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https://read.qxmd.com/read/30770579/gene-environment-interactions-related-to-blood-pressure-traits-in-two-community-based-korean-cohorts
#1
Ji Eun Lim, Hye Ok Kim, Sang Youl Rhee, Mi Kyung Kim, Yeon-Jung Kim, Bermseok Oh
Hypertension is a complex disorder caused by genetic and environmental risk factors. Recently, genome-wide association studies (GWASs) identified more than 100 genetic variants for blood pressure traits and hypertension. However, the interactions between these genetic variants and environmental factors have not been systematically investigated. Therefore, we examined the interaction between genetic and environmental risk factors in blood pressure traits using the genetic risk score (GRS). Two Korean community-based cohorts, Cohort I (KARE; N = 8,840) and Cohort II (CAVAS; N = 9,599), were used for this study, and GRSs were calculated from 42 GWAS single-nucleotide polymorphisms (SNPs) that were validated for their association in these cohorts...
February 15, 2019: Genetic Epidemiology
https://read.qxmd.com/read/30651383/genetic-and-lifestyle-risk-factors-for-mri-defined-brain-infarcts-in-a-population-based-setting
#2
Ganesh Chauhan, Hieab H H Adams, Claudia L Satizabal, Joshua C Bis, Alexander Teumer, Muralidharan Sargurupremraj, Edith Hofer, Stella Trompet, Saima Hilal, Albert Vernon Smith, Xueqiu Jian, Rainer Malik, Matthew Traylor, Sara L Pulit, Philippe Amouyel, Bernard Mazoyer, Yi-Cheng Zhu, Sara Kaffashian, Sabrina Schilling, Gary W Beecham, Thomas J Montine, Gerard D Schellenberg, Olafur Kjartansson, Vilmundur Guðnason, David S Knopman, Michael E Griswold, B Gwen Windham, Rebecca F Gottesman, Thomas H Mosley, Reinhold Schmidt, Yasaman Saba, Helena Schmidt, Fumihiko Takeuchi, Shuhei Yamaguchi, Toru Nabika, Norihiro Kato, Kumar B Rajan, Neelum T Aggarwal, Philip L De Jager, Denis A Evans, Bruce M Psaty, Jerome I Rotter, Kenneth Rice, Oscar L Lopez, Jiemin Liao, Christopher Chen, Ching-Yu Cheng, Tien Y Wong, Mohammad K Ikram, Sven J van der Lee, Najaf Amin, Vincent Chouraki, Anita L DeStefano, Hugo J Aparicio, Jose R Romero, Pauline Maillard, Charles DeCarli, Joanna M Wardlaw, Maria Del C Valdés Hernández, Michelle Luciano, David Liewald, Ian J Deary, John M Starr, Mark E Bastin, Susana Muñoz Maniega, P Eline Slagboom, Marian Beekman, Joris Deelen, Hae-Won Uh, Robin Lemmens, Henry Brodaty, Margaret J Wright, David Ames, Giorgio B Boncoraglio, Jemma C Hopewell, Ashley H Beecham, Susan H Blanton, Clinton B Wright, Ralph L Sacco, Wei Wen, Anbupalam Thalamuthu, Nicola J Armstrong, Elizabeth Chong, Peter R Schofield, John B Kwok, Jeroen van der Grond, David J Stott, Ian Ford, J Wouter Jukema, Meike W Vernooij, Albert Hofman, André G Uitterlinden, Aad van der Lugt, Katharina Wittfeld, Hans J Grabe, Norbert Hosten, Bettina von Sarnowski, Uwe Völker, Christopher Levi, Jordi Jimenez-Conde, Pankaj Sharma, Cathie L M Sudlow, Jonathan Rosand, Daniel Woo, John W Cole, James F Meschia, Agnieszka Slowik, Vincent Thijs, Arne Lindgren, Olle Melander, Raji P Grewal, Tatjana Rundek, Kathy Rexrode, Peter M Rothwell, Donna K Arnett, Christina Jern, Julie A Johnson, Oscar R Benavente, Sylvia Wasssertheil-Smoller, Jin-Moo Lee, Quenna Wong, Braxton D Mitchell, Stephen S Rich, Patrick F McArdle, Mirjam I Geerlings, Yolanda van der Graaf, Paul I W de Bakker, Folkert W Asselbergs, Velandai Srikanth, Russell Thomson, Rebekah McWhirter, Chris Moran, Michele Callisaya, Thanh Phan, Loes C A Rutten-Jacobs, Steve Bevan, Christophe Tzourio, Karen A Mather, Perminder S Sachdev, Cornelia M van Duijn, Bradford B Worrall, Martin Dichgans, Steven J Kittner, Hugh S Markus, Mohammad A Ikram, Myriam Fornage, Lenore J Launer, Sudha Seshadri, W T Longstreth, Stéphanie Debette
OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI...
