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Background: Cardiac troponins are associated with adverse cardiovascular disease (CVD) outcomes. The value of high-sensitivity cardiac troponin I (hs-cTnI) independently and in concert with troponin T (hs-cTnT) in the management of hypertension has not been well studied., Methods: We assessed the utility of hs-cTnI independently and with hs-cTnT in identifying the highest risk individuals in the Systolic Blood Pressure Intervention Trial (SPRINT). Among 8796 eligible SPRINT participants, hs-cTnI was measured at baseline and 1 year. The association of baseline level and 1-year change in hs-cTnI with CVD events and all-cause death was evaluated using adjusted Cox regression models. We further assessed the complementary value of hs-cTnI and hs-cTnT by identifying concordant and discordant categories and assessing their association with outcomes., Results: hs-cTnI was positively associated with composite CVD risk [myocardial infarction, other acute coronary syndrome, stroke, or cardiovascular death: hazard ratio 1.23, 95% confidence interval 1.08-1.39 per 1-unit increase in log(troponin I)] independent of traditional risk factors, N-terminal pro-B-type natriuretic peptide, and hs-cTnT. Intensive blood pressure lowering was associated with greater absolute risk reduction (4.5% vs 1.7%) and lower number needed to treat (23 vs 59) for CVD events among those with higher baseline hs-cTnI (≥6 ng/L in men, ≥4 ng/L in women). hs-cTnI increase at 1 year was also associated with increased CVD risk. hs-cTnI and hs-cTnT were complementary, and elevations in both identified individuals with the highest risk for CVD and death., Conclusions: Baseline levels and change in hs-cTnI over 1 year identified higher-risk individuals who may derive greater cardiovascular benefit with intensive blood pressure treatment. hs-TnI and hs-TnT have complementary value in CVD risk assessment. ClinicalTrials.gov Registration Number: NCT01206062., (© Association for Diagnostics & Laboratory Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The objective of this study was to evaluate the interaction between obesity and obstructive sleep apnea on acute MI in hospital mortality., Methods: This retrospective cohort study utilized Veterans Health Administration data from years 1999-2020. Participants were categorized according to their body mass index (BMI) to non-obese (BMI <30) and obese (BMI ≥30) groups. Clinical obstructive sleep apnea (SA) diagnosis was confirmed using ICD9/10 codes and the study subgroups included non-obese with no obstructive sleep apnea (nOB-nSA), non-Obese with obstructive sleep apnea (nOB-SA), obese with no obstructive sleep apnea (OB-nSA), and obese with obstructive sleep apnea (OB-SA). The primary outcome was odds ratio of in-hospital mortality during the hospitalization with acute MI as the principal diagnosis adjusted for age, gender, race, ethnicity, and Charlson comorbidity index (CCI) with the nOB-nSA group as the comparison group., Results: Among 72,036 veterans with acute-MI hospitalization, individuals with obesity and obstructive sleep apnea (OB-SA) had the lowest in-hospital mortality rate (1.0%) compared to those without obesity and obstructive sleep apnea (nOB-nSA, 2.8%), with obesity but without obstructive sleep apnea (OB-nSA, 2.4%), and with obesity and obstructive sleep apnea (nOB-SA, 1.4%). The adjusted odds ratio for mortality, compared to nOB-nSA, was 9% higher but not significant in OB-nSA (aOR, 1.09, 95%CI: 0.95, 1.25), 46% lower in OB-nSA (aOR, 0.54, 95%CI: 0.45, 0.66), and 52% lower in OB-SA (aOR, 0.48: 95%CI: 0.41, 0.57)., Conclusion: Our data suggest that the association between obesity and improved survival in acute MI is largely driven by the presence of sleep apnea., Competing Interests: Declaration of competing interest Authors declare none., (Published by Elsevier B.V.)

Background: While the longer-term Obstructive Sleep apnea (OSA)-related intermittent hypoxia (IH) leads to various comorbidities, it has become increasingly evident that OSA confers protective advantages during and after acute myocardial infarction (AMI). We hypothesized in patients who were admitted with acute MI, the presence of OSA is associated with lower in-hospital mortality compared to those without a prior diagnosis of OSA., Methods: In this nationwide retrospective study utilizing Veterans Health Administration records, we included patients hospitalized for MI with a history of sleep disorders from 1999 to 2020. We divided patients into two cohorts: those with OSA and those without OSA. The primary outcome was in-hospital mortality during AMI hospitalization. We analyzed the data using logistic regression and calculated the odds ratio of in-hospital mortality., Results: Out of more than four million veterans with any sleep diagnosis, 76,359 patients were hospitalized with a diagnosis of AMI. We observed 30,116 with OSA (age, 64 ± 10 years; BMI, 33 ± 7 kg/m 2 ) and 43,480 without OSA (age, 68 ± 12 years; BMI, 29 ± 6 kg/m 2 ). The aOR of in-patient mortality (n = 333 (1.1%)) was lower in those with OSA (aOR, 0.43; 95% CI, 0.38 to 0.49) compared to without-OSA (n = 1,102, 2.5%). However, the OSA cohort had a higher proportion of the prolonged length of stay (28.1%)., Conclusions: Presence of OSA is associated with lower in-hospital mortality among patients admitted for AMI, after adjusting for various demographic and co-morbidity factors. This study highlights the complex relationship between OSA and cardiovascular health and highlights the need for further research in this area., Competing Interests: Conflict of interest The authors report NO conflict of interests relevant to this work., (Published by Elsevier Ltd.)

