Aggressive Secondary Prevention Research Articles

Abstract 11735: The Effect of Different NLRP3 Inflammasome Inhibitors on High-Sensitivity C-reactive Protein in Patients After Percutaneous Coronary Intervention

Background: Colchicine treatment inhibits the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome assembly and reduces atherothrombotic cardiovascular events in coronary artery disease (CAD). However, the effects of other inhibitors targeting NLRP3 inflammasome needs further verification in CAD. Aims: This study aimed to investigate whether inhibitors targeting NLRP3 inflammasome besides colchicine are effective in patients after percutaneous coronary interventions (PCI). Methods: The study included 132 patients aged 18-80 years who completed the planned PCI and were treated with aggressive secondary prevention strategies for four weeks. The subjects were randomly assigned to one of the following treatment groups for four weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in hsCRP levels at the end of four weeks. Results: In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male and 28 (25.69%) were female. The percentage changes in hsCRP after four weeks of treatment were -11.62%, -48.28%, -21.60%, and -7.81%, in the control, colchicine, tranilast, and the oridonin groups respectively. Compared with the control group, the colchicine group showed significantly greater reduction in hsCRP levels (P=0.022). The tranilast and oridonin groups did not show obvious changes. In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin,myeloperoxidase, myeloblastin), platelet aggregation (glycoprotein VI) and endothelial damage (galectin-3) were reduced with colchicine therapy. Conclusions: Colchicine could reduce hsCRP in patients after PCI, which is likely to act on neutrophils. Colchicine may still be the important choice for anti-inflammatory treatment of CAD.

The Role of Lipid-Lowering Therapy in Post-Stroke Patients: Update and Recommendations.

Stroke is the second leading cause of death and disability-adjusted life years worldwide, and the global lifetime risk of stroke is rising. Moreover, patients with a prior stroke are at high risk of recurrent events. We aimed at reviewing the evidence supporting aggressive secondary prevention strategies for lipid-lowering treatment in this population. Statins are the key players in such aggressive management; however, stroke survivors remain at significant residual risk suggesting the need for both better implementation of statin use as well as additional lipid lowering therapies. Newer drugs have become available and represent important tools in the management of patients with prior ischemic stroke. The role of lipid lowering treatment in hemorrhagic stroke is more controversial, given epidemiological data linking low lipid levels with increased risk of first and recurrent events. Aggressive secondary prevention strategies, including lipid lowering treatments, have proven to mitigate the risk of recurrent events in post-stroke patients. The tools available for treating such high-risk population have expanded beyond statins, and clinicians should familiarize themselves with them.

Influence of Race/Ethnicity and Sex on Coronary Stent Outcomes in Diabetic Patients.

How diabetes mellitus (DM), race/ethnicity, and sex impact ischemic events following coronary artery stent procedures is unknown. Using the PLATINUM Diversity and PROMUS Element Plus Post-Approval Pooled Study (N = 4184), we examined the impact of race/ethnicity, sex, and DM on coronary stent outcomes. Primary outcome was 1-year major adverse cardiac events (MACE) (MACE composite: death, myocardial infarction [MI], and target vessel revascularization). The study sample included 1437 diabetic patients (501 White men, 470 White women, 246 minority men, 220 minority women) and 2641 patients without medically treated DM (561 minority, 1090 women). Mean age (years) ranged from 61 in minority men to 65 in White women. Diabetic patients had a higher prevalence of atherosclerotic risk factors and comorbidities. Diabetic minority women (DMW; 70% Black, 27% Hispanic) had similar atherosclerotic risk factors to other diabetics, but experienced higher 1-year MACE (14.4% vs 7.5%, P <.01) and MI (4.3% vs 1.6%, P <.01) rates compared with patients without medically treated DM. No other diabetic cohort (White men, White women, minority men) showed an increased risk of MACE vs patients without medically treated DM. The incremental risk of MACE in DMW was associated with insulin use and persisted after risk adjustment (adjusted odds ratio 1.6 vs patients without medically treated DM; 95% CI, 1.0-2.5). Independent predictors of 1-year MACE included insulin use, hyperlipidemia, renal disease, and prior MI. DMW face the highest risk of ischemic events following coronary stenting, driven, in part, by insulin use. Aggressive secondary prevention and strict glycemic control are imperative in this cohort, and further research is warranted to elucidate the biologic mechanisms underpinning these observations. NCT02240810 (http://clinicaltrials.gov/).

