Variability in High-Sensitivity Cardiac Troponin T Testing in Stable Patients With and Without Coronary Artery Disease.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is used to diagnosis acute myocardial infarction, often based on values exceeding the 99th percentile threshold (14 ng/L) of normal populations. The short- and long-term variability of hs-cTnT in stable patients with or without coronary artery disease (CAD) is unknown. METHODS: Prospective cohort study of 75 stable patients with CAD and 3 differing clinical profiles (stable angina [SA]; remote myocardial infarction [MI]; repetitive acute coronary syndrome [ACS]) and 25 controls without angiographic CAD, each with 15 hs-cTnT measurements over 1 year. RESULTS: Individual results (1491 measurements) did not vary over within-day, daily, weekly, monthly, seasonal, or yearly time windows. The overall median was 2.8 ng/L (interquartile range [IQR] 5.2 ng/L) with the highest median (6.3 ng/L) and variability (IQR 6. 9 ng/L) in the repetitive ACS group. Diabetes, impaired renal function, and raised C-reactive protein were independent predictors of higher hs-cTnT values (average increase by 8.5 ng/L [95% CI, 5.0-11.9], 5.0 ng/L [95% CI, 2.0-8.1] and 4.0 ng/L (95% CI, 1.0-7.0), respectively). The 99th percentile value of all hs-cTnT measurements in the combined stable patients with CAD was 39 ng/L compared with 14 ng/L in the non-CAD patients. CONCLUSIONS: Individual hs-cTnT readings in both patients with and without CAD were stable over hours, days, weeks, and months. Diabetes, poor renal function, and elevated C-reactive protein were independent predictors of higher median and IQR hs-cTnT values, often exceeding conventional thresholds. These findings highlight the need for caution and clinical contextualization in the interpretation of hs-cTnT results.

Effects of basal insulin glargine and omega-3 on lower limb arterial disease outcome in patients with dysglycaemia: An analysis of the Outcome Reduction with an Initial Glargine INtervention (ORIGIN) trial.

The impact of insulin or omega-3 supplements on the incidence and progression of peripheral artery disease (PAD) in patients with dysglycaemia has not been well studied. The Outcome Reduction with an Initial Glargine INtervention (ORIGIN) trial randomized participants with dysglycaemia and cardiovascular risk factors to titrated insulin glargine vs standard care, and to either 1 g of omega-3 per day or placebo. We assessed incident PAD, defined as the composite of either asymptomatic or symptomatic PAD according to the randomized interventions in the 11 119 ORIGIN participants whose baseline ankle-brachial index (ABI) was >0.9 (no PAD), and PAD progression in the 971 ORIGIN participants whose baseline ABI was ≤0.9. Hazard ratios (HR) were adjusted for confounders. During a 6.2-year follow-up period, allocation to insulin glargine vs standard care had a neutral effect on the composite of PAD incidence (HR, 0.99; 95% CI, 0.86-1.15) and progression (HR, 0.88; 95% CI, 0.63-1.22). Similar findings were noted for allocation to omega-3 vs placebo for PAD incidence (HR, 1.02; 95% CI, 0.89-1.18) and progression (HR, 0.93; 95% CI, 0.67-1.28). In this large study, neither insulin glargine nor omega-3 affected the incidence or progression of PAD.

Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE-3 Trial.

BACKGROUND: It is not clear whether the effects of lipid-lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE-3 (Heart Outcomes Prevention Evaluation) trial. METHODS AND RESULTS: In this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow-up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with ≥2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73-1.00). Rosuvastatin reduced CVD events in participants with ≥2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62-0.90) and in participants with <2 factors (HR: 0.79; 95% CI, 0.61-1.01). Consistent results were observed with combination therapy (≥2 factors: HR: 0.74; 95% CI, 0.57-0.97; <2 factors: HR: 0.61; 95% CI, 0.43-0.88). Candesartan/hydrochlorothiazide tends to reduce CVD only in participants with <2 healthy lifestyle factors (HR: 0.78; 95% CI, 0.61-1.00). CONCLUSIONS: Healthy lifestyles are associated with lower CVD. Rosuvastatin alone and combined with candesartan/hydrochlorothiazide is beneficial regardless of healthy lifestyle status; however, the benefit of antihypertensive treatment appears to be limited to patients with less healthy lifestyles. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE 3 Trial

BACKGROUND: It is not clear whether the effects of lipid-lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE-3 (Heart Outcomes Prevention Evaluation) trial. METHODS AND RESULTS: In this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow-up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with ≥2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73­1.00). Rosuvastatin reduced CVD events in participants with ≥2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62­0.90) and in participants with. < 2 factors: HR: 0.61; 95% CI, 0.43­0.88). Candesartan/ hydrochlorothiazide tends to reduce CVD only in participants with <2 healthy lifestyle factors (HR: 0.78; 95% CI, 0.61­1.00). CONCLUSIONS: Healthy lifestyles are associated with lower CVD. Rosuvastatin alone and combined with candesartan/ hydrochlorothiazide is beneficial regardless of healthy lifestyle status; however, the benefit of antihypertensive treatment appears to be limited to patients with less healthy lifestyles.

