The Association Between High-Sensitivity Cardiac Troponin T and Major Adverse Cardiovascular Events in Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have a 1.5-times excess risk of cardiovascular (CV) disease compared to the general population, attributed to chronic inflammation.1,2 In the general population, detectable levels of high-sensitivity cardiac troponin (hs-cTn) are associated with higher risk of major adverse CV events (MACE) and all-cause mortality.3.

Personalizing cardiovascular risk prediction for patients with systemic lupus erythematosus.

OBJECTIVE: Cardiovascular disease (CVD) risk is increased in SLE and underestimated by general population prediction algorithms. We aimed to develop a novel SLE-specific prediction tool, SLECRISK, to provide a more accurate estimate of CVD risk in SLE. METHODS: We studied patients in the Brigham and Women's Hospital SLE cohort. We collected one-year baseline data including the presence of traditional CVD factors and SLE-related features at cohort enrollment. Ten-year follow-up for the first major adverse cardiovascular event (MACE; myocardial infarction (MI), stroke, or cardiac death) began at day +1 following the baseline period (index date). ICD-9/10 codes identified MACE were adjudicated by board-certified cardiologists. Least absolute shrinkage and selection operator regression selected SLE-related variables to add to the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equations 10-year risk Cox regression model. Model fit statistics and performance (sensitivity, specificity, positive/negative predictive value, c-statistic) for predicting moderate/high 10-year risk (≥7.5 %) of MACE were assessed and compared to ACC/AHA, Framingham risk score (FRS), and modified FRS (mFRS). Optimism adjustment internal validation was performed using bootstrapping. RESULTS: We included 1,243 patients with 90 MACEs (46 MIs, 36 strokes, 19 cardiac deaths) over 8946.5 person-years of follow-up. SLE variables selected for the new prediction algorithm (SLECRISK) were SLE activity (remission/mild vs. moderate/severe), disease duration (years), creatinine (mg/dL), anti-dsDNA, anti-RNP, lupus anticoagulant, anti-Ro positivity, and low C4. The sensitivity for detecting moderate/high-risk (≥7.5 %) of MACE using SLECRISK was 0.74 (95 %CI: 0.65, 0.83), which was better than the sensitivity of the ACC/AHA model (0.38 (95 %CI: 0.28, 0.48)). It also identified 3.4-fold more moderate/high-risk patients than the ACC/AHA. Patients who were moderate/high-risk according to SLECRISK but not ACC/AHA, were more likely to be young women with severe SLE and few other traditional CVD risk factors. Model performance between SLECRISK, FRS, and mFRS were similar. CONCLUSION: The novel SLECRISK tool is more sensitive than the ACC/AHA for predicting moderate/high 10-year risk for MACE and may be particularly useful in predicting risk for young females with severe SLE. Future external validation studies utilizing cohorts with more severe SLE are needed.

Coronary Microvascular Function Following Severe Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. METHODS: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging. RESULTS: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (ß, -0.67 [95% CI, -1.21 to -0.13]; P=0.016), lower stress myocardial blood flow (ß, -0.68 [95% CI, -1.07 to -0.29] mL/min per g; P=0.001), and higher stress coronary vascular resistance (ß, +12.4 [95% CI, 6.0 to 18.7] mm Hg/mL per min/g; P=0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow (r=0.71; P<0.001), independent of hemodynamics. CONCLUSIONS: In this exploratory cross-sectional study, we observed reduced coronary microvascular function in the early postpartum period following preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves coronary microcirculation. Further research is needed to establish interventions to mitigate the risk of preeclampsia-associated cardiovascular disease.

Colchicine for the Prevention of Cardiovascular Disease: Potential Global Implementation.

PURPOSE OF REVIEW: Targeting traditional cardiovascular risk factors is effective in reducing recurrent cardiovascular events, yet the presence of residual cardiovascular risk due to underlying systemic inflammation is a largely unaddressed opportunity. This review aims to comprehensively assess the evolving role of colchicine as a therapeutic approach targeting residual inflammatory risk in the context of those with coronary artery disease (CAD). RECENT FINDINGS: Inflammation plays a significant role in promoting atherosclerosis, and targeting anti-inflammatory pathways has the potential to decrease cardiovascular events. Low-dose colchicine (0.5 mg/day orally), when added to guideline-directed medical care for CAD, safely decreases major adverse cardiovascular events (MACE) by 31% in stable atherosclerosis patients and 23% in those after recent myocardial infarctions. Meta-analyses of recent randomized control trials further support both the efficacy and safety of colchicine, particularly when added to other standard cardiovascular therapies, including statin therapy. The European Society of Cardiology and other national guidelines endorse the use of low-dose colchicine in patients across the spectrum of CAD. Recently, colchicine was FDA-approved in the United States as the first anti-inflammatory therapy for the reduction of cardiovascular events. In a period of a rising incidence of CAD across the globe, colchicine represents a unique opportunity to decrease MACE due to its large magnitude of benefits and general affordability. However, challenges with drug interactions must be addressed, especially in those regions where HIV, hepatitis, and tuberculosis are prevalent. Colchicine is safe and effective at reducing cardiovascular events across a broad spectrum of coronary syndromes. The ability to simultaneously target traditional risk factors and mitigate residual inflammatory risk marks a substantial advancement in cardiovascular prevention strategies, heralding a new era in the global battle against CAD.