January 16, 2019: Neurology
https://read.qxmd.com/read/30645721/pharmacogenomics-of-amlodipine-and-hydrochlorothiazide-therapy-and-the-quest-for-improved-control-of-hypertension-a-mini-review
#3
REVIEW
Rabia Johnson, Phiwayinkosi Dludla, Sihle Mabhida, Mongi Benjeddou, Johan Louw, Faghri February
Blood pressure (BP) is a complex trait that is regulated by multiple physiological pathways and include but is not limited to extracellular fluid volume homeostasis, cardiac contractility, and vascular tone through renal, neural, or endocrine systems. Uncontrolled hypertension (HTN) has been associated with an increased mortality risk. Therefore, understanding the genetics that underpins and influence BP regulation will have a major impact on public health. Moreover, uncontrolled HTN has been linked to inter-individual variation in the drugs' response and this has been associated with an individual's genetics architecture...
January 15, 2019: Heart Failure Reviews
https://read.qxmd.com/read/30566436/hypertension-genetic-risk-score-is-associated-with-burden-of-coronary-heart-disease-among-patients-referred-for-coronary-angiography
#4
Maria Lukács Krogager, Regitze Kuhr Skals, Emil Vincent R Appel, Theresia M Schnurr, Line Engelbrechtsen, Christian Theil Have, Oluf Pedersen, Thomas Engstrøm, Dan M Roden, Gunnar Gislason, Henrik Enghusen Poulsen, Lars Køber, Steen Stender, Torben Hansen, Niels Grarup, Charlotte Andersson, Christian Torp-Pedersen, Peter E Weeke
BACKGROUND: Recent GWAS studies have identified more than 300 SNPs associated with variation in blood pressure. We investigated whether a genetic risk score constructed from these variants is associated with burden of coronary heart disease. METHODS: From 2010-2014, 4,809 individuals admitted to coronary angiography in Capital Region of Copenhagen were genotyped. We calculated hypertension GRS comprised of GWAS identified SNPs associated with blood pressure. We performed logistic regression analyses to estimate the risk of hypertension and prevalent CHD...
2018: PloS One
https://read.qxmd.com/read/30531941/gwas-identifies-14-loci-for-device-measured-physical-activity-and-sleep-duration
#5
Aiden Doherty, Karl Smith-Byrne, Teresa Ferreira, Michael V Holmes, Chris Holmes, Sara L Pulit, Cecilia M Lindgren
Physical activity and sleep duration are established risk factors for many diseases, but their aetiology is poorly understood, partly due to relying on self-reported evidence. Here we report a genome-wide association study (GWAS) of device-measured physical activity and sleep duration in 91,105 UK Biobank participants, finding 14 significant loci (7 novel). These loci account for 0.06% of activity and 0.39% of sleep duration variation. Genome-wide estimates of ~ 15% phenotypic variation indicate high polygenicity...
