Future Myocardial Infarction Research Articles

The association between serum high-sensitivity cardiac troponin T and acute myocardial infarction in patients with suspected chronic coronary syndrome is modified by body mass index

BackgroundHigher systemic concentrations of cardiac troponins and biomarkers of inflammation and endothelial dysfunction as well as obesity are associated with increased risk of cardiovascular disease (CVD) and may share pathophysiological pathways. We sought to explore the association between serum high sensitive cardiac troponin T (hs-cTnT) and future acute myocardial infarction (AMI) according to body mass index (BMI) among patients with suspected chronic coronary syndrome (CCS), as well as interactions with C-reactive protein (CRP) and asymmetric dimethylarginine (ADMA). MethodsA total of 3879 patients with baseline hs-cTnT ≤ 30 ng/L who underwent elective coronary angiography due to chronic coronary syndrome (CCS) were followed to subsequent AMI or end of 2009. Risk associations between hs-cTnT and incident AMI were explored with Cox regression according to BMI categories <25 kg/m 2, 25–30kg/m2 and >30kg/m2 and quartiles of serum CRP and plasma ADMA. ResultsMedian (25 th −75 th percentile) age was 62 (54–69) years and 2773 (77.5%) were men. During median 7.5 (25 th −75 th percentile) (6.9–9.2) years of follow-up, 460 (11.9%) patients experienced an AMI. The risk relationship between hs-cTnT and incident AMI was stronger among patients in the higher vs lower BMI categories, HR 1.087 (1.055–1.119), P for interaction 0.043. A similar interaction was not found in categories of CRP or ADMA. ConclusionThe risk relationship of hs-cTnT with incident AMI was stronger in patients with higher BMI. Our results motivate further studies into potential pathophysiological mechanisms connecting hs-cTnT with increased cardiovascular risk.

Risk of Stroke, Myocardial Infarction, and Death Among Patients With Retinal Artery Occlusion and the Effect of Antithrombotic Treatment.

PurposeTo evaluate the risk of future stroke, myocardial infarction (MI), and death of patients with retinal artery occlusion (RAO) and the effect of various antithrombotic treatments as secondary prevention.MethodsThis cohort study was based on nationwide health registries and included the entire Danish population from 2000 to 2018. All patients with RAO were identified and their adjusted risks of stroke, MI, or death in time periods since RAO were compared with those of the Danish population. Furthermore, antithrombotic treatment of patients with RAO was determined by prescription claims, and the association with the risk of stroke, MI, or death was assessed using multivariate Poisson regression models and expressed as rate ratios (RR) with 95% confidence intervals (95% CIs).ResultsAfter inclusion, 6628 individuals experienced a first-time RAO, of whom 391 had a stroke, 66 had a MI, and 402 died within the first year after RAO. RAO was associated with an increased risk of stroke, MI, or death which persisted for more than 1 year for all three outcomes but was highest on days 3 to 14 after RAO for stroke, with an adjusted RR of 50.71 (95% CI, 41.55–61.87), and on days 14 to 90 after RAO for MI and death, with adjusted RRs of 1.98 (95% CI, 1.25–3.15) and 1.64 (95% CI, 1.28–189), respectively. Overall, antithrombotic treatment was not associated with any protective effect the first year.ConclusionsPatients with RAO had an increased risk of stroke, MI, or death. No protective effect of antithrombotic treatment was shown.Translational RelevanceThese findings are relevant to the management of patients with RAO.

Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk of a future first-ever myocardial infarction in women

