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1. Genetic variants for head size share genes and pathways with cancer

Author

Knol, Maria J, Poot, Raymond A, Evans, Tavia E, Satizabal, Claudia L, Mishra, Aniket, Sargurupremraj, Muralidharan, van der Auwera, Sandra, Duperron, Marie-Gabrielle, Jian, Xueqiu, Hostettler, Isabel C, van Dam-Nolen, Dianne HK, Lamballais, Sander, Pawlak, Mikolaj A, Lewis, Cora E, Carrion-Castillo, Amaia, van Erp, Theo GM, Reinbold, Céline S, Shin, Jean, Scholz, Markus, Håberg, Asta K, Kämpe, Anders, Li, Gloria HY, Avinun, Reut, Atkins, Joshua R, Hsu, Fang-Chi, Amod, Alyssa R, Lam, Max, Tsuchida, Ami, Teunissen, Mariël WA, Aygün, Nil, Patel, Yash, Liang, Dan, Beiser, Alexa S, Beyer, Frauke, Bis, Joshua C, Bos, Daniel, Bryan, R Nick, Bülow, Robin, Caspers, Svenja, Catheline, Gwenaëlle, Cecil, Charlotte AM, Dalvie, Shareefa, Dartigues, Jean-François, DeCarli, Charles, Enlund-Cerullo, Maria, Ford, Judith M, Franke, Barbara, Freedman, Barry I, Friedrich, Nele, Green, Melissa J, Haworth, Simon, Helmer, Catherine, Hoffmann, Per, Homuth, Georg, Ikram, M Kamran, Jack, Clifford R, Jahanshad, Neda, Jockwitz, Christiane, Kamatani, Yoichiro, Knodt, Annchen R, Li, Shuo, Lim, Keane, Longstreth, WT, Macciardi, Fabio, Consortium, The Cohorts for Heart and Aging Research in Genomic Epidemiology, Amouyel, Philippe, Arfanakis, Konstantinos, Aribisala, Benjamin S, Bastin, Mark E, Chauhan, Ganesh, Chen, Christopher, Cheng, Ching-Yu, de Jager, Philip L, Deary, Ian J, Fleischman, Debra A, Gottesman, Rebecca F, Gudnason, Vilmundur, Hilal, Saima, Hofer, Edith, Janowitz, Deborah, Jukema, J Wouter, Liewald, David CM, Lopez, Lorna M, Lopez, Oscar, Luciano, Michelle, Martinez, Oliver, Niessen, Wiro J, Nyquist, Paul, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Schmidt, Helena, Tiemeier, Henning, Trompet, Stella, van der Grond, Jeroen, Völzke, Henry, Wardlaw, Joanna M, Yanek, Lisa, Yang, Jingyun, and Consortium, The Enhancing NeuroImaging Genetics through Meta-Analysis

Subjects
Biomedical and Clinical Sciences, Biotechnology, Neurosciences, Stem Cell Research, Genetics, Cancer, Human Genome, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Humans, Genome-Wide Association Study, Head, Neoplasms, Female, Male, Polymorphism, Single Nucleotide, Genetic Variation, Organ Size, Signal Transduction, Adult, Genetic Predisposition to Disease, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium, cancer, genetics, genome-wide association study, head circumference, head size, intracranial volume, meta-analysis, Biomedical and clinical sciences
Abstract

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

Published
2024

3. Subclinical left ventricular systolic dysfunction and incident stroke in the elderly: long-term findings from Cardiovascular Abnormalities and Brain Lesions

Author

Yoshida, Yuriko, Jin, Zhezhen, Russo, Cesare, Homma, Shunichi, Nakanishi, Koki, Ito, Kazato, Mannina, Carlo, Elkind, Mitchell SV, Rundek, Tatjana, Yoshita, Mitsuhiro, DeCarli, Charles, Wright, Clinton B, Sacco, Ralph L, and Di Tullio, Marco R

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Stroke, Brain Disorders, Cardiovascular, Aging, Prevention, Neurosciences, Biomedical Imaging, Heart Disease, Acquired Cognitive Impairment, Clinical Research, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Brain, Brain Ischemia, Cardiovascular Abnormalities, Ischemic Stroke, Stroke Volume, Ventricular Dysfunction, Left, Ventricular Function, Left, stroke • left ventricular function • global longitudinal strain • speckle-tracking echocardiography, Cardiovascular medicine and haematology
Abstract

AimsHeart disease is associated with an increased risk for ischaemic stroke. However, the predictive value of reduced left ventricular ejection fraction (LVEF) for stroke is controversial and only observed in patients with severe reduction. LV global longitudinal strain (LV GLS) can detect subclinical LV systolic impairment when LVEF is normal. We investigated the prognostic role of LV GLS for incident stroke in a predominantly elderly cohort.Methods and resultsTwo-dimensional echocardiography with speckle tracking was performed in the Cardiac Abnormalities and Brain Lesions (CABL) study. Among 708 stroke-free participants (mean age 71.4 ± 9.4 years, 60.9% women), abnormal LV GLS (>-14.7%: 95% percentile of the subgroup without risk factors) was detected in 133 (18.8%). During a mean follow-up of 10.8 ± 3.9 years, 47 participants (6.6%) experienced an ischaemic stroke (26 cardioembolic or cryptogenic, 21 other subtypes). The cumulative incidence of ischaemic stroke was significantly higher in participants with abnormal LV GLS than with normal LV GLS (P < 0.001). In multivariate stepwise logistic regression analysis, abnormal LV GLS was associated with ischaemic stroke independently of cardiovascular risk factors including LVEF, LV mass, left atrial volume, subclinical cerebrovascular disease at baseline, and incident atrial fibrillation [hazard ratio (HR): 2.69, 95% confidence interval (CI): 1.47-4.92; P = 0.001]. Abnormal LV GLS independently predicted cardioembolic or cryptogenic stroke (adjusted HR: 3.57, 95% CI: 1.51-8.43; P = 0.004) but not other subtypes.ConclusionLV GLS was a strong independent predictor of ischaemic stroke in a predominantly elderly stroke-free cohort. Our findings provide insights into the brain-heart interaction and may help improve stroke primary prevention strategies.

Published
2023

4. Association of Obesity With Cognitive Decline in Black and White Americans

Author

Quaye, Emmanuel, Galecki, Andrzej T, Tilton, Nicholas, Whitney, Rachael, Briceño, Emily M, Elkind, Mitchell SV, Fitzpatrick, Annette L, Gottesman, Rebecca F, Griswold, Michael, Gross, Alden L, Heckbert, Susan R, Hughes, Timothy M, Longstreth, WT, Sacco, Ralph L, Sidney, Stephen, Windham, B Gwen, Yaffe, Kristine, and Levine, Deborah A

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Neurosciences, Obesity, Brain Disorders, Neurodegenerative, Acquired Cognitive Impairment, Clinical Research, Nutrition, Aging, Dementia, Stroke, Female, Humans, Male, Middle Aged, Cognition, Cognitive Dysfunction, Risk Factors, White, Black or African American, Aged, United States, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

Background and objectivesThere are disparities in the prevalence of obesity by race, and the relationship between obesity and cognitive decline is unclear. The objective of this study was to determine whether obesity is independently associated with cognitive decline and whether the association between obesity and cognitive decline differs in Black and White adults. We hypothesized that obesity is associated with greater cognitive decline compared with normal weight and that the effect of obesity on cognitive decline is more pronounced in Black adults compared with their White counterparts.MethodsWe pooled data from 28,867 participants free of stroke and dementia (mean, SD: age 61 [10.7] years at the first cognitive assessment, 55% female, 24% Black, and 29% obese) from 6 cohorts. The primary outcome was the annual change in global cognition. We performed linear mixed-effects models with and without time-varying cumulative mean systolic blood pressure (SBP) and fasting plasma glucose (FPG). Global cognition was set to a t-score metric (mean 50, SD 10) at a participant's first cognitive assessment; a 1-point difference represents a 0.1 SD difference in global cognition across the 6 cohorts. The median follow-up was 6.5 years (25th percentile, 75th percentile: 5.03, 20.15).ResultsObese participants had lower baseline global cognition than normal-weight participants (difference in intercepts, -0.36 [95% CI, -0.46 to -0.17]; p < 0.001). This difference in baseline global cognition was attenuated but was borderline significant after accounting for SBP and FPG (adjusted differences in intercepts, -0.19 [95% CI, -0.39 to 0.002]; p = 0.05). There was no difference in the rate of decline in global cognition between obese and normal-weight participants (difference in slope, 0.009 points/year [95% CI, -0.009 to 0.03]; p = 0.32). After accounting for SBP and FPG, obese participants had a slower decline in global cognition (adjusted difference in slope, 0.03 points/year slower [95% CI, 0.01 to 0.05]; p < 0.001). There was no evidence that race modified the association between body mass index and global cognitive decline (p = 0.34).DiscussionThese results suggest that obesity is associated with lower initial cognitive scores and may potentially attenuate declines in cognition after accounting for BP and FPG.

