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1. Abstract 16397: Correlates of Successfully Achieving Statin Therapy Targets in Pediatric Patients

Author

Michael Mendelson, Todd Regh, Heather Harker, Nicole Palumbo, James Nevin, Phillip K Johnson, Suzanne Griggs, Meera Boghani, Nirav Desai, Elizabeth Yellen, Lucy Buckley, Annette Baker, Mathew Gillman, Justin Zachariah, Dionne Graham, and Sarah D de Ferranti

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Targeting LDL-C goals for statin therapy is currently recommended for children and adolescents in NHLBI pediatric guidelines; however, there is limited information about clinical factors, especially modifiable ones, that impact successful achievement of LDL-C goals. Methods: We analyzed data prospectively collected as part of a quality improvement initiative, SCAMP® (Standardized Clinical Assessment and Management Program), in the Preventive Cardiology Clinic at Boston Children’s Hospital, Boston, MA. We included patients initiated on statin therapy from September 2010 to March 2014. Achieving LDL target was defined as an LDL-C < 130 mg/dL or an LDL-C < 100mg/dL with a high level risk factor (i.e. diabetes, etc.). The impact of baseline CVD risk factors were assessed in Cox proportional hazards models. Results: Among the 1521 pediatric patients and 3813 clinical encounters that occurred over the 3.5 year period, 116 patients were defined as initiating statin therapy. Complete data was available on 79 patients (mean [SD] age 14 [4] years; 47% female; median [IQR] LDL-C 215 [79] mg/dL). The probability of achieving LDL-C goal within 365 and 500 days of starting a statin was 0.55 (95% CI 0.44-0.68) and 0.67 (0.55-0.79), respectively; Figure 1. In univariate analyses, female sex (p=0.01) and lower baseline LDL-C (p=0.04) was associated with more rapid achievement of LDL-C goals, but not age (p=0.8), BMI (p=0.2), exercise (p=0.6), nutritional factors (p=0.3), screen time (p=0.3), cigarette smoking (p=0.9), or family history of early CVD (p=0.3). Conclusions: The majority of children reached LDL-C treatment goals with statin therapy. Baseline modifiable lifestyle CVD risk factors such as diet and exercise were not associated with achieving LDL-C goal on statin therapy in children and adolescents. Increased support and monitoring may be needed, particularly for males, in order to achieve therapy goals.

Published
2014
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2. A genome-wide association study of anorexia nervosa