Impaired renal function is associated both with the development of cardiovascular disease and its prognosis. A new syndrome called ′Shrunken Pore Syndrome′ has been suggested, as the estimated glomerular filtration rate for cystatin C (eGFRcystatin C) is affected earlier due to differences in molecular size compared to eGFRcreatinine. The aim was to investigate if a lower eGFRcystatin C/eGFRcreatinine ratio in a prospective setting increases the risk of later developing a first-ever myocardial infarction (MI) independently of other cardiovascular risk factors. We used a nested case-referent study design within the Northern Sweden Health and Disease Study, and 545 subjects (29.0% women) were identified who prospectively developed a first-ever MI, and their 1054 matched referents. For women, but not for men, one standard deviation (SD) increase of ln z-scores of eGFRcystatin C/eGFRcreatinine ratio was associated with a lower risk of a future MI: odds ratio [95% confidence interval] 0.58 [0.34–0.99], adjusted for apolipoprotein B/A1 ratio, CRP, homocysteine, systolic blood pressure, body mass index, and diabetes. Furthermore, a high eGFRcreatinine associated independently with an increased risk of future MI in men only: OR 1.25 [1.05–1.48]. Thus, for women, a lower eGFRcystatin C/eGFRcreatinine ratio is associated with a higher risk of having a future first-ever MI, and it may be a valuable, easily implemented biomarker for risk of cardiovascular disease.

Panoramic imaged carotid atheromas are associated with increased neutrophil count: both validated, independent predictors of near-term myocardial infarction

Panoramic images (PXs) demonstrating calcified carotid artery atheromas (CCAAs) are associated with heightened risk of near-term myocardial infarction (MI). Elevated neutrophil counts (NC) within normal range 2,500-6,000 per mm3 are likewise associated with future MI signaling the role neutrophils play in the chronic inflammation process underlying coronary artery atherogenesis. We determined if CCAAs on PXs are associated with increased NC. Investigators implemented a retrospective study of PXs and accompanying medical records of white males ≥ 65 years treated by a VA dental service. Two groups (N = 60 each) were constituted, one with atheromas (CCAA+) and one without (CCAA-). Predictor variable was CCAA + and outcome variable was NC. Bootstrapping analysis determined the difference in mean NCs between two groups, significance set at ≤0.05. The study group of (CCAA+) (mean age 75.9; range 69-91 years) demonstrated a mean NC of 4,843 per mm3 and control group (CCAA-) (mean age 75.3; range; 66-94) a mean NC of 4,108 per mm3. The difference between the groups was significant (p = 0.0008) (95% CI of difference of mean: -432, 431; observed effect size 736). CCAAs on PXs of elderly white males are associated with elevated NC; amplifying need for medical consultation prior to invasive dental procedures.

The beneficial effect over 3 years by pictorial information to patients and their physician about subclinical atherosclerosis and cardiovascular risk: Results from the VIPVIZA randomized clinical trial

ObjectiveNon-adherence to guidelines and preventive measures is a major challenge, particularly so to obtain long-term adherence to lifestyle changes and recommended medication. The objective was to investigate if pictorial information regarding subclinical carotid atherosclerosis provided to individuals and physicians gave sustained effects on cardiovascular risk beyond the previously reported effect after 1 year and up to 3 years. MethodsA Prospective Randomized Open Blinded End-point (PROBE) trial. Within a CVD prevention program in Västerbotten County, Sweden, 3532 healthy individuals aged 40, 50 or 60 years were enrolled and 1:1 randomized to intervention (n = 1749; pictorial information with additional prevention materials to participants and physicians) or control group (n = 1783; no pictorial information to participants and physicians). Preventive measures were managed within primary care. Participants were investigated at baseline during 2013–2016 and at follow-up after 1 and 3 years. ResultsA beneficial effect on cardiovascular risk was observed at 3-year follow-up; Framingham Risk Score (FRS) was 13.38 for the intervention group and 14.08 for the control group (p = 0.047) and SCORE was 1.69 vs. 1.82 (p = 0.022). The effect observed at 1-year was sustained over 3 years after adjustment for sex and education and more pronounced among participants with a severe atherosclerotic picture at baseline. ConclusionsThis study provides evidence of sustained beneficial effects on the adherence to prevention guidelines over 3 years of pictorial information about subclinical carotid atherosclerosis, resulting in lower cardiovascular risk regardless of sex and educational level. Direct visualization of the underlying still subclinical atherosclerotic disease, rather than just indirect information about risk factors and statistical risk of future myocardial infarction, stroke and death, is one way to tackle the problem of non-adherence to prevention of cardiovascular diseases.

IL-6 as a Mediator of the Association Between Traditional Risk Factors and Future Myocardial Infarction: A Nested Case-Control Study.

