The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

Normal values of myocardial blood flow measured with dynamic myocardial CT perfusion.

AIMS: Dynamic myocardial CT perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD.We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. METHODS AND RESULTS: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 mL/min/g and 3.58 ± 1.14 mL/min/g respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress) and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant inter-segmental differences were found (P < 0.01), which was not related to age, sex or coronary dominance. CONCLUSION: Myocardial blood flow assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex or coronary dominance. Normal values of myocardial blood flow may be helpful in the clinical evaluation of suspected myocardial ischemia using DM-CTP.

Quantification of myocardial blood flow using dynamic myocardial CT perfusion compared with 82Rb PET.

PURPOSE: Absolute measures of myocardial blood flow (MBF) obtained with dynamic myocardial CT perfusion (DM-CTP) are underestimated when compared with reference standards. This is to some extent explained by incomplete extraction of iodinated contrast agent (iCA) to the myocardial tissue. We aimed to establish an extraction function for iCA, use the function to calculate MBFCT and to compare this with MBF measured with 82Rb positron emission tomography (PET). MATERIALS AND METHODS: Healthy individuals without coronary artery disease (CAD) were examined with 82Rb PET and DM-CTP. The factors a and ß of the generalized Renkin-Crone model were estimated using a non-linear least squares model. The factors providing the best fit for the data were subsequently used to calculate MBFCT. RESULTS: Of consecutive 91 individuals examined, 79 were eligible for analysis. The factors a and ß providing the best fit of the nonlinear least-squares model to the data were a â€‹= â€‹0.614 and ߠ​= â€‹0.218 (R-squared â€‹= â€‹0.81). Conversion of the CT inflow parameter (K1) values using the derived extraction function resulted in a significant correlation between MBF measured during stress using CT and PET (P â€‹= â€‹0.039). CONCLUSION: In healthy individuals, flow estimates obtained with dynamic myocardial CT perfusion during stress were, after conversion to MBF using the extraction of iodinated CT contrast agent, correlated with absolute MBF quantified with 82Rb PET.

Early Coronary Atherosclerosis in Women With Previous Preeclampsia.

BACKGROUND: Women with previous preeclampsia have an increased risk of coronary artery disease later in life. OBJECTIVES: This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population. METHODS: Women aged 40-55 years with previous preeclampsia were matched 1:1 on age and parity with women from the general population. Participants completed an extensive questionnaire, a clinical examination, and a coronary computed tomography angiography (CTA). The main study outcome was the prevalence of any coronary atherosclerosis on coronary CTA or a calcium score >0 in case of a nondiagnostic coronary CTA. RESULTS: A total of 1,417 women, with a mean age of 47 years, were included (708 women with previous preeclampsia and 709 control subjects from the general population). Women with previous preeclampsia were more likely to have hypertension (284 [40.1%] vs 162 [22.8%]; P < 0.001), dyslipidemia (338 [47.7%] vs 296 [41.7%]; P = 0.023), diabetes mellitus (24 [3.4%] vs 8 [1.1%]; P = 0.004), and high body mass index (27.3 ± 5.7 kg/m2 vs 25.0 ± 4.2 kg/m2; P < 0.001). Cardiac computed tomography was performed in all women. The prevalence of any coronary atherosclerosis was higher in the preeclampsia group (193 [27.4%] vs 141 [20.0%]; P = 0.001) with an OR: 1.41 (95% CI: 1.08-1.85; P = 0.012) after adjustment for age, dyslipidemia, diabetes mellitus, smoking, body mass index, menopause, and parity. CONCLUSIONS: Younger women with previous preeclampsia had a slightly higher prevalence of coronary atherosclerosis compared with age- and parity-matched women from the general population. Preeclampsia remained an independent risk factor after adjustment for traditional cardiovascular risk factors. (The CoPenHagen PREeClampsia and cardIOvascUlar diSease study [CPH-PRECIOUS]; NCT03949829).

Temporal patterns of multi-morbidity in 570157 ischemic heart disease patients: a nationwide cohort study.

