimated using the Kaplan-Meier method. We performed sensitivity analyses using a smaller patient cohort that underwent next-generation sequencing testing., Principal Findings: Compared with the NDI across 18 cancer types (overall N = 160 436): sensitivity, 83.9%-91.5% (17/18 cancer types had sensitivity ≥85.0%); specificity, 93.5%-99.7%; PPV, 96.3%-98.3%; NPV, 75.0%-98.7%; ±15-day agreement, 95.6%-97.6%; and median rwOS estimates ranging from 2.8% to 12.7% greater. Sensitivity analysis results (n = 17 540) were consistent with the main analysis., Conclusions: Across all cancer types analyzed, this composite mortality variable showed high sensitivity, specificity, PPV, NPV, and ±15-day agreement, and yielded median rwOS values modestly overestimated when compared to NDI-based results., (© 2021 Flatiron Health, Inc. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

There is growing interest in leveraging real-world data to complement knowledge gained from randomized clinical trials and inform the design of prospective randomized studies in oncology. The present study compared clinical outcomes in women with metastatic breast cancer who received letrozole as first-line monotherapy in oncology practices across the United States versus patients in the letrozole-alone cohort of the PALOMA-2 phase 3 trial. The real-world cohort (N = 107) was derived from de-identified patient data from the Flatiron Health electronic health record database. The clinical trial cohort (N = 222) comprised postmenopausal women in the letrozole-alone arm of PALOMA-2. Patients in the real-world cohort received letrozole monotherapy per labeling and clinical judgment; patients in PALOMA-2 received letrozole 2.5 mg/d, continuous. Real-world survival and response rates were based on evidence of disease burden curated from clinician notes, radiologic reports, and pathology reports available in the electronic health record. Progression-free survival and objective response rate in PALOMA-2 were based on Response Evaluation Criteria in Solid Tumors v1.1. Concordance of survival and response rates were retrospectively assessed using inverse probability of treatment weighting-adjusted Cox regression analysis. Inverse probability of treatment weighting-adjusted Cox regression results showed similar median progression-free survival in the real-world and PALOMA-2 cohorts (18.4 and 16.6 months, respectively): the hazard ratio using real-world data as reference was 1.04 (95% CI, 0.69-1.56). No significant difference was observed in response rates: 41.8% in the real-world cohort vs 39.4% in the PALOMA-2 cohort (odds ratio using real-world data as reference: 0.91 [95% CI, 0.57-1.44]). These findings indicate that data abstracted from electronic health records with proper quality controls can yield meaningful information on clinical outcomes. These data increase confidence in the use of real-world assessments of progression and response as efficacy endpoints. Trial registration NCT01740427; Funding: Pfizer., Competing Interests: I have read the journal's policy and wish to report the following conflicts: Cynthia Huang Bartlett is a former employee of and owns stock in Pfizer Inc. Jack Mardekian, Matthew James Cotter, Xin Huang, and Zhe Zhang are employees of and own stock in Pfizer Inc. Christina M. Parrinello, and Ariel Bulua Bourla are employees of Flatiron Health, Inc., which is an independent subsidiary of the Roche Group, and which received funding from Pfizer for the conduct of this study; they also report equity ownership in Flatiron Health Inc. All authors affirm that these competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Associations of insulin resistance and hyperglycemia with a panel of liver enzymes have not been well studied in a young, heterogenous Hispanic/Latino population. We aimed to assess the associations of insulin resistance and glycemia with nonalcoholic fatty liver disease (NAFLD), as measured by liver enzymes and the pediatric NAFLD fibrosis index (PNFI), and whether these associations are modified by body mass index and mediated by inflammation or endothelial dysfunction., Materials and Methods: We conducted a cross-sectional study of 1317 boys and girls aged 8 to 16 years from the Hispanic Community Children's Health Study/Study of Latino Youth. We used Poisson regression to assess the associations of fasting glucose, hemoglobin A1c, and homeostasis model assessment of insulin resistance (HOMA-IR) with elevated alanine aminotransferase (ALT) (>25 U/L in boys, >22 U/L in girls), aspartate aminotransferase (AST) (≥37 U/L), gamma-glutamyl transpeptidase (GGT) (≥17 U/L), and PNFI (≥9; a function of age, waist circumference, and triglyceride level)., Results: HOMA-IR was associated with elevated ALT, AST, GGT, and PNFI [prevalence ratios (95% confidence intervals) for each 1-unit increase in the natural log of HOMA-IR: 1.99 (1.40-2.81), 2.15 (1.12-4.12), 1.70 (1.26-2.30), and 1.98 (1.43-2.74), respectively]. Associations were observed in overweight/obese children, but not in normal weight children (P-interaction=0.04 for AST and P-interaction=0.07 for GGT). After further adjustment for adiponectin, high-sensitivity C-reactive protein, e-selectin, and PAI-1, associations of HOMA-IR with liver enzymes and PNFI were attenuated, but remained statistically significant for AST and PNFI., Conclusion: Insulin resistance was associated with NAFLD in overweight/obese Hispanic/Latino youth, and this association may be partially mediated by inflammation and endothelial dysfunction.

