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Search Results for all work with filters:

  • Alonso, Alvaro
  • Health Sciences, Epidemiology
  • Epidemiology

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Article

Whole Exome Sequencing in Atrial Fibrillation.

by Steven A. Lubitz; Jennifer A. Brody; Nathan A. Bihlmeyer; Carolina Roselli; Lu-Chen Weng; Ingrid E. Christophersen; Alvaro Alonso; Eric Boerwinkle; Richard A. Gibbs; Joshua C. Bis; NHLBI GO Exome Sequencing Project; L. Adrienne Cupples; Peter J. Mohler; Deborah A. Nickerson; Donna Muzny; Marco V. Perez; Bruce M. Psaty; Elsayed Z. Soliman; Nona Sotoodehnia; Kathryn L. Lunetta; Emelia J. Benjamin; Susan R. Heckbert; Dan E. Arking; Patrick T. Ellinor; Honghuang Lin

2016

Subjects
  • Biology, Genetics
  • Health Sciences, Epidemiology
  • File Download
  • View Abstract

Abstract:Close

Atrial fibrillation (AF) is a morbid and heritable arrhythmia. Over 35 genes have been reported to underlie AF, most of which were described in small candidate gene association studies. Replication remains lacking for most, and therefore the contribution of coding variation to AF susceptibility remains poorly understood. We examined whole exome sequencing data in a large community-based sample of 1,734 individuals with and 9,423 without AF from the Framingham Heart Study, Cardiovascular Health Study, Atherosclerosis Risk in Communities Study, and NHLBI-GO Exome Sequencing Project and meta-analyzed the results. We also examined whether genetic variation was enriched in suspected AF genes (N = 37) in AF cases versus controls. The mean age ranged from 59 to 73 years; 8,656 (78%) were of European ancestry. None of the 99,404 common variants evaluated was significantly associated after adjusting for multiple testing. Among the most significantly associated variants was a common (allele frequency = 86%) missense variant in SYNPO2L (rs3812629, p.Pro707Leu, [odds ratio 1.27, 95% confidence interval 1.13-1.43, P = 6.6x10-5]) which lies at a known AF susceptibility locus and is in linkage disequilibrium with a top marker from prior analyses at the locus. We did not observe significant associations between rare variants and AF in gene-based tests. Individuals with AF did not display any statistically significant enrichment for common or rare coding variation in previously implicated AF genes. In conclusion, we did not observe associations between coding genetic variants and AF, suggesting that large-effect coding variation is not the predominant mechanism underlying AF. A coding variant in SYNPO2L requires further evaluation to determine whether it is causally related to AF. Efforts to identify biologically meaningful coding variation underlying AF may require large sample sizes or populations enriched for large genetic effects.

Article

Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans

by Daniel S. Evans; Christy L. Avery; Mike A. Nalls; Guo Li; John Barnard; Erin N. Smith; Toshiko Tanaka; Anne M. Butler; Sarah G. Buxbaum; Alvaro Alonso; Dan E. Arking; Gerald S. Berenson ; Joshua C. Bis; Steven Buyske; Cara L. Carly; Wei Chen; Mina K. Chung; Steven R. Cummings; Rajat Deo; Charles B. Eaton; Ervin R. Fox; Susan R. Heckbert; Gerardo Heiss; Lucia A. Hindorff; Wen-Chi Hsueh; Aaron Isaacs; Yalda Jamshidi; Kathleen F. Kerr ; Felix Liu; Yongmei Liu; Kurt K. Lohman; Jared W. Magnani; Joseph F. Maher ; Reena Mehra; Yan A. Meng; Solomon K. Musani; Christopher Newton-Cheh; Kari E. North; Bruce M. Psaty; Susan Redline; Jerome I. Rotter; Renate B. Schnabel; Nicholas J. Schork; Ralph V. Schohet; Andrew B. Singleton; Jonathan D. Smith ; Elsayed Z. Soliman; Sathanur R. Srinivasan; Herman A. Taylor, Jr.; David R. Van Wagoner; James G. Wilson ; Taylor Young ; Zhu-MIng Zhang; Alan B. Zonderman; Michelle K. Evans; Luigi Ferucci; Sarah S. Murray; Gregory J. Tranah; Eric A. Whitsel; Alex P. Reiner; Nona Sotoodehnia

2016

Subjects
  • Biology, Genetics
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
  • File Download
  • View Abstract

Abstract:Close

The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10-14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10-4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10-8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10-9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10-7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.

