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Albert, Christine

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Christine

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Albert, Christine
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    Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium
    (Nature Publishing Group UK, 2017) Weng, Lu-Chen; Lunetta, Kathryn L.; Müller-Nurasyid, Martina; Smith, Albert Vernon; Thériault, Sébastien; Weeke, Peter E.; Barnard, John; Bis, Joshua C.; Lyytikäinen, Leo-Pekka; Kleber, Marcus E.; Martinsson, Andreas; Lin, Henry J.; Rienstra, Michiel; Trompet, Stella; Krijthe, Bouwe P.; Dörr, Marcus; Klarin, Derek; Chasman, Daniel; Sinner, Moritz F.; Waldenberger, Melanie; Launer, Lenore J.; Harris, Tamara B.; Soliman, Elsayed Z.; Alonso, Alvaro; Paré, Guillaume; Teixeira, Pedro L.; Denny, Joshua C.; Shoemaker, M. Benjamin; Van Wagoner, David R.; Smith, Jonathan D.; Psaty, Bruce M.; Sotoodehnia, Nona; Taylor, Kent D.; Kähönen, Mika; Nikus, Kjell; Delgado, Graciela E.; Melander, Olle; Engström, Gunnar; Yao, Jie; Guo, Xiuqing; Christophersen, Ingrid E.; Ellinor, Patrick; Geelhoed, Bastiaan; Verweij, Niek; Macfarlane, Peter; Ford, Ian; Heeringa, Jan; Franco, Oscar H.; Uitterlinden, André G.; Völker, Uwe; Teumer, Alexander; Rose, Lynda M.; Kääb, Stefan; Gudnason, Vilmundur; Arking, Dan E.; Conen, David; Roden, Dan M.; Chung, Mina K.; Heckbert, Susan R.; Benjamin, Emelia J.; Lehtimäki, Terho; März, Winfried; Smith, J. Gustav; Rotter, Jerome I.; van der Harst, Pim; Jukema, J. Wouter; Stricker, Bruno H.; Felix, Stephan B.; Albert, Christine; Lubitz, Steven
    It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10−5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10−8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.
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    Novel genetic markers improve measures of atrial fibrillation risk prediction
    (Oxford University Press, 2013) Everett, Brendan; Cook, Nancy; Conen, David; Chasman, Daniel; Ridker, Paul; Albert, Christine
    Aims Atrial fibrillation (AF) is associated with adverse outcome. Whether recently discovered genetic risk markers improve AF risk prediction is unknown. Methods and results We derived and validated a novel AF risk prediction model from 32 possible predictors in the Women's Health Study (WHS), a cohort of 20 822 women without cardiovascular disease (CVD) at baseline followed prospectively for incident AF (median: 14.5 years). We then created a genetic risk score (GRS) comprised of 12 risk alleles in nine loci and assessed model performance in the validation cohort with and without the GRS. The newly derived WHS AF risk algorithm included terms for age, weight, height, systolic blood pressure, alcohol use, and smoking (current and past). In the validation cohort, this model was well calibrated with good discrimination [C-index (95% CI) = 0.718 (0.684–0.753)] and improved all reclassification indices when compared with age alone. The addition of the genetic score to the WHS AF risk algorithm model improved the C-index [0.741 (0.709–0.774); P = 0.001], the category-less net reclassification [0.490 (0.301–0.670); P < 0.0001], and the integrated discrimination improvement [0.00526 (0.0033–0.0076); P < 0.0001]. However, there was no improvement in net reclassification into 10-year risk categories of <1, 1–5, and 5+% [0.041 (−0.044–0.12); P = 0.33]. Conclusion: Among women without CVD, a simple risk prediction model utilizing readily available risk markers identified women at higher risk for AF. The addition of genetic information resulted in modest improvements in predictive accuracy that did not translate into improved reclassification into discrete AF risk categories.
