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Background: Very low levels of cardiac troponin T are associated with an increased risk of cardiovascular death in patients with stable chronic coronary disease. Whether high-sensitivity cardiac troponin T levels are associated with adverse cardiovascular outcomes in individuals without cardiovascular disease (CVD) has not been well studied.Methods and Results: Using 2 complementary study designs, we evaluated the relationship between baseline cardiac troponin and incident CVD events among diabetic and nondiabetic participants in the Women's Health Study (median follow-up, 12.3 years). All diabetic women with blood specimens were included in a cohort study (n=512 diabetic women, n=65 events), and nondiabetic women were sampled for inclusion in a case-cohort analysis (n=564 comprising the subcohort, n=479 events). High-sensitivity cardiac troponin T was detectable (≥ 0.003 μg/L) in 45.5% of diabetic women and 30.3% of nondiabetic women (P<0.0001). In models adjusted for traditional risk factors and hemoglobin A(1c), detectable high-sensitivity cardiac troponin T was associated with subsequent CVD (myocardial infarction, stroke, cardiovascular death) in diabetic women (adjusted hazard ratio, 1.79; 95% confidence interval, 1.04 to 3.07, P=0.036) but not nondiabetic women (adjusted hazard ratio, 1.13; 95% confidence interval, 0.82 to 1.55; P=0.46). Further adjustment for amino-terminal pro-B-type natriuretic peptide and estimated renal function did not substantially alter this relationship among diabetic women (hazard ratio, 1.76; 95% confidence interval, 1.00 to 3.08; P=0.0499), which appeared to be driven by a 3-fold increase in CVD death that was not observed in nondiabetic women.Conclusions: Very low but detectable levels of cardiac troponin T are associated with total CVD and CVD death in women with diabetes mellitus. Among healthy nondiabetic women, detectable compared with undetectable troponin was not associated with CVD events. [ABSTRACT FROM AUTHOR]

Background: Smoking has a well-documented detrimental effect on risk for myocardial infarction and stroke, but less information is available regarding peripheral artery disease (PAD), particularly among women.Objective: To prospectively assess the association of current smoking status, cumulative smoking exposure, and smoking cessation with incident symptomatic PAD in women.Design: Prospective cohort study.Setting: U.S. female health care professionals in the Women's Health Study.Participants: 39,825 women with no cardiovascular disease who were prospectively followed for a median of 12.7 years.Measurements: Incidence of symptomatic PAD. Cox proportional hazards models were used to compare PAD risk across smoking categories.Results: 178 confirmed PAD events occurred. Across the 4 smoking categories (never, former, <15 cigarettes/d, and ≥15 cigarettes/d), age-adjusted incidence rates were 0.12, 0.34, 0.95, and 1.63 per 1000 person-years of follow-up, respectively. Multivariate adjustment had little effect on this relationship (adjusted hazard ratios [HRs], 3.14 [95% CI, 2.01 to 4.90], 8.93 [CI, 5.02 to 15.89], and 16.95 [CI, 10.77 to 26.67], respectively, vs. women who never smoked). Additional adjustment for high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 levels among women with available blood samples (28,314 participants, 117 events) attenuated risk estimates (HR, 5.58 [CI, 2.61 to 11.93] for smoking <15 cigarettes/d and 9.52 [CI, 5.17 to 17.53] for smoking ≥15 cigarettes/d). Lifetime exposure showed a strong dose-response relationship; fully adjusted HRs for smoking abstinence of fewer than 10, 10 to 29, and 30 or more pack-years were 2.52 (CI, 1.49 to 4.25), 6.75 (CI, 4.33 to 10.52), and 11.09 (CI, 6.94 to 17.72), respectively. Compared with current smokers, the adjusted HRs for fewer than 10 years, 10 to 20 years, more than 20 years, or lifelong abstinence were 0.39 (CI, 0.24 to 0.66), 0.28 (CI, 0.17 to 0.46), 0.16 (CI, 0.10 to 0.26), and 0.08 (CI, 0.05 to 0.12), respectively.Limitation: The use of symptomatic PAD as the a priori primary end point excludes asymptomatic disease.Conclusion: Among initially healthy women, smoking is a potent risk factor for symptomatic PAD and was associated with subclinical inflammation. Smoking cessation substantially reduces risk for PAD, but an increased occurrence of PAD persists even among former smokers who maintain abstinence.Primary Funding Source: The National Heart, Lung, and Blood Institute and National Cancer Institute. [ABSTRACT FROM AUTHOR]

