Selective FFRCT testing in suspected stable angina in clinical practice - initial experiences.

Coronary CT angiography (CTA) derived fractional flow reserve (FFRCT) is recommended for physiological assessment in intermediate coronary stenosis for guiding referral to invasive coronary angiography (ICA). In this study, we report real-world data on the feasibility of implementing a CTA/FFRCT test algorithm as a gatekeeper to ICA at referral hospitals. Retrospective all-comer study of patients with new onset stable symptoms and suspected coronary stenosis (30-89%) by CTA. Evaluation of CTA datasets, interpretation of FFRCT analysis, and decisions on downstream testing were performed by skilled CT-cardiologists. CTA was performed in 3974 patients, of whom 381 (10%) were referred directly to ICA, whereas 463 (12%) to non-invasive functional testing: FFRCT 375 (81%) and perfusion imaging 88 (19%). FFRCT analysis was rejected in 8 (2%) due to inadequate CTA image quality. Number of patients deferred from ICA after FFRCT was 267 (71%), while 100 (27%) were referred to ICA. Obstructive coronary artery disease (CAD) was confirmed in 62 (62%) patients and revascularization performed in 53 (53%). Revascularization rates, n (%), were higher in patients undergoing FFRCT-guided versus CTA-guided referral to ICA: 30-69% stenosis, 28 (44%) versus 8 (21%); 70-89% stenosis, 39 (69%) versus 25 (46%), respectively, both p < 0.05. Implementation of FFRCT at referral hospitals was feasible, reduced the number of invasive procedures, and increased the revascularization rate.

Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial.

INTRODUCTION: Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. Supplementation with vitamin K2 and D3 has been suggested to have a protective role in the progression of CAC. In this study, we will examine the effect of vitamins K2 and D3 in men and women with severe CAC. We hypothesise that supplementation with vitamins K2 and D3 will slow down the calcification process. METHOD AND ANALYSIS: In this multicentre and double-blinded placebo-controlled study, 400 men and women with CAC score≥400 are randomised (1:1) to treatment with vitamin K2 (720 µg/day) and vitamin D3 (25 µg/day) or placebo treatment (no active treatment) for 2 years. Among exclusion criteria are treatment with vitamin K antagonist, coagulation disorders and prior coronary artery disease. To evaluate progression in coronary plaque, a cardiac CT-scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is progression in CAC score from baseline to follow-up at 2 years. Among secondary outcomes are coronary plaque composition and cardiac events. Intention-to-treat principle is used for all analyses. ETHICS AND DISSEMINATION: There are so far no reported adverse effects associated with the use of vitamin K2. The protocol was approved by the Regional Scientific Ethical Committee for Southern Denmark and the Data Protection Agency. It will be conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported. TRIAL REGISTRATION NUMBER: NCT05500443.

Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A RCT.

Background: Extent and progression of coronary artery calcification (CAC) are strong predictors of myocardial infarction and mortality. Objectives: This study aims to investigate if vitamin K2 and D supplementation can reduce CAC progression. Methods: A total of 389 participants were randomized to supplementation with vitamin K2 (720 µg/day) and D (25 µg/day) vs placebo in a multicenter double-blinded randomized controlled trial. The primary endpoint (progression of aortic valve calcification) has been reported. This study reports CAC progression in participants with no ischemic heart disease. CT scans were performed at baseline, 12, and 24 months. ΔCAC and coronary plaque volume were evaluated in the entire group and in 2 subgroups. A safety endpoint was the composite of myocardial infarction, coronary revascularization, and all-cause mortality. Results: In total, 304 participants (male, mean age 71 years) were identified. The intervention and placebo group both increased in mean CAC scores from baseline to 24-month follow-up (Δ203 vs Δ254 AU, P = 0.089). In patients with CAC scores ≥400 AU, CAC progression was lower by intervention (Δ288 vs Δ380 AU, P = 0.047). Plaque analyses showed no significant difference in progression of noncalcified plaque volume (Δ-6 vs Δ46 mm3, P = 0.172). Safety events were fewer in participants receiving supplementation (1.9% vs 6.7%, P = 0.048). Conclusions: Patients with no prior ischemic heart disease randomized to vitamin K2 and D supplementation had no significant reduction in mean CAC progression over a 2-year follow-up compared to placebo. Although the primary endpoint is neutral, differential responses to supplementation in those with CAC scores ≥400 AU and in safety endpoints are hypothesis-generating for future studies.