December 10, 2018: Nature Communications
https://read.qxmd.com/read/30527956/genetic-determinants-of-risk-in-pulmonary-arterial-hypertension-international-genome-wide-association-studies-and-meta-analysis
#6
Christopher J Rhodes, Ken Batai, Marta Bleda, Matthias Haimel, Laura Southgate, Marine Germain, Michael W Pauciulo, Charaka Hadinnapola, Jurjan Aman, Barbara Girerd, Amit Arora, Jo Knight, Ken B Hanscombe, Jason H Karnes, Marika Kaakinen, Henning Gall, Anna Ulrich, Lars Harbaum, Inês Cebola, Jorge Ferrer, Katie Lutz, Emilia M Swietlik, Ferhaan Ahmad, Philippe Amouyel, Stephen L Archer, Rahul Argula, Eric D Austin, David Badesch, Sahil Bakshi, Christopher Barnett, Raymond Benza, Nitin Bhatt, Harm J Bogaard, Charles D Burger, Murali Chakinala, Colin Church, John G Coghlan, Robin Condliffe, Paul A Corris, Cesare Danesino, Stéphanie Debette, C Gregory Elliott, Jean Elwing, Melanie Eyries, Terry Fortin, Andre Franke, Robert P Frantz, Adaani Frost, Joe G N Garcia, Stefano Ghio, Hossein-Ardeschir Ghofrani, J Simon R Gibbs, John Harley, Hua He, Nicholas S Hill, Russel Hirsch, Arjan C Houweling, Luke S Howard, Dunbar Ivy, David G Kiely, James Klinger, Gabor Kovacs, Tim Lahm, Matthias Laudes, Rajiv D Machado, Robert V MacKenzie Ross, Keith Marsolo, Lisa J Martin, Shahin Moledina, David Montani, Steven D Nathan, Michael Newnham, Andrea Olschewski, Horst Olschewski, Ronald J Oudiz, Willem H Ouwehand, Andrew J Peacock, Joanna Pepke-Zaba, Zia Rehman, Ivan Robbins, Dan M Roden, Erika B Rosenzweig, Ghulam Saydain, Laura Scelsi, Robert Schilz, Werner Seeger, Christian M Shaffer, Robert W Simms, Marc Simon, Olivier Sitbon, Jay Suntharalingam, Haiyang Tang, Alexander Y Tchourbanov, Thenappan Thenappan, Fernando Torres, Mark R Toshner, Carmen M Treacy, Anton Vonk Noordegraaf, Quinten Waisfisz, Anna K Walsworth, Robert E Walter, John Wharton, R James White, Jeffrey Wilt, Stephen J Wort, Delphine Yung, Allan Lawrie, Marc Humbert, Florent Soubrier, David-Alexandre Trégouët, Inga Prokopenko, Richard Kittles, Stefan Gräf, William C Nichols, Richard C Trembath, Ankit A Desai, Nicholas W Morrell, Martin R Wilkins
BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension...
December 5, 2018: Lancet Respiratory Medicine
https://read.qxmd.com/read/30387736/backpropagation-approach-supported-by-image-compression-algorithm-for-the-classification-of-chronic-condition-diseases
#7
Abir Hussain, Dhiya Al-Jumeily, Ahmed Aljaaf, Naeem Radi
Diabetes is one of the main public health chronic conditions that are potentially reaching epidemic proportions globally. Worldwide, the occurrence of these types of diseases are increasing sharply at a worrying degree, with death of around 18 million people every year from cardiovascular disease, for which diabetes and hypertension are major predisposing factors. Two major concerns are that much of this increase in Diabetes is predicated to be happened in developing countries, with a growing incidence of Type 2 Diabetes (T2D) at a younger age including some obese children even before puberty...
October 30, 2018: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://read.qxmd.com/read/30352878/genome-wide-and-abdominal-mri-imaging-data-provides-evidence-that-a-genetically-determined-favourable-adiposity-phenotype-is-characterized-by-lower-ectopic-liver-fat-and-lower-risk-of-type-2-diabetes-heart-disease-and-hypertension
#8
Yingjie Ji, Andrianos M Yiorkas, Francesca Frau, Dennis Mook-Kanamori, Harald Staiger, E Louise Thomas, Naeimeh Atabaki-Pasdar, Archie Campbell, Jessica Tyrrell, Samuel E Jones, Robin N Beaumont, Andrew R Wood, Marcus A Tuke, Katherine S Ruth, Anubha Mahajan, Anna Murray, Rachel M Freathy, Michael N Weedon, Andrew T Hattersley, Caroline Hayward, Jürgen Machann, Hans-Ulrich Häring, Paul Franks, Renée de Mutsert, Ewan Pearson, Norbert Stefan, Timothy M Frayling, Karla V Allebrandt, Jimmy D Bell, Alexandra I Blakemore, Hanieh Yaghootkar
Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such "favourable adiposity" alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile...
October 23, 2018: Diabetes
https://read.qxmd.com/read/30334629/vascular-biology-of-superoxide-generating-nadph-oxidase-5-nox5-implications-in-hypertension-and-cardiovascular-disease
#9
Rhian M Touyz, Aikaterini Anagnostopoulou, Livia Camargo, Francisco Rios, Augusto Montezano
SIGNIFICANCE:  NADPH oxidases (Nox) of which there are 7 isoforms (Nox1-5, Duox1/Duox2) are professional oxidases functioning as ROS-generating enzymes. ROS are signaling molecules important in physiological processes. Increased ROS production and altered redox signaling in the vascular system have been implicated in the pathophysiology of cardiovascular diseases, including hypertension, and have been attributed, in part, to increased Nox activity. RECENT ADVANCES:  Nox1,2,4,5 are expressed and functionally active in human vascular cells...