Context: As diabetes is in part an inflammatory condition, the initiation of insulin and/or metformin may beneficially reduce levels of inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP).Objective: To determine whether insulin alone or combined with metformin lowers levels of hsCRP, IL-6, and soluble tumor necrosis factor receptor 2 (sTNFr2) in patients with recent-onset type 2 diabetes mellitus.Design, Setting, and Participants: Randomized 2 x 2 factorial trial of open-label insulin glargine and placebo-controlled metformin in 500 adults with type 2 diabetes (median time from diagnosis, 2.0 years), suboptimal glycemic control, and elevated hsCRP levels. Patients were recruited from US office-based practices between October 2006 and December 2008.Intervention: Random allocation to 1 of 4 treatments (placebo metformin only, placebo metformin and insulin glargine, active metformin only, or active metformin and insulin glargine) with dose titration targeting fasting blood glucose less than 110 mg/dL.Main Outcome Measures: Change in hsCRP level (primary end point) and change in IL-6 and sTNFr2 levels (secondary end points) from baseline to 14 weeks.Results: Levels of glucose and glycated hemoglobin (HbA(1c)) were significantly reduced with active treatment vs placebo (all P values <.001). Levels of hsCRP were reduced in all 4 groups. There was no significant difference in hsCRP reduction among those allocated to insulin (-11.8%; 95% CI, -18.7% to -4.4%) or to no insulin (-17.5%; 95% CI, -23.9% to -10.5%) (P for difference = .25), or among those allocated to active metformin (-18.1%; 95% CI, -24.4% to -11.1%) or placebo metformin (-11.2%; 95% CI, -18.1% to -3.7%) (P for difference = .17). In the individual treatment groups, despite a differential impact on glucose control, reductions in hsCRP in the metformin (-16.1%; 95% CI, -25.1% to -6.1%) and metformin plus insulin (-20.1%; 95% CI, -28.8% to -10.4%) groups were no different than reductions with placebo alone (-19.0%; 95% CI, -27.8% to -9.1%; P = .67 and .87 vs placebo, respectively). By contrast, hsCRP reduction was attenuated with insulin alone (-2.9%, 95% CI, -13.2% to 8.6%; P = .03 vs placebo). Similar findings were noted for levels of IL-6 and sTNFr2.Conclusion: In patients with recent-onset type 2 diabetes, treatment with insulin or metformin compared with placebo did not reduce inflammatory biomarker levels despite improving glucose control.Trial Registration: clinicaltrials.gov Identifier: NCT00366301. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Val-MARC trial showed that the angiotensin receptor blocker valsartan reduces high-sensitivity C reactive protein (hsCRP) levels, an effect that is independent of blood pressure, and seems to be neutralised by the addition of hydrochlorothiazide. OBJECTIVE: To evaluate whether valsartan influences soluble intercellular adhesion molecule 1 (sICAM-1) or vascular cell adhesion molecule 1 (sVCAM-1). DESIGN: Post-hoc analysis from a randomised trial. SETTING: Val-MARC trial. PATIENTS: 1188 patients with stage 2 hypertension. INTERVENTION: Random allocation to either valsartan 320 mg (n = 607) or combination therapy with valsartan/hydrochlorothiazide 320 mg/12.5 mg (n = 581) for 6 weeks. MAIN OUTCOME MEASURE: Change in sICAM-1 and sVCAM-1 from baseline to 6 weeks of follow-up RESULTS: After treatment, median (interquartile range) sICAM-1 levels were reduced by both valsartan alone (-4 (-25 to 16) ng/ml, p = 0.005) and valsartan/hydrochlorothiazide (-4 (-22 to 17) ng/ml, p = 0.028), such that the between-group difference was not significant (p = 0.7). The median percentage change from baseline was small in both groups (-1.6% and -1.3%). Median (interquartile range) sVCAM-1 levels were reduced by both valsartan alone (-13 (-70 to 42) ng/ml, p = 0.001) and valsartan/hydrochlorothiazide (-26 (-88 to 38), p<0.001); the between-group difference was of borderline significance (p = 0.051). The median percentage change from baseline was small (-2.1% and -4.4%). The reduction of sICAM-1 and sVCAM-1 was independent of blood pressure reduction (rs = 0.03 and rs = 0.06 for the relationship of change in systolic blood pressure with change in sICAM-1 and sVCAM-1, respectively). CONCLUSION: In contrast to hsCRP, both valsartan and valsartan/hydrochlorothiazide induced reductions of sICAM-1 and sVCAM-1 in the Val-MARC trial. These effects, although statistically significant, were small and independent of changes in blood pressure. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Dr. Choi has consulted for Celltrion, Werfen, Organon, MitogenDx, AstraZeneca, and Mallinckrodt Canada Inc. Dr. Everett has grants from Novo Nordisk and has consulted for Ipsen Pharmaceuticals, Eli Lilly and Company, Janssen, Novo Nordisk, and Roche Diagnostics. Dr. Costenbader has consulted for or collaborated on research projects with Glaxo Smith Kline, Gilead, CabalettaBio, Exagen Diagnostics, Eli Lilly, Merck, Astra Zeneca and Neutrolis (less than $10,000 each). Dr. Weber has consulted for Bristol-Myers Squibb(BMS), Horizon Therapeutics, Kiniksa, and Novo Nordisk., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Funding Support and Author Disclosures Dr Marinho is supported by the Lemann Foundation Cardiovascular Research Fellowship. Dr Everett has received grants from PCORI and Novo Nordisk; has received royalties from UpToDate; and has been a consultant for Circulation/American Heart Association, Eli Lilly and Company, U.S. Food and Drug Administration, Novo Nordisk, Gilead Pharmaceuticals, Ipsen Biosciences Inc, Johnson & Johnson, Provention Bio, and Roche Diagnostics. Dr Aday has received compensation for consultant services from Aeglea. Ms MacFadyen has received salary support from a research grant to BWH from Kowa Research Institute. Dr Santos has received honoraria related to consulting and/or speaker activities from Aché, Abbott, Amryt, Amgen, Biolab, EMS, Eli Lilly, Getz Pharma, Pfizer, PTC Therapeutics, Novartis, Novo Nordisk, and Sanofi/Regeneron; and has received research grants from Amgen, Esperion, Kowa, Novartis, and Sanofi/Regeneron. Dr Libby is an unpaid consultant to or involved in clinical trials for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa, Medimmune, Merck, Moderna, Novo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; and is a member of the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, PlaqueTec, TenSixteen Bio, Soley Therapeutics, and XBiotech, Inc. Dr Libby’s laboratory has received research funding in the last 2 years from Novartis, Novo Nordisk, and Genentech; is on the Board of Directors of XBiotech, Inc; and has a financial interest in Xbiotech (a company developing therapeutic human antibodies), in TenSixteen Bio (a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential to discover and develop novel therapeutics to treat age-related diseases), and in Soley Therapeutics (a biotechnology company that is combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics). Dr Fruchart is a consultant to Kowa. Dr Ridker has received institutional research grant support from Kowa Research Institute, Novartis, Amarin, Pfizer, Esperion, Novo Nordisk, and the National Heart, Lung, and Blood Institute; has served as a consultant to Novartis, Flame, Agepha, Ardelyx, AstraZeneca, Janssen, CiVi Biopharma, GlaxoSmithKline, SOCAR, Novo Nordisk, Health Outlook, Montai Health, Eli Lilly, New Amsterdam, Boehringer Ingelheim, RTI, Zomagen, Cytokinetics, Horizon Therapeutics, and Cardiol Therapeutics; has minority shareholder equity positions in Uppton, Bitterroot Bio, and ANGIOWave; and receives compensation for service on the Peter Munk Advisory Board (University of Toronto), the Leducq Foundation, Paris FR, and the Baim Institute. Dr Pradhan has received research grants from Kowa Research Europe and Denka, LTD; has received compensation for consultant services from Optum, Novo Nordisk, and Reliant Medical Foundation; receives compensation for lectures from Medtelligence and NACE; and is currently employed by Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Aims/hypothesis: Limited evidence exists on the comparative safety and effectiveness of empagliflozin against alternative glucose-lowering medications in individuals with type 2 diabetes with the broad spectrum of cardiovascular risk. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) cohort study was designed to monitor the safety and effectiveness of empagliflozin periodically for a period of 5 years with data collection from electronic healthcare databases., Methods: We identified individuals ≥18 years old with type 2 diabetes who initiated empagliflozin or dipeptidyl peptidase-4 inhibitors (DPP-4i) from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we identified four a priori-defined effectiveness outcomes: (1) myocardial infarction (MI) or stroke; (2) hospitalisation for heart failure (HHF); (3) major adverse cardiovascular events (MACE); and (4) cardiovascular mortality or HHF. Safety outcomes included lower-limb amputations, non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), severe hypoglycaemia, retinopathy progression, and short-term kidney and bladder cancers. We estimated HRs and rate differences (RDs) per 1000 person-years, overall and stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD) and heart failure., Results: We identified 115,116 matched pairs. Compared with DPP-4i, empagliflozin was associated with lower risks of MI/stroke (HR 0.88 [95% CI 0.81, 0.96]; RD -2.08 [95% CI (-3.26, -0.90]), HHF (HR 0.50 [0.44, 0.56]; RD -5.35 [-6.22, -4.49]), MACE (HR 0.73 [0.62, 0.86]; RD -6.37 [-8.98, -3.77]) and cardiovascular mortality/HHF (HR 0.57 [0.47, 0.69]; RD -10.36 [-12.63, -8.12]). Absolute benefits were larger in older individuals and in those with ASCVD/heart failure. Empagliflozin was associated with an increased risk of DKA (HR 1.78 [1.44, 2.19]; RD 1.59 [1.08, 2.09]); decreased risks of AKI (HR 0.62 [0.54, 0.72]; RD -2.39 [-3.08, -1.71]), hypoglycaemia (HR 0.75 [0.67, 0.84]; RD -2.46 [-3.32, -1.60]) and retinopathy progression (HR 0.78 [0.63, 0.96)]; RD -9.49 [-16.97, -2.10]); and similar risks of other safety events., Conclusions/interpretation: Empagliflozin relative to DPP-4i was associated with risk reductions of MI or stroke, HHF, MACE and the composite of cardiovascular mortality or HHF. Absolute risk reductions were larger in older individuals and in those who had history of ASCVD or heart failure. Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression to proliferative retinopathy, with no difference in the short-term risks of lower-extremity amputation, non-vertebral fractures, kidney and renal pelvis cancer, and bladder cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cardiovascular disease is a major cause of morbidity and mortality in patients with type 2 diabetes. The effects of glucose-lowering medications on cardiovascular outcomes in individuals with type 2 diabetes and low cardiovascular risk are unclear. We investigated cardiovascular outcomes by treatment group in participants randomly assigned to insulin glargine, glimepiride, liraglutide, or sitagliptin, added to baseline metformin, in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study)., Methods: A total of 5047 participants with a mean±SD age of 57.2±10.0 years, type 2 diabetes duration of 4.0±2.7 years, and low baseline prevalence of cardiovascular disease (myocardial infarction, 5.1%; cerebrovascular accident, 2.0%) were followed for a median of 5 years. Prespecified outcomes included between-group time-to-first event analyses of MACE-3 (composite of major adverse cardiovascular events: cardiovascular death, myocardial infarction, and stroke), MACE-4 (MACE-3+unstable angina requiring hospitalization or revascularization), MACE-5 (MACE-4+coronary revascularization), MACE-6 (MACE-5+hospitalization for heart failure), and the individual components. MACE outcomes and hospitalization for heart failure in the liraglutide-treated group were compared with the other groups combined using Cox proportional hazards models. MACE-6 was also analyzed as recurrent events using a proportional rate model to compare all treatment groups., Results: We observed no statistically significant differences in the cumulative incidence of first MACE-3, MACE-4, MACE-5, or MACE-6, or their individual components, by randomized treatment group. However, when compared with the other treatment groups combined, the liraglutide-treated group had a significantly lower risk of MACE-5 (adjusted hazard ratio, 0.70 [95% CI, 0.54-0.91]; P =0.021), MACE-6 (adjusted hazard ratio, 0.70 [95% CI, 0.55-0.90]; P =0.021), and hospitalization for heart failure (adjusted hazard ratio, 0.49 [95% CI, 0.28-0.86]; P =0.022). Compared with the liraglutide group, significantly higher rates of recurrent MACE-6 events occurred in the groups treated with glimepiride (rate ratio, 1.61 [95% CI, 1.13-2.29]) or sitagliptin (rate ratio 1.75; [95% CI, 1.24-2.48])., Conclusions: This comparative effectiveness study of a contemporary cohort of adults with type 2 diabetes, largely without established cardiovascular disease, suggests that liraglutide treatment may reduce the risk of cardiovascular events in patients at relatively low risk compared with other commonly used glucose-lowering medications., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01794143., Competing Interests: Disclosures Dr Green reports research support from Boehringer Ingelheim/Lilly, Merck, Bluedrop, Sanofi/Lexicon, and Roche, and serving as an advisor or consultant for Boehringer Ingelheim/Lilly, Bayer, AstraZeneca, Merck, Hawthorne Effect, Sanofi/Lexicon, Pfizer, Valo, Anji, Vertex, and Novo Nordisk. Dr Everett reports research support from Novo Nordisk and PCORI; consulting fees from the American Heart Association, Eli Lilly and Company, Ipsen Pharmaceuticals, Janssen Pharmaceuticals, and Novo Nordisk; and royalties from UpToDate. Dr Desouza reports serving as a consultant for Novo Nordisk, AstraZeneca, Asahi, and Bayer. Dr Inzucchi reports serving as an advisor or consultant to Boehringer Ingelheim, AstraZeneca, Bayer, Novo Nordisk, Merck, Pfizer, Lexicon, Abbott, VTV Therapeutics, and Esperion, and delivering lectures sponsored by Boehringer Ingelheim and AstraZeneca. Dr Tan is a retiree of and receives a pension from Eli Lilly and Company. Dr Utzschneider reports personal fees from Nevro Corporation, research support from Eli Lilly and Company, and research support from AVID, outside the submitted work. Dr Mudaliar reports serving as a speaker for AstraZeneca and a consultant for Bayer. The other authors have nothing to disclose.

