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Cardiovascular genetic risk testing

Juan Zhao, QiPing Feng, Patrick Wu, Jeremy L Warner, Joshua C Denny, Wei-Qi Wei
Genome-wide and phenome-wide association studies are commonly used to identify important relationships between genetic variants and phenotypes. Most studies have treated diseases as independent variables and suffered from the burden of multiple adjustment due to the large number of genetic variants and disease phenotypes. In this study, we used topic modeling via non-negative matrix factorization (NMF) for identifying associations between disease phenotypes and genetic variants. Topic modeling is an unsupervised machine learning approach that can be used to learn patterns from electronic health record data...
2019: PloS One
Seohyuk Lee, Leo E Akioyamen, Sumayah Aljenedil, Jean-Baptiste Rivière, Isabelle Ruel, Jacques Genest
AIMS: Familial hypercholesterolemia (FH) is the most common genetic disorder in medicine, with a prevalence of 1/250. Affected individuals have elevated low-density lipoprotein cholesterol (LDL-C) and an increased lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The diagnosis of FH is based on algorithms that include LDL-C levels, physical manifestations, family history of high LDL-C and premature ASCVD, and, more recently, genetic testing. We sought to determine the impact of genetic testing on the: 1) diagnosis of 'definite familial hypercholesterolemia', 2) initiation and adherence of lipid-lowering therapy and 3) risk of ASCVD...
February 12, 2019: European Journal of Preventive Cardiology
Troy J Smith, Jessica L Johnson, Abiy Habtewold, Melissa A Burmeister
This update presents evidence for new antiplatelet therapies including modified P2Y12 inhibitors and a new class of thromboxane antagonists. Discussed are emerging data on established antihyperlipidemic medications that support an additional antiplatelet effect. Current information about the effectiveness of several bleeding reversal agents is discussed, and the concept of personalized antiplatelet therapy, wherein selection of an antiplatelet therapy is based on genetic factors or laboratory testing that predict response to therapy and risk of adverse effects...
March 2019: Critical Care Nursing Clinics of North America
Rachele M Hendricks-Sturrup, Christine Y Lu
Cardiovascular disease (CVD) is the leading cause of death in the United States (US), with familial hypercholesterolemia (FH) being a major inherited and genetic risk factor for premature CVD and atherosclerosis. Genetic testing has helped patients and providers confirm the presence of known pathogenic and likely pathogenic variations in FH-associated genes. Key organizations, such as the Centers for Disease Control and Prevention (CDC), American Heart Association (AHA), FH Foundation, and National Lipid Association (NLA), have recognized the clinical utility of FH genetic testing...
February 1, 2019: Journal of Personalized Medicine
Giuliano Generoso, Carolina C P S Janovsky, Marcio S Bittencourt
PURPOSE OF REVIEW: In this review, we intend to show the heterogenicity of the triglyceride group, including the triglyceride-rich lipoproteins and its subparticles, apolipoproteins, and its role in atherogenesis through epidemiological and genetic studies, observing the association of these various components and subclasses with subclinical atherosclerosis and cardiovascular events. Also, we reevaluated the moment of blood collection for the triglyceride measurement and its repercussion in atherosclerosis...
January 28, 2019: Current Opinion in Endocrinology, Diabetes, and Obesity
Hannah E Ison, Stephanie M Ware, Tae-Hwi Schwantes-An, Samantha Freeze, Lindsey Elmore, Katherine G Spoonamore
Cardiovascular genetic counseling (CVGC) is recommended for a variety of inherited heart conditions; however, its impact on patient empowerment has not been assessed. The Genetic Counseling Outcome Scale (GCOS) is a validated patient reported outcome tool which measures empowerment to capture the impact of clinical genetics services. As a routine clinical practice at our center, adult patients attending a CVGC appointment complete the 24-item GCOS survey and a 5-item survey on knowledge of cardiac surveillance recommendations for relatives prior to the clinic visit...
