The Need to Expand the Framework of Environmental Determinants of Cardiovascular Health From Climate Change to Planetary Health: Trial by Wildfire

Andrew Y. Chang, Michele Barry, Robert A. Harrington

doi : 10.1161/CIRCULATIONAHA.120.051892

Circulation. 2021;143:2029–2031

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Preterm Delivery and Long-Term Risk of Stroke in Women: A National Cohort and Cosibling Study

Casey Crump, Jan Sundquist, Kristina Sundquist

doi : 10.1161/CIRCULATIONAHA.120.052268

Circulation. 2021;143:2032–2044

Stroke has a high burden of disease in women, and adverse pregnancy outcomes have been identified as important risk factors for stroke later in life. However, long-term risks of stroke associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment and stroke prevention in women.

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Pregnancy as Oracle: What It Augurs for Women’s Health

Padma Kaul, Winnie W. Sia

doi : 10.1161/CIRCULATIONAHA.121.054617

Circulation. 2021;143:2045–2048

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Impact of Socioeconomic Status, Race and Ethnicity, and Geography on Prenatal Detection of Hypoplastic Left Heart Syndrome and Transposition of the Great Arteries

Anita Krishnan, Marni B. Jacobs, Shaine A. Morris, Shabnam Peyvandi, Aarti H. Bhat, Anjali Chelliah, Joanne S. Chiu, Bettina F. Cuneo, Grace Freire, Lisa K. Hornberger, Lisa Howley, Nazia Husain, Catherine Ikemba, Ann Kavanaugh-McHugh, Shelby Kutty, Caroline Lee, Keila N. Lopez, Angela McBrien, Erik C. Michelfelder, Nelangi M. Pinto, Rachel Schwartz, Kenan W.D. Stern, Carolyn Taylor, Varsha Thakur, Wayne Tworetzky, Carol Wittlieb-Weber, Kris Woldu, Mary T. Donofrio,

doi : 10.1161/CIRCULATIONAHA.120.053062

Circulation. 2021;143:2049–2060

Prenatal detection (PND) has benefits for infants with hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), but associations between sociodemographic and geographic factors with PND have not been sufficiently explored. This study evaluated whether socioeconomic quartile (SEQ), public insurance, race and ethnicity, rural residence, and distance of residence (distance and driving time from a cardiac surgical center) are associated with the PND or timing of PND, with a secondary aim to analyze differences between the United States and Canada.

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Oxygen Pathway Limitations in Patients With Chronic Thromboembolic Pulmonary Hypertension

Erin J. Howden, Sergio Ruiz-Carmona, Mathias Claeys, Ruben De Bosscher, Rik Willems, Bart Meyns, Tom Verbelen, Geert Maleux, Laurent Godinas, Catharina Belge, Jan Bogaert, Piet Claus, Andre La Gerche, Marion Delcroix, Guido Claessen

doi : 10.1161/CIRCULATIONAHA.120.052899

Circulation. 2021;143:2061–2073

Exertional intolerance is a limiting and often crippling symptom in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally the pathogenesis has been attributed to central factors, including ventilation/perfusion mismatch, increased pulmonary vascular resistance, and right heart dysfunction and uncoupling. Pulmonary endarterectomy and balloon pulmonary angioplasty provide substantial improvement of functional status and hemodynamics. However, despite normalization of pulmonary hemodynamics, exercise capacity often does not return to age-predicted levels. By systematically evaluating the oxygen pathway, we aimed to elucidate the causes of functional limitations in patients with CTEPH before and after pulmonary vascular intervention.

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ALDH1A3 Coordinates Metabolism With Gene Regulation in Pulmonary Arterial Hypertension

Dan Li, Ning-Yi Shao, Jan-Renier Moonen, Zhixin Zhao, Minyi Shi, Shoichiro Otsuki, Lingli Wang, Tiffany Nguyen, Elaine Yan, David P. Marciano, Kévin Contrepois, Caiyun G. Li, Joseph C. Wu, Michael P. Snyder, Marlene Rabinovitch

doi : 10.1161/CIRCULATIONAHA.120.048845

Circulation. 2021;143:2074–2090

Metabolic alterations provide substrates that influence chromatin structure to regulate gene expression that determines cell function in health and disease. Heightened proliferation of smooth muscle cells (SMC) leading to the formation of a neointima is a feature of pulmonary arterial hypertension (PAH) and systemic vascular disease. Increased glycolysis is linked to the proliferative phenotype of these SMC.

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Extracellular Tuning of Mitochondrial Respiration Leads to Aortic Aneurysm

Jorge Oller, Enrique Gabandé-Rodr?guez, Mar?a Jes?s Ruiz-Rodr?guez, Gabriela Desd?n-Mic?, Juan Francisco Aranda, Raquel Rodrigues-Diez, Constanza Ballesteros-Mart?nez, Eva Mar?a Blanco, Raquel Roldan-Montero, Pedro Acu?a, Alberto Forteza Gil, Carlos E. Mart?n-L?pez, J. Francisco Nistal, Christian L. Lino Cardenas, Mark Evan Lindsay, José Lu?s Mart?n-Ventura, Ana M. Briones, Juan Miguel Redondo, Mar?a Mittelbrunn

doi : 10.1161/CIRCULATIONAHA.120.051171

Circulation. 2021;143:2091–2109

Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue caused by mutations in the FBN1 (fibrillin-1) gene encoding a large glycoprotein in the extracellular matrix called fibrillin-1. The major complication of this connective disorder is the risk to develop thoracic aortic aneurysm. To date, no effective pharmacologic therapies have been identified for the management of thoracic aortic disease and the only options capable of preventing aneurysm rupture are endovascular repair or open surgery. Here, we have studied the role of mitochondrial dysfunction in the progression of thoracic aortic aneurysm and mitochondrial boosting strategies as a potential treatment to managing aortic aneurysms.