Published
2023

5. Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design

Author

Oelsner, Elizabeth C, Krishnaswamy, Akshaya, Balte, Pallavi P, Allen, Norrina Bai, Ali, Tauqeer, Anugu, Pramod, Andrews, Howard F, Arora, Komal, Asaro, Alyssa, Barr, R Graham, Bertoni, Alain G, Bon, Jessica, Boyle, Rebekah, Chang, Arunee A, Chen, Grace, Coady, Sean, Cole, Shelley A, Coresh, Josef, Cornell, Elaine, Correa, Adolfo, Couper, David, Cushman, Mary, Demmer, Ryan T, Elkind, Mitchell SV, Folsom, Aaron R, Fretts, Amanda M, Gabriel, Kelley P, Gallo, Linda C, Gutierrez, Jose, Han, Mei Lan K, Henderson, Joel M, Howard, Virginia J, Isasi, Carmen R, Jacobs, David R, Judd, Suzanne E, Mukaz, Debora Kamin, Kanaya, Alka M, Kandula, Namratha R, Kaplan, Robert C, Kinney, Gregory L, Kucharska-Newton, Anna, Lee, Joyce S, Lewis, Cora E, Levine, Deborah A, Levitan, Emily B, Levy, Bruce D, Make, Barry J, Malloy, Kimberly, Manly, Jennifer J, Mendoza-Puccini, Carolina, Meyer, Katie A, Min, Yuan-I Nancy, Moll, Matthew R, Moore, Wendy C, Mauger, David, Ortega, Victor E, Palta, Priya, Parker, Monica M, Phipatanakul, Wanda, Post, Wendy S, Postow, Lisa, Psaty, Bruce M, Regan, Elizabeth A, Ring, Kimberly, Roger, Véronique L, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Schembri, Michael, Schwartz, David A, Seshadri, Sudha, Shikany, James M, Sims, Mario, Stukovsky, Karen D Hinckley, Talavera, Gregory A, Tracy, Russell P, Umans, Jason G, Vasan, Ramachandran S, Watson, Karol E, Wenzel, Sally E, Winters, Karen, Woodruff, Prescott G, Xanthakis, Vanessa, Zhang, Ying, Zhang, Yiyi, and Investigators, for the C4R

Subjects
Public Health, Health Sciences, Social Determinants of Health, Basic Behavioral and Social Science, Coronaviruses Disparities and At-Risk Populations, Prevention, Coronaviruses, Infectious Diseases, Clinical Research, Emerging Infectious Diseases, Behavioral and Social Science, Aetiology, 2.4 Surveillance and distribution, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, COVID-19, Cohort Studies, Humans, Middle Aged, Pandemics, Prospective Studies, SARS-CoV-2, United States, Young Adult, cohort studies, coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, %22">>, C4R Investigators, severe acute respiratory syndrome coronavirus 2, Mathematical Sciences, Medical and Health Sciences, Epidemiology
Abstract

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.

Published
2022

6. Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE‐SPECT ESUS Trial

Author

Del Brutto, Victor J, Diener, Han‐Christoph, Easton, J Donald, Granger, Christopher B, Cronin, Lisa, Kleine, Eva, Grauer, Claudia, Brueckmann, Martina, Toyoda, Kazunori, Schellinger, Peter D, Lyrer, Philippe, Molina, Carlos A, Chutinet, Aurauma, Bladin, Christopher F, Estol, Conrado J, and Sacco, Ralph L

Subjects
Neurosciences, Stroke, Brain Disorders, Clinical Trials and Supportive Activities, Clinical Research, Prevention, Aspirin, Cerebral Infarction, Dabigatran, Embolic Stroke, Humans, Intracranial Embolism, Male, Risk Factors, Tomography, Emission-Computed, Single-Photon, embolic stroke of undetermined source, risk factors, secondary prevention, stroke predictors, Cardiorespiratory Medicine and Haematology
Abstract

Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE-SPECT ESUS (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow-up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83-2.82]), creatinine clearance

Published
2022

7. Blood Pressure and Later-Life Cognition in Hispanic and White Adults (BP-COG): A Pooled Cohort Analysis of ARIC, CARDIA, CHS, FOS, MESA, and NOMAS.

Author

Levine, Deborah A, Gross, Alden L, Briceño, Emily M, Tilton, Nicholas, Whitney, Rachael, Han, Dehua, Giordani, Bruno J, Sussman, Jeremy B, Hayward, Rodney A, Burke, James F, Elkind, Mitchell SV, Moran, Andrew E, Tom, Sarah, Gottesman, Rebecca F, Gaskin, Darrell J, Sidney, Stephen, Yaffe, Kristine, Sacco, Ralph L, Heckbert, Susan R, Hughes, Timothy M, Lopez, Oscar L, Allen, Norrina Bai, and Galecki, Andrzej T

Subjects
Biological Psychology, Psychology, Aging, Brain Disorders, Acquired Cognitive Impairment, Dementia, Behavioral and Social Science, Neurosciences, Clinical Research, Cardiovascular, Aged, Blood Pressure, Cognition, Cohort Studies, Female, Hispanic or Latino, Humans, Male, Risk Factors, White People, Blood pressure, cognition, dementia, ethnic groups, Hispanic Americans, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundEthnic differences in cognitive decline have been reported. Whether they can be explained by differences in systolic blood pressure (SBP) is uncertain.ObjectiveDetermine whether cumulative mean SBP levels explain differences in cognitive decline between Hispanic and White individuals.MethodsPooled cohort study of individual participant data from six cohorts (1971-2017). The present study reports results on SBP and cognition among Hispanic and White individuals. Outcomes were changes in global cognition (GC) (primary), executive function (EF) (secondary), and memory standardized as t-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1 SD difference in cognition. Median follow-up was 7.7 (Q1-Q3, 5.2-20.1) years.ResultsWe included 24,570 participants free of stroke and dementia: 2,475 Hispanic individuals (median age, cumulative mean SBP at first cognitive assessment, 67 years, 132.5 mmHg; 40.8% men) and 22,095 White individuals (60 years,134 mmHg; 47.3% men). Hispanic individuals had slower declines in GC, EF, and memory than White individuals when all six cohorts were examined. Two cohorts recruited Hispanic individuals by design. In a sensitivity analysis, Hispanic individuals in these cohorts had faster decline in GC, similar decline in EF, and slower decline in memory than White individuals. Higher time-varying cumulative mean SBP was associated with faster declines in GC, EF, and memory in all analyses. After adjusting for time-varying cumulative mean SBP, differences in cognitive slopes between Hispanic and White individuals did not change.ConclusionWe found no evidence that cumulative mean SBP differences explained differences in cognitive decline between Hispanic and White individuals.

Published
2022

8. Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease

Author

Duperron, Marie-Gabrielle, Knol, Maria J., Le Grand, Quentin, Evans, Tavia E., Mishra, Aniket, Tsuchida, Ami, Roshchupkin, Gennady, Konuma, Takahiro, Trégouët, David-Alexandre, Romero, Jose Rafael, Frenzel, Stefan, Luciano, Michelle, Hofer, Edith, Bourgey, Mathieu, Dueker, Nicole D., Delgado, Pilar, Hilal, Saima, Tankard, Rick M., Dubost, Florian, Shin, Jean, Saba, Yasaman, Armstrong, Nicola J., Bordes, Constance, Bastin, Mark E., Beiser, Alexa, Brodaty, Henry, Bülow, Robin, Carrera, Caty, Chen, Christopher, Cheng, Ching-Yu, Deary, Ian J., Gampawar, Piyush G., Himali, Jayandra J., Jiang, Jiyang, Kawaguchi, Takahisa, Li, Shuo, Macalli, Melissa, Marquis, Pascale, Morris, Zoe, Muñoz Maniega, Susana, Miyamoto, Susumu, Okawa, Masakazu, Paradise, Matthew, Parva, Pedram, Rundek, Tatjana, Sargurupremraj, Muralidharan, Schilling, Sabrina, Setoh, Kazuya, Soukarieh, Omar, Tabara, Yasuharu, Teumer, Alexander, Thalamuthu, Anbupalam, Trollor, Julian N., Valdés Hernández, Maria C., Vernooij, Meike W., Völker, Uwe, Wittfeld, Katharina, Wong, Tien Yin, Wright, Margaret J., Zhang, Junyi, Zhao, Wanting, Zhu, Yi-Cheng, Schmidt, Helena, Sachdev, Perminder S., Wen, Wei, Yoshida, Kazumichi, Joutel, Anne, Satizabal, Claudia L., Sacco, Ralph L., Bourque, Guillaume, Lathrop, Mark, Paus, Tomas, Fernandez-Cadenas, Israel, Yang, Qiong, Mazoyer, Bernard, Boutinaud, Philippe, Okada, Yukinori, Grabe, Hans J., Mather, Karen A., Schmidt, Reinhold, Joliot, Marc, Ikram, M. Arfan, Matsuda, Fumihiko, Tzourio, Christophe, Wardlaw, Joanna M., Seshadri, Sudha, Adams, Hieab H. H., and Debette, Stéphanie

Published
2023
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10. Pragmatic solutions to reduce the global burden of stroke: a World Stroke Organization–Lancet Neurology Commission