January 24, 2019: Journal of Genetic Counseling
Maria Messing, Letícia Chaves de Souza, Franco Cavalla, Krishna Kumar Kookal, Gabriella Rizzo, Muhammad Walji, Renato Silva, Ariadne Letra
INTRODUCTION: Apical periodontitis (AP) and cardiovascular diseases (CVDs) are chronic conditions triggered by an inflammatory process and sharing similar pathogeneses and molecular players. Previous studies have suggested that AP may perpetuate a systemic inflammation state and, in turn, contribute to CVD. In this study, we investigated the potential association between endodontic pathology and CVD using epidemiological and genetic approaches. METHODS: Epidemiologic analysis was performed by querying the medical and dental records of >2 million patients...
January 17, 2019: Journal of Endodontics
D Piancatelli, D Maccarone, P Sebastiani, A Colanardi, S Iesari, K Clemente, Q Lai, F Pisani
The fat mass and obesity-associated (FTO) gene is one of the most important obesity susceptibility genes. Some FTO gene polymorphisms have been associated with obesity, diabetes, and hypertension, all conditions for which, after transplant, there is increased susceptibility, due to effects of immunosuppressive regimens. To evaluate whether FTO could be a candidate for targeted preventive intervention in the transplant setting, we investigated whether the common genetic variation, FTO rs9939609T>A, could affect weight gain and risk of cardiovascular complications in kidney transplantation...
June 30, 2018: Transplantation Proceedings
Andrew J Sandford, Amanda Ha, David A Ngan, Loubna Akhabir, Aabida Saferali, Nurit Fox, A J Hirsch Allen, Simon C Warby, Stephan F van Eeden, Najib T Ayas
STUDY OBJECTIVES: Untreated obstructive sleep apnea (OSA) patients have an increased risk of cardiovascular disease (CVD). Adhesion molecules, including soluble E-selectin (sE-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1), are associated with incident CVD. We hypothesized that specific genetic variants will be associated with plasma levels of adhesion molecules in suspected OSA patients. We also hypothesized that there may be an interaction between these variants and OSA...
2019: PloS One
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
R Preston Mason
PURPOSE OF REVIEW: Treatment of hypercholesterolemia with statins results in significant reductions in cardiovascular risk; however, individuals with well-controlled low-density lipoprotein cholesterol (LDL-C) levels, but persistent high triglycerides (TG), remain at increased risk. Genetic and epidemiologic studies have shown that elevated fasting TG levels are associated with incident cardiovascular events. At effective doses, omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower TG levels but may have additional atheroprotective properties compared to other TG-lowering therapies such as niacin and fibrates...
January 12, 2019: Current Atherosclerosis Reports
