Translation of experimental cardioprotective capability of P2Y12 inhibitors into clinical outcome in patients with ST-elevation myocardial infarction.

We studied the translational cardioprotective potential of P2Y12 inhibitors against acute myocardial ischemia/reperfusion injury (IRI) in an animal model of acute myocardial infarction and in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). P2Y12 inhibitors may have pleiotropic effects to induce cardioprotection against acute myocardial IRI beyond their inhibitory effects on platelet aggregation. We compared the cardioprotective effects of clopidogrel, prasugrel, and ticagrelor on infarct size in an in vivo rat model of acute myocardial IRI, and investigated the effects of the P2Y12 inhibitors on enzymatic infarct size (48-h area-under-the-curve (AUC) troponin T release) and clinical outcomes in a retrospective study of STEMI patients from the CONDI-2/ERIC-PPCI trial using propensity score analyses. Loading with ticagrelor in rats reduced infarct size after acute myocardial IRI compared to controls (37 ± 11% vs 52 ± 8%, p < 0.01), whereas clopidogrel and prasugrel did not (50 ± 11%, p > 0.99 and 49 ± 9%, p > 0.99, respectively). Correspondingly, troponin release was reduced in STEMI patients treated with ticagrelor compared to clopidogrel (adjusted 48-h AUC ratio: 0.67, 95% CI 0.47-0.94). Compared to clopidogrel, the composite endpoint of cardiac death or hospitalization for heart failure within 12 months was reduced in STEMI patients loaded with ticagrelor (HR 0.63; 95% CI 0.42-0.94) but not prasugrel (HR 0.84, 95% CI 0.43-1.63), prior to PPCI. Major adverse cardiovascular events did not differ between clopidogrel, ticagrelor, or prasugrel. The cardioprotective effects of ticagrelor in reducing infarct size may contribute to the clinical benefit observed in STEMI patients undergoing PPCI.

Cardiovascular risk and mortality in rheumatoid arthritis compared with diabetes mellitus and the general population.

OBJECTIVES: To compare risk of cardiovascular disease and mortality in patients with incident RA, diabetes mellitus (DM) and the general population (GP). METHODS: Patients diagnosed with incident RA were matched 1:5 by age, sex and year of RA diagnosis with the GP. In the same period, patients with incident DM were included. Outcomes were heart failure (HF), myocardial infarction (MI), coronary revascularization, stroke, major adverse cardiovascular events (MACE) and death up to 10 years after diagnosis. RESULTS: We included 15 032 patients with incident RA, 301 246 patients with DM and 75 160 persons from the GP. RA patients had an increased risk of HF [hazard ratio (HR) 1.51, 95% CI: 1.38, 1.64], MI (HR 1.58, 95% CI: 1.43, 1.74), percutaneous coronary intervention (PCI; HR 1.44, 95% CI: 1.27, 1.62), coronary artery bypass grafting (CABG; HR 1.30, 95% CI: 1.05, 1.62) and stroke (HR 1.22, 95% CI: 1.12-1.33) compared with the GP. However, the 10-year all-cause mortality was at the same level as observed in the GP. Cardiac death and MACE were increased in RA compared with the GP. When compared with patients with DM, RA patients had a lower adjusted risk of HF (HR 0.79, 95% CI: 0.73, 0.85), CABG (HR 0.62, 95% CI: 0.51, 0.76) and stroke (HR 0.82, 95% CI: 0.76, 0.89), and similar risk of MI and PCI. DM patients had the highest risk of 10-year mortality, cardiac death and MACE. CONCLUSION: This study demonstrates that RA is associated with an increased risk of HF, MI, stroke and coronary revascularization than found in the GP but without reaching the risk levels observed in DM patients.

16-year follow-up of the Danish Acute Myocardial Infarction 2 (DANAMI-2) trial: primary percutaneous coronary intervention vs. fibrinolysis in ST-segment elevation myocardial infarction.