History of peripheral artery disease and cardiovascular risk of real-world patients with acute coronary syndrome: Role of inflammation and comorbidities

BackgroundPatients with acute coronary syndromes (ACS) remain at risk of cardiovascular disease (CVD) recurrences. Peripheral artery disease (PAD) may identify a very high risk (VHR) group who may derive greater benefit from intensified secondary prevention. MethodsAmong ACS-patients enrolled in the prospective multi-center Special Program University Medicine (SPUM), we assessed the impact of PAD on major cardiovascular events (MACE: composite of myocardial infarction, stroke and all-cause death) and major bleeding. Multivariate analysis tested the relation of each significant variable with MACE, as well as biomarkers of inflammation and novel markers of atherogenesis. ResultsOut of 4787 ACS patients, 6.0% (n = 285) had PAD. PAD-patients were older (p < 0.001), with established CVD and signs of increased persistent inflammation (hs-CRP; 23.6 ± 46.5 vs 10.4 ± 27.2 mg/l, p < 0.001 and sFlt-1; 1399.5 ± 1501.3 vs 1047.2 ± 1378.6 ng/l, p = 0.018). In-hospital-death (3.2% vs 1.4%, p = 0.022) and -MACE (5.6% vs 3.0%, p = 0.017) were higher in PAD-patients. MACE at 1 year (18.6% vs 7.9%,p < 0.001) remained increased even after adjustment for confounders (Adj. HR 1.53, 95% CI: 1.14–2.08, p = 0.005). Major bleeding did not differ between groups (Adj. HR 1.18; 95% CI 0.71–1.97, p = 0.512). Although PAD predicted MACE, PAD-patients were prescribed less frequently for secondary prevention at discharge. ConclusionsIn this real-world ACS patient cohort, concomitant PAD is a marker of VHR and is associated with increased and persistent inflammation, higher risk for MACE without an increased risk of major bleeding. Therefore, a history of PAD may be useful to identify those ACS patients at VHR who require more aggressive secondary prevention.

Abstract 14367: Residual Cardiovascular Risk Despite Secondary Prevention: Data From Contemporary Cardiovascular Outcomes Trials Spanning 2010 - 2021

Introduction: Despite aggressive secondary prevention, a persistent risk of cardiovascular (CV) events exists among patients with coronary artery disease (CAD). In addition to traditional risk factors, this residual risk results, at least in part, from persistent pro-inflammatory and metabolic contributors. This study evaluated the incidence of recurrent CV events in contemporary CV outcome trials between 2010-2021. Methods: A total of 45 randomised, controlled trials were included. Studies were categorized based on patient population and enrollment strategy into 3 groups: 1) Early post-ACS (enrolled within 72h of event), 2) late post-ACS (enrolled after 72h of event), and 3) chronic CAD or risk equivalent (type 2 diabetes or 2 or more CV risk factors). Due to a wide range of follow-up durations, data were normalized to events per 100 patient-years. Results: Follow-up duration ranged from 30 to 2957 days. Overall, recurrent CV events varied between 2% and 10%. Trials that enrolled patients within 72h of ACS demonstrated the highest risk for recurrent events with a median of 21.8 events per 100 patient-years (IQR 11.3-66.0). Patients enrolled &gt;72h after ACS had significantly lower risk with a median of 3.4 events per 100 patient-years (IQR 2.9-4.1), likely due to a survival bias in those enrolled later after their index event. The rate of recurrent events was comparable between trials that enrolled patients 72h post-ACS and trials that enrolled patients with chronic CAD. There was no correlation between trial year and event rate. Conclusions: Despite standard of care therapy, there is a persistent residual risk of recurrent events especially early after ACS. Our study demonstrates a residual risk ranging from 3 to as high as 22 events per 100 patient-years. This risk is likely higher in a non-trial setting where medication adherence and follow-up are not strictly controlled. Novel strategies for secondary prevention comprise a major unmet need to further decrease this risk.

Long-term follow-up in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.