Influence of intensive lipid-lowering on CT derived fractional flow reserve in patients with stable chest pain: Rationale and design of the FLOWPROMOTE study.

INTRODUCTION: Coronary CT angiography (CTA) derived fractional flow reserve (FFRCT ) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated. AIM: To test whether lipid lowering therapy is associated with significant improvement in FFRCT , and whether there is a dose-response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery. METHODS: Investigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first-line CTA, and FFRCT ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFRCT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18-month difference in FFRCT using (1) the FFRCT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study. CONCLUSION: The results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease.

Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.

BACKGROUND: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. METHODS: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events. RESULTS: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, -0.09 to 0.12 cm2; P=0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; P=0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P=0.99), all-cause death (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; P<0.001). CONCLUSIONS: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03243890.

Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial.

INTRODUCTION: Aortic stenosis is a common heart valve disease, and due to the growing elderly population, the prevalence is increasing. The disease is progressive with increasing calcification of the valve cusps. A few attempts with medical preventive treatment have failed; thus, presently, the only effective treatment of aortic stenosis is surgery. This study will examine the effect of menaquinone-7 (MK-7) supplementation on progression of aortic valve calcification (AVC). We hypothesise that MK-7 supplementation will slow down the calcification process. METHODS AND ANALYSIS: In this multicenter and double-blinded, placebo-controlled study, 400 men aged 65-74 years with substantial AVC are randomised (1:1) to treatment with MK-7 (720 µg/day) supplemented by the recommended daily dose of vitamin D (25 µg/day) or placebo treatment (no active treatment) for 2 years. Exclusion criteria are treatment with vitamin K antagonist or coagulation disorders. To evaluate AVC score, a non-contrast CT scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is difference in AVC score from baseline to follow-up at 2 years. Intention-to-treat principle is used for all analyses. ETHICS AND DISSEMINATION: There are no reported adverse effects associated with the use of MK-7. The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20170059) and the Data Protection Agency (17/19010). It is conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported. TRIAL REGISTRATION NUMBER: NCT03243890.

Different Causes of Death in Patients with Myocardial Infarction Type 1, Type 2, and Myocardial Injury.

BACKGROUND: Data outlining the mortality and the causes of death in patients with type 1 myocardial infarction, type 2 myocardial infarction, and those with myocardial injury are limited. METHODS: During a 1-year period from January 2010 to January 2011, all hospitalized patients who had cardiac troponin I measured on clinical indication were prospectively studied. Patients with at least one cardiac troponin I value >30 ng/L underwent case ascertainment and individual evaluation by an experienced adjudication committee. Patients were classified as having type 1 myocardial infarction, type 2 myocardial infarction, or myocardial injury according to the criteria of the universal definition of myocardial infarction. Follow-up was ensured until December 31, 2014. Data on mortality and causes of death were obtained from the Danish Civil Registration System and the Danish Register of Causes of Death. RESULTS: Overall, 3762 consecutive patients were followed for a mean of 3.2 years (interquartile range 1.3-3.6 years). All-cause mortality differed significantly among categories: Type 1 myocardial infarction 31.7%, type 2 myocardial infarction 62.2%, myocardial injury 58.7%, and 22.2% in patients with nonelevated troponin values (log-rank test; P < .0001). In patients with type 1 myocardial infarction, 61.3% died from cardiovascular causes, vs 42.6% in patients with type 2 myocardial infarction (P = .015) and 41.2% in those with myocardial injury (P < .0001). The overall mortality and the causes of death did not differ substantially between patients with type 2 myocardial infarction and those with myocardial injury. CONCLUSIONS: Patients with type 2 myocardial infarction and myocardial injury exhibit a significantly higher long-term mortality compared with patients with type 1 myocardial infarction . However, most patients with type 1 myocardial infarction die from cardiovascular causes in contrast to patients with type 2 myocardial infarction and myocardial injury, in whom noncardiovascular causes of death predominate.