Background: No randomized clinical trials have directly compared the cardiorenal effectiveness of empagliflozin and GLP-1RA agents with demonstrated cardioprotective effects in patients with a broad spectrum of cardiovascular risk. We reported the final-year results of the EMPRISE study, a monitoring program designed to evaluate the cardiorenal effectiveness of empagliflozin across broad patient subgroups., Methods: We identified patients ≥ 18 years old with type 2 diabetes who initiated empagliflozin or GLP-1RA from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we evaluated risks of outcomes including myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE - MI, stroke, or cardiovascular mortality), a composite of HHF or cardiovascular mortality, and progression to end-stage kidney disease (ESKD) (in patients with chronic kidney disease stages 3-4). We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years, overall and within subgroups of age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF)., Results: We identified 141,541 matched pairs. Compared with GLP-1RA, empagliflozin was associated with similar risks of MI or stroke [HR: 0.99 (0.92, 1.07); RD: -0.23 (-1.25, 0.79)], and lower risks of HHF [HR: 0.50 (0.44, 0.56); RD: -2.28 (-2.98, -1.59)], MACE [HR: 0.90 (0.82, 0.99); RD: -2.54 (-4.76, -0.32)], cardiovascular mortality or HHF [HR: 0.77 (0.69, 0.86); RD: -4.11 (-5.95, -2.29)], and ESKD [0.75 (0.60, 0.94); RD: -6.77 (-11.97, -1.61)]. Absolute risk reductions were larger in older patients and in those with baseline ASCVD/HF. They did not differ by sex., Conclusions: The cardiovascular benefits of empagliflozin vs. cardioprotective GLP-1RA agents were larger in older patients and in patients with history of ASCVD or HF, while they did not differ by sex. In patients with advanced CKD, empagliflozin was associated with risk reductions of progression to ESKD., (© 2024. The Author(s).)

Here, we combined the use of 2 technologies that have not previously been used together-a positively pressurized isolator IVC (IsoIVC-P) and a modular isolator with integrated vaporized hydrogen peroxide (VHP) technology???to develop highly tractable and scalable methods to support long-term maintenance of germfree mouse colonies and the concurrent use of germfree and gnotobiotic mice in the same room. This space-efficient system increases the practicality of microbiome studies. Specifically, the exterior surfaces of microbially similar IsoIVC-P were sterilized by using VHP prior to opening the cages and handling the mice therein. This space-efficient system increases the feasibility of microbiome studies. After over 74 wk of experimentation and handling equivalent to more than 1,379,693 germfree mouse-days, we determined that the method and practices we developed have a weekly performance metric of 0.0001 sterility breaks per husbandry unit; this rate is comparable to the isolator 'gold standard.' These data were achieved without adverse incidents while maintaining an Altered Schaedler Flora colony and multiple gnotobiotic studies involving fecal microbial transplants in the same room. Our novel IsoIVC-P???VHP workstation housing system thus improves microbiome research efficiency, eliminates hazards, and reduces risks associated with traditional methods.