Prognostic value of myocardial flow reserve vs corrected myocardial flow reserve in patients without obstructive coronary artery disease.

BACKGROUND: Myocardial flow reserve (MFR) by positron emission tomography (PET) is a validated measure of cardiovascular risk. Elevated resting rate pressure product (RPP = heart rate x systolic blood pressure) can cause high resting myocardial blood flow (MBF), resulting in reduced MFR despite normal/near-normal peak stress MBF. When resting MBF is high, it is not known if RPP-corrected MFR (MFRcorrected) helps reclassify CV risk. We aimed to study this question in patients without obstructive coronary artery disease (CAD). METHODS: We retrospectively studied patients referred for rest/stress cardiac PET at our center from 2006 to 2020. Patients with abnormal perfusion (summed stress score >3) or prior coronary artery bypass grafting (CABG) were excluded. MFRcorrected was defined as stress MBF/corrected rest MBF where corrected rest MBF = rest MBF x 10,000/RPP. The primary outcome was major cardiovascular events (MACE): cardiovascular death or myocardial infarction. Associations of MFR and MFRcorrected with MACE were assessed using unadjusted and adjusted Cox regression. RESULTS: 3276 patients were followed for a median of 7 (IQR 3-12) years. 1685 patients (51%) had MFR <2.0, and of those 366 (22%) had an MFR ≥2.0 after RPP correction. MFR <2.0 was associated with an increased absolute risk of MACE (HR 2.24 [1.79-2.81], P < 0.0001). Among patients with MFR <2.0, the risk of MACE was not statistically different between patients with an MFRcorrected ≥2.0 compared with those with MFRcorrected <2.0 (1.9% vs 2.3% MACE/year, HR 0.84 [0.63-1.13], P = 0.26) even after adjustment for confounders (P = 0.66). CONCLUSIONS: In patients without overt obstructive CAD and MFR< 2.0, there was no significant difference in cardiovascular risk between patients with discordant (≥2.0) and concordant (<2) MFR following RPP correction. This suggests that RPP-corrected MFR may not consistently provide accurate risk stratification in patients with normal perfusion and MFR <2.0. Stress MBF and uncorrected MFR should be reported to more reliably convey cardiovascular risk beyond perfusion results.

Rheumatoid arthritis and cardiovascular complications during delivery: a United States inpatient analysis.

BACKGROUND AND AIMS: Persons with rheumatoid arthritis (RA) have an increased risk of obstetric-associated complications, as well as long-term cardiovascular (CV) risk. Hence, the aim was to evaluate the association of RA with acute CV complications during delivery admissions. METHODS: Data from the National Inpatient Sample (2004-2019) were queried utilizing ICD-9 or ICD-10 codes to identify delivery hospitalizations and a diagnosis of RA. RESULTS: A total of 12 789 722 delivery hospitalizations were identified, of which 0.1% were among persons with RA (n = 11 979). Individuals with RA, vs. those without, were older (median 31 vs. 28 years, P < .01) and had a higher prevalence of chronic hypertension, chronic diabetes, gestational diabetes mellitus, obesity, and dyslipidaemia (P < .01). After adjustment for age, race/ethnicity, comorbidities, insurance, and income, RA remained an independent risk factor for peripartum CV complications including preeclampsia [adjusted odds ratio (aOR) 1.37 (95% confidence interval 1.27-1.47)], peripartum cardiomyopathy [aOR 2.10 (1.11-3.99)], and arrhythmias [aOR 2.00 (1.68-2.38)] compared with no RA. Likewise, the risk of acute kidney injury and venous thromboembolism was higher with RA. An overall increasing trend of obesity, gestational diabetes mellitus, and acute CV complications was also observed among individuals with RA from 2004-2019. For resource utilization, length of stay and cost of hospitalization were higher for deliveries among persons with RA. CONCLUSIONS: Pregnant persons with RA had higher risk of preeclampsia, peripartum cardiomyopathy, arrhythmias, acute kidney injury, and venous thromboembolism during delivery hospitalizations. Furthermore, cardiometabolic risk factors among pregnant individuals with RA rose over this 15-year period.