Long-term follow-up after primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) beyond 5 years is poorly described. There are no risk-stratification systems available for routine use. This retrospective, academic, two-centre analysis included consecutive patients who presented with acute STEMI between March 2008 and December 2019. In total, 5263 patients underwent pPCI; all patients were included in the analysis only once. Baseline characteristics were gathered from prospective local registries and based on initial hospitalization. The study enrolled 5263 patients who had been treated with pPCI; it found that cardiovascular mortality was the most frequent cause of death (65.0%) on long-term follow-up to 12 years. Myocardial infarction associated mortality was 27.2%. Cardiovascular mortality was dominant, including in the landmark analysis beyond 1 year. Multivariate analysis identified significant predictors for long-term cardiovascular mortality: age, history of diabetes mellitus, history of renal insufficiency, history of heart failure, Killip class, and successful pPCI at presentation. A predictive model was built to evaluate the risk of cardiovascular death with a high discrimination value (C-statistic = 0.84). Cardiovascular diseases remain the leading cause of long-term mortality after pPCI in the Central European population. Our novel predictive model provides risk stratification; it could identify patients who would experience the greatest benefit from aggressive secondary prevention measures.

Modifiable Risk Factors and Residual Risk Following Coronary Revascularization: Insights From a Regionalized Dedicated Follow-Up Clinic.

ObjectiveTo ensure compliance with optimal secondary prevention strategies and document the residual risk of patients following revascularization, we established a postrevascularization clinic for risk-factor optimization at 1 year, with outcomes recorded in a web-based registry. Although coronary revascularization can reduce ischemia, medical treatment of coronary artery disease (CAD) remains the cornerstone of ongoing risk reduction. While standardized referral pathways and protocols for revascularization are prevalent and well studied, post-revascularization care is often less formalized.Patients and MethodsThe University of Ottawa Heart Institute is a tertiary-care center providing coronary revascularization services. From 2015 to 2019, data were prospectively recorded in the CAPITAL revascularization registry, and patient-level procedural, clinical, and outcome data are collected in the year following revascularization. Major adverse cardiovascular event (MACE) was defined as death, myocardial infarction, unplanned revascularization, or cerebrovascular accident. Kaplan-Meier curves were generated to evaluate time-to-event data for clinical outcomes by risk-factor management, and comparisons were performed using log-rank tests and reported by hazard ratio (HR) and 95% confidence intervals (CIs).ResultsA cohort of 4147 patients completed 1-year follow-up after revascularization procedure that included 3462 undergoing percutaneous coronary intervention (PCI), 589 undergoing coronary artery bypass graft (CABG), and 96 undergoing both PCI and CABG. In the year following revascularization (median follow-up 13.3 months—interquartile range [IQR]: 11.9-16.5) 11% of patients experienced MACE, with female patients being disproportionately at risk. Moreover, 47.7% of patients had ≥2 risk factors (diabetes, dyslipidemia, overweight, active smoker) at the time of follow-up, with 45.0% of patients with diabetes failing to achieve target hemoglobin (Hb) A1c, 54.8% of smokers continuing to smoke, and 27.1% of patients failing to achieve guideline-directed lipid targets.ConclusionPatients who have undergone revascularization procedures remain at elevated risk for MACE, and inadequately controlled risk factors are prevalent in follow-up. This highlights the need for aggressive secondary prevention strategies and implementation of programs to optimize postrevascularization care.

Arterial tortuosity syndrome causing recurrent transient ischemic attacks in young adult: a case report

BackgroundArterial Tortuosity Syndrome (ATS) is a rare autosomal recessive disorder characterized by elongated and tortuous arteries. Although ATS showed a significant clinical and pathophysiological overlap with other syndromes involving connective tissues, only few cases of cerebrovascular events related to this syndrome have been described so far.Case presentationWe report the case of a 33-years-old male diagnosed with ATS since childhood, that experienced three sudden episodes of expressive aphasia and right hemiparesis with spontaneous resolution. He was treated with recombinant tissue plasminogen activator (r-TPA) at a dosage of 0.9 mg/kg with a complete recovery. Brain Magnetic Resonance Imaging (MRI) showed the absence of acute ischemic lesions and the patient was diagnosed with recurrent transient ischemic attacks (TIA).Intracranial and supra-aortic trunks Magnetic Resonance Angiography (MRA) and Angio-CT scan of the thoracic and abdominal aorta showed marked vessel tortuosity without stenosis.To our knowledge, this is the first reported case of an ATS patient with TIA in young age that was treated with intravenous thrombolysis with recombinant plasminogen activator.ConclusionOur report strengthens the relationship between ATS and juvenile cerebrovascular events, suggesting that an extensive study of body vessels in order to detect potential stenoses or occlusions in these cases is needed.The greater predisposition to cerebrovascular events in ATS could benefit from a more aggressive primary and secondary prevention therapy.

