Systolic Blood Pressure, Diastolic Blood Pressure and Pulse Pressure and the Risk of Subclinical Myocardial Injury: The HUNT Study.

BACKGROUND: Subclinical myocardial injury expressed as higher cardiac troponin concentrations may represent an important intermediary between hypertension and the risk of cardiovascular disease. The study aimed to assess the relative strength of associations between systolic blood pressure (BP), diastolic BP, and pulse pressure, and subclinical myocardial injury, and how change in BP variables over time associates with subclinical myocardial injury. METHODS AND RESULTS: cTnl (cardiac troponin I) was measured in 32 968 participants of the fourth wave of the population-based cohort HUNT4 (Trøndelag Health Study) without a history of cardiovascular disease. An additional longitudinal analysis included participants from HUNT4 with BP measurements from HUNT3 (n=18 681). Associations between BP variables and cTnI concentrations were assessed by linear and logistic regression analyses. The median cTnI concentration was 1.6 ng/L (25th-75th percentiles, 0.6-3.1 ng/L), median age was 52 years (39.1-65.6 years), and 57% were female subjects. Cross-sectionally, only systolic BP categories ≥130 mm Hg associated with higher cTnI concentrations, compared with a reference systolic BP of <110 mm Hg. All categories of diastolic BP and pulse pressure were positively associated with higher cTnI concentrations when diastolic BP 70 to 79 mm Hg and pulse pressure <40 mm Hg were used as references, respectively. When comparing systolic BP, diastolic BP, and pulse pressure as continuous variables, cross-sectionally, pulse pressure most strongly associated with cTnI concentrations (P for all comparisons <0.001), whereas longitudinally, change in diastolic BP was most strongly associated with cTnI concentrations (P for all comparisons <0.05). CONCLUSIONS: Subjects with high pulse pressure and longitudinal increase in diastolic BP are at higher risk for subclinical myocardial injury.

Mortality and length of hospital stay after bloodstream infections caused by ESBL-producing compared to non-ESBL-producing E. coli.

OBJECTIVE: To compare mortality and length of hospital stay between patients with ESBL-producing E. coli bloodstream infections (BSIs) and patients with non-ESBL E. coli BSIs. We also aimed at describing risk factors for ESBL-producing E. coli BSIs and time to effective antibiotic treatment for the two groups. METHODS: A retrospective case-control study among adults admitted between 2014 and 2021 to a Norwegian University Hospital. RESULTS: A total of 468 E. coli BSI episodes from 441 patients were included (234 BSIs each in the ESBL- and non-ESBL group). Among the ESBL-producing E. coli BSIs, 10.9% (25/230) deaths occurred within 30 days compared to 9.0% (21/234) in the non-ESBL group. The adjusted 30-day mortality OR was 1.6 (95% CI 0.7-3.7, p = 0.248). Effective antibiotic treatment was administered within 24 hours to 55.2% (129/234) in the ESBL-group compared to 86.8% (203/234) in the non-ESBL group. Among BSIs of urinary tract origin (n = 317), the median length of hospital stay increased by two days in the ESBL group (six versus four days, p < 0.001). No significant difference in the length of hospital stay was found for other sources of infection (n = 151), with a median of seven versus six days (p = 0.550) in the ESBL- and non-ESBL groups, respectively. CONCLUSION: There was no statistically significant difference in 30-day mortality in ESBL-producing E. coli compared to non-ESBL E. coli BSI, despite a delay in the administration of an effective antibiotic in the former group. ESBL-production was associated with an increased length of stay in BSIs of urinary tract origin.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

Cardiac Troponin T and NT-proBNP for Prediction of 30-Day Readmission or Death in Patients with Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study.

INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to NT-proBNP for 30-day readmission or death in patients hospitalized with acute dyspnea. METHODS: We measured cTnT and NT-proBNP within 24 h in 314 patients hospitalized with acute dyspnea and adjudicated the cause of the index admission. Time to first event of readmission or death ≤30 days after hospital discharge was recorded, and cTnT and NT-proBNP measurements were compared head-to-head. RESULTS: Patients who died (12/314) or were readmitted (71/314) within 30 days had higher cTnT concentrations (median: 32.6, Q1-Q3: 18.4-74.2 ng/L vs. median: 19.4, Q1-Q3: 8.4-36.1 ng/L; p for comparison <0.001) and NT-proBNP concentrations (median: 1,753.6, Q1-Q3: 464.2-6,862.0 ng/L vs. median 984, Q1-Q3 201-3,600 ng/L; for comparison p = 0.027) compared to patients who survived and were not readmitted. cTnT concentrations were associated with readmission or death within 30 days after discharge both in the total cohort (adjusted hazard ratio [aHR]: 1.64, 95% confidence interval [CI]: 1.30-2.05) and in patients with heart failure (HF) (aHR: 1.58, 95% CI: 1.14-2.18). In contrast, NT-proBNP concentrations were not associated with short-term events, neither in the total cohort (aHR: 1.10, 95% CI: 0.94-1.30) nor in patients with adjudicated HF (aHR: 1.06, 95% CI: 0.80-1.40). CONCLUSION: cTnT concentrations are associated with 30-day readmission or death in patients hospitalized with acute dyspnea, as well as in patients adjudicated HF.

Patterns of Cardiac Troponin I Concentrations as Risk Predictors of Cardiovascular Disease and Death: The Trøndelag Health Study.

BACKGROUND: Concentrations of cardiac troponin predict risk of cardiovascular disease and death in the general population. There is limited evidence on changing patterns of cardiac troponin in the years preceding cardiovascular events. METHODS: We analyzed cardiac troponin I (cTnI) with a high-sensitivity assay in 3272 participants in the Trøndelag Health (HUNT) Study at study visit 4 (2017-2019). Of these, 3198 had measurement of cTnI at study visit 2 (1995-1997), 2661 at study visit 3, and 2587 at all 3 study visits. We assessed the trajectories of cTnI concentrations in the years prior to cardiovascular events using a generalized linear mixed model, with adjustment for age, sex, cardiovascular risk factors, and comorbidities. RESULTS: At HUNT4 baseline, median age was 64.8 (range 39.4-101.3) years, and 55% were women. Study participants who were admitted because of heart failure or died from cardiovascular cause on follow-up had a steeper increase in cTnI compared with study participants with no events (P < .001). The average yearly change in cTnI was 0.235 (95% confidence interval, 0.192-0.289) ng/L for study participants with heart failure or cardiovascular death, and -0.022 (95% confidence interval, -0.022 to -0.023) ng/L for study participants with no events. Study participants who experienced myocardial infarction, ischemic stroke, or noncardiovascular mortality exhibited similar cTnI patterns. CONCLUSIONS: Fatal and nonfatal cardiovascular events are preceded by slowly increasing concentrations of cardiac troponin, independently of established cardiovascular risk factors. Our results support the use of cTnI measurements to identify at-risk subjects who progress to subclinical and later overt cardiovascular disease.

Prediction of incident atrial fibrillation with cardiac biomarkers and left atrial volumes.

OBJECTIVE: Atrial fibrillation is a common arrhythmia associated with risk of stroke, heart failure and death. We aimed to elucidate the associations of cardiac biomarkers, echocardiographic left atrial volumetric indices and risk of prevalent and incident atrial fibrillation in the general population. METHODS: We assessed cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), maximum (LAVimax) and minimum (LAVimin) indexed left atrial volumes and left atrial emptying fraction (LAEF) in subjects born in 1950 participating in the prospective observational cohort, Akershus Cardiac Examination 1950 Study. The Cohorts for Heart and Ageing Research in Genomic Epidemiology for Atrial Fibrillation risk score and sex was used to adjust for residual risk of atrial fibrillation. RESULTS: Out of 3487 subjects, 157 (4.5%) had prevalent and 123 (3.5%) had incident atrial fibrillation. Echocardiographic left atrial volumes and cardiac biomarkers associated with prevalent atrial fibrillation, but GDF-15 was non-significant in adjusted analysis. Incident atrial fibrillation was predicted by LAVimax (adjusted HR 1.51, 95% CI 1.30 to 1.75), LAVimin (adjusted HR 1.52, 95% CI 1.35 to 1.72), LAEF (adjusted HR 1.24, 95% CI 1.04 to 1.48) and NT-proBNP (adjusted HR 1.57, 95% CI 1.32 to 1.85). cTnT and NT-proBNP provided incremental prognostic information to left atrial volumes, but GDF-15 demonstrated no prognostic value for incident atrial fibrillation. CONCLUSIONS: In the general population, echocardiographic left atrial volumetric indices and NT-proBNP, but not cTnT and GDF-15, associate with prevalent atrial fibrillation and with risk of incident atrial fibrillation. cTnT and NT-proBNP provide incremental prognostic information to echocardiography.

