The association of TNF inhibitor use with incident cardiovascular events in radiographic axial spondyloarthritis.

BACKGROUND: Whether tumor necrosis factor inhibitor (TNFi) use is cardioprotective among individuals with radiographic axial spondyloarthritis (r-axSpA), who have heightened cardiovascular (CV) risk, is unclear. We tested the association of TNFi use with incident CV outcomes in r-axSpA. METHODS: We identified a r-axSpA cohort within a Veterans Affairs database between 2002 and 2019 using novel phenotyping methods and secondarily using ICD codes. TNFi use was assessed as a time-varying exposure using pharmacy dispense records. The primary outcome was incident CV disease identified using ICD codes for coronary artery disease, myocardial infarction or stroke. We fit Cox models with inverse probability weights to estimate the risk of each outcome with TNFi use versus non-use. Analyses were performed in the overall cohort, and separately in two periods (2002-2010, 2011-2019) to account for secular trends. RESULTS: Using phenotyping we identified 26,928 individuals with an r-axSpA diagnosis (mean age 63.4 years, 94 % male); at baseline 3633 were TNFi users and 23,295 were non-users. During follow-up of a mean 3.3 ± 4.2 years, 674 (18.6 %) TNFi users had incident CVD versus 11,838 (50.8 %) non-users. In adjusted analyses, TNFi use versus non-use was associated with lower risk of incident CVD (HR 0.34, 95 % CI 0.29-0.40) in the cohort overall, and in the two time periods separately. CONCLUSION: In this r-axSpA cohort identified using phenotyping methods, TNFi use versus non-use had a lower risk of incident CVD. These findings provide reassurance regarding the CV safety of TNFi agents for r-axSpA treatment. Replication of these results in other cohorts is needed.

Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias.

BACKGROUND: Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT). METHODS: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies. RESULTS: Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicate NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate SCN5A, SCN10A, and TTN/CCDC141. Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals. CONCLUSIONS: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility.

Incidence and prognostic significance of newly-diagnosed atrial fibrillation among older U.S. veterans hospitalized with COVID-19.

Most prior studies on the prognostic significance of newly-diagnosed atrial fibrillation (AF) in COVID-19 did not differentiate newly-diagnosed AF from pre-existing AF. To determine the association between newly-diagnosed AF and in-hospital and 30-day mortality among regular users of Veterans Health Administration using data linked to Medicare. We identified Veterans aged ≥ 65 years who were hospitalized for ≥ 24 h with COVID-19 from 06/01/2020 to 1/31/2022 and had ≥ 2 primary care visits within 24 months prior to the index hospitalization. We performed multivariable logistic regression analyses to estimate adjusted risks, risk differences (RD), and odds ratios (OR) for the association between newly-diagnosed AF and the mortality outcomes adjusting for patient demographics, baseline comorbidities, and presence of acute organ dysfunction on admission. Of 23,299 patients in the study cohort, 5.3% had newly-diagnosed AF, and 29.2% had pre-existing AF. In newly-diagnosed AF adjusted in-hospital and 30-day mortality were 16.5% and 22.7%, respectively. Newly-diagnosed AF was associated with increased mortality compared to pre-existing AF (in-hospital: OR 2.02, 95% confidence interval [CI] 1.72-2.37; RD 7.58%, 95% CI 5.54-9.62) (30-day: OR 1.86; 95% CI 1.60-2.16; RD 9.04%, 95% CI 6.61-11.5) or no AF (in-hospital: OR 2.24, 95% CI 1.93-2.60; RD 8.40%, 95% CI 6.44-10.4) (30-day: 2.07, 95% CI 1.80-2.37; RD 10.2%, 95% CI 7.89-12.6). There was a smaller association between pre-existing AF and the mortality outcomes. Newly-diagnosed AF is an important prognostic marker for patients hospitalized with COVID-19. Whether prevention or treatment of AF improves clinical outcomes in these patients remains unknown.

New statin use, mortality, and first cardiovascular events in older US Veterans by frailty status.

