Circulating levels of P-selectin and E-selectin relate to cardiovascular magnetic resonance-derived aortic characteristics in young adults from the general population, a cross-sectional study.

BACKGROUND: Although endothelial cell adhesion molecules (CAMs) are postulated to play a key role in early atherosclerosis, studies on endothelial CAMs are mainly pertained to middle-aged populations and populations with an unfavourable cardiovascular risk burden. Therefore, this study evaluated whether circulating endothelial CAMs are related to cardiovascular magnetic resonance imaging (CMR) derived indicators of arterial wall alterations in a random sample of young adults from the general population. METHODS: This cross-sectional study is part of the general-population-based Atherosclerosis-Monitoring-and-Biomarker-measurements-In-The-YOuNg (AMBITYON) cohort study. In 131 adults (age: 25-35 years), demography, anthropometry and a lipid spectrum was acquired. Thoracic aortic wall area, wall thickness and pulse wave velocity (PWV) were measured using a 3 T CMR-system. From stored blood samples, four CAMs (E-selectin, P-selectin, vascular CAM-1 and intercellular CAM-1) were measured using dedicated methods. Linear mixed-effects regression analysis was used to evaluate the relation of these CAMs with the selected aortic characteristics. RESULTS: Of the studied endothelial CAMs, P-selectin related to natural logarithm transformed aortic wall thickness (ß = 0.18 mm/(µg/ml), [95% confidence interval: 0.04, 0.31], p = 0.01) whereas E-selectin related to natural logarithm transformed aortic PWV (ß = 3.01 (m/s)/(µg/ml), [95% confidence interval: 0.08, 5.95], p = 0.04). Of note, VCAM-1 and ICAM-1 did not relate to the selected aortic characteristics. CONCLUSIONS: In young adults from the general population, circulating P-selectin and E-selectin levels appear positively related to CMR-derived aortic wall thickness and PWV, possibly pointing towards atherogenic inflammatory arterial wall alterations inflicted by these CAMs already in young adulthood. TRIAL REGISTRATION: Netherlands National Trial Register (NTR): NTR4742 , Registered 18 August 2014, retrospectively registered.

Sex, body mass index, and blood pressure are related to aortic characteristics in healthy, young adults using magnetic resonance vessel wall imaging: the AMBITYON study.

OBJECTIVES: More detailed evaluation of atherosclerosis and its key determinants in young individuals is warranted to improve knowledge on the pathophysiology of its development and progression. This study evaluated associations of magnetic resonance imaging (MRI)-derived aortic wall area, wall thickness, and pulse wave velocity (PWV) with cardiovascular risk factors in asymptomatic, young adults. MATERIALS AND METHODS: In 124 adults (age: 25-35 years) from the general population-based Atherosclerosis Monitoring and Biomarker Measurements in the Young study, demography, anthropometry, and blood samples were collected. The studied MRI-parameters were measured using a 3.0T MRI system. Relations between cardiovascular risk factors and aortic characteristics were assessed using multivariable linear regression analyses. RESULTS: Mean age was 31.8 years, 47.6% was male. Aortic wall area was positively associated with age [ß = 0.01, (95% confidence interval (CI) 2.00 × 10-3, 0.02), p = 0.01] and BMI [ß = 0.01, (0.01, 0.02), p = 0.003] and negatively associated with sex (reference: men) [ß = -0.06, (-0.11, -0.01), p = 0.02]. Natural logarithm transformed (ln) aortic wall thickness was positively associated with BMI [ß = 0.01, (1.00 × 10-3, 0.02), p = 0.02]. Ln aortic PWV was positively associated with 10 mmHg increment of SBP [ß = 0.06, (0.03, 0.09), p < 0.001] and DBP [ß = 0.06, (0.02, 0.09), p = 0.006]. No relations were observed for smoking and lipids. CONCLUSIONS: Already in early adulthood, aortic wall geometry and stiffness vary by age, sex, BMI, and blood pressure.

Fast 3D isotropic imaging of the aortic vessel wall by application of 2D spatially selective excitation and a new way of inversion recovery for black blood imaging.