AIMS: The DANish Acute Myocardial Infarction 2 (DANAMI-2) trial found that interhospital transport to primary percutaneous coronary intervention (pPCI) was superior to fibrinolysis at the local hospital in patients with ST-segment elevation myocardial infarction (STEMI) at 30 days. The present study investigates the 16-year cardiovascular outcomes. METHODS AND RESULTS: We randomized 1572 STEMI patients to pPCI or fibrinolysis at 24 referral hospitals and 5 invasive centres in Denmark. Patients randomized to pPCI at referral hospitals were immediately transported to the nearest invasive centre. The main endpoint of the current study was a composite of death or rehospitalization for myocardial infarction (MI). Outcome information beyond 3 years was obtained through Danish health registries. After 16 years, pPCI-treated patients had a sustained lower rate of composite endpoint compared to patients treated with fibrinolysis in the overall cohort [58.7% vs. 62.3%; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76-0.98], and among patients transported for pPCI (58.7% vs. 64.1%; HR 0.82, 95% CI 0.71-0.96). No difference in all-cause mortality was found, but cardiac mortality was reduced by an absolute of 4.4% in favour of pPCI (18.3% vs. 22.7%; HR 0.78, 95% CI 0.63-0.98). pPCI postponed a main event with 12.3 months in average compared to fibrinolysis (95% CI 5.0-19.5). CONCLUSION: The benefit of pPCI over fibrinolysis was maintained at 16-year follow-up. pPCI reduced the composite endpoint of death or rehospitalization for MI, reduced cardiac mortality, and delayed average time to a main event by approximately 1 year.

Diabetes Mellitus Is Associated With Increased Risk of Ischemic Stroke in Patients With and Without Coronary Artery Disease.

Background and Purpose- Diabetes mellitus (DM) and non-DM patients without coronary artery disease (CAD) have a similar low risk of myocardial infarction after coronary angiography. The risk of ischemic stroke in DM patients dependent on CAD status is less explored. We examined whether DM patients without CAD have a risk of ischemic stroke similar to that in patients with neither DM nor CAD. Methods- We conducted a cohort study of patients who underwent coronary angiography between 2004 and 2012 in Western Denmark. Patients diagnosed with previous ischemic stroke or transient ischemic attack were excluded. Patients were stratified according to the presence of DM and CAD. Follow-up started 30 days after coronary angiography. We computed event rates and adjusted incidence rate ratios using patients without DM or CAD as reference. We examined the trend between CAD extent and ischemic stroke in patients with DM. Results- A total of 81 909 patients were included. Median follow-up was 3.8 years. Patients with both DM and CAD were at the highest risk of ischemic stroke (1.32 events per 100 person-years; adjusted incidence rate ratio, 2.00 [95% CI, 1.72-2.32]). Patients with CAD alone (0.77 events per 100 person-years; adjusted incidence rate ratio, 1.27 [95% CI, 1.12-1.44]) or DM alone (0.95 events per 100 person-years; adjusted incidence rate ratio, 1.74 [95% CI, 1.42-2.15]) were at intermediate risk, whereas patients with neither DM nor CAD (0.52 events per 100 person-years) were at the lowest risk. Among patients with DM, extent of CAD was further predictive of risk (Ptrend<0.001). Conclusions- Not only CAD but also DM are associated with the risk of ischemic stroke after coronary angiography. Their combination further increases the risk of ischemic stroke depending on the extent of CAD.

Predicting stroke in patients without atrial fibrillation.