Background: Metabolic syndrome (MetS), a cluster of cardiovascular risk factors, is being diagnosed in youth. Specific diagnostic criteria used to define MetS influence prevalence estimates and populations considered at risk for cardiovascular disease. The National Cholesterol Education Program's Adult Treatment Panel III (ATP), the World Health Organization (WHO), and the International Diabetes Federation (IDF) provide three MetS definitions used in medical research. This study examined concordance among these definitions in 1137 children 10-16 years of age, who participated in the Hispanic Community Children's Health Study/Study of Latino Youth., Methods: Prevalence of MetS and of individual components was estimated using SAS. Mplus was used to test a single-factor model of MetS components (triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, waist circumference, and fasting glucose)., Results: The ATP definition identified most MetS cases in 10-15 (N = 19, 4.7%) and 16-year-old girls (N = 3, 7.3%). The IDF definition identified most cases of MetS in 10-15 (N = 16, 3.1%) and 16-year-old boys (N = 2, 2.8%). Fewest cases of MetS were identified with the WHO definition across age and sex groups., Conclusion: Only one participant was classified as having MetS across all three definitions. Confirmatory factor analysis indicated fasting glucose and systolic blood pressure did not reliably cluster with other risk factors that define MetS in Hispanic/Latino adolescents. We conclude that prevalence estimates of MetS in youth are unstable across current criteria, calling into question the accuracy of defining and diagnosing MetS in youth.

Aims: We hypothesized that Hispanic/Latino youth at high risk for diabetes would have elevated biomarkers of endothelial dysfunction., Methods: Among 1316 children 8-16years old from the Study of Latino Youth (SOL Youth), we used Poisson regression to obtain prevalence ratios (PRs) and 95% CIs for the cross-sectional association of quartiles of fasting glucose, HbA1c, and insulin resistance with E-selectin and plasminogen activator inhibitor-1 (PAI-1) levels above the median (≥48.1 and ≥2.02ng/mL, respectively)., Results: Levels of E-selectin and PAI-1 were higher in children who were obese or had higher levels of hs-CRP (p<0.05). Insulin resistance was independently associated with higher levels of PAI-1 (adjusted PR and 95% CI for the highest versus lowest quartile (Q4 vs Q1): 2.25 [1.64, 3.09]). We found stronger evidence of associations of insulin resistance with higher levels of PAI-1 among boys as compared with girls (p-interaction = 0.10)., Conclusions: Insulin resistance was associated with endothelial dysfunction, as measured by higher levels of PAI-1, in Hispanic/Latino youth. These biomarkers may be useful in risk stratification and prediction of diabetes and cardiovascular disease in high-risk youth., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: There is a need for continued surveillance of diabetes-related functional disability. In the present study, we examined associations between diabetes, hyperglycemia, and the burden of functional disability in a community-based population., Methods: A cross-sectional analysis was conducted of 5035 participants who attended Visit 5 (2011-13) of the Atherosclerosis Risk in Communities study. Functional disability was dichotomously defined by any self-reported difficulty performing 12 tasks essential to independent living grouped into four functional domains. Associations of diagnosed diabetes (via self-report) and undiagnosed diabetes and prediabetes (via HbA1c) with functional disability were evaluated using Poisson regression., Results: Participants had a mean age of 75 years, 42 % were male, 22 % were Black, and 31 % had diagnosed diabetes. Those with diagnosed diabetes had a significantly greater burden of functional disability than those without diabetes, even after adjustment for demographics, health behaviors, and comorbidities: prevalence ratios (95 % confidence intervals) were 1.24 (1.15, 1.34) for lower extremity mobility, 1.14 (1.07, 1.21) for general physical activities, 1.33 (1.16, 1.52) for instrumental activities of daily living (ADL), and 1.46 (1.24, 1.73) for ADL (all P < 0.05). The associations of undiagnosed diabetes and prediabetes with disability were not statistically significant (all P > 0.05)., Conclusions: Among older adults, the burden of functional disability associated with diabetes was not entirely explained by known risk factors, including comorbidities. Hyperglycemia below the threshold for the diagnosis of diabetes was not associated with disability. Research into effective strategies for the prevention of functional disability among older adults with diabetes is needed., (© 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Quantifying the variability of biomarkers is important, as high within-person variability can lead to misclassification of individuals. Short-term variability of important markers of vitamin D metabolism is relatively unknown., Methods: A repeatability study was conducted in 160 Atherosclerosis Risk in Communities study participants (60% female, 28% black, mean age 76 years). Fasting serum was drawn at 2 time points, a median of 6 (range 3-13) weeks apart. Vitamin D binding protein (VDBP) and 25-hydroxyvitamin D [25(OH)D] were measured by LC-MS, fibroblast growth factor (FGF23) and parathyroid hormone (PTH) by enzyme-linked immunoassay, and calcium and phosphorus by Roche Cobas 6000. Free and bioavailable 25(OH)D were calculated. We calculated the within-person CV (CV W ), intraclass correlation coefficient (ICC), Spearman rank correlation coefficient (r), and percent reclassified., Results: The CV W was lowest for calcium (2.0%), albumin (3.6%), 25(OH)D (6.9%), VDBP (7.0%) and phosphorus (7.6%); intermediate for free 25(OH)D (9.0%) and bioavailable 25(OH)D (9.9%); and highest for PTH (16.7%) and FGF23 (17.8%). Reclassification was highest for PTH, VDBP, and phosphorus (all 7.5%). The ICC and r were highest (≥0.80) for 25(OH)D, free 25(OH)D, bioavailable 25(OH)D and PTH, but somewhat lower (approximately 0.60-0.75) for the other biomarkers., Conclusions: Six-week short-term variability, as assessed by CV W , was quite low for VDBP, calcium and phosphorus, but fairly high for FGF23 and PTH. As such, multiple measurements of FGF23 and PTH may be needed to minimize misclassification. These results provide insight into the extent of potential misclassification of vitamin D markers in research and clinical settings., (© 2016 American Association for Clinical Chemistry.)