A Mesut Erzurumluoglu, Mengzhen Liu, Victoria E Jackson, Daniel R Barnes, Gargi Datta, Carl A Melbourne, Robin Young, Chiara Batini, Praveen Surendran, Tao Jiang, Sheikh Daud Adnan, Saima Afaq, Arpana Agrawal, Elisabeth Altmaier, Antonis C Antoniou, Folkert W Asselbergs, Clemens Baumbach, Laura Bierut, Sarah Bertelsen, Michael Boehnke, Michiel L Bots, David M Brazel, John C Chambers, Jenny Chang-Claude, Chu Chen, Janie Corley, Yi-Ling Chou, Sean P David, Rudolf A de Boer, Christiaan A de Leeuw, Joe G Dennis, Anna F Dominiczak, Alison M Dunning, Douglas F Easton, Charles Eaton, Paul Elliott, Evangelos Evangelou, Jessica D Faul, Tatiana Foroud, Alison Goate, Jian Gong, Hans J Grabe, Jeff Haessler, Christopher Haiman, Göran Hallmans, Anke R Hammerschlag, Sarah E Harris, Andrew Hattersley, Andrew Heath, Chris Hsu, William G Iacono, Stavroula Kanoni, Manav Kapoor, Jaakko Kaprio, Sharon L Kardia, Fredrik Karpe, Jukka Kontto, Jaspal S Kooner, Charles Kooperberg, Kari Kuulasmaa, Markku Laakso, Dongbing Lai, Claudia Langenberg, Nhung Le, Guillaume Lettre, Anu Loukola, Jian'an Luan, Pamela A F Madden, Massimo Mangino, Riccardo E Marioni, Eirini Marouli, Jonathan Marten, Nicholas G Martin, Matt McGue, Kyriaki Michailidou, Evelin Mihailov, Alireza Moayyeri, Marie Moitry, Martina Müller-Nurasyid, Aliya Naheed, Matthias Nauck, Matthew J Neville, Sune Fallgaard Nielsen, Kari North, Markus Perola, Paul D P Pharoah, Giorgio Pistis, Tinca J Polderman, Danielle Posthuma, Neil Poulter, Beenish Qaiser, Asif Rasheed, Alex Reiner, Frida Renström, John Rice, Rebecca Rohde, Olov Rolandsson, Nilesh J Samani, Maria Samuel, David Schlessinger, Steven H Scholte, Robert A Scott, Peter Sever, Yaming Shao, Nick Shrine, Jennifer A Smith, John M Starr, Kathleen Stirrups, Danielle Stram, Heather M Stringham, Ioanna Tachmazidou, Jean-Claude Tardif, Deborah J Thompson, Hilary A Tindle, Vinicius Tragante, Stella Trompet, Valerie Turcot, Jessica Tyrrell, Ilonca Vaartjes, Andries R van der Leij, Peter van der Meer, Tibor V Varga, Niek Verweij, Henry Völzke, Nicholas J Wareham, Helen R Warren, David R Weir, Stefan Weiss, Leah Wetherill, Hanieh Yaghootkar, Ersin Yavas, Yu Jiang, Fang Chen, Xiaowei Zhan, Weihua Zhang, Wei Zhao, Wei Zhao, Kaixin Zhou, Philippe Amouyel, Stefan Blankenberg, Mark J Caulfield, Rajiv Chowdhury, Francesco Cucca, Ian J Deary, Panos Deloukas, Emanuele Di Angelantonio, Marco Ferrario, Jean Ferrières, Paul W Franks, Tim M Frayling, Philippe Frossard, Ian P Hall, Caroline Hayward, Jan-Håkan Jansson, J Wouter Jukema, Frank Kee, Satu Männistö, Andres Metspalu, Patricia B Munroe, Børge Grønne Nordestgaard, Colin N A Palmer, Veikko Salomaa, Naveed Sattar, Timothy Spector, David Peter Strachan, Pim van der Harst, Eleftheria Zeggini, Danish Saleheen, Adam S Butterworth, Louise V Wain, Goncalo R Abecasis, John Danesh, Martin D Tobin, Scott Vrieze, Dajiang J Liu, Joanna M M Howson
Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits...
January 7, 2019: Molecular Psychiatry
Hong-Mi Choi, Myung-Soo Park, Jong-Chan Youn
Heart failure (HF) is an important cardiovascular disease because of its increasing prevalence, significant morbidity, high mortality, and rapidly expanding health care cost. The number of HF patients is increasing worldwide, and Korea is no exception. There have been marked advances in definition, diagnostic modalities, and treatment of HF over the past four decades. There is continuing effort to improve risk stratification of HF using biomarkers, imaging and genetic testing. Newly developed medications and devices for HF have been widely adopted in clinical practice...