BACKGROUND: Only few studies in selected cohorts have examined whether the CHA2 DS2 -VASc score can predict the risk of atrial fibrillation and thromboembolic events in patients without atrial fibrillation. MATERIALS AND METHODS: Patients with coronary angiography performed between 2004 and 2012 were grouped according to CHA2 DS2 -VASc score. We excluded patients with atrial fibrillation, anticoagulant therapy and follow-up <30 days. The endpoints were atrial fibrillation and a composite of ischaemic stroke, transient ischaemic attack and systemic embolism. Event rates per 100 person-years were estimated for each CHA2 DS2 -VASc score (0, 1, 2, 3, 4, and >4). Incidence rate ratios were calculated using low-risk patients (CHA2 DS2 -VASc score 0 in males or 1 in females) as reference. RESULTS: In total, 78 233 patients were included with group sizes varying between 8299 (CHA2 DS2 -VASc >4) and 19 882 (CHA2 DS2 -VASc 2). An increasing CHA2 DS2 -VASc score was significantly associated with a future diagnosis of atrial fibrillation (P for trend <0.0001) and an incremental risk of ischaemic stroke, transient ischaemic attack, systemic embolism (P for trend <0.0001) and all-cause death (P for trend <0.0001). Patients with a CHA2 DS2 -VASc score of 3 had a rate of ischaemic stroke/transient ischaemic attack/systemic embolism of 1.30 per 100 person-years. CONCLUSIONS: Among patients undergoing coronary angiography, the CHA2 DS2 -VASc score predicted a future diagnosis of atrial fibrillation and the composite risk of ischaemic stroke, transient ischaemic attack or systemic embolism in patients without atrial fibrillation. A CHA2 DS2 -VASc score of 3 was associated with a risk that would justify prophylactic oral anticoagulation treatment in a patient with atrial fibrillation.

Invasively Measured Aortic Systolic Blood Pressure and Office Systolic Blood Pressure in Cardiovascular Risk Assessment in CKD.

Introduction: Central aortic blood pressure (BP) could be a better risk predictor than brachial BP. This study examined whether invasively measured aortic systolic BP improved outcome prediction beyond risk prediction by conventional cuff-based office systolic BP in patients with and without chronic kidney disease (CKD). Methods: In a prospective, longitudinal cohort study, aortic and office systolic BPs were registered in patients undergoing elective coronary angiography (CAG). CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. Multivariable Cox models were used to determine the association with incident myocardial infarction (MI), stroke, and death. Results: Aortic and office systolic BPs were available in 39,866 patients (mean age: 64 years; 58% males; 64% with hypertension) out of which 6605 (17%) had CKD. During a median follow-up of 7.2 years (interquartile range: 4.6-10.1 years), 1367 strokes (CKD: 353), 1858 MIs (CKD: 446), and 7551 deaths (CKD: 2515) occurred. CKD increased the risk of stroke, MI, and death significantly. Office and aortic systolic BP were both associated with stroke in non-CKD patients (adjusted hazard ratios with 95% confidence interval per 10 mm Hg: 1.08 [1.05-1.12] and 1.06 [1.03-1.09], respectively) and with MI in patients with CKD (adjusted hazard ratios: 1.08 [1.03-1.13] and 1.08 [1.04-1.12], respectively). There was no significant difference between prediction of outcome with office or aortic systolic BP when adjusted models were compared with C-statistics. Conclusion: Regardless of CKD status, invasively measured central aortic systolic BP does not improve the ability to predict outcome compared with brachial office BP measurement.

Diabetes and Coronary Artery Disease as Risk Factors for Dementia.

AIM: Diabetes is associated with increased risk of dementia, but it is still debated to which degree this risk depends on the presence of atherosclerotic cardiovascular disease. We hypothesized that patients with diabetes and co-existing coronary artery disease (CAD), as a marker of systemic atherosclerotic cardiovascular disease, have substantially higher risk of developing dementia. METHODS: Patients ≥65 years, who underwent coronary angiography were stratified by diabetes and CAD. Outcomes were all-cause dementia, Alzheimer's dementia, and vascular dementia. We estimated adjusted hazard ratios (aHRs) using patients with neither diabetes nor CAD as a reference. RESULTS: A total of 103,859 patients were included. Of these, 23,189 (22%) had neither diabetes nor CAD, 3,876 (4%) had diabetes, 61,020 (59%) had CAD, and 15,774 (15%) had diabetes and CAD. During a median follow-up of 6.3 years, 5,592 (5.5%) patients were diagnosed with all-cause dementia. Patients with diabetes and CAD had the highest hazard rate of all-cause dementia (aHR 1.37, 95% CI 1.24-1.51), including Alzheimer's dementia (aHR 1.41, 95% CI 1.23-1.62) and vascular dementia (aHR 2.03, 95% CI 1.69-2.45). Patients with diabetes alone (aHR 1.14, 95% CI 0.97-1.33) or CAD alone (aHR 1.11, 95% CI 1.03-1.20) had a modestly increased rate of all-cause dementia. CONCLUSION: The combination of diabetes and CAD is associated with increased rate of dementia, in particular vascular dementia, suggesting that the diabetes-related risk of dementia is partly mediated through concomitant atherosclerotic cardiovascular disease. This underscores the importance of atherosclerotic cardiovascular disease prevention in diabetes patients to reduce cognitive decline.