Aims: To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers., Methods: We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics., Results: Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [β-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%)., Conclusions: These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications., (© 2016 John Wiley & Sons Ltd.)

Objective: To determine the prevalence of obesity and cardiometabolic risk in US Hispanic/Latino youth and examine whether there are disparities by sex in cardiometabolic risk factors., Study Design: Study of Latino Youth is a population-based cross-sectional study of 1466 Hispanic/Latino youth (8-16 years old) who were recruited from 4 urban US communities (Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA) in 2012-2014. The majority of children were US-born (78%) and from low-income and immigrant families. Cardiometabolic risk factors were defined by the use of national age- and sex-specific guidelines., Results: The prevalence of obesity was 26.5%. The prevalence of class II-III obesity, diabetes, and dyslipidemia was high (9.7%, 16.5%, and 23.3%, respectively). The prevalence of cardiometabolic risk factors increased with severity of obesity in both boys and girls. Boys had a greater prevalence of diabetes and of elevated blood pressure than girls (20.9% vs 11.8% and 8.5% vs 3.3%). In multivariable analyses, younger boys were more likely to have obesity class II-III than girls (OR 3.59; 95% CI 1.44-8.97). Boys were more likely to have prediabetes than girls (OR 2.02; 95% CI 1.35-3.02), and the association was stronger at older ages., Conclusions: The prevalence of cardiometabolic risk factors was high in this sample of Hispanic youth. Boys had a more adverse cardiometabolic profile compared with girls that may put them at higher risk of diabetes and cardiovascular disease later in life. Reasons for this disparity and the long-term clinical implications remain to be elucidated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Extreme values that arise for any reason, including those through nonlaboratory measurement procedure-related processes (inadequate mixing, evaporation, mislabeling), lead to outliers and inflate errors in recalibration studies. We present an approach termed iterative outlier removal (IOR) for identifying such outliers., Methods: We previously identified substantial laboratory drift in uric acid measurements in the Atherosclerosis Risk in Communities (ARIC) Study over time. Serum uric acid was originally measured in 1990-1992 on a Coulter DACOS instrument using an uricase-based measurement procedure. To recalibrate previous measured concentrations to a newer enzymatic colorimetric measurement procedure, uric acid was remeasured in 200 participants from stored plasma in 2011-2013 on a Beckman Olympus 480 autoanalyzer. To conduct IOR, we excluded data points >3 SDs from the mean difference. We continued this process using the resulting data until no outliers remained., Results: IOR detected more outliers and yielded greater precision in simulation. The original mean difference (SD) in uric acid was 1.25 (0.62) mg/dL. After 4 iterations, 9 outliers were excluded, and the mean difference (SD) was 1.23 (0.45) mg/dL. Conducting only one round of outlier removal (standard approach) would have excluded 4 outliers [mean difference (SD) = 1.22 (0.51) mg/dL]. Applying the recalibration (derived from Deming regression) from each approach to the original measurements, the prevalence of hyperuricemia (>7 mg/dL) was 28.5% before IOR and 8.5% after IOR., Conclusions: IOR is a useful method for removal of extreme outliers irrelevant to recalibrating laboratory measurements, and identifies more extraneous outliers than the standard approach., (© 2016 American Association for Clinical Chemistry.)

Objective: We compared levels and associations of traditional (fasting glucose, HbA1c) and nontraditional (fructosamine, glycated albumin, and 1,5-anhydroglucitol [1,5-AG]) biomarkers of hyperglycemia with incident cardiovascular disease (CVD), incident end-stage renal disease (ESRD), and prevalent retinopathy in black and white adults., Research Design and Methods: We included 10,373 participants without (8,096 white, 2,277 black) and 727 with diagnosed diabetes (425 white, 302 black) from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox proportional hazards models to compare hazards ratios of CVD and ESRD among blacks and whites from baseline (1990-1992) through 2012. We compared the odds ratios (from logistic regression) of retinopathy among blacks and whites. We tested for the interaction of each biomarker with race., Results: Median values of biomarkers were higher among blacks versus whites (all P < 0.001). Relative risks for each biomarker with incident CVD and ESRD, and odds ratios for each biomarker with prevalent retinopathy, were similar by race (all P values for interaction by race >0.10)., Conclusions: The prognostic value of HbA1c, fructosamine, glycated albumin, and 1,5-AG with incident CVD, incident ESRD, and prevalent retinopathy were similar by race. Our results support similar interpretation of HbA1c and nontraditional biomarkers of hyperglycemia among black and whites with respect to long-term complications., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