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    Gene-gene Interaction Analyses for Atrial Fibrillation
    (Nature Publishing Group, 2016) Lin, Honghuang; Mueller-Nurasyid, Martina; Smith, Albert V.; Arking, Dan E.; Barnard, John; Bartz, Traci M.; Lunetta, Kathryn L.; Lohman, Kurt; Kleber, Marcus E.; Lubitz, Steven; Geelhoed, Bastiaan; Trompet, Stella; Niemeijer, Maartje N.; Kacprowski, Tim; Chasman, Daniel; Klarin, Derek; Sinner, Moritz F.; Waldenberger, Melanie; Meitinger, Thomas; Harris, Tamara B.; Launer, Lenore J.; Soliman, Elsayed Z.; Chen, Lin Y.; Smith, Jonathan D.; Van Wagoner, David R.; Rotter, Jerome I.; Psaty, Bruce M.; Xie, Zhijun; Hendricks, Audrey E.; Ding, Jingzhong; Delgado, Graciela E.; Verweij, Niek; van der Harst, Pim; Macfarlane, Peter W.; Ford, Ian; Hofman, Albert; Uitterlinden, André; Heeringa, Jan; Franco, Oscar H.; Kors, Jan A.; Weiss, Stefan; Völzke, Henry; Rose, Lynda M.; Natarajan, Pradeep; Kathiresan, Sekar; Kääb, Stefan; Gudnason, Vilmundur; Alonso, Alvaro; Chung, Mina K.; Heckbert, Susan R.; Benjamin, Emelia J.; Liu, Yongmei; März, Winfried; Rienstra, Michiel; Jukema, J. Wouter; Stricker, Bruno H.; Dörr, Marcus; Albert, Christine; Ellinor, Patrick
    Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an independent cohort for replication, which included more than 2,363 AF cases and 114,746 AF-free referents. One interaction, between rs7164883 at the HCN4 locus and rs4980345 at the SLC28A1 locus, was found to be significantly associated with AF in the discovery cohorts (interaction OR = 1.44, 95% CI: 1.27–1.65, P = 4.3 × 10–8). Eight additional gene-gene interactions were also marginally significant (P < 5 × 10–7). However, none of the top interactions were replicated. In summary, we did not find significant interactions that were associated with AF susceptibility. Future increases in sample size and denser genotyping might facilitate the identification of gene-gene interactions associated with AF.
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    Plasma Levels of Fetuin‐A and Risk of Coronary Heart Disease in US Women: The Nurses' Health Study
    (Blackwell Publishing Ltd, 2014) Sun, Qi; Jimenez, Monik; Townsend, Mary K.; Rimm, Eric; Manson, JoAnn; Albert, Christine; Rexrode, Kathryn
    Background: Fetuin‐A may be involved in the etiology of coronary heart disease (CHD) through opposing pathways (ie, promoting insulin resistance and inhibiting ectopic calcification). We aimed to explicitly examine whether systemic inflammation, a factor leading to elevated vascular calcification, may modify the association between fetuin‐A and CHD risk. Method and Results During 16 years of follow‐up (1990–2006), we prospectively identified and confirmed 466 incident fatal or nonfatal CHD case in the Nurses' Health Study. For each case, 1 healthy control was selected using risk‐set sampling from 26 245 eligible participants. Cases and controls were matched for age, smoking status, fasting status, and date of blood draw. After multivariate adjustment for lifestyle factors, body mass index, diet, and blood lipids, fetuin‐A levels were not associated with CHD risk in the whole population: odds ratio (OR) (95% CI) comparing extreme quintiles of fetuin‐A was 0.79 (0.44 to 1.40). However, a significant inverse association was observed among participants with higher C‐reactive protein levels (Pinteraction=0.04). The OR (95% CI) comparing highest versus lowest quintiles of fetuin‐A was 0.50 (0.26 to 0.97; Ptrend=0.004) when C‐reactive protein levels were above population median (0.20 mg/dL), whereas among the remainder of the participants, the corresponding OR (95% CI) was 1.09 (0.58 to 2.05; Ptrend=0.75). Conclusions: In this population of US women, fetuin‐A levels were associated with lower CHD risk when C‐reactive protein levels were high, but null association was observed among participants with lower C‐reactive protein levels. This divergent pattern of association needs replication in future studies.