Septic shock is a life-threatening host response to infection and a significant contributor to cost burden in the United States. Furthermore, sepsis-related inflammation has been linked to myocardial infarction (MI). We sought to examine the association of type 1 and type 2 MI with outcomes in hospitalizations admitted with septic shock. The National Readmission Database 2018 was queried to identify hospitalizations with hospital discharge diagnoses of septic shock without MI, septic shock with type 1 MI, or septic shock with type 2 MI. Complex-sample multivariable logistic and linear regression models were used to determine the association of these conditions with clinical outcomes. Of 354,528 hospitalizations with septic shock, 11,519 had type 1 MI (3.2%) and 13,970 had type 2 MI (3.9%). Compared with septic shock without MI, type 1 MI was associated with higher mortality (adjusted odds ratio [OR] 1.67, 95% confidence interval [CI] 1.57 to 1.77), costs (adjusted parameter estimate $4,571, 95% CI 3,020 to 6,122), and discharge to facility (adjusted OR 1.09, 95% CI 1.01 to 1.17). In contrast, septic shock with type 2 MI was associated with similar mortality and discharge to nursing facility and higher costs (adjusted parameter estimate 1,798, 95% CI 549 to 3,047). Septic shock hospitalizations with type 1 MI had higher in-hospital mortality (adjusted OR 1.74, 95% CI 1.60 to 1.90, p <0.001) compared with type 2 MI. In conclusion, type 1 MI is associated with higher mortality and resource utilization among septic shock hospitalizations. Furthermore, type 2 MI was associated with higher resource utilization., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

Background: There is a paucity of contemporary data regarding the outcomes of acute myocardial infarction among patients with familial hypercholesteremia., Methods: We queried the Nationwide Readmissions Database (2016-2018) for hospitalizations with acute myocardial infarction. Multivariable regression analysis was used to compare in-hospital outcomes and 30-day readmissions among patients with and without familial hypercholesteremia., Results: The analysis included 1,363,488 hospitalizations with acute myocardial infarction. The prevalence of familial hypercholesteremia was 0.07% among acute myocardial infarction admissions. Compared with those without familial hypercholesteremia, admissions with familial hypercholesteremia were younger and had less comorbidities but were more likely to have had prior infarct and revascularization. Admissions with familial hypercholesteremia were more likely to present with ST-elevation myocardial infarction and undergo revascularization. After multivariable adjustment, there was no difference in in-hospital case fatality among patients with hypercholesteremia compared with those without it (adjusted odds ratio [aOR] = 0.76; 95% confidence interval [CI] 0.41-1.39). Admissions with acute myocardial infarction and familial hypercholesteremia had higher adjusted rates of cardiac arrest and utilization of mechanical support. There were no group differences in overall 30-day readmission (aOR 0.75; 95% CI 0.51-1.10) or 30-day readmission for acute myocardial infarction. However, a nonsignificant trend toward higher readmission for percutaneous coronary intervention was observed among patients with familial hypercholesteremia (aOR 1.89; 95% CI 0.98-3.64)., Conclusion: In this contemporary nationwide observational analysis, patients with familial hypercholesteremia represent a small proportion of the overall population with acute myocardial infarction and have a distinctive clinical profile but do not appear to have worse in-hospital case fatality compared with those without familial hypercholesteremia., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: It remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden., Objective: To assess associations of CA MRI plaque characteristics with incident CVD events., Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020., Exposures: Incident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed., Main Outcomes and Measures: Proportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics., Results: Of 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P < .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; P = .03), respectively. The presence of a lipid core was independently associated with incident CVD events when adjusted for traditional CVD risk factors and maximum CA wall thickness (hazard ratio, 2.48 [95% CI, 1.36-4.51]; P = .003), whereas the presence of calcification was not. The frequency of intraplaque hemorrhage presence in this population of individuals free of CVD at baseline who were not recruited for carotid stenosis was too small to draw any meaningful conclusions (intraplaque hemorrhage presence: 68 of 1256 participants [5.4%]). Carotid artery lumen area and maximum stenosis, which were overall low, were independently associated with incident CVD events when adjusted for traditional CVD risk factors, as anticipated., Conclusions and Relevance: The presence of a CA lipid core on MRI is associated with incident CVD events independent of maximum CA wall thickness in asymptomatic participants.