Serial blood pressure measurements, left ventricular remodelling and cardiovascular outcomes.

BACKGROUND: Hypertension is a risk factor for the development of cardiovascular disease. Whether serial blood pressure (BP) measurements are more closely associated with subclinical left ventricular (LV) remodelling and better predict risk of cardiovascular events over individual BP measurements are not known. METHODS: We assessed systolic BP, diastolic BP and pulse pressure at several time points during adulthood in 1333 women and 1211 men participating in the Akershus Cardiac Examination 1950 Study. We defined serial BP measurements as the sum of averaged BPs from adjacent consecutive visits indexed to total exposure time between measurements. We assessed the associations between serial and individual BP measurements and (1) LV structure, function and volumes and (2) incident myocardial infarction, ischemic stroke, heart failure and cardiovascular death. RESULTS: All indices of higher serial BP measurements were associated with increased indexed LV mass, and the associations were stronger than those of individual BP measurements. Serial diastolic BP pressure was strongly and inversely associated with LV systolic function, while higher serial systolic BP was primarily associated with higher LV volumes. Both serial systolic (incidence rate ratio [IRR] 1.10, 95% CI 1.03 to 1.17) and diastolic BPs (IRR 1.14, 95% CI 1.02 to 1.27) were associated with increased incidence of clinical events. CONCLUSION: In healthy community dwellers without established cardiovascular disease, different serial BP indices associate strongly with LV remodelling and cardiovascular outcomes. Whether the use of serial BP indices for guiding treatment is superior to individual measurements should be explored in additional prospective studies.

Impact of Blood Pressure in the Early 40s on Left Atrial Volumes in the Mid-60s: Data From the ACE 1950 Study.

Background Echocardiographic measures of left atrial volumes are powerful predictors of cardiovascular events and important for assessing diastolic dysfunction. Despite this, there is limited knowledge of factors influencing left atrial remodeling. In particular, the impact of blood pressure in those in their early 40s on left atrial volumes later in life has not been sufficiently elucidated. Methods and Results We linked data from individuals born in 1950 who participated in the Age 40 Program, and the ACE (Akershus Cardiac Examination) 1950 Study. We divided the study population into quartiles of systolic blood pressure in their early 40s and assessed the proportion of individuals with an enlarged left atrium in their mid-60s. The associations between blood pressure and left atrial volumes were assessed in linear regression analyses. Of the 2591 individuals included in this study, 1302 (50.3%) were women, and the mean age in the Age 40 Program was 40.1±0.3 years. Systolic blood pressure was 128.1±13.6 mm Hg and diastolic blood pressure was 78.3±9.5 mm Hg. Mean age in the ACE 1950 Study was 64.0±0.6 years. The proportion of individuals with an enlarged left atrium increased across the quartiles of systolic blood pressure (P=0.001). Systolic blood pressure was independently associated with left atrial volumes; the end-systolic volume was 0.09 mL (95% CI, 0.04-0.14 mL) larger per 1-mm Hg higher systolic blood pressure. Conclusions Our findings suggest that increased blood pressure in those in their early 40s is relevant for left atrial remodeling later in life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01555411.

Prognostic value of cardiac biomarkers and National Early Warning Score 2 in acute dyspnoea.

