Search

Background: Inflammation, measured by traditional biomarkers such as C-reactive protein, has been linked to cardiovascular (CV) events. Recent technological advancement has allowed for measuring larger numbers of inflammatory biomarkers. A contemporary evaluation with established and novel biomarkers of inflammation is needed., Methods: 1,090 individuals who underwent coronary angiography were enrolled. Twenty-four inflammatory biomarkers were collected prior to angiography. Unsupervised machine learning cluster analyses determined unique patterns of inflammatory biomarkers. Cox proportional hazard regression assessed both association of inflammatory biomarker clusters and individual biomarker associations with major adverse cardiovascular events (MACE; non-fatal myocardial infarction or stroke, and CV death) during a median follow-up of 3.67 years., Results: Four distinct clusters were recognized. Incremental increases in inflammatory biomarkers were observed from cluster 1 to cluster 4. During follow-up, 263 MACE were ascertained. Considering cluster 1 as a reference, study participants with inflammatory cluster 2 (Hazard ratio [HR] 1.55, 95% confidence interval [CI]: 1.01-2.37), cluster 3 (HR 1.89, CI: 1.25-2.85), and cluster 4 (HR 2.93, CI: 1.95-4.42) were at increased risk of MACE. Interleukin (IL)-1α IL-6, IL-8, IL-10, IL-12, Adhesion molecule-1 high-sensitivity C-reactive protein, ferritin, myeloperoxidase, macrophage inflammatory protein (MIP)-1a, MIP 3, and macrophage colony-stimulating factor-1 were independently associated with MACE., Conclusions: Among persons undergoing coronary angiography procedures, distinct clusters of inflammatory biomarker distributions with significant prognostic meaning may be identified. These results may identify unique targets for anti-inflammatory treatments aimed at CV disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Understanding trends in cardiovascular (CV) risk factors and CV disease according to age, sex, race, and ethnicity is important for policy planning and public health interventions., Objectives: The goal of this study was to project the number of people with CV risk factors and disease and further explore sex, race, and ethnical disparities., Methods: The prevalence of CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and obesity) and CV disease (ischemic heart disease, heart failure, myocardial infarction, and stroke) according to age, sex, race, and ethnicity was estimated by using logistic regression models based on 2013-2018 National Health and Nutrition Examination Survey data and further combining them with 2020 U.S. Census projection counts for years 2025-2060., Results: By the year 2060, compared with the year 2025, the number of people with diabetes mellitus will increase by 39.3% (39.2 million [M] to 54.6M), hypertension by 27.2% (127.8M to 162.5M), dyslipidemia by 27.5% (98.6M to 125.7M), and obesity by 18.3% (106.3M to 125.7M). Concurrently, projected prevalence will similarly increase compared with 2025 for ischemic heart disease by 31.1% (21.9M to 28.7M), heart failure by 33.0% (9.7M to 12.9M), myocardial infarction by 30.1% (12.3M to 16.0M), and stroke by 34.3% (10.8M to 14.5M). Among White individuals, the prevalence of CV risk factors and disease is projected to decrease, whereas significant increases are projected in racial and ethnic minorities., Conclusions: Large future increases in CV risk factors and CV disease prevalence are projected, disproportionately affecting racial and ethnic minorities. Future health policies and public health efforts should take these results into account to provide quality, affordable, and accessible health care., Competing Interests: Funding Support and Author Disclosures Dr Mohebi is supported by the Barry Fellowship. Dr McCarthy is supported by a National. Heart, Lung, and Blood Institute T32 postdoctoral training grant (5T32HL094301-12). Dr Hyle is supported by the National Institute on Aging (R01 AG069575). Dr Januzzi is supported by the Hutter Family Professorship. Dr Ibrahim has received honoraria from Cytokinetics, Medtronic, Novartis, and Roche. Dr Gaggin has received research grant support from Roche Diagnostics, Jana Care, Ortho Clinical, Novartis, Pfizer, Alnylam, and Akcea; has received consulting income from Amgen, Eko, Merck, Roche Diagnostics, and Pfizer; has stock ownership for Eko; has received research payments for clinical endpoint committees from Radiometer; and has received research payment for clinical endpoint committees from the Baim Institute for Clinical Research for Abbott, Siemens, and Beckman Coulter. Dr Singer receives research support from Bristol Myers Squibb; and has received consulting income from Bristol Myers Squibb, Fitbit, Medtronic, and Pfizer. Dr