BACKGROUND:F/TAF was shown to be noninferior to F/TDF as pre-exposure prophylaxis (PrEP) in men, but approval was not extended to cisgender women. We report the results of PrEPVacc, in which a predominantly female population was randomly allocated to receive daily oral F/TDF or F/TAF for ∼6 months within a HIV-1 prophylactic vaccine trial. SETTING:Four study sites in 3 African countries (Uganda, Tanzania, South Africa). METHODS:The 2 regimens were compared by the averted infections ratio (AIR)-the proportion of infections averted by F/TAF relative to F/TDF. The counterfactual HIV incidence, an essential component of this metric, was derived from a preceding registration cohort. Dried blood spots (DBS) were collected at regular time points for later assessment of tenofovir diphosphate levels in selected subpopulations. RESULTS:1380 participants (697 F/TDF, 683 F/TAF) were included in the primary analysis (total follow-up 709.2 person-years); 87% were cisgender women. Three HIV infections (0.86/100 person-years) occurred in the F/TAF group versus 2 in the F/TDF group (0.56/100 person-years). The counterfactual HIV incidence was estimated to be 2.59/100 person-years (90% CI: 1.86 to 3.52), giving an AIR of 0.85 (90% CI: 0.31 to 1.66). Based on the week 8 DBS sample, only an estimated 14% of participants were classified as taking 2-3 tablets per week and 9% ≥4 tablets per week. CONCLUSIONS:Despite similar HIV incidence rates, the noninferiority of F/TAF was not demonstrated, probably because of low statistical power primarily driven by low adherence. However, there is compelling evidence from multiple studies supporting the efficacy of F/TAF as PrEP regardless of sex.

Abstract Human gene therapy is defined as the introduction of new genetic material into the cells of an individual with the intention of producing a therapeutic benefit for that individual. Gene therapy may be applied to any infectious disease whereby the infecting organism inserts its own genetic material into the genome of the host cell genome.

Immunogens and vaccination regimens can influence patterns of immune-epitope recognition, steering them towards or away from epitopes of potential viral vulnerability. HIV-1 envelope (Env)-specific antibodies targeting variable region 2 (V2) or 3 (V3) correlated with protection during the RV144 trial, however, it was suggested that the immunodominant V3 region might divert antibody responses away from other relevant sites. We mapped IgG responses against linear Env epitopes in five clinical HIV vaccine trials, revealing a specific pattern of Env targeting for each regimen. Notable V2 responses were only induced in trials administering CRF01_AE based immunogens, but targeting of V3 was seen in all trials, with the soluble, trimeric CN54gp140 protein eliciting robust V3 recognition. Strong V3 targeting was linked to greater overall response, increased number of total recognised antigenic regions, and where present, stronger V2 recognition. Hence, strong induction of V3-specific antibodies did not negatively impact the targeting of other linear epitopes in this study, suggesting that the induction of antibodies against V3 and other regions of potential viral vulnerability need not be necessarily mutually exclusive.

PrEPVacc is an international, multi-centre, double-blind vaccine study comparing experimental combination vaccine regimens including DNA/AIDSVAX BE and DNA/CN54gp140 with placebo control. Simultaneously, daily oral PrEP is compared for efficacy against daily Truvada in the context of the current PrEP availability situation at the study sites. An important clinical trial outcome is the accurate measurement of in vivo antibody titer induced through vaccination. Here we report the validation of two ELISAs for CN54gp140 and AIDSVAX BE at Uganda Virus Research Institute that demonstrates precision, specificity, and robustness for assessing the reciprocal antibody end point titer in human serum. This is a critical endpoint for determining whether vaccination can provide any protection against HIV in populations at risk of acquiring HIV.

OBJECTIVE:Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts. DESIGN AND METHODS:Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time. RESULTS:In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3-4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes. CONCLUSION:This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.

Background: Although antiretroviral treatments have improved survival of persons living with HIV, their long-term use may limit available drug options. We estimated the prevalence of heavily treatment-experienced (HTE) status and the potential clinical consequences of becoming HTE. Setting: EuroSIDA, a European multicenter prospective cohort study. Methods: A composite definition for HTE was developed, based on estimates of antiretroviral resistance and prior exposure to specific antiretroviral regimens. Risks of progressing to clinical outcomes were assessed by Poisson regression, comparing every HTE individual with 3 randomly selected controls who never became HTE. Results: Of 15,570 individuals under follow-up in 2010–2016, 1617 (10.4%, 95% CI: 9.9% to 10.9%) were classified as HTE. 1093 individuals became HTE during prospective follow-up (HTE incidence rate 1.76, CI: 1.66 to 1.87 per 100 person-years of follow-up). The number of HTE individuals was highest in West/Central Europe (636/4019 persons, 15.7%) and lowest in East Europe (26/2279 persons, 1.1%). Although most HTE individuals maintained controlled viral loads (<400 copies/mL), many had low CD4 counts (≤350 cells/µL). After controlling for age, immunological parameters and pre-existing comorbidities, HTE status was not associated with the risk of new AIDS (adjusted incidence rate ratio, aIRR 1.44, CI: 0.86 to 2.40, P = 0.16) or non-AIDS clinical events (aIRR 0.96, CI: 0.74 to 1.25, P = 0.77). Conclusions: HTE prevalence increased with time. After adjusting for key confounding factors, there was no evidence for an increased risk of new AIDS or non-AIDS clinical events in HTE. Additional therapeutic options and effective management of comorbidities remain important to reduce clinical complications in HTE individuals.

DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P<0.001). In both groups, vaccine regimens induced HIV-specific polyfunctional CD4 and CD8 T cells and the production of Th1, Th2 and Th17/IL-21 cytokines. Antibody responses were also elicited in up to 81% of vaccines. A higher percentage of IgG responders was noted in the 2xDNA arm compared to the 3xDNA arm, while the 3xDNA group tended to elicit a higher magnitude of IgG3 response against specific Env antigens. We show here that the modulation of the prime strategy, without modifying the route or the dose of administration, or the combination of vectors, may influence the quality of the responses.

BackgroundPrevious trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI.MethodsRoutine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure.FindingsOf the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82–89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2–4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55–0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48–0·93).InterpretationThe survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.FundingNIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.

Background Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all‐cause mortality in real‐world patients presenting with AF. Methods and Results We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median follow‐up of 1462 (interquartile range, 929–1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associated with a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01–1.43; P<0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9–3.4) at ≈250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography. The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42–0.89; P=0.01). Conclusions Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.

Background: A better understanding of the parameters influencing vaccine-induced IgG recognition of individual antigenic regions and their variants within the HIV Envelope protein (Env) can help to improve design of preventive HIV vaccines.Methods: Env-specific IgG responses were mapped in samples of the UKHVC003 Standard Group (UK003SG, n = 11 from UK) and TaMoVac01 (TMV01, n = 17 from Tanzania) HIV vaccine trials. Both trials consisted of three immunizations with DNA, followed by two boosts with recombinant Modified Vaccinia Virus Ankara (MVA), either mediating secretion of gp120 (UK003SG) or the presentation of cell membrane bound gp150 envelopes (TMV01) from infected cells, and an additional two boosts with 5 μg of CN54gp140 protein adjuvanted with glucopyranosyl lipid adjuvant (GLA). Env immunogen sequences in UK003SG were solely based on the clade C isolate CN54, whereas in TMV01 these were based on clades A, C, B, and CRF01AE. The peptide microarray included 8 globally representative Env sequences, CN54gp140 and the MVA-encoded Env immunogens from both trials, as well as additional peptide variants for hot spots of immune recognition.Results: After the second MVA boost, UK003SG vaccinees almost exclusively targeted linear, non-glycosylated antigenic regions located in the inter-gp120 interface. In contrast, TMV01 recipients most strongly targeted the V2 region and an immunodominant region in gp41. The V3 region was frequently targeted in both trials, with a higher recognition magnitude for diverse antigenic variants observed in the UK003SG (p < 0.0001). After boosting with CN54gp140/GLA, the overall response magnitude increased with a more comparable recognition pattern of antigenic regions and variants between the two trials. Recognition of most immunodominant regions within gp120 remained significantly stronger in UK003SG, whereas V2-region recognition was not boosted in either group.Conclusions: IgG recognition of linear antigenic Env regions differed between the two trials particularly after the second MVA boost. Structural features of the MVA-encoded immunogens, such as secreted, monomeric gp120 vs. membrane-anchored, functional gp150, and differences in prime-boost immunogen sequence variability most probably contributed to these differences. Prime-boosting with multivalent Env immunogens during TMV01 did not improve variant cross-recognition of immunodominant peptide variants in the V3 region.