We used national Danish healthcare registries to follow 103,859 patients examined by coronary angiography for up to 10 years to estimate the risk of dementia associated with diabetes and/or coronary artery disease. We found that diabetes and coronary artery disease are, separately, only modest risk factors of dementia. However, diabetes and coronary artery disease in combination were associated with highest risk of dementia, in particular vascular dementia. Out results suggests that the risk of dementia associated with diabetes is partly mediated through the presence atherosclerotic cardiovascular disease, which underscores the importance of atherosclerotic cardiovascular disease prevention in diabetes patients to reduce the risk of cognitive decline.

Antithrombotic treatment beyond 1 year after percutaneous coronary intervention in patients with atrial fibrillation.

AIMS: Beyond 1 year after percutaneous coronary intervention (PCI), guidelines recommend anticoagulant monotherapy in patients with atrial fibrillation (AF) rather than dual therapy with an anticoagulant and an antiplatelet drug. The risks and benefits of this strategy, however, remain uncertain. We examined hospitalization for bleeding and ischaemic risk beyond 1 year after PCI in patients with AF treated with monotherapy vs. dual therapy. Furthermore, among patients treated with monotherapy, we compared direct oral anticoagulant (DOAC) therapy and vitamin K antagonist (VKA) therapy. METHODS AND RESULTS: We included all patients with AF undergoing first-time PCI between 2003 and 2017 from the Western Denmark Heart Registry and followed them for up to 4 years. Follow-up started 15 months after PCI to enable assessment of medical treatment after 12 months. Using a Cox regression model, we computed weighted hazard ratios (HRw) of hospitalization for bleeding and major adverse cardiac events (MACEs). Analyses comparing monotherapy vs. dual therapy included 3331 patients, and analyses comparing DOAC vs. VKA monotherapy included 1275 patients. Risks of hospitalization for bleeding [HRw 0.90, 95% confidence interval (CI) 0.75-1.09] and MACE (HRw 1.04, 95% CI 0.90-1.19) were similar with monotherapy and dual therapy. Similarly, risks of hospitalization for bleeding (HRw 1.27, 95% CI 0.84-1.92) and MACE (HRw 1.15, 95% CI 0.87-1.50) were equal with DOAC and VKA monotherapy. CONCLUSION: Our results support long-term OAC monotherapy beyond 1 year after PCI in patients with atrial fibrillation and suggest that DOAC monotherapy is as safe and effective as VKA monotherapy.

Twenty-Year Temporal Trends in Risk of Ischemic Stroke in Incident Type 2 Diabetes: A Danish Population-Based Cohort Study.