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Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Deep Learning From Coronary Computed Tomography Angiography for Atherosclerotic Plaque and Stenosis Quantification and Cardiac Risk Prediction

Background: Atherosclerotic plaque quantification from coronary computed tomography angiography (CCTA) enables accurate assessment of coronary artery disease burden and prognosis. We sought to develop and externally validate a deep learning (DL) system for CCTA-derived measures of plaque volume and stenosis severity. Methods: This was an international multicenter study of patients undergoing CCTA at 11 sites. A novel DL convolutional neural network was trained to segment coronary plaque in 921 patients (5,045 lesions). The DL network was then applied to an independent test set, which included an external validation cohort of 175 patients (1,081 lesions) as well 50 patients (84 lesions) assessed by intravascular ultrasound (IVUS) within one month of CCTA. Thereafter, we evaluated the prognostic value of DL-based plaque measurements for fatal or nonfatal myocardial infarction (MI) in 1,611 patients from the prospective SCOT-HEART trial. Findings: In the overall test set, there was excellent agreement between DL and expert reader measurements of total plaque volume (intraclass correlation coefficient [ICC] 0·964) and percent diameter stenosis (ICC 0·879; both p<0.001). When compared with IVUS, there was excellent agreement for DL total plaque volume (ICC 0·949) and minimal luminal area (ICC 0·904). The average per-patient DL plaque analysis time was 5.7 seconds versus 25-30 minutes taken by experts. Over a median follow-up of 4·7 years, MI occurred in 41 patients (2·5%) from the SCOT-HEART trial. DL-based total plaque volume ≥238·5mm 3 was associated with an increased risk of MI (HR 5·36, 95% CI 1·70-16·86; p=0·004) after adjustment for the presence of DL-based obstructive stenosis (HR 2·49, 95% CI 1·07-5·50; p=0·009) and the cardiovascular risk score (HR 1·01, 95% CI 0·99-1·04; p=0·35). Interpretation: A novel externally validated DL system provides rapid measurements of plaque volume and stenosis severity from CCTA which agree closely with expert readers and IVUS and carry prognostic value for future MI. Funding: National Heart, Lung, and Blood Institute. Declaration of Interest: Outside of the current work, S.C., P.S., and D.D. received software royalties from Cedars-Sinai Medical Center. D.B, P.S., and D.D. hold a patent (US8885905B2 in USA and WO patent WO2011069120A1, Method and System for Plaque Characterization). All other authors have nothing to declare. Ethical Approval: This work was approved by the Institutional Review Boards and all patients provided written informed consent.

Cardiac Troponin Assays With Improved Analytical Quality: A Trade-Off Between Enhanced Diagnostic Performance and Reduced Long-Term Prognostic Value.

BackgroundCardiac troponin (cTn) permits early rule‐out/rule‐in of patients admitted with possible non–ST‐segment–elevation myocardial infarction. In this study, we developed an admission and a 0/1 hour rule‐out/rule‐in algorithm for a troponin assay with measurable results in >99% of healthy individuals. We then compared its diagnostic and long‐term prognostic properties with other protocols.Methods and ResultsBlood samples were collected at 0, 1, 3, and 8 to 12 hours from patients admitted with possible non–ST‐segment–elevation myocardial infarction. cTnT (Roche Diagnostics), cTnI(Abbott) (Abbott Diagnostics), and cTnI(sgx) (Singulex Clarity System) were measured in 971 admission and 465 1‐hour samples. An admission and a 0/1 hour rule‐out/rule‐in algorithm were developed for the cTnI(sgx) assay and its diagnostic properties were compared with cTnTESC (European Society of Cardiology), cTnI(Abbott)ESC, and 2 earlier cTnI(sgx) algorithms. The prognostic composite end point was all‐cause mortality and future nonfatal myocardial infarction during a median follow‐up of 723 days. non–ST‐segment–elevation myocardial infarction prevalence was 13%. The novel cTnI(sgx) algorithms showed similar performance regardless of time from symptom onset, and area under the curve was significantly better than comparators. The cTnI(sgx)0/1 hour algorithm classified 92% of patients to rule‐in or rule‐out compared with ≤78% of comparators. Patients allocated to rule‐out by the prior published 0/1 hour algorithms had significantly fewer long‐term events compared with the rule‐in and observation groups. The novel cTnI(sgx)0/1 hour algorithm used a higher troponin baseline concentration for rule‐out and did not allow for prognostication.ConclusionsIncreasingly sensitive troponin assays may improve identification of non–ST‐segment–elevation myocardial infarction but could rule‐out patients with subclinical chronic myocardial injury. Separate protocols for diagnosis and risk prediction seem appropriate.