Intraoperative transit time flow measurement in patients with diffuse coronary artery disease in the prevention of aortocoronary bypass graft occlusion

Aim. To study the parameters of transit time flow measurement (TTFM) for coronary bypass grafts in patients with diffuse lesions with different diameter of target coronary arteries.Material and methods. The study included 150 patients with diffuse coronary artery disease. All patients underwent microscope-assisted coronary artery bypass grafting (CABG), during which the TTFM parameters were evaluated. Depending on the diameter of target coronary arteries, patients were divided into 3 groups: group 1 included grafts to arteries ≤1 mm (n=101), group 2 — 1-1,5 mm (n=138), group 3 — ≥1,5 mm (n=308). Comparative analysis of TTFM parameters was performed.Results. Mostly participants were male (76%); mean age was 62,9±7,6 years. During hospitalization, we recorded 1 death, 2 perioperative myocardial infarctions (1,3%) and 1 cerebrovascular accident (0,7%). TTFM analysis showed the worst hemodynamic parameters and a higher rate of suboptimal function in group 1; blood flow parameters were comparable in groups 2 and 3. The additional analysis in group 1 and combined groups 2 and 3 allows us to make an opinion about the negative impact of coronary artery diameter less than 1 mm on optimal blood flow through the grafts (odds ratio=2,1, 95% confidence interval, 1,2-3,8, p=0,011).Conclusion. Diffuse coronary atherosclerosis with a diameter of target coronary arteries less than 1 mm significantly increase the risk of suboptimal graft function that requires considering more aggressive secondary prevention. TTFM demonstrate high effectiveness of microscope-assisted CABG in target coronary artery diameter of 1-1,5 mm and higher.

Abstract 12133: Association Between Polyvascular Disease and Adverse Outcomes Among Patients Undergoing Coronary Artery Bypass Grafting in a Regional Registry

Introduction: Polyvascular disease is defined as the simultaneous presence of coronary artery disease (CAD) and peripheral artery disease (PAD) or cerebrovascular disease (CVD). Hypothesis: We hypothesized that polyvascular disease may be associated with worse short- and long-term outcomes in patients undergoing coronary artery bypass grafting (CABG). Methods: We performed a retrospective, multi-center analysis of patients undergoing isolated CABG from 2005-2018 among 7 medical centers in Northern New England. Patients were stratified by number of vascular beds affected: CAD only, CAD+PAD or CVD, and CAD+PAD+CVD. The primary outcomes of 30-day and long-term mortality were assessed using multivariable logistic and Cox regression, respectively. Results: Of 18,984 patients, 18% had either PAD or CVD, while 4.8% had PAD and CVD. Compared to those with CAD alone, patients with polyvascular disease were older, more likely to be female, and had a higher prevalence of comorbidities including diabetes, smoking, and renal failure (all p&lt;0.001). The risk-adjusted odds of 30-day mortality was higher for patients with either CVD or PAD (OR=1.57, 95% CI: 1.2-2.07) and combination of CVD and PAD (OR=1.56, 95% CI: 1.00-2.42) versus CAD alone. Polyvascular disease patients had higher risk of long-term all-cause mortality compared to CAD only patients (Figure). Conclusions: Among patients undergoing CABG in Northern New England, those with polyvascular disease had a higher risk of short- and long-term adverse outcomes compared to CAD alone, with incremental increase in risk dependent on number of vascular beds affected. Aggressive secondary prevention measures, prior to and after CABG, should be routinely employed for these patients.

Abstract 13946: Subclinical Atherosclerosis and Peri-Operative Cardiac Events in Patients Undergoing Peripheral Bypass Surgery

Introduction: Coronary artery disease (CAD) is associated with a higher risk of peri-operative adverse events after vascular surgery. Subclinical CAD, defined as presence of coronary calcium, has not been established as a risk factor for adverse events after vascular surgery. Hypothesis: We sought to describe the epidemiology and peri-operative outcomes in patients with subclinical coronary atherosclerosis (SCA) undergoing supra- and infra-inguinal peripheral bypass. Methods: Using the Vascular Quality Initiative, we identified patients at a single institution undergoing supra- and infra-inguinal peripheral bypass surgery (2009-2020). Retrospective chart review was performed to identify chest computed tomography (CT) within one year prior to revascularization; imaging was reviewed for presence of coronary calcifications, a marker of SCA. Individuals were stratified by: no atherosclerosis, SCA, and CAD. Comorbidities and peri-operative outcomes were compared among groups with the chi-square or ANOVA, as appropriate. Results: Of 1018 patients undergoing peripheral bypass surgery, 199 (20%) had a CT available. SCA was noted in 96 patients (48%) while 72 (36%) had known CAD. Patients with SCA had similar comorbidities to patients with CAD (Table) but were less likely to be on a pre-operative beta-blocker or P2Y12 inhibitor. The incidence of postoperative myocardial infarction and congestive heart failure was similar in patients with SCA (13% and 9%, respectively) as those with CAD (10%, 6% respectively), compared to those without atherosclerosis (3% and 0, respectively). Conclusions: SCA is common in patients undergoing peripheral bypass surgery and is associated with a risk of peri-operative myocardial infarction or congestive heart failure similar to occult CAD. Aggressive secondary prevention measures should be considered in patients with polyvascular disease, including subclinical CAD.