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    Predisposing Factors Associated With Development of Persistent Compared With Paroxysmal Atrial Fibrillation
    (Blackwell Publishing Ltd, 2014) Sandhu, Roopinder K.; Conen, David; Tedrow, Usha; Fitzgerald, Kathryn C.; Pradhan, Aruna; Ridker, Paul; Glynn, Robert; Albert, Christine
    Background: Once atrial fibrillation (AF) progresses to sustained forms, adverse outcomes increase and treatment success rates decrease. Therefore, identification of risk factors predisposing to persistence of AF may have a significant impact on AF morbidity. Methods and Results: We prospectively examined the differential associations between traditional, lifestyle, and biomarker AF risk factors and development of paroxysmal versus nonparoxysmal AF (persistent/permanent) among 34 720 women enrolled in the Women's Health Study who were free of cardiovascular disease and AF at baseline. AF patterns were defined based on current guidelines and classified according to the most sustained form of AF within 2 years of diagnosis. During a median follow‐up of 16.4 years, 690 women developed paroxysmal AF and 349 women developed nonparoxysmal AF. In multivariable time‐varying competing risk models, increasing age (hazard ratio [HR] 1.11, 95% CI 1.10 to 1.13, versus HR 1.08, 1.07 to 1.09, per year), body mass index (HR 1.07, 1.05 to 1.09, versus HR 1.03, 1.02 to 1.05, per kg/m2), and weight (HR 1.30, 1.22 to 1.39, versus HR 1.14, 1.08 to 1.20, per 10 kg) were more strongly associated with the development of nonparoxysmal AF compared with paroxysmal AF. Hemoglobin A1c levels at baseline were directly related to the development of nonparoxysmal AF but inversely associated with paroxysmal AF in multivariable competing risk models (P for nonequal association=0.01). Conclusions: In women without AF or CVD at baseline, increasing age, adiposity, and higher hemoglobin A1c levels were preferentially associated with the early development of nonparoxysmal AF. These data raise the hypothesis that efforts aimed at weight reduction or glycemic control may affect the proportion of the population with sustained AF.
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    Lifestyle‐Based Prediction Model for the Prevention of CVD: The Healthy Heart Score
    (Blackwell Publishing Ltd, 2014) Chiuve, Stephanie; Cook, Nancy; Shay, Christina M.; Rexrode, Kathryn; Albert, Christine; Manson, JoAnn; Willett, Walter; Rimm, Eric
    Background: Clinical practice focuses on the primary prevention of cardiovascular (CV) disease (CVD) through the modification and pharmacological treatment of elevated risk factors. Prediction models based on established risk factors are available for use in the primary prevention setting. However, the prevention of risk factor development through healthy lifestyle behaviors, or primordial prevention, is of paramount importance to achieve optimal population‐wide CV health and minimize long‐term CVD risk. Methods and Results: We developed a lifestyle‐based CVD prediction model among 61 025 women in the Nurses’ Health Study and 34 478 men in the Health Professionals Follow‐up Study, who were free of chronic disease in 1986 and followed for ≤24 years. Lifestyle factors were assessed by questionnaires in 1986. In the derivation step, we used the Bayes Information Criterion to create parsimonious 20‐year risk prediction models among a random two thirds of participants in each cohort separately. The scores were validated in the remaining one third of participants in each cohort. Over 24 years, there were 3775 cases of CVD in women and 3506 cases in men. The Healthy Heart Score included age, smoking, body mass index, exercise, alcohol, and a composite diet score. In the validation cohort, the risk score demonstrated good discrimination (Harrell's C‐index, 0.72; 95% confidence interval [CI], 0.71, 0.74 [women]; 0.77; 95% CI, 0.76, 0.79 [men]), fit, and calibration, particularly among individuals without baseline hypertension or hypercholesterolemia. Conclusions: The Healthy Heart Score accurately identifies individuals at elevated risk for CVD and may serve as an important clinical and public health screening tool for the primordial prevention of CVD.