Anatomic and Flow Characteristics of Left Anterior Descending Coronary Artery Angiographic Stenoses Predisposing to Myocardial Infarction

The impact of the anatomic characteristics of coronary stenoses on the development of future coronary thrombosis has been controversial. This study aimed at identifying the anatomic and flow characteristics of left anterior descending (LAD) coronary artery stenoses that predispose to myocardial infarction, by examining angiograms obtained before the index event. We identified 90 patients with anterior ST-elevation myocardial infarction (STEMI) for whom coronary angiograms and their reconstruction in the three-dimensional space were available at 6 to 12 months before the STEMI, and at the revascularization procedure. The majority of culprit lesions responsible for STEMI occurred between 20 and 40 mm from the LAD ostium, whereas the majority of stable lesions not associated with STEMI were found in distances >60 mm (p < 0.001). Culprit lesions were significantly more stenosed (diameter stenosis 68.6 ± 14.2% vs 44.0 ± 10.4%, p < 0.001), and significantly longer than stable ones (15.3 ± 5.4 mm vs 9.2 ± 2.5 mm, p < 0.001). Bifurcations at culprit lesions were significantly more frequent (88.8%) compared with stable lesions (34.4%, p < 0.001). Computational fluid dynamics simulations demonstrated that hemodynamic conditions in the vicinity of culprit lesions promote coronary thrombosis due to flow recirculation. A multiple logistic regression model with diameter stenosis, lesion length, distance from the LAD ostium, distance from bifurcation, and lesion symmetry, showed excellent accuracy in predicting the development of a culprit lesion (AUC: 0.993 [95% CI: 0.969 to 1.000], p < 0.0001). In conclusion, specific anatomic and hemodynamic characteristics of LAD stenoses identified on coronary angiograms may assist risk stratification of patients by predicting sites of future myocardial infarction.

Socio-Economic Burden of Myocardial Infarction Among Cancer Patients

Cancer patients face a higher risk of future myocardial infarction (MI), even after completion of anticancer therapies. MI is a critical source of physical and financial stress in noncancer patients, but its impacts associated with cancer patients also saddled with the worry (stress) of potential reoccurrence is unknown. Therefore, we aimed to quantify MI's stress and financial burden after surviving cancer and compare to those never diagnosed with cancer. Utilizing cross-sectional national survey data from 2013 to 2018 derived from publicly available United States datasets, the National Health Interview Survey , and economic data from the National Inpatient Sample , we compared the socio-economic outcomes in those with MI by cancer-status. We adjusted for social, demographic, and clinical factors. Overall, 19,504 (10.2%) of the 189,836 National Health Interview Survey responders reported having cancer for more than 1 year. There was an increased prevalence of MI in cancer survivors compared with noncancer patients (8.8% vs 3.2%, p <0.001). MI was associated with increased financial worry, food insecurity, and financial burden of medical bills (p <0.001, respectively); however, concurrent cancer did not seem to be an effect modifier (p >0.05). There was no difference in annual residual family income by cancer status; however, 3 lowest deciles of residual income representing 21.1% cancer-survivor with MI had a residual income of <$9,000. MI continues to represent an immense source of financial and perceived stress. In conclusion, although cancer patients face a higher risk of subsequent MI, this does not appear to advance their reported stress significantly.