The study examined the association of childhood and current economic hardship with anthropometric indices in Hispanic/Latino adults, using data from the HCHS/SOL Socio-cultural ancillary study (N = 5,084), a community-based study of Hispanic/Latinos living in four urban areas (Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA). Childhood economic hardship was defined as having experienced a period of time when one's family had trouble paying for basic needs (e.g., food, housing), and when this economic hardship occurred: between 0-12, 13-18 years old, or throughout both of those times. Current economic hardship was defined as experiencing trouble paying for basic needs during the past 12 months. Anthropometry included height, body mass index (BMI), waist circumference (WC), and percentage body fat (%BF). Complex survey linear regression models were used to test the associations of childhood economic hardship with adult anthropometric indices, adjusting for potential confounders (e.g., age, sex, Hispanic background). Childhood economic hardship varied by Hispanic background, place of birth, and adult socio-economic status. Childhood economic hardship during both periods, childhood and adolescence, was associated with shorter height. Childhood economic hardship was associated with greater adiposity among US born individuals only. Current economic hardship was significantly associated with all three measures of adiposity (BMI, WC, %BF). These findings suggest that previous periods of childhood economic hardship appear to influence adult height more than adiposity, whereas current economic hardship may be a better determinant of adult adiposity in Hispanics.

Background: Single measurements of elevated high-sensitivity C-reactive protein (hs-CRP) are associated with increased risk of diabetes, cardiovascular disease, and mortality. Large increases or sustained elevations in hs-CRP may be associated with even greater risk of these outcomes. The objective of this study was to characterize the association of 6-year change in hs-CRP with incident diabetes, incident cardiovascular events (heart disease, stroke, and heart failure), and mortality., Methods: We included 10,160 ARIC participants with hs-CRP measured at visits 2 (1990-1992) and 4 (1996-1998). Change in hs-CRP was categorized as sustained low/moderate (<3 mg/L at both visits), decreased (≥3 mg/L at visit 2 and <3 mg/L at visit 4), increased (<3 mg/L at visit 2 and ≥3 mg/L at visit 4), and sustained elevated (≥3 mg/L at both visits). Cox proportional hazards models were used to assess the association of 6-year change in hs-CRP with incident diabetes, cardiovascular events, and death during ~15 years after visit 4., Results: Compared with persons with sustained low/moderate hs-CRP, those with increased or sustained elevated hs-CRP had an increased risk of incident diabetes (hazard ratios [95% CIs] 1.56 [1.38-1.76] and 1.39 [1.25-1.56], respectively), whereas those with deceased hs-CRP did not. Persons with sustained elevated hs-CRP had an increased risk of coronary heart disease, ischemic stroke, heart failure, and mortality (hazard ratios [95% CIs] 1.51 [1.23-1.85], 1.70 [1.32-2.20], 1.60 [1.35-1.89], and 1.52 [1.37-1.69], respectively) compared with those with sustained low/moderate hs-CRP. Associations for sustained elevated hs-CRP were greater than for those with increased hs-CRP over 6 years., Conclusions: Large increases or sustained elevations in hs-CRP over a 6-year period were associated with a subsequent increased risk of diabetes, and persons with sustained elevations in hs-CRP were at the highest risk for cardiovascular disease and mortality. Two measurements of hs-CRP are better than one for characterizing risk, and large increases are particularly prognostic., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Equivalence of laboratory tests over time is important for longitudinal studies. Even a small systematic difference (bias) can result in substantial misclassification., Methods: We selected 200 Atherosclerosis Risk in Communities Study participants attending all 5 study visits over 25 years. Eight analytes were remeasured in 2011-2013 from stored blood samples from multiple visits: creatinine, uric acid, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and high-sensitivity C-reactive protein. Original values were recalibrated to remeasured values with Deming regression. Differences >10% were considered to reflect substantial bias, and correction equations were applied to affected analytes in the total study population. We examined trends in chronic kidney disease (CKD) pre- and postrecalibration., Results: Repeat measures were highly correlated with original values [Pearson r > 0.85 after removing outliers (median 4.5% of paired measurements)], but 2 of 8 analytes (creatinine and uric acid) had differences >10%. Original values of creatinine and uric acid were recalibrated to current values with correction equations. CKD prevalence differed substantially after recalibration of creatinine (visits 1, 2, 4, and 5 prerecalibration: 21.7%, 36.1%, 3.5%, and 29.4%, respectively; postrecalibration: 1.3%, 2.2%, 6.4%, and 29.4%). For HDL cholesterol, the current direct enzymatic method differed substantially from magnesium dextran precipitation used during visits 1-4., Conclusions: Analytes remeasured in samples stored for approximately 25 years were highly correlated with original values, but 2 of the 8 analytes showed substantial bias at multiple visits. Laboratory recalibration improved reproducibility of test results across visits and resulted in substantial differences in CKD prevalence. We demonstrate the importance of consistent recalibration of laboratory assays in a cohort study., (© 2015 American Association for Clinical Chemistry.)