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    Aspirin Use and Risk of Atrial Fibrillation in the Physicians' Health Study
    (Blackwell Publishing Ltd, 2014) Ofman, Peter; Petrone, Andrew B.; Peralta, Adelqui; Hoffmeister, Peter; Albert, Christine; Djousse, Luc; Gaziano, John; Rahilly‐Tierney, Catherine R.
    Background: Inflammatory processes have been associated with an increased risk of atrial fibrillation (AF), potentially allowing for preventive therapy by anti‐inflammatory agents such as aspirin. However, the effect of chronic aspirin on the incidence of AF has not been evaluated in a prospective cohort followed for an extended period. Methods and Results: This study was comprised of a prospective cohort of 23 480 male participants of the Physicians' Health Study. Aspirin intake and covariates were estimated using self‐reported questionnaires. Incident AF was ascertained through yearly follow‐up questionnaires. Cox's regression, with adjustment for multiple covariates, was used to estimate relative risk of AF. Average age at baseline was 65.1±8.9 years. During a mean follow‐up of 10.0 years, 2820 cases of AF were reported. Age‐standardized incidence rates were 12.6, 11.1, 12.7, 11.3, 15.8, and 13.8/1000 person‐years for people reporting baseline aspirin intake of 0, <14 days per year, 14 to 30 days per year, 30 to 120 days per year, 121 to 180 days per year, and >180 days per year, respectively. Multivariable adjusted hazard ratios (95% confidence interval) for incident AF were 1.00 (reference), 0.88 (0.76 to 1.02), 0.93 (0.76 to 1.14), 0.96 (0.80 to 1.14), 1.07 (0.80 to 1.14), and 1.04 (0.94 to 1.15) across consecutive categories of aspirin intake. Analysis of the data using time‐varying Cox's regression model to update aspirin intake over time showed similar results. Conclusions: In a large cohort of males followed for a long period, we did not find any association between aspirin use and incident AF.
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    Incidence and Risk Factors of Ventricular Fibrillation Before Primary Angioplasty in Patients With First ST‐Elevation Myocardial Infarction: A Nationwide Study in Denmark
    (Blackwell Publishing Ltd, 2014) Jabbari, Reza; Engstrøm, Thomas; Glinge, Charlotte; Risgaard, Bjarke; Jabbari, Javad; Winkel, Bo Gregers; Terkelsen, Christian Juhl; Tilsted, Hans‐Henrik; Jensen, Lisette Okkels; Hougaard, Mikkel; Chiuve, Stephanie; Pedersen, Frants; Svendsen, Jesper Hastrup; Haunsø, Stig; Albert, Christine; Tfelt‐Hansen, Jacob
    Background: We aimed to investigate the incidence and risk factors for ventricular fibrillation (VF) before primary percutaneous coronary intervention (PPCI) among patients with ST‐segment elevation myocardial infarction (STEMI) in a prospective nationwide setting. Methods and Results: In this case‐control study, patients presenting within the first 12 hours of first STEMI who survived to undergo angiography and subsequent PPCI were enrolled. Over 2 years, 219 cases presenting with VF before PPCI and 441 controls without preceding VF were enrolled. Of the 219 case patients, 182 (83%) had STEMI with out‐of‐hospital cardiac arrest due to VF, and 37 (17%) had cardiac arrest upon arrival to the emergency room. Medical history was collected by standardized interviews and by linkage to national electronic health records. The incidence of VF before PPCI among STEMI patients was 11.6%. Multivariable logistic regression analysis identified novel associations between atrial fibrillation and alcohol consumption with VF. Patients with a history of atrial fibrillation had a 2.80‐fold odds of experiencing VF before PPCI (95% CI 1.10 to 7.30). Compared with nondrinkers, patients who consumed 1 to 7 units, 8 to 14 units, or >15 units of alcohol per week had an odds ratio (OR) of 1.30 (95% CI, 0.80 to 2.20), 2.30 (95% CI, 1.20 to 4.20), or 3.30 (95% CI, 1.80 to 5.90), respectively, for VF. Previously reported associations for preinfarction angina (OR 0.46; 95% CI 0.32 to 0.67), age of <60 years (OR 1.75; 95% CI 1.20 to 2.60), anterior infarction (OR 2.10; 95% CI 1.40 to 3.00), preprocedural thrombolysis in myocardial infarction flow grade 0 (OR 1.65; 95% CI 1.14 to 2.40), and family history of sudden death (OR 1.60; 95% CI 1.10 to 2.40) were all associated with VF. Conclusion: Several easily assessed risk factors were associated with VF occurring out‐of‐hospital or on arrival at the emergency room before PPCI in STEMI patients, thus providing potential avenues for investigation regarding improved identification and prevention of life‐threatening ventricular arrhythmias.