PURPOSE: Aortic vessel wall imaging requires large coverage and a high spatial resolution, which makes it prohibitively time-consuming for clinical use. This work explores the feasibility of imaging the descending aorta in acceptable scan time, using two-dimensional (2D) spatially selective excitation and a new way of inversion recovery for black blood imaging. METHODS: The excitation pattern and field of view in a 3D gradient echo sequence are reduced in two dimensions, following the aorta's anisotropic geometry. Black blood contrast is obtained by partially inverting the blood's magnetization in the heart at the start of the cardiac cycle. Imaging is delayed until the inverted blood has filled the desired part of the aorta. The flip angle and delay are determined such that the blood signal is nulled upon arrival in the aorta. RESULTS: Experiments on eight volunteers showed that the descending aortic vessel wall could be imaged over more than 15 cm at a maximal resolution of 1.5 × 1.5 × 1.5 mm(3) in less than 5 min minimal scan time. CONCLUSION: This feasibility study demonstrates that time-efficient isotropic imaging of the descending aorta is possible by using 2D spatially selective excitation for motion artifact reduction and a new way of inversion recovery for black blood imaging.

Inter-observer and inter-examination variability of manual vertebral bone attenuation measurements on computed tomography.

OBJECTIVE: To determine inter-observer and inter-examination variability of manual attenuation measurements of the vertebrae in low-dose unenhanced chest computed tomography (CT). METHODS: Three hundred and sixty-seven lung cancer screening trial participants who underwent baseline and repeat unenhanced low-dose CT after 3 months because of an indeterminate lung nodule were included. The CT attenuation value of the first lumbar vertebrae (L1) was measured in all CTs by one observer to obtain inter-examination reliability. Six observers performed measurements in 100 randomly selected CTs to determine agreement with limits of agreement and Bland-Altman plots and reliability with intraclass correlation coefficients (ICCs). Reclassification analyses were performed using a threshold of 110 HU to define osteoporosis. RESULTS: Inter-examination reliability was excellent with an ICC of 0.92 (p < 0.001). Inter-examination limits of agreement ranged from -26 to 28 HU with a mean difference of 1 ± 14 HU. Inter-observer reliability ICCs ranged from 0.70 to 0.91. Inter-examination variability led to 11.2 % reclassification of participants and inter-observer variability led to 22.1 % reclassification. CONCLUSIONS: Vertebral attenuation values can be manually quantified with good to excellent inter-examination and inter-observer reliability on unenhanced low-dose chest CT. This information is valuable for early detection of osteoporosis on low-dose chest CT. KEY POINTS: • Vertebral attenuation values can be manually quantified on low-dose unenhanced CT reliably. • Vertebral attenuation measurements may be helpful in detecting subclinical low bone density. • This could become of importance in the detection of osteoporosis.

3D black blood VISTA vessel wall cardiovascular magnetic resonance of the thoracic aorta wall in young, healthy adults: reproducibility and implications for efficacy trial sample sizes: a cross-sectional study.

BACKGROUND: Pre-clinical detection of atherosclerosis enables personalized preventive strategies in asymptomatic individuals. Cardiovascular magnetic resonance (CMR) has evolved as an attractive imaging modality for studying atherosclerosis in vivo. Yet, the majority of aortic CMR studies and proposed sequences to date have been performed at 1.5 tesla using 2D BB techniques and a slice thickness of 4-5 mm. Here, we evaluate for the first time the reproducibility of an isotropic, T1-weighted, three-dimensional, black-blood, CMR VISTA sequence (3D-T1-BB-VISTA) for quantification of aortic wall characteristics in healthy, young adults. METHODS: In 20 healthy, young adults (10 males, mean age 31.3 years) of the AMBITYON cohort study the descending thoracic aorta was imaged with a 3.0 T MR system using the 3D-T1-BB-VISTA sequence. The inter-scan, inter-rater and intra-rater reproducibility of aortic lumen, total vessel and wall area and mean and maximum wall thickness was evaluated using Bland-Altman analyses and Intraclass Correlation Coefficients (ICC). Based on these findings, sample sizes for detecting differences in aortic wall characteristics between groups were calculated. RESULTS: For each studied parameter, the inter-scan, inter-rater and intra-rater reproducibility was excellent as indicated by narrow limits of agreement and high ICCs (ranging from 0.76 to 0.99). Sample sizes required to detect a 5% difference in aortic wall characteristics between two groups were 203, 126, 136, 68 and 153 per group for lumen area, total vessel area and vessel wall area and for mean and maximum vessel wall thickness, respectively. CONCLUSION: The 3D-T1-BB-VISTA sequence provides excellent reproducibility for quantification of aortic wall characteristics and can detect small differences between groups with reasonable sample sizes. Hence, it may be a valuable tool for assessment of the subtle vascular wall changes of early atherosclerosis in asymptomatic populations.