Background Trials and registry studies suggest lower long-term mortality after invasive than medical management among patients with non-ST elevated myocardial infarction (NSTEMI), but elderly patients were underrepresented. The aim of our study was to estimate the effect of invasive compared with medical management on survival in patients with NSTEMI aged ≥80 years, using routine clinical data. Methods We used National Institute for Health Research Health Informatics Collaborative data to identify eligible patients admitted during 2010–2017 at five tertiary centres. We compared patients who did and did not have invasive management within 3 days of their peak troponin level. To limit the effect of immortal time bias, follow-up started 3 days after peak troponin: deaths within three days were excluded. We conducted intention-to-treat analyses. Propensity scores were derived from a logistic regression model based on pre-treatment variables: patient demographics, blood test results, cardiovascular risk factors, history of cardiovascular disease and other comorbidities. We modelled non-linear relationships using splines. Patients with high probability (based on propensity score) of medical or invasive intervention were excluded. We used Cox models to estimate hazard ratios (HR) comparing invasive with medical management. Three methods were used to control confounding; multivariable-adjusted, multivariable-adjusted additionally for continuous propensity score and inverse-probability-of-treatment (IPT) weighting. Kaplan-Meier survival curves were plotted. The robustness of the results to unmeasured confounding was assessed in sensitivity analyses. Results The 1,636 patients (59.8% medical management) included in analyses had a median age of 85 (IQR 82–89) years. During a median follow-up of 32.4 (IQR 11.5–53.9) months, there were 717 (43.8%) deaths. At 3-years, cumulative survival was 76.9% and 53.6% in the invasive and medical management groups, respectively (figure 1). The crude HR comparing invasive with medical management was 0.41 (95% CI 0.34–0.50). The multivariable-adjusted HR was 0.51 (95% CI 0.42–0.63), was 0.50 (95% CI 0.40–0.61) with additional adjustment for propensity score, and was 0.54 (95% CI 0.48–0.61) in the IPT-weighted model (all p<0.0001). The E-value for the point estimate was 2.61: this implies that residual confounding could explain the association if there is an unmeasured covariate with a relative risk of at least 2.61 for both mortality and undergoing invasive management. The highest mortality HR for comorbidities included in our model were heart failure (HR 2.06 (95% CI 1.60–2.63)) and aortic stenosis (HR 1.95 (95% CI 1.42–2.67)).Abstract 57 Figure 1 Cumulative survival in the invasive and medical management groups Conclusion This study provides evidence that the survival advantage from invasive management may extend to elderly patients with NSTEMI. Future research should address the possibility of unmeasured confounding, including by post-admission prognostic factors that affect choice of invasive or medical management. Conflict of Interest No conflict of interest

Objectives: The aim of this study was to investigate associations between baseline characteristics and CD4 cell count response on first-line antiretroviral therapy and risk of virological failure (VF) with or without drug resistance. Methods: We conducted an analysis of UK Collaborative HIV Cohort data linked to the UK HIV Drug Resistance Database. Inclusion criteria were viral sequence showing no resistance prior to initiation of first-line efavirenz +tenofovir disoproxil fumarate +emtricitabine and virological suppression within 6 months. Outcomes of VF (>= 200 copies/mL) with or without drug resistance were assessed using a competing risks approach fitted jointly with a model for CD4 cell count recovery. Hazard ratios for each VF outcome were estimated for baseline CD4 cell count and viral load and characteristics of CD4 cell count response using latent variables on a standard normal scale. Results: A total of 3640 people were included with 338 VF events; corresponding viral sequences were available in 134 with >= 1 resistance mutation in 36. VF with resistance was associated with lower baseline CD4 (0.30, 0.09-0.62), lower CD4 recovery (0.04, 0.00-0.17) and higher CD4 variability (4.40, 1.22-12.68). A different pattern of associations was observed for VF without resistance, but the strength of these results was less consistent across sensitivity analyses. Cumulative incidence of VF with resistance was estimated to be <2% at 3 years for baseline CD4 350 cells/L. Conclusion: Lower baseline CD4 cell count and suboptimal CD4 recovery are associated with VF with drug resistance. People with low CD4 cell count before ART or with suboptimal CD4 recovery on treatment should be a priority for regimens with high genetic barrier to resistance.

Soluble forms of the coinhibitory receptors programmed death 1 (PD-1) and Tim-3 exist, but their relationship with T-cell surface expression remains unclear. When measured by an enzyme-linked immunosorbent assay in plasma, soluble PD-1, and soluble Tim-3 were elevated during primary HIV infection, decreased on antiretroviral therapy to levels found in controls, and correlated with cell surface expression. We conclude that soluble PD-1 and soluble Tim-3 are easy to measure biomarkers of immune exhaustion which potentially eliminate the need for flow cytometry.

M icrobes, including myriad pathogens, have demon- strated their tenacity and malleability to endure, even flourish, under extreme conditions thought to be inhospitable to life.These microbes evolve at a pace that proves hard to fathom: they can undergo as many as 500,000 generations during a single human generation.The proliferation and abundance of modern antibiotics have accelerated the pace of pathogens' evolutionary adaptation through mutation and acquisition of genetic material conferring resistance from other species.The World Health Organization notes that new resistance mechanisms are emerging and spreading around the world and that without effective antimicrobials, treating infectious diseases is becoming increasingly challenging.Researchers Julian and Dorothy Davies offer this perspective: "What happened during

Abstract Objective To determine the relation between age and troponin level and its prognostic implication. Design Retrospective cohort study. Setting Five cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC). Participants 257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017. Main outcome measure All cause mortality. Results 257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient’s hospital stay. Troponin levels were standardised as a multiple of each laboratory’s 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively. Conclusions A positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks. Study registration ClinicalTrials.gov NCT03507309.