OBJECTIVE: We examined temporal trends in risk of first-time ischemic stroke in patients with incident type 2 diabetes mellitus (T2DM) and no prior atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS: Using nationwide health registries, we identified all patients with incident T2DM without a prior hospital diagnosis of ASCVD from 1996 to 2015 in Denmark. Patients were assigned to 5-year periods based on the date of T2DM diagnosis and were followed for 5 years. Each patient was matched by sex and age with up to three individuals from the general population. Temporal trends in ischemic stroke were examined using Cox regression to compute hazard ratios (HRs). Temporal use of prophylactic cardiovascular medications was also assessed. RESULTS: The study comprised 288,825 patients with incident T2DM and 782,232 general population individuals. From 1996-2000 to 2011-2015, the 5-year risk of first-time ischemic stroke was approximately halved in the T2DM cohort (5.2% vs. 2.7%; sex- and age-adjusted HR 0.52 [95% CI 0.49-0.55]). Patients diagnosed in 2011-2015 had increased risk of ischemic stroke compared with individuals in the general population; however, the risk difference narrowed over time (5.2% vs. 2.9% in 1996-1999 [difference 2.3%]; 2.7% vs. 2.0% in 2011-2015 [difference 0.7%]). Use of prophylactic cardiovascular medications increased markedly during the overall study period, especially use of statins (from 5% to 50%) and multiple antihypertensive drugs (from 18% to 33%). CONCLUSIONS: From 1996 to 2015, the 5-year risk of first-time ischemic stroke was approximately halved in patients with incident T2DM and no prior ASCVD, coinciding with markedly increased use of prophylactic cardiovascular medications.

Estimated Pulse Wave Velocity Is Associated With All-Cause Mortality During 8.5 Years Follow-up in Patients Undergoing Elective Coronary Angiography.

Background Estimated pulse wave velocity (ePWV) calculated by equations using age and blood pressure has been suggested as a new marker of mortality and cardiovascular risk. However, the prognostic potential of ePWV during long-term follow-up in patients with symptoms of stable angina remains unknown. Methods and Results In this study, ePWV was calculated in 25 066 patients without diabetes, previous myocardial infarction (MI), stroke, heart failure, or valvular disease (mean age 63.7±10.5 years, 58% male) with stable angina pectoris undergoing elective coronary angiography during 2003 to 2016. Multivariable Cox models were used to assess the association with incident all-cause mortality, MI, and stroke. Discrimination was assessed using Harrell´s C-index. During a median follow-up period of 8.5 years (interquartile range 5.5-11.3 years), 779 strokes, 1233 MIs, and 4112 deaths were recorded. ePWV was associated with all-cause mortality (hazard ratio [HR] per 1 m/s, 1.13; 95% CI, 1.05-1.21) and MI (HR per 1 m/s 1.23, 95% CI, 1.09-1.39) after adjusting for age, systolic blood pressure, body mass index, smoking, estimated glomerular filtration rate, Charlson Comorbidity Index score, antihypertensive treatment, statins, aspirin, and number of diseased coronary arteries. Compared with traditional risk factors, the adjusted model with ePWV was associated with a minor but likely not clinically relevant increase in discrimination for mortality, 76.63% with ePWV versus 76.56% without ePWV, P<0.05. Conclusions In patients with stable angina pectoris, ePWV was associated with all-cause mortality and MI beyond traditional risk factors. However, the added prediction of mortality was not improved to a clinically relevant extent.

Development and validation of an artificial neural network algorithm to predict mortality and admission to hospital for heart failure after myocardial infarction: a nationwide population-based study.