October 18, 2018: Antioxidants & Redox Signaling
https://read.qxmd.com/read/30281215/ccl21-as-a-potential-biomarker-for-pulmonary-arterial-hypertension-in-systemic-sclerosis
#10
Anna-Maria Hoffmann-Vold, Øyvind Molberg
We thank Zhou and co-workers for their interest regarding our newly published manuscript on the role of CCL21 in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). Here, we want to respond to their concerns. Genome-wide association studies (GWASs) have been foreshadowed to be a major advance in biomedical discovery, with many robust associations to complex diseases. However, although there are found polymorphisms with SSc, there are, to date, no existing genetic loci for SSc-PAH...
October 3, 2018: Arthritis & Rheumatology
https://read.qxmd.com/read/30211179/hypertension-genomics-and-cardiovascular-prevention
#11
REVIEW
Fu Liang Ng, Helen R Warren, Mark J Caulfield
Hypertension continues to be a major risk factor for global mortality, and recent genome-wide association studies (GWAS) have expanded in size, leading to the identification of further genetic loci influencing blood pressure. In light of the new knowledge from the largest cardiovascular GWAS to date, we review the potential impact of genomics on discovering potential drug targets, risk stratification with genetic risk scores, drug selection with pharmacogenetics, and exploring insights provided by gene-environment interactions...
August 2018: Annals of Translational Medicine
https://read.qxmd.com/read/30149742/a-gwas-supported-variant-interacting-with-diabetes-predicts-risk-of-atherothrombotic-stroke-in-han-chinese-population
#12
Zibao Li, Bo Sun, Mengmeng Gu, Mengmeng Wang, Xi Cheng, Jia Lv, Si Cen, Shuai Zhang, Zhengze Dai, Yongjie Bai, Shun Li, Guiling Wang, Zhiqiang Weng, Yonghui Shi, Zhizhong Zhang, Xinfeng Liu
BACKGROUND: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population. METHODS: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool...
October 31, 2018: International Journal of Neuroscience
https://read.qxmd.com/read/30146708/association-of-genetic-risk-score-and-chronic-kidney-disease-in-a-japanese-population
#13
Ryosuke Fujii, Asahi Hishida, Masahiro Nakatochi, Norihiro Furusyo, Masayuki Murata, Keitaro Tanaka, Chisato Shimanoe, Sadao Suzuki, Miki Watanabe, Nagato Kuriyama, Teruhide Koyama, Toshiro Takezaki, Ippei Shimoshikiryo, Kokichi Arisawa, Sakurako Katsuura-Kamano, Naoyuki Takashima, Tanvir C Turin, Kiyonori Kuriki, Kaori Endoh, Haruo Mikami, Yohko Nakamura, Isao Oze, Hidemi Ito, Michiaki Kubo, Yukihide Momozawa, Takaaki Kondo, Mariko Naito, Kenji Wakai
Chronic kidney disease (CKD) is a public health problem worldwide including Japan. Recent genome-wide association studies (GWAS) have discovered CKD susceptibility variants. We developed a genetic risk score (GRS) based on CKD-associated variants and assessed a possibility that the GRS can improve the discrimination capability for the prevalence of CKD in a Japanese population. The present study consists of 11,283 participants randomly selected from 12 Japan Multi-Institutional Collaborative Cohort (J-MICC) Study sites...
August 26, 2018: Nephrology
https://read.qxmd.com/read/30137437/in-silico-drug-screening-by-using-genome-wide-association-study-data-repurposed-dabrafenib-an-anti-melanoma-drug-for-parkinson-s-disease
#14
Takeshi Uenaka, Wataru Satake, Pei-Chieng Cha, Hideki Hayakawa, Kousuke Baba, Shiying Jiang, Kazuhiro Kobayashi, Motoi Kanagawa, Yukinori Okada, Hideki Mochizuki, Tatsushi Toda
Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss. At present, there are no drugs that stop the progression of PD. As with other multifactorial genetic disorders, genome-wide association studies (GWASs) found multiple risk loci for PD, although their clinical significance remains uncertain. Here, we report the identification of candidate drugs for PD by a method using GWAS data and in silico databases. We identified 57 Food and Drug Administration-approved drug families as candidate neuroprotective drugs for PD...