Cardiac valve calcifications on low-dose unenhanced ungated chest computed tomography: inter-observer and inter-examination reliability, agreement and variability.

OBJECTIVES: To determine inter-observer and inter-examination variability for aortic valve calcification (AVC) and mitral valve and annulus calcification (MC) in low-dose unenhanced ungated lung cancer screening chest computed tomography (CT). METHODS: We included 578 lung cancer screening trial participants who were examined by CT twice within 3 months to follow indeterminate pulmonary nodules. On these CTs, AVC and MC were measured in cubic millimetres. One hundred CTs were examined by five observers to determine the inter-observer variability. Reliability was assessed by kappa statistics (κ) and intra-class correlation coefficients (ICCs). Variability was expressed as the mean difference ± standard deviation (SD). RESULTS: Inter-examination reliability was excellent for AVC (κ = 0.94, ICC = 0.96) and MC (κ = 0.95, ICC = 0.90). Inter-examination variability was 12.7 ± 118.2 mm(3) for AVC and 31.5 ± 219.2 mm(3) for MC. Inter-observer reliability ranged from κ = 0.68 to κ = 0.92 for AVC and from κ = 0.20 to κ = 0.66 for MC. Inter-observer ICC was 0.94 for AVC and ranged from 0.56 to 0.97 for MC. Inter-observer variability ranged from -30.5 ± 252.0 mm(3) to 84.0 ± 240.5 mm(3) for AVC and from -95.2 ± 210.0 mm(3) to 303.7 ± 501.6 mm(3) for MC. CONCLUSIONS: AVC can be quantified with excellent reliability on ungated unenhanced low-dose chest CT, but manual detection of MC can be subject to substantial inter-observer variability. Lung cancer screening CT may be used for detection and quantification of cardiac valve calcifications. KEY POINTS: • Low-dose unenhanced ungated chest computed tomography can detect cardiac valve calcifications. • However, calcified cardiac valves are not reported by most radiologists. • Inter-observer and inter-examination variability of aortic valve calcifications is sufficient for longitudinal studies. • Volumetric measurement variability of mitral valve and annulus calcifications is substantial.

Coronary calcification measures predict mortality in symptomatic women and men.

OBJECTIVE: To assess the prognostic value of absolute and sex-specific, age-specific and race/ethnicity-specific (Multi-Ethnic Study of Atherosclerosis, MESA) percentiles of coronary artery calcification in symptomatic women and men. METHODS: The study population consisted of 4985 symptomatic patients (2793 women, 56%) visiting a diagnostic outpatient cardiology clinic between 2009 and 2018 who were referred for cardiac CT to determine Coronary Artery Calcium Score (CACS). Regular care data were used and these data were linked to the databases of Statistics Netherlands for all-cause mortality data. Kaplan-Meier curves, multivariate Cox proportional hazards regression and concordance statistics were used to evaluate the prognostic value of CACS and MESA percentiles. Women were older compared with men (60 vs 59 years). RESULTS: Median CACS was 0 (IQR: 0-54) in women and 42 (IQR: 0-54) in men. After a median follow-up of 4.4 years (IQR: 3.1-6.3), 116 (2.3%; 53 women and 63 men) patients died. MESA percentiles did not perform better compared with absolute CACS (C-statistic 0.65, 95% CI 0.57 to 0.73, vs 0.66, 95% CI 0.58 to 0.74, in women and 0.59, 95% CI 0.51 to 0.67, vs 0.62, 95% CI 0.55 to 0.69, in men, for the percentiles and absolute CACS, respectively). CONCLUSIONS: In symptomatic individuals absolute CACS predicts mortality with a moderately good performance. MESA percentiles did not perform better compared with absolute CACS, thus there is no need to use them. Including degree of stenosis in the model might slightly improve mortality risk prediction in women, but not in men.

Preclinical Aortic Atherosclerosis in Adolescents With Chronic Disease.