Author

Feigin, Valery L, Abd-Allah, Foad, Akinyemi, Rufus O, Bhattacharjee, Natalia V, Brainin, Michael, Cao, Jackie, Caso, Valeria, Dalton, Bronte, Davis, Alan, Dempsey, Robert, Duprey, Joseph, Feng, Wuwei, Ford, Gary A, Gall, Seana, Gandhi, Dorcas, Good, David C, Hachinski, Vladimir, Hacke, Werner, Hankey, Graeme J, Ishida, Marie, Johnson, Walter, Kim, Julie, Lavados, Pablo, Lindsay, Patrice, Mahal, Ajay, Martins, Sheila, Murray, Christopher, Nguyen, Thuy Phuong, Norrving, Bo, Olaiya, Muideen T, Olalusi, Oladotun V, Pandian, Jeyaraj, Phan, Hoang, Platz, Thomas, Ranta, Anna, Rehman, Sabah, Roth, Greg, Sebastian, Ivy Anne, Smith, Amanda E, Suwanwela, Nijasri C, Sylaja, P N, Thapa, Rajshree, Thrift, Amanda G, Uvere, Ezinne, Vollset, Stein Emil, Yavagal, Dileep, Yaria, Joseph, Owolabi, Mayowa O, Abera, Semaw Ferede, Akinyemi, Rufus, Dempsey, Robert J, Ibrahim, Norlinah Mohamed, Liu, Liping, Ovbiagele, Bruce, Piradov, Michael, Suwanwela, Nijasri, Abanto, Carlos, Addissie, Adamu, Adeleye, Amos O, Adilbekov, Yerzhan, Adilbekova, Bibigul, Adoukonou, Thierry A, Aguiar de Sousa, Diana, Akhmetzhanova, Zauresh, Akpalu, Albert, El Alaoui-Faris, Mustapha, Ameriso, Sebastian F, Andonova, Silva, Arsovska, Anita, Awoniyi, Folorunso E, Bakhiet, Moiz, Barboza, Miguel A, Basri, Hamidon, Bath, Philip M, Bereczki, Daniel, Beretta, Simone, Berkowitz, Aaron L, Bernhardt, Julie, Berzina, Guna, Bhavsar, Bhavan, Bisharyan, Mher S, Bohara, Manoj, Bovet, Pascal, Budincevic, Hrvoje, Cadilhac, Dominique A, Čerimagić, Denis, Charway-Felli, Augustina, Chen, Christopher, Chin, Jerome H, Christensen, Hanne, Chwojnicki, Kamil, Conforto, Adriana B, Correia, Manuel, Mora Cuervo, Daissy L, Członkowska, Anna, D'Amelio, Marco, Danielyan, Kristine E, Davis, Stephen, Demarin, Vida, Demchuk, Andrew M, Dichgans, Martin, Dokova, Klara, Donnan, Geoffrey, Duran, Juan Carlos, Ekeng, Gloria, Elkind, Mitchell S, Endres, Matthias, Fischer, Urs, Flomin, Yuriy, Gankpe, Fortuné, Gavidia, Martin, Gaye Saavedra, Andrés, Gebreyohanns, Mehari, George, Mary, Gierlotka, Marek, Giroud, Maurice, Gnedovskaya, Elena V, Gonçalves, Ivete Pillo, Gongora-Rivera, Fernando, Gunaratne, Padma S, Hamadeh, Randah R, Hamzat, Tal-hatu K, Heldner, Mirjam R, Ibrahim, Etedal, Ihle-Hansen, Hanne, Jee, Sungju, Jiann-Shing, Jeng, Johnston, S Clay, Jovanovic, Dejana, Jurjāns, Kristaps, Kalani, Rizwan, Kalkonde, Yogeshwar, Kamenova, Saltanat, Karaszewski, Bartosz, Kelly, Peter, Kiechl, Stefan, Kondybayeva, Aida, Kõrv, Janika, Kozera, Grzegorz, Kravchenko, Michael, Krespi, Yakup, Krishnamurthi, Rita, Kruja, Jera, Kutluk, Kursad, Langhorne, Peter, Law, Zhe K, Lebedynets, Dmytro, Lee, Tsong-Hai, Leung, Thomas W, Liebeskind, David S, López-Jaramillo, Patricio, Lotufo, Paulo A, Machline-Carrion, M Julia, Maia, Luis F, Malojcic, Branko, Markus, Hugh S, Marquez-Romero, Juan M, Medina, Marco T, Medukhanova, Sabina, Mehndiratta, Man Mohan, Miglāne, Evija, Mihejeva, Illa, Mikulik, Robert, Mirrakhimov, Erkin, Mohl, Stephanie, Munakomi, Sunil, Murphy, Sean, Musa, Kamarul I, Nasreldein, Ahmed, Nogueira, Raul G, Nolte, Christian H, Noubiap, Jean Jacques, Novarro-Escudero, Nelson, Ocampo, Cassandra, O'Donnell, Martin, Ogun, Yomi, Ogunniyi, Adesola, Oraby, Mohammed I, Ōrken, Dilek N, Ōzdemir, Atilla O, Ozturk, Serefnur, Paccot, Mélanie, Pereira, Telmo, Peeters, André, Potpara, Tatjana, Proios, Hariklia, Rathore, Farooq A, Sacco, Ralph L, Sahathevan, Ramesh, Sandset, Else S, Renato Santos, Irving, Saposnik, Gustavo, Sarfo, Fred S, Sargento-Freitas, João, Sharma, Mukul, Shaw, Louise, Sheth, Kevin N, Shin, Yong-Il, Shobhana, A, Silva, S Nishan, Tedim Cruz, Vitor, Thakur, Kiran, Thapa, Lekh Jung, Toni, Danilo, Topcuoglu, Mehmetakif A, Torales, Julio, Towfighi, Amytis, Truelsen, Thomas, Tsiskaridze, Alexander, Tulloch-Reid, Marshall, Useche, Juan N, Vanacker, Peter, Vassilopoulou, Sophia, Vukorepa, Gorana, Vuletic, Vladimira, Wahab, Kolawole W, Wang, Wenzhi, Wijeratne, Tissa, Wojtyniak, Bogdan, Wolfe, Charles, Yacouba, Mapoure N, Yang, Jie, Yifru, Yared M, Yock-Corrales, Adriana, Yonemoto, Naohiro, Yperzeele, Laetitia, and Zagożdżon, Pawel

Published
2023
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11. Pre-Statistical Considerations for Harmonization of Cognitive Instruments: Harmonization of ARIC, CARDIA, CHS, FHS, MESA, and NOMAS.

Author

Briceño, Emily M, Gross, Alden L, Giordani, Bruno J, Manly, Jennifer J, Gottesman, Rebecca F, Elkind, Mitchell SV, Sidney, Stephen, Hingtgen, Stephanie, Sacco, Ralph L, Wright, Clinton B, Fitzpatrick, Annette, Fohner, Alison E, Mosley, Thomas H, Yaffe, Kristine, and Levine, Deborah A

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Aging, Behavioral and Social Science, Clinical Research, Brain Disorders, Atherosclerosis, Genetics, Cardiovascular, Aetiology, 2.4 Surveillance and distribution, Blood Pressure, Cognition, Cohort Studies, Data Interpretation, Statistical, Humans, Meta-Analysis as Topic, Neuropsychological Tests, Research Design, Surveys and Questionnaires, dementia, epidemiology, methods, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundMeta-analyses of individuals' cognitive data are increasing to investigate the biomedical, lifestyle, and sociocultural factors that influence cognitive decline and dementia risk. Pre-statistical harmonization of cognitive instruments is a critical methodological step for accurate cognitive data harmonization, yet specific approaches for this process are unclear.ObjectiveTo describe pre-statistical harmonization of cognitive instruments for an individual-level meta-analysis in the blood pressure and cognition (BP COG) study.MethodsWe identified cognitive instruments from six cohorts (the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Coronary Artery Risk Development in Young Adults study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study) and conducted an extensive review of each item's administration and scoring procedures, and score distributions.ResultsWe included 153 cognitive instrument items from 34 instruments across the six cohorts. Of these items, 42%were common across ≥2 cohorts. 86%of common items showed differences across cohorts. We found administration, scoring, and coding differences for seemingly equivalent items. These differences corresponded to variability across cohorts in score distributions and ranges. We performed data augmentation to adjust for differences.ConclusionCross-cohort administration, scoring, and procedural differences for cognitive instruments are frequent and need to be assessed to address potential impact on meta-analyses and cognitive data interpretation. Detecting and accounting for these differences is critical for accurate attributions of cognitive health across cohort studies.

Published
2021

12. Race/Ethnic Disparities in Mild Cognitive Impairment and Dementia: The Northern Manhattan Study

Author

Wright, Clinton B, DeRosa, Janet T, Moon, Michelle P, Strobino, Kevin, DeCarli, Charles, Cheung, Ying Kuen, Assuras, Stephanie, Levin, Bonnie, Stern, Yaakov, Sun, Xiaoyan, Rundek, Tatjana, Elkind, Mitchell SV, and Sacco, Ralph L

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease, Vascular Cognitive Impairment/Dementia, Aging, Acquired Cognitive Impairment, Prevention, Clinical Research, Neurodegenerative, Behavioral and Social Science, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Dementia, Neurological, Mental health, Aged, Aged, 80 and over, Cognitive Dysfunction, Cohort Studies, Cross-Sectional Studies, Ethnicity, Female, Humans, Male, Middle Aged, New York City, Prevalence, African American, cohort studies, dementia, Hispanic American, mild cognitive impairment, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundVariability in dementia rates across racial and ethnic groups has been estimated at 60%. Studies suggest disparities in Caribbean Hispanic and Black populations, but community-based data are limited.ObjectiveEstimate the prevalence of mild cognitive impairment (MCI) and dementia in the racially and ethnically diverse community-based Northern Manhattan Study cohort and examine sociodemographic, vascular risk factor, and brain imaging correlates.MethodsCases of MCI and dementia were adjudicated by a team of neuropsychologists and neurologists and prevalence was estimated across race/ethnic groups. Ordinal proportional odds models were used to estimate race/ethnic differences in the prevalence of MCI or dementia adjusting for sociodemographic variables (model 1), model 1 plus potentially modifiable vascular risk factors (model 2), and model 1 plus structural imaging markers of brain integrity (model 3).ResultsThere were 989 participants with cognitive outcome determinations (mean age 69±9 years; 68% Hispanic, 16% Black, 14% White; 62% women; mean (±SD) follow-up five (±0.6) years). Hispanic and Black participants had greater likelihood of MCI (20%) and dementia (5%) than White participants accounting for age and education differences. Hispanic participants had greater odds of MCI or dementia than both White and Black participants adjusting for sociodemographic variables, vascular risk factors, and brain imaging factors. White matter hyperintensity burden was significantly associated with greater odds of MCI or dementia (OR = 1.3, 1.1 to 1.6), but there was no significant interaction by race/ethnicity.ConclusionIn this diverse community-based cohort, cross-sectional data revealed significant race/ethnic disparities in the prevalence of MCI and dementia. Longer follow-up and incidence data are needed to further clarify these relationships.

