Cardiology Commons^™

Loss-Of-Function Genomic Variants Highlight Potential Therapeutic Targets For Cardiovascular Disease, Jonas B. Nielsen, Oren Rom, Ida Surakka, Sarah E. Graham, Wei Zhou, Tanmoy Roychowdhury, Lars G. Fritsche, Sarah A. Gagliano Taliun, Carlo Sidore, Yuhao Liu, Maiken E. Gabrielsen, Anne Heidi Skogholt, Brooke Wolford, William Overton, Ying Zhao, Jin Chen, He Zhang, Whitney E. Hornsby, Akua Acheampong, Austen Grooms, Amanda Schaefer, Gregory J. M. Zajac, Luis Villacorta, Jifeng Zhang, Ben Brumpton, Mari Løset, Vivek Rai, Pia R. Lundegaard, Morten S. Olesen, Kent D. Taylor, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of …

Cardiac Biomarkers And Subsequent Risk Of Hospitalization With Bleeding In The Community: Atherosclerosis Risk In Communities Study, Lena Mathews, Junichi Ishigami, Ning Ding, Ron C. Hoogeveen, Anna Kucharska-Newton, Christie M. Ballantyne, Rebecca Gottesman, Elizabeth Selvin, Kunihiro Matsushita

Epidemiology and Environmental Health Faculty Publications

Background

hs-cTnT (high-sensitivity cardiac troponin T), but not NT-proBNP (N-terminal pro-B natriuretic peptide), has been shown to predict bleeding in patients with atrial fibrillation. Whether these biomarkers are independently associated with bleeding in the general population is unknown.

Methods and Results

We used Cox proportional hazards models to examine the association of hs‐cTnT and NT‐proBNP with incident bleeding (defined by International Classification of Diseases, Ninth Revision [ICD‐9] codes) among 9550 middle‐aged men and women without a history of cardiovascular disease or bleeding. There were 847 hospitalizations with bleeding (92% from gastrointestinal bleeding) during a median follow‐up of …

Prevalence And Prognostic Features Of Ecg Abnormalities In Acute Stroke: Findings From The Siren Study Among Africans, Abiodun M. Adeoye, Okechukwu S. Ogah, Bruce Ovbiagele, Rufus Akinyemi, Vincent Shidali, Francis Agyekum, Akinyemi Aje, Oladimeji Adebayo, Joshua O. Akinyemi, Philip Kolo, Lambert Tetteh Appiah, Henry Iheonye, Uwanuruochi Kelechukwu, Amusa Ganiyu, Taiwo O. Olunuga, Onoja Akpa, Ojo Olakanmi Olagoke, Fred Stephen Sarfo, Kolawole Wahab, Samuel Olowookere, Adekunle Fakunle, Albert Akpalu, Philip B. Adebayo, Kwadwo Nkromah, Joseph Yaria, Philip Ibinaiye, Godwin Ogbole, Aridegbe Olumayowa, Sulaiman Lakoh, Benedict Calys-Tagoe, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

Africa has a growing burden of stroke with associated high morbidity and a 3-year fatality rate of 84%. Cardiac disease contributes to stroke occurrence and outcomes, but the precise relationship of abnormalities as noted on a cheap and widely available test, the electrocardiogram (ECG), and acute stroke outcomes have not been previously characterized in Africans.

Objectives

The study assessed the prevalence and prognoses of various ECG abnormalities among African acute stroke patients encountered in a multisite, cross-national epidemiologic study.

Methods

We included 890 patients from Nigeria and Ghana with acute stroke who had 12-lead ECG recording within first 24 …

Exploring Overlaps Between The Genomic And Environmental Determinants Of Lvh And Stroke: A Multicenter Study In West Africa, Abiodun M. Adeoye, Bruce Ovbiagele, Philip Kolo, Lambert Appiah, Akinyemi Aje, Oladimeji Adebayo, Fred Sarfo, Joshua Akinyemi, Gregory Adekunle, Francis Agyekum, Vincent Shidali, Okechukwu Ogah, Dan Lackland, Mulugeta Gebregziabher, Donna K. Arnett, Hemant K. Tiwari, Rufus Akinyemi, Ojo Olakanmi Olagoke, Ayodipupo Sikiru Oguntade, Taiwo Olunuga, Kelechi Uwanruochi, Carolyn Jenkins, Patrick Adadey, Henry Iheonye, Lukman Owolabi, Reginald Obiako, Samuel Akinjopo, Kevin Armstrong, Albert Akpalu, Adekunle Fakunle

Epidemiology and Environmental Health Faculty Publications

Background

Whether left ventricular hypertrophy (LVH) is determined by similar genomic and environmental risk factors with stroke, or is simply an intermediate stroke marker, is unknown.

Objectives

We present a research plan and preliminary findings to explore the overlap in the genomic and environmental determinants of LVH and stroke among Africans participating in the SIREN (Stroke Investigative Research and Education Network) study.

Methods

SIREN is a transnational, multicenter study involving acute stroke patients and age-, ethnicity-, and sex-matched control subjects recruited from 9 sites in Ghana and Nigeria. Genomic and environmental risk factors and other relevant phenotypes for stroke and …

Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10^–7) in the discovery panel …

Epigenetics Of Lipid Phenotypes, Sergi Sayols-Baixeras, Marguerite R. Irvin, Donna K. Arnett, Roberto Elosua, Stella W. Aslibekyan

Epidemiology and Environmental Health Faculty Publications

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay …

Limited Association Between Perceived Control And Health-Related Quality Of Life In Patients With Heart Failure, Teesta Banerjee, Kyoung Suk Lee, Steven R. Browning, Claudia Hopenhayn, Susan C. Westneat, Martha J. Biddle, Cynthia Arslanian-Angoren, Jo-Ann Eastwood, Gia Mudd, Debra K. Moser

Epidemiology and Environmental Health Faculty Publications

Background: Perceived control has been suggested as a modifiable factor associated with health-related quality of life (HRQOL). However, the relationship between perceived control and HRQOL has not been evaluated in patients with heart failure (HF). The purpose of this study was to determine whether perceived control independently predicts HRQOL in HF patients. Methods: A total of 423 HF patients were included. Hierarchical linear regression was performed to determine the independent association of perceived control to HRQOL after controlling for covariates. Results: Higher levels of perceived control were associated with better HRQOL in univariate analysis. However, this relationship was strongly attenuated …