Abstract 16587: More Than Five Years After FDA Approval, There Remains Very Limited Adoption of New Evidence-Based, Highly Effective Medications for the Treatment of Patients With Heart Failure, Especially Among Those on Medicare

Background: Over the past decade, the FDA has approved several new medications that are highly effective when added to existing standard therapy in the treatment of heart failure with reduced ejection fraction (HFrEF). It is possible that, despite the presence of substantial evidence regarding the clinical effectiveness of these new medications, their high cost and the complex medical reimbursement system in America may prevent their routine adoption. Methods: We analyzed 5,824 Intermountain Healthcare patients, age ≥18 years with a new clinical diagnosis of HFrEF (LVEF ≤35%), from 1/1/2015 onward, for the use of newly-approved sacubitril/valsartan or any sodium-glucose cotransporter-2 inhibitor (SGLT2-I). We collected baseline characteristics and medication utilization data. We followed the patients for 1.7±1.4 years for future major adverse cardiovascular events (MACE), including death, myocardial infarction (MI), stroke, and heart failure hospitalization (HFH). We identified differences between groups by multivariable Cox regression analysis. Results: Baseline characteristics and incidence of MACE, according to insurance status and the use of common HFrEF medications, are shown in the Table. Overall, only 344 (5.9%) and 169 (2.9%) of patients ever received a prescription for sacubitril/valsartan or an SGLT2 inhibitor, respectively. The figures show survival curves for MACE of patients receiving or not receiving the newly-approved medications. Conclusion: In this large, modern, real-world HFrEF population, the adoption of newly-approved evidence-based HFrEF medications is minimal in all patients and especially in Medicare patients. This lack of adoption is associated with a significant worsening in patient outcomes. These findings demonstrate a critical need to resolve our present healthcare financial crisis, which is almost certainly the reason for these findings.

Elevated White Blood Cell Count Resultant Atherogenesis is Associated With Panoramic-Imaged Carotid Plaque

Atherosclerotic plaques develop as a result of a low-grade, chronic, systemic inflammatory response to the injury of endothelial cells arising from lipid deposition within the intima. Increased white blood cell count (WBCC) is both a validated "biologic marker" of the extent of this inflammatory process and a key participant in the development of subsequent atherosclerotic ischemic heart disease manifesting as myocardial infarction. We sought to determine if calcified carotid artery plaque (CCAP) on a panoramic image (PI), also a validated risk indicator of future myocardial infarction, is associated with increased WBCC. We retrospectively evaluated the PI and medical records of White male military veterans aged 55years and older treated by a VA dental service. Established were 2 cohorts of patients, 50 having plaques (CCAP+) and 50 without plaques (CCAP-). Predictor variable was CCAP+; outcome variable was WBCC. Bootstrapping analysis determined the differences in mean WBCCs between groups. Statistical significance set at ≤ 0.05. The study group, (mean age 74; range 59 to 91years) demonstrated a mean WBCC of 8,062 permm3. The control group, (mean age 72 range; 57 to 94) evidenced a mean WBCC of 7,058 permm3. Bootstrapping analysis of WBCC values demonstrated a significant (P=.012) difference (95% confidence interval of difference of mean, -806, 742; observed effect size, 1004) between groups. The presence of CCAP demonstrated on PIs of older Caucasian men is associated with elevated WBCC. Concomitant presence of CCAP on PI and increased WBCC (≥7,800 per mm3) amplifies need for medical consultation before intravenous anesthesia and maxillofacial surgical procedures.

Size of low wall shear stress areas in coronary arteries is related to epicardial physiology and not to microcirculatory resistance