Published
2021

13. Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O’Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie

Published
2022
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15. Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities

Author

Armstrong, Nicola J, Mather, Karen A, Sargurupremraj, Muralidharan, Knol, Maria J, Malik, Rainer, Satizabal, Claudia L, Yanek, Lisa R, Wen, Wei, Gudnason, Vilmundur G, Dueker, Nicole D, Elliott, Lloyd T, Hofer, Edith, Bis, Joshua, Jahanshad, Neda, Li, Shuo, Logue, Mark A, Luciano, Michelle, Scholz, Markus, Smith, Albert V, Trompet, Stella, Vojinovic, Dina, Xia, Rui, Alfaro-Almagro, Fidel, Ames, David, Amin, Najaf, Amouyel, Philippe, Beiser, Alexa S, Brodaty, Henry, Deary, Ian J, Fennema-Notestine, Christine, Gampawar, Piyush G, Gottesman, Rebecca, Griffanti, Ludovica, Jack, Clifford R, Jenkinson, Mark, Jiang, Jiyang, Kral, Brian G, Kwok, John B, Lampe, Leonie, C.M. Liewald, David, Maillard, Pauline, Marchini, Jonathan, Bastin, Mark E, Mazoyer, Bernard, Pirpamer, Lukas, Rafael Romero, José, Roshchupkin, Gennady V, Schofield, Peter R, Schroeter, Matthias L, Stott, David J, Thalamuthu, Anbupalam, Trollor, Julian, Tzourio, Christophe, van der Grond, Jeroen, Vernooij, Meike W, Witte, Veronica A, Wright, Margaret J, Yang, Qiong, Morris, Zoe, Siggurdsson, Siggi, Psaty, Bruce, Villringer, Arno, Schmidt, Helena, Haberg, Asta K, van Duijn, Cornelia M, Jukema, J Wouter, Dichgans, Martin, Sacco, Ralph L, Wright, Clinton B, Kremen, William S, Becker, Lewis C, Thompson, Paul M, Mosley, Thomas H, Wardlaw, Joanna M, Ikram, M Arfan, Adams, Hieab HH, Seshadri, Sudha, Sachdev, Perminder S, Smith, Stephen M, Launer, Lenore, Longstreth, William, DeCarli, Charles, Schmidt, Reinhold, Fornage, Myriam, Debette, Stephanie, and Nyquist, Paul A

Subjects
Epidemiology, Health Sciences, Dementia, Acquired Cognitive Impairment, Aging, Neurosciences, Genetics, Stroke, Brain Disorders, Biotechnology, Clinical Research, Human Genome, Prevention, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Brain, Cerebral Small Vessel Diseases, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, White Matter, brain, genome-wide association study, neuroimaging, risk factors, white matter, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background and purposePeriventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings.MethodsParticipants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC.ResultsIn the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (NBEAL), 10q23.1 (TSPAN14/FAM231A), and 10q24.33 (SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 (NOS3) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype.ConclusionsOur study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.

Published
2020

16. Antithrombotic Treatment of Embolic Stroke of Undetermined Source

Author

Diener, Hans-Christoph, Sacco, Ralph L, Easton, J Donald, Granger, Christopher B, Bar, Michal, Bernstein, Richard A, Brainin, Michael, Brueckmann, Martina, Cronin, Lisa, Donnan, Geoffrey, Gdovinová, Zuzana, Grauer, Claudia, Kleine, Eva, Kleinig, Timothy J, Lyrer, Philippe, Martins, Sheila, Meyerhoff, Juliane, Milling, Truman, Pfeilschifter, Waltraud, Poli, Sven, Reif, Michal, Rose, David Z, Šaňák, Daniel, and Schäbitz, Wolf-Rüdiger

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Brain Disorders, Clinical Trials and Supportive Activities, Stroke, Hematology, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Aged, 80 and over, Aspirin, Dabigatran, Double-Blind Method, Female, Fibrinolytic Agents, Humans, Intracranial Embolism, Kidney Diseases, Male, Middle Aged, Recurrence, anticoagulants, atrial fibrillation, cardiovascular disease, risk factors, secondary prevention, Cardiorespiratory Medicine and Haematology, Neurosciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to

Published
2020

17. Association Between Central Blood Pressure and Subclinical Cerebrovascular Disease in Older Adults

Author

Matsumoto, Kenji, Jin, Zhezhen, Homma, Shunichi, Elkind, Mitchell SV, Rundek, Tatjana, Mannina, Carlo, Lee, Tetz C, Yoshita, Mitsuhiro, DeCarli, Charles, Wright, Clinton B, Sacco, Ralph L, and Di Tullio, Marco R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biomedical Imaging, Aging, Clinical Trials and Supportive Activities, Cardiovascular, Hypertension, Neurosciences, Brain Disorders, Clinical Research, Age Factors, Aged, Blood Pressure, Brain, Cerebrovascular Disorders, Echocardiography, Female, Humans, Incidence, Magnetic Resonance Imaging, Male, Risk Assessment, Risk Factors, United States, brain infarction, cardiovascular diseases, hypertension, stroke, white matter, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Elevated blood pressure (BP) level is one of the most consistently identified risk factors for silent brain disease. BP values obtained at the proximal segment of the aorta (central BP) are more directly involved than brachial BP in the pathogenesis of cardiovascular disease. However, the association between central BP and silent cerebrovascular disease has not been clearly established. Participants in the CABL (Cardiovascular Abnormalities and Brain Lesions) study (n=993; mean age, 71.7±9.3 years; 37.9% men) underwent 2-dimensional echocardiography, arterial wave reflection analysis for determination of central BPs, and brain magnetic resonance imaging. Central BPs were calculated from the radial pulse waveform. Subclinical silent cerebrovascular disease was defined as silent brain infarction and white matter hyperintensity volume. Both brachial (P=0.014) and central pulse pressure (P=0.026) were independently associated with silent brain infarctions after adjustment for clinical variables, but not adjusting for each other. None of the brachial BP values was associated with upper quartile of white matter hyperintensity volume in multivariable analysis. Both central systolic BP (P

Published
2020

18. Cognitive Decline Over Time in Patients With Systolic Heart Failure Insights From WARCEF

Author

Lee, Tetz C, Qian, Min, Liu, Yutong, Graham, Susan, Mann, Douglas L, Nakanishi, Koki, Teerlink, John R, Lip, Gregory YH, Freudenberger, Ronald S, Sacco, Ralph L, Mohr, Jay P, Labovitz, Arthur J, Ponikowski, Piotr, Lok, Dirk J, Matsumoto, Kenji, Estol, Conrado, Anker, Stefan D, Pullicino, Patrick M, Buchsbaum, Richard, Levin, Bruce, Thompson, John LP, Homma, Shunichi, Di Tullio, Marco R, and Investigators, WARCEF

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Clinical Research, Cardiovascular, Brain Disorders, Aged, Anticoagulants, Aspirin, Cognitive Dysfunction, Female, Fibrinolytic Agents, Heart Failure, Systolic, Humans, Male, Middle Aged, Retrospective Studies, Stroke Volume, Time Factors, Warfarin, cognitive function, comorbidities, dementia, longitudinal analysis, Mini-Mental State Examination, WARCEF Investigators, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

ObjectivesThis study sought to characterize cognitive decline (CD) over time and its predictors in patients with systolic heart failure (HF).BackgroundDespite the high prevalence of CD and its impact on mortality, predictors of CD in HF have not been established.MethodsThis study investigated CD in the WARCEF (Warfarin versus Aspirin in Reduced Ejection Fraction) trial, which performed yearly Mini-Mental State Examinations (MMSE) (higher scores indicate better cognitive function; e.g., normal score: 24 or higher). A longitudinal time-varying analysis was performed among pertinent covariates, including baseline MMSE and MMSE scores during follow-up, analyzed both as a continuous variable and a 2-point decrease. To account for a loss to follow-up, data at the baseline and at the 12-month visit were analyzed separately (sensitivity analysis).ResultsA total of 1,846 patients were included. In linear regression, MMSE decrease was independently associated with higher baseline MMSE score (p

Published
2019

22. Predictors and Temporal Trends of Withdrawal of Life-Sustaining Therapy After Acute Stroke in the Florida Stroke Registry

Author

Alkhachroum, Ayham, Zhou, Lili, Asdaghi, Negar, Gardener, Hannah, Ying, Hao, Gutierrez, Carolina M., Manolovitz, Brian M., Samano, Daniel, Bass, Danielle, Foster, Dianne, Sur, Nicole B., Rose, David Z., Jameson, Angus, Massad, Nina, Kottapally, Mohan, Merenda, Amedeo, Starke, Robert M., O’Phelan, Kristine, Romano, Jose G., Claassen, Jan, Sacco, Ralph L., and Rundek, Tatjana

Published
2023
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26. Measures of obesity are associated with MRI markers of brain aging: The Northern Manhattan Study.

Author

Caunca, Michelle R, Gardener, Hannah, Simonetto, Marialaura, Cheung, Ying Kuen, Alperin, Noam, Yoshita, Mitsuhiro, DeCarli, Charles, Elkind, Mitchell SV, Sacco, Ralph L, Wright, Clinton B, and Rundek, Tatjana

Subjects
Aging, Clinical Research, Nutrition, Biomedical Imaging, Neurosciences, Obesity, Prevention, 2.3 Psychological, social and economic factors, Aetiology, Stroke, Metabolic and endocrine, Adiponectin, Aged, Atrophy, Biomarkers, Body Size, Brain, Brain Infarction, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, White Matter, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo examine associations between measures of obesity in middle to early-old age with later-life MRI markers of brain aging.MethodsWe analyzed data from the Northern Manhattan MRI Sub-Study (n = 1,289). Our exposures of interest were body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and plasma adiponectin levels. Our outcomes of interest were total cerebral volume (TCV), cortical thickness, white matter hyperintensity volume (WMHV), and subclinical brain infarcts (SBI). Using multivariable linear and logistic regression models adjusted for sociodemographics, health behaviors, and vascular risk factors, we estimated β coefficients (or odds ratios) and 95% confidence intervals (CIs) and tested interactions with age, sex, and race/ethnicity.ResultsOn average at baseline, participants were aged 64 years and had 10 years of education; 60% were women and 66% were Caribbean Hispanic. The mean (SD) time lag between baseline and MRI was 6 (3) years. Greater BMI and WC were significantly associated with thinner cortices (BMI β [95% CI] -0.089 [-0.153, -0.025], WC β [95% CI] -0.103 [-0.169, -0.037]) in fully adjusted models. Similarly, compared to those with BMI

Published
2019

27. Night-time systolic blood pressure and subclinical cerebrovascular disease: the Cardiovascular Abnormalities and Brain Lesions (CABL) study

Author

Nakanishi, Koki, Jin, Zhezhen, Homma, Shunichi, Elkind, Mitchell SV, Rundek, Tatjana, Schwartz, Joseph E, Lee, Tetz C, Tugcu, Aylin, Yoshita, Mitsuhiro, DeCarli, Charles, Wright, Clinton B, Sacco, Ralph L, and Di Tullio, Marco R

Subjects
Hypertension, Heart Disease, Brain Disorders, Cardiovascular, Aging, Biomedical Imaging, Clinical Research, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Aged, Blood Pressure Monitoring, Ambulatory, Cerebrovascular Disorders, Circadian Rhythm, Echocardiography, Female, Florida, Humans, Magnetic Resonance Imaging, Male, Middle Aged, New York City, Predictive Value of Tests, Risk Factors, Systole, ambulatory blood pressure monitoring, night-time blood pressure, silent brain infarcts, white matter hyperintensity, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology
Abstract

