Browsing by Author "D'Agostino, Ralph B"

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    ItemOpen Access
    A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.
    (J Gerontol A Biol Sci Med Sci, 2010-05) Newman, Anne B; Walter, Stefan; Lunetta, Kathryn L; Garcia, Melissa E; Slagboom, P Eline; Christensen, Kaare; Arnold, Alice M; Aspelund, Thor; Aulchenko, Yurii S; Benjamin, Emelia J; Christiansen, Lene; D'Agostino, Ralph B; Fitzpatrick, Annette L; Franceschini, Nora; Glazer, Nicole L; Gudnason, Vilmundur; Hofman, Albert; Kaplan, Robert; Karasik, David; Kelly-Hayes, Margaret; Kiel, Douglas P; Launer, Lenore J; Marciante, Kristin D; Massaro, Joseph M; Miljkovic, Iva; Nalls, Michael A; Hernandez, Dena; Psaty, Bruce M; Rivadeneira, Fernando; Rotter, Jerome; Seshadri, Sudha; Smith, Albert V; Taylor, Kent D; Tiemeier, Henning; Uh, Hae-Won; Uitterlinden, André G; Vaupel, James W; Walston, Jeremy; Westendorp, Rudi GJ; Harris, Tamara B; Lumley, Thomas; van Duijn, Cornelia M; Murabito, Joanne M
    BACKGROUND: Genome-wide association studies (GWAS) may yield insights into longevity. METHODS: We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. RESULTS: There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. CONCLUSION: Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings.
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    C-reactive protein, fibrinogen, and cardiovascular disease prediction.
    (The New England journal of medicine, 2012-10) Emerging Risk Factors Collaboration; Kaptoge, Stephen; Di Angelantonio, Emanuele; Pennells, Lisa; Wood, Angela M; White, Ian R; Gao, Pei; Walker, Matthew; Thompson, Alexander; Sarwar, Nadeem; Caslake, Muriel; Butterworth, Adam S; Amouyel, Philippe; Assmann, Gerd; Bakker, Stephan JL; Barr, Elizabeth LM; Barrett-Connor, Elizabeth; Benjamin, Emelia J; Björkelund, Cecilia; Brenner, Hermann; Brunner, Eric; Clarke, Robert; Cooper, Jackie A; Cremer, Peter; Cushman, Mary; Dagenais, Gilles R; D'Agostino, Ralph B; Dankner, Rachel; Davey-Smith, George; Deeg, Dorly; Dekker, Jacqueline M; Engström, Gunnar; Folsom, Aaron R; Fowkes, F Gerry R; Gallacher, John; Gaziano, J Michael; Giampaoli, Simona; Gillum, Richard F; Hofman, Albert; Howard, Barbara V; Ingelsson, Erik; Iso, Hiroyasu; Jørgensen, Torben; Kiechl, Stefan; Kitamura, Akihiko; Kiyohara, Yutaka; Koenig, Wolfgang; Kromhout, Daan; Kuller, Lewis H; Lawlor, Debbie A; Meade, Tom W; Nissinen, Aulikki; Nordestgaard, Børge G; Onat, Altan; Panagiotakos, Demosthenes B; Psaty, Bruce M; Rodriguez, Beatriz; Rosengren, Annika; Salomaa, Veikko; Kauhanen, Jussi; Salonen, Jukka T; Shaffer, Jonathan A; Shea, Steven; Ford, Ian; Stehouwer, Coen DA; Strandberg, Timo E; Tipping, Robert W; Tosetto, Alberto; Wassertheil-Smoller, Sylvia; Wennberg, Patrik; Westendorp, Rudi G; Whincup, Peter H; Wilhelmsen, Lars; Woodward, Mark; Lowe, Gordon DO; Wareham, Nicholas J; Khaw, Kay-Tee; Sattar, Naveed; Packard, Chris J; Gudnason, Vilmundur; Ridker, Paul M; Pepys, Mark B; Thompson, Simon G; Danesh, John
    There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events.We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen.The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P<0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (<10%), "intermediate" (10% to <20%), and "high" (≥20%) (P<0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of ≥20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years.In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.).
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    Deriving Real-World Insights From Real-World Data: Biostatistics to the Rescue.
    (Annals of internal medicine, 2018-09) Pencina, Michael J; Rockhold, Frank W; D'Agostino, Ralph B
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    Effect at One Year of Adjuvant Trastuzumab for HER2+ Breast Cancer Combined with Radiation or an Anthracycline on Left Ventricular Ejection Fraction.
    (The American journal of cardiology, 2020-06) Andersen, Mousumi M; Ayala-Peacock, Diandra; Bowers, Jessie; Kooken, Banks W; D'Agostino, Ralph B; Jordan, Jennifer H; Vasu, Sujethra; Thomas, Alexandra; Klepin, Heidi D; Brown, Doris R; Hundley, W Gregory
    To determine the impact of radiation therapy (XRT) in addition to trastuzumab (TZB) adjuvant chemotherapy for HER2+ breast cancer on left ventricular systolic function, we assessed demographics, oncologic treatment history including XRT exposure, and serial measurements of left ventricular ejection fraction (LVEF) in 135 consecutively identified women receiving TZB for treatment of adjuvant breast cancer. Longitudinal mixed effects models were fit to identify baseline to treatment changes in LVEF among those receiving TZB with or without concomitant anthracycline or XRT. Women averaged 53 ± 3 years in age, 77% were white, 62% patients had 1 or more cardiovascular risk factors at baseline, and mean duration of TZB was 11 ± 5 months. Seventy-seven women were treated with XRT and received between 4000 and 5500 cGy of radiation. The LVEF declined by an average of 3.4% after 1 year for those in the study. Relative to baseline upon completion of adjuvant TZB, LVEF remained reduced for those receiving anthracycline with or without XRT (p=0.002 for both), or XRT alone (p=0.002), but not in those without these therapies. Amongst patients treated only with XRT and TZB, LVEF declined 3.1% on average in those with left-sided disease and 6.9% on average in those with right-sided disease (p= 0.06, p= 0.008 respectively). Among women receiving TZB for adjuvant treatment of HER-2 positive breast cancer, the administration of XRT, anthracycline, or the combination of the 2 is associated with a persistent post-treatment as opposed to a temporary treatment related decline in LVEF.