Myocardial perfusion imaging using computed tomography: Current status, clinical value and prognostic implications

AbstractCombined anatomical and functional evaluation of coronary artery disease (CAD) using computed tomography (CT) has recently emerged as an accurate, robust, and non-invasive tool for the evaluation of ischemic heart disease. Cardiac CT has become a one-stop-shop imaging modality that allows the simultaneous depiction, characterization, and quantification of coronary atherosclerosis and the assessment of myocardial ischemia. Advancements in scanner technology (improvements in spatial and temporal resolution, dual-energy imaging, wide detector panels) and the implementation of iterative reconstruction algorithms enables the detection of myocardial ischemia in both qualitative and quantitative fashion using low-dose scanning protocols. The addition of CT perfusion (CTP) to standard coronary CT angiography is a reliable tool to improve diagnostic accuracy. CTP using static first-pass imaging enables qualitative assessment of the myocardial tissue, whereas dynamic perfusion imaging can also provide quantitative information on myocardial blood flow. Myocardial tissue assessment by CTP holds the potential to refine risk in stable chest pain or microvascular dysfunction. CTP can aid the detection of residual ischemia after coronary intervention. Comprehensive evaluation of CAD using CTP might therefore improve the selection of patients for aggressive secondary prevention therapy or coronary revascularization with high diagnostic certainty. In addition, prognostic information provided by perfusion CT imaging could improve patient outcomes by quantifying the ischemic burden of the left ventricle. The current review focuses on the clinical value of myocardial perfusion imaging by CT, current status of CTP imaging and the use of myocardial CTP in various patient populations for the diagnosis of ischemic heart disease.

Secondary prevention of acute disorders of brain-blood circulation in patients with asymptomatic vertebral arteries lesion

Almost 50% of patients who experience a stroke in the vertebrobasilar pool die within the first year after the stroke, and approximately 80% of patients experience disability. Additionally, the risk of re-stroke in these patients is significantly higher compared with damage to the carotid pool. Prospects for the restoration of brain functions and the ability to work in patients who have had a stroke in the vertebrobasilar pool remain very limited. In this connection, the problem of preventing cerebrovascular disorders in patients with chronic cerebral ischaemia with lesions of the vertebral arteries is currently extremely urgent.Particular attention should be paid to patients with asymptomatic chronic brain ischaemia. Possible reasons for the low efficiency of drug therapy and complications arising against this background are discussed. The feasibility of a more aggressive secondary prevention of cerebrovascular disorders, which includes endovascular interventions in combination with medical therapy, is demonstrated.Received 7 July 2020. Revised 6 August 2020. Accepted 17 September 2020.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.

Abstract P592: Admission Hyperglycemia is Associated With Subsequent Ischemic Stroke After Transient Ischemic Attack or Minor Stroke: A Secondary Analysis of the POINT Trial