Wasfy is supported by a grant from the American Heart Association (18 CDA 34110215); and has received consulting income from Pfizer and Biotronik. Dr Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The relation of high-sensitivity cardiac troponin I (hs-cTnI) concentration and presence of obstructive coronary artery disease (CAD) in patients without myocardial infarction (MI) is unclear. Study participants selected from patients free of MI who underwent coronary angiography with or without intervention were enrolled, and hs-cTnI measured. A gradient boosting model was implemented to build a model for detection of CAD. Cox proportional hazard regression was used to assess the association of hs-cTnI and adverse cardiovascular (CV) outcome. Among 978 study participants, 607 patients (62%) had CAD. Higher concentrations of hs-cTnI were associated with chronic kidney disease, heart failure, CAD, male gender, current tobacco use, anemia, age, and low-density lipoprotein cholesterol. History of CAD, male gender, type 2 diabetes mellitus, hs-cTnI, anemia, age, and high-density lipoprotein cholesterol were the most influential factors for detection of CAD. The gradient boosting model had an area under the curve of 0.82, accuracy of 75%, sensitivity of 88%, specificity of 52%, positive predictive value of 76%, and negative predictive value of 72% for detection of CAD. Increase in 1 log unit of hs-cTnI was significantly associated with increased risk of incident MI (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.22 to 1.47, p <0.001), CV mortality (HR 1. 24, 95% CI 1.11 to 1.39, p <0.001), and composite of incident MI or CV mortality (HR 1.29, 95% CI 1.20 to 1.40, p <0.001). In conclusion, among patients without acute MI and CAD, higher concentrations of hs-cTnI were associated with the presence of CAD and linked to increased risk of future CV events. ClinicalTrials.gov Identifier: NCT00842868., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Type 2 myocardial infarction (T2MI) refers to myocardial necrosis caused by an imbalance in myocardial oxygen supply and demand and in the absence of acute coronary thrombosis. Despite growing recognition of this entity, there remains little understanding of the pathophysiology and uncertainty over the diagnostic criteria for this subtype of MI. Alarmingly, recent studies suggest that a diagnosis of T2MI pertains a prognosis similar to, if not worse than, type 1 MI. With increasing clinical use of high-sensitivity cardiac troponin assays, the frequency of recognition of T2MI is expected to increase. Yet, there remains a scarcity of prospective studies examining this cohort of patients, let alone randomized clinical trials identifying optimum treatment strategies. Further evaluation of the prevalence, pathophysiology and management of this patient cohort is warranted by the scientific community.

The best-accepted definition of myocardial infarction (MI) is provided by statements from the Universal Definition of MI Global Task force. This article, now in its third iteration, defines MI as myocardial cell death due to prolonged myocardial ischemia. It further delineates an increasingly incident subclassification of MI known as type 2 MI (T2MI). T2MI identifies instances of myocardial necrosis in which an imbalance between myocardial oxygen supply and/or demand occurs for reasons other than atherosclerotic plaque disruption. While associated with considerable risk (comparable to that of type 1 MI, which has well-defined management strategies), the spectrum of potential etiologies for T2MI makes development of precise diagnostic criteria and therapeutic implications of the diagnosis challenging., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Despite growing recognition of type 2 myocardial infarction (T2MI; related to supply/demand mismatch), little is known about its risk factors or its association with outcome., Methods: A single-center cohort of patients undergoing coronary or peripheral angiography with or without intervention was prospectively enrolled and followed for incident type 1 and T2MI, and major adverse cardiovascular events (MACE, a composite of all-cause death, nonfatal myocardial infarction [MI], heart failure, stroke, transient ischemic attack, peripheral arterial complication, and cardiac arrhythmia), as well. T2MI was adjudicated using criteria from the Third Universal Definition of MI. Baseline characteristics, blood samples, and angiography information were obtained. Major end points subsequent to first MI were assessed using landmark analyses to compare the rates of first events only where everyone with a prior history of any MACE before MI were censored and adjusted for follow-up times. Cox proportional hazard models were used for