OBJECTIVE: Patients hospitalised with acute dyspnoea due to acute heart failure (AHF) have a grave prognosis, but the European Society of Cardiology guidelines recommend no system to risk stratify these patients. The prognostic value of combining National Early Warning Score (NEWS) 2 and established cardiac biomarkers is not known. METHODS: We measured high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and calculated NEWS2 in 314 patients with acute dyspnoea within 24 hours of hospitalisation. Their prognostic merits were assessed in the total cohort and for the subgroup with AHF separately. RESULTS: The median age was 73 (quartile (Q) 1-3, 63-81) years, 48% were women and 143 patients (46%) were hospitalised with AHF. The 114 patients (36%) who died during follow-up (median 823 days, Q1-3, 471-998) had higher concentrations of hs-cTnT (62 vs 33 ng/L, p<0.001) and NT-proBNP (6995 vs 2605 ng/L, p<0.001), and higher NEWS2 (6.1 vs 4.5 points, p<0.001), compared with survivors. Patients with increased vs low NEWS2 clinical risk had higher mortality rates in adjusted analyses in the total cohort (HR 2.11, 95% CI 1.28 to 3.48) and in patients with AHF (HR 2.00, 95% CI 1.54 to 2.60). NEWS2 provided incremental prognostic information compared with biomarkers alone for the total cohort: area under the curve 0.72 vs 0.70, p=0.042, and for the subpopulation with AHF: 0.70 vs 0.67, p=0.014. CONCLUSION: NEWS2 predicts long-term mortality in patients hospitalised due to acute dyspnoea and the subgroup with AHF and provide incremental prognostic information to hs-cTnT and NT-proBNP.

Treatable Traits in Misdiagnosed Chronic Obstructive Pulmonary Disease: Data from the Akershus Cardiac Examination 1950 Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often misdiagnosed. We aimed to estimate the prevalence of misdiagnosed COPD in middle-aged Norwegians, and to assess potentially treatable clinical traits in over- and undiagnosed individuals. METHODS AND FINDINGS: The Akershus Cardiac Examination (ACE) 1950 Study is a population-based study of the 1950 birth cohort of Akershus county including 3706 participants aged 62-65 years at baseline. COPD was defined as a forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio < lower limit of normal (LLN). Misdiagnosed COPD was defined according to self-reported COPD. A total of 259 (7.1%) participants had spirometry confirmed COPD. Of these, only 72 (28%) reported having COPD, thus 187 (72%) were undiagnosed. A total of 92 (2.5%) of the 164 particpants who reported having COPD had an FEV1/FVC ratio ≥ LLN and were overdiagnosed. They had lower lung function, and more respiratory symptoms, self-reported asthma, eosinophils, and sleep apnea than other non-COPD participants . The main predictor of being overdiagnosed was overweight. Spirometry in participants reporting wheezing or cough and current smokers or participants with ≥20 tobacco pack-year history would have identified 85% of the undiagnosed cases. CONCLUSION: Both over- and underdiagnosis of COPD is frequent. Undiagnosed individuals have better lung function and less symptoms, but similar prevalence of comorbidities and systemic inflammation. Overdiagnosed individuals have treatable traits including asthma, eosinophilic inflammation, and sleep apnea. The main predictor of being overdiagnosed was being overweight.

Tobacco Consumption and High-Sensitivity Cardiac Troponin I in the General Population: The HUNT Study.

