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Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people.

Background Most studies assessing the diagnostic value of high-sensitivity troponin in the diagnosis of myocardial infarction used batch-wise analyses of frozen samples for high-sensitivity troponin measurements. Whether the accuracy of these batch-wise high-sensitivity troponin measurements described in diagnostic studies is comparable to clinical routine is unknown.Methods We enrolled 937 patients presenting with suspected myocardial infarction in this prospective cohort study. Measurements of high-sensitivity troponin I (Abbott Architect) and high-sensitivity troponin T (Roche) were performed in two settings: (a) on-demand in clinical routine using fresh blood samples; and (b) in batches using frozen blood samples from the same individuals at three timepoints (0 hours, 1 hour and 3 hours after presentation).Results Median troponin levels were not different between on-demand and batch-wise measurements. Troponin levels in the range of 0 to 40 ng/L showed a very high correlation between the on-demand and batch setting (Pearson correlation coefficient (r) was 0.92–0.95 for high-sensitivity troponin I and 0.96 for high-sensitivity troponin T). However, at very low troponin levels (0 to 10 ng/L) correlation between the two settings was moderate (rfor high-sensitivity troponin I 0.59–0.66 and 0.65–0.69 for high-sensitivity troponin T). Application of guideline-recommended rapid diagnostic algorithms showed similar diagnostic performance with both methods.Conclusions Overall on-demand and batch-wise measurements of high-sensitivity troponin provided similar results, but their correlation was moderate, when focusing on very low troponin levels. The application of rapid diagnostic algorithms was safe in both settings. Trial Registration:www.clinicaltrials.gov(NCT02355457)

Aims: The new European Society of Cardiology guideline for ST-segment elevation myocardial infarction recommends that left and right bundle branch block should be considered equal for recommending urgent angiography in patients with suspected myocardial infarction. We aimed to evaluate this novel recommendation in two prospective studies of patients with suspected myocardial infarction.Methods and results: We included 4067 patients presenting to the emergency department with suspected myocardial infarction. All patients had an ECG recorded immediately upon admission. Patients were classified as having right bundle branch block (RBBB), left bundle branch block (LBBB), bifascicular block (BFB) or no bundle branch block. All patients were followed for up to two years to assess mortality. In the overall population 125 (3.1%) patients had RBBB, 281 (6.9%) LBBB and 60 (1.5%) BFB. The final diagnosis of myocardial infarction was adjudicated in 20.8% (RBBB), 28.5% (LBBB), 23.3% (BFB) and 21.6% (no complete block) of patients. The mortality rate after one year was 10.7% (RBBB), 7% (LBBB), 17.5% (BFB) and 3.2% (no complete block). The adjusted hazard ratios were 1.29 (95% confidence interval (CI) 0.71–2.34; P=0.40) for RBBB, 1.71 (95% CI 1.17–2.50; P=0.006) for LBBB and 2.27 (95% CI 1.28–4.05; P=0.005) for BFB.Conclusion: Our results support the new European Society of Cardiology ST-segment elevation myocardial infarction guideline describing RBBB as a high risk for mortality in patients with suspected myocardial infarction. However, the data challenge the concept of RBBB as a trigger of acute angiography because the likelihood of myocardial infarction in a chest pain unit setting is equally frequent in patients without bundle branch block.

Troponin is a widely used biomarker in patients with cardiac diseaseHigh-sensitivity assays enable the detection of very low concentrations of troponinRapid diagnostic strategies for patients with suspected acute myocardial infarction have been introducedNoncoronary and nonacute applications of troponin assays are on the horizon, and might improve individual risk stratification

AbstractBackground:Renal denervation has been proposed as a therapeutic option in patients with resistant hypertension. Circulating blood borne biomarkers might be helpful to identify individuals responding to RDN therapy. MR-proADM is a strong prognostic marker in patients with cardiovascular disease. The aim of this multicenter study was to evaluate the effect of RDN on MR-proADM concentrations.Methods and results:We measured MR-proADM, BNP, and MR-proANP in 110 patients before and after RDN in a multicenter setting. All patients were followed up after 1 and 6 months by office and ambulatory blood pressure (BP) measurements. The mean office BP decreased from 165/89 to 152/87 mmHg 6 months after RDN (systolic: p < 0.001; diastolic: ns), the responder-rate was 74%. Intriguingly MR-proADM concentrations increased from 0.66 to 0.69 nmol/L (p < 0.001) and were significantly associated with reduction of systolic office BP after 6 months in multivariate analyses (coefficient −0.0018, p < 0.001). In therapy-responders MR-proADM concentrations showed a significantly higher increase over time (coefficient 0.0105, p < 0.05), as compared to non-responders. There were no significant differences in BP change for individuals with low and high baseline MR-proADM (BP-Delta low MR-proADM −23/−4 mmHg vs. high MR-proADM −24/−5 mmHg). The natriuretic biomarkers BNP and MR-proANP did not change significantly after 6 months. Biomarkers at baseline were not able to predict for therapy-responder.Conclusion:In patients undergoing RDN, baseline measurements of various biomarkers had no prognostic use for therapy success in this short time follow-up period in a multicenter approach. Intriguingly, MR-proADM showed a significant association with BP reduction after 6 months.

IMPORTANCE: Rapid and accurate diagnosis of acute myocardial infarction (AMI) currently constitutes an unmet need. OBJECTIVE: To test a 1-hour diagnostic algorithm to diagnose AMI using a high-sensitivity troponin I assay with a new cutoff level of 6 ng/L. DESIGN, SETTING, AND PARTICIPANTS: The Biomarkers in Acute Cardiac Care study is a prospective study that investigated the application of the troponin I assay for the diagnosis of AMI in 1040 patients presenting to the emergency department with acute chest pain from July 19, 2013, to December 31, 2014. Results were validated in 2 independent cohorts of 4009 patients. Final follow-up was completed on July 1, 2015, and data were assessed from July 2 to December 15, 2015. EXPOSURE: Acute chest pain suggestive of AMI. MAIN OUTCOMES AND MEASURES: Accurate diagnosis or exclusion of AMI and 12-month mortality in patients with acute chest pain. RESULTS: Of the 1040 patients included from the study cohort, 673 (64.7%) were male and had a median age of 65 (interquartile range, 52-75) years. With application of a low troponin I cutoff value of 6 ng/L, the rule-out algorithm showed a high negative predictive value of 99.8% (95% CI, 98.6%-100.0%) after 1 hour for non–ST-segment elevation MI type 1. The 1-hour approach was comparable to a 3-hour approach. Similarly, a rule-in algorithm based on troponin I levels provided a high positive predictive value with 82.8% (95% CI, 73.2%-90.0%). Moreover, application of the cutoff of 6 ng/L resulted in lower follow-up mortality (1.0%) compared with the routinely used 99th percentile (3.7%) for this assay. Two independent cohorts further validated the performance of this algorithm with high negative and positive predictive values. CONCLUSIONS AND RELEVANCE: Patients with possible AMI can be triaged within 1 hour after admission with no loss of safety compared with a 3-hour approach, when a low and sensitive cutoff is applied. This concept enables safe discharge or rapid treatment initiation after 1 hour.