Aims: The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) in routine clinical practice is not extensively studied. This study aimed to evaluate the comparative effectiveness of SGLT2i vs. sitagliptin in older adults with HF and type 2 diabetes and to investigate whether there were any differences between agents within the SGLT2i class or for reduced and preserved ejection fraction., Methods and Results: Using Medicare claims data (April 2013 to December 2019), 16 253 SGLT2i initiators vs. 43 352 initiators of sitagliptin aged ≥65 years with type 2 diabetes and HF were included. The primary outcome was a composite of all-cause mortality, hospitalization for HF or urgent visit requiring intravenous diuretics; secondary outcomes included its individual components. Propensity score fine stratification weighted Cox regression was used to adjust for 100 pre-exposure characteristics. Mean age was 74 years; 49.8% were women. Initiation of SGLT2i vs. sitagliptin was associated with a lower risk of the primary composite outcome [adjusted hazard ratio (HR) 0.72; 95% confidence interval 0.67-0.77]. The adjusted HRs were 0.70 (0.63-0.78) for all-cause mortality, 0.64 (0.58-0.70) for hospitalization for HF, and 0.77 (0.69-0.86) for urgent visit requiring intravenous diuretics. Similar associations with the primary composite outcome were observed for all three agents within the SGLT2i class, for reduced and preserved ejection fraction, and subgroups based on demographics, comorbidities, and other HF treatments. Bias-calibrated HRs for the primary endpoint using negative and positive control outcomes ranged between 0.81 and 0.89, suggesting that the observed benefit could not be fully explained by residual confounding., Conclusion: In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HF and type 2 diabetes compared with sitagliptin, with no evidence of heterogeneity across the SGLT2i class or across ejection fraction., Competing Interests: Conflict of interest E.P. is investigator of an investigator-initiated grant to the Brigham and Women’s Hospital from Boehringer Ingelheim, not directly related to the topic of the submitted work. B.M.E reports consulting fees from Gilead, Johnson & Johnson, Provention Bio, Eli Lilly and Company, Ipsen, Circulation Journal, Up to Date, and the NIDDK unrelated to the current work. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, and Sanofi, speaker engagements with Novartis, and Roche Diagnostics and participates in clinical trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. S.D.S. has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Cardiac Dimensions, Celladon, CellProThera, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and Us2.ai; has consulted for Abbott, Action, Akros, Alnylam, American Regent, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, and Sarepta and has stock options in Dinaqor. S.S. is participating in investigator-initiated grants to the Brigham and Women’s Hospital from Boehringer Ingelheim unrelated to the topic of this study; he is a consultant to Aetion, Inc., a software manufacturer of which he owns equity; his interests were declared, reviewed, and approved by the Brigham and Women’s Hospital in accordance with their institutional compliance policies. R.J.D. reports serving as Principal Investigator on research grants to Brigham and Women’s Hospital from Vertex, Novartis, and Bayer. No other potential conflicts of interest relevant to this article were reported., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The objective of this study was to quantify the value of early suppression of high-sensitivity C-reactive protein (hsCRP) levels as a biomarker of the protective role of canakinumab against future gout flares., Methods: We conducted a post hoc causal mediation analysis of the Canakinumab Anti-Inflammatory Thrombosis Outcome Study for gout flares. The 3-month change in the log hsCRP level was the mediator of interest. We used linear regression for the hsCRP level mediator and Cox or Weibull regression for gout-flare outcomes, combining them in causal mediation analysis. We examined the cohort overall, as well as stratified by prevalent gout at baseline., Results: We analyzed 9,221 patients without prevalent gout and 747 with prevalent gout. The Cox regression hazard ratio (HR) for a gout flare was 0.50 (95% confidence interval [95% CI] 0.37-0.68) comparing canakinumab with placebo, of which 6% was explained by the mediated effect through hsCRP level reduction in the first 3 months. In the prevalent-gout subgroup, the HR was 0.58 (95% CI 0.36-0.95), of which 31% was explained by the mediated effect through hsCRP level reduction. The Weibull analysis gave a proportion-mediated estimate of 47%. The indirect effect via hsCRP level reductions was unclear in the subgroup without prevalent gout., Conclusion: The first 3-month reduction in hsCRP level was not a good biomarker for canakinumab's protective effect on future gout flares in the overall cohort. Among patients with prevalent gout, there may be a potential role for early hsCRP level reduction as a biomarker for interleukin-1β inhibitors' future gout-flare benefit., (© 2021 American College of Rheumatology.)

Background: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear., Objective: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization., Design: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087)., Setting: Done during 2021 to 2022 among 127 U.S. hospitals., Participants: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation., Intervention: 2.5 mg of apixaban versus placebo twice daily for 30 days., Measurements: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding., Results: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment., Limitations: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity., Conclusion: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive., Primary Funding Source: National Institutes of Health.

Inflammation is a key determinant of cardiovascular outcomes, but its role in heart failure is uncertain. In patients with cardiometabolic disease enrolled in the prospective, multicenter ancillary study of CIRT (Cardiovascular Inflammation Reduction Trial), CIRT-CFR (Coronary Flow Reserve to Assess Cardiovascular Inflammation), impaired coronary flow reserve was independently associated with increased inflammation and myocardial strain despite well-controlled lipid, glycemic, and hemodynamic profiles. Inflammation modified the relationship between CFR and myocardial strain, disrupting the association between cardiac blood flow and function. Future studies are needed to investigate whether an early inflammation-mediated reduction in CFR capturing microvascular ischemia may lead to heart failure in patients with cardiometabolic disease. (Cardiovascular Inflammation Reduction Trial [CIRT]; NCT01594333; Coronary Flow Reserve to Assess Cardiovascular Inflammation [CIRT-CFR]; NCT02786134)., Competing Interests: This research was supported by National Institutes of Health (NIH) R01HL132021 (to Drs Di Carli and Taqueti) and K23HL135438 (to Dr Taqueti). Dr Shah was supported by NIH R01HL135008, R01HL143224, R01HL150342, R01HL14818, and K24HL152008. Dr Libby was supported by R01HL134892. Dr Shah has received research support from Novartis; and consulting fees from Philips Ultrasound and Edwards Lifesciences. Dr Dorbala has received research support from Pfizer, GE Healthcare, and Attralus; and consulting honoraria from Pfizer and GE Healthcare. Dr Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research; has received research support from TD Bank, AusculSciences, Siemens Healthineers, and Artrya; and has equity interest in General Electric. Dr Hage has received grant support from GE Healthcare, Novartis, and Idorsia Pharmaceuticals. Dr Beanlands holds the Chair in Cardiology at the University of Ottawa Heart Institute; is a University of Ottawa Distinguished Research Chair in Cardiovascular Imaging; and is a consultant for and has received grant funding from GE Healthcare, Lantheus Medical Imaging, and Jubilant DraxImage. Dr Libby is an unpaid consultant to or involved in clinical trials for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Norvo Nordisk, Novartis, Pfizer, Sanofi-Regeneron; is on the Scientific Advisory Board for Amgen, Caristo, Cartesian, Corvidia Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, PlaqueTec, and XBiotech, Inc; is on the Board of Directors and has a financial interest in XBiotech, Inc; and has received research funding from Novartis, the American Heart Association, the RRM Charitable Fund, and the Simard Fund. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background: The effect of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the total (first and recurrent) burden of cardiovascular (CV) hospitalizations, including hospitalization for heart failure, myocardial infarction, and stroke, is poorly understood., Objective: To assess the effect of empagliflozin, an SGLT2i, on total CV hospitalizations among older adults with T2D., Methods: Using data from Medicare fee-for-service (08/2014-09/2017), we identified 1:1 propensity score-matched cohorts of patients with T2D initiating empagliflozin versus sitagliptin or empagliflozin versus glucagon-like peptide-1 receptor agonists (GLP-1RA), balancing >140 baseline covariates. We compared the risk of first and recurrent hospitalizations with any CV condition as the primary discharge diagnosis (ICD-9: 390-459; ICD-10: I00-I99), hospitalizations for heart failure (HHF), and myocardial infarctions (MI) or stroke. We estimated treatment effects based on the Ghosh-Lin semiparametric model for recurrent events as primary and joint frailty model as secondary analysis., Results: We included 11,429 matched-pairs of empagliflozin and sitagliptin initiators and 17,502 matched-pairs of empagliflozin and GLP1-RA initiators with an average age of 72 years. Empagliflozin was associated with a reduced risk of total CV hospitalizations (0.80 [0.69-0.93] vs sitagliptin; 0.88 [0.77-1.00] vs GLP-1RA) and total HHF (0.70 [0.51-0.98] vs sitagliptin; 0.76 [0.56-1.03] vs GLP1-RA) over a mean follow up of 6.3 months. No differences between treatments were observed for MI or stroke. Results were consistent for joint frailty models., Conclusion: Empagliflozin, compared to sitagliptin or to a lesser extent GLP1-RA, was associated with a reduction in the burden of total CV hospitalizations and HHF in older patients with T2D., (Copyright © 2022. Published by Elsevier Inc.)

Background: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels., Methods: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes., Results: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease., Conclusions: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.)., (Copyright © 2022 Massachusetts Medical Society.)