Objective: Controversy surrounds appropriate risk factor targets in older adults with diabetes. We evaluated the proportion of older adults with diabetes meeting different targets, focusing on possible differences by race, and assessed whether demographic and clinical characteristics explained disparities., Research Design and Methods: We conducted a cross-sectional study of 5,018 participants aged 67-90 years (1,574 with and 3,444 without diagnosed diabetes) who attended visit 5 of the Atherosclerosis Risk in Communities (ARIC) study (2011-2013). Risk factor targets were defined using both stringent (and less stringent) goals: hemoglobin A1c (HbA1c) <7%, <53 mmol/mol (<8%, <64 mmol/mol); LDL cholesterol (LDL-c) <100 mg/dL (<130 mg/dL); and blood pressure (BP) <140/90 mmHg (<150/90 mmHg). We used Poisson regression to obtain prevalence ratios (PRs)., Results: Most older adults with diabetes met stringent (and less stringent) targets: 72% (90%) for HbA1c, 63% (86%) for LDL-c, and 73% (87%) for BP; but only 35% (68%) met all three. A higher proportion of whites than blacks met targets, however defined. Among people treated for risk factors, racial disparities in prevalence of meeting stringent targets persisted even after adjustment: PRs (whites vs. blacks) were 1.03 (95% CI 0.91, 1.17) for HbA1c, 1.21 (1.09, 1.35) for LDL-c, 1.10 (1.00, 1.21) for BP, and 1.28 (0.99, 1.66) for all three. Results were similar but slightly attenuated using less stringent goals. Black women were less likely than white women to meet targets for BP and all three risk factors; this disparity was not observed in men., Conclusions: Black-white disparities in risk factor control in older adults with diabetes were not fully explained by demographic or clinical characteristics and were greater in women than men. Further study of determinants of these disparities is important., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objectives: We assessed risk of cigarette smoking initiation among Hispanics/Latinos during adolescence by migration status and gender., Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) surveyed persons aged 18 to 74 years in 2008 to 2011. Our cohort analysis (n = 2801 US-born, 13 200 non-US-born) reconstructed participants' adolescence from 10 to 18 years of age. We assessed the association between migration status and length of US residence and risk of cigarette smoking initiation during adolescence, along with effects of gender and Hispanic/Latino background., Results: Among individuals who migrated by 18 years of age, median age and year of arrival were 13 years and 1980, respectively. Among women, but not men, risk of smoking initiation during adolescence was higher among the US-born (hazard ratio [HR] = 2.10; 95% confidence interval [CI] = 1.73, 2.57; P < .001), and those who had resided in the United States for 2 or more years (HR = 1.47; 95% CI = 1.11, 1.96; P = .01) than among persons who lived outside the United States., Conclusions: Research examining why some adolescents begin smoking after moving to the United States could inform targeted interventions.