Background Adolescents with chronic disease are often exposed to inflammatory, metabolic, and hemodynamic risk factors for early atherosclerosis. Since postmortem studies have shown that atherogenesis starts in the aorta, the CDACD (Cardiovascular Disease in Adolescents with Chronic Disease) study investigated preclinical aortic atherosclerosis in these adolescents. Methods and Results The cross-sectional CDACD study enrolled 114 adolescents 12 to 18 years old with chronic disorders including juvenile idiopathic arthritis, cystic fibrosis, obesity, corrected coarctation of the aorta, and healthy controls with a corrected atrial septal defect. Cardiovascular magnetic resonance was used to assess aortic pulse wave velocity and aortic wall thickness, as established aortic measures of preclinical atherosclerosis. Cardiovascular magnetic resonance showed a higher aortic pulse wave velocity, which reflects aortic stiffness, and higher aortic wall thickness in all adolescent chronic disease groups, compared with controls (P<0.05). Age (ß=0.253), heart rate (ß=0.236), systolic blood pressure (ß=-0.264), and diastolic blood pressure (ß=0.365) were identified as significant predictors for aortic pulse wave velocity, using multivariable linear regression analysis. Aortic wall thickness was predicted by body mass index (ß=0.248) and fasting glucose (ß=0.242), next to aortic lumen area (ß=0.340). Carotid intima-media thickness was assessed using ultrasonography, and was only higher in adolescents with coarctation of the aorta, compared with controls (P<0.001). Conclusions Adolescents with chronic disease showed enhanced aortic stiffness and wall thickness compared with controls. The enhanced aortic pulse wave velocity and aortic wall thickness in adolescents with chronic disease could indicate accelerated atherogenesis. Our findings underscore the importance of the aorta for assessment of early atherosclerosis, and the need for tailored cardiovascular follow-up of children with chronic disease.

Persistent Symptoms and Health Needs of Women and Men With Non-Obstructed Coronary Arteries in the Years Following Coronary Angiography.

Background: The prognosis of women and men with persistent anginal complaints and non-obstructed coronary arteries is impaired as compared with asymptomatic women and men. The increased healthcare burden in the hospital due to repeated coronary angiography in these women and men has been documented, yet little is known about the percentage of women and men who remain symptomatic and under care of the general practitioner in the years following a coronary angiographic outcome of non-obstructed coronary arteries. Methods: From the Utrecht Coronary Biobank study, including individuals who underwent a coronary angiography from 2011 to 2015 (N = 2,546, 27% women), we selected women and men with non-obstructed coronary arteries (N = 687, 39% women). This population was linked to the Julius General Practitioners Network (JGPN); a database with routine care data of general practitioners. For every individual with non-obstructed coronary arteries, we selected an asymptomatic non-referred age-, sex-, and general practitioner-matched individual from the JGPN. We compared the healthcare consumption of men and women with non-obstructed coronary arteries to these matched individuals. The McNemar's test was used for pairwise comparison, and sex differences were assessed using stratified analyses. Results: The prevalence of non-obstructed coronary arteries was higher in women as compared with men (39 vs. 23%). During a median follow-up of 7 years [IQR 6.4-8.0], 89% of the individuals with non-obstructed coronary arteries (91% women and 87% men) visited their general practitioner for one or more cardiovascular consultations. This was compared to 34% of the matched individuals (89 vs. 34%, p < 0.001). The consultations were most often for angina (equivalents) (57 vs. 11%, p < 0.001) and heart failure (10 vs. 2%, p = 0.015). In addition, they more often consulted the general practitioner for psychosocial complaints (31 vs. 15%, p = 0.005). Findings were similar for women and men. Conclusions: A coronary angiographic outcome of non-obstructed coronary arteries is more common in women than in men. In the years following the coronary angiography, the majority of the population remains symptomatic. Both women and men with non-obstructed coronary arteries had higher health needs for angina, heart failure, and psychosocial complaints than matched asymptomatic individuals.

Sex-Specific Aspects in the Pathophysiology and Imaging of Coronary Macro- and Microvascular Disease.

Sex differences in coronary artery disease (CAD) are well established, with women presenting with non-obstructive CAD more often than men do. However, recent evidence has identified coronary microvascular dysfunction as the underlying cause for cardiac complaints, yet sex-specific prevalence numbers are inconclusive. This review summarises known sex-specific aspects in the pathophysiology of both macro- and microvascular dysfunction and identifies currently existing knowledge gaps. In addition, this review describes current diagnostic approaches and whether these should take underlying sex differences into account by, for example, using different techniques or cut-off values for women and men. Future research into both innovation of imaging techniques and perfusion-related sex differences is needed to fill evidence gaps and enable the implementation of the available knowledge in daily clinical practice.