BACKGROUND: Patients diagnosed with ischemic heart disease (IHD) are becoming increasingly multi-morbid, and studies designed to analyze the full spectrum are few. METHODS: Disease trajectories, defined as time-ordered series of diagnoses, were used to study the temporality of multi-morbidity. The main data source was The Danish National Patient Register (NPR) comprising 7,179,538 individuals in the period 1994-2018. Patients with a diagnosis code for IHD were included. Relative risks were used to quantify the strength of the association between diagnostic co-occurrences comprised of two diagnoses that were overrepresented in the same patients. Multiple linear regression models were then fitted to test for temporal associations among the diagnostic co-occurrences, termed length two disease trajectories. Length two disease trajectories were then used as basis for constructing disease trajectories of three diagnoses. RESULTS: In a cohort of 570,157 IHD disease patients, we identified 1447 length two disease trajectories and 4729 significant length three disease trajectories. These included 459 distinct diagnoses. Disease trajectories were dominated by chronic diseases and not by common, acute diseases such as pneumonia. The temporal association of atrial fibrillation (AF) and IHD differed in different IHD subpopulations. We found an association between osteoarthritis (OA) and heart failure (HF) among patients diagnosed with OA, IHD, and then HF only. CONCLUSIONS: The sequence of diagnoses is important in characterization of multi-morbidity in IHD patients as the disease trajectories. The study provides evidence that the timing of AF in IHD marks distinct IHD subpopulations; and secondly that the association between osteoarthritis and heart failure is dependent on IHD.

Bleeding Episodes in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Very Early Versus Standard Care Invasive Examination (from the Very EaRly vs Deferred Invasive Evaluation Using Computerised Tomography [VERDICT] Trial).

Bleeding is known to influence the prognosis in patients with acute coronary syndromes. In this predefined secondary outcome analysis of the Very EaRly vs Deferred Invasive evaluation using Computerized Tomography (VERDICT) trial, we investigated whether a very early invasive coronary angiography (ICA), compared with one performed within 48 to 72 hours (standard care), was associated with fewer serious bleedings. Furthermore, we tested the association between demographic data including GRACE score and serious bleedings as well as bleedings and mortality. In the 2,147 patients included in the main study, bleedings within 30 days of admission were assessed based on Thrombolysis In Myocardial Infarction and Bleeding Academic Research Consortium criteria. Differences were calculated by cumulative incidence methods and Grays test. Variables associated with bleeding and mortality were estimated by Cox proportional hazard models. Serious (Bleeding Academic Research Consortium 3abc) bleeding rates were low (15 [1.4%, standard] vs 12 [1.2%, early], p = 0.56). There were no fatal bleedings or serious bleedings before ICA in either group. By multivariate analysis, there was no difference in bleedings between the 2 groups. Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.2 to 6.4; p = 0.02), anemia (HR 7.0, 95% CI 2.8 to 17.0; p <0.001), and increasing blood pressure (HR 1.3, 95% CI 1.1 to 1.5; p = 0.01) were individually associated with serious bleeding, whereas GRACE score >140 was not (HR 1.03, 95% CI 0.4 to 2.9; p = 0.96). In conclusion, serious bleedings were few, and there were none before ICA in either group. A very early invasive strategy did not reduce serious bleedings within 30 days, which was associated with female gender, increasing blood pressure, and anemia.

Aortic enlargement and coronary artery calcification in a general population cohort.

AIMS: The role of atherosclerosis in the pathogenesis of aortic enlargement is uncertain. We aimed to evaluate the relationship between the diameters of the ascending, descending and abdominal aorta, and coronary artery calcification. METHODS AND RESULTS: Individuals in the Copenhagen General Population Study underwent thoracic and abdominal computed tomography. Maximal aortic diameters were measured in each aortic segment and coronary artery calcium scores (CACS) were calculated. Participants were stratified into five predefined groups according to CACSs and compared to aortic dimensions. The relation between aortic diameter and CACS was adjusted for risk factors for aortic dilatation in a multivariable model. A total of 2678 eligible individuals were included. In all segments of the aorta, aortic diameter was associated to CACSs, with mean increases in aortic diameters ranging from 0.7 to 3.5 mm in individuals with calcified coronary arteries compared to non-calcified subjects (P-value < 0.001). After correction for risk factors, individuals with CACS above 400 had larger ascending, descending and abdominal aortic diameter than the non-calcified reference group (P-value < 0.01). CONCLUSION: Enlarged thoracic and abdominal aortic vascular segments are associated with co-existing coronary artery calcification in the general population.