Article

Validation of self reported diagnosis of hypertension in a cohort of university graduates in Spain.

by Alvaro Alonso; Juan José Beunza; Miguel Delgado-Rodríguez; Miguel Angel Martínez-González

2005

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Medicine and Surgery
  • Health Sciences, Public Health
  • File Download
  • View Abstract

Abstract:Close

BACKGROUND: The search for risk factors of hypertension requires the study of large populations. Sometimes, the only feasible way of studying these populations is to rely on self-reported data of the outcome. The objective of this study was to evaluate validity of self-reported diagnosis of hypertension in a cohort of university graduates in Spain. METHODS: The Seguimiento Universidad de Navarra (SUN) Study is a cohort of more than 15,000 university graduates in Spain. We selected a random sample of 79 cohort participants who reported a diagnosis of hypertension and 48 participants who did not report such diagnosis (76% participation proportion). Then, we compared information on the self-reported diagnosis of hypertension and hypertension status as assessed through two personal blood pressure measurements and an interview. Additionally, we compared self-reported and measured blood pressure levels with intraclass correlation coefficients and the survival-agreement plot. RESULTS: From those 79 reporting a diagnosis of hypertension, 65 (82.3%, 95% CI 72.8-92.8) were confirmed through conventional measurement of blood pressure and the interview. From those 48 that did not report a diagnosis of hypertension, 41 (85.4%, 95% CI 72.4-89.1) were confirmed as non hypertensives. Results were similar among men and women, but were worse for overweight and obese individuals, and for those with a family history of hypertension. The agreement between self-reported and measured blood pressure levels (as a continuous variable), as estimated by the intraclass correlation coefficient, was 0.35 for both systolic and diastolic blood pressure. CONCLUSION: Self-reported hypertension among highly educated participants in a cohort study is a relatively valid tool to assess the hypertensive status of participants. However, the investigators should be cautious when using self-reported blood pressure values.

Article

The Prevalence of Anosmia and Associated Factors Among U.S. Black and White Older Adults

by Jing Dong; Jayant M. Pinto; Xuguang Guo; Alvaro Alonso; Gregory Tranah; Jane A. Cauley; Melissa Garcia; Suzanne Satterfield; Xuemei Huang; Tamara Harris; Thomas H. Mosley; Honglei Chen

2017

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
  • File Download
  • View Abstract

Abstract:Close

Olfactory impairment is common among older adults; however, data are largely limited to whites. Methods: We conducted pooled analyses of two community-based studies: the Atherosclerosis Risk in Communities study (ARIC, 1,398 blacks and 4,665 whites), and the Health, Aging, and Body Composition study (Health ABC, 958 blacks and 1,536 whites) to determine the prevalence of anosmia and associated factors for black and white older adults in the United States. Results: The overall prevalence of anosmia was 22.3% among blacks and 10.4% among whites. Blacks had a markedly higher odds of anosmia compared to whites in age and sex adjusted analyses (odds ratio [OR] 2.96, 95% confidence interval [CI] = 2.59-3.38). In both blacks and whites, higher anosmia prevalence was associated with older age and male sex. The highest prevalence was found in black men 85 years or older (58.3%), and the lowest in white women aged 65-69 years (2.4%). Higher education level, lower cognitive score, ApoE 4, daytime sleepiness, poorer general health status, lower body mass index, and Parkinson disease were associated with higher prevalence of anosmia in one or both races. However, the racial difference in anosmia remained statistically significant after adjusting for these factors (fully adjusted OR = 1.76, 95%CI: 1.50-2.07). Results were comparable between the two cohorts. Discussion: Anosmia is common in older adults, particularly among blacks. Further studies are needed to identify risk factors for anosmia and to investigate racial disparities in this sensory deficit.