Background: Ticagrelor is a P2Y 12 receptor inhibitor with superior clinical efficacy compared with clopidogrel. However, it is associated with reduced efficacy when combined with a high-dose aspirin., Methods and Results: Patients in the acute coronary treatment and intervention outcomes network (ACTION) Registry-Get With The Guidelines (GWTG) with acute myocardial infarction from October 2013 through December 2014 were included in the study (167 455 patients; 622 sites). We evaluated temporal trends in the prescription of P2Y 12 inhibitors, and identified factors associated with ticagrelor use at discharge. Among patients discharged on ticagrelor and aspirin (21 262 patients), we evaluated the temporal trends and independent factors associated with high-dose aspirin prescription at discharge. Ticagrelor prescription at discharge increased significantly from 12% to 16.7% ( P <0.0001). Decreases in prasugrel and clopidogrel use at discharge (15.7%-13.9% and 54.2%-51.1%, respectively, P <0.0001) were also observed. Independent factors associated with preferential ticagrelor prescription at discharge over clopidogrel included younger age, white race, home ticagrelor use, invasive management, and in-hospital re-infarction and stroke ( P <0.0001 for all), whereas older age, female sex, prior stroke, home ticagrelor use, and in-hospital stroke ( P <0.0001 for all) were associated with preferential ticagrelor prescription at discharge over prasugrel. High-dose aspirin was used in 3.1% of patients discharged on ticagrelor. Independent factors associated with high-dose aspirin prescription at discharge included home aspirin use, diabetes mellitus, previous myocardial infarction, previous coronary artery bypass graft, ST-segment-elevation myocardial infarction, cardiogenic shock, and geographic region ( P =0.01)., Conclusions: Our contemporary analysis shows a modest but significant increase in the use of ticagrelor and a high rate of adherence to the use of low-dose aspirin at discharge., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: There is controversy regarding whether to report concentrations of high-sensitivity cardiac troponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs-cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes compared to concentrations below the LOB., Methods: hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentrations below the limit of blank (LOB) (<3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3-4.99 ng/L). Cross-sectional associations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal associations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined., Results: Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older, more likely to be male, and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95% CI, 1.02-1.38) and cardiovascular mortality (hazard ratio, 1.29; 95% CI, 1.06-1.57)., Conclusions: hs-cTnT concentrations between the LOB and LOD (3-4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations below the LOB (<3 ng/L)., (© 2015 American Association for Clinical Chemistry.)

Objectives: The study sought to evaluate the association of obesity with a novel biomarker of subclinical myocardial injury, cardiac troponin T measured with a new high-sensitivity assay (hs-cTnT), among adults without clinical cardiovascular disease (CVD)., Background: Laboratory evidence suggests a relationship between obesity and myocardial injury that may play a role in the development of heart failure (HF), but there is limited clinical data regarding this association., Methods: We evaluated 9,507 participants in the ARIC (Atherosclerosis Risk in Communities) study without baseline CVD (Visit 4, 1996 to 1999). We assessed the cross-sectional association of body mass index (BMI) with high (≥14 ng/l) and measurable (≥3 ng/l) hs-cTnT levels after multivariable regression. We further evaluated the independent and combined associations of BMI and hs-cTnT with incident HF., Results: Higher BMI was independently associated with a positive, linear increase in the likelihood of high hs-cTnT, with severe obesity (BMI >35 kg/m(2)) associated with an odds ratio of 2.20 (95% confidence interval: 1.59 to 3.06) for high hs-cTnT after adjustment. Over 12 years of follow-up, there were 869 incident HF events. Obesity and hs-cTnT were both independently associated with incident HF, and individuals with severe obesity and high hs-cTnT had a greater than 9-fold higher risk of incident HF (hazard ratio: 9.20 [95% confidence interval: 5.67 to 14.93]) than individuals with normal weight and undetectable hs-cTnT., Conclusions: Among individuals without CVD, higher BMI has an independent, linear association with subclinical myocardial injury, as assessed by hs-cTnT levels. Obesity and hs-cTnT provide independent and complementary prognostic information regarding the risk of incident HF., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The study sought to determine the 99th percentile upper reference limit for the high-sensitivity cardiac troponin T assay (hs-cTnT) in 3 large independent cohorts., Background: The presently recommended 14 ng/l cut point for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization., Methods: Data were included from 3 well-characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease, and kidney disease (subcohort 1), and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex, and race., Results: The 99th percentile values for the hs-cTnT assay in DHS, ARIC, and CHS were 18, 22, and 36 ng/l (subcohort 1) and 14, 21, and 28 ng/l (subcohort 2), respectively. These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men 65 to 74 years of age with no cardiovascular disease in our study had cardiac troponin T values above the current myocardial infarction threshold., Conclusions: Use of a uniform 14 ng/l cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown., Objective: To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes., Design, Setting, and Participants: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012)., Interventions: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies., Main Outcomes and Measures: The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated., Results: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04)., Conclusions and Relevance: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS., Trial Registration: clinicaltrials.gov Identifier: NCT01130246.