Background Cardiac troponins represent a sensitive index of subclinical myocardial injury and are associated with increased risk of cardiovascular events in the general population. Despite positive associations with cardiovascular risk of both cardiac troponins and cigarette smoking, concentrations of cardiac troponin I measured by high-sensitivity assays (hs-cTnI) are paradoxically lower in current smokers than in never-smokers. The impact of smoking intensity and time from smoking cessation on hs-cTnI remains unknown. Methods and Results hs-cTnI concentrations were measured in 32028 subjects free from cardiovascular disease enrolled in the prospective, population-based HUNT (Trøndelag Health Study). Tobacco habits were self-reported and classified as never (n=14 559), former (n=14 248), and current (n=3221) smokers. Current smokers exhibited significantly lower concentrations of hs-cTnI than never-smokers (P<0.001). In adjusted models, both current smoking (-17.3%; 95% CI, -20.6 to -13.9%) and former smoking (-6.6%; 95% CI, -8.7 to -4.5%) were associated with significantly lower hs-cTnI concentrations. Among former smokers, higher smoking burden (>10 pack-years) were associated with lower concentrations of hs-cTnI. Time since smoking cessation was associated with increasing concentrations of hs-cTnI in a dose-dependent manner (P for trend<0.001), and subjects who quit smoking >30 years ago had concentrations of hs-cTnI comparable with those of never-smokers. Conclusions In the general population, both current and former cigarette smoking is associated with lower concentrations of hs-cTnI. In former smokers, there was a dose-response relationship between pack-years of smoking, and hs-cTnI. Time since smoking cessation was associated with increasing concentrations of hs-cTnI, indicating a continuum of hs-cTnI from current smoker to never-smokers.

Lifetime obesity trends are associated with subclinical myocardial injury: The Trøndelag health study.

BACKGROUND: Obesity is associated with subclinical myocardial injury as quantified by concentrations of cardiac troponin T, but whether lifetime excess weight history is associated with increased concentrations of cardiac troponin I (cTnI) and how indices of abdominal adiposity and glycemic dysregulation affect these associations remain unclear. METHODS: We analyzed cTnI with a high-sensitivity assay in 9739 participants in the Trøndelag Health (HUNT) Study at study visit 4 (2017-2019). BMI was assessed at study Visit 1 (1984-1986), 2 (1995-1997), 3 (2006-2008), and 4. RESULTS: Median age at visit 4 was 68.7 years and 59% were women. Concentrations of cTnI were detectable in 84.1% of study participants, with a median of 2.5 (1.5-4.5 ng/L). We identified three clusters of BMI trajectories from visit 1 to 4, (1) stable normal weight, (2) stable overweight, and (3) stable obesity. Participants in clusters 2 and 3 were at increased risk of elevated concentrations of cTnI at visit 4 (odds ratio 1.27, 95% CI 1.09-1.47, and odds ratio 1.70, 95% CI 1.33-2.17, p for trend <0.001). Participants in cluster 3 had 22.0 (95% CI 14.1-29.9) higher concentrations of cTnI compared to participants in cluster 1 (p for trend <0.001). Dysregulated glucose metabolism and abdominal obesity did not influence our results. CONCLUSIONS: Individuals with stable overweight or obesity are at increased risk of subclinical myocardial injury, independently of glycemic dysregulation and abdominal adiposity. Our data support a direct detrimental effect of long-standing obesity on cardiovascular health.

Pragmatic trials - what are they? / Pragmatiske studier ­ hva er det?

Pragmatic clinical trials are based on data from unselected patients recruited from common clinical practice. These trials therefore bridge the gap between evidence-based medicine and clinical practice.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Cardiac troponin I measured with a very high sensitivity assay predicts subclinical carotid atherosclerosis: The Akershus Cardiac Examination 1950 Study.

AIMS: Concentrations of cardiac troponin I (cTnI) are associated with incident ischemic stroke and predict the presence and severity of coronary atherosclerosis. Accordingly, we hypothesized that concentrations of cTnI measured with a very high sensitivity (hs-) assay would be associated with subclinical stages of carotid atherosclerosis in the general population. METHODS: We measured hs-cTnI on the Singulex Clarity System in 1745 women and 1666 men participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants were free from known coronary heart disease and underwent extensive cardiovascular phenotyping at baseline, including carotid ultrasound. We quantified carotid atherosclerosis by the carotid plaque score, carotid intima-media thickness (cIMT) and the presence of hypoechoic plaques. RESULTS: Concentrations of hs-cTnI were measurable in 99.8% of study participants and were significantly associated with increased carotid plaque score (odds ratio for quartile 4 of hs-cTnI 1.59, 95% CI 1.22 to 2.07, p for trend < 0.001) and cIMT (odds ratio for quartile 4 of hs-cTnI 1.57, 95% CI 1.02 to 2.42, p for trend = 0.036), but not with the presence of hypoechoic plaques. hs-cTnI concentrations significantly improved reclassification and discrimination models in predicting carotid plaques when added to cardiovascular risk factors, no improvements were evident in predicting cIMT or hypoechoic plaques. CONCLUSION: Concentrations of cTnI measured with a very high sensitivity assay are predictive of carotid atherosclerotic burden, a phenomenon likely attributable to common risk factors of subclinical myocardial injury, coronary and carotid atherosclerosis.