Article

Genetic Risk Prediction of Atrial Fibrillation

by Steven A. Lubitz; Xiaoyan Yin Yin; Henry J. Lin; Matthew Kolek; J. Gustav Smith; Stella Trompet; Michiel Rienstra; Natalia S. Rost; Pedro L. Teixeira; Peter Almgren; Christopher D. Anderson; Lin Y Chen; Gunnar Engstrom; Ian Ford; Karen L Furie; Xiuqng Guo; Martin G. Larson; Kathryn L. Lunetta; Peter W. Macfarlane; Bruce M. Psaty; Elsayed Z. Soliman; Nona Sotoodehnia; David J. Stott; Kent D. Taylor; Lu-Chen Weng; Jie Yao; Bastiaan Geelhoed; Niek Verweij; Joylene Siland; Sekar Kathiresan; Carolina Roselli; Dan Roden; Pim van der Harst; Dawood Darbar; J. Wouter Jukema; Olle Melander; Jonathan Rosand; Jerome I. Rotter; Susan R. Heckbert; Patrick T. Ellinor; Alvaro Alonso; Emelia J. Benjamin

2017

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
  • File Download
  • View Abstract

Abstract:Close

BACKGROUND: Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. METHODS: To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in 5 prospective studies comprising 18 919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P values ranging from < 1×10 -3 to < 1×10 -8 in a prior independent genetic association study. RESULTS: Incident AF occurred in 1032 individuals (5.5%). AF genetic risk scores were associated with new-onset AF after adjustment for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95% confidence interval, 1.13-1.46; P=1.5×10 -4 ) to 1.67 (25 variants; 95% confidence interval, 1.47-1.90; P=9.3×10 -15 ). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ΔC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in ageand sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95% confidence interval, 1.39-4.58; P=2.7×10 -3 ). The effect persisted after the exclusion of individuals (n=70) with known AF (odds ratio, 2.25; 95% confidence interval, 1.20-4.40; P=0.01). CONCLUSIONS: Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors but offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms.

Article

Highlights From the American Heart Association's EPI

by Alvaro Alonso; Madison D. Anderson; Michael P. Bancks; Sherry-Ann Brown; Melissa C. Caughey; Alex R. Chang; Erin Delker; Kathryn Foti; Veronique Gingras; Michael G. Nanna; Alexander C. Razavi; Jewel Scott; Elizabeth Selvin; Catherine Tcheandjieu; Alvin G. Thomas; Ruth-Alma N. Turkson-Ocran; Allison Webel; Deborah Young; Bailey M. DeBarmore

2019

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
  • File Download

Article

Coronary Artery Calcium and Risk of Dementia in MESA (Multi-Ethnic Study of Atherosclerosis)

by Akira Fujiyoshi; David R. Jacobs; Annette L. Fitzpatrick; Alvaro Alonso; Daniel A. Duprez; A. Richey Sharrett; Teresa Seeman; Michael J. Blaha; Jose A. Luchsinger; Stephen R. Rapp

2017

Subjects
  • Health Sciences, Public Health
  • Health Sciences, Epidemiology
  • Psychology, Behavioral
  • File Download
  • View Abstract