Introduction: Hyperglycemia is associated with increased lesion volume and worse functional outcome after acute ischemic stroke, however, it is not known whether it is associated with further cerebrovascular events. The aim of this study was to examine the association between admission hyperglycemia and subsequent ischemic stroke. Methods: This was an exploratory analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which compared combined clopidogrel/aspirin with aspirin alone with respect to the primary outcome of subsequent ischemic stroke, myocardial infarction, or vascular death. We dichotomized patients based on a serum glucose threshold of 180mg/dl (chosen a priori based on the upper boundary of the active control arm of SHINE). We calculated hazard ratios (HR) for subsequent ischemic stroke at 90 days via a Cox proportional hazards model adjusting for age, sex, study treatment assignment and vascular risk factors. We performed sensitivity analyses excluding patients with a known history of diabetes and in patients whose index event was a TIA vs. minor stroke. Results: Of 4,878 patients in this analysis (mean age 64.6 years), 594 (12.2%) were hyperglycemic on presentation and 267 (5.5%) had a subsequent ischemic stroke within 90 days. Admission hyperglycemia was associated with subsequent ischemic stroke (HR 1.88; 95% CI:1.39-2.53, p&lt;0.01). This association persisted after adjustment for relevant covariates (aHR 1.86, 95% CI: 1.37-2.52, p&lt;0.01), in non-diabetic patients (n=3,529, aHR 3.1, 95% CI:1.7-5.7, p&lt;0.01), in patients with TIA (n=2,327, aHR 2.2, 95% CI: 1.2-4.1, p&lt;0.01), and in patients with minor ischemic stroke (n=2,304, aHR = 1.5, 95% CI: 1.1-2.2, p=0.02). Conclusions: Hyperglycemia portends a higher risk of subsequent ischemic stroke after adjusting for known predictors of stroke recurrence. This study may provide further support to pursuing aggressive secondary prevention strategies in this population.

Macrophage infiltrates in coronary plaque erosion portend a worse cardiovascular outcome in patients with acute coronary syndrome

Abstract Background Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS). Inflammatory activation is considered a key mechanism of plaque instability in patients with plaque rupture through the release of metalloproteinases and the inhibition of collagen synthesis that in turns lead to fibrous cap degradation. However, the clinical relevance of macrophage infiltration has never been investigated in patients with PE. Purpose In our study, we aimed at assessing the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. Methods ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site and in non-culprit segments along the culprit vessel was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03–2.58) years]. Results We included 153 patients [median age (IQR) 64 (53–75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. In particular, culprit lesion analysis demonstrated that patients with PE with MØI had a significantly thinner fibrous cap [median (IQR) 100 (60–120) μm vs. 160 (95–190) μm, p&amp;lt;0.001], higher prevalence of thrombus [41 (80.4%) vs. 64 (62.7%), p=0.028], lipid plaque [39 (76.5%) vs. 50 (49.0%), p&amp;lt;0.001], TCFA [20 (39.2%) vs. 14 (13.7%), p=0.001], and a higher maximum lipid arc [median [IQR] 250.0° (177.5°-290.0°) vs. 190.0° (150.0°-260.0°), p=0.018) at the culprit lesion compared with PE without MØI. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p=0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression model, PE with MØI [HR=2.95, 95% CI (1.09–8.02), p=0.034] was an independent predictor of MACEs. Conclusion Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with a more aggressive phenotype of coronary atherosclerosis with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up. These findings are of the utmost importance in the era of precision medicine because clearly show that macrophage infiltrates may identify patients with a higher cardiovascular risk requiring more aggressive secondary prevention therapies and a closer clinical follow-up. Prognosis Funding Acknowledgement Type of funding source: None

Derivation and validation of a scoring system to predict after discharge risk of cardiac events in patients with acute myocardial infarction undergoing percutaneous coronary revascularization

Abstract Background In the acute coronary syndromes (ACS) setting, despite the extensive use of coronary revascularization and P2Y12 inhibitors such as prasugrel and ticagrelor, with a more pronounced inhibitory effect on platelets than clopidogrel, the rate of death and recurrent myocardial infarction (MI) at 1 year is still high. In this clinical setting the development of a risk score which takes into account patient's and procedural characteristics could represent a useful tool to identify patients at high risk for ischaemic events at 1 year who could take advantage from more aggressive secondary prevention strategies. Purpose The aim of our study was to develop a risk score to predict 1-year probability of after discharge cardiac events (recurrent MI and cardiac death) in patients with acute MI treated with percutaneous coronary intervention (PCI). Methods We prospectively enrolled all consecutive patients hospitalized for acute MI between 2003 and 2017 treated with PCI with/without stent placement at our center. We excluded patients who died in-hospital or who experienced in-hospital recurrent MI and patients undergoing surgical revascularization by coronary artery bypass graft (CABG). The patients of the final study cohort were therefore randomly assigned to either a derivation sample (60%) or a validation sample (40%). Based on the multivariate analysis we developed a point system according to the “Framingham Risk Score” method. Results The final study cohort, represented by 4922 patients, was split in a derivation sample of 2972 patients and in a validation sample of 1950 patients: in both groups the median age was around 70 years; the male prevalence was 73%; 65% of patients were dagnosed with ST-segment elevation MI. The clinical prediction score underlined as risk factors for recurrent cardiac events older age, diabetes mellitus, peripheral arterial disease, prior MI, Killip class &amp;gt;2 at presentation, higher platelet count and creatinine values, lower left ventricular ejection fraction; radial access and the use of second generation drug eluting stents resulted to be protective. This model showed a good discrimination power in both the derivation and the validation samples with an area under the curve (AUC) of 0.75 and 0.71, respectively. The calibration showed a good concordance between predicted and observed events in both the derivation and the validation samples. Same results were observed in patients with/without ST-segment elevation MI and in gender subgroups. Conclusions The present study, conducted retrospectively on a large population of patients with acute MI treated with PCI enrolled prospectively, enabled us to derivate and validate a risk score of cardiac death and recurrent MI at 1 year which took into account both clinical and procedural characteristics and which demonstrated a good predictive performance. After-discharge events by risk subgroups Funding Acknowledgement Type of funding source: None