Outcomes of Patients With ST-Elevation Myocardial Infarction Receiving and Not Receiving Reperfusion Therapy: The Importance of Examining All Patients.

BACKGROUND: Hospitals treating patients with ST-elevation myocardial infarction (STEMI) may show good results with reperfusion treatment (fibrinolysis or primary percutaneous coronary intervention [PPCI]), but a comprehensive evaluation should factor in outcomes of patients with STEMI who do not receive reperfusion. We compared outcomes of patients receiving and not receiving reperfusion within a complete system of STEMI care by hospital type: PPCI centres, fibrinolysis centres, centres that only transfer for PPCI, and centres providing a mix of fibrinolysis and PPCI transfer. METHODS: All patients presenting to 82 Quebec hospitals with characteristic symptoms, a final diagnosis of acute myocardial infarction, and core-laboratory confirmed STEMI over two 6-month periods were studied. RESULTS: Of the total 3731 patients with STEMI, 2918 (78.2%) received reperfusion treatment (81% PPCI, 19% fibrinolysis); 813 (21.8%) did not. For reperfusion-treated patients, 30-day mortality was 5.4% in PPCI centres, 5.4% in fibrinolysis centres, 6.9% in transfer PPCI centres, and 6.0% in mixed centres (P = 0.55). For untreated patients, 30-day mortality was 15.7% (PPCI centres), 16.1% (fibrinolysis centres), 21.8% (transfer PPCI), and 24.6% (mixed) (P = 0.08). Adjusted mortality odds ratios for all patients were 1.00 (PPCI centres), 1.50 (95% CI: 0.97-2.32; fibrinolysis centres), 1.30 (0.95-1.78; transfer PPCI centres), and 1.58 (1.09-2.29; mixed centres). PPCI was within recommended delays in 35.4%, 11.9%, and 1.2% of PPCI, transfer, and mixed centres, respectively. CONCLUSIONS: Mixed centres had the highest crude and adjusted all-patient 30-day STEMI mortality. Relatively good outcomes of reperfusion-treated patients, despite long treatment delays, can misrepresent overall performance if untreated patients are not examined.

Clinical Profiles Related to Timing of Death, Including In-Hospital Deaths Before Admission, in Patients With ST-Elevation Myocardial Infarction.

Patients with ST-elevation myocardial infarction (STEMI) who die in hospital before inpatient admission are generally not included in clinical studies and registries, and the clinical profiles of patients who die earlier versus later are not well defined. We aimed to characterize all patients with STEMI who arrived at emergency departments in the province of Quebec (Canada) based on inpatient admission status and when they died. All patients who presented with symptoms and core laboratory-confirmed STEMI or left bundle branch block during 6 months in 82 hospitals in Quebec were included. Death certificates were used to identify nonadmitted deaths. Of the 2017 patients with STEMI, 340 (16.9%) died within 1 year. Of the latter, 63 (18.5%) were nonadmitted deaths (group A), 179 (52.6%) were deaths after admission but within 30 days (group B), and 98 (28.8%) were deaths after 30 days to 1 year (group C). Group A was younger and most often hemodynamically unstable, followed for both features by B then C. Earliest presentation from symptom onset and most frequent ambulance use were found in group A, followed by B, then C. Presenting electrocardiogram (ECG) features were most severe in A, then B, then C (more arrhythmias, more anterior STEMI, more leads with ST elevation, and higher ST elevation). Patients who died earliest had the least frequency of previous myocardial infarction, coronary revascularization, vascular disease, and heart failure, and the least noncardiac co-morbidity. In conclusion, patients with STEMI dying in hospital before inpatient admission contributed substantially to overall STEMI mortality. Although dying patients who presented earlier had severer presenting clinical profiles, they were paradoxically younger and had less co-morbidity. Previous co-morbidities may favor adaptive protective mechanisms on initial presentation with STEMI.

