Adipose Tissue in Cardiovascular Disease: From Basic Science to Clinical Translation.

The perception of adipose tissue as a metabolically quiescent tissue, primarily responsible for lipid storage and energy balance (with some endocrine, thermogenic, and insulation functions), has changed. It is now accepted that adipose tissue is a crucial regulator of metabolic health, maintaining bidirectional communication with other organs including the cardiovascular system. Additionally, adipose tissue depots are functionally and morphologically heterogeneous, acting not only as sources of bioactive molecules that regulate the physiological functioning of the vasculature and myocardium but also as biosensors of the paracrine and endocrine signals arising from these tissues. In this way, adipose tissue undergoes phenotypic switching in response to vascular and/or myocardial signals (proinflammatory, profibrotic, prolipolytic), a process that novel imaging technologies are able to visualize and quantify with implications for clinical prognosis. Furthermore, a range of therapeutic modalities have emerged targeting adipose tissue metabolism and altering its secretome, potentially benefiting those at risk of cardiovascular disease.

Cardiac Computed Tomography: Assessment of Coronary Inflammation and Other Plaque Features.

Unstable coronary plaques that are prone to erosion and rupture are the major cause of acute coronary syndromes. Our expanding understanding of the biological mechanisms of coronary atherosclerosis and rapid technological advances in the field of medical imaging has established cardiac computed tomography as a first-line diagnostic test in the assessment of suspected coronary artery disease, and as a powerful method of detecting the vulnerable plaque and patient. Cardiac computed tomography can provide a noninvasive, yet comprehensive, qualitative and quantitative assessment of coronary plaque burden, detect distinct high-risk morphological plaque features, assess the hemodynamic significance of coronary lesions and quantify the coronary inflammatory burden by tracking the effects of arterial inflammation on the composition of the adjacent perivascular fat. Furthermore, advances in machine learning, computational fluid dynamic modeling, and the development of targeted contrast agents continue to expand the capabilities of cardiac computed tomography imaging. In our Review, we discuss the current role of cardiac computed tomography in the assessment of coronary atherosclerosis, highlighting its dual function as a clinical and research tool that provides a wealth of structural and functional information, with far-reaching diagnostic and prognostic implications.

Exposure to parental smoking in childhood is associated with increased risk of carotid atherosclerotic plaque in adulthood: the Cardiovascular Risk in Young Finns Study.

BACKGROUND: The association between passive smoking exposure in childhood and adverse cardiovascular health in adulthood is not well understood. Using a 26-year follow-up study, we examined whether childhood exposure to passive smoking was associated with carotid atherosclerotic plaque in young adults. METHODS AND RESULTS: Participants were from the Cardiovascular Risk in Young Finns Study (n=2448). Information on childhood exposure to parental smoking was collected in 1980 and 1983. Carotid ultrasound data were collected in adulthood in 2001 or 2007. Childhood serum cotinine levels from 1980 were measured from frozen samples in 2014 (n=1578). The proportion of children with nondetectable cotinine levels was highest among households in which neither parent smoked (84%), was decreased in households in which 1 parent smoked (62%), and was lowest among households in which both parents smoked (43%). Regardless of adjustment for potential confounding and mediating variables, the relative risk of developing carotid plaque in adulthood increased among those children with 1 or both parents who smoked (relative risk, 1.7; 95% confidence interval, 1.0-2.8; P=0.04). Although children whose parents exercised good "smoking hygiene" (smoking parents whose children had nondetectable cotinine levels) had increased risk of carotid plaque compared with children with nonsmoking parents (relative risk, 1.6; 95% confidence interval, 0.6-4.0; P=0.34), children of smoking parents with poor smoking hygiene (smoking parents whose children had detectable serum cotinine levels) had substantially increased risk of plaque as adults (relative risk, 4.0; 95% confidence interval, 1.7-9.8; P=0.002). CONCLUSIONS: Children of parents who smoke have increased risk of developing carotid atherosclerotic plaque in adulthood. However, parents who exercise good smoking hygiene can lessen their child's risk of developing plaque.

Advances in Clinical Imaging of Vascular Inflammation: A State-of-the-Art Review.

Vascular inflammation is a major contributor to cardiovascular disease, particularly atherosclerotic disease, and early detection of vascular inflammation may be key to the ultimate reduction of residual cardiovascular morbidity and mortality. This review paper discusses the progress toward the clinical utility of noninvasive imaging techniques for assessing vascular inflammation, with a focus on coronary atherosclerosis. A discussion of multiple modalities is included: computed tomography (CT) imaging (the major focus of the review), cardiac magnetic resonance, ultrasound, and positron emission tomography imaging. The review covers recent progress in new technologies such as the novel CT biomarkers of coronary inflammation (eg, the perivascular fat attenuation index), new inflammation-specific tracers for positron emission tomography-CT imaging, and others. The strengths and limitations of each modality are explored, highlighting the potential for multi-modality imaging and the use of artificial intelligence image interpretation to improve both diagnostic and prognostic potential for common conditions such as coronary artery disease.

Deep-Learning for Epicardial Adipose Tissue Assessment With Computed Tomography: Implications for Cardiovascular Risk Prediction.

BACKGROUND: Epicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented. OBJECTIVES: This study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care. METHODS: The deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value. RESULTS: External validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio [OR] per SD increase in EAT volume: 1.13 [95% CI: 1.04-1.30]; P = 0.01), and atrial fibrillation (OR: 1.25 [95% CI: 1.08-1.40]; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 [95% CI: 1.10-1.37]; P = 0.02), myocardial infarction (HR: 1.26 [95% CI:1.09-1.38]; P = 0.001), and stroke (HR: 1.20 [95% CI: 1.09-1.38]; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 [95% CI: 1.26-3.73]; P ≤ 0.01) and long-term post-cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 [95% CI: 1.19-2.97]; P ≤ 0.01). CONCLUSIONS: Automated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification.

Imaging and Targeting Coronary Artery Inflammation.

Significance: Coronary artery disease (CAD) continues to be a leading cause of morbidity and mortality across the world despite significant progress in the prevention, diagnosis, and treatment of atherosclerotic disease. Recent Advances: The focus of the cardiovascular community has shifted toward seeking a better understanding of the inflammatory mechanisms driving residual CAD risk that is not modulated by current therapies. Significant progress has been achieved in revealing both proinflammatory and anti-inflammatory mechanisms, and how shift of the balance in favor of the former can drive the development of disease. Critical Issues: Advances in the noninvasive detection of coronary artery inflammation have been forthcoming. These advances include multiple imaging modalities, with novel applications of computed tomography both with and without positron emission tomography, and experimental ultrasound techniques. These advances will enable better selection of patients for anti-inflammatory treatments and assessment of treatment response. The rapid advancement in pharmaceutical design has enabled the production of specific antibodies against inflammatory pathways of atherosclerosis, with modest success to date. The pursuit of demonstrating the efficacy and safety of novel anti-inflammatory and/or proinflammatory resolution therapies for atherosclerotic CAD has become a major focus. Future Directions: This review seeks to provide an update of the latest evidence of all three of these highly related but disparate areas of inquiry: Our current understanding of the key mechanisms by which inflammation contributes to coronary artery atherosclerosis, the evidence for noninvasive assessment of coronary artery inflammation, and finally, the evidence for targeted therapies to treat coronary inflammation for the reduction of CAD risk. Antioxid. Redox Signal. 34, 1217-1243.