Early blood pressure assessment after acute myocardial infarction: Insights using digital health technology

ObjectiveThere is rising interest in digital health in preventive cardiology, particularly for blood pressure (BP) management. In a digital health study of early BP assessment following acute myocardial infarction (AMI), we sought to examine feasibility and the (1) proportion of post-AMI patients with controlled BP and hypotension, and (2) association between prior cardiovascular disease (CVD) and BP post-AMI. MethodsIn this substudy of the parent Myocardial infarction, COmbined-device, Recovery Enhancement (MiCORE) study, type 1 AMI patients were enrolled between October 2017 and April 2019. Participants self-monitored their BP through 30 days after hospital discharge using an FDA-approved wireless BP monitor connected with a smartphone application. Linear mixed-effects models assessed the association between prior CVD and BP trajectory post-discharge, adjusting for antihypertensive medications and a propensity score inclusive of CVD risk factors. ResultsSixty-eight AMI patients (mean age 58 ​± ​10 years, 75% male, 68% white race, 68% history of hypertension, 24% prior CVD) provided 2638 measurements over 30 days. The percentage of BP control <130/80 ​mmHg was 59.6% (95% CI: 54.3–64.9%) and <140/90 ​mmHg was 83.7% (95% CI: 80.3–87.2%). The percentage of systolic BP ​<90 ​mmHg was 1.1% (95% CI: 0.17–2.0%) and the percentage of diastolic BP ​<60 ​mmHg was 3.9% (95% CI: 2.6–5.2%). Prior CVD was associated with 12.2 ​mmHg higher mean daily systolic BP during admission (95% CI: 3.5–20.9 ​mmHg), which persisted over follow-up. There was no association between prior CVD and diastolic BP. ConclusionThe digital health program was feasible and ~40% of post-AMI patients who engaged in it had uncontrolled BP according to recent guideline cutpoints, while hypotension occurred rarely. The gap in BP control was especially large in patients in whom AMI represented recurrent CVD. These data suggest an opportunity for more aggressive secondary prevention early after MI as care models integrate digital health.

Echocardiographic parameters determining cardiovascular outcomes in patients after acute ischemic stroke.

Previous studies have focused on only 1 or 2 echocardiographic parameters as prognostic markers in patients with acute ischemic stroke (AIS). A total of 900 patients with AIS who underwent transthoracic echocardiography (72.6 ± 12.0years and 60% males) were retrospectively reviewed. Composite clinical events, including all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and coronary revascularization, were assessed during clinical follow-ups. During a median follow-up of 3.3years (interquartile range 0.6-5.1years), there were 151 (16.8%) composite events. In the multivariable analyses after controlling for potential confounders, left ventricular ejection fraction (LVEF) < 62% (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.14-2.30; p = 0.007) and AV sclerosis (AVs) (HR 1.56; 95% CI 1.10-2.21; p = 0.013) were independent prognostic factors associated with composite events. Multivariable analyses showed that HR for composite events gradually increased according to LVEF and AVs: HR was 2.6-fold higher in the highest-risk group than in the lowest group (p < 0.001). Compared with a clinical model (global chi-square = 69.6), LVEF, AVs, and both of them were significantly improved outcome prediction in sequential Cox model analysis (global chi-square = 75.6, 75.7, and 78.8, respectively; p < 0.05 for each) for each. In patients with AIS, LVEF < 62%, and the presence of AV sclerosis can predict future vascular events. Patients with AIS exhibiting reduced LVEF and AV sclerosis may benefit from aggressive secondary prevention.

Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial.