Abstract Background Wall shear stress (WSS) plays an important role in coronary atherosclerosis. Low WSS is associated with inflammation, endothelial dysfunction, and progression of atherosclerosis; while high WSS leads to vulnerable plaque transformation and future myocardial infarction. Defining the relationship between WSS and the currently available coronary physiology indices would provide valuable insights into potential mechanisms for predicting future adverse cardiac events. Purpose To investigate the relationship between WSS and the coronary epicardial/microvascular physiology indices. Methods Patients undergoing coronary angiography and physiology testing were prospectively recruited. Physiology measurements were performed under resting and hyperaemic conditions using a pressure/temperature sensor guidewire. Fractional flow reserve (FFR), non-hyperaemic pressure ratios (NHPRs), coronary flow reserve (CFR), and corrected index of microcirculatory resistance (IMR) were measured. The NHPRs including resting full-cycle ratio (RFR), resting distal/aortic pressure (Pd/Pa), instantaneous wave-free ratio (iFR), diastolic pressure ratio (dPR) and diastolic hyperaemia-free ratio (DFR) were derived offline by a blinded expert reader. Values of FFR ≤0.80, NHPR ≤0.89, CFR &amp;lt;2, or IMR &amp;gt;25 were considered ischaemic/abnormal. Computational fluid dynamics analysis was performed and fluid motion equations were solved using finite-volume based software. The inlet and outlet boundary conditions were set to the patient-specific Pa and Pd respectively. The lesion WSS, mean WSS in five segments (WSSupstream = 5mm proximal to lesion, WSSprox = proximal third of lesion, WSSmid = middle third of lesion, WSSdistal = distal third of lesion, WSSdownstream = 5mm distal to lesion), and the total area of low WSS (defined as &amp;lt;1 Pa) along the entire vessel were calculated (Figure A). Results A total of 112 vessels from 93 patients were included in the study. The total area of low WSS was significantly larger in lesions with ischaemic FFR, NHPRs, and CFR values (Figure B), and not significantly different in lesions with abnormal IMR values. There was no significant difference in lesion WSS between groups stratified by all physiology indices. Within the lesion WSS sub-segments, WSSprox was significant higher in ischaemic lesions stratified by normal/abnormal FFR, iFR, and dPR (4.2 vs 3.3 Pa, 4.2 vs 3.3 Pa, 4.3 vs 3.3 Pa respectively, all p=0.04), and not significantly different when stratified by RFR, DFR, Pd/Pa, CFR, and IMR. Conclusion Functionally significant coronary lesions classified by the epicardial physiology indices have significantly larger total area of low WSS and higher WSSprox which may explain the higher cardiovascular event rates in patients with ischaemic lesions. There was no significant relationship between WSS and coronary microcirculatory resistance. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation of Australia Health Professional Scholarship

Triglyceride-Rich Lipoprotein Cholesterol, Small Dense LDL Cholesterol, and Incident Cardiovascular Disease

BackgroundElevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease. ObjectivesThe purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD). MethodsIn a prospective case-cohort study within the Women’s Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. ResultsThe risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; ptrend = 0.002; PAD HRQ4: 2.58 [95% CI: 1.18 to 5.63]; ptrend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HRQ4: 3.71 [95% CI: 1.59 to 8.63]; ptrend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl). ConclusionsTRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women’s Health Study; NCT00000479)

Iron Metabolism Contributes to Prognosis in Coronary Artery Disease: Prognostic Value of the Soluble Transferrin Receptor Within the AtheroGene Study.

BackgroundCoronary heart disease is a leading cause of mortality worldwide. Iron deficiency, a frequent comorbidity of coronary heart disease, causes an increased expression of transferrin receptor and soluble transferrin receptor levels (sTfR) levels, while iron repletion returns sTfR levels to the normal physiological range. Recently, sTfR levels were proposed as a potential new marker of iron metabolism in cardiovascular diseases. Therefore, we aimed to evaluate the prognostic value of circulating sTfR levels in a large cohort of patients with coronary heart disease.Methods and ResultsThe disease cohort comprised 3423 subjects who had angiographically documented coronary heart disease and who participated in the AtheroGene study. Serum levels of sTfR were determined at baseline using an automated immunoassay (Roche Cobas Integra 400). Two main outcomes were considered: a combined end point of myocardial infarction and cardiovascular death and cardiovascular death alone. During a median follow‐up of 4.0 years, 10.3% of the patients experienced an end point. In Cox regression analyses for sTfR levels, the hazard ratio (HR) for future cardiovascular death and/or myocardial infarction was 1.27 (95% CI, 1.11–1.44, P<0.001) after adjustment for sex and age. This association remained significant (HR, 1.23; 95% CI, 1.03–1.46, P=0.02) after additional adjustment for body mass index, smoking status, hypertension, diabetes mellitus, dyslipidemia, C‐reactive protein, and surrogates of cardiac function, size of myocardial necrosis (hs‐Tnl), and hemoglobin levels.ConclusionsIn this large cohort study, sTfR levels were strongly associated with future myocardial infarction and cardiovascular death. This implicates a role for sTfR in secondary cardiovascular risk prediction.