Abstract:Close

Background-Studies suggest a link between vascular injuries and dementia. Only a few studies, however, examined a longitudinal relation of subclinical vascular disease with dementia. We tested whether baseline coronary artery calcium (CAC), a biomarker of subclinical vascular disease, is associated with incident dementia independent of vascular risk factors and APOE-e4 genotype in a community-based sample. Methods and Results-We analyzed 6293 participants of MESA (Multi-Ethnic Study of Atherosclerosis), aged 45 to 84 years at baseline (2000-2002), initially free of cardiovascular disease and noticeable cognitive deficit. Dementia cases were identified using hospital and death certificate International Statistical Classification of Diseases and Related Health Problems codes. Cox models were used to obtain hazard ratios according to CAC category, or per 1 SD log2[CAC+1], adjusted for vascular risk factor, APOE-e4, with or without exclusion of interim stroke or cardiovascular disease. We observed 271 dementia cases in a median follow-up of 12.2 years. Baseline CAC had a graded positive association with dementia risk. Compared with no CAC, CAC score of 1 to 400, 401 to 1000, and =1001 had increased risk of dementia by 23%, 35%, and 71%, respectively, (Ptrend=0.026) after adjustment. 1 SD higher log2[CAC+1] was associated with 24% (95% confidence interval, 8%-41%; P=0.002) increase in dementia risk. Although the association was partially explained by interim stroke/cardiovascular disease, it remained significant even after excluding the interim events, or regardless of baseline age. Conclusions-Higher baseline CAC was significantly associated with increased risk of dementia independent of vascular risk factor, APOE-e4, and incident stroke. This is consistent with a hypothesis that vascular injuries play a role in the development of dementia.

Article

Association of Atrial Fibrillation With Cognitive Decline and Dementia Over 20 Years: The ARIC‐NCS (Atherosclerosis Risk in Communities Neurocognitive Study)

by Lin Y. Chen; Faye L. Norby; Rebecca F. Gottesman; Thomas H. Mosley; Elsayed Z. Soliman; Sunil K. Agarwal; Laura R. Loehr; Aaron R. Folsom; Josef Coresh; Alvaro Alonso

2018

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
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Previous studies have reported that atrial fibrillation (AF) is associated with cognitive decline and dementia. These studies, however, had limited follow-up, were based mostly on white and highly selected populations, and did not account for attrition. We evaluated the association of incident AF with 20-year change in cognitive performance (accounting for attrition) and incident dementia in the ARIC (Atherosclerosis Risk in Communities) Study. Methods and Results--We analyzed data from 12 515 participants (mean age, 56.9 [SD, 5.7] years in 1990-1992; 56% women and 24% black) from 1990 to 1992 through 2011 to 2013. Incident AF was ascertained from study ECGs and hospital discharge codes. Cognitive tests were performed in 1990 to 1992, 1996 to 1998, and 2011 to 2013. Incident dementia was clinician adjudicated. We used generalized estimating equations and Cox proportional hazards models to assess the association of timedependent AF with change in Z scores of cognitive tests and incident dementia, respectively. During 20 years, 2106 participants developed AF and 1157 participants developed dementia. After accounting for cardiovascular risk factors, including ischemic stroke, the average decline over 20 years in global cognitive Z score was 0.115 (95% confidence interval, 0.014-0.215) greater in participants with AF than in those without AF. Further adjustment for attrition by multiple imputation by chained equations strengthened the association. In addition, incident AF was associated with an increased risk of dementia (hazard ratio, 1.23; 95% confidence interval, 1.04-1.45), after adjusting for cardiovascular risk factors, including ischemic stroke. Conclusions--AF is associated with greater cognitive decline and increased risk of dementia, independent of ischemic stroke. Because cognitive decline is a precursor to dementia, our findings prompt further investigation to identify specific treatments for AF that will delay the trajectory of cognitive decline and, thus, prevent dementia in patients with AF.