AimsAlthough ambulatory blood pressure (BP) is a better predictor of cardiovascular outcomes than office BP, its association with subclinical cerebrovascular disease is not clarified. We investigated the associations of office and ambulatory BP values with subclinical cerebrovascular disease in a population based, predominantly elderly cohort without prior stroke.Methods and resultsEight hundred and twenty-eight participants underwent 24-h ambulatory BP monitoring (ABPM), 2D echocardiography and brain magnetic resonance imaging in the Cardiac Abnormalities and Brain Lesion (CABL) study. Daytime, night-time, and 24-h BPs, nocturnal dipping pattern, morning surge (MS), and 24-h variability were assessed. Subclinical cerebrovascular disease was defined as silent brain infarcts (SBIs) and white matter hyperintensity volume (WMHV). The association of BP measures with the presence of SBI and upper quartile of log-WMHV (log-WMHV4) was analysed. SBIs were detected in 111 patients (13.4%). Mean log-WMHV was -0.99 ± 0.94. In multivariable analysis, only night-time systolic BP (SBP) was significantly associated with SBI [odds ratio (OR) 1.15 per 10 mmHg, P = 0.042], independent of cardiovascular risk factors, and pertinent echocardiographic parameters. Although daytime, night-time, 24-h BPs, and non-dipping pattern were all significantly associated with log-WMHV4 (all P

Published
2019

28. Association between mortality and implantable cardioverter‐defibrillators by aetiology of heart failure: a propensity‐matched analysis of the WARCEF trial

Author

Lee, Tetz C, Qian, Min, Mu, Lan, Di Tullio, Marco R, Graham, Susan, Mann, Douglas L, Nakanishi, Koki, Teerlink, John R, Lip, Gregory YH, Freudenberger, Ronald S, Sacco, Ralph L, Mohr, Jay P, Labovitz, Arthur J, Ponikowski, Piotr, Lok, Dirk J, Estol, Conrado, Anker, Stefan D, Pullicino, Patrick M, Buchsbaum, Richard, Levin, Bruce, Thompson, John LP, Homma, Shunichi, Ye, Siqin, and Investigators, for the WARCEF

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Clinical Research, Cardiovascular, Aged, Anticoagulants, Aspirin, Cardiomyopathies, Cause of Death, Defibrillators, Implantable, Echocardiography, Female, Follow-Up Studies, Heart Failure, Heart Ventricles, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors, Propensity Score, Radionuclide Ventriculography, Retrospective Studies, Risk Factors, Stroke Volume, Survival Rate, United States, Ventricular Function, Left, Warfarin, Heart failure with reduced ejection fraction, Implantable cardioverter-defibrillator, Non-ischaemic cardiomyopathy, Propensity score matching, WARCEF Investigators, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

AimsThere is debate on whether the beneficial effect of implantable cardioverter-defibrillators (ICDs) is attenuated in patients with non-ischaemic cardiomyopathy (NICM). We assess whether any ICD benefit differs between patients with NICM and those with ischaemic cardiomyopathy (ICM), using data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial.Methods and resultsWe performed a post hoc analysis using WARCEF (N = 2293; ICM, n = 991 vs. NICM, n = 1302), where participants received optimal medical treatment. We developed stratified propensity scores for having an ICD at baseline using 41 demographic and clinical variables and created 1:2 propensity-matched cohorts separately for ICM patients with ICD (N = 223 with ICD; N = 446 matched) and NICM patients (N = 195 with ICD; N = 390 matched). We constructed a Cox proportional hazards model to assess the effect of ICD status on mortality for patients with ICM and those with NICM and tested the interaction between ICD status and aetiology of heart failure. During mean follow-up of 3.5 ± 1.8 years, 527 patients died. The presence of ICD was associated with a lower risk of all-cause death among those with ICM (hazard ratio: 0.640; 95% confidence interval: 0.448 to 0.915; P = 0.015) but not among those with NICM (hazard ratio: 0.984; 95% confidence interval: 0.641 to 1.509; P = 0.941). There was weak evidence of interaction between ICD status and the aetiology of heart failure (P = 0.131).ConclusionsThe presence of ICD is associated with a survival benefit in patients with ICM but not in those with NICM.

Published
2019

29. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author

Chauhan, Ganesh, Adams, Hieab HH, Satizabal, Claudia L, Bis, Joshua C, Teumer, Alexander, Sargurupremraj, Muralidharan, Hofer, Edith, Trompet, Stella, Hilal, Saima, Smith, Albert Vernon, Jian, Xueqiu, Malik, Rainer, Traylor, Matthew, Pulit, Sara L, Amouyel, Philippe, Mazoyer, Bernard, Zhu, Yi-Cheng, Kaffashian, Sara, Schilling, Sabrina, Beecham, Gary W, Montine, Thomas J, Schellenberg, Gerard D, Kjartansson, Olafur, Guðnason, Vilmundur, Knopman, David S, Griswold, Michael E, Windham, B Gwen, Gottesman, Rebecca F, Mosley, Thomas H, Schmidt, Reinhold, Saba, Yasaman, Schmidt, Helena, Takeuchi, Fumihiko, Yamaguchi, Shuhei, Nabika, Toru, Kato, Norihiro, Rajan, Kumar B, Aggarwal, Neelum T, De Jager, Philip L, Evans, Denis A, Psaty, Bruce M, Rotter, Jerome I, Rice, Kenneth, Lopez, Oscar L, Liao, Jiemin, Chen, Christopher, Cheng, Ching-Yu, Wong, Tien Y, Ikram, Mohammad K, van der Lee, Sven J, Amin, Najaf, Chouraki, Vincent, DeStefano, Anita L, Aparicio, Hugo J, Romero, Jose R, Maillard, Pauline, DeCarli, Charles, Wardlaw, Joanna M, del C. Valdés Hernández, Maria, Luciano, Michelle, Liewald, David, Deary, Ian J, Starr, John M, Bastin, Mark E, Maniega, Susana Muñoz, Slagboom, P Eline, Beekman, Marian, Deelen, Joris, Uh, Hae-Won, Lemmens, Robin, Brodaty, Henry, Wright, Margaret J, Ames, David, Boncoraglio, Giorgio B, Hopewell, Jemma C, Beecham, Ashley H, Blanton, Susan H, Wright, Clinton B, Sacco, Ralph L, Wen, Wei, Thalamuthu, Anbupalam, Armstrong, Nicola J, Chong, Elizabeth, Schofield, Peter R, Kwok, John B, van der Grond, Jeroen, Stott, David J, Ford, Ian, Jukema, J Wouter, Vernooij, Meike W, Hofman, Albert, Uitterlinden, André G, van der Lugt, Aad, Wittfeld, Katharina, Grabe, Hans J, Hosten, Norbert, von Sarnowski, Bettina, Völker, Uwe, Levi, Christopher, and Jimenez-Conde, Jordi

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Prevention, Cardiovascular, Human Genome, Aging, Brain Disorders, Genetics, Stroke, Cerebrovascular, 2.1 Biological and endogenous factors, Good Health and Well Being, Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer's Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe 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.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.

Published
2019

30. Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.

Author

Morris, Andrew P, Le, Thu H, Wu, Haojia, Akbarov, Artur, van der Most, Peter J, Hemani, Gibran, Smith, George Davey, Mahajan, Anubha, Gaulton, Kyle J, Nadkarni, Girish N, Valladares-Salgado, Adan, Wacher-Rodarte, Niels, Mychaleckyj, Josyf C, Dueker, Nicole D, Guo, Xiuqing, Hai, Yang, Haessler, Jeffrey, Kamatani, Yoichiro, Stilp, Adrienne M, Zhu, Gu, Cook, James P, Ärnlöv, Johan, Blanton, Susan H, de Borst, Martin H, Bottinger, Erwin P, Buchanan, Thomas A, Cechova, Sylvia, Charchar, Fadi J, Chu, Pei-Lun, Damman, Jeffrey, Eales, James, Gharavi, Ali G, Giedraitis, Vilmantas, Heath, Andrew C, Ipp, Eli, Kiryluk, Krzysztof, Kramer, Holly J, Kubo, Michiaki, Larsson, Anders, Lindgren, Cecilia M, Lu, Yingchang, Madden, Pamela AF, Montgomery, Grant W, Papanicolaou, George J, Raffel, Leslie J, Sacco, Ralph L, Sanchez, Elena, Stark, Holger, Sundstrom, Johan, Taylor, Kent D, Xiang, Anny H, Zivkovic, Aleksandra, Lind, Lars, Ingelsson, Erik, Martin, Nicholas G, Whitfield, John B, Cai, Jianwen, Laurie, Cathy C, Okada, Yukinori, Matsuda, Koichi, Kooperberg, Charles, Chen, Yii-Der Ida, Rundek, Tatjana, Rich, Stephen S, Loos, Ruth JF, Parra, Esteban J, Cruz, Miguel, Rotter, Jerome I, Snieder, Harold, Tomaszewski, Maciej, Humphreys, Benjamin D, and Franceschini, Nora

Subjects
Kidney, Humans, Kidney Calculi, Hypertension, Histones, Glomerular Filtration Rate, Histone Code, Blood Pressure, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Ethnic Groups, Female, Male, Renal Insufficiency, Chronic, Genome-Wide Association Study, Genetic Loci, Polymorphism, Single Nucleotide, Renal Insufficiency, Chronic
Abstract

Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

Published
2019

31. Coronary artery calcium and carotid artery intima-media thickness for the prediction of stroke and benefit from statins

Author

Osawa, Kazuhiro, Trejo, Maria Esther Perez, Nakanishi, Rine, McClelland, Robyn L, Blaha, Michael J, Blankstein, Ron, McEvoy, John W, Ceponiene, Indre, Stein, James H, Sacco, Ralph L, Polak, Joseph F, and Budoff, Matthew J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Neurosciences, Brain Disorders, Heart Disease, Stroke, Heart Disease - Coronary Heart Disease, Cardiovascular, Atherosclerosis, Prevention, Good Health and Well Being, Aged, Carotid Intima-Media Thickness, Clinical Decision-Making, Computed Tomography Angiography, Coronary Angiography, Coronary Artery Disease, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Ischemic Attack, Transient, Longitudinal Studies, Male, Middle Aged, Patient Selection, Predictive Value of Tests, Prevalence, Primary Prevention, Protective Factors, Risk Assessment, Risk Factors, Time Factors, United States, Vascular Calcification, Carotid artery intima-media thickness, ischemic stroke/transient ischemic attack, coronary artery calcification, Cardiovascular medicine and haematology
Abstract