Repolarization and ventricular arrhythmia during targeted temperature management post cardiac arrest.

BACKGROUND: Targeted temperature management (TTM) following out-of-hospital cardiac arrest (OHCA) prolongs the QT-interval but our knowledge of different temperatures and risk of arrhythmia is incomplete. OBJECTIVE: To assess whether the QTc, QT-peak (QTp) and T-peak to T-end interval (TpTe) may be useful markers of ventricular arrhythmia in contemporary post cardiac arrest treatment. METHODS: An ECG-substudy of the TTM-trial (TTM at 33 °C vs. 36 °C) with serial ECGs from 680 (94%) patients. Bazett's (B) and Fridericia's (F) formula were used for heart rate correction of the QT, QTp and TpTe. Ventricular arrhythmia (VT/VF) were registered during the first three days of post cardiac arrest care. RESULTS: The QT, QTc and QTp intervals were prolonged more at 33 °C compared to 36 °C and restored to similar and lower levels after rewarming. The TpTe-interval remained between 92-100 ms throughout TTM in both groups. The QTc intervals were associated with ventricular arrhythmia, but not after adjustment for cardiac arrest characteristics. The QTp-interval was not associated with risk of ventricular arrhythmia. Heart rate corrected TpTe-intervals were associated with higher risk of arrhythmia (Odds ratio (OR): TpTe(B): 1.12 (1.02-1.23, p = 0.01 TpTe(F): 1.12 (1.02-1.23, p = 0.02) per 20 ms). Further a prolonged TpTe-interval ≥ 90 ms was consistently associated with higher risk (ORadjusted: TpTe(B): 2.05 (1.25-3.37), p < 0.01, TpTe(F): 2.14 (1.32-3.49), p < 0.01). CONCLUSIONS: TTM prolongs the QT-interval by prolongation of the QTp-interval without association to increased risk. The TpTe-interval is not significantly affected by core temperature, but heart rate corrected TpTe intervals are robustly associated with risk of ventricular arrhythmia. TRIAL REGISTRATION: The TTM-trial is registered and accessible at ClinicalTrials.gov (Identifier: NCT01020916).

Development and external validation of prognostic models to predict sudden and pump-failure death in patients with HFrEF from PARADIGM-HF and ATMOSPHERE.

BACKGROUND: Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF). OBJECTIVE: Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies. METHODS: We developed models in 7156 patients with HFrEF from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, using Fine-Gray regressions counting other deaths as competing risks. The derived models were externally validated in the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) trial. RESULTS: NYHA class and NT-proBNP were independent predictors for both modes of death. The SD model additionally included male sex, Asian or Black race, prior CABG or PCI, cancer history, MI history, treatment with LCZ696 vs. enalapril, QRS duration and ECG left ventricular hypertrophy. While LVEF, ischemic etiology, systolic blood pressure, HF duration, ECG bundle branch block, and serum albumin, chloride and creatinine were included in the PFD model. Model discrimination was good for SD and excellent for PFD with Harrell's C of 0.67 and 0.78 after correction for optimism, respectively. The observed and predicted incidences were similar in each quartile of risk scores at 3 years in each model. The performance of both models remained robust in ATMOSPHERE. CONCLUSION: We developed and validated models which separately predict SD and PFD in patients with HFrEF. These models may help clinicians and patients consider therapies targeted at these modes of death. TRIAL REGISTRATION NUMBER: PARADIGM-HF: ClinicalTrials.gov NCT01035255, ATMOSPHERE: ClinicalTrials.gov NCT00853658.