Coronary artery disease prediction in women and men using chest pain characteristics and risk factors: an observational study in outpatient clinics.

OBJECTIVES: To assess the diagnostic value of non-acute chest pain characteristics for coronary artery disease in women and men referred to outpatient cardiology clinics. DESIGN AND SETTING: This is an observational study performed at outpatient cardiology centres of the Netherlands. PARTICIPANTS: The study population consisted of 1028 patients with non-acute chest pain (505 women). ANALYSIS AND RESULTS: Twenty-four women (5%) and 75 men (15%) were diagnosed with coronary artery disease by invasive coronary angiography or CT angiography during regular care follow-up. Elastic net regression was performed to assess which chest pain characteristics and risk factors were of diagnostic value. The overall model selected age, provocation by temperature or stress, relief at rest and functional class as determinants and was accurate in both sexes (area under the curve (AUC) of 0.76 (95% CI 0.68 to 0.85) in women and 0.83 (95% CI 0.78 to 0.88) in men). Both sex-specific models selected age, pressuring nature, radiation, duration, frequency, progress, provocation and relief at rest as determinants. The female model additionally selected dyspnoea, body mass index, hypertension and smoking while the male model additionally selected functional class and diabetes. The sex-specific models performed better than the overall model, but more so in women (AUC: 0.89, 95% CI 0.81 to 0.96) than in men (AUC: 0.84, 95% CI 0.73 to 0.90). CONCLUSIONS: In both sexes, the diagnostic value of non-acute chest pain characteristics and risk factors for coronary artery disease was high. Provocation, relief at rest and functional class of chest pain were the most powerful diagnostic predictors in both women and men. When stratified by sex the performance of the model improved, mostly in women.

Cardiovascular imaging of women and men visiting the outpatient clinic with chest pain or discomfort: design and rationale of the ARGUS Study.

INTRODUCTION: Chest pain or discomfort affects 20%-40% of the general population over the course of their life and may be a symptom of myocardial ischaemia. For the diagnosis of obstructive macrovascular coronary artery disease (CAD), algorithms have been developed; however, these do not exclude microvascular angina. This may lead to false reassurance of symptomatic patients, mainly women, with functionally significant, yet non-obstructive coronary vascular disease. Therefore, this study aims to estimate the prevalence of both macrovascular and microvascular coronary vascular disease in women and men presenting with chest pain or discomfort, and to subsequently develop a decision-support tool to aid cardiologists in referral to cardiovascular imaging for both macrovascular and microvascular CAD evaluation. METHODS AND ANALYSIS: Women and men with chest pain or discomfort, aged 45 years and older, without a history of cardiovascular disease, who are referred to an outpatient cardiology clinic by their general practitioner are eligible for inclusion. Coronary CT angiography is used for anatomical imaging. Additionally, myocardial perfusion imaging by adenosine stress cardiac MRI is performed to detect functionally significant coronary vascular disease. Electronic health record data, collected during regular cardiac work-up, including medical history, cardiovascular risk factors, physical examination, echocardiography, (exercise) ECG and blood samples for standard cardiovascular biomarkers and research purposes, are obtained. Participants will be classified as positive or negative for coronary vascular disease based on all available data by expert panel consensus (a cardiovascular radiologist and two cardiologists). After completion of the clinical study, all collected data will be used to develop a decision support tool using predictive modelling and machine-learning techniques. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of the University Medical Center Utrecht. Results will be disseminated through national and international conferences and in peer-reviewed journals in cardiovascular disease. TRIAL REGISTRATION NUMBER: Trialregister.nl Registry NL8702.

Adverse Drug Reactions to Guideline-Recommended Heart Failure Drugs in Women: A Systematic Review of the Literature.

OBJECTIVES: This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication. BACKGROUND: Women are more likely to experience ADRs than men, and these reactions may negatively affect women's immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs. METHODS: A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, ß-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF. RESULTS: The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor-related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist-related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and ß-blockers. Sex-stratified data were not available for ivabradine. CONCLUSIONS: These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.

Women in Translational Medicine: Tools to Break the Glass Ceiling.