BACKGROUND: Patients have an estimated mortality of 15-20% within the first year following myocardial infarction and one in four patients who survive myocardial infarction will develop heart failure, severely reducing quality of life and increasing the risk of long-term mortality. We aimed to establish the accuracy of an artificial neural network (ANN) algorithm in predicting 1-year mortality and admission to hospital for heart failure after myocardial infarction. METHODS: In this nationwide population-based study, we used data for all patients admitted to hospital for myocardial infarction and discharged alive from a coronary care unit in Sweden (n=139 288) between Jan 1, 2008, and April 1, 2017, from the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) nationwide registry; these patients were randomly divided into training (80%) and testing (20%) datasets. We developed an ANN using 21 variables (including age, sex, medical history, previous medications, in-hospital characteristics, and discharge medications) associated with the outcomes of interest with a back-propagation algorithm in the training dataset and tested it in the testing dataset. The ANN algorithm was then validated in patients with incident myocardial infarction enrolled in the Western Denmark Heart Registry (external validation cohort) between Jan 1, 2008, and Dec 31, 2016. The predictive ability of the model was evaluated using area under the receiver operating characteristic curve (AUROC) and Youden's index was established as a means of identifying an empirical dichotomous cutoff, allowing further evaluation of model performance. FINDINGS: 139 288 patients who were admitted to hospital for myocardial infarction in the SWEDEHEART registry were randomly divided into a training dataset of 111 558 (80%) patients and a testing dataset of 27 730 (20%) patients. 30 971 patients with myocardial infarction who were enrolled in the Western Denmark Heart Registry were included in the external validation cohort. A first event, either all-cause mortality or admission to hospital for heart failure 1 year after myocardial infarction, occurred in 32 308 (23·2%) patients in the testing and training cohorts only. For 1-year all-cause mortality, the ANN had an AUROC of 0·85 (95% CI 0·84-0·85) in the testing dataset and 0·84 (0·83-0·84) in the external validation cohort. The AUROC for admission to hospital for heart failure within 1 year was 0·82 (0·81-0·82) in the testing dataset and 0·78 (0·77-0·79) in the external validation dataset. With an empirical cutoff the ANN algorithm correctly classified 73·6% of patients with regard to all-cause mortality and 61·5% of patients with regard to admission to hospital for heart failure in the external validation cohort, ruling out adverse outcomes with 97·1-98·7% probability in the external validation cohort. INTERPRETATION: Identifying patients at a high risk of developing heart failure or death after myocardial infarction could result in tailored therapies and monitoring by the allocation of resources to those at greatest risk. FUNDING: The Swedish Heart and Lung Foundation, Swedish Scientific Research Council, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, ALF Agreement on Medical Education and Research, Skane University Hospital, The Bundy Academy, the Märta Winkler Foundation, the Anna-Lisa and Sven-Eric Lundgren Foundation for Medical Research.

Patient-oriented risk score for predicting death 1 year after myocardial infarction: the SweDen risk score.

OBJECTIVES: Our aim was to derive, based on the SWEDEHEART registry, and validate, using the Western Denmark Heart registry, a patient-oriented risk score, the SweDen score, which could calculate the risk of 1-year mortality following a myocardial infarction (MI). METHODS: The factors included in the SweDen score were age, sex, smoking, diabetes, heart failure and statin use. These were chosen a priori by the SWEDEHEART steering group based on the premise that the factors were information known by the patients themselves. The score was evaluated using various statistical methods such as time-dependent receiver operating characteristics curves of the linear predictor, area under the curve metrics, Kaplan-Meier survivor curves and the calibration slope. RESULTS: The area under the curve values were 0.81 in the derivation data and 0.76 in the validation data. The Kaplan-Meier curves showed similar patient profiles across datasets. The calibration slope was 1.03 (95% CI 0.99 to 1.08) in the validation data using the linear predictor from the derivation data. CONCLUSIONS: The SweDen risk score is a novel tool created for patient use. The risk score calculator will be available online and presents mortality risk on a colour scale to simplify interpretation and to avoid exact life span expectancies. It provides a validated patient-oriented risk score predicting the risk of death within 1 year after suffering an MI, which visualises the benefit of statin use and smoking cessation in a simple way.

Nationwide Trends in Cardiac Risk and Mortality in Patients With Incident Type 2 Diabetes: A Danish Cohort Study.