BackgroundCurrent guidelines suggest treatment for many individuals who may never develop a stroke. We hypothesized that a combination of coronary artery calcification (CAC) and carotid artery intima-media thickness (C IMT) data could better individualize risk assessment for ischemic stroke and transient ischemic attack events.MethodsA total of 4720 individuals from the Multi-Ethnic Study of Atherosclerosis were evaluated for ischemic stroke and transient ischemic attack. Cox proportional hazards models for time to incident ischemic stroke/transient ischemic attack were used to examine CAC and CIMT as ischemic stroke/transient ischemic attack predictors in addition to traditional risk factors. We calculated the 10-year number needed to treat by applying the benefit observed in ASCOT-LLA to the observed event rates within CAC and CIMT strata.ResultsMedian follow-up was 13.1 years. Compared with individuals with no CAC and with CIMT ≤ 75th percentile, stroke/transient ischemic attack risk increased progressively with each CAC category (0, 1-100, >100) among individuals with CIMT > 75th percentile. Among participants eligible for statin therapy based on the 2013 atherosclerotic cardiovascular disease (ASCVD) guidelines (ASCVD risk of >5%), 739/2906 (25%) had no CAC and CIMT ≤ 75th percentile and an observed ischemic stroke/transient ischemic attack rate of 2.49 per 1000 person-years. The predicted 10-year number needed to treat was 292 for no CAC and CIMT ≤ 75th percentile and 57 for CAC > 100 and CIMT > 75th percentile.ConclusionThe combination of CIMT and CAC could serve to further refine risk calculation for ischemic stroke/transient ischemic attack prevention and may prioritize those in most need of statin therapy to reduce ischemic stroke/transient ischemic attack risk.

Published
2018

32. Left atrial volume and cardiovascular outcomes in systolic heart failure: effect of antithrombotic treatment

Author

Di Tullio, Marco R, Qian, Min, Thompson, John LP, Labovitz, Arthur J, Mann, Douglas L, Sacco, Ralph L, Pullicino, Patrick M, Freudenberger, Ronald S, Teerlink, John R, Graham, Susan, Lip, Gregory YH, Levin, Bruce, Mohr, Jay P, Buchsbaum, Richard, Estol, Conrado J, Lok, Dirk J, Ponikowski, Piotr, Anker, Stefan D, Homma, Shunichi, and Investigators, for the WARCEF

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Cardiovascular, Heart Disease - Coronary Heart Disease, Patient Safety, Clinical Trials and Supportive Activities, Hematology, Heart Disease, Clinical Research, Prevention, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Stroke, Anticoagulants, Argentina, Aspirin, Canada, Cardiac Volume, Dose-Response Relationship, Drug, Echocardiography, Female, Heart Atria, Heart Failure, Systolic, Humans, Incidence, Male, Middle Aged, Platelet Aggregation Inhibitors, Stroke Volume, Survival Rate, Thromboembolism, Treatment Outcome, United States, Warfarin, Heart failure, Left atrium, WARCEF Investigators, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

AimsLeft atrium (LA) dilation is associated with adverse cardiovascular (CV) outcomes. Blood stasis, thrombus formation and atrial fibrillation may occur, especially in heart failure (HF) patients. It is not known whether preventive antithrombotic treatment may decrease the incidence of CV events in HF patients with LA enlargement. We investigated the relationship between LA enlargement and CV outcomes in HF patients and the effect of different antithrombotic treatments.Methods and resultsTwo-dimensional echocardiography with LA volume index (LAVi) measurement was performed in 1148 patients with systolic HF from the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) trial. Patients were randomized to warfarin or aspirin and followed for 3.4 ± 1.7 years. While the primary aim of the trial was a composite of ischaemic stroke, death, and intracerebral haemorrhage, the present report focuses on the individual CV events, whose incidence was compared across different LAVi and treatment subgroups. After adjustment for demographics and clinical covariates, moderate or severe LA enlargement was significantly associated with total death (hazard ratio 1.6 and 2.7, respectively), CV death (HR 1.7 and 3.3), and HF hospitalization (HR 2.3 and 2.6) but not myocardial infarction (HR 1.0 and 1.4) or ischaemic stroke (1.1 and 1.5). The increased risk was observed in both patients treated with warfarin or aspirin. In warfarin-treated patients, a time in therapeutic range >60% was associated with lower event rates, and an interaction between LAVi and time in therapeutic range was observed for death (P = 0.034).ConclusionsIn patients with systolic HF, moderate or severe LA enlargement is associated with death and HF hospitalization despite treatment with antithrombotic medications. The possibility that achieving a more consistent therapeutic level of anticoagulation may decrease the risk of death requires further investigation.

Published
2018

34. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank W.G., Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L, Peyser, Patricia A, Elliot, Paul, de Vries, Paul S, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, Kraft, Peter, Hansen, John‐Bjarne, Heit, John A, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten‐Jacobs, Loes, Giese, Anne‐Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez‐Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin‐Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei‐Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Pulit, Sara L, Rannikmäe, Kristiina, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Rost, Natalia S, Rothwell, Peter M, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, W T, Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S, Howson, Joanna MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2022
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36. Radiomics-Derived Brain Age Predicts Functional Outcome After Acute Ischemic Stroke

Author

Bretzner, Martin, Bonkhoff, Anna K, Schirmer, Markus D., Hong, Sungmin, Dalca, Adrian, Donahue, Kathleen, Giese, Anne-Katrin, Etherton, Mark R, Rist, Pamela M, Nardin, Marco, Regenhardt, Robert W, Leclerc, Xavier, Lopes, Renaud, Gautherot, Morgan, Wang, Clinton, Benavente, Oscar R, Cole, John W., Donatti, Amanda, Griessenauer, Christoph, Heitsch, Laura, Holmegaard, Lukas, Jood, Katarina, Jimenez-Conde, Jordi, Kittner, Steven J, Lemmens, Robin, Levi, Christopher R, McArdle, Patrick F, McDonough, Caitrin W., Meschia, James F, Phuah, Chia-Ling, Rolfs, Arndt, Ropele, Stefan, Rosand, Jonathan, Roquer, Jaume, Rundek, Tatjana, Sacco, Ralph L., Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Sousa, Alessandro, Stanne, Tara M, Strbian, Daniel, Tatlisumak, Turgut, Thijs, Vincent, Vagal, Achala, Wasselius, Johan, Woo, Daniel, Wu, Ona, Zand, Ramin, Worrall, Bradford B, Maguire, Jane, Lindgren, Arne G, Jern, Christina, Golland, Polina, Kuchcinski, Grégory, and Rost, Natalia S

Published
2022
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38. Primary stroke prevention worldwide: translating evidence into action

Author

Abanto, Carlos, Abera, Semaw Ferede, Addissie, Adamu, Adebayo, Oluwadamilola, Adeleye, Amos Olufemi, Adilbekov, Yerzhan, Adilbekova, Bibigul, Adoukonou, Thierry Armel, Aguiar de Sousa, Diana, Ajagbe, Temitope, Akhmetzhanova, Zauresh, Akpalu, Albert, Álvarez Ahlgren, Jhon, Ameriso, Sebastián, Andonova, Silva, Awoniyi, Foloruso Emmanuel, Bakhiet, Moiz, Barboza, Miguel, Basri, Hamidon, Bath, Philip, Bello, Olamide, Bereczki, Dániel, Beretta, Simone, Berkowitz, Aaron, Bernabé-Ortiz, Antonio, Bernhardt, Julie, Berzina, Guna, Bisharyan, Mher, Bovet, Pascal, Budincevic, Hrvoje, Cadilhac, Dominique, Caso, Valeria, Chen, Christopher, Chin, Jerome, Chwojnicki, Kamil, Conforto, Adriana, Cruz, Vitor Tedim, D'Amelio, Marco, Danielyan, Kristine, Davis, Stephen, Demarin, Vida, Dempsey, Robert, Dichgans, Martin, Dokova, Klara, Donnan, Geoffrey, Elkind, Mitchell S., Endres, Matthias, Fischer, Urs, Gankpé, Fortuné, Gaye Saavedra, Andrés, Gil, Artyom, Giroud, Maurice, Gnedovskaya, Elena, Hachinski, Vladimir, Hafdi, Melanie, Hamadeh, Randah, Hamzat, T. Kolapo, Hankey, Graeme, Heldner, Mirjam, Ibrahim, Etedal Ahmed, Ibrahim, Norlinah Mohamed, Inoue, Manabu, Jee, Sungju, Jeng, Jiann-Shing, Kalkonde, Yogesh, Kamenova, Saltanat, Karaszewski, Bartosz, Kelly, Peter, Khan, Taskeen, Kiechl, Stefan, Kondybayeva, Aida, Kõrv, Janika, Kravchenko, Michael, Krishnamurthi, Rita V., Kruja, Jera, Lakkhanaloet, Mongkol, Langhorne, Peter, Lavados, Pablo M., Law, Zhe Kang, Lawal, Abisola, Lazo-Porras, Maria, Lebedynets, Dmytro, Lee, Tsong-Hai, Leung, Thomas, Liebeskind, David S., Lindsay, Patrice, López-Jaramillo, Patricio, Lotufo, Paulo Andrade, Machline-Carrion, Julia, Makanjuola, Akintomiwa, Markus, Hugh Stephen, Marquez-Romero, Juan Manuel, Medina, Marco, Medukhanova, Sabina, Mehndiratta, Man Mohan, Merkin, Alexandr, Mirrakhimov, Erkin, Mohl, Stephanie, Moscoso-Porras, Miguel, Müller-Stierlin, Annabel, Murphy, Sean, Musa, Kamarul Imran, Nasreldein, Ahmed, Nogueira, Raul Gomes, Nolte, Christian, Noubiap, Jean Jacques, Novarro-Escudero, Nelson, Ogun, Yomi, Oguntoye, Richard Ayobami, Oraby, Mohammed Ibrahim, Osundina, Morenike, Ovbiagele, Bruce, Orken, Dilek Necioglu, Ozdemir, Atilla Özcan, Ozturk, Serefnur, Paccot, Melanie, Phromjai, Jurairat, Piradov, Piradov, Platz, Thomas, Potpara, Tatjana, Ranta, Annemarei, Rathore, Farooq, Richard, Edo, Sacco, Ralph L., Sahathevan, Ramesh, Santos Carquín, Irving, Saposnik, Gustavo, Sarfo, Fred Stephen, Sharma, Mike, Sheth, Kevin, Shobhana, A., Suwanwela, Nijasri, Svyato, Irina, Sylaja, P.N., Tao, Xuanchen, Thakur, Kiran T., Toni, Danilo, Topcuoglu, Mehmet Akif, Torales, Julio, Towfighi, Amytis, Truelsen, Thomas Clement, Tsiskaridze, Alexander, Tulloch-Reid, Marshall, Useche, Nicolás, Vanacker, Peter, Vassilopoulou, Sophia, Vukorepa, Gorana, Vuletic, Vladimira, Wahab, Kolawole W., Wang, Wenzhi, Wijeratne, Tissa, Wolfe, Charles, Yifru, Yared Mamushet, Yock-Corrales, Adriana, Yonemoto, Naohiro, Yperzeele, Laetitia, Zhang, Puhong, Owolabi, Mayowa O, Thrift, Amanda G, Mahal, Ajay, Ishida, Marie, Martins, Sheila, Johnson, Walter D, Pandian, Jeyaraj, Abd-Allah, Foad, Yaria, Joseph, Phan, Hoang T, Roth, Greg, Gall, Seana L, Beare, Richard, Phan, Thanh G, Mikulik, Robert, Akinyemi, Rufus O, Norrving, Bo, Brainin, Michael, and Feigin, Valery L