Diagnostic and prognostic value of a careful symptom evaluation and high sensitive troponin in patients with suspected stable angina pectoris without prior cardiovascular disease.

BACKGROUND AND AIMS: Typical angina pectoris (AP) and high-sensitive troponin I (hs-TnI) are independently associated with coronary artery disease (CAD) and future cardiovascular events (CVE). This study aimed to assess the individual and combined diagnostic and prognostic impact of symptoms and hs-TnI in stable chest pain patients without prior cardiovascular disease. METHODS: During a one-year period, 487 patients with suspected stable AP underwent invasive or CT-coronary angiography (significant stenosis ≥50%). At study inclusion, a careful symptom evaluation was obtained, and patients were classified as having typical AP, atypical AP, or non-cardiac chest pain. Hs-TnI was measured in all patients and divided into tertiles for analysis. Follow-up was a median of 4.9 years with cardiovascular death, non-fatal myocardial infarction, unstable AP, ischemic stroke, coronary-artery-bypass-grafting, percutaneous coronary intervention, and peripheral vascular surgery as combined endpoint. RESULTS: Hs-TnI was detected in 486 patients (99.8%). By multivariate regression analysis, typical AP and hs-TnI elevation were associated with increased risk of having significant CAD (typical AP, OR: 3.46; 95% CI: 2.07-5.79; p < 0.0001, hs-TnI, OR: 1.50; 95% CI: 1.12-2.01; p = 0.007) and experiencing future CVE (typical AP, HR: 2.64; 95% CI: 1.74-3.99; p = 0.001, hs-TnI, HR: 1.26; 95% CI: 1.06-1.49; p = 0.008). Patients in the lowest hs-TnI tertile, without typical AP (n = 107) had a 1.9% absolute risk of significant CAD and a 3.7% absolute risk of long-term CVE. CONCLUSIONS: In clinical stable patients without known cardiovascular disease, a thorough chest-pain history in combination with hs-TnI testing can identify a significant low-risk group. The prognostic need for coronary angiography in these patients seems limited.

Prognostic Impact of Myocardial Injury Related to Various Cardiac and Noncardiac Conditions.

BACKGROUND: Elevated cardiac troponins in clinical conditions other than myocardial infarction are well known. For such occurrences, the term "myocardial injury" has been proposed. The long-term outcome in patients with myocardial injury related to various cardiac and noncardiac clinical disorders is unknown. METHODS: During January 2010 to January 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. Patients with cardiac troponin I values >30 ng/L and no evidence of myocardial ischemia were diagnosed as having myocardial injury. Patients were classified into 5 categories of plausible related conditions: cardiac ischemic, cardiac nonischemic, noncardiac, multifactorial, or indeterminate. Follow-up was a minimum of 3 years, with all-cause mortality as the single end-point. RESULTS: A total of 3762 patients were considered, of whom 1089 (29%) had myocardial injury. The most common associated conditions were noncardiac (n = 346) or multifactorial (n = 359). Cardiac ischemic (n = 183) and cardiac nonischemic (n = 134) conditions occurred less frequently. After a median of 3.2 years, 645 patients (59%) had died. A multivariate Cox regression analysis showed no difference in mortality between patients with cardiac ischemic and cardiac nonischemic conditions (hazard ratio [HR] 0.75; 95% confidence interval [CI], 0.50-1.13; P = .2). Patients with noncardiac or multifactorial disorders, however, had significantly higher mortality than those with associated cardiac ischemic conditions (HR 1.39; 95% CI, 1.06-1.80; P = .02, and HR 1.94; 95% CI, 1.50-2.51; P <.001), respectively. CONCLUSIONS: In patients with myocardial injury, the most common associated conditions were noncardiac or multifactorial. Of notice, these patients had significantly higher long-term mortality when compared with those with associated cardiac conditions.

Clinical Characteristics and Outcomes of Patients with Myocardial Infarction, Myocardial Injury, and Nonelevated Troponins.