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    Obesity, Physical Activity, and Their Interaction in Incident Atrial Fibrillation in Postmenopausal Women
    (Blackwell Publishing Ltd, 2014) Azarbal, Farnaz; Stefanick, Marcia L.; Salmoirago‐Blotcher, Elena; Manson, JoAnn; Albert, Christine; LaMonte, Michael J.; Larson, Joseph C.; Li, Wenjun; Martin, Lisa W.; Nassir, Rami; Garcia, Lorena; Assimes, Themistocles L.; Tharp, Katie M.; Hlatky, Mark A.; Perez, Marco V.
    Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased risk of stroke and death. Obesity is an independent risk factor for AF, but modifiers of this risk are not well known. We studied the roles of obesity, physical activity, and their interaction in conferring risk of incident AF. Methods and Results: The Women's Health Initiative (WHI) Observational Study was a prospective observational study of 93 676 postmenopausal women followed for an average of 11.5 years. Incident AF was identified using WHI‐ascertained hospitalization records and diagnostic codes from Medicare claims. A multivariate Cox's hazard regression model adjusted for demographic and clinical risk factors was used to evaluate the interaction between obesity and physical activity and its association with incident AF. After exclusion of women with prevalent AF, incomplete data, or underweight body mass index (BMI), 9792 of the remaining 81 317 women developed AF. Women were, on average, 63.4 years old, 7.8% were African American, and 3.6% were Hispanic. Increased BMI (hazard ratio [HR], 1.12 per 5‐kg/m2 increase; 95% confidence interval [CI], 1.10 to 1.14) and reduced physical activity (>9 vs. 0 metabolic equivalent task hours per week; HR, 0.90; 95% CI, 0.85 to 0.96) were independently associated with higher rates of AF after multivariate adjustment. Higher levels of physical activity reduced the AF risk conferred by obesity (interaction P=0.033). Conclusions: Greater physical activity is associated with lower rates of incident AF and modifies the association between obesity and incident AF.
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    Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation: The AFGen Consortium
    (Public Library of Science, 2016) Norby, Faye L.; Eryd, Samuel Adamsson; Niemeijer, Maartje N.; Rose, Lynda M.; Smith, Albert V.; Yin, Xiaoyan; Agarwal, Sunil K.; Arking, Dan E.; Chasman, Daniel L.; Chen, Lin Y.; Eijgelsheim, Mark; Engström, Gunnar; Franco, Oscar H.; Heeringa, Jan; Hindy, George; Hofman, Albert; Lutsey, Pamela L.; Magnani, Jared W.; McManus, David D.; Orho-Melander, Marju; Pankow, James S.; Rukh, Gull; Schulz, Christina-Alexandra; Uitterlinden, André G.; Albert, Christine; Benjamin, Emelia J.; Gudnason, Vilmundur; Smith, J. Gustav; Stricker, Bruno H. C.; Alonso, Alvaro
    Background: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts. Methods: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score. Results: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98–1.03); 0.98 (0.96–1.01); 0.98 (0.95–1.02); 0.99 (0.97–1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97–1.03); 1.01 (0.99–1.04). Conclusions: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.