Coronary Microvascular Function Following Severe Preeclampsia.

Background: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating pro- and anti-angiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. Methods: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography (PET) within 4 weeks of delivery. A control group of pre-menopausal, non-postpartum women was also included. Myocardial flow reserve (MFR), myocardial blood flow (MBF), and coronary vascular resistance (CVR) were compared across groups. Soluble fms-like tyrosine kinase receptor-1 (sFlt-1) and placental growth factor (PlGF) were measured at imaging. Results: The primary cohort included 19 women with severe preeclampsia (imaged at a mean 16.0 days postpartum), 5 with normotensive pregnancy (mean 14.4 days postpartum), and 13 non-postpartum female controls. Preeclampsia was associated with lower MFR (ß=-0.67 [95% CI -1.21 to -0.13]; P=0.016), lower stress MBF (ß=-0.68 [95% CI, -1.07 to -0.29] mL/min/g; P=0.001), and higher stress CVR (ß=+12.4 [95% CI 6.0 to 18.7] mmHg/mL/min/g; P=0.001) vs. non-postpartum controls. MFR and CVR after normotensive pregnancy were intermediate between preeclamptic and non-postpartum groups. Following preeclampsia, MFR was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest MBF (r=0.71; P<0.001), independent of hemodynamics. Conclusions: In this exploratory study, we observed reduced coronary microvascular function in the early postpartum period following severe preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves the coronary microcirculation. Further research is needed to establish interventions to mitigate risk of preeclampsia-associated cardiovascular disease.

Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease.

BACKGROUND: Lipoprotein(a) [Lp(a)] is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether the optimal Lp(a) threshold for risk assessment should differ based on baseline ASCVD status is unknown. OBJECTIVES: The purpose of this study was to assess the association between Lp(a) and major adverse cardiovascular events (MACE) among patients with and without baseline ASCVD. METHODS: We studied a retrospective cohort of patients with Lp(a) measured at 2 medical centers in Boston, Massachusetts, from 2000 to 2019. To assess the association of Lp(a) with incident MACE (nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or cardiovascular mortality), Lp(a) percentile groups were generated with the reference group set at the first to 50th Lp(a) percentiles. Cox proportional hazards modeling was used to assess the association of Lp(a) percentile group with MACE. RESULTS: Overall, 16,419 individuals were analyzed with a median follow-up of 11.9 years. Among the 10,181 (62%) patients with baseline ASCVD, individuals in the 71st to 90th percentile group had a 21% increased hazard of MACE (adjusted HR: 1.21; P < 0.001), which was similar to that of individuals in the 91st to 100th group (adjusted HR: 1.26; P < 0.001). Among the 6,238 individuals without established ASCVD, there was a continuously higher hazard of MACE with increasing Lp(a), and individuals in the 91st to 100th Lp(a) percentile group had the highest relative risk with an adjusted HR of 1.93 (P < 0.001). CONCLUSIONS: In a large, contemporary U.S. cohort, elevated Lp(a) is independently associated with long-term MACE among individuals with and without baseline ASCVD. Our results suggest that the threshold for risk assessment may be different in primary vs secondary prevention cohorts.

Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases: A Systematic Review and Meta-Analysis.

Importance: Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions. Objective: To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions. Data Sources: PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023. Study Selection: This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded. Data Extraction and Synthesis: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO. Main Outcomes and Measures: Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE. Results: The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04). Conclusions and Relevance: In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.

Novel Imaging Approaches to Cardiac Manifestations of Systemic Inflammatory Diseases: JACC Scientific Statement.

Derangements in the innate and adaptive immune responses observed in systemic inflammatory syndromes contributes to unique elevated atherosclerotic risk and incident cardiovascular disease. Novel multimodality imaging techniques may improve diagnostic precision for the screening and monitoring of disease activity. The integrated application of these technologies lead to earlier diagnosis and noninvasive monitoring of cardiac involvement in systemic inflammatory diseases that will aid in preclinical studies, enhance patient selection, and provide surrogate endpoints in clinical trials, thereby improving clinical outcomes. We review the common cardiovascular manifestations of immune-mediated systemic inflammatory diseases and address the clinical and investigational role of advanced multimodality cardiac imaging.

Feasibility of Simultaneous Quantification of Myocardial and Renal Perfusion With Cardiac Positron Emission Tomography.