OBJECTIVE: Trends in cardiac risk and death have not been examined in patients with incident type 2 diabetes and no prior cardiovascular disease. Therefore, we aimed to examine trends in cardiac risk and death in relation to the use of prophylactic cardiovascular medications in patients with incident type 2 diabetes without prior cardiovascular disease. RESEARCH DESIGN AND METHODS: In this population-based cohort study, we included patients with incident type 2 diabetes between 1996 and 2011 through national health registries. Each patient was matched by age and sex with up to five individuals without diabetes from the general population. All individuals were followed for 7 years. RESULTS: We identified 209,311 patients with incident diabetes. From 1996-1999 to 2008-2011, the 7-year risk of myocardial infarction decreased from 6.9 to 2.8% (adjusted hazard ratio [aHR] 0.39 [95% CI 0.37-0.42]), cardiac death from 7.1 to 1.6% (aHR 0.23 [95% CI 0.21-0.24]), and all-cause death from 28.9 to 16.8% (aHR 0.68 [95% CI 0.66-0.69]). Compared with the general population, 7-year risk differences decreased from 3.3 to 0.8% for myocardial infarction, from 2.7 to 0.5% for cardiac death, and from 10.6 to 6.0% for all-cause death. Use of cardiovascular medications within ±1 year of diabetes diagnosis, especially statins (5% of users in 1996-1999 vs. 60% in 2008-2011), increased during the study period. CONCLUSIONS: From 1996 to 2011, Danish patients with incident type 2 diabetes and no prior cardiovascular disease experienced major reductions in cardiac risk and mortality. The risk reductions coincided with increased use of prophylactic cardiovascular medications.

Invasive aortic pulse pressure is not superior to cuff pulse pressure in cardiovascular risk prediction.

OBJECTIVE: Aortic pulse pressure (PP) represents the hemodynamic cardiac and cerebral burden more directly than cuff PP. The objective of this study was to investigate whether invasively measured aortic PP confers additional prognostic value beyond cuff PP for cardiovascular events and death. With increasing age, cuff PP progressively underestimates aortic PP. Whether the prognostic association between cuff PP and outcomes is age-dependent remains to be elucidated. METHODS: Cuff PP and invasively measured aortic PP were recorded in 21 908 patients (mean age 63 years, 58% men, 14% with diabetes) with stable angina pectoris undergoing elective coronary angiography during January 2001--December 2012. Multivariate Cox models were used to assess the association with incident myocardial infarction, stroke, and death. Discrimination was assessed using Harrell's C-index. RESULTS: During a median follow-up period of 3.7 years (range 0.1-10.8 years), 422 strokes, 511 myocardial infarctions, and 1530 deaths occurred. Both cuff and aortic PP were associated with stroke, myocardial infarction, and death in crude analyses. However, only cuff PP remained associated with stroke (hazard ratio per 10 mmHg, 1.06 (95% confidence interval (CI) 1.01--1.12)] and myocardial infarction [hazard ratio per 10 mmHg 1.05 (95% CI 1.01--1.11)] in multivariate Cox models. Both cuff and aortic PP lost significance as predictors of death in multivariate models. Age did not modify the prognostic association between cuff PP and stroke, myocardial infarction, and death. CONCLUSION: Invasively measured aortic PP did not add prognostic information about cardiovascular outcomes and death beyond cuff PP in patients with stable angina pectoris.

Ten-Year Outcomes of Sirolimus-Eluting Versus Zotarolimus-Eluting Coronary Stents in Patients With Versus Without Diabetes Mellitus (SORT OUT III).

We compared 10-year clinical outcomes in diabetes and nondiabetes patients treated with Endeavor zotarolimus-eluting (ZES) or Cypher sirolimus-eluting coronary stents (SES). A total of 1,162 patients were randomized to ZES (169 with diabetes) and 1,170 patients were randomized to SES (168 with diabetes). Patients were further stratified by diabetes status at the time of inclusion. A subgroup of patients with diabetes (n = 88) underwent angiographic re-evaluation 10 months after stent implantation. End points included a combined end point of death or myocardial infarction, and the individual end points of death, myocardial infarction, and revascularization. In patients with diabetes, we found no difference in the combined end point (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.53 to 1.24), death (OR 0.80, 95% CI 0.51 to 1.25), or in MI (OR 1.07, 95% CI 0.60 to 1.91). However, diabetics with ZES more frequently underwent coronary revascularization compared with SES patients (OR 1.93, 95% CI 1.05 to 3.66). In patients without diabetes, ZES and SES had similar 10-year rates of all end points (death: OR 1.13, 95% CI 0.93 to 1.39; MI: OR 0.80, 95% CI 0.61 to 1.05; revascularization: OR 0.81, 95% CI 0.61 to 1.09). Landmark analysis from 5 to 10 years showed no difference in outcomes between SES and ZES in either subgroup. In conclusion, at 10 years, SES and ZES performed similarly in patients with and without diabetes. Although coronary revascularization was more prevalent in diabetes patients with ZES, this may, in part, have been related to the angiographic follow-up that was offered to a subgroup of diabetes patients.