Objectives: To determine whether changes in insulin-like growth factor (IGF) protein levels are greater in participants with type 2 diabetes mellitus or worsening glycemia than in normoglycemic individuals over a 9-year follow-up period., Design: Retrospective analysis of a cohort study., Setting: Participants were recruited from North Carolina, California, Maryland, and Pennsylvania., Participants: Cardiovascular Health Study All Stars participants, a cohort study of community-dwelling adults aged 65 and older (N=897)., Measurements: Plasma IGF-I, IGF binding protein (IGFBP)-1, and IGFBP-3 levels were assessed and American Diabetes Association cut-points for impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus were used to classify participants at baseline (1996-97) and follow-up (2005-06)., Results: At baseline, mean age was 76.3±3.6, and 18.5% had diabetes mellitus. Participants with IFG alone and IGT plus IFG had higher IGF-I levels and lower IGFBP-1 levels than those with normoglycemia or diabetes mellitus. The greatest percentage change in IGF levels occurred in those who had diabetes mellitus at baseline (9-year changes: -9.3% for IGF-I, 59.7% for IGFBP-1, -13.4% for IGFBP-3), the smallest in individuals who remained normoglycemic at follow-up (9-year changes: -3.7% for IGF-I, 25.6% for IGFBP-1, -6.4% for IGFBP-3), and intermediate in those who were normoglycemic but developed IFG at follow-up., Conclusion: Degrees of glycemic impairment are associated with varying degrees of change in IGF protein levels. The changes observed in the diabetes mellitus group have been previously shown to be associated with heart failure, cancer, and noncancer mortality., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Objective: Advanced glycation end products (AGEs) may cause inflammation by binding to their cellular receptors (RAGE). Soluble RAGE (sRAGE) acts as a decoy receptor for AGEs and may prevent inflammation. Chronic low-grade inflammation is a risk factor for cardiovascular disease, including atrial fibrillation (AF)., Methods: We studied 1,068 participants in a subsample of the Atherosclerosis Risk in Communities (ARIC) Study who had baseline measurements of sRAGE (mean age 56, 60% female, 21% Black). Inflammation was assessed using measurements of high sensitivity C-reactive protein (hsCRP), fibrinogen, gamma-glutamyl transferase (GGT) and white blood cell (WBC) count. AF events were identified using ECG data, hospitalization discharge codes, and linkage to the National Death Index., Results: Compared to the highest quartile (>1272.4 pg/mL), the lowest quartile of sRAGE (<714 pg/mL) was associated with higher baseline levels of inflammation (hsCRP ≥3 mg/L: OR=2.21 [95% CI 1.41-3.49], fibrinogen ≥400 mg/dL: OR=4.31 [95% CI 1.50-12.41], GGT ≥36 U/L in women and ≥61 U/L in men: OR=5.22 [95% CI 2.66-10.22], WBC >6.2×10⁹/L: OR=2.38 [95% CI 1.52-3.72]). sRAGE was not prospectively associated with 6-year change in inflammatory markers (hsCRP or GGT). There was no significant association of sRAGE and risk of AF (HR 1.49 [95% CI: 0.80-2.78] for the 1st vs. 4th quartile of sRAGE)., Conclusions: sRAGE was strongly inversely associated with markers of inflammation at baseline, but not prospectively. sRAGE was not significantly associated with incident AF. This supports a role for sRAGE in attenuating current inflammation, but it remains unclear whether sRAGE plays a role in the development of AF., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Adults infected with HIV have increased atherosclerosis potentially associated with both HIV and non-HIV associated factors. We characterized risk factors for atherosclerosis as measured by noninvasive vascular imaging., Methods and Results: We used B-mode ultrasound to examine levels and correlates of echogenicity and vessel wall thickness of the carotid artery intima-media complex in 1282 HIV-infected and 510 HIV-uninfected women of the Women's Interagency HIV Study. Levels of gray scale median (GSM, a measure of echogenicity) did not vary between HIV infection groups. In both groups, smokers had increased GSM, whereas age, diabetes, elevated blood pressure, and high BMI were associated with lower (rather than higher) GSM. Each of these non-lipid CVD risk factors, especially age and blood pressure, was also associated with higher levels of carotid artery intima-media thickness (cIMT). Higher serum triglyceride levels were associated with lower GSM in both HIV-infected and HIV-uninfected groups. Additional lipid risk factors for low GSM including high LDL cholesterol and low HDL cholesterol levels were identified in HIV uninfected but not in HIV infected women. In contrast to findings for GSM, among the lipid parameters only LDL cholesterol level had an association with cIMT, which was observed only in the HIV uninfected group., Conclusions: Lipid and non-lipid risk factor associations with echolucency of the carotid artery and the thickness of the common carotid artery intima-media layer suggest that these measures capture different aspects of atherosclerosis., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Purpose: To examine the association of psychosocial stress with obesity, adiposity, and dietary intake in a diverse sample of Hispanic/Latino adults., Methods: Participants were 5077 men and women, aged 18 to 74 years, from diverse Hispanic/Latino ethnic backgrounds. Linear regression models were used to assess the association of ongoing chronic stressors and recent perceived stress with measures of adiposity (waist circumference and percentage body fat) and dietary intake (total energy, saturated fat, alternative healthy eating index-2010). Multinomial logistic models were used to describe the odds of obesity or overweight relative to normal weight., Results: Greater number of chronic stressors and greater perceived stress were associated with higher total energy intake. Greater recent perceived stress was associated with lower diet quality as indicated by alternative healthy eating index-2010 scores. Compared with no stressors, reporting three or more chronic stressors was associated with higher odds of being obese (odds ratio = 1.5, 95% confidence interval [CI] 1.01-2.1), greater waist circumference (β = 3.3, 95% CI 1.0-5.5), and percentage body fat (β = 1.5, 95% CI 0.4-2.6)., Conclusions: The study found an association between stress and obesity and adiposity measures, suggesting that stress management techniques may be useful in obesity prevention and treatment programs that target Hispanic/Latino populations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: All major Hispanic/Latino groups in the United States have a high prevalence of obesity, which is often severe. Little is known about cardiovascular disease (CVD) risk factors among those at very high levels of body mass index (BMI)., Methods and Results: Among US Hispanic men (N=6547) and women (N=9797), we described gradients across the range of BMI and age in CVD risk factors including hypertension, serum lipids, diabetes, and C-reactive protein. Sex differences in CVD risk factor prevalences were determined at each level of BMI, after adjustment for age and other demographic and socioeconomic variables. Among those with class II or III obesity (BMI ≥35 kg/m(2), 18% women and 12% men), prevalences of hypertension, diabetes, low high-density lipoprotein cholesterol level, and high C-reactive protein level approached or exceeded 40% during the fourth decade of life. While women had a higher prevalence of class III obesity (BMI ≥40 kg/m(2)) than did men (7% and 4%, respectively), within this highest BMI category there was a >50% greater relative prevalence of diabetes, hypertension, and hyperlipidemia in men versus women, while sex differences in prevalence of these CVD risk factors were ≈20% or less at other BMI levels., Conclusions: Elevated BMI is common in Hispanic/Latino adults and is associated with a considerable excess of CVD risk factors. At the highest BMI levels, CVD risk factors often emerge in the earliest decades of adulthood and they affect men more often than women., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Trends in the prevalence and control of diabetes defined by hemoglobin A1c (HbA1c) levels are important for health care policy and planning., Objective: To update trends in the prevalence of diabetes, prediabetes, and glycemic control., Design: Cross-sectional., Setting: NHANES (National Health and Nutrition Examination Survey) in 1988-1994 and 1999-2010., Participants: Adults aged 20 years or older., Measurements: We used calibrated HbA1c levels to define undiagnosed diabetes (≥6.5%); prediabetes (5.7% to 6.4%); and, among persons with diagnosed diabetes, glycemic control (&lt;7.0% or &lt;8.0%). Trends in HbA1c categories were compared with fasting glucose levels (≥7.0 mmol/L [≥126 mg/dL] and 5.6 to 6.9 mmol/L [100 to 125 mg/dL])., Results: In 2010, approximately 21 million U.S. adults aged 20 years or older had total confirmed diabetes (self-reported diabetes or diagnostic levels for both fasting glucose and calibrated HbA1c). During 2 decades, the prevalence of total confirmed diabetes increased, but the prevalence of undiagnosed diabetes remained fairly stable, reducing the proportion of total diabetes cases that are undiagnosed to 11% in 2005-2010. The prevalence of prediabetes was lower when defined by calibrated HbA1c levels than when defined by fasting glucose levels but has increased from 5.8% in 1988-1994 to 12.4% in 2005-2010 when defined by HbA1c levels. Glycemic control improved overall, but total diabetes prevalence was greater and diabetes was less controlled among non-Hispanic blacks and Mexican Americans compared with non-Hispanic whites., Limitation: Cross-sectional design., Conclusion: Over the past 2 decades, the prevalence of total diabetes has increased substantially. However, the proportion of undiagnosed diabetes cases decreased, suggesting improvements in screening and diagnosis. Among the growing number of persons with diagnosed diabetes, glycemic control improved but remains a challenge, particularly among non-Hispanic blacks and Mexican Americans., Primary Funding Source: National Institutes of Health.