Importance: Limited evidence is available on the comparative effectiveness of empagliflozin vs alternative second-line glucose-lowering agents in patients with type 2 diabetes (T2D) receiving routine care who have a broad spectrum of cardiorenal risk., Objective: To evaluate the association of empagliflozin with cardiovascular outcomes relative to liraglutide and sitagliptin, stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD)., Design, Setting, and Participants: This retrospective comparative effectiveness cohort study used deidentified Medicare claims data from August 1, 2014, to September 30, 2018, with follow-up from drug initiation until treatment changes, death, or gap in Medicare enrollment (>30 days). Data analysis was performed from October 1, 2021, to April 30, 2022. Medicare fee-for-service beneficiaries older than 65 years with T2D were included. A total of 45 788 patients (22 894 propensity score-matched pairs initiating treatment with either empagliflozin or liraglutide) were included in cohort 1, and 45 624 patients (22 812 propensity score-matched pairs initiating treatment with either empagliflozin or sitagliptin) were included in cohort 2., Exposures: Empagliflozin vs liraglutide (cohort 1) or empagliflozin vs sitagliptin (cohort 2)., Main Outcomes and Measures: Primary outcomes were (1) modified major adverse cardiovascular events (MACEs), including a composite of myocardial infarction, stroke, and all-cause mortality, and (2) hospitalization for heart failure (HHF). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, adjusting for 143 baseline covariates using 1:1 propensity score matching., Results: Among 45 788 patients in cohort 1, the mean (SD) age was 71.9 (5.1) years; 23 396 patients (51.1%) were female, 22 392 (48.9%) were male, and 38 049 (83.1%) were White. Among 45 624 patients in cohort 2, the mean (SD) age was 72.1 (5.1) years; 21 418 patients (46.9%) were female, 24 206 (53.1%) were male, and 37 814 (82.9%) were White. Relative to patients initiating liraglutide, those initiating empagliflozin had a similar risk of the modified MACE outcome (HR, 0.90; 95% CI, 0.79-1.03) and a reduced risk of HHF (HR, 0.66; 95% CI, 0.52-0.82). Across subgroups, empagliflozin was associated with a lower risk of the modified MACE outcome in patients with a history of ASCVD (HR, 0.83; 95% CI, 0.71-0.98) and HF (HR, 0.77; 95% CI, 0.60-1.00) compared with liraglutide, and potential heterogeneity in estimates was observed by sex (male: HR, 0.85 [95% CI, 0.71-1.01]; female: HR, 1.16 [95% CI, 0.94-1.42]; P = .02 for homogeneity). However, reductions in the risk of HHF were observed across most subgroups (eg, ASCVD: HR, 0.66 [95% CI, 0.51-0.85]; HF: HR, 0.66 [95% CI, 0.49-0.88]). Compared with sitagliptin, empagliflozin was associated with reduced risks of the modified MACE outcome (HR, 0.68; 95% CI, 0.60-0.77) and HHF (HR, 0.45; 95% CI, 0.36-0.56), which were consistent across all subgroups. Absolute benefits of empagliflozin vs sitagliptin were larger in patients with a history of ASCVD (modified MACE: RD, -17.6 [95% CI, -24.9 to -10.4]; HHF: RD, -16.7 [95% CI, -21.7 to -11.9]), HF (modified MACE: RD, -41.1 [95% CI, -59.9 to -22.6]; HHF: RD, -50.4 [95% CI, -67.5 to -33.9]), or CKD (modified MACE: RD, -26.7 [95% CI, -41.3 to -12.3]; HHF: RD, -31.9 [95% CI, -43.5 to -20.8])., Conclusions and Relevance: In this comparative effectiveness study of older adults, empagliflozin was associated with a lower risk of HHF (relative to both liraglutide and sitagliptin) and the modified MACE outcome (relative to sitagliptin), with larger absolute benefits in patients with established cardiorenal diseases. These findings suggest that older adults with T2D might benefit more from empagliflozin vs liraglutide or sitagliptin with respect to the risk of HHF; with respect to the risk of MACEs, empagliflozin might be preferable to liraglutide only in patients with cardiovascular disease history and to sitagliptin across all patient subgroups.

Importance: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated many cardiovascular and kidney function benefits for patients with type 2 diabetes (T2D). However, the results of SGLT-2i use in primary prevention of atrial fibrillation (AF) were inconsistent in clinical trials, and incident AF was not a prespecified end point., Objective: To examine incident AF with initiation of an SGLT-2i compared with initiation of a dipeptidyl peptidase-4 inhibitor (DPP-4i) or a glucagonlike peptide-1 receptor agonist (GLP-1RA) among older adults (aged ≥66 years) with T2D in routine clinical practice., Design, Setting, and Participants: A population-based new-user cohort study included older adults with T2D who had no history of AF and were enrolled in Medicare fee-for-service from April 1, 2013, to December 31, 2018. Data analysis was performed from June 28 to December 1, 2021., Exposures: To control for potential confounding, new users of SGLT-2i were 1:1 propensity score (PS)-matched to new users of DPP-4is or GLP-1RAs in 2 pairwise comparisons based on 138 baseline covariates., Main Outcomes and Measures: The primary outcome was incident AF, defined as an inpatient diagnosis code for AF. Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years, with their 95% CIs, were estimated in the PS-matched groups., Results: New users of SGLT-2is were 1:1 PS-matched to new users of a DPP-4i (n = 74 868) or GLP-1RA (n = 80 475). Overall, the mean (SD) age of study participants was 72 (5) years, and 165 984 were women (53.4%). The risk of incident AF was lower in the SGLT-2i group than the matched DPP-4i group (HR, 0.82; 95% CI, 0.76 to 0.89; RD, -3.7; 95% CI, -5.2 to -2.2 per 1000 person-years) or the matched GLP-1RA group (HR, 0.90; 95% CI, 0.83 to 0.98; RD, -1.8; 95% CI, -3.2 to -0.3 per 1000 person-years). Results were consistent across several sensitivity and subgroup analyses., Conclusions and Relevance: The findings of this study suggest that the initiation of an SGLT-2i was associated with a reduced risk of incident AF compared with a DPP-4i or GLP-1RA. The results may be helpful when weighing the potential risks and benefits of various glucose level-lowering agents in older adults with T2D.

Aims: To evaluate the performance of the WATCH-DM risk score, a clinical risk score for heart failure (HF), in patients with dysglycaemia and in combination with natriuretic peptides (NPs)., Methods and Results: Adults with diabetes/pre-diabetes free of HF at baseline from four cohort studies (ARIC, CHS, FHS, and MESA) were included. The machine learning- [WATCH-DM(ml)] and integer-based [WATCH-DM(i)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrell's concordance index (C-index) and calibration by the Greenwood-Nam-D'Agostino (GND) statistic. Improvement in model performance with the addition of NP levels was assessed by C-index and continuous net reclassification improvement (NRI). Of the 8938 participants included, 3554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5 years. The WATCH-DM(ml) and WATCH-DM(i) scores demonstrated high discrimination for predicting HF risk among individuals with dysglycaemia (C-indices = 0.80 and 0.71, respectively), with no evidence of miscalibration (GND P ≥0.10). The C-index of elevated NP levels alone for predicting incident HF among individuals with dysglycaemia was significantly higher among participants with low/intermediate (<13) vs. high (≥13) WATCH-DM(i) scores [0.71 (95% confidence interval 0.68-0.74) vs. 0.64 (95% confidence interval 0.61-0.66)]. When NP levels were combined with the WATCH-DM(i) score, HF risk discrimination improvement and NRI varied across the spectrum of risk with greater improvement observed at low/intermediate risk [WATCH-DM(i) <13] vs. high risk [WATCH-DM(i) ≥13] (C-index = 0.73 vs. 0.71; NRI = 0.45 vs. 0.17)., Conclusion: The WATCH-DM risk score can accurately predict incident HF risk in community-based individuals with dysglycaemia. The addition of NP levels is associated with greater improvement in the HF risk prediction performance among individuals with low/intermediate risk than those with high risk., (© 2021 European Society of Cardiology.)