Complement Activation in Association with Markers of Neutrophil Extracellular Traps and Acute Myocardial Infarction in Stable Coronary Artery Disease.

Complement activation and neutrophil extracellular traps (NETs) have both been suggested to drive atherosclerotic plaque progression. Although experimental studies suggest interplay between these two innate immunity components, the relevance in patients with coronary artery disease (CAD) is unclear. The aim of this study was to assess associations between complement activation and NETs in patients with stable CAD and examine the role of complement activation on clinical outcome. Blood samples from a cohort of patients with angiographically verified stable CAD (n = 1001) were analyzed by ELISA for the terminal complement complex (TCC) and by relative quantification for gene expression of the C5a receptor 1 (C5aR1) as markers of complement activation. As markers of NETs, dsDNA was analyzed by fluorescent nucleic acid stain and myeloperoxidase-DNA (MPO-DNA) by ELISA. Clinical outcome was defined as unstable angina, nonhemorrhagic stroke, acute myocardial infarction (MI), or death (n = 106, whereof 36 MI). Levels of TCC and C5aR1 were not significantly correlated to dsDNA (TCC: r = −0.045, p = 0.153; C5aR1: r = −0.060, p = 0.434) or MPO-DNA (TCC: r = 0.026, p = 0.414; C5aR1: r = 0.123, p = 0.107). When dividing TCC and C5aR1 levels into quartiles (Q), levels of MPO-DNA differed significantly across quartiles (TCC: p = 0.008, C5aR1: 0.049), while dsDNA did not (TCC: p = 0.181, C5aR1: p = 0.771). Patients with TCC levels in Q4 had significantly higher levels of MPO-DNA than Q1-3 (p = 0.019), and C5aR1 levels in Q3-4 had significantly higher levels of MPO-DNA than Q1-2 (p = 0.046). TCC levels did not differ between patients experiencing a clinical endpoint or not, but high levels were associated with increased risk of acute MI (OR. 1.97, 95% CI: 0.99-3.90, p = 0.053) during two-year follow up, also when adjusted for relevant covariates. In conclusion, TCC and C5aR1 were moderately associated with the NET marker MPO-DNA, and TCC levels were related to the risk of future MI in this cohort of patients with stable CAD.

Associations among Periodontitis, Calcified Carotid Artery Atheromas, and Risk of Myocardial Infarction

Cardiovascular disease is a common cause of morbidity and premature mortality. Cardiovascular disease can be prevented when risk factors are identified early. Calcified carotid artery atheromas (CCAAs), detected in panoramic radiographs, and periodontitis have both been associated with increased risk of cardiovascular disease. This case-control study aimed to 1) investigate associations between periodontitis and CCAA detected in panoramic radiographs and 2) determine the risk of future myocardial infarctions due to CCAA combined with periodontitis. We evaluated 1,482 participants (738 cases and 744 controls) with periodontitis and CCAAs recruited from the PAROKRANK study (Periodontitis and Its Relation to Coronary Artery Disease). Participants were examined with panoramic radiographs, including the carotid regions. Associations between myocardial infarction and periodontitis combined with CCAA were evaluated in 696 cases and 696 age-, sex-, and residential area–matched controls. Periodontitis was evaluated radiographically (as degree of bone loss) and with a clinical periodontal disease index score (from clinical and radiographic assessments). We found associations between CCAA and clinical periodontal disease index score among cases (odds ratio [OR], 1.51; 95% CI, 1.09 to 2.10; P = 0.02) and controls (OR, 1.70; 95% CI, 1.22 to 2.38; P < 0.01), although not between CCAA and the degree of bone loss. In a multivariable model, myocardial infarction was associated with CCAA combined with periodontitis, as assessed by degree of bone loss (OR, 1.75; 95% CI, 1.11 to 2.74; P = 0.01). When the cohort was stratified by sex, only men showed a significant association between myocardial infarction and CCAA combined with periodontitis. Participants with clinically diagnosed periodontitis exhibited CCAA in panoramic radiographs more often than those without periodontitis, irrespective of the presence of a recent myocardial infarction. Participants with combined periodontitis and CCAA had a higher risk of having had myocardial infarction as compared with participants with either condition alone. These findings implied that patients in dental care might benefit from dentists assessing panoramic radiographs for CCAA—particularly, patients with periodontitis who have not received any preventive measures for cardiovascular disease.