Optimization of image sampling rate to lower the radiation dose of dynamic myocardial CT perfusion.

BACKGROUND: Dynamic myocardial CT perfusion (CTP) has emerged as a potential strategy to combine anatomical and functional evaluation in a single modality. However, this method results in a high radiation dose. METHODS: Dynamic CTP was performed in 56 patients with suspected or known ischemic heart disease of whom 48 had complete CT-data. Datasets with reduced sampling rate of 2- and 3 RR-intervals (2RR and 3RR) were constructed post hoc. Myocardial blood flow (MBF) estimates from the 2RR and 3RR datasets were compared with estimates based on the full dataset (1RR) using the two one-sided test of equivalence for paired samples. RESULTS: Significant equivalence was found for rest MBFLV (p â€‹< â€‹0.001), stress MBFLV (p â€‹< â€‹0.001) and for the CFRLV (p â€‹= â€‹0.005) when comparing 2RR blood flow estimates with the results based on the 1RR dataset. The 2RR reconstruction protocol led to an estimated reduction in radiation dose of 35.4 â€‹± â€‹3.8%. CONCLUSION: MBF can be quantitated with dynamic CTP using a sampling strategy of one volume for every second heartbeat. This strategy could lead to a significant reduction in radiation dose.

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Arterial hypertension and morphologic abnormalities of cardiac chambers: results from the Copenhagen General Population Study.

OBJECTIVES: In patients with arterial hypertension (AH), hypertension-mediated organ damage may be manifested by cardiac chamber enlargement and/or remodeling. Cardiac computed tomography imaging has emerged as an important method for morphological assessment of cardiac chambers. We tested the hypothesis that prevalence of cardiac chamber abnormalities is specifically related to clinical categories of AH in the general population. METHODS: We studied 4747 individuals, mean age was 60 years (range: 40-93), 46% were men, undergoing 320-detector computed tomography in the Copenhagen General Population Study. Clinical categories of AH were: normotensive (n = 2484), untreated hypertensive (n = 1301), treated controlled hypertensive (n = 412) and treated uncontrolled hypertensive (n = 550). Chamber abnormalities in the form of left ventricular (LV) concentric remodeling, LV eccentric hypertrophy, LV concentric hypertrophy or left atrial enlargement were assessed, in addition to LV or right ventricular enlargement. RESULTS: Chamber abnormalities were present in 23% of all individuals. Combined LV and left atrial abnormalities were rare (<2%). LV concentric remodeling (10%) was the most prevalent abnormality, and most commonly found in individuals with treated hypertension. LV and right ventricular enlargements were unrelated to hypertension. The highest frequencies of chamber abnormalities were found in individuals of elevated blood pressure (BP) with (40%) or without (32%) treatment, as opposed to individuals of normal BP with (27%) or without (14%) treatment, P less than 0.0001. CONCLUSION: In a general population cohort, untreated or inadequately treated AH was associated with the highest prevalence of cardiac chamber enlargement and remodeling. These observations suggest a strong link between elevated BPs and development of hypertension-mediated organ damage.

Hyperglycaemia, ejection fraction and the risk of heart failure or cardiovascular death in patients with type 2 diabetes and a recent acute coronary syndrome.

AIMS: Chronic hyperglycaemia, assessed by elevated glycated haemoglobin (A1C), is a known risk factor for heart failure (HF) and cardiovascular (CV) death among subjects with diabetes. Whether this risk varies with left ventricular ejection fraction (LVEF) is unknown. This study evaluated whether A1C influences a composite outcome of either HF hospitalization or CV death differently along the spectrum of LVEF. METHODS AND RESULTS: We assessed the relationships of baseline A1C and LVEF with a composite outcome of either CV death or HF hospitalization in the 4091 patients with type 2 diabetes and a recent acute coronary syndrome enrolled in the ELIXA trial who had available LVEF. We assessed for interaction between A1C and LVEF as continuous variables with respect to this outcome. During a median follow-up of 25.7 months, 343 patients (8.4%) had HF hospitalization or died of CV causes. In a multivariable model, A1C and LVEF were each associated with an increased risk of HF hospitalization or CV death [adjusted hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01-1.21 per 1% higher A1C, and adjusted HR 1.39, 95% CI 1.27-1.51 per 10% lower in LVEF]. Both A1C and LVEF were independently and incrementally associated with risk without evidence of interaction (P for interaction = 0.31). Patients with A1C ≥ 8% and LVEF <40% were at threefold higher risk than those with A1C < 7% and LVEF ≥50% (adjusted HR 3.18, 95% CI 2.03-4.98, P < 0.001). CONCLUSION: In a contemporary cohort of patients with type 2 diabetes and acute coronary syndrome, baseline chronic hyperglycaemia was associated with an increased risk of HF hospitalization or CV death independently of LVEF.

