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Background: Individuals with rheumatoid arthritis (RA) have an increased risk of obstetric-associated complications as well as long term cardiovascular (CV) risk. However data on acute CV complications during pregnancy delivery remains limited. Methods: We used data from the National Inpatient Sample (2004-2019) utilizing ICD-9 or ICD-10 codes to identify delivery hospitalizations and a diagnosis of RA. Results: A total of 63,005,648 weighted delivery hospitalizations were identified, of which 0.1% were among persons with RA (n=62,402). Individuals with RA, vs those without, were older (median 31 vs. 28 years, p Conclusions: Pregnant individuals with RA had higher risk of preeclampsia, peripartum cardiomyopathy, arrhythmias, AKI, stroke and VTE during delivery hospitalizations. Furthermore, cardiometabolic risk factors among pregnant individuals with RA rose over this 15 year period.

Janus kinase (JAK) inhibition effectively treats immune-mediated inflammatory diseases (IMIDs); however, concern over the risk of major adverse cardiac events (MACE) and venous thromboembolism (VTE) remains. We aimed to evaluate the safety (VTE and MACE outcomes) of JAK inhibitors in the treatment of IMIDs.A search in PubMed, Embase, and ClinicalTrials.gov databases was conducted for randomized clinical trials (RCTs) of JAK inhibitors across IMIDs. Primary outcomes were VTE and MACE with JAK inhibitors compared with placebo and active comparator arms stratified by follow-up time.Sixty-six RCTs enrolled 38,574 patients with a mean age of 48.8 years and a mean follow-up of 10.5 months. JAK inhibitors had a numerically higher rate of VTE when compared with controls (odds ratio [OR] 1.65; 95% confidence interval [CI]: 0.97-2.79), driven by trials with a follow-up duration of 12 or more months (OR 2.17; 95% CI: 1.16-4.05; PJAK inhibitors when compared with active comparator arms increased the risk of VTE, which was dependent on duration of exposure. Future clinical trials with extended follow-up are needed to clarify the safety profiles of JAK inhibitors.

Background: Retinal microvascular evaluation could serve as a marker for cardiovascular disease risk. OCTA is a noninvasive method to quantitatively assess the retinal microvasculature. Coronary flow reserve (CFR), an integrated measure of focal, diffuse, and small-vessel coronary artery disease, identifies patients at risk for cardiac death. We aimed to identify associations between OCTA findings and CFR in patients undergoing cardiac positron emission tomography (PET) testing. Methods: Subjects (n=60) underwent a stress myocardial perfusion PET scan to quantify CFR and OCTA of both eyes on same day. CFR is the ratio of myocardial blood flow at peak stress compared to rest and adjusted for baseline cardiac work. OCTA scans were analyzed using a custom-built software to quantify foveal avascular zone (FAZ) geometry and vessel density metrics in the retina, reflecting retinal microvasculature. We used Spearman to correlate markers of retinal microvasculature with CFR. Results: Demographics of enrolled subjects are shown in Table I. Baseline cardiac risk factors were common and 22 (37%) subjects had an abnormal stress test. Retinal perfusion as indicated by the vessel index (ρ=0.35, p=0.006) and vessel diameter index (ρ=0.27, p=0.039) in the superficial 6x6 mm slabs were positively correlated with CFR. There was a trend towards negative association between FAZ area in the retina slab and CFR (ρ= -0.17, p=0.1). Conclusions: CFR was correlated with retinal perfusion indices based on OCTA, suggesting a relationship between coronary and retinal vascular health. These data provide potential insight into systemic vascular health and could provide an additional tool to assess cardiac risk.

SUMMARY CD4+ T cells regulate inflammation and metabolism in obesity. An imbalance of CD4+ T regulatory cells (Tregs) is critical in the development of insulin resistance and diabetes. Although cytokine control of this process is well understood, transcriptional regulation is not. KLF10, a member of the Kruppel-like transcription factor family, is an emerging regulator of immune cell function. We generated CD4+-T-cell-specific KLF10 knockout (TKO) mice and identified a predisposition to obesity, insulin resistance, and fatty liver due to defects of CD4+ Treg mobilization to liver and adipose tissue depots and decreased transforming growth factor β3 (TGF-β3) release in vitro and in vivo. Adoptive transfer of wild-type CD4+ Tregs fully rescued obesity, insulin resistance, and fatty liver. Mechanistically, TKO Tregs exhibit reduced mitochondrial respiration and glycolysis, phosphatidylinositol 3-kinase (PI3K)-Akt-mTOR signaling, and consequently impaired chemotactic properties. Collectively, our study identifies CD4+ T cell KLF10 as an essential regulator of obesity and insulin resistance by altering Treg metabolism and mobilization., Graphical Abstract, In Brief Immune cell accumulation in adipose tissues and liver contributes to the development of insulin resistance and obesity. Wara et al. demonstrate that the transcription factor KLF10 is a critical regulator of CD4+ T regulatory cell accumulation in liver and adipose depots, leading to obesity, insulin resistance, and fatty liver.