BACKGROUND: Given the central importance of cardiorenal interactions, mechanistic tools for evaluating cardiorenal physiology are needed. In the heart and kidneys, shared pathways of neurohormonal activation, hypertension, and vascular and interstitial fibrosis implicate the relevance of systemic vascular health. The availability of a long axial field of view positron emission tomography (PET)/computed tomography (CT) system enables simultaneous evaluation of cardiac and renal blood flow. METHODS: This study evaluated the feasibility of quantification of renal blood flow using data acquired during routine, clinically indicated 13N-ammonia myocardial perfusion PET/CT. Dynamic PET image data were used to calculate renal blood flow. Reproducibility was assessed by the intraclass correlation coefficient among 3 independent readers. PET-derived renal blood flow was correlated with imaging and clinical parameters in the overall cohort and with histopathology in a small companion study of patients with a native kidney biopsy. RESULTS: Among 386 consecutive patients with myocardial perfusion PET/CT, 296 (76.7%) had evaluable images to quantify renal perfusion. PET quantification of renal blood flow was highly reproducible (intraclass correlation coefficient 0.98 [95% CI, 0.93-0.99]) and was correlated with the estimated glomerular filtration rate (r=0.64; P<0.001). Compared across vascular beds, resting renal blood flow was correlated with maximal stress myocardial blood flow and myocardial flow reserve (stress/rest myocardial blood flow), an integrated marker of endothelial health. In patients with kidney biopsy (n=12), resting PET renal blood flow was strongly negatively correlated with histological interstitial fibrosis (r=-0.85; P<0.001). CONCLUSIONS: Renal blood flow can be reliably measured from cardiac 13N-ammonia PET/CT and allows for simultaneous assessment of myocardial and renal perfusion, opening a potential novel avenue to interrogate the mechanisms of emerging therapies with overlapping cardiac and renal benefits.

Acute cardiovascular complications of immune-mediated systemic inflammatory diseases.

Immune-mediated systemic inflammatory conditions (IMIDs) are associated with an increased risk of atherosclerosis and adverse cardiovascular (CV) events secondary to pathogenic inflammation and derangements in the innate and adaptive immune responses inherent to the underlying rheumatic diseases. As the intersection of cardio-rheumatology continues to expand, a multi-disciplinary approach must be considered to optimize clinical outcomes and long-term survival. This review will highlight acute cardiac manifestations of systemic inflammatory diseases and propose a clinically relevant framework for diagnosis, management, and the role of integrated multimodality imaging.

Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease.

The association between chronic inflammation and increased risk of cardiovascular disease in rheumatoid arthritis (RA) is well established. In the general population, inflammation is an established independent risk factor for cardiovascular disease, and much interest is placed on controlling inflammation to reduce cardiovascular events. As inflammation encompasses numerous pathways, the development of targeted therapies in RA provides an opportunity to understand the downstream effect of inhibiting specific pathways on cardiovascular risk. Data from these studies can inform cardiovascular risk management in patients with RA, and in the general population. This Review focuses on pro-inflammatory pathways targeted by existing therapies in RA and with mechanistic data from the general population on cardiovascular risk. Specifically, the discussions include the IL-1, IL-6 and TNF pathways, as well as the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signalling pathway, and the role of these pathways in RA pathogenesis in the joint alongside the development of atherosclerotic cardiovascular disease. Overall, some robust data support inhibition of IL-1 and IL-6 in decreasing the risk of cardiovascular disease, with growing data supporting IL-6 inhibition in both patients with RA and the general population to reduce the risk of cardiovascular disease.

An inflammatory transcriptomic signature in psoriasis associates with future cardiovascular events.