Article

Provider Specialty, Anticoagulation Prescription Patterns, and Stroke Risk in Atrial Fibrillation

by Wesley T. O'Neal; Pratik B. Sandesara; J'Neka S. Claxton; Richard F. MacLehose; Lin Y. Chen; Lindsay G. S. Bengtson; Alanna M. Chamberlain; Faye L. Norby; Pamela L. Lutsey; Alvaro Alonso

2018

Subjects
  • Health Sciences, Public Health
  • Health Sciences, Epidemiology
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Differences in anticoagulation rates and direct oral anticoagulant use by provider specialty may identify an area of practice improvement to reduce future stroke events in patients with atrial fibrillation (AF). Methods and Results--We examined anticoagulant prescription fills in 388 045 (mean age, 68±15 years; 59% male) patients with incident AF from the MarketScan databases between 2009 and 2014. Provider specialty and filled anticoagulant prescriptions around the time of AF diagnosis (3 months before through 6 months after) were obtained from outpatient services and pharmacy claims. We estimated the association of provider specialty (cardiology versus primary care) with filling oral anticoagulant prescriptions, adjusting for patient characteristics. The risk of stroke and bleeding events also was explored. A total of 235 739 patients (61%) had a cardiology provider claim, whereas 152 306 (39%) were exclusively managed by primary care. Patients seen by cardiology providers were more likely to fill anticoagulant prescriptions than those seen by primary care (39% versus 27%; relative risk, 1.39; 95% confidence interval [CI], 1.37-1.40). Differences were observed for direct oral anticoagulants (relative risk, 1.74; 95% CI, 1.71-1.78) and warfarin (relative risk, 1.24; 95% CI, 1.22-1.26). A reduced risk of stroke events was observed among those seen by cardiology providers (hazard ratio, 0.90; 95% CI, 0.86-0.94) compared with primary care, without an increased bleeding risk (hazard ratio, 1.03; 95% CI, 0.98-1.07). Conclusions--Patients seen by an outpatient cardiology provider shortly after AF diagnosis were more likely to initiate oral anticoagulation and were at lower risk of future stroke events without a higher rate of bleeding. Early referral to cardiology specialists may increase initiation of anticoagulant therapies and improve outcomes in AF.

Article

Relation of Prolonged P-Wave Duration to Risk of Sudden Cardiac Death in the General Population (from the Atherosclerosis Risk in Communities Study)

by Ankit Maheshwari; Faye L. Norby; Elsayed Z. Soliman; M. Chadi Alraies; Selcuk Adabag; Wesley T. O'Neal; Alvaro Alonso; Lin Y. Chen

2017

Subjects
  • Health Sciences, Public Health
  • Health Sciences, Epidemiology
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Prolonged P-wave duration, a marker of left atrial abnormality, is associated with myocardial fibrosis, atrial fibrillation, and all-cause death. It is not known if prolonged P-wave duration is associated with sudden cardiac death (SCD) in the general population. We aimed to evaluate whether prolonged P-wave duration is independently associated with SCD risk in the Atherosclerosis Risk in Communities Study, a community-based prospective cohort study. We included 15,321 participants in our analysis (age 54.2 ± 5.7 years, 55.2% women, 26.4% black). Prolonged P-wave duration was defined as maximum P-wave duration > 120 ms and was determined from 12-lead electrocardiograms obtained during 4 exams (1987 to 1999). SCD was physician adjudicated and defined as a sudden, pulseless condition in a previously stable patient without evidence for noncardiac cause of death. We used Cox proportional hazard models to assess the association between prolonged P-wave duration and SCD, adjusting for cardiovascular risk factors and conditions including atrial fibrillation. During a mean follow-up of 12.5 years (1987 to 2001), 268 SCDs were identified. The multivariable hazard ratio (95% confidence interval) of prolonged P-wave duration for SCD was 1.70 (1.31 to 2.20). This association was attenuated but remained significant after updating covariates to the end of follow-up with a hazard ratio of 1.35 (1.04 to 1.76). In conclusion, prolonged P-wave duration is independently associated with an increased risk of SCD in the general population. This association is independent of atrial fibrillation and is only partially mediated by shared cardiovascular risk factors.
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