January 2019: Korean Journal of Internal Medicine
Anne Langsted, Pia R Kamstrup, Børge G Nordestgaard
Aims: Several lipoprotein(a)-lowering therapies are currently being developed with the long-term goal of reducing cardiovascular disease and mortality; however, the relationship between lipoprotein(a) and mortality is unclear. We tested the hypothesis that lipoprotein(a) levels are associated with risk of mortality. Methods and results: We studied individuals from two prospective studies of the Danish general population, of which 69 764 had information on lipoprotein(a) concentrations, 98 810 on LPA kringle-IV type 2 (KIV-2) number of repeats, and 119 094 on LPA rs10455872 genotype...
January 4, 2019: European Heart Journal
Aldi T Kraja, Chunyu Liu, Jessica L Fetterman, Mariaelisa Graff, Christian Theil Have, Charles Gu, Lisa R Yanek, Mary F Feitosa, Dan E Arking, Daniel I Chasman, Kristin Young, Symen Ligthart, W David Hill, Stefan Weiss, Jian'an Luan, Franco Giulianini, Ruifang Li-Gao, Fernando P Hartwig, Shiow J Lin, Lihua Wang, Tom G Richardson, Jie Yao, Eliana P Fernandez, Mohsen Ghanbari, Mary K Wojczynski, Wen-Jane Lee, Maria Argos, Sebastian M Armasu, Ruteja A Barve, Kathleen A Ryan, Ping An, Thomas J Baranski, Suzette J Bielinski, Donald W Bowden, Ulrich Broeckel, Kaare Christensen, Audrey Y Chu, Janie Corley, Simon R Cox, Andre G Uitterlinden, Fernando Rivadeneira, Cheryl D Cropp, E Warwick Daw, Diana van Heemst, Lisa de Las Fuentes, He Gao, Ioanna Tzoulaki, Tarunveer S Ahluwalia, Renée de Mutsert, Leslie S Emery, A Mesut Erzurumluoglu, James A Perry, Mao Fu, Nita G Forouhi, Zhenglong Gu, Yang Hai, Sarah E Harris, Gibran Hemani, Steven C Hunt, Marguerite R Irvin, Anna E Jonsson, Anne E Justice, Nicola D Kerrison, Nicholas B Larson, Keng-Hung Lin, Latisha D Love-Gregory, Rasika A Mathias, Joseph H Lee, Matthias Nauck, Raymond Noordam, Ken K Ong, James Pankow, Amit Patki, Alison Pattie, Astrid Petersmann, Qibin Qi, Rasmus Ribel-Madsen, Rebecca Rohde, Kevin Sandow, Theresia M Schnurr, Tamar Sofer, John M Starr, Adele M Taylor, Alexander Teumer, Nicholas J Timpson, Hugoline G de Haan, Yujie Wang, Peter E Weeke, Christine Williams, Hongsheng Wu, Wei Yang, Donglin Zeng, Daniel R Witte, Bruce S Weir, Nicholas J Wareham, Henrik Vestergaard, Stephen T Turner, Christian Torp-Pedersen, Evie Stergiakouli, Wayne Huey-Herng Sheu, Frits R Rosendaal, M Arfan Ikram, Oscar H Franco, Paul M Ridker, Thomas T Perls, Oluf Pedersen, Ellen A Nohr, Anne B Newman, Allan Linneberg, Claudia Langenberg, Tuomas O Kilpeläinen, Sharon L R Kardia, Marit E Jørgensen, Torben Jørgensen, Thorkild I A Sørensen, Georg Homuth, Torben Hansen, Mark O Goodarzi, Ian J Deary, Cramer Christensen, Yii-Der Ida Chen, Aravinda Chakravarti, Ivan Brandslund, Klaus Bonnelykke, Kent D Taylor, James G Wilson, Santiago Rodriguez, Gail Davies, Bernardo L Horta, Bharat Thyagarajan, D C Rao, Niels Grarup, Victor G Davila-Roman, Gavin Hudson, Xiuqing Guo, Donna K Arnett, Caroline Hayward, Dhananjay Vaidya, Dennis O Mook-Kanamori, Hemant K Tiwari, Daniel Levy, Ruth J F Loos, Abbas Dehghan, Paul Elliott, Afshan N Malik, Robert A Scott, Diane M Becker, Mariza de Andrade, Michael A Province, James B Meigs, Jerome I Rotter, Kari E North
Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing...