time-to-event analyses with age and sex forced into all models and additional covariates evaluated by using the stepwise option for the selection., Results: One thousand two hundred fifty-one patients were enrolled and followed for a median of 3.4 years. Of these patients, 152 (12.2%) had T2MI during follow-up; T2MI was frequently recurrent. Multivariable predictors of T2MI were older age, lower systolic blood pressure, history of coronary artery disease, heart failure, chronic obstructive pulmonary disease, diabetes mellitus, nitrate use, and elevated concentrations of glucose, N-terminal pro-B type natriuretic peptide, and cystatin C. Patients with T2MI had higher rates of subsequent adverse events than those without T2MI (per 100 person-years: MACE, 53.7 versus 21.1, P<0.001; all-cause death, 23.3 versus 3.3, P<0.001; cardiovascular death, 17.5 versus 2.6, P<0.001; heart failure events, 22.4 versus 7.4, P<0.001); these rates are similar to those seen in patients with type 1 MI. Incident diagnosis of T2MI strongly predicted risk for subsequent MACE (adjusted hazard ratio, 1.90; 95% confidence interval, 1.46-2.48; P<0.001), all-cause death (adjusted hazard ratio, 2.96; 95% confidence interval, 2.01-4.36; P<0.001), and cardiovascular death (adjusted hazard ratio, 2.16; 95% confidence interval, 1.36-3.43; P=0.001)., Conclusions: T2MI is common and associated with poor prognosis. Studies evaluating treatment strategies for management of T2MI are needed., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842868., (© 2016 American Heart Association, Inc.)

Background: Reference intervals of high-sensitivity troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been determined from Western populations. No data are available regarding expected values in Asian populations., Methods: A total of 1157 age- and sex-matched healthy individuals (mean age, 41.2 years; 48.0% male) were prospectively enrolled from the US (n = 565) and Vietnam (n = 592). Blood samples were analyzed for hs-cTnT and NT-proBNP. Median values were determined for each country and compared in unadjusted analyses and in analyses adjusted for age, sex, body mass index, study site, race, and vital signs., Results: Median hs-cTnT concentrations were slightly higher for individuals from the US than for those from Vietnam, but both were below the limit of detection (3.7 vs 3.0 ng/L, respectively; P = 0.03). More US participants had an hs-cTnT concentration above the limit of detection (57.2% vs 47.3%; P = 0.001), but the 99th percentile concentration was slightly higher for Asians (US 15.1 vs Vietnam 19.0 ng/L). Concentrations for >98% of both populations were below the standard hs-cTnT 99th percentile of 14.0 ng/L (P = 0.54). Median NT-proBNP concentrations were slightly higher for US participants compared with Vietnamese participants (28 vs 16 ng/L, respectively; P < 0.001). Following adjustment, differences in concentrations of NT-proBNP between healthy US and Vietnamese populations remained significant, whereas for hs-cTnT the differences were no longer significant. Inclusion of hs-cTnT values down to the limit of blank did not change the result., Conclusions: The differences in hs-cTnT and NT-proBNP between healthy individuals from the US and Vietnam are small. Previously derived reference intervals for both analytes may be applied in Asian populations.

Background: Positive psychological constructs, such as optimism, are associated with beneficial health outcomes. However, no study has separately examined the effects of multiple positive psychological constructs on behavioral, biological, and clinical outcomes after an acute coronary syndrome (ACS). Accordingly, we aimed to investigate associations of baseline optimism and gratitude with subsequent physical activity, prognostic biomarkers, and cardiac rehospitalizations in post-ACS patients.Methods and Results: Participants were enrolled during admission for ACS and underwent assessments at baseline (2 weeks post-ACS) and follow-up (6 months later). Associations between baseline positive psychological constructs and subsequent physical activity/biomarkers were analyzed using multivariable linear regression. Associations between baseline positive constructs and 6-month rehospitalizations were assessed via multivariable Cox regression. Overall, 164 participants enrolled and completed the baseline 2-week assessments. Baseline optimism was significantly associated with greater physical activity at 6 months (n=153; β=102.5; 95% confidence interval, 13.6-191.5; P=0.024), controlling for baseline activity and sociodemographic, medical, and negative psychological covariates. Baseline optimism was also associated with lower rates of cardiac readmissions at 6 months (n=164), controlling for age, sex, and medical comorbidity (hazard ratio, 0.92; 95% confidence interval, [0.86-0.98]; P=0.006). There were no significant relationships between optimism and biomarkers. Gratitude was minimally associated with post-ACS outcomes.Conclusions: Post-ACS optimism, but not gratitude, was prospectively and independently associated with superior physical activity and fewer cardiac readmissions. Whether interventions that target optimism can successfully increase optimism or improve cardiovascular outcomes in post-ACS patients is not yet known, but can be tested in future studies.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01709669. [ABSTRACT FROM AUTHOR]