In epidemiologic cohorts initiated >30 years ago, inflammatory biomarkers, such as interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were shown to independently predict future cardiovascular events with a magnitude of effect comparable to that of low-density lipoprotein cholesterol (LDLC). Whether aggressive contemporary therapy for atherosclerosis has altered these relationships is unknown yet has major implications for future drug development. Interleukin-6, hsCRP, and LDLC were measured at baseline in up to 4168 North American patients enrolled in the contemporary Cardiovascular Inflammation Reduction Trial with prior myocardial infarction or multivessel coronary disease who additionally had diabetes or metabolic syndrome and were followed for a period of up to 5 years for incident major recurrent cardiovascular events and all-cause mortality. Three-quarters of the cohort were previously revascularized and the great majority was taking statins, angiotensin blocking agents, beta-blockers, and antithrombotic agents. Participants were randomly allocated to low-dose methotrexate 15 mg weekly or to placebo. Randomized use of methotrexate had no effect on event rates nor plasma levels of IL-6, hsCRP, or LDL over time. Yet, baseline levels of IL-6, hsCRP, and LDLC were all predictors of major recurrent cardiovascular events; adjusted hazard ratios [HR; 95% confidence interval (CI)] for the lowest to highest baseline quartiles of IL-6 were 1.0 (referent), 1.66 (1.18-2.35), 1.92 (1.36-2.70), and 2.11 (1.49-2.99; P < 0.0001), while adjusted HRs for increasing quartiles of hsCRP were 1.0 (referent), 1.28 (0.92-1.79), 1.73 (1.25-2.38), and 1.79 (1.28-2.50; P < 0.0001) and adjusted HRs for increasing quartiles of LDLC were 1.0 (referent), 1.12 (0.78-1.62), 1.25 (0.87-1.79), and 2.38 (1.72-3.30; P < 0.0001). Effect estimates were not statistically different in these analyses for comparisons between IL-6, hsCRP, or LDLC, although IL-6 was the strongest predictor of all-cause mortality. The highest absolute risks were observed among those with elevated levels of both cholesterol and inflammation [HR 6.4 (95% CI 2.9-14.1) for those in the top quartiles of baseline IL-6 and LDLC, HR 4.9 (95% CI 2.6-9.4) for those in the top quartiles of baseline hsCRP and LDLC, both P < 0.0001]. Despite aggressive contemporary secondary prevention efforts, the relationships between inflammation, cholesterol, and cardiovascular risk are largely unchanged from those described two decades ago. These data are consistent with the hypothesis that future treatments for atherosclerosis may require a combination of inflammation inhibition and additional cholesterol reduction. ClinicalTrials.gov NCT01594333.

Cardiovascular Mortality After Type 1 and Type 2 Myocardial Infarction in Young Adults

BackgroundType 2 myocardial infarction (MI) and myocardial injury are associated with increased short-term mortality. However, data regarding long-term mortality are lacking. ObjectivesThis study compared long-term mortality among young adults with type 1 MI, type 2 MI, or myocardial injury. MethodsAdults age 50 years or younger who presented with troponin >99th percentile or the International Classification of Diseases code for MI over a 17-year period were identified. All cases were adjudicated as type 1 MI, type 2 MI, or myocardial injury based on the Fourth Universal Definition of MI. Cox proportional hazards models were constructed for survival free from all-cause and cardiovascular death. ResultsThe cohort consisted of 3,829 patients (median age 44 years; 30% women); 55% had type 1 MI, 32% had type 2 MI, and 13% had myocardial injury. Over a median follow-up of 10.2 years, mortality was highest for myocardial injury (45.6%), followed by type 2 MI (34.2%) and type 1 MI (12%) (p < 0.001). In an adjusted model, type 2 MI was associated with higher all-cause (hazard ratio: 1.8; 95% confidence interval: 1.2 to 2.7; p = 0.004) and cardiovascular mortality (hazard ratio: 2.7; 95% confidence interval: 1.4 to 5.1; p = 0.003) compared with type 1 MI. Those with type 2 MI or myocardial injury were younger and had fewer cardiovascular risk factors but had more noncardiovascular comorbidities. They were significantly less likely to be prescribed cardiovascular medications at discharge. ConclusionsYoung patients who experience a type 2 MI have higher long-term all-cause and cardiovascular mortality than those who experience type 1 MI, with nearly one-half of patients with myocardial injury and more than one-third of patients with type 2 MI dying within 10 years. These findings emphasize the need to provide more aggressive secondary prevention for patients who experience type 2 MI and myocardial injury.