Published
2022
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39. Nationally Certified Stroke Centers Outperform Self-Attested Stroke Centers in the Florida Stroke Registry

Author

Marulanda, Erika, Bustillo, Antonio, Gutierrez, Carolina M., Rose, David Z., Jameson, Angus, Gardener, Hannah, Alkhachroum, Ayham, Zhou, Lili, Ying, Hao, Dong, Chuanhui, Foster, Dianne, Hanel, Ricardo, Mehta, Brijesh, Mokin, Maxim, Mueller-Kronast, Nils, Landreth, Mark, Sand, Charles, Romano, Jose G., Rundek, Tatjana, Asdaghi, Negar, and Sacco, Ralph L.

Published
2023
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40. Impact of Time to Treatment on Endovascular Thrombectomy Outcomes in the Early Versus Late Treatment Time Windows

Author

Asdaghi, Negar, Wang, Kefeng, Gardener, Hannah, Jameson, Angus, Rose, David Z., Alkhachroum, Ayham, Gutierrez, Carolina M., Ying, Hao, Mueller-Kronast, Nils, Sur, Nicole B., Dong, Chuanhui, Gordon Perue, Gillian, LePain, Marissa, Koch, Sebastian, Krementz, Nastajjia, Marulanda-Londoño, Erika, Hanel, Ricardo, Mehta, Brijesh, Yavagal, Dileep R., Rundek, Tatjana, Sacco, Ralph L., and Romano, Jose G.

Published
2023
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42. Heart Failure Severity and Quality of Warfarin Anticoagulation Control (From the WARCEF Trial)

Author

Lee, Tetz C, Qian, Min, Lip, Gregory YH, Di Tullio, Marco R, Graham, Susan, Mann, Douglas L, Nakanishi, Koki, Teerlink, John R, Freudenberger, Ronald S, Sacco, Ralph L, Mohr, JP, Labovitz, Arthur J, Ponikowski, Piotr, Lok, Dirk J, Estol, Conrado, Anker, Stefan D, Pullicino, Patrick M, Buchsbaum, Richard, Levin, Bruce, Thompson, John LP, Homma, Shunichi, Ye, Siqin, and Investigators, The WARCEF

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Cardiovascular, Hematology, Clinical Research, Anticoagulants, Aspirin, Atrial Fibrillation, Double-Blind Method, Female, Heart Failure, Humans, Male, Middle Aged, Quality of Life, Severity of Illness Index, Stroke Volume, Thromboembolism, Treatment Outcome, Warfarin, WARCEF Investigators, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Previous studies in patients with atrial fibrillation showed that a history of heart failure (HF) could negatively impact anticoagulation quality, as measured by the average time in therapeutic range (TTR). Whether additional markers of HF severity are associated with TTR has not been investigated thoroughly. We aimed to examine the potential role of HF severity in the quality of warfarin control in patients with HF with reduced ejection fraction. Data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial were used to investigate the association between TTR and HF severity. Multivariable logistic regression models were used to examine the association of markers of HF severity, including New York Heart Association (NYHA) class, Minnesota Living with HF (MLWHF) score, and frequency of HF hospitalization, with TTR ≥70% (high TTR). We included 1,067 participants (high TTR, N = 413; low TTR, N = 654) in the analysis. In unadjusted analysis, patients with a high TTR were older and less likely to have had strokes or receive other antiplatelet agents. Those patients also had lower NYHA class, better MLWHF scores, greater 6-minute walk distance, and lower frequency of HF hospitalizations. Multivariable analysis showed that NYHA class III and/or IV (Odds ratio [OR] 0.68 [95% confidence intervals [CIs] 0.49 to 0.94]), each 10-point increase in MLWHF score (i.e., worse health-related quality of life) (OR 0.92 [0.86 to 0.99]), and higher number of HF hospitalization per year (OR0.45 [0.30 to 0.67]) were associated with decreased likelihood of having high TTR. In HF patients with systolic dysfunction, NYHA class III and/or IV, poor health-related quality of life, and a higher rate of HF hospitalization were independently associated with suboptimal quality of warfarin anticoagulation control. These results affirm the need to assess the new approaches, such as direct oral anticoagulants, to prevent thromboembolism in this patient population.

Published
2018

43. Ischemic stroke/transient ischemic attack events and carotid artery disease in the absence of or with minimal coronary artery calcification: Results from the Multi-Ethnic Study of Atherosclerosis

Author

Osawa, Kazuhiro, Nakanishi, Rine, McClelland, Robyn L, Polak, Joseph F, Bishop, Warrick, Sacco, Ralph L, Ceponiene, Indre, Nezarat, Negin, Rahmani, Sina, Qi, Hong, Kanisawa, Mitsuru, and Budoff, Matthew J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Prevention, Heart Disease, Neurosciences, Stroke, Heart Disease - Coronary Heart Disease, Atherosclerosis, Cardiovascular, Aging, Brain Disorders, Aged, Aged, 80 and over, Asymptomatic Diseases, Brain Ischemia, Carotid Artery Diseases, Coronary Artery Disease, Female, Humans, Incidence, Ischemic Attack, Transient, Male, Middle Aged, Plaque, Atherosclerotic, Prevalence, Prognosis, Risk Assessment, Risk Factors, Severity of Illness Index, Time Factors, United States, Vascular Calcification, Ischemic stroke/Transient ischemic attack, Coronary artery calcification, Carotid artery lesion, Carotid artery intima-media thickness, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Background and aimsThe association between minimally elevated coronary artery calcification (CAC) and cerebrovascular disease is not well known. We assessed whether individuals with minimal CAC (Agatston scores of 1-10) have higher ischemic stroke or transient ischemic attack (TIA) frequencies compared with those with no CAC. We also investigated the relative prevalence of carotid atherosclerosis in these two groups.MethodsA total of 3924 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) without previous cardiovascular events, including stroke, and with baseline CAC scores of 0-10 were followed for the occurrence of incident ischemic stroke/TIA. We used carotid ultrasound to detect carotid artery plaques and to measure the intima-media thickness (IMT).ResultsDuring a median follow-up of 13.2 years, 130 participants developed incident ischemic stroke/TIA. There was no significant difference in the ischemic stroke/TIA incidence between those with minimal CAC and no CAC (3.7 versus 2.7 per 1000 person-years). In participants with minimal CAC, we observed a significant association of the condition with an internal carotid artery (ICA) that had a greater-than-average IMT (ICA-IMT; β = 0.071, p = 0.001) and a higher odds ratio (OR) for carotid artery plaques (OR 1.46; with a 95% confidence interval [CI] of 1.18-1.80; p

Published
2018

44. Greater depressive symptoms, cognition, and markers of brain aging

Author

Zeki Al Hazzouri, Adina, Caunca, Michelle R, Nobrega, Juan Carlos, Elfassy, Tali, Cheung, Ying Kuen, Alperin, Noam, Dong, Chuanhui, Elkind, Mitchell SV, Sacco, Ralph L, DeCarli, Charles, and Wright, Clinton B

Subjects
Mental Health, Stroke, Depression, Aging, Behavioral and Social Science, Brain Disorders, Clinical Research, Neurosciences, Mental health, Aged, Aged, 80 and over, Brain, Cohort Studies, Community Health Planning, Cross-Sectional Studies, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Memory, Episodic, Middle Aged, New York City, Psychiatric Status Rating Scales, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveWe examined whether greater depressive symptoms were associated with domain-specific cognitive performance, change in cognition, and MRI markers of brain atrophy and subclinical cerebrovascular disease in a diverse sample of older adults from the Northern Manhattan Study.MethodsData were analyzed from the Northern Manhattan Study, a prospective cohort study of mostly Caribbean Hispanic, stroke-free, older adults. A total of 1,111 participants had baseline measures of depressive symptoms, measured as the Center of Epidemiological Studies-Depression Scale, MRI markers, and cognitive function. A Center of Epidemiological Studies-Depression score ≥16 was considered indicative of greater depressive symptoms. Multivariable linear and logistic regression models were used to examine the associations of interest.ResultsAt baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographic, vascular risk factor, behavioral, and antidepressive medication variables (β [95% confidence interval] = -0.21 [-0.33 to -0.10], p = 0.0003). Greater depressive symptoms were also associated with smaller cerebral parenchymal fraction (β [95% confidence interval] = -0.56 [-1.05 to -0.07], p = 0.02) and increased odds of subclinical brain infarcts (odds ratio [95% confidence interval] = 1.55 [1.00-2.42], p = 0.05), after adjustment for sociodemographic, behavioral, and vascular risk factor variables. Greater depressive symptoms were not significantly associated with white matter hyperintensity volume, hippocampal volume, or change in cognition over an average of 5 years. Results were unchanged when stabilized inverse probability weights were applied to address selective attrition during the study period.ConclusionsIn this sample of mostly Caribbean Hispanic, stroke-free, older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts.