Fasting glucose and hemoglobin A1c (HbA1c) are the standard measures for diagnosis and monitoring of diabetes. There has been recent interest in nontraditional markers of hyperglycemia, including fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG), as alternatives or adjuncts to standard measures. There is a growing literature linking these nontraditional markers with microvascular and macrovascular complications. Fructosamine and glycated albumin have also been shown to improve identification of persons with diabetes. However, long-term prospective studies with clinical outcomes are lacking. Some modern laboratory assays for fructosamine, glycated albumin, and 1,5-AG have excellent performance. Expanded use of these tests has the potential to improve diabetes care as these measures may overcome limitations of HbA1c in certain patients, complement traditional measures by providing additional information on shorter-term glycemic control, and improve risk stratification for diabetes and its complications. Nonetheless, studies are needed to demonstrate if their routine use will benefit patients and improve outcomes.

Among 127 HIV-infected women, the magnitude of high-density lipoprotein cholesterol (HDLc) increases after HAART initiation predicted the magnitude of concurrent decreases in inflammation biomarkers. After HAART initiation, changes in low-density lipoprotein cholesterol (LDLc) and inflammation were unrelated. In the same population, predicted risk of coronary heart disease, based upon levels of standard clinical risk factors, was similar before and after HAART. Thus, it remains unknown whether short-term treatment-related changes in standard risk factors may appreciably change risk of cardiovascular disease (CVD).

Background: Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV., Methods: Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing., Results: In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 - 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (P(interaction) = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤ 45.3 years of age; β = 6.21, 95% CI:3.30 - 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV., Conclusions: CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.

Background: Noncompliance with medications may have major impacts on outcomes measured in research, potentially distorting the validity of controlled clinical trials. Riboflavin is frequently used in trials as a marker of adherence. It can be combined with study medication and is excreted in urine where it fluoresces under UV light. This study compares qualitative visual inspection of fluorescence to quantitative fluorometric analysis of riboflavin concentration in its ability to detect the presence of riboflavin in urine., Methods: Twenty-four volunteers received 0mg, 25mg, and 50mg doses of riboflavin under single-blind conditions, with 20 also receiving a 100mg dose. Five serial urine samples were collected over the following 36h. Quantitative measurement of riboflavin by fluorometric analysis and qualitative assessment of each sample using visual inspection were performed., Results: The overall false positive rate for qualitative assessment was 53%. For quantitative assessment, a riboflavin concentration of 900ng/mL was established to classify positive samples. More than 80% of samples were positive 2-24h following ingestion of 25mg and 50mg, and less than 80% were positive at 36h. At least 95% of observations for the 100mg dose were above 900ng/mL at all timepoints., Conclusions: Quantitative fluorometric assessment is superior to qualitative visual inspection alone in determining medication adherence. The combination of 25-50mg of daily riboflavin and a cut-off level of 900ng/mL allows for the acceptable sensitivity of missing detection of non-compliant participants while preserving a high level of power to detect all cases of medication compliance., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: We examined serum lipids in association with carotid artery intima-media thickness (CIMT) in HIV-infected and HIV-uninfected women., Methods: In 2003-4, among 1827 Women's Interagency HIV Study participants, we measured CIMT and lipids (high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), non-HDL-c). A subset of 520 treated HIV-infected women had pre-1997 lipid measures. We used multivariable linear regression to examine associations between lipids and CIMT., Results: In HIV-uninfected women, higher TC, LDL-c and non-HDL-c were associated with increased CIMT. Among HIV-infected women, associations of lipids with CIMT were observed in treated but not untreated women. Among the HIV-infected women treated in 2003-4, CIMT was associated both with lipids measured a decade earlier in infection, and with late lipid measurements., Conclusion: Among HIV-infected women, hyperlipidemia is most strongly associated with subclinical atherosclerosis in treated women. Among treated women, the association appeared strongest early in the disease course., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART)., Methods: In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound., Results: Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-α (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 μg/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-α levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness., Conclusions: Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-α), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.