November 15, 2018: Human Molecular Genetics
https://read.qxmd.com/read/30110940/pervasive-modulation-of-obesity-risk-by-the-environment-and-genomic-background
#15
Sini Nagpal, Greg Gibson, Urko M Marigorta
The prevalence of the so-called diseases of affluence, such as type 2 diabetes or hypertension, has increased dramatically in the last two generations. Although genome-wide association studies (GWAS) have discovered hundreds of genes involved in disease etiology, the sudden increase in disease incidence suggests a major role for environmental risk factors. Obesity constitutes a case example of a modern trait shaped by contemporary environment, although with considerable debates about the extent to which gene-by-environment (G×E) interactions accentuate obesity risk in individuals following obesogenic lifestyles...
August 14, 2018: Genes
https://read.qxmd.com/read/30022276/genetics-of-coronary-artery-disease-in-the-light-of-genome-wide-association-studies
#16
REVIEW
Heribert Schunkert, Moritz von Scheidt, Thorsten Kessler, Barbara Stiller, Lingyao Zeng, Baiba Vilne
As clinicians, we understand the development of atherosclerosis as a consequence of cholesterol deposition and inflammation in the arterial wall, both being triggered by traditional risk factors such as hypertension, hyperlipidaemia or diabetes mellitus. Another risk factor is genetic predisposition, as indicated by the predictive value of a positive family history. However, we had to wait until recently to appreciate the abundant contribution of genetic variation to the manifestation of atherosclerosis. Indeed, by now 164 chromosomal loci have been identified by genome-wide association studies (GWAS) to affect the risk of coronary artery disease...
August 2018: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://read.qxmd.com/read/29973135/genome-wide-association-study-of-nocturnal-blood-pressure-dipping-in-hypertensive-patients
#17
Jenni M Rimpelä, Ilkka H Pörsti, Antti Jula, Terho Lehtimäki, Teemu J Niiranen, Lasse Oikarinen, Kimmo Porthan, Antti Tikkakoski, Juha Virolainen, Kimmo K Kontula, Timo P Hiltunen
BACKGROUND: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. METHODS: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo...
July 4, 2018: BMC Medical Genetics
https://read.qxmd.com/read/29912321/genome-wide-studies-of-heart-failure-and-endophenotypes-lessons-learned-and-future-directions
#18
Maaike Yldau van der Ende, Mir Abdullah Said, Dirk Jan van Veldhuisen, Niek Verweij, Pim van der Harst
Heart failure (HF) is a complex clinical syndrome resulting from structural or functional impairments of ventricular filling or ejection of blood. HF has a poor prognosis and the burden to society remains tremendous. The unfulfilled expectation is that expanding our knowledge of the genetic architecture of HF will help to quickly advance the quality of risk assessment, diagnoses, and treatment. To date, genome-wide association studies (GWAS) of HF have led to disappointing results with only limited progress in our understanding and tempering the earlier expectations...
July 15, 2018: Cardiovascular Research
https://read.qxmd.com/read/29881931/recent-findings-in-the-genetics-of-blood-pressure-how-to-apply-in-practice-or-is-a-moonshot-required
#19
REVIEW
Sandosh Padmanabhan, Alisha Aman, Anna F Dominiczak
PURPOSE OF REVIEW: Hypertension is recognised as the biggest contributor to the global burden of disease, but it is controlled in less than a fifth of patients worldwide, despite being relatively easy to detect and the availability of inexpensive safe generic drugs. Blood pressure is regulated by a complex network of physiologic pathways with currently available drugs targeting key receptors or enzymes in the top pathways. Major advances in the dissection of both monogenic and polygenic determinants of blood pressure regulation and variation have not resulted in rapid translation of these discoveries into clinical applications or precision medicine...
June 7, 2018: Current Hypertension Reports
https://read.qxmd.com/read/29849051/birth-weight-variants-are-associated-with-variable-fetal-intrauterine-growth-from-20-weeks-of-gestation
#20
L Engelbrechtsen, D Gybel-Brask, Y Mahendran, M Crusell, T H Hansen, T M Schnurr, E Hogdall, L Skibsted, T Hansen, H Vestergaard
Fetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression. A genetic risk score (GRS) of birth weight-raising variants was associated with intrauterine growth showing an attenuating effect on the unconditional daily reduction in proportional weight gain of 8...
May 30, 2018: Scientific Reports
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