Author

Boraska, V., Franklin, C. S., Floyd, J. A. B., Thornton, L. M., Huckins, L. M., Southam, L., Rayner, N. W., Tachmazidou, I., Klump, K. L., Treasure, J., Lewis, C. M., Schmidt, U., Tozzi, F., Kiezebrink, K., Hebebrand, J., Gorwood, P., Adan, R. A. H., Kas, M. J. H., Favaro, Angela, Santonastaso, Paolo, Fernández Aranda, F., Gratacos, M., Rybakowski, F., Dmitrzak Weglarz, M., Kaprio, J., Keski Rahkonen, A., Raevuori, A., Van Furth, E. F., Slof Op 't Landt, M. C. T., Hudson, J. I., Reichborn Kjennerud, T., Knudsen, G. P. S., Monteleone, P., Kaplan, A. S., Karwautz, A., Hakonarson, H., Berrettini, W. H., Guo, Y., Li, D., Schork, N. J., Komaki, G., Ando, T., Inoko, H., Esko, T., Fischer, K., Männik, K., Metspalu, A., Baker, J. H., Cone, R. D., Dackor, J., Desocio, J. E., Hilliard, C. E., O'Toole, J. K., Pantel, J., Szatkiewicz, J. P., Taico, C., Zerwas, S., Trace, S. E., Davis, O. S. P., Helder, S., Bühren, K., Burghardt, R., de Zwaan, M., Egberts, K., Ehrlich, S., Herpertz Dahlmann, B., Herzog, W., Imgart, H., Scherag, A., Scherag, S., Zipfel, S., Boni, C., Ramoz, N., Versini, A., Brandys, M. K., Danner, U. N., de Kovel, C., Hendriks, J., Koeleman, B. P. C., Ophoff, R. A., Strengman, E., van Elburg, A. A., Bruson, Alice, Clementi, Maurizio, Degortes, Daniela, Forzan, Monica, Tenconi, Elena, Docampo, E., Escaramís, G., Jiménez Murcia, S., Lissowska, J., Rajewski, A., Szeszenia Dabrowska, N., Slopien, A., Hauser, J., Karhunen, L., Meulenbelt, I., Slagboom, P. E., Tortorella, A., Maj, M., Dedoussis, G., Dikeos, D., Gonidakis, F., Tziouvas, K., Tsitsika, A., Papezova, H., Slachtova, L., Martaskova, D., Kennedy, J. L., Levitan, R. D., Yilmaz, Z., Huemer, J., Koubek, D., Merl, E., Wagner, G., Lichtenstein, P., Breen, G., Cohen Woods, S., Farmer, A., Mcguffin, P., Cichon, S., Giegling, I., Herms, S., Rujescu, D., Schreiber, S., Wichmann, H. E., Dina, C., Sladek, R., Gambaro, G., Soranzo, N., Julia, A., Marsal, S., Rabionet, R., Gaborieau, V., Dick, D. M., Palotie, A., Ripatti, S., Widén, E., Andreassen, O. A., Espeseth, T., Lundervold, A., Reinvang, I., Steen, V. M., Le Hellard, S., Mattingsdal, M., Ntalla, I., Bencko, V., Foretova, L., Janout, V., Navratilova, M., Gallinger, S., Pinto, D., Scherer, S. W., Aschauer, H., Carlberg, L., Schosser, A., Alfredsson, L., Ding, B., Klareskog, L., Padyukov, L., Courtet, P., Guillaume, S., Jaussent, I., Finan, C., Kalsi, G., Roberts, M., Logan, D. W., Peltonen, L., Ritchie, G. R. S., Barrett, J. C., Anderson, Carl A., Barrett, Jeffrey C., Floyd, James A. B., Franklin, Christopher S., Ralph, Mcginnis, Nicole, Soranzo, Eleftheria, Zeggini, Jennifer, Sambrook, Jonathan, Stephens, Ouwehand, Willem H., Mcardle, Wendy L., Ring, Susan M., Strachan, David P., Graeme, Alexander, Bulik, Cynthia M., Collier, David A., Conlon, Peter J., Anna, Dominiczak, Audrey, Duncanson, Adrian, Hill, Cordelia, Langford, Graham, Lord, Maxwell, Alexander P., Linda, Morgan, Leena, Peltonen, Sandford, Richard N., Neil, Sheerin, Vannberg, Fredrik O., Hannah, Blackburn, Wei Min Chen, Sarah, Edkins, Mathew, Gillman, Emma, Gray, Hunt, Sarah E., Suna Onengut Gumuscu, Simon, Potter, Rich, Stephen S., Douglas, Simpkin, Pamela, Whittaker, Estivill, X., Hinney, A., Sullivan, P. F., Collier, D. A., Zeggini, E., Bulik, C. M., Boraska, V., Franklin, Christopher S., Floyd, James A. B., Thornton, L. M., Huckins, L. M., Southam, L., Rayner, N. W., Tachmazidou, I., Klump, K. L., Treasure, J., Lewis, C. M., Schmidt, U., Tozzi, F., Kiezebrink, K., Hebebrand, J., Gorwood, P., Adan, R. A. H., Kas, M. J. H., Favaro, A., Santonastaso, P., Fernández-Aranda, F., Gratacos, M., Rybakowski, F., Dmitrzak-Weglarz, M., Kaprio, J., Keski-Rahkonen, A., Raevuori, A., Van Furth, E. F., Slof-Op 't Landt, M. C. T., Hudson, J. I., Reichborn-Kjennerud, T., Knudsen, G. P. S., Monteleone, P., Kaplan, A. S., Karwautz, A., Hakonarson, H., Berrettini, W. H., Guo, Y., Li, D., Schork, N. J., Komaki, G., Ando, T., Inoko, H., Esko, T., Fischer, K., Männik, K., Metspalu, A., Baker, J. H., Cone, R. D., Dackor, J., Desocio, J. E., Hilliard, C. E., O'Toole, J. K., Pantel, J., Szatkiewicz, J. P., Taico, C., Zerwas, S., Trace, S. E., Davis, O. S. P., Helder, S., Bühren, K., Burghardt, R., De Zwaan, M., Egberts, K., Ehrlich, S., Herpertz-Dahlmann, B., Herzog, W., Imgart, H., Scherag, A., Scherag, S., Zipfel, S., Boni, C., Ramoz, N., Versini, A., Brandys, M. K., Danner, U. N., De Kovel, C., Hendriks, J., Koeleman, B. P. C., Ophoff, R. A., Strengman, E., Van Elburg, A. A., Bruson, A., Clementi, M., Degortes, D., Forzan, M., Tenconi, E., Docampo, E., Escaramís, G., Jiménez-Murcia, S., Lissowska, J., Rajewski, A., Szeszenia-Dabrowska, N., Slopien, A., Hauser, J., Karhunen, L., Meulenbelt, I., Slagboom, P. E., Tortorella, A., Maj, M., Dedoussis, G., Dikeos, D., Gonidakis, F., Tziouvas, K., Tsitsika, A., Papezova, H., Slachtova, L., Martaskova, D., Kennedy, J. L., Levitan, R. D., Yilmaz, Z., Huemer, J., Koubek, D., Merl, E., Wagner, G., Lichtenstein, P., Breen, G., Cohen-Woods, S., Farmer, A., Mcguffin, P., Cichon, S., Giegling, I., Herms, S., Rujescu, D., Schreiber, S., Wichmann, H. -E., Dina, C., Sladek, R., Gambaro, G., Soranzo, Nicole, Julia, A., Marsal, S., Rabionet, R., Gaborieau, V., Dick, D. M., Palotie, A., Ripatti, S., Widén, E., Andreassen, O. A., Espeseth, T., Lundervold, A., Reinvang, I., Steen, V. M., Le Hellard, S., Mattingsdal, M., Ntalla, I., Bencko, V., Foretova, L., Janout, V., Navratilova, M., Gallinger, S., Pinto, D., Scherer, S. W., Aschauer, H., Carlberg, L., Schosser, A., Alfredsson, L., Ding, B., Klareskog, L., Padyukov, L., Courtet, P., Guillaume, S., Jaussent, I., Finan, C., Kalsi, G., Roberts, M., Logan, D. W., Peltonen, Leena, Ritchie, G. R. S., Barrett, Jeffrey C., Anderson, Carl A., Mcginnis, Ralph, Zeggini, Eleftheria, Sambrook, Jennifer, Stephens, Jonathan, Ouwehand, Willem H., Mcardle, Wendy L., Ring, Susan M., Strachan, David P., Alexander, Graeme, Bulik, C. M., Collier, David A., Conlon, Peter J., Dominiczak, Anna, Duncanson, Audrey, Hill, Adrian, Langford, Cordelia, Lord, Graham, Maxwell, Alexander P., Morgan, Linda, Sandford, Richard N., Sheerin, Neil, Vannberg, Fredrik O., Blackburn, Hannah, Chen, Wei-Min, Edkins, Sarah, Gillman, Mathew, Gray, Emma, Hunt, Sarah E., Onengut-Gumuscu, Suna, Potter, Simon, Rich, Stephen S., Simpkin, Dougla, Whittaker, Pamela, Estivill, X., Hinney, A., Sullivan, P. F., Martaskova D., Wellcome Trust Case Control Consortium 3, Anderson, CA., Barrett, JC., Floyd, JA., Franklin, CS., McGinnis, R., Soranzo, N., Zeggini, E., Sambrook, J., Stephens, J., Ouwehand, WH., McArdle, WL., Ring, SM., Strachan, DP., Alexander, G., Bulik, CM., Collier, DA., Conlon, PJ., Dominiczak, A., Duncanson, A., Hill, A., Langford, C., Lord, G., Maxwell, AP., Morgan, L., Peltonen, L., Sandford, RN., Sheerin, N., Vannberg, FO., Blackburn, H., Chen, WM., Edkins, S., Gillman, M., Gray, E., Hunt, SE., Onengut-Gumuscu, S., Potter, S., Rich, SS., Simpkin, D., and Whittaker, P.