BACKGROUND: Cardiac troponins have emerged as the preferred biomarkers for detecting myocardial necrosis and diagnosing myocardial infarction. However, current cardiac troponin assays do not discriminate between ischemic and nonischemic causes of myocardial cell death. Thus, when an increased troponin value is encountered in the absence of obvious myocardial ischemia, a careful search for other clinical conditions is crucial. METHODS: In 2010 to 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. An acute myocardial infarction was diagnosed in cases of a cardiac troponin I increase or decrease pattern with at least 1 value >30 ng/L (99th percentile) together with myocardial ischemia. Myocardial injury was defined as cardiac troponin I values >30 ng/L, but without signs or symptoms indicating overt cardiac ischemia. Patients with peak values ≤30 ng/L were classified as nonelevated cardiac troponin I. Follow-up was at least 3 years with all-cause mortality as the sole clinical end point. RESULTS: A total of 3762 patients were included. Of these, 488 (13%) had acute myocardial infarction, 1089 (29%) had myocardial injury, and 2185 (58%) had nonelevated cardiac troponin I values. Patients with myocardial injury frequently presented with dyspnea, were older, and had more comorbidity than patients in the 2 other groups. During a median follow-up of 3.2 years, 1342 patients died. Mortality differed significantly between groups: 39% in those with myocardial infarction, 59% in those with myocardial injury, and 23% in those with nonelevated cardiac troponin I (log-rank test; P < .0001). No significant difference in mortality between patients with type 2 myocardial infarction and patients with myocardial injury was observed (63% and 59%, respectively). CONCLUSIONS: Patients with myocardial injury are older and have more comorbidity than those with acute myocardial infarction. Both groups exhibit a poorer prognosis than patients with nonelevated cardiac troponin I values. Of note, a very high long-term mortality is observed in patients with type 2 myocardial infarction and patients with myocardial injury.

Diagnosis of unstable angina pectoris has declined markedly with the advent of more sensitive troponin assays.

BACKGROUND: Since the arrival of the universal definition of myocardial infarction more sensitive troponin assays have been developed. How these occurrences have influenced the proportions and clinical features of the components of acute coronary syndrome have not been studied prospectively in unselected hospital patients. METHODS: During 2010 we evaluated all patients in whom cardiac troponin I had been measured at a single university hospital. The diagnosis of acute myocardial infarction (ST-elevation myocardial infarction [STEMI] or non-ST-elevation myocardial infarction [NSTEMI]) was established in cases of a rise and/or fall of cardiac troponin I together with cardiac ischemic features. Patients with unstable chest discomfort and cardiac troponin I values below the decision limit of myocardial infarction were diagnosed as having unstable angina pectoris. The definition of acute coronary syndrome included unstable angina pectoris, NSTEMI, and STEMI. Mortality data were obtained from the Danish Civil Personal Registration System. RESULTS: Of 3762 consecutive patients, 516 had acute coronary syndrome. Unstable angina pectoris was present in 7%, NSTEMI in 67%, and STEMI in 26%. The NSTEMI patients were older, more frequently women, and had more comorbidities than patients with unstable angina pectoris and STEMI. At median follow-up of 3.2 years 195 patients had died: 14% of unstable angina pectoris, 45% of NSTEMI, and 25% of STEMI patients. Age-adjusted log-rank statistics revealed differences in mortality: NSTEMI vs unstable angina pectoris (P = .0091) and NSTEMI vs STEMI (P = .0045). CONCLUSIONS: The application of the universal definition together with the use of a contemporary troponin assay seems to have reduced the proportion of patients with unstable angina pectoris to the benefit of patients with NSTEMI. Despite this, NSTEMI patients have a sustained higher mortality than patients with STEMI.

Comparison of mortality in patients with acute myocardial infarction accidentally admitted to non-cardiology departments versus that in patients admitted to coronary care units.