BACKGROUND: Statins are part of long-term medical regimens for many older adults. Whether frailty modifies the protective relationship between statins, mortality, and major adverse cardiovascular events (MACE) is unknown. METHODS: This was a retrospective study of US Veterans ≥65, without CVD or prior statin use seen in 2002-2012, followed through 2017. A 31-item frailty index was used. The co-primary endpoint was all-cause mortality or MACE (MI, stroke/TIA, revascularization, or cardiovascular death). Cox proportional hazards models were developed to evaluate the association of statin use with outcomes; propensity score overlap weighting accounted for confounding by indication. RESULTS: We identified 710,313 Veterans (mean age (SD) 75.3(6.5), 98% male, 89% white); 86,327 (12.1%) were frail. Over mean follow-up of 8 (5) years, there were 48.6 and 72.6 deaths per 1000 person-years (PY) among non-frail statin-users vs nonusers (weighted Incidence Rate Difference (wIRD)/1000 person years (PY), -24.0[95% CI, -24.5 to -23.6]), and 90.4 and 130.4 deaths per 1000PY among frail statin-users vs nonusers (wIRD/1000PY, -40.0[95% CI, -41.8 to -38.2]). There were 51.7 and 60.8 MACE per 1000PY among non-frail statin-users vs nonusers (wIRD/1000PY, -9.1[95% CI, -9.7 to -8.5]), and 88.2 and 102.0 MACE per 1000PY among frail statin-users vs nonusers (wIRD/1000PY, -13.8[95% CI, -16.2 to -11.4]). There were no significant interactions by frailty for statin users vs non-users by either mortality or MACE outcomes, p-interaction 0.770 and 0.319, respectively. Statin use was associated with lower risk of all-cause mortality (HR, 0.61 (0.60-0.61)) and MACE (HR 0.86 (0.85-0.87)). CONCLUSIONS: New statin use is associated with a lower risk of mortality and MACE, independent of frailty. These findings should be confirmed in a randomized clinical trial.

Egg consumption and risk of acute stroke in the Million Veteran Program.

BACKGROUND: While observational data suggest a higher risk of coronary artery disease with frequent egg consumption, only limited and inconsistent data are available on the relation of egg consumption with stroke. OBJECTIVE: The primary objective was to assess whether egg consumption is associated with a higher risk of ischemic and hemorrhagic stroke among US veterans. METHODS: In a prospective cohort study of US veterans from the Million Veteran Program (MVP), egg intake was collected through a self-reported food frequency questionnaire at baseline. Incidence of stroke was ascertained via ICD9/ICD10 codes from the electronic health records. Multivariable Cox proportional hazard models were used to estimate the multivariable adjusted hazard ratios. RESULTS: A total of 233,792 veterans (91.6% men) were studied with a mean age of 65.6 ± 11.7 years. During a mean follow-up of 3.3 years, a total of 5740 cases of fatal and non-fatal ischemic stroke and 423 cases of fatal and non-fatal hemorrhagic stroke occurred. Median egg consumption was 2-4 eggs/week. Crude incidence rates for acute ischemic stroke were 6.5, 7.2, 7.1, 7.4, 8.0, 8.1, and 8.6 cases per 1000 person-years for egg consumption of <1/month, 1-3/month, 1/week, 2-4/week, 5-6/week, 1/day, and ≥2/day, respectively. Corresponding multivariable adjusted hazard ratios (95% CI) were 1.00 (ref), 1.10 (0.96-1.25), 1.09 (0.96-1.23), 1.10 (0.98-1.25), 1.16 (1.01-1.33), 1.20 (1.03-1.40), and 1.22 (1.03-1.45) controlling for age, sex, ethnicity, body mass index, diabetes, smoking, alcohol intake, modified DASH score, and education (p linear trend 0.0085). For hemorrhagic stroke, multivariable adjusted hazard ratios (95% CI) after controlling for age, sex, ethnicity, body mass index, modified DASH score, and level of education were 1.00 (ref), 1.28 (0.96-1.72), 1.22 (0.93-1.61), and 1.19 (0.88-1.61) for egg consumption of <1/week, 1/week, 2-4/week, 5+/week, respectively. CONCLUSION: Our data are consistent with a positive association of egg consumption with acute ischemic stroke but not hemorrhagic stroke among veterans.