Background: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in placebo-controlled trials of patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD)., Objective: To evaluate whether SGLT2 inhibitors and GLP-1 RAs are associated with differential cardiovascular benefit among T2D patients with and without CVD., Design: Population-based cohort study., Setting: Medicare and 2 U.S. commercial claims data sets (April 2013 to December 2017)., Participants: 1:1 propensity score-matched adult T2D patients with and without CVD (52 901 and 133 139 matched pairs) initiating SGLT2 inhibitor versus GLP-1 RA therapy., Measurements: Primary outcomes were myocardial infarction (MI) or stroke hospitalization and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, with 95% CIs, controlling for 138 preexposure covariates., Results: The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with a slightly lower risk for MI or stroke in patients with CVD (HR, 0.90 [95% CI, 0.82 to 0.98]; RD, -2.47 [CI, -4.45 to -0.50]) but similar risk in those without CVD (HR, 1.07 [CI, 0.97 to 1.18]; RD, 0.38 [CI, -0.30 to 1.07]). The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with reductions in HHF risk regardless of baseline CVD in patients with CVD (HR, 0.71 [CI, 0.64 to 0.79]; RD, -4.97 [CI, -6.55 to -3.39]) and in those without CVD (HR, 0.69 [CI, 0.56 to 0.85]; RD, -0.58 [CI, -0.91 to -0.25])., Limitation: Treatment selection was not randomized., Conclusion: Use of SGLT2 inhibitors versus GLP-1 RAs was associated with consistent reductions in HHF risk among T2D patients with and without CVD, although the absolute benefit was greater in patients with CVD. There were no large differences in risk for MI or stroke among T2D patients with and without CVD., Primary Funding Source: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School.

Objectives: SLE patients have elevated cardiovascular disease (CVD) risk, but it is unclear whether this risk is affected by choice of immunosuppressive drug. We compared CVD risks among SLE patients starting MMF, CYC or AZA., Methods: Using Medicaid Analytic eXtract (2000-2012), adult SLE patients starting MMF, CYC or AZA were identified and propensity scores (PS) were estimated for receipt of MMF vs CYC and MMF vs AZA. We examined rates of first CVD event (primary outcome), all-cause mortality, and a composite of first CVD event and all-cause mortality (secondary outcomes). After 1:1 PS-matching, Fine-Gray regression models estimated subdistribution hazard ratios (HRs.d.) for risk of CVD events. Cox regression models estimated HRs for all-cause mortality. The primary analysis was as-treated; 6- and 12-month intention-to-treat (ITT) analyses were secondary., Results: We studied 680 PS-matched pairs of patients with SLE initiating MMF vs CYC and 1871 pairs initiating MMF vs AZA. Risk of first CVD event was non-significantly reduced for MMF vs CYC [HRs.d 0.72 (95% CI: 0.37, 1.39)] and for MMF vs AZA [HRs.d 0.88 (95% CI: 0.59, 1.32)] groups. In the 12-month ITT, first CVD event risk was lower among MMF than AZA new users [HRs.d 0.68 (95% CI: 0.47, 0.98)]., Conclusion: In this head-to-head PS-matched analysis, CVD event risks among SLE patients starting MMF vs CYC or AZA were not statistically reduced except in one 12-month ITT analysis of MMF vs AZA, suggesting longer-term use may convey benefit. Further studies of potential cardioprotective benefit of MMF are necessary., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study evaluated the application of a biomarker-based risk score to identify individuals with dysglycemia who are at high risk for incident heart failure (HF) and to inform allocation of effective preventive interventions., Background: Risk stratification tools to identify patients with diabetes and pre-diabetes at highest risk for HF are needed to inform cost-effective allocation of preventive therapies. Whether a biomarker score can meaningfully stratify HF risk is unknown., Methods: Participants free of cardiovascular disease from 3 cohort studies (ARIC [Atherosclerosis Risk In Communities], DHS [Dallas Heart Study], and MESA [Multi-Ethnic Study of Atherosclerosis]) were included. An integer-based biomarker score included high-sensitivity cardiac troponin T ≥6 ng/l, N-terminal pro-B-type natriuretic peptide ≥125 pg/ml, high-sensitivity C-reactive protein ≥3 mg/l, and left ventricular hypertrophy by electrocardiography, with 1 point for each abnormal parameter. The 5-year risk of HF was estimated among participants with diabetes and pre-diabetes across biomarker score groups (0 to 4)., Results: The primary analysis included 6,799 participants with dysglycemia (diabetes: 33.2%; pre-diabetes: 66.8%). The biomarker score demonstrated good discrimination and calibration for predicting 5- and 10-year HF risk among pre-diabetes and diabetes cohorts. The 5-year risk of HF among subjects with a biomarker score of ≤1 was low and comparable to participants with euglycemia (0.78%). The 5-year risk for HF increased in a graded fashion with an increasing biomarker score, with the highest risk noted among those with scores of ≥3 (diabetes: 12.0%; pre-diabetes: 7.8%). The estimated number of HF events that could be prevented using a sodium-glucose cotransporter-2 inhibitor per 1,000 treated subjects over 5 years was 11 for all subjects with diabetes and ranged from 4 in the biomarker score zero group to 44 in the biomarker score ≥3 group., Conclusions: Among adults with diabetes and pre-diabetes, a biomarker score can stratify HF risk and inform allocation of HF prevention therapies., Competing Interests: Funding Support and Author Disclosures Dr. Pandey was supported by the Texas Health Resources Clinical Scholarship, Gilead Sciences Research Scholar Program, and the National Institute of Aging GEMSSTAR Grant (1R03AG067960-01). The ARIC study is conducted as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN2 68201100006C, HHSN268201100007C, HHSN268201100008C, HHSN26820 1100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201 100012C). The Dallas Heart Study was funded by a grant from the Donald W. Reynolds Foundation. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (award number UL1TR001105) to the University of Texas Southwestern Medical Center. The Multi-Ethnic Study of Atherosclerosis was supported by the National Heart, Lung, and Blood Institute (R01 HL071739 and contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, and N01-C-95169). Dr. Vaduganathan has been supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541); and has served on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Pandey has served on the advisory board of Roche Diagnostics. Dr. Patel was supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant (5T32HL125247-03). Dr. Kosiborod has received research grant support from AstraZeneca and Boehringer Ingelheim; has served as a consultant or on advisory boards for Amgen, Applied Therapeutics, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Merck (Diabetes), Novo Nordisk, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca and honorarium from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. de Lemos has received grant support from Roche Diagnostics and Abbott Diagnostics; and has received consulting fees from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, Siemen’s Health Care Diagnostics, Quidel Cardiovascular, Inc, Novo Nordisk, Amgen, Regeneron, Eli Lilly, and Esperion. Drs. DeFilippi and de Lemos hold a patent pending (U.S. Patent Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” Dr. McGuire has received personal fees for trial leadership from GlaxoSmithKline, Janssen, Lexicon, AstraZeneca, CSL Behring, Sanofi, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Eisai Inc., Esperion, and Lilly USA; and has received personal consultancy fees from AstraZeneca, Lilly USA, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Metavant, Applied Therapeutics, Sanofi, and Afimmune. Dr. Everett has received personal consultancy fees from Amarin, Amgen, Gilead, FDA, Merck & Co., National Institute of Diabetes and Digestive and Kidney Diseases, and Roche Diagnostics outside the present work; and has received significant investigator-initiated grant funding from the National Institute of Heart, Lung, and Blood Institute outside the present work. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Certain antihyperglycemic therapies modify cardiovascular and kidney outcomes among patients with type 2 diabetes, but early uptake in practice appears restricted to particular demographics. We examine the association of Medicaid expansion with use of and expenditures related to antihyperglycemic therapies among Medicaid beneficiaries., Research Design and Methods: We employed a difference-in-difference design to analyze the association of Medicaid expansion on prescription of noninsulin antihyperglycemic therapies. We used 2012-2017 national and state Medicaid data to compare prescription claims and costs between states that did ( n = 25) and did not expand ( n = 26) Medicaid by January 2014., Results: Following Medicaid expansion in 2014, average noninsulin antihyperglycemic therapies per state/1,000 enrollees increased by 4.2%/quarter in expansion states and 1.6%/quarter in nonexpansion states. For sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA), quarterly growth rates per 1,000 enrollees were 125.3% and 20.7% for expansion states and 87.6% and 16.0% for nonexpansion states, respectively. Expansion states had faster utilization of SGLT2i and GLP-1RA than nonexpansion states. Difference-in-difference estimates for change in volume of prescriptions after Medicaid expansion between expansion versus nonexpansion states was 1.68 (95% CI 1.09-2.26; P < 0.001) for all noninsulin therapies, 0.125 (-0.003 to 0.25; P = 0.056) for SGLT2i, and 0.12 (0.055-0.18; P < 0.001) for GLP-1RA., Conclusions: Use of noninsulin antihyperglycemic therapies, including SGLT2i and GLP-1RA, increased among low-income adults in both Medicaid expansion and nonexpansion states, with a significantly greater increase in overall use and in GLP-1RA use in expansion states. Future evaluation of the population-level health impact of expanded access to these therapies is needed., (© 2020 by the American Diabetes Association.)