Despite the recent movements for female equality and empowerment, few women occupy top positions in scientific decision-making. The challenges women face during their career may arise from societal biases and the current scientific culture. We discuss the effect of such biases at three different levels of the career and provide suggestions to tackle them. At the societal level, gender roles can create a negative feedback loop in which women are discouraged from attaining top positions and men are discouraged from choosing a home-centred lifestyle. This loop can be broken early in life by providing children with female role models that have a work-centred life and opening up the discussion about gender roles at a young age. At the level of hiring, unconscious biases can lead to a preference for male candidates. The introduction of (unbiased) artificial intelligence algorithms and gender champions in the hiring process may restore the balance and give men and women an equal chance. At the level of coaching and evaluation, barriers that women face should be addressed on a personal level through the introduction of coaching and mentoring programmes. In addition, women may play a pivotal role in shifting the perception of scientific success away from bibliometric outcomes only towards a more diverse assessment of quality and societal relevance. Taken together, these suggestions may break the glass ceiling in the scientific world for women; create more gender diversity at the top and improve translational science in medicine.

Relation Between Adolescent Cardiovascular Risk Factors and Carotid Intima-Media Echogenicity in Healthy Young Adults: The Atherosclerosis Risk in Young Adults (ARYA) Study.

BACKGROUND: Echogenicity is an ultrasound measure that reflects arterial wall composition. In adult populations, lower carotid intima-media echogenicity relates to an unfavorable cardiovascular risk burden yet appears to reflect a different aspect of arterial wall remodeling than carotid intima-media thickness (CIMT). Since studies on carotid intima-media echogenicity earlier in life are lacking, we investigated associations between adolescent cardiovascular risk factors and young adulthood carotid intima-media echogenicity and compared this to CIMT. METHODS AND RESULTS: In 736 participants of the Atherosclerosis Risk in Young Adults study, information on adolescent anthropometrics, puberty stage, and systolic blood pressure (SBP) was available. In young adulthood, demographics, anthropometrics, and fasting plasma samples were collected. Common CIMT and echogenicity, quantified as gray-scale median (GSM), were evaluated using B-mode ultrasonography. Lower and higher GSM values, respectively, represented lower and higher echogenicity. Associations of adolescent body mass index and SBP with young adulthood GSM and CIMT were evaluated using linear regression analysis. Mean age was 13.5 years in adolescence and 28.4 years in young adulthood (difference: 14.9 years). After full adjustment, adolescent body mass index related to GSM (ß=-1.62/SD; 95% CI: -2.79, -0.46; P=0.006), independent of CIMT. Adolescent SBP did not relate to GSM. Moreover, adolescent body mass index (ß=8.06 µm/SD [95% CI: 4.12, 11.99], P<0.001) and SBP (ß=4.69 µm/SD [95% CI: 0.84, 8.54], P=0.02) related to CIMT. CONCLUSIONS: Adolescent body mass index related to GSM and CIMT in young adulthood; SBP only related to CIMT. Hence, carotid intima-media echogenicity appears to be involved in arterial wall remodeling, yet may mimic a different facet of this process than CIMT.

Reference Values for Cardiac and Aortic Magnetic Resonance Imaging in Healthy, Young Caucasian Adults.

BACKGROUND: Reference values for morphological and functional parameters of the cardiovascular system in early life are relevant since they may help to identify young adults who fall outside the physiological range of arterial and cardiac ageing. This study provides age and sex specific reference values for aortic wall characteristics, cardiac function parameters and aortic pulse wave velocity (PWV) in a population-based sample of healthy, young adults using magnetic resonance (MR) imaging. MATERIALS AND METHODS: In 131 randomly selected healthy, young adults aged between 25 and 35 years (mean age 31.8 years, 63 men) of the general-population based Atherosclerosis-Monitoring-and-Biomarker-measurements-In-The-YOuNg (AMBITYON) study, descending thoracic aortic dimensions and wall thickness, thoracic aortic PWV and cardiac function parameters were measured using a 3.0T MR-system. Age and sex specific reference values were generated using dedicated software. Differences in reference values between two age groups (25-30 and 30-35 years) and both sexes were tested. RESULTS: Aortic diameters and areas were higher in the older age group (all p<0.007). Moreover, aortic dimensions, left ventricular mass, left and right ventricular volumes and cardiac output were lower in women than in men (all p<0.001). For mean and maximum aortic wall thickness, left and right ejection fraction and aortic PWV we did not observe a significant age or sex effect. CONCLUSION: This study provides age and sex specific reference values for cardiovascular MR parameters in healthy, young Caucasian adults. These may aid in MR guided pre-clinical identification of young adults who fall outside the physiological range of arterial and cardiac ageing.