BACKGROUND: Psoriasis is an inflammatory skin disease associated with increased cardiovascular (CV) risk, whose pathogenesis is not fully known. OBJECTIVE: We identified a transcriptomic signature in psoriasis and investigated its association with prevalent and future risk of a CV event to understand the connection between psoriasis and CV disease (CVD). METHODS: Psoriasis patients (n = 37) with a history of moderate-severe skin disease without CVD and 11 matched controls underwent whole blood RNA sequencing. This transcriptomic signature in psoriasis versus controls was evaluated in two CVD cohorts: Women referred for cardiac catheterization with (n = 76) versus without (n = 97) myocardial infarction (MI), and patients with peripheral artery disease (n = 106) followed over 2.5 years for major adverse CV or limb events (MACLE). The association between genes differentially expressed in psoriasis and prevalent and incident CV events was assed. RESULTS: In psoriasis, median age was 44 (IQR; 34-51) years, 49% male and ACC/AHA ASCVD Risk Score of 1.0% (0.6-3.4) with no significant difference versus controls. The median psoriasis area and severity index score (PASI) was 4.0 (IQR 2.9-8.2) with 36% on biologic therapy. Overall, 247 whole blood genes were upregulated and 228 downregulated in psoriasis versus controls (p < 0.05), and 1302 genes positively and 1244 genes negatively correlated with PASI (p < 0.05). Seventy-three genes overlapped between psoriasis prevalence and PASI with key regulators identified as IL-6, IL-1ß and interferon gamma. In the CVD cohorts, 50 of 73 genes (68%) identified in psoriasis associated with prevalent MI, and 29 (40%) with incident MACLE. Key regulator transcripts identified in psoriasis and CVD cohorts included SOCS3, BCL3, OSM, PIM2, PIM3 and STAT5A. CONCLUSIONS: A whole blood transcriptomic signature of psoriasis diagnosis and severity associated with prevalent MI and incident MACLE. These data have implications for better understanding the link between psoriasis, systemic inflammation and CVD.

Association Between Inflammation, Incident Heart Failure, and Heart Failure Subtypes in Patients With Rheumatoid Arthritis.

OBJECTIVE: In rheumatoid arthritis (RA), there are limited data on risk factors for the clinical heart failure (HF) subtypes of HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). This study examined the association between inflammation and incident HF subtypes in RA. Because inflammation changes over time with disease activity, we hypothesized that the effect of inflammation may be stronger at the 5-year follow-up than at the standard 10-year follow-up from general population studies of cardiovascular risk. METHODS: We studied an electronic health record (EHR)-based RA cohort with data pre- and post-RA incidence. We applied a validated approach to identify HF and extract ejection fraction to classify HFrEF and HFpEF. Follow-up started from the RA incidence date (index date) to the earliest occurrence of incident HF, death, last EHR encounter, or 10 years. Baseline inflammation was assessed using erythrocyte sedimentation rate or C-reactive protein values. Covariates included demographic characteristics, established HF risk factors, and RA-related factors. We tested the association between baseline inflammation with incident HF and its subtypes using Cox proportional hazards models. RESULTS: We studied 9,087 patients with RA; 8.2% developed HF during 10 years of follow-up. Elevated inflammation was associated with increased risk for HF at both 5- and 10-year follow-ups (hazard ratio [HR] 1.66, 95% confidence interval [95% CI] 1.12-2.46 and HR 1.46, 95% CI 1.13-1.90, respectively), which is also seen for HFpEF at 5 years (HR 1.72, 95% CI 1.09-2.70) and 10 years (HR 1.45, 95% CI 1.07-1.94). HFrEF was not associated with inflammation for either follow-up time. CONCLUSION: Elevated inflammation early in RA diagnosis was associated with HF; this association was driven by HFpEF and not HFrEF, suggesting a window of opportunity for prevention of HFpEF in RA.

Cardiovascular and Venous Thromboembolic Risk With Janus Kinase Inhibitors in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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; Pinteraction = 0.05). When compared with active comparators, JAK inhibitors increased VTE in clinical trials with 12 or more months' versus less than 12 months' follow-up time (OR 2.38 [95% CI: 1.24-4.57] vs 0.30 [95% CI: 0.07-1.26], respectively; Pinteraction = 0.01). No increased risk of VTE was seen when comparing JAK inhibitors with placebo arms. For the outcome of MACE, the results were largely similar but did not reach statistical significance (OR 1.19; 95% CI: 0.86-1.64). CONCLUSION: JAK 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.

Apparent Risks of Postural Orthostatic Tachycardia Syndrome Diagnoses After COVID-19 Vaccination and SARS-Cov-2 Infection.

Postural orthostatic tachycardia syndrome (POTS) has been previously described after SARS-CoV-2 infection; however, limited data is available on the relation of POTS with COVID-19 vaccination. Here we show in a cohort of 284,592 COVID-19 vaccinated individuals using a sequence-symmetry analysis, that the odds of POTS are higher 90 days after vaccine exposure than 90 days prior to exposure, and that the odds for POTS are higher than referent conventional primary care diagnoses, but lower than the odds of new POTS diagnosis after SARS-CoV-2 infection. Our results identify a possible association between COVID-19 vaccination and incidence of POTS. Notwithstanding the probable low incidence of POTS after COVID-19 vaccination, particularly when compared to SARS-Cov-2 post-infection odds which were five times higher, our results suggest that further studies, are needed to investigate the incidence and etiology of POTS occurring after COVID-19 vaccination.