The aim of this study was to prospectively investigate the clinical characteristics including symptoms and long-term mortality in patients with acute myocardial infarction (AMI) accidentally admitted to non-cardiology departments (NCDs). For comparison, similar observations in patients admitted to the coronary care unit (CCU) were collected. During a 1-year period, consecutive patients having cardiac troponin I measured at the Odense University Hospital were considered. The hospital has 27 clinical departments. Patients were classified as having an AMI if the diagnostic criteria of the universal definition were met. Follow-up was at least 1 year with mortality as the clinical end point. Of 3,762 consecutive patients, an AMI was diagnosed in 479, of whom 114 patients (24%) were hospitalized in NCDs and 365 (76%) in the CCU. Chest pain or chest discomfort more frequently occurred in patients from the CCU (83%) than in patients from the NCDs (45%, p <0.0001). At median follow-up of 2.1 years, 150 patients had died: 73 (64%) of patients from the NCDs and 77 (21%) of the patients from the CCU. In the multivariable Cox regression analysis, the adjusted hazard ratio of mortality for patients from the NCDs versus CCU was 2.0 (95% confidence interval 1.3 to 3.2). In conclusion, chest pain/discomfort was absent in more than half of the patients with AMI admitted to NCDs, and admission to NCDs was an independent predictor of a 2 times higher long-term mortality in comparison with admission to the CCU.

Coronary computed tomography angiography - tolerability of ß-blockers and contrast media, and temporal changes in radiation dose.

OBJECTIVE: To determine the risk in administering ß-blockers, contrast-induced nephropathy (CIN) and the trend in X-ray use, during coronary computed tomography angiography (CCTA). METHODS: A total of 416 patients were referred for elective CCTA. To achieve a resting heart rate below 60 beats per minute, oral and/or intravenous ß-blockers were administered. Using questionnaires, information on the adverse effects of ß-blockers was collected from the patients. The levels of s-creatinine and estimated GFR (eGFR) were measured before and after contrast enhanced CCTA. Radiation exposure was compared with the exposure 3 years earlier. RESULTS: There was no significant difference in the symptoms (dizziness, lipothymia and palpitations) between patients with and patients without ß-blocker pretreatment. Compared to baseline values, the decrease in s-creatinine was not significant (75.2 vs. 74.6 µmol/L, p = 0.09), while the increase in eGFR was not significant (78 vs. 79 mL/min, p = 0.17). Also, subgroups of patients with hypertension, hypercholesterolemia, diabetes or pre-existing slight impairment in renal function did not develop CIN. The mean radiation exposure decreased from 17.5 to 6.7 mSv, p < 0.0001. CONCLUSIONS: In terms of the side effects of ß-blockers and contrast media, there were no short term complications to CCTA. Furthermore, the radiation dose has been dramatically diminished over the last three years.

Can osteoprotegerin be used to identify the presence and severity of coronary artery disease in different clinical settings?

PURPOSE: The biomarker Osteoprotegerin (OPG) is associated with coronary artery disease (CAD). The main purpose of this study was to evaluate the diagnostic value of OPG in healthy subjects and in patients with suspected angina pectoris (AP). METHODS: A total of 1805 persons were enrolled: 1152 healthy subjects and 493 patients with suspected AP. For comparison 160 patients with acute myocardial infarction (MI) were included. To uncover subclinical coronary atherosclerosis, a non-contrast cardiac-CT scan was performed in healthy subjects; while in patients with suspected AP a contrast coronary angiography was used to detect significant stenosis. OPG concentrations were analyzed and compared between groups. ROC-analyses were performed to estimate OPG cut-off values. RESULTS: OPG concentrations increased according to disease severity with the highest levels found in patients with acute MI. No significant difference (p = 0.97) in OPG concentrations was observed between subgroups of healthy subjects according to severity of coronary calcifications. A significant difference (p < 0.0001) in OPG concentrations was found between subgroups of patients with suspected stable AP according to severity of CAD. ROC-analysis showed an AUC of 0.62 (95% CI: 0.57-0.67). The optimal cut-off value of OPG (<2.29 ng/mL) had a sensitivity of 56.2% (95% CI: 49.2-63.0%) and a specificity of 62.9% (95% CI: 57.3-68.2%). CONCLUSION: OPG cannot be used to differentiate between healthy subjects with low versus high levels of coronary calcifications. In patients with suspected AP a single OPG measurement is of limited use in the diagnosis of CAD.

Lipocalin-type prostaglandin D synthase is not a biomarker of atherosclerotic manifestations.