A Novel Model for Prediction of Thromboembolic and Cardiovascular Events in Patients Without Atrial Fibrillation.

Patients without atrial fibrillation (AF) constitute approximately 75% of patients suffering thromboembolism and major adverse cardiovascular events (MACE), but evidence supporting risk stratification in these patients is sparse. We aimed to develop a risk prediction model for identification of patients without AF at high risk of first-time thromboembolic events. We included 72,381 coronary angiography patients without AF and without previous ischemic stroke or transient ischemic attack. The cohort was randomly divided into a derivation cohort (80%, n = 57,680) and a validation cohort (20%, n = 14,701). The primary thromboembolic end point was a composite of ischemic stroke, transient ischemic attack, and systemic embolism. MACE was defined as a composite of cardiac death, myocardial infarction, and ischemic stroke. The final model was compared with 2 validated clinical risk models (CHADS2 and CHA2DS2-VASc). The risk prediction model assigned 1 point to heart failure, hypertension, diabetes mellitus, renal disease, age 65 to 74 years, active smoking, and multivessel obstructive coronary artery disease, and 2 points to age ≥75 years and peripheral artery disease. A C-index of 0.66 (95% CI 0.64 to 0.69) for prediction of the composite thromboembolic end point was found in the validation cohort, which was higher than for CHADS2 (C-index 0.63 [95% CI 0.60 to 0.67]; p < 0.001) and CHA2DS2-VASc (C-index 0.64 [95% CI 0.62 to 0.67]; p = 0.034). The model also predicted MACE (C-index 0.71 [95% CI 0.69 to 0.73]). In conclusion it is possible to identify patients without AF at high risk of first-time thromboembolic events and MACE by use of a simple clinical prediction model.

Risk stratification by assessment of coronary artery disease using coronary computed tomography angiography in diabetes and non-diabetes patients: a study from the Western Denmark Cardiac Computed Tomography Registry.

AIMS: We examined whether severity of coronary artery disease (CAD) measured by coronary computed tomography angiography can be used to predict rates of myocardial infarction (MI) and death in patients with and without diabetes. METHODS AND RESULTS: A cohort study of consecutive patients (n = 48 731) registered in the Western Denmark Cardiac Computed Tomography Registry from 2008 to 2016. Patients were stratified by diabetes status and CAD severity (no, non-obstructive, or obstructive). Endpoints were MI and death. Event rates per 1000 person-years, unadjusted and adjusted incidence rate ratios were computed. Median follow-up was 3.6 years. Among non-diabetes patients, MI event rates per 1000 person-years were 1.4 for no CAD, 4.1 for non-obstructive CAD, and 9.1 for obstructive CAD. Among diabetes patients, the corresponding rates were 2.1 for no CAD, 4.8 for non-obstructive CAD, and 12.6 for obstructive CAD. Non-diabetes and diabetes patients without CAD had similar low rates of MI [adjusted incidence rate ratio 1.40, 95% confidence interval (CI): 0.71-2.78]. Among diabetes patients, the adjusted risk of MI increased with severity of CAD (no CAD: reference; non-obstructive CAD: adjusted incidence rate ratio 1.71, 95% CI: 0.79-3.68; obstructive CAD: adjusted incidence rate ratio 4.42, 95% CI: 2.14-9.17). Diabetes patients had higher death rates than non-diabetes patients, irrespective of CAD severity. CONCLUSION: In patients without CAD, diabetes patients have a low risk of MI similar to non-diabetes patients. Further, MI rates increase with CAD severity in both diabetes and non-diabetes patients; with diabetes patients with obstructive CAD having the highest risk of MI.