Background: Cytomegalovirus (CMV) infection has been implicated in immune activation and accelerated progression of immunodeficiency from human immunodeficiency virus (HIV) coinfection. We hypothesized that CMV is associated with vascular disease in HIV-infected adults., Methods: In the Women's Interagency HIV Study, we studied 601 HIV-infected and 90 HIV-uninfected participants. We assessed the association of CMV immunoglobulin G (IgG) level with carotid artery intima-media thickness, carotid artery distensibility, Young's elastic modulus, and blood pressures. Multivariable models adjusted for age, race/ethnicity, smoking, diabetes, and body mass index., Results: Mean CMV IgG levels were higher in HIV-infected women compared with HIV-uninfected women (P < .01). Among HIV-infected women, higher CMV IgG level was associated with decreased carotid artery distensibility (P < .01) and increased Young's modulus (P = .02). Higher CMV IgG antibody level was associated with increased prevalence of carotid artery lesions among HIV-infected women who achieved HIV suppression on antiretroviral therapy, but not among viremic or untreated HIV-infected women. Adjustment for Epstein-Barr virus antibody levels and C-reactive protein levels had no effect on the associations between CMV IgG levels and vascular parameters., Conclusions: Cytomegalovirus antibody titers are increased in HIV-infected women and associated with subclinical cardiovascular disease. Host responses to CMV may be abnormal in HIV infection and associated with clinical disease.

Setting: Several non-US-based studies have found seasonal fluctuations in the incidence of tuberculosis (TB)., Objective: The current study examined patterns of TB seasonality for New York City verified TB cases from January 1990 to December 2007., Design: Autocorrelation functions and Fourier analysis were used to detect a cyclical pattern in monthly incidence rates. Analysis of variance was used to compare seasonal mean case proportions., Results: A cyclical pattern was detected every 12 months. Of the 34,004 TB cases included, 21.9% were in the fall (September-November), 24.7% in winter (December-February), 27.3% in spring (March-May), and 26.1% in the summer (June-August). The proportion of cases was lowest in fall (P < 0.0001) and highest in the spring (P < 0.0002)., Conclusion: Possible explanations for seasonal variations in TB incidence include lower vitamin D levels in winter, leading to immune suppression and subsequent reactivation of latent TB; indoor winter crowding, increasing the likelihood of TB transmission; and providers attributing TB symptoms to other respiratory illnesses in winter, resulting in a delay in TB diagnosis until spring. Understanding TB seasonality may help TB programs better plan and allocate resources for TB control activities.

Objectives: HIV disease is associated with increased arterial stiffness, which may be related to inflammation provoked by HIV-related immune perturbation. We assessed the association of T cell markers of immune activation and immunosenescence with carotid artery stiffness among HIV-infected women., Methods: Among 114 HIV-infected and 43 HIV-uninfected women, we measured CD4+ and CD8+ T cell populations expressing activation (CD38+HLA-DR+) and senescence (CD28-CD57+) markers. We then related these measures of immune status with parameters of carotid artery stiffness, including decreased distensibility, and increased Young's elastic modulus, as assessed by B-mode ultrasound., Results: HIV infection was associated with increased CD4+ T cell activation, CD8+ T cell activation and CD8+ T cell senescence. Among HIV-infected women, adjusted for age, HIV medications, and vascular risk factors, higher CD4+CD38+HLA-DR+ T cell frequency was associated with decreased carotid artery distensibility (β=-2.00, 95% confidence interval [CI]=-3.86, -0.14, P=0.04) and increased Young's modulus (β=1.00, 95% CI=0.03, 1.97, P=0.04). These associations were affected little by further adjustment for CD4+ T cell count and viral load. Among HIV-infected women, higher frequencies of immunosenescent T cells, including CD4+CD28-CD57+ and CD8+CD28-CD57+ T cells, were also associated with decreased arterial distensibility. Among HIV-uninfected women, frequencies of activated or senescent T cells were not significantly associated with measures of carotid stiffness., Discussion: T cell activation and senescence are associated with arterial stiffness, suggesting that pro-inflammatory populations of T cells may produce functional or structural vascular changes in HIV-infected women., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)