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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. [ABSTRACT FROM AUTHOR]

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).

ObjectiveWe examined serum lipids in association with carotid artery intima-media thickness (CIMT) in HIV-infected and HIV-uninfected women.MethodsIn 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.ResultsIn 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.ConclusionAmong 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.

BackgroundInflammation 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).MethodsIn 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.ResultsRelative 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.ConclusionsUntreated 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.

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. [ABSTRACT FROM AUTHOR]