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    Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies.
    (European heart journal, 2019-02) Pennells, Lisa; Kaptoge, Stephen; Wood, Angela; Sweeting, Mike; Zhao, Xiaohui; White, Ian; Burgess, Stephen; Willeit, Peter; Bolton, Thomas; Moons, Karel GM; van der Schouw, Yvonne T; Selmer, Randi; Khaw, Kay-Tee; Gudnason, Vilmundur; Assmann, Gerd; Amouyel, Philippe; Salomaa, Veikko; Kivimaki, Mika; Nordestgaard, Børge G; Blaha, Michael J; Kuller, Lewis H; Brenner, Hermann; Gillum, Richard F; Meisinger, Christa; Ford, Ian; Knuiman, Matthew W; Rosengren, Annika; Lawlor, Debbie A; Völzke, Henry; Cooper, Cyrus; Marín Ibañez, Alejandro; Casiglia, Edoardo; Kauhanen, Jussi; Cooper, Jackie A; Rodriguez, Beatriz; Sundström, Johan; Barrett-Connor, Elizabeth; Dankner, Rachel; Nietert, Paul J; Davidson, Karina W; Wallace, Robert B; Blazer, Dan G; Björkelund, Cecilia; Donfrancesco, Chiara; Krumholz, Harlan M; Nissinen, Aulikki; Davis, Barry R; Coady, Sean; Whincup, Peter H; Jørgensen, Torben; Ducimetiere, Pierre; Trevisan, Maurizio; Engström, Gunnar; Crespo, Carlos J; Meade, Tom W; Visser, Marjolein; Kromhout, Daan; Kiechl, Stefan; Daimon, Makoto; Price, Jackie F; Gómez de la Cámara, Agustin; Wouter Jukema, J; Lamarche, Benoît; Onat, Altan; Simons, Leon A; Kavousi, Maryam; Ben-Shlomo, Yoav; Gallacher, John; Dekker, Jacqueline M; Arima, Hisatomi; Shara, Nawar; Tipping, Robert W; Roussel, Ronan; Brunner, Eric J; Koenig, Wolfgang; Sakurai, Masaru; Pavlovic, Jelena; Gansevoort, Ron T; Nagel, Dorothea; Goldbourt, Uri; Barr, Elizabeth LM; Palmieri, Luigi; Njølstad, Inger; Sato, Shinichi; Monique Verschuren, WM; Varghese, Cherian V; Graham, Ian; Onuma, Oyere; Greenland, Philip; Woodward, Mark; Ezzati, Majid; Psaty, Bruce M; Sattar, Naveed; Jackson, Rod; Ridker, Paul M; Cook, Nancy R; D'Agostino, Ralph B; Thompson, Simon G; Danesh, John; Di Angelantonio, Emanuele; Emerging Risk Factors Collaboration
    AIMS:There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. METHODS AND RESULTS:Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. CONCLUSION:Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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    Myocardial Function in Premenopausal Women Treated With Ovarian Function Suppression and an Aromatase Inhibitor.
    (JNCI cancer spectrum, 2021-08) Jordan, Jennifer H; D'Agostino, Ralph B; Ansley, Katherine; Douglas, Emily; Melin, Susan; Sorscher, Steven; Vasu, Sujethra; Park, Sung; Kotak, Anuj; Romitti, Paul A; O'Connell, Nathanial S; Hundley, William G; Thomas, Alexandra
    Premenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) with aromatase inhibitor therapy; however, abrupt menopause induction, together with further decrements in estrogen exposure through aromatase inhibition, may affect cardiovascular microcirculatory function. We examined adenosine-induced changes in left ventricular (LV) myocardial T1, a potential subclinical marker of LV microcirculatory function in premenopausal women undergoing treatment for breast cancer. Twenty-one premenopausal women (14 with HR-positive breast cancer receiving OFS with an aromatase inhibitor and 7 comparator women with triple-negative breast cancer [TNBC] who had completed primary systemic therapy) underwent serial resting and adenosine cardiovascular magnetic resonance imaging measurements of LV myocardial T1 and LV volumes, mass, and ejection fraction. All statistical tests were 2-sided. After a median of 4.0 months (range = 3.1-5.7 months), the stress to resting ratio of LV myocardial T1 declined in women with HR-positive breast cancer (-1.3%, 95% confidence interval [CI] = -3.4% to 0.7%) relative to those with TNBC (3.2%, 95% CI = -1.2% to 7.6%, P = .02). After accounting for age, LV stroke volume, LV ejection fraction, diastolic blood pressure, and breast cancer subtype women with HR-positive breast cancer experienced a blunted T1 response after adenosine relative to women with TNBC (difference = -4.7%, 95% CI = -7.3% to -2.1%, Pdifference = .002). Over the brief interval examined, women with HR-positive breast cancer receiving OFS with an aromatase inhibitor experienced reductions in adenosine-associated changes in LV myocardial T1 relative to women who received nonhormonal therapy for TNBC. These findings suggest a possible adverse impact on LV myocardial microcirculatory function in premenopausal women with breast cancer receiving hormone deprivation therapy.