Utility of a genetic risk score to predict recurrent cardiovascular events 1 year after an acute coronary syndrome: A pooled analysis of the RISCA, PRAXY, and TRIUMPH cohorts.

BACKGROUND: Limited evidence exists regarding the utility of genetic risk scores (GRS) in predicting recurrent cardiovascular events after acute coronary syndrome (ACS). We sought to determine whether a GRS would predict early recurrent cardiovascular events within 1 year of ACS. METHODS & RESULTS: Participants admitted with acute coronary syndromes from the RISCA, PRAXY, and TRIUMPH cohorts, were genotyped for 30 single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) or myocardial infarction (MI) in prior genome wide association studies. A 30 SNP CAD/MI GRS was constructed. The primary endpoint was defined as all-cause mortality, recurrent ACS or cardiac re-hospitalization within 1 year of ACS admission. Results across all cohorts for the 30 SNP CAD/MI GRS were pooled using a random-effects model. There were 1040 patients from the RISCA cohort, 691 patients from the PRAXY cohort, and 1772 patients from the TRIUMPH cohort included in the analysis and 389 occurrences of the primary endpoint of recurrent events at 1-year post-ACS. In unadjusted and fully adjusted analyses, a 30 SNP GRS was not significantly associated with recurrent events (HR per allele 0.97 (95%CI 0.91-1.03) for RISCA, HR 0.99 (95%CI 0.93-1.05) for PRAXY, 0.98 (95%CI 0.94-1.02) for TRIUMPH, and 0.98 (95%CI 0.95-1.01) for the pooled analysis). Addition of this GRS to the GRACE risk model did not significantly improve risk prediction. CONCLUSION: The 30 MI SNP GRS was not associated with recurrent events 1-year post ACS in pooled analyses across cohorts and did not improve risk discrimination or reclassification indices. Our results suggest that the genetic etiology of early events post-ACS may differ from later events.

Comparison of outcomes of ambulance users and nonusers in ST elevation myocardial infarction.

In a systematic province-wide evaluation of care and outcomes of ST elevation myocardial infarction (STEMI), we sought to examine whether a previously documented association between ambulance use and outcome remains after control for clinical risk factors. All 82 acute care hospitals in Quebec (Canada) that treated at least 30 acute myocardial infarctions annually participated in a 6-month evaluation in 2008 to 2009. Medical record librarians abstracted hospital chart data for consecutive patients with a discharge diagnosis of myocardial infarction who presented with characteristic symptoms and met a priori study criteria for STEMI. Linkage to administrative databases provided outcome data (to 1 year) and co-morbidities. Of 1,956 patients, 1,222 (62.5%) arrived by ambulance. Compared with nonusers of an ambulance, users were older, more often women, and more likely to have co-morbidities, low systolic pressure, abnormal heart rate, and a higher Thrombolysis In Myocardial Infarction risk index at presentation. Ambulance users were less likely to receive fibrinolysis or to be sent for primary angioplasty (78.5% vs 83.2% for nonusers, p = 0.01), although if they did, treatment delays were shorter (p <0.001). The 1-year mortality rate was 18.7% versus 7.1% for nonusers (p <0.001). Greater mortality persisted after adjusting for presenting risk factors, co-morbidities, reperfusion treatment, and symptom duration (hazard ratio 1.56, 95% confidence interval 1.30 to 1.87). In conclusion, ambulance users with STEMI were older and sicker than nonusers. Mortality of users was substantially greater after adjustment for clinical risk factors, although they received faster reperfusion treatment overall.

Impact of ECG findings and process-of-care characteristics on the likelihood of not receiving reperfusion therapy in patients with ST-elevation myocardial infarction: results of a field evaluation.