Subjects
Male, Candidate gene, Anorexia Nervosa, Medizin, Genome-wide association study, anorexia nervosa, body mass index, eating disorders, genome-wide association study, GWAS, metabolic, Japan, Settore MED/14 - NEFROLOGIA, Guanine Nucleotide Exchange Factors, genome wide association study, Nuclear Protein, Genetics, Calcineurin, Eating disorder, Anorèxia nerviosa, Nuclear Proteins, Genomics, Cullin Proteins, 3. Good health, Anorexia, VDP::Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical genetics: 714, Anorexia nervosa (differential diagnoses), Psychiatry and Mental Health, Female, Case-Control Studie, Human, Asian Continental Ancestry Group, European Continental Ancestry Group, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, Cellular and Molecular Neuroscience, Asian People, Meta-Analysis as Topic, Genetic linkage, Humans, Genotyping, Molecular Biology, anorexia nervosa, body mass index, eating disorders, genome wide association study, GWAS, metabolic, Cullin Protein, Case-control study, Anorexia nervosa, VDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, Guanine Nucleotide Exchange Factor, Genòmica, Case-Control Studies, Carrier Protein, Carrier Proteins, Body mass index, Genome-Wide Association Study
Abstract

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 x 10(-7)) in SOX2OT and rs17030795 (P = 5.84 x 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 x 10(-6)) between CUL3 and FAM124B and rs1886797 (P = 8.05 x 10(-6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4x10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Published
2014

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