Background: Chromosome 9p21 single nucleotide polymorphisms (SNPs) have been shown to be associated with coronary heart disease in multiple studies. The aim of the present study was to identify whether these SNPs are associated with recurrent myocardial infarction (MI), revascularization, or death in acute coronary syndrome (ACS) patients or in those undergoing coronary artery bypass grafting (CABG)., Methods and Results: TexGen registry participants with ACS (n=2,067) or CABG (n=1,176) were evaluated, to assess whether 9p21 SNPs (rs1333049, rs2383206, rs10757278, rs10757274) were associated with recurrent MI (primary outcome), recurrent revascularization, or death (secondary outcomes) at approximately 3.2 years of follow-up. Carriers of risk allele (C) for rs1333049 presented at an earlier age (62 vs. 63.5 years in non-carriers, P=0.0004) with more extensive disease (number of vessels with significant stenosis: 1.9 vs. 1.7 in non-carriers, P=0.001) in the ACS group. In adjusted models, the C allele was not associated with recurrent MI (hazard ratio [HR], 1.01; 95% confidence interval [CI]: 0.74-1.38), recurrent revascularization (HR, 0.98; 95%CI: 0.78-1.23), or death (HR, 0.91; 95%CI: 0.69-1.18) in the ACS or CABG groups (recurrent MI: HR, 0.64; 95%CI: 0.40-1.05; recurrent revascularization: HR, 0.98; 95%CI: 0.61-1.55; death: HR, 0.89; 95%CI: 0.61-1.30). Results were similar for the other 3 SNPs., Conclusions: 9p21 SNPs were not associated with recurrent MI, revascularization, or mortality after ACS or CABG. Individuals with the rs1333049 C allele, however, may present with earlier and more extensive disease.

Although each revision of the US National Cholesterol Education Program guidelines has made increasing provision for the use of global risk assessment in determining need for and intensity of therapy, the guidelines' continued focus on low-density lipoprotein (LDL) cholesterol may result in inadequate or no treatment for individuals at high risk for coronary artery disease (CAD) who do not have substantially elevated LDL cholesterol. However, recent clinical trial evidence has shown that high-risk patients benefit from lipid-regulating therapy regardless of LDL cholesterol level. In the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm, high-risk hypertensive patients had reductions in clinical events despite not having substantially elevated LDL cholesterol at baseline. These results suggest that all hypertensive patients with additional risk factors should receive lipid-regulating statin therapy to prevent CAD events.

Background: Inflammation is linked to adverse outcomes in acute coronary syndromes. Myeloperoxidase, an abundant leukocyte enzyme, is elevated in culprit lesions that have fissured or ruptured in patients with sudden death from cardiac causes. Numerous lines of evidence suggest mechanistic links between myeloperoxidase and both inflammation and cardiovascular disease., Methods: We assessed the value of plasma levels of myeloperoxidase as a predictor of the risk of cardiovascular events in 604 sequential patients presenting to the emergency department with chest pain., Results: Initial plasma myeloperoxidase levels predicted the risk of myocardial infarction, even in patients who are negative for troponin T (<0.1 ng per milliliter) at base line (P<0.001). Myeloperoxidase levels at presentation also predicted the risk of major adverse cardiac events (myocardial infarction, the need for revascularization, or death) within 30 days and 6 months after presentation (P<0.001). In patients without evidence of myocardial necrosis (defined as those who were negative for troponin T), the base-line myeloperoxidase levels independently predicted the risk of major adverse coronary events at 30 days (unadjusted 2nd, 3rd, and 4th quartile odds ratios, 2.2 [95 percent confidence interval, 1.1 to 4.6], 4.2 [95 percent confidence interval, 2.1 to 8.4], and 4.1 [95 percent confidence interval, 2.0 to 8.4], respectively) and at 6 months., Conclusions: A single initial measurement of plasma myeloperoxidase independently predicts the early risk of myocardial infarction, as well as the risk of major adverse cardiac events in the ensuing 30-day and 6-month periods. Myeloperoxidase levels, in contrast to troponin T, creatine kinase MB isoform, and C-reactive protein levels, identified patients at risk for cardiac events in the absence of myocardial necrosis, highlighting its potential usefulness for risk stratification among patients who present with chest pain., (Copyright 2003 Massachusetts Medical Society)