BACKGROUND: Many patients with ST-elevation myocardial infarction (STEMI) do not receive reperfusion therapy and are known to have poorer outcomes. We aimed to perform the first population-level, integrated analysis of clinical, ECG and hospital characteristics associated with non-receipt of reperfusion therapy in patients with STEMI. METHODS AND RESULTS: This systematic evaluation of STEMI care in 82 hospitals in Quebec included all patients with a discharge diagnosis of myocardial infarction, presenting with characteristic symptoms and an ECG showing STEMI as attested by at least one of two study cardiologists or left bundle branch block (LBBB). Excluding LBBB, an ECG was considered a definite STEMI diagnosis if both cardiologists scored 'certain STEMI' and ambiguous if one scored 'uncertain' or 'not STEMI'. Centers were classified according to accessibility to primary percutaneous coronary intervention (PPCI): 1) on-site PPCI; 2) routine transfer for PPCI; 3) varying mix of PPCI transfer and on-site fibrinolysis; and 4) routine on-site fibrinolysis. Of 3730 STEMI/LBBB patients, 812 (21.8%) did not receive reperfusion therapy. In multivariate analysis, likelihood of no reperfusion therapy was a function of PPCI accessibility (odds ratio [OR] for fibrinolysis versus PPCI centers = 3.1; 95% CI: 2.2-4.4), presence of LBBB (OR = 24.1; 95% CI: 17.8-32.9) and an ECG ambiguous for STEMI (OR = 4.1; 95% CI: 3.3-5.1). When the ECG was ambiguous, likelihood of no reperfusion therapy was highest in hospitals most distant from PPCI centers. CONCLUSIONS: ECG diagnostic ambiguity, LBBB and PPCI accessibility are important predictors of not receiving reperfusion therapy, suggesting opportunities for improving outcomes.

Traditional risk factors and a Genetic Risk Score are associated with age of first acute coronary syndrome.

OBJECTIVE: To examine the association between traditional risk factors (TRF) and a Genetic Risk Score (GRS) with age of first acute coronary syndrome (ACS). Early onset ACS may occur due to a high burden of TRFs or to genetic factors that accelerate atherosclerosis. Whether recently discovered genetic variants for ACS are more prevalent at earlier age of first ACS remains unknown. METHODS: To construct a multilocus GRS, participants were genotyped for 30 single nucleotide polymorphisms (SNP) identified from prior genome-wide association studies. Linear regression models were fit to estimate the association between TRFs and GRS with age of first ACS. RESULTS: We included 460 participants with a first ACS enrolled in the Recurrence and Inflammation in the Acute Coronary Syndromes (RISCA) cohort. Several TRFs were associated (all p<0.05) with earlier age of first ACS: male sex (6.9 years earlier (95% CI 4.1 to 9.7)), current cigarette smoking (8.1 years (95% CI 6.1 to 10.0)), overweight (Body Mass Index, BMI >25) and obesity (BMI>30) (5.2 years (95% CI 2.6 to 7.9)). In women, hormone replacement therapy was also associated with earlier age of first ACS (4.8 years earlier (95% CI 0.3 to 8.4)). After multivariable adjustment for TRFs, a 1 SD increment in the GRS was associated with a 1.0 (95% CI 0.1 to 2.0) year earlier age of first ACS. CONCLUSIONS: Among individuals with a first ACS, a GRS composed of 30 SNPs is associated with younger age of presentation. Although genetic predisposition modestly contributes to earlier ACS, a heavy burden of TRF is associated with markedly earlier ACS.

Transfer of patients with ST-elevation myocardial infarction for primary percutaneous coronary intervention: a province-wide evaluation of "door-in to door-out" delays at the first hospital.

BACKGROUND: Interhospital transfer of patients with ST-elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PPCI) is associated with longer delays to reperfusion, related in part to turnaround ("door in" to "door out," or DIDO) time at the initial hospital. As part of a systematic, province-wide evaluation of STEMI care, we examined DIDO times and associations with patient, hospital, and process-of-care factors. METHODS AND RESULTS: We performed medical chart review for STEMI patients transferred for PPCI during a 6-month period (October 1, 2008, through March 31, 2009) and linked these data to ambulance service databases. Two core laboratory cardiologists reviewed presenting ECGs to identify left bundle-branch block and, in the absence of left bundle-branch block, definite STEMI (according to both cardiologists) or an ambiguous reading. Median DIDO time was 51 minutes (25th to 75th percentile: 35-82 minutes); 14.1% of the 988 patients had a timely DIDO interval (≤30 minutes as recommended by guidelines). The data-to-decision delay was the major contributor to DIDO time. Female sex, more comorbidities, longer symptom duration, arrival by means other than ambulance, arrival at a hospital not exclusively transferring for PPCI, arrival at a center with a low STEMI volume, and an ambiguous ECG were independently associated with longer DIDO time. When turnaround was timely, 70% of patients received timely PPCI (door-to-device time ≤90 minutes) versus 14% if turnaround was not timely (P<0.0001). CONCLUSIONS: Benchmark DIDO times for STEMI patients transferred for PPCI were rarely achieved. Interventions aimed at facilitating the transfer decision, particularly in cases of ECGs that are difficult to interpret, are likely to have the best impact on reducing delay to reperfusion.