Background: Inflammation reduction with the interleukin (IL)-1β inhibitor canakinumab significantly reduces the first major adverse cardiovascular event in patients with prior myocardial infarction (MI) and residual inflammatory risk (high-sensitivity C-reactive protein ≥ 2 mg/l). However, the effect of canakinumab on the total number of cardiovascular events, including recurrent events collected after a first event, is unknown., Objectives: This study sought to determine whether randomly allocated canakinumab would reduce the total burden of serious cardiovascular events., Methods: We randomized 10,061 patients to placebo or canakinumab 50 mg, 150 mg, or 300 mg once every 3 months and compared the rates of the composite of all serious cardiovascular events (MI, stroke, coronary revascularization, and cardiovascular death) in active versus placebo groups. We used negative binomial regression to account for correlations among repeated events in the same person and to estimate rate ratios and 95% confidence intervals., Results: During a median of 3.7 years of follow-up, 3,417 total serious cardiovascular events occurred in 2,003 individuals among the 10,061 unique patients randomized. Canakinumab reduced the rates of total serious cardiovascular events, with rates per 100 person-years in the placebo, 50 mg, 150 mg, and 300 mg canakinumab groups of 10.4, 8.4, 8.3, and 8.2, respectively. The corresponding rate ratios (95% confidence intervals) compared with placebo were 0.80 (0.69 to 0.93) for 50 mg, 0.79 (0.68 to 0.92) for 150 mg, and 0.78 (0.67 to 0.91) for 300 mg., Conclusions: Anti-inflammatory therapy with canakinumab significantly reduced the total number of cardiovascular events in patients with prior MI and evidence of residual inflammatory risk. (Cardiovascular Risk Reduction Study [Reduction in Recurrent Major CV Disease Events] (CANTOS); NCT01327846., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Cardiovascular disease (CVD) risk is elevated in patients with systemic lupus erythematosus (SLE) and diabetes mellitus (DM), but whether risk of CVD in patients with SLE is as high as in those with DM is unknown. The present study was undertaken to compare CVD risks between patients with SLE and DM and general population US Medicaid recipients., Methods: In a cohort study, we identified age- and sex-matched adults (1:2:4) with SLE or DM and those from the general population using Medicaid Analytic eXtract, 2007-2010. We collected data on baseline sociodemographic factors, comorbidities, and medications. We used Cox regression models to calculate hazard ratios (HRs) of hospitalized nonfatal CVD events (combined myocardial infarction [MI] and stroke) and MI and stroke separately, accounting for competing risk of death and adjusting for covariates. We compared risks in age-stratified models., Results: We identified 40,212 SLE patients, 80,424 DM patients, and 160,848 general population patients; 92.5% were female, and the mean ± SD age was 40.3 ± 12.1 years. Nonfatal CVD incidence rate per 1,000 person-years was 8.99 for patients with SLE, 7.07 for those with DM, and 2.36 for the general population. Nonfatal CVD risk was higher in SLE compared to DM (HR 1.27 [95% confidence interval (95% CI) 1.15-1.40]), driven by excess risk at ages 18-39 years (HR 2.22 [95% CI 1.81-2.71]). Patients with SLE had higher risk of CVD compared to the general population (HR 2.67 [95% CI 2.38-2.99])., Conclusion: SLE patients had a 27% higher risk of nonfatal CVD events compared to age- and sex-matched patients with DM and more than twice the risk of the Medicaid general population. The highest relative risk occurred at ages 18-39 years. These high risks merit aggressive evaluation for modifiable factors and research to identify prevention strategies., (© 2020, American College of Rheumatology.)

Background: The majority of sudden cardiac deaths (SCDs) occur in low-risk populations often as the first manifestation of cardiovascular disease (CVD). Biomarkers are screening tools that may identify subclinical cardiovascular disease and those at elevated risk for SCD. We aimed to determine whether the total to high-density lipoprotein cholesterol ratio, high-sensitivity cardiac troponin I, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity C-reactive protein individually or in combination could identify individuals at higher SCD risk in large, free-living populations with and without cardiovascular disease., Methods: We performed a nested case-control study within 6 prospective cohort studies using 565 SCD cases matched to 1090 controls (1:2) by age, sex, ethnicity, smoking status, and presence of cardiovascular disease., Results: The median study follow-up time until SCD was 11.3 years. When examined as quartiles or continuous variables in conditional logistic regression models, each of the biomarkers was significantly and independently associated with SCD risk after mutually controlling for cardiac risk factors and other biomarkers. The mutually adjusted odds ratios for the top compared with the bottom quartile were 1.90 (95% CI, 1.30-2.76) for total to high-density lipoprotein cholesterol ratio, 2.59 (95% CI, 1.76-3.83) for high-sensitivity cardiac troponin I, 1.65 (95% CI, 1.12-2.44) for NT-proBNP, and 1.65 (95% CI, 1.13-2.41) for high-sensitivity C-reactive protein. A biomarker score that awarded 1 point when the concentration of any of those 4 biomarkers was in the top quartile (score range, 0-4) was strongly associated with SCD, with an adjusted odds ratio of 1.56 (95% CI, 1.37-1.77) per 1-unit increase in the score., Conclusions: Widely available measures of lipids, subclinical myocardial injury, myocardial strain, and vascular inflammation show significant independent associations with SCD risk in apparently low-risk populations. In combination, these measures may have utility to identify individuals at risk for SCD.

Purpose of Review: Patients with established cardiovascular disease are at high risk for recurrent myocardial infarction, stroke, and cardiovascular death. The term residual risk refers to this risk that persists, even after optimal treatment. Considerable progress has been made to understand the biological basis of residual risk and to devise therapies that can safely and effectively reduce risk. The presence of ongoing subclinical vascular inflammation is known to be a marker of elevated residual risk, and reductions in measures of vascular inflammation predict improved outcome in these patients., Recent Findings: Recent trials of anti-inflammatory agents have specifically tested the hypothesis that inflammation reduction reduces residual cardiovascular risk. Most prominent among these are the CANTOS, COLCOT, and CIRT trials. CANTOS enrolled patients with prior myocardial infarction (MI) and a high-sensitivity C-reactive protein ≥ 2 mg/L and reported a 15% reduction in major adverse cardiovascular events (MACE; HR 0.85, 95% CI 0.74-0.98) with the interleukin-1β inhibitor canakinumab. In COLCOT, colchicine 0.5 mg daily led to a 23% relative risk reduction (HR 0.77, 95% CI 0.61-0.96) in major vascular events in patients with recent acute coronary syndrome. By contrast, CIRT was stopped early for lack of benefit of low-dose methotrexate in preventing MACE in patients with coronary artery disease and either type 2 diabetes or the metabolic syndrome. Ongoing subclinical inflammation is an important marker of risk in patients with established cardiovascular disease, and novel therapies targeted at specific inflammatory pathways now demonstrate efficacy for the prevention of major adverse cardiovascular events.