Single Breath-Hold T1ρ-Mapping of the Heart for Endogenous Assessment of Myocardial Fibrosis.

OBJECTIVES: In this study, we propose a method to acquire high spatial-resolution T1ρ-maps, which allows bright and black-blood imaging, in a single breath-hold. To validate this innovative method, the reproducibility was tested in phantoms and volunteers. Lastly, the sensitivity and specificity for infarct detection was compared with the criterion standard late gadolinium enhancement (LGE). METHODS: T1ρ-mapping was performed using a T1ρ-prepared balanced steady-state free precession sequence at 1.5 T and 3 T. Five images with increasing spin-lock preparation times (spin-lock = 0, 10, 20, 30, 40 milliseconds, amplitude = 500 Hz) were acquired with an interval of 3 beats. Black-blood imaging was performed using a double inversion pulse sequence. The method was tested in 2 times 10 healthy volunteers at 1.5 and 3 T and in 9 myocardial infarction patients at 1.5 T. T1ρ-maps, and LGE images were scored for presence and extent of myocardial scarring. RESULTS: Phantom results show that the proposed T1ρ-mapping method gives accurate T1ρ-values. The mean T1ρ-relaxation time of the myocardium in healthy controls was 52.8 ± 1.8 milliseconds at 1.5 T and 46.4 ± 1.8 milliseconds at 3 T. In patients, the T1ρ of infarcted myocardium was (82.4 ± 5.2 milliseconds), and the T1ρ of remote myocardium was (54.2 ± 2.8 milliseconds; P < 0.0001). Sensitivity of infarct detection on a T1ρ-map was 70%, with a specificity of 94%, compared with LGE. CONCLUSIONS: In this study, we have investigated a method to acquire high spatial-resolution T1ρ-maps of the heart in a single breath-hold. This method proved to be reproducible and had high specificity compared with LGE and can thus be used for the endogenous detection of myocardial fibrosis in patients with ischemic cardiomyopathy.

Relation Between Circulating Inflammatory Chemokines and Vascular Characteristics in Healthy, Young Children.

BACKGROUND: Atherosclerosis begins in childhood with the occurrence of inflammatory vascular wall alterations that are detectable with B-mode ultrasound. Chemokines appear to be involved in the development of these alterations given that they occur early in the atherosclerotic pathway as mediators of vascular inflammation. However, this has not extensively been investigated. Therefore, we studied in healthy young children whether chemokines monocyte chemotactic protein 1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES), and vascular and intercellular adhesion molecules (VCAM and ICAM) related to vascular characteristics of the carotid artery. METHODS AND RESULTS: We obtained demography, anthropometry, and overnight fasting plasma of 139 eight-year-old children of the Wheezing Illnesses Study Leidsche Rijn birth cohort. Carotid intima-media thickness (CIMT), distensibility, and Young's Elastic Modulus (YEM) of the common carotid artery were measured sonographically. Chemokine plasma levels were assessed using a multiplex assay. We studied the relation between the chemokines and vascular characteristics using multivariable linear regression analyses with adjustments for sex, systolic blood pressure, homeostasis model assessment of insulin resistance, triglycerides, low-density lipoprotein- and high-density lipoprotein-cholesterol. Of the studied chemokines, RANTES related to common carotid distensibility and YEM. One standard deviation increase in RANTES level related to a 5.45-MPA(-1) (95% confidence interval [CI], -9.43, -1.39; P=0.01) decrease in distensibility and to a 5.55-kPa increase in YEM (95% CI, 0.40, 10.85; P=0.03). RANTES did not relate to CIMT. MCP-1, VCAM, and ICAM did not relate to any of the studied vascular characteristics. CONCLUSION: RANTES appears to be involved in the development of preatherosclerotic inflammatory vascular alterations already in healthy, young children. This may provide further insight into the early-life origins of atherosclerosis.

Common carotid intima-media thickness relates to cardiovascular events in adults aged <45 years.

Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population-based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixed-effects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11-1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavorable risk factor burden.