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease. OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard. RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group. CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

Relationship between heart rate and outcomes in patients in sinus rhythm or atrial fibrillation with heart failure and reduced ejection fraction.

AIMS: To investigate the relationship between heart rate and outcomes in heart failure and reduced ejection fraction (HFrEF) patients in sinus rhythm (SR) and atrial fibrillation (AF) adjusting for natriuretic peptide concentration, a powerful prognosticator. METHODS AND RESULTS: Of 13 562 patients from two large HFrEF trials, 10 113 (74.6%) were in SR and 3449 (25.4%) in AF. The primary endpoint was the composite of cardiovascular death or heart failure hospitalization. Heart rate was analysed as a categorical (tertiles, T1-3) and continuous variable (per 10 bpm), separately in patients in SR and AF. Outcomes were adjusted for prognostic variables, including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and also examined using change from baseline heart rate to 1 year (≤ -10 bpm, ≥ +10 bpm, < ±10 bpm). SR patients with a higher heart rate had worse symptoms and quality of life, more often had diabetes and higher NT-proBNP concentrations. They had higher risk of the primary endpoint [T3 vs. T1 adjusted hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.35-1.66; P < 0.001; per 10 bpm: 1.12, 95% CI 1.09-1.16; P < 0.001]. In SR, heart rate was associated with a relatively higher risk of pump failure than sudden death (adjusted HR per 10 bpm 1.17, 95% CI 1.09-1.26; P < 0.001 vs. 1.07, 95% CI 1.02-1.13; P = 0.011). Heart rate was not predictive of any outcome in AF. CONCLUSIONS: In HFrEF, an elevated heart rate was an independent predictor of adverse cardiovascular outcomes in patients in SR, even after adjustment for NT-proBNP. There was no relationship between heart rate and outcomes in AF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifiers NCT01035255 and NCT00853658.

Normal values of aortic dimensions assessed by multidetector computed tomography in the Copenhagen General Population Study.

AIMS: Accurate assessment of aortic dimensions can be achieved using contrast-enhanced computed tomography. The aim of this study was to define normal values and determinants of aortic dimensions throughout multiple key anatomical landmarks of the aorta in healthy individuals from the Copenhagen General Population Study. METHODS AND RESULTS: The study group consisted of 902 healthy subjects selected from 3000 adults undergoing cardiovascular thoracic and abdominal computed tomography-angiography (CTA), where systematic measurements of aortic dimensions were performed retrospectively. Individuals included were without any of the following predefined cardiovascular risk factors: (i) self-reported angina pectoris; (ii) hypertension; (iii) hypercholesterolaemia; (iv) taking cardiovascular prescribed medication including diuretics, statins, or aspirin; (v) overweight (defined as body mass index ≥30 kg/m2); (vi) diabetes mellitus (self-reported or blood glucose >8 mmol/L); and (vii) chronic obstructive pulmonary disease. Maximal aortic diameters were measured at seven aortic regions: sinuses of Valsalva, sinotubular junction, ascending aorta, mid-descending aorta, abdominal aorta at the diaphragm, abdominal aorta at the coeliac trunk, and infrarenal abdominal aorta. Median age was 52 years, and 396 (40%) were men. Men had significantly larger aortic diameters at all levels compared with women (P < 0.001). Multivariable analysis revealed that sex, age, and body surface area were associated with increasing aortic dimensions. CONCLUSION: Normal values of maximal aortic dimensions at key aortic anatomical locations by contrast-enhanced CTA have been defined. Age, sex, and body surface area were significantly associated with these measures at all levels of aorta. Aortic dimensions follow an almost identical pattern throughout the vessel regardless of sex.