OBJECTIVE: Over the last decades Lipocalin-type prostaglandin D synthase (L-PGDS), Osteoprotegerin (OPG), Osteopontin (OPN) and Pregnancy associated plasma protein A (PAPP-A) have been reported to be associated with coronary artery disease, and L-PGDS has been proposed as a potential new diagnostic tool in the setting of stable coronary artery disease. We set out to investigate if measurement of concentrations of these biomarkers could be used to differentiate between four groups of individuals with different atherosclerotic manifestations. METHODS: A total of 120 individuals from four equal gender- and age-matched groups were studied: (i) no previous cardiovascular disease (CVD) and no coronary calcifications [CAC-negative group], (ii) no previous CVD but evidence of severe coronary calcifications [CAC-positive group], (iii) acute coronary syndrome [ACS-group], and (iv) clinical stable patients with CVD, who were referred for cardiovascular surgery [CVD-group]. Concentrations of L-PGDS, OPG, OPN and PAPP-A were analyzed and compared between the four groups. RESULTS: We did not find any significant differences in L-PGDS concentrations between the four groups (p = 0.32). OPG concentrations differed significantly (p = 0.003), with the highest concentration observed in ACS patients. Considering OPN (p = 0.12) and PAPP-A (p = 0.53) their concentrations between groups did not differ significantly. CONCLUSION: The main message from this study is the observation that L-PGDS based on a single blood test appears to be less valuable than previously proposed in identification of patients with coronary artery disease. However, ACS patients have higher OPG concentrations than patients with different manifestations of stable atherosclerosis. Neither OPN nor PAPP-A concentrations differed between groups.

Mortality rate in type 2 myocardial infarction: observations from an unselected hospital cohort.

BACKGROUND: The classification of myocardial infarction into 5 types was introduced in 2007. The prognostic impact of this universal definition, with particular focus on type 2 myocardial infarction, has not been studied prospectively in unselected hospital patients. METHODS: During a 1-year period, all hospitalized patients having cardiac troponin I measured were considered. The diagnosis of a myocardial infarction was according to the universal definition, and specified criteria were used in the classification of type 2 myocardial infarction. Follow-up was at least 1 year, with mortality as the end point. RESULTS: A total of 3762 consecutive patients were studied, of whom 488 (13%) had a myocardial infarction. In 119 patients a type 2 myocardial infarction was diagnosed. After a median of 2.1 years (interquartile range, 1.6-2.5 years), 150 patients had died, with a mortality rate of 49% (58/119) in those with type 2 myocardial infarction and 26% (92/360) in those with type 1 myocardial infarction (P < .0001). In a multivariable Cox regression analysis the following variables were independently associated with mortality: current or prior smoker, high age, prior myocardial infarction, type 2 myocardial infarction, hypercholesterolemia, high p-creatinine, and diabetes mellitus. The multivariable-adjusted hazard ratio for type 2 myocardial infarction was 2.0 (95% confidence interval, 1.3-3.0). With shock as the only exception, mortality was independent of the triggering conditions leading to type 2 myocardial infarction. CONCLUSIONS: Mortality in patients with type 2 myocardial infarction is high, reaching approximately 50% after 2 years. Further descriptive and survival studies are needed to improve the scientific evidence on which treatment of type 2 myocardial infarction is based.

Can lipoprotein-associated phospholipase A2 be used as a predictor of long-term outcome in patients with acute coronary syndrome?

Studies indicate that elevated plasma concentrations of lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with increased risk of cardiovascular disease. Lp-PLA2 seems to play a crucial role in the formation of plaques and acute inflammation, and plasma Lp-PLA2 could therefore potentially be used as a predictor of long-term outcome in ACS patients. To evaluate this, data concerning Lp-PLA2 as a predictor in ACS patients was gathered through a systematic literature review, and studies on this issue were extracted from relevant databases, incl. PubMed and Cochrane. A total of 14 articles were retrieved, but after thorough evaluation and elimination of irrelevant articles only seven studies were eligible for the literature review. All studies except two showed significant correlation between Lp-PLA2 and CV events in ACS patients. Only one study found an independent value to predict CV events 30 days after ACS. Altogether, there was inconsistency in the findings regarding the potential use of Lp-PLA2 and a lack of knowledge on several issues. Lp-PLA2 seems to give valuable information on which ACS patients are prone to new events and also provides important information on plaque size. However, more focused studies concerning genetic variations, time-window impact, patients with and without CV risk factors (e.g. diabetes), and treatment effects are needed. In conclusion, Lp-PLA2 offers new insight in the pathophysiological development of ACS, but until the aforementioned issues are addressed the biomarker will mainly be of interest in a research setting, not as a predictive parameter in a clinical setting.

