Effect of Hormone Replacement Therapy on Liver and Cardiometabolic Outcomes in Peri-Menopausal MASLD.

Coffee and Tea Consumption Are Associated With a Lower Incidence of Chronic Liver Disease in the United States

Hormone replacement therapy and cardiovascular disease: does route of administration and formulation matter?

Introduction & Objectives Long-term incidence rates of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancy (excluding nonmelanoma skin cancer [exNMSC]) according to baseline oral contraceptive pill (OCP) and hormone replacement therapy (HRT) use were assessed among patients with moderate-to-severe Atopic Dermatitis (AD) with up to 6 years of upadacitinib (UPA) treatment. Materials & Methods This analysis evaluated pooled data from the randomized, double-blind, multicenter, placebo-controlled, phase 3 Measure Up 1/2 (NCT03569293/NCT03607422) and AD Up (NCT03568318) studies. Patients with moderate-to-severe AD (aged 12–75 years) were randomized 1:1:1 to receive once-daily oral UPA 15 mg, UPA 30 mg, or placebo as monotherapy (Measure Up 1/2) or with concomitant topical corticosteroids (AD Up) for 16 weeks. At week 16, patients receiving placebo were rerandomized 1:1 to UPA 15 mg or 30 mg, while patients initially randomized to UPA continued their assigned treatment. Incidence of MACE, VTE, and malignancy (exNMSC) was reported as exposure-adjusted incidence rates per 100 patient-years (n/100PY). For context, background rates of MACE, VTE, and malignancy (exNMSC) in the general US AD population were assessed in a retrospective observational claims-based analysis from Optum’s deidentified Clinformatics Data Mart database; this analysis included females who had a diagnosis of AD during the study period (March 2017–September 2024) determined by International Classification of Diseases 9th or 10th edition codes (≥ 1 inpatient or ≥ 2 outpatient claims for AD). Age restrictions from the UPA phase 3 studies (12–75 years) were implemented for the real-world reference population and background rates were weighted to mimic the age and sex distribution in the combined UPA trial population. Safety cohorts were stratified by OCP use (yes vs no) among females aged 15–55 years or HRT use (yes vs no) among females aged > 55 years. Results A total of 1178 females in the UPA phase 3 studies were evaluated (UPA 15 mg, n = 593; UPA 30 mg, n = 585). Long-term incidence rates were low for MACE and VTE (all < 0.1 n/100PY) and malignancy (exNMSC; all ≤ 0.4 n/100PY) among UPA-treated females in the OCP and non-OCP groups. There were no MACE or VTE events in patients using OCP or HRT and no malignancy (exNMSC) events in the HRT group; however, HRT results are limited by a small sample size (n = 5). While upadacitinib-treated patients using OCPs had no events of MACE or VTE, incidence rates for malignancy (excluding NMSC) from upadacitinib phase 3 studies were consistent with real-world incidence rates in patients with AD in the United States (n = 5137). Conclusions In females with moderate-to-severe AD who received up to 6 years of UPA treatment, long-term incidence rates of MACE, VTE, and malignancy (exNMSC) were low, regardless of OCP use, and similar to those in the real-world population of patients with AD.

The recent availability of cardiovascular risk-reducing type 2 diabetes (T2D) therapies makes it imperative to optimally identify individuals who could derive benefit. Current clinical risk prediction may misclassify individuals as low risk and could be improved. Our aim was to determine the incremental prognostic value of a coronary heart disease (CHD) genome-wide polygenic risk score (PRS) to a clinical risk score in prediction of major adverse cardiovascular events (MACE) in patients with T2D. We evaluated 10,556 individuals with T2D aged 40-79 without a prior cardiovascular hospitalization. We calculated 10-year clinical cardiovascular risk at the date of recruitment using the Pooled Cohort Equation (PCE Risk) and constructed a CHD PRS. The primary outcome was time to first MACE incidence, and we assessed the additional incremental predictive value of the CHD PRS to the PCE risk. At 10 years, there were 1,477 MACE. After adjustment for clinical risk, the CHD PRS was significantly associated with MACE (hazard ratio [HR] 1.69 per SD increase, 95% CI 1.60-1.79). Individuals with PCE Risk <7.5% but in the top quintile of CHD PRS had a significantly increased likelihood of MACE (HR 10.69, 95% CI 5.07-22.55) compared with those in the lowest. The addition of the PRS to the clinical risk score led to significant improvements in risk prediction, particularly in those at low clinical risk. The addition of a CHD PRS to clinical assessment improved MACE prediction in T2D individuals without prior cardiovascular disease, particularly in those at low clinical risk.

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Direct oral anticoagulants (DOACs; namely, rivaroxaban and apixaban) and warfarin are approved for venous thromboembolism (VTE) treatment. Few direct comparisons exist of DOACs on risk of death among patients with VTE, and for patients with concomitant conditions (eg, kidney disease, liver disease), clinical guidelines are unclear. We evaluated 6-month all-cause mortality by anticoagulant prescribed for primary treatment of VTE. Using data from a 20% sample of Medicare beneficiaries, we created a propensity score-matched analytic data set of 47 860 beneficiaries with noncancer incident VTE. We used Cox regression to estimate adjusted hazard ratios (HRs) of OACs with 6-month mortality, and tested interactions by liver and kidney disease. There were 3422 deaths over 6months of follow-up. In adjusted models, patients prescribed rivaroxaban (HR = 0.82; 95% CI, 0.76-0.90) had lower mortality rates than those prescribed warfarin. There was no association when comparing apixaban with warfarin (HR = 0.96; 95% CI, 0.87-1.07). In head-to-head comparisons of apixaban and rivaroxaban, the HR was 1.14 (95% CI, 1.01-1.28). Findings were similar among patients with liver and kidney disease. Overall, risk of death was similar by OAC prescribed. Though it is possible residual confounding remained, there was some suggestion of lower risk with rivaroxaban than warfarin. Treatment with DOACs appears safe among patients with VTE who have concomitant kidney or liver disease. This article is part of a Special Collection on Pharmacoepidemiology.