The incremental long-term prognostic value of hsCRP above troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We used the National Institute for Health Research (NIHR) Health Informatics Collaborative (NHIC) data of 257948

Objectives In subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data. Methods We analysed 1710 subjects who started a PI/b in combination with tenofovir or abacavir plus emtricitabine or lamivudine, and compared their virological outcomes with those of 4889 patients who started an NNRTI (predominantly efavirenz), according to the presence of 1 TAM as the sole form of transmitted drug resistance. Results Participants with 1 TAM comprised predominantly MSM (213 of 269, 79.2%), subjects of white ethnicity (206 of 269, 76.6%) and HIV-1 subtype B infections (234 of 269, 87.0%). Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). Over a median of 2.5years of follow-up, 834 of 6599 (12.6%) subjects experienced viraemia (HIV-1 RNA >50 copies/mL). The adjusted HR for viraemia was 2.17 with PI/b versus NNRTI-based therapy (95% CI 1.88-2.51; P<0.001). Other independent predictors of viraemia included injecting drug use, black ethnicity, higher viral load and lower CD4 cell count at baseline, and receiving abacavir instead of tenofovir. Resistance showed no overall impact (adjusted HR 0.77 with 1 TAM versus no resistance; 95% CI 0.54-1.10; P=0.15). Conclusions In this cohort, patients harbouring 1 TAM as the sole form of transmitted drug resistance gained no apparent virological advantage from starting first-line ART with a PI/b.

Limited evidence suggests a direct relationship between the magnitude of troponin elevation and mortality over a limited range of troponin levels. We investigated the relationship between troponin and mortality across the full spectrum of troponin levels using big data analytics. We used the

The clinical importance of troponin level in patients presenting with atrial fibrillation (AF) is uncertain. We investigated the relationship between troponin level, angiography and mortality in patients undergoing troponin testing with a primary diagnosis of AF. We used the National Institute for

Background Patients presenting with atrial fibrillation (AF) often undergo measurement of troponin level, but interpretation of the result is impeded by uncertainty around its clinical importance. Although coronary artery disease (CAD) has been implicated in the prognostic significance of troponin levels in AF, the role of investigating for CAD and its effect on mortality remain unclear. We investigated the relationship between troponin level, coronary angiography and all-cause mortality in real-world patients presenting with AF. Methods We utilised National Institute for Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centres with a primary diagnosis of AF who underwent at least one troponin measurement. Patients meeting the eligibility criteria were followed up using routinely collected data, until death or censoring in April 2017. The peak troponin result during the index admission was scaled across assays as multiples of the upper limit of normal (xULN). To model non-linear relationships, we used restricted cubic splines for regression analyses. Results 3,121 patients were included in the analysis. Over a median follow-up of 48.1 (IQR 30.5–64.9) months, there were 586 (18.8%) deaths. While troponin levels below 1.3 xULN showed no significant relationship with hazard ratio, at higher troponin levels, a significant positive relationship was demonstrated (figure 1A). 216 (6.9%) patients underwent coronary angiography, with 78 (36.1%) of these patients subsequently undergoing coronary revascularisation. Above the ULN, there was a positive relationship between troponin level and odds of angiography (figure 1B). While there was no significant relationship between troponin level and mortality in patients who underwent angiography (figure 1C), a significant relationship was observed in patients who did not undergo angiography with troponin levels above the ULN (figure 1D). On cox regression analysis, following adjustment for demographic and clinical factors, including troponin level, angiography was associated with a 39% reduction in mortality during follow-up (hazard ratio 0.61, 95% CI 0.42–0.89, p=0.01). Conclusion Above the ULN, higher troponin levels were associated with higher mortality. Within the normal range, this was not the case. While angiography was not common in patients presenting with AF, the likelihood of angiography increased at higher troponin levels. In cases where angiography was not performed, there was a direct relationship between troponin levels above the ULN and mortality; this was not evident where angiography was performed. Following adjustment for troponin level, angiography was associated with a significant reduction in mortality. The risk of mortality in patients presenting with AF may be mediated by CAD. Clinical trials are warranted to clarify the investigation and treatment of CAD in patients presenting with AF with elevated troponin levels. Conflict of Interest No conflicts of interest