Circulating MicroRNA-210 Concentrations in Patients with Acute Heart Failure: Data from the Akershus Cardiac Examination 2 Study.

BACKGROUND: MicroRNA (miR)-210 expression is induced by acute and chronic hypoxia and provides prognostic information in patients with aortic stenosis and acute coronary syndrome. We hypothesized that circulating miR-210 concentrations could provide diagnostic and prognostic information in patients with acute heart failure (HF). METHODS: We measured miR-210 concentrations in serum samples on admission from 314 patients hospitalized for acute dyspnea and 9 healthy control subjects. The diagnostic and prognostic properties of miR-210 were tested in patients after adjudication of all diagnoses and with median follow-up of 464 days. RESULTS: All patients and control subjects had miR-210 concentrations within the range of detection, and the analytical variation was low as the coefficient of variation of synthetic spike-in RNA was 4%. Circulating miR-210 concentrations were increased in patients with HF compared to healthy control subjects, but miR-210 concentrations did not separate patients with acute HF (n = 143) from patients with non-HF-related dyspnea (n = 171): the area under the curve was 0.50 (95% CI 0.43-0.57). Circulating miR-210 concentrations were associated with mortality (n = 114) after adjustment for clinical risk factors (hazard ratio 1.65 [95% CI 1.03-2.62] per unit miR-210 increase), but this association was attenuated and not significant after adjustment for established cardiac protein biomarkers. CONCLUSIONS: Circulating miR-210 concentrations are associated with mortality, but do not add to established protein biomarkers for diagnosis or prognosis in patients with acute dyspnea.

High-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide in acute heart failure: Data from the ACE 2 study.

BACKGROUND: To assess if cardiac troponins can improve diagnostics of acute heart failure (AHF) and provide prognostic information in patients with acute dyspnea. METHODS: We measured cardiac troponin T with a high-sensitivity assay (hs-cTnT) in 314 patients hospitalized with acute dyspnea. The index diagnosis was adjudicated and AHF patients were stratified into AHF with reduced or preserved ejection fraction (HFrEF/HFpEF). The prognostic and diagnostic merit of hs-cTnT was compared to the merit of N-terminal pro-B-type natriuretic peptide (NT-proBNP). RESULTS: In the total population, median age was 73 (quartile [Q] 1-3 63-81) years and 48% were women. One-hundred-forty-three patients were categorized as AHF (46%) and these patients had higher hs-cTnT concentrations than patients with non-AHF-related dyspnea: median 38 (Q1-3 22-75) vs. 13 (4-25) ng/L; p < 0.001. hs-cTnT concentrations were similar between patients with HFrEF and HFpEF (p = 0.80), in contrast to NT-proBNP, which was higher in HFrEF (p < 0.001). C-statistics for discriminating HFpEF from non-AHF-related dyspnea was 0.80 (95% CI 0.73-0.86) for hs-cTnT, 0.79 (0.73-0.86) for NT-proBNP, and 0.83 (0.76-0.89) for hs-cTnT and NT-proBNP in combination. Elevated hs-cTnT remained associated with HFpEF in logistic regression analysis after adjusting for demographics, comorbidities and renal function. During median 27 months of follow-up, 114 (36%) patients died in the total population. Higher hs-cTnT concentrations were associated with increased risk of all-cause mortality after adjustment for clinical variables and NT-proBNP: hazard ratio 1.30 (95% CI 1.07-1.58), p = 0.009. CONCLUSION: hs-cTnT measurements improve diagnostic accuracy for HFpEF and provide independent prognostic information in unselected patients with acute dyspnea.