Physical activity is associated with reduced risk of liver disease in the prospective UK Biobank cohort

BackgroundORAL Surveillance was a post-authorisation safety study of tofacitinib vs TNF inhibitors (TNFi) in rheumatoid arthritis (RA) patients (pts) aged ≥50 yrs with ≥1 additional cardiovascular (CV) risk factor and...

Effect of Human Immunodeficiency Virus and Antiretrovirals on Outcomes of Hepatitis C: A Systematic Review From an Epidemiologic Perspective

Investigation and management of heritable thrombophilia.

In 1993, individuals with a hereditary predisposition to venous thromboembolism whose plasmas exhibited a poor response to activated protein C (APC) in an activated partial thromboplastin time assay were identified.1 The molecular basis for this laboratory phenotype of resistance to APC was a guanine to adenine mutation at nucleotide 1691 in the factor V gene.2 This results in the replacement of arginine (R) at position 506 by glutamine in the resulting protein, a defect which has been termed factor V Leiden. R506 is the first of three sites at which APC normally cleaves and inactivates procoagulant factor Va. The Q506 substitution causes factor Va to be inactivated approximately l0-fold more slowly than normal, thereby making the cofactor relatively resistant to the anticoagulant action of APC.3 This allows for increased factor Va availability within the prothrombinase complex, thereby enhancing thrombin generation and the development of a hypercoagulable state. See page 1012 Factor V Leiden is the most common inherited risk factor for venous thromboembolism, increasing the risk of venous thrombosis by 4- to 10-fold in heterozygotes and 50- to 100-fold in homozygotes.4,5⇓ Heterozygosity can be identified in 12% to 20% of unselected white patients presenting with venous thrombosis and 40% to 50% of patients with a strong positive family history. Approximately 3% to 7% of normal white patients are heterozygous carriers of factor V Leiden, but the mutation is rare in …

Established and new-generation antithrombotic drugs in patients with cirrhosis – Possibilities and caveats

BackgroundCurrent guidelines recommend life-long use of statin for patients with type 2 diabetes (T2D), however, a number of patients discontinue statin therapy in clinical practice. We aimed to estimate the optimal statin therapy including statin therapy duration, statin intensity, and low-density lipoprotein cholesterol (LDL-C) level among patients with T2D in a real-world setting.MethodsFrom Korean National Health Insurance Service Cohort (2007–2015), 8937 patients with T2D (≥ 40 years of age) who received statin therapy for at least 90 days were included. Risk of major adverse cardiovascular event (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death was estimated according to statin intensity, achieved serum LDL-C level, and statin therapy duration, respectively. The relative contributions of these factors to MACE risk were quantified by calculating the proportion of log-likelihood explained by each factor.ResultsThe hazard ratio (HR) of MACE was lower in patients receiving moderate- or high-intensity statins than in those receiving low-intensity statins (HR, 0.72; p = 0.027). Among patients who received moderate- or high-intensity statins, lower achieved LDL-C level was associated with lower cardiovascular risk. Notably, the longer the patients received statins, the lower was the risk of MACE; the HR of MACE was significantly reduced after at least 18 months (adjusted HR, 0.70; p = 0.009) as a reference to 3–6 months of therapy. The proportion of explainable log-likelihood for MACE was greatest for statin duration (2.55), followed by achieved LDL-C level (2.18), and statin intensity (0.95).ConclusionsStatin therapy duration is as important as or more crucial than statin intensity or achieved LDL-C level for the reduction of cardiovascular risk in T2D patients. The concept of “longer is better” regarding statin therapy should be considered in clinical practice.

Introduction: Truncated variants in the genes ApoB and PSCK9 have been shown to be associated with low levels of low-density lipoprotein cholesterol (LDL-C), however, there is concern about the increased risk of liver disease. Using Intermountain Health’s HerediGene Population Study, a population-based genetic study, we sought to understand the impact of these variants on major adverse cardiovascular events (MACE) and liver disease. Methods: Of the 32,159 sequenced patients (pts), 58 (0.18%) had a truncating variant in ApoB (n=49) and PCSK9 (n=10). Among those with a truncating variant, we compared the demographics, LDL-C levels, statin use, and disease by MACE (including, myocardial infarction [MI], heart failure (HF) hospitalization, stroke, peripheral artery disease, and carotid artery disease). Results: MACE occurred in 32% of pts, with HF hospitalization followed by MI being the most frequent. The rates of MACE were similar for pts with ApoB (n=15, 30.6%) and PCSK9 (n= 4, 40%). Differences in demographics and clinical characteristics stratified by MACE are shown in the Table. LDL-C levels were low in both groups, with approximately half having an LDL-C &lt;70 mg/dL. Hypertension was more common in the MACE group (95% vs 50%). Both groups had high rates of liver disease (47%) compared to the general patient population (9%). Renal failure was also common among these pts (36%). Only 2 of the deaths (both in the MACE group) were cardiovascular-related, 1 due to stroke and 1 due to heart failure. Conclusion: Low LDL-C was associated with truncated variants in the ApoB and PSCK9 genes. However, these patients still had a high rate of MACE, which was driven mainly by hypertensive diseases. Frequency of liver disease and renal failure was high, which may also be attributed to hypertension. While this is a small sample, these findings suggest that continued screening for cardiovascular disease is needed despite low LDL-C, with liver disease screening also needing to be performed.

Celiac Disease and Risk of Liver Disease: A General Population-Based Study