P5719Plasma proteomics identify plaque-related proteins that predict long-term recurrent coronary events in patients with acute coronary syndrome

Abstract Background Coronary plaque burden and composition drive recurrent ischaemic events in coronary artery disease. Purpose We first investigated the association between plasma proteins and coronary plaque characteristics in a cohort of asymptomatic individuals with low-intermediate Framingham Risk Score. Plaque-related proteins were further evaluated in a second cohort of patients with acute coronary syndrome (ACS) to determine their prognostic value for predicting future myocardial infarction (MI). Methods We profiled 1305 plasma proteins using an aptamer-based array (SOMAscan) in asymptomatic individuals who had undergone 384-slice coronary computed tomography angiography. Plaques were categorized by composition as calcified or non-calcified. First, we identified proteins that were different (based on multiple testing adjusted p-values: q-value &lt;0.05) between 250 ACS patients who suffered a recurrent MI event on follow-up compared with another 250 ACS patients who remained event-free using Mann-Whitney U test. Next, protein candidates that also correlated (Pearson's p&lt;0.05) with specific categories of plaque composition were evaluated using a cox proportional hazards model to determine the risk of recurrent MI, adjusting for potential confounders in the second cohort. Results A total of 65 and 120 plasma proteins were significantly associated with calcified and non-calcified plaques respectively in the asymptomatic cohort (N=79). Of these 185 proteins, 23 proteins were differentially expressed (DE) between ACS patients with and without recurrent MI events (median follow-up 1811 days). The top three up-and down-regulated proteins in the recurrent MI group were macrophage-capping protein, trefoil factor 3 and cystatin-SN (median FC 1.22, 1.17 and 1.17; q-value 4.34x10–6, 2.18x10–4, 3.17x10–3 respectively) and fibroblast growth factor 20, lymphotoxin a2/b1 and vascular endothelial growth factor receptor 2 (median FC 0.92, 0.94 and −0.090; q-value 1.31x10–3, 9.45x10–3 and 3.90x10–3) respectively. The quartiles of these protein concentrations were also associated with risk of recurrent MI, (log-rank test p-value range from 2.71x10–7 to 0.04). Of the DE proteins, the adjusted hazards ratio (HR) of cystatin-SN in the highest quartile (Q4) was 1.44 times that of the first quartile (Q1) (adjusted HR: 1.44, 95% CI: 0.93–2.2) and higher plasma concentration of cystatin-SN was associated with increasing risk of recurrent MI events (Trend test p=0.004). On the other hand, the highest quartile of fibroblast growth factor 20 was associated with 44% reduction in risks of recurrent MI adjusted HR: 0.56, 95% CI of HR: 0.35–0.87), with significant trend test (p=0.0096). Conclusions Large-scale plasma proteomics identified novel plaque-related proteins predictive of recurrent coronary events in patients with ACS. Further studies may help unravel the biological underpinnings of these circulating proteins and their potential as novel prognostic biomarkers. Acknowledgement/Funding This work was supported by grant NMRC/CSA-INV/0001/2016 from the National Medical Research Council, Singapore.

Immune Biomarkers in the Prediction of Future Myocardial Infarctions in People With Human Immunodeficiency Virus.

In a retrospective case control analysis, following adjustments for high-sensitivity C-reactive protein (hsCRP), traditional cardiovascular risk factors, and the CD4/CD8 T-cell ratio, higher lipopolysaccharide-binding protein (LBP) was associated with future myocardial infarctions in hsCRP human immunodeficiency virus (HIV). LBP may be a marker of cardiovascular risk with utility in HIV.