The relationship between volumetric thoracic bone mineral density and coronary calcification in men and women - results from the Copenhagen General Population Study.

BACKGROUND: The association between low bone mineral density (BMD) and the presence of coronary artery calcium (CAC) as a marker of atherosclerosis is unclear. The aim of this study was to assess the potential relationship between volumetric thoracic bone mineral density and coronary calcification in a large population of men and women. METHODS: Participants from the Copenhagen General Population Study underwent multidetector computed tomography. Volumetric thoracic BMD and CAC were assessed in the same scan. CAC was measured using calibrated mass score (cMS). cMS was dichotomized as cMS = 0 or cMS > 0. The association between BMD and cMS was analyzed using multiple logistic regression in men, premenopausal and postmenopausal women. The model was adjusted for age, BMI, hypertension, hypercholesterolemia, diabetes, known cardiovascular disease and smoking. RESULTS: Of 2548 eligible participants, 1163 men and 1385 women, mean age 61 ±â€¯10 were included in the study. Mean BMD was 138 ±â€¯46 mg/cm3 for men and 151 ±â€¯49 mg/cm3 women. In 696 men (67%) and 537 women (41%) cMS was found to be above zero. For men, a decrease in BMD of 100 mg/cm3 was associated to an odds ratio of 1.49 for cMS > 0 (95% confidence interval: 1.04-2.13, P = 0.03). In postmenopausal women, a decrease in BMD of 100 mg/cm3 was associated to an odds ratio of 1.47 for MS > 0 (95% confidence interval: 1.04-2.08, P = 0.03). For premenopausal women, no significant association was found between BMD and cMS (odds ratio = 0.74, 95% confidence interval: 0.36-1.52, P = 0.4). CONCLUSION: Bone mineral density and coronary calcification are inversely related in both men and postmenopausal women, supporting the hypothesis that a direct relation between bone loss and development of atherosclerosis exists irrespective of gender.

Relationship between patient presentation and morphology of coronary atherosclerosis by quantitative multidetector computed tomography.

AIMS: Quantitative computed tomography (QCT) allows assessment of morphological features of coronary atherosclerosis. We aimed to test the hypothesis that clinical patient presentation is associated with distinct morphological features of coronary atherosclerosis. METHODS AND RESULTS: A total of 1652 participants, representing a spectrum of clinical risk profiles [787 asymptomatic individuals from the general population, 468 patients with acute chest pain without acute coronary syndrome (ACS), and 397 patients with acute chest pain and ACS], underwent multidetector computed tomography. Of these, 274 asymptomatic individuals, 254 patients with acute chest pain without ACS, and 327 patients with acute chest pain and ACS underwent QCT to assess coronary plaque volumes and proportions of dense calcium (DC), fibrous, fibro fatty (FF), and necrotic core (NC) tissue. Furthermore, the presence of vulnerable plaques, defined by plaque volume and tissue composition, was examined. Coronary plaque volume increased significantly with worsening clinical risk profile [geometric mean (95% confidence interval): 148 (129-166) mm3, 257 (224-295) mm3, and 407 (363-457) mm3, respectively, P < 0.001]. Plaque composition differed significantly across cohorts, P < 0.0001. The proportion of DC decreased, whereas FF and NC increased with worsening clinical risk profile (mean proportions DC: 33%, 23%, 23%; FF: 50%, 61%, 57%; and NC: 17%, 17%, 20%, respectively). Significant differences in plaque composition persisted after multivariable adjustment for age, gender, body surface area, hypertension, statin use at baseline, diabetes, smoking, family history of ischaemic heart disease, total plaque volume, and tube voltage, P < 0.01. CONCLUSION: Coronary atherosclerotic plaque volume and composition are strongly associated to clinical presentation.