Background: Noninvasive models to predict the presence of coronary artery disease (CAD) may help reduce the societal burden of CAD.Objectives: From a prospective registry of patients referred for coronary angiography, the goal of this study was to develop a clinical and biomarker score to predict the presence of significant CAD.Methods: In a training cohort of 649 subjects, predictors of ≥70% stenosis in at least 1 major coronary vessel were identified from >200 candidate variables, including 109 biomarkers. The final model was then validated in a separate cohort (n = 278).Results: The scoring system consisted of clinical variables (male sex and previous percutaneous coronary intervention) and 4 biomarkers (midkine, adiponectin, apolipoprotein C-I, and kidney injury molecule-1). In the training cohort, elevated scores were predictive of ≥70% stenosis in all subjects (odds ratio [OR]: 9.74; p < 0.001), men (OR: 7.88; p <0.001), women (OR: 24.8; p < 0.001), and those with no previous CAD (OR: 8.67; p < 0.001). In the validation cohort, the score had an area under the receiver-operating characteristic curve of 0.87 (p < 0.001) for coronary stenosis ≥70%. Higher scores were associated with greater severity of angiographic stenosis. At optimal cutoff, the score had 77% sensitivity, 84% specificity, and a positive predictive value of 90% for ≥70% stenosis. Partitioning the score into 5 levels allowed for identifying or excluding CAD with >90% predictive value in 42% of subjects. An elevated score predicted incident acute myocardial infarction during 3.6 years of follow up (hazard ratio: 2.39; p < 0.001).Conclusions: We described a clinical and biomarker score with high accuracy for predicting the presence of anatomically significant CAD. (The CASABLANCA Study: Catheter Sampled Blood Archive in Cardiovascular Diseases; NCT00842868). [ABSTRACT FROM AUTHOR]

Introduction: Concentrations of circulating apolipoproteins are strongly linked to risk for coronary artery disease (CAD). However, relative importance of the additional knowledge of apolipoprotein concentrations within specific lipoprotein species for CAD risk prediction is limited. Hypothesis: Apolipoproteins (apo) directly within high density lipoprotein (HDL) particles among patients undergoing coronary angiography associate with CAD quantitative measures and outcomes. Methods: HDL-associated apoA-1, apoC-1, apoC-2, apoC-3, and apoC-4 were measured in 938 participants without prevalent myocardial infarction (MI) referred for coronary angiography in the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA, NCT00842868) study. A composite score (pCAD) was calculated using these features based on a model to predict angiographic CAD from an independent set of patients. The pCAD score was then associated with likelihood of prevalent CAD (>=70% lesion in >=1 vessel) and with incident cardiovascular outcomes over a 4-year follow up period. Results: There were 587 (62.6%) patients with prevalent CAD. The pCAD HDL-specific proteomic score was associated with the presence of CAD (odds ratio per standard deviation [OR/SD]: 1.44; 95% confidence interval [CI]: 1.29-1.60). Association was independent of conventional cardiovascular risk factors, including circulating plasma apoA-1 and apoB measures. The C-statistic for CAD odds was 0.64 (95% CI 0.60-0.68). Additionally, pCAD was associated with the composite endpoint of incident MI and cardiovascular mortality (hazard ratio per SD [HR/SD]: 1.18, 95% CI: 1.01-1.38), in a model adjusting for conventional risk factors, including circulating plasma apoA-1 and apoB concentrations. In stratified analyses, the association with incident MI and cardiovascular mortality was similar (P for interaction = 0.41) in those with prevalent CAD (HR/SD: 1.21, 95% CI: 1.01-1.44) and those without prevalent CAD (HR/SD: 1.07, 95% CI: 0.73-1.58). Conclusions: An HDL proteomic score, independent of circulating apoA-1 and apoB concentrations, is strongly associated with the prevalence of CAD. Among those with CAD, this score predicted risk of future MI and cardiovascular death. [ABSTRACT FROM AUTHOR]