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Fate and State of Vascular Smooth Muscle Cells in Atherosclerosis

Joseph M. Miano, Edward A. Fisher, Mark W. Majesky

doi : 10.1161/CIRCULATIONAHA.120.049922

Circulation. 2021;143:2110–2116

Vascular smooth muscle cells (VSMCs) have long been associated with phenotypic modulation/plasticity or dedifferentiation. Innovative technologies in cell lineage tracing, single-cell RNA sequencing, and human genomics have been integrated to gain unprecedented insights into the molecular reprogramming of VSMCs to other cell phenotypes in experimental and clinical atherosclerosis. The current thinking is that an apparently small subset of contractile VSMCs undergoes a fate switch to transitional, multipotential cells that can adopt plaque-destabilizing (inflammation, ossification) or plaque-stabilizing (collagen matrix deposition) cell states. Several candidate mediators of such VSMC fate and state changes are coming to light with intriguing implications for understanding coronary artery disease risk and the development of new treatment modalities. Here, we briefly summarize some technical and conceptual advancements derived from 2 publications in Circulation and another in Nature Medicine that, collectively, illuminate new research directions to further explore the role of VSMCs in atherosclerotic disease.

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Highlights From the Circulation Family of Journals

doi : 10.1161/CIRCULATIONAHA.121.055443

Circulation. 2021;143:2117–2122

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Overexpression of Gata4, Mef2c, and Tbx5 Generates Induced Cardiomyocytes Via Direct Reprogramming and Rare Fusion in the Heart

Mari Isomi, Taketaro Sadahiro, Hiroyuki Yamakawa, Ryo Fujita, Yu Yamada, Yuto Abe, Yoshiko Murakata, Tatsuya Akiyama, Tsugumine Shu, Hiroaki Mizukami, Keiichi Fukuda, Masaki Ieda

doi : 10.1161/CIRCULATIONAHA.120.052799

Circulation. 2021;143:2123–2125

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Letter by Pengo et al Regarding Article, “Nighttime Blood Pressure Phenotype and Cardiovascular Prognosis: Practitioner-Based Nationwide JAMP Study”

Martino F. Pengo, Valeria Bisogni, Miguel Angel Mart?nez-Garc?a

doi : 10.1161/CIRCULATIONAHA.120.052728

Circulation. 2021;143:e980–e981

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Response by Kario et al to Letter Regarding Article, “Nighttime Blood Pressure Phenotype and Cardiovascular Prognosis: Practitioner-Based Nationwide JAMP Study”

Kazuomi Kario, Hiroshi Kanegae, Satoshi Hoshide

doi : 10.1161/CIRCULATIONAHA.121.053993

Circulation. 2021;143:e982–e983

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Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association

Tiffany M. Powell-Wiley, Paul Poirier, Lora E. Burke, Jean-Pierre Després, Penny Gordon-Larsen, Carl J. Lavie, Scott A. Lear, Chiadi E. Ndumele, Ian J. Neeland, Prashanthan Sanders, Marie-Pierre St-Onge, and On behalf of the American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Epidemiology and Prevention; and Stroke Council

doi : 10.1161/CIR.0000000000000973

Circulation. 2021;143:e984–e1010

The global obesity epidemic is well established, with increases in obesity prevalence for most countries since the 1980s. Obesity contributes directly to incident cardiovascular risk factors, including dyslipidemia, type 2 diabetes, hypertension, and sleep disorders. Obesity also leads to the development of cardiovascular disease and cardiovascular disease mortality independently of other cardiovascular risk factors. More recent data highlight abdominal obesity, as determined by waist circumference, as a cardiovascular disease risk marker that is independent of body mass index. There have also been significant advances in imaging modalities for characterizing body composition, including visceral adiposity. Studies that quantify fat depots, including ectopic fat, support excess visceral adiposity as an independent indicator of poor cardiovascular outcomes. Lifestyle modification and subsequent weight loss improve both metabolic syndrome and associated systemic inflammation and endothelial dysfunction. However, clinical trials of medical weight loss have not demonstrated a reduction in coronary artery disease rates. In contrast, prospective studies comparing patients undergoing bariatric surgery with nonsurgical patients with obesity have shown reduced coronary artery disease risk with surgery. In this statement, we summarize the impact of obesity on the diagnosis, clinical management, and outcomes of atherosclerotic cardiovascular disease, heart failure, and arrhythmias, especially sudden cardiac death and atrial fibrillation. In particular, we examine the influence of obesity on noninvasive and invasive diagnostic procedures for coronary artery disease. Moreover, we review the impact of obesity on cardiac function and outcomes related to heart failure with reduced and preserved ejection fraction. Finally, we describe the effects of lifestyle and surgical weight loss interventions on outcomes related to coronary artery disease, heart failure, and atrial fibrillation.

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