Published
2018

45. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chasman, Daniel I, Chen, Wei-Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Heckbert, Susan R, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I, Ikram, M Arfan, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei-Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Psaty, Bruce M, Pulit, Sara L, Rannikmäe, Kristiina, Reiner, Alexander P, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Ridker, Paul M, Rost, Natalia S, Rothwell, Peter M, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, and Sale, Michele M

Subjects
Biological Sciences, Genetics, Human Genome, Stroke, Clinical Research, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Computational Biology, Databases, Genetic, Epigenesis, Genetic, Female, Gene Regulatory Networks, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, INDEL Mutation, Linkage Disequilibrium, Male, Models, Genetic, Polymorphism, Single Nucleotide, Risk Factors, AFGen Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, International Genomics of Blood Pressure (iGEN-BP) Consortium, INVENT Consortium, STARNET, BioBank Japan Cooperative Hospital Group, COMPASS Consortium, EPIC-CVD Consortium, EPIC-InterAct Consortium, International Stroke Genetics Consortium, METASTROKE Consortium, Neurology Working Group of the CHARGE Consortium, NINDS Stroke Genetics Network, UK Young Lacunar DNA Study, MEGASTROKE Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

Published
2018

46. Association Between Heart Rate and Subclinical Cerebrovascular Disease in the Elderly

Author

Nakanishi, Koki, Jin, Zhezhen, Homma, Shunichi, Elkind, Mitchell SV, Rundek, Tatjana, Lee, Seitetz C, Tugcu, Aylin, Yoshita, Mitsuhiro, DeCarli, Charles, Wright, Clinton B, Sacco, Ralph L, and Di Tullio, Marco R

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Clinical Research, Cardiovascular, Biomedical Imaging, Heart Disease, Aging, Brain Disorders, Stroke, Neurosciences, Aged, Aged, 80 and over, Blood Pressure Monitoring, Ambulatory, Brain Infarction, Cerebrovascular Disorders, Female, Heart Rate, Humans, Male, Middle Aged, Risk Factors, echocardiography, heart rate, magnetic resonance imaging, multivariate analysis, odds ratio, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background and purposeAlthough increased heart rate (HR) is a predictor of cardiovascular events and mortality, its possible association with subclinical cerebrovascular disease, which is prevalent in the elderly, has not been evaluated. This study aimed to investigate the association of daytime, nighttime, 24-hour HR, and HR variability with subclinical cerebrovascular disease in an elderly cohort without history of stroke.MethodsThe study cohort consisted of 680 participants (mean age, 73±7 years; 42% men) in sinus rhythm who underwent 24-hour ambulatory blood pressure and HR monitoring, 2-dimensional echocardiography, and brain magnetic resonance imaging as part of the CABL study (Cardiac Abnormalities and Brain Lesion). Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume (WMHV). The relationship of HR measures with the presence of silent brain infarct and upper quartile of log WMHV (log WMHV4) was analyzed.ResultsPresence of silent brain infarct was detected in 93 participants (13.7%); mean log WMHV was -0.92±0.93 (median, -1.05; min, -5.88; max, 1.74). Multivariate analysis showed that only nighttime HR (adjusted odds ratio, 1.29 per 10 bpm; 95% confidence interval, 1.03-1.61; P=0.026) was significantly associated with log WMHV4, independent of traditional cardiovascular risk factors, ambulatory systolic blood pressure, and echocardiographic parameters. No similar association was observed for daytime HR and HR variability. There was no significant association between all HR measures and silent brain infarct.ConclusionsIn a predominantly elderly cohort, elevated nighttime HR was associated with WMHV, suggesting an independent role of HR in subclinical cerebrovascular disease.

Published
2018

47. Genome-wide scan in Hispanics highlights candidate loci for brain white matter hyperintensities

Author

Beecham, Ashley, Dong, Chuanhui, Wright, Clinton B, Dueker, Nicole, Brickman, Adam M, Wang, Liyong, DeCarli, Charles, Blanton, Susan H, Rundek, Tatjana, Mayeux, Richard, and Sacco, Ralph L

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Biotechnology, Aging, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Neurosciences, Clinical sciences
Abstract

ObjectiveTo investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population.MethodsUsing 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genome-wide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project. Multiple linear modeling with PLINK was performed to examine the additive genetic effects on ln(WMHV) after controlling for age, sex, total intracranial volume, and principal components of ancestry. Gene-based tests of association were performed using VEGAS. Replication was performed in independent samples of Europeans, African Americans, and Asians.ResultsFrom the SNP analysis, a total of 17 independent SNPs in 7 genes had suggestive evidence of association with WMHV in Hispanics (p < 1 × 10-5) and 5 genes from the gene-based analysis with p < 1 × 10-3. One SNP (rs9957475 in GATA6) and 1 gene (UBE2C) demonstrated evidence of association (p < 0.05) in the African American sample. Four SNPs with p < 1 × 10-5 were shown to affect binding of SPI1 using RegulomeDB.ConclusionsThis GWAS of 2 community-based Hispanic cohorts revealed several novel WMH-associated genetic variants. Further replication is needed in independent Hispanic samples to validate these suggestive associations, and fine mapping is needed to pinpoint causal variants.

Published
2017

48. Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke

Author

Jaworek, Thomas, Xu, Huichun, Gaynor, Brady J, Cole, John W., Rannikmae, Kristiina, Stanne, Tara M, Tomppo, Liisa, Abedi, Vida, Amouyel, Philippe, Armstrong, Nicole D, Attia, John, Bell, Steven, Benavente, Oscar R, Boncoraglio, Giorgio B, Butterworth, Adam, Carcel-Marquez, Jara, Chen, Zhengming, Chong, Michael, Cruchaga, Carlos, Cushman, Mary, Danesh, John, Debette, Stephanie, Duggan, David J, Durda, Jon Peter, Engstrom, Gunnar, Enzinger, Chris, Faul, Jessica D, Fecteau, Natalie S, Fernandez-Cadenas, Israel, Gieger, Christian, Giese, Anne-Katrin, Grewal, Raji P, Grittner, Ulrike, Havulinna, Aki S, Heitsch, Laura, Hochberg, Marc C, Holliday, Elizabeth, Hu, Jie, Ilinca, Andreea, Irvin, Marguerite R, Jackson, Rebecca D, Jacob, Mina A., Janssen, Raquel Rabionet, Jimenez-Conde, Jordi, Johnson, Julie A, Kamatani, Yoichiro, Kardia, Sharon L, Koido, Masaru, Kubo, Michiaki, Lange, Leslie, Lee, Jin-Moo, Lemmens, Robin, Levi, Christopher R, Li, Jiang, Li, Liming, Lin, Kuang, Lopez, Haley, Luke, Sothear, Maguire, Jane, McArdle, Patrick F, McDonough, Caitrin W., Meschia, James F, Metso, Tiina, Muller-Nurasyid, Martina, OʼConnor, Timothy D, OʼDonnell, Martin, Peddareddygari, Leema R, Pera, Joanna, Perry, James A, Peters, Annette, Putaala, Jukka, Ray, Debashree, Rexrode, Kathryn, Ribases, Marta, Rosand, Jonathan, Rothwell, Peter M, Rundek, Tatjana, Ryan, Kathleen A, Sacco, Ralph L., Salomaa, Veikko, Sanchez-Mora, Cristina, Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Smith, Jennifer A, Smith, Nicholas L, Wassertheil-Smoller, Sylvia, Soederholm, Martin, Stine, O. C, Strbian, Daniel, Sudlow, Cathie L, Tatlisumak, Turgut, Terao, Chikashi, Thijs, Vincent, Torres-Aguila, Nuria P, Tregouet, David-Alexandre, Tuladhar, Anil M., Veldink, Jan H, Walters, Robin G, Weir, David R, Woo, Daniel, Worrall, Bradford B, Hong, Charles C, Ross, Owen, Zand, Ramin, Leeuw, Frank-Erik de, Lindgren, Arne G, Pare, Guillaume, Anderson, Christopher D., Markus, Hugh S, Jern, Christina, Malik, Rainer, Dichgans, Martin, Mitchell, Braxton D, and Kittner, Steven J

Published
2022
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49. Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome

Author

Bonkhoff, Anna K, Hong, Sungmin, Bretzner, Martin, Schirmer, Markus D., Regenhardt, Robert W, Arsava, E. Murat, Donahue, Kathleen, Nardin, Marco, Dalca, Adrian, Giese, Anne-Katrin, Etherton, Mark R, Hancock, Brandon L., Mocking, Steven J.T., McIntosh, Elissa, Attia, John, Benavente, Oscar, Cole, John W., Donatti, Amanda, Griessenauer, Christoph, Heitsch, Laura, Holmegaard, Lukas, Jood, Katarina, Jimenez-Conde, Jordi, Kittner, Steven, Lemmens, Robin, Levi, Christopher, McDonough, Caitrin W., Meschia, James, Phuah, Chia-Ling, Rolfs, Arndt, Ropele, Stefan, Rosand, Jonathan, Roquer, Jaume, Rundek, Tatjana, Sacco, Ralph L., Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Soederholm, Martin, Sousa, Alessandro, Stanne, Tara M, Strbian, Daniel, Tatlisumak, Turgut, Thijs, Vincent, Vagal, Achala, Wasselius, Johan, Woo, Daniel, Zand, Ramin, McArdle, Patrick, Worrall, Bradford B, Jern, Christina, Lindgren, Arne G, Maguire, Jane, Golland, Polina, Bzdok, Danilo, Wu, Ona, and Rost, Natalia S

Published
2022
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