December 21, 2018: American Journal of Human Genetics
Borzu Rouhani, Sayyed Mohammad Hossein Ghaderian, Zivar Salehi
BACKGROUND: Conventional coronary artery disease (CAD) is the leading cause of morbidity and mortality in the general population. In recent years, multiple CAD promising risk factors have been reported and used for risk stratification. Lipoprotein(a) [LPA] concentration in plasma was shown associated with CAD risk and LPA genetic variants in different ethnic groups remains less clear. METHODS: We obtained data from 100 affected patients with established CAD and 100 healthy controls...
December 21, 2018: Human Antibodies
Akihiro Nomura, Hayato Tada, Hirofumi Okada, Atsushi Nohara, Hideki Ishikawa, Kenichi Yoshimura, Masa-Aki Kawashiri
INTRODUCTION: Familial hypercholesterolemia (FH) is an autosomal-dominant inherited genetic disease. High-throughput sequencing quickly and comprehensively detects causative variants of FH-related genes ( LDLR , PCSK9 , APOB and LDLRAP1 ). Although the presence of causative variants in FH-related genes correlates with future cardiovascular events, it remains unclear whether detection of causative gene mutation and disclosure of its associated cardiovascular risk affects outcomes in patients with FH...
December 28, 2018: BMJ Open
Han Qi, Bin Liu, Chunyue Guo, Zheng Liu, Han Cao, Kuo Liu, Weiping Sun, Ling Zhang
PURPOSE: The systemic epidemiology of salt sensitivity (EpiSS) study aims to combine molecular biology, epidemiology and bioinformatics methods to discover the potential causes of salt sensitivity of blood pressure (SSBP) using single-nucleotide polymorphisms in the genome and non-coding RNAs in the transcriptome to uncover both the genetic and environmental factors of SSBP. PARTICIPANTS: Between July 2014 and July 2016, we enrolled adults from 11 study centres in Beijing and Liaoning Province; participants were of the Han population and were 35-70 years of age...
December 28, 2018: BMJ Open
Melody Lok-Yi Chan, Ching-Lung Cheung, Alan Chun-Hong Lee, Chun-Yip Yeung, Chung-Wah Siu, Jenny Yin-Yan Leung, Ho-Kwong Pang, Kathryn Choon-Beng Tan
BACKGROUND: Familial hypercholesterolemia (FH) is a monogenic disorder of lipoprotein metabolism leading to an increased risk of premature cardiovascular disease. Genetic testing for FH is not commonly used in Asian countries. We aimed to define the genetic spectrum of FH in Hong Kong and to test the feasibility of cascade genetic screening. METHODS: Ninety-six Chinese subjects with a clinical diagnosis of FH were recruited, and family-based cascade screening incorporating genetic testing results was performed...
December 27, 2018: Molecular Genetics & Genomic Medicine
Marios K Georgakis, Dipender Gill, Kristiina Rannikmae, Matthew Traylor, Christopher D Anderson, Jin-Moo Lee, Yoichiro Kamatani, Jemma C Hopewell, Bradford B Worrall, Jürgen Bernhagen, Cathie Lm Sudlow, Rainer Malik, Martin Dichgans
BACKGROUND: Cytokines and growth factors have been implicated in the initiation and propagation of vascular disease. Observational studies have shown associations of their circulating levels with stroke. Our objective was to explore whether genetically determined circulating levels of cytokines and growth factors are associated with stroke and its etiologic subtypes by conducting a two-sample Mendelian randomization (MR) study. METHODS: Genetic instruments for 41 cytokines and growth factors were obtained from a genome-wide association study (GWAS) of 8,293 healthy adults...
September 26, 2018: Circulation
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