Objective: Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory autoimmune disease with high prevalence of several risk factors for atrial fibrillation/flutter (AF). However, the incidence and risk of AF in SLE have not been well quantified., Methods: We used the United States Medicaid Analytic eXtract from 2007 to 2010 to identify beneficiaries aged 18-65 years, with prevalent SLE, each matched by age and sex to 4 non-SLE general Medicaid recipients. We estimated the incidence rates (IR) per 1000 person-years (PY) for AF hospitalizations and used multivariable Cox regression to estimate the HR for AF hospitalization., Results: We identified 46,876 US Medicaid recipients with SLE, and 187,504 age- and sex-matched non-SLE controls (93% female; mean age 41.5 ± 12.2 yrs). Known AF risk factors such as hypertension (HTN), cardiovascular disease (CVD), and kidney disease were more prevalent in patients with SLE. During a mean followup of 1.9 ± 1.1 years for SLE, and 1.8 ± 1.1 years for controls, the IR per 1000 PY for AF was 1.4 (95% CI 1.1-1.6) among patients with SLE and 0.7 (95% CI 0.6-0.8) among non-SLE controls. In age- and sex-matched and race-adjusted Cox models, the HR for AF was 1.79 (95% CI 1.43-2.24); after adjustment for baseline HTN and CVD, the adjusted HR was reduced to 1.17 (95% CI 0.92-1.48)., Conclusion: SLE was associated with a doubled rate of hospitalization for AF compared to age- and sex-matched general Medicaid patients. In a race-adjusted model, the risk was 80% higher. However, the AF risk factors HTN and CVD were more prevalent among patients with SLE and accounted for the excess risk.

Background: Low-dose methotrexate (LD-MTX) is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis. Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred., Objective: To investigate AE rates, risk, and risk differences comparing LD-MTX versus placebo., Design: Prespecified secondary analyses of a double-blind, placebo-controlled, randomized trial. (ClinicalTrials.gov: NCT01594333)., Setting: North America., Participants: Adults with known cardiovascular disease and diabetes or metabolic syndrome., Intervention: Random allocation to LD-MTX (≤20 mg/wk) or placebo. All participants received folic acid, 1 mg/d, 6 days per week., Measurements: Risks for specific AEs of interest, as well as for all AEs, were compared across treatment groups after blinded adjudication., Results: After an active run-in period, 6158 patients were enrolled and 4786 randomly assigned to a group; median follow-up was 23 months and median dosage 15 mg/wk. Among the randomly assigned participants, 81.2% were male, median age was 65.7 years, and median body mass index was 31.5 kg/m2. Of 2391 participants assigned to LD-MTX, 2080 (87.0%) had an AE of interest, compared with 1951 of 2395 (81.5%) assigned to placebo (hazard ratio [HR], 1.17 [95% CI, 1.10 to 1.25]). The relative hazards of gastrointestinal (HR, 1.91 [CI, 1.75 to 2.10]), pulmonary (HR, 1.52 [CI, 1.16 to 1.98]), infectious (HR, 1.15 [CI, 1.01 to 1.30]), and hematologic (HR, 1.15 [CI, 1.07 to 1.23]) AEs were elevated for LD-MTX versus placebo. With the exception of increased risk for skin cancer (HR, 2.05 [CI, 1.28 to 3.28]), the treatment groups did not differ in risk for other cancer or mucocutaneous, neuropsychiatric, or musculoskeletal AEs. Renal AEs were reduced in the LD-MTX group (HR, 0.85 [CI, 0.78 to 0.93])., Limitation: The trial was done in patients without rheumatic disease who tolerated LD-MTX during an active run-in period., Conclusion: Use of LD-MTX was associated with small to moderate elevations in risks for skin cancer and gastrointestinal, infectious, pulmonary, and hematologic AEs, whereas renal AEs were decreased., Primary Funding Source: National Institutes of Health.

Systemic lupus erythematosus (SLE) severity, reflecting both disease intensity and duration, is heterogeneous making it challenging to study in administrative databases where severity may confound or mediate associations with outcomes. Garris et al. developed an administrative claims-based algorithm employing claims over a 1-year period to classify SLE severity as mild, moderate or severe. We sought to compare this administrative algorithm to a measure of SLE activity, the SLE Disease Activity Index-2000 (SLEDAI-2K) score at clinical visits. We identified 100 SLE patients followed in the Brigham and Women's Hospital (BWH) Lupus Center (in 2008-2010) with SLEDAI-2K scores at each visit over a 1-year period per person. We obtained data for the Garris algorithm for the same year per subject. We compared Garris SLE severity to the highest SLEDAI-2K in that year, with SLEDAI-2K categories of mild < 3, moderate 3-6, and severe > 6. We compared classification using weighted kappa statistics, and positive and negative predictive values (PPV, NPV). We also assessed the binary comparison of mild vs. moderate/severe. We calculated sensitivity, specificity, and McNemar's test. We analyzed 377 SLEDAI-2K assessments (mean 3.8 [SD 2.6] per subject/year). For classifying moderate/severe vs. mild SLE severity, the sensitivity was 85.7%, specificity 67.6%, PPV 81.8% and NPV 73.5%. The Garris algorithm for classifying SLE severity in administrative datasets had moderate agreement for classification of mild vs. moderate/severe SLE activity assessed by SLEDAI-2K assessments in an academic lupus center. It may be a useful tool for classifying SLE severity in administrative database studies.

Background: Patients with systemic lupus erythematosus (SLE) have a similar risk of myocardial infarction as those with diabetes mellitus (DM). Whether the risk of heart failure (HF) in SLE is similar to the elevated risk in DM is unknown. We sought to estimate the rates and risks for HF hospitalization among US Medicaid patients with SLE and to compare them to those for DM and the general Medicaid population., Methods: Using U.S. Medicaid data from 2007-2010, we identified patients with SLE or DM, and a matched cohort from the general Medicaid population and calculated incidence rates (IR), incidence rate ratios (IRR) and adjusted hazard ratios (HR) of a first HF hospitalization., Results: We identified 37,902 SLE (93% female, mean age 40.1 ± 12.1), 76,657 DM (93% female, mean age 40.0 ± 12.1), and 158,695 general Medicaid patients (93% female, mean age 40.2 ± 12.1). The IR per 1000-person years was 6.9 (95% CI 6.3-7.5) for SLE, 6.6 (95% CI 6.2-7.0) for DM, and 1.6 (95% CI 1.5-1.8) for general Medicaid patients. The highest IRR compared to general Medicaid was seen among SLE patients in age group 18-39 (14.7, 95% CI 13.9-15.5). Multivariable-adjusted HRs for HF compared to general Medicaid population were similar for SLE (2.7, 95% CI 2.3-3.1) and DM (3.0, 95% CI 2.6-3.4)., Conclusion: The incidence of HF among SLE patients was 2.7-fold higher than general Medicaid patients, and similar to DM. Further investigation into the biologic mechanism of HF among SLE compared to non-SLE and DM patients may shed light on the findings of this study., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In patients with diabetes, where cardiovascular morbidity is highly prevalent, recent cardiovascular outcomes trials have identified therapies in the modern glucagon-like peptide 1 receptor agonist (GLP-1RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) classes that significantly reduce cardiovascular events. A number of drugs in both classes have demonstrated reductions in the risk of the composite outcome of major adverse cardiovascular events (myocardial infarction, stroke, and cardiovascular death). In addition, SGLT2i drugs have a substantial impact on hospitalization for heart failure. Because GLP-1RA and SGLT2i are effective in reducing cardiovascular events, independent of their effects on blood glucose, cardiologists should be familiar with how to use them. This review outlines the evidence of cardiovascular benefit for current GLP-1RA and SGLT2i drugs, practical information for prescribing them, and putative mechanisms, so that these therapies can be incorporated along with antihypertensives, statins, and antiplatelet therapies into the routine care of patients., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)