Classification of myocardial infarction: frequency and features of type 2 myocardial infarction.

BACKGROUND: The classification of myocardial infarction into 5 types was introduced in 2007 as an important component of the universal definition. In contrast to the plaque rupture-related type 1 myocardial infarction, type 2 myocardial infarction is considered to be caused by an imbalance between demand and supply of oxygen in the myocardium. However, no specific criteria for type 2 myocardial infarction have been established. METHODS: We prospectively studied unselected hospital patients who had cardiac troponin I measured on clinical indication. The diagnosis and classification of myocardial infarction were established, and the frequency and features of type 2 myocardial infarction were investigated by use of novel developed criteria. RESULTS: From January 2010 to January 2011, a total of 7230 consecutive patients who had cardiac troponin I measured were evaluated, and 4499 patients qualified for inclusion. The diagnosis of myocardial infarction was established in 553 patients, of whom 386 (72%) had a type 1 myocardial infarction and 144 (26%) had a type 2 myocardial infarction. Patients in the group with type 2 myocardial infarction were older and more likely to be female, and had more comorbidities. The proportion of patients without significant coronary artery disease was higher in those with type 2 myocardial infarction (45%) than in those with type 1 myocardial infarction (12%) (P < .001). Tachyarrhythmias, anemia, and respiratory failure were the most prevalent mechanisms causing type 2 myocardial infarction. CONCLUSIONS: In a cohort of patients with myocardial infarction who were admitted consecutively through 1 year, the category of type 2 myocardial infarction comprised one fourth when diagnosed by the use of newly developed criteria. Approximately half of patients with type 2 myocardial infarction had no significant coronary artery disease.

A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease.

Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current study was to develop an immunoassay to detect a specific MMP-12 derived versican degradation fragment (VCANM) and assess its potential as a biomarker for extracellular matrix remodelling in atherosclerosis. A mouse monoclonal antibody raised against VCANM was used for the development of a competitive ELISA for detection of the fragment in plasma. VCANM was measured in plasma of patients with different levels of heart diseases. Patients experiencing I) acute coronary syndrome, II) stable ischemic heart disease and III) demonstrating high levels of coronary calcium deposits had significantly higher plasma levels of VCANM compared to a control group of individuals with no detectable coronary calcium deposits. VCANM was also detected by immunohistochemistry in coronary artery sections of patients with different degrees of atherosclerosis. VCANM ability to separate patients with atherosclerotic diseases from healthy individuals suggested VCANM as a potential biomarker for the pathological arterial matrix remodelling associated with atherosclerosis.

Time telling devices used in Danish health care are not synchronized.

INTRODUCTION: Many patients begin their encounter with the health-care services in an ambulance. In some critical patients, it is pivotal that the timing of treatment and events is registered correctly. When patients are transferred from one health care provider to another, there is a risk that the time telling devices used are not synchronized. It has never been examined if this is a problem in Denmark. We performed the present study to examine if time telling devices used in the pre-hospital setting were synchronized with devices used in emergency departments. MATERIAL AND METHODS: We used an on-line atomic clock as reference time. The reference time was compared to watches found in the resuscitation rooms at emergency departments at two hospitals in Denmark. Furthermore, we compared the reference time to the watches on the defibrillators in the ambulances at two ambulance stations. RESULTS: The watches in the Emergency Department at Sydvestjysk Hospital Esbjerg had a median deviation of minus three minutes. In the Emergency Department at Hospital Lillebælt Kolding, we found a median deviation of minus 30 seconds. The watches in the defibrillators of 11 ambulances had a median deviation of minus 45 seconds. The maximum deviation between two devices was 19 minutes and 5 seconds, and the maximum deviation between a wall-mounted clock in an emergency department and a defibrillator in an ambulance was five minutes and 22 seconds. CONCLUSION: Examining the time telling devices at two Danish emergency departments and 11 ambulances demonstrated that they are not synchronized. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. The study was not registered, as it is an observational study.