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Glynn, Robert

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Glynn

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Glynn, Robert
Author's Publications: search.filters.isAuthorOfPublication.63a10458-6805-4bc7-8f03-e538b1bf3db0

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Now showing 1 - 10 of 23
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    Association Between High-Sensitivity C-Reactive Protein and Total Stroke by Hypertensive Status Among Men
    (John Wiley & Sons, Ltd, 2015) Jimenez, Monik; Rexrode, Kathryn; Glynn, Robert; Ridker, Paul; Gaziano, J Michael; Sesso, Howard
    Background: High-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, may promote atherosclerosis, particularly among adults with elevated blood pressure; however, data are sparse. We examined the association between hsCRP concentrations and risk of total stroke by hypertension status (normotension, prehypertension, and hypertension) among men in the Physicians’ Health Study (PHS). Methods and Results: Blood samples were collected (1996–1997) and assayed for hsCRP among 10 456 initially healthy men from PHS I and PHS II and followed from 1997 to 2012. Self-reported hypertension status, cardiovascular risk factors, lifestyle, and alcohol consumption were obtained from the baseline questionnaire prior to randomization in PHS II. Strokes were updated approximately annually and confirmed by medical records according to the National Survey of Stroke criteria. Multivariable Cox models were used. We observed 395 incident total strokes over 115 791 person-years. In analyses adjusted for potential confounders and stroke risk factors, clinically elevated hsCRP (>3 mg/L) was associated with a 40% significantly greater hazard of total stroke compared with hsCRP <1 mg/L (hazard ratio 1.40, 95% CI 1.06 to 1.87; Ptrend=0.01). Additional adjustment for blood pressure and biomarkers associated with cardiovascular risk marginally attenuated the estimates. Results were similar by hypertension status, although not statistically significant among normotensive and prehypertensive participants due to limited events. Conclusions: Elevated hsCRP levels were associated with a greater risk of total stroke, even after adjustment for potential confounders and cardiovascular risk factors. Risk of total stroke was significantly higher among hypertensive men with elevated hsCRP compared with normotensive men with low hsCRP.
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    Residual Risk of Atherosclerotic Cardiovascular Events in Relation to Reductions in Very‐Low‐Density Lipoproteins
    (John Wiley and Sons Inc., 2017) Lawler, Patrick R.; Akinkuolie, Akintunde; Harada, Paulo; Glynn, Robert; Chasman, Daniel; Ridker, Paul; Mora, Samia
    Background: It is uncertain whether pharmacological reductions in very‐low‐density lipoproteins (VLDLs), and their component triglyceride and cholesterol could reduce residual risk of atherosclerotic cardiovascular disease (ASCVD) events among individuals in whom low‐density lipoprotein cholesterol (LDL‐C) has been adequately lowered. We examined whether individuals with greater on‐statin reductions in VLDL‐related measures—beyond reductions in LDL‐C—were at further reduced risk of ASCVD. Methods and Results: In 9423 participants in the JUPITER (Justification for the Use of Statins in Prevention) trial (NCT00239681), at baseline and on statin we measured standard lipids, 400‐MHz proton nuclear magnetic resonance spectroscopy‐measured VLDL particle subclasses (small, medium, and large VLDL lipoprotein particle concentration), and total VLDL cholesterol mass. Compared with individuals allocated to placebo, we examined risk of incident ASCVD (N=211) among statin‐allocated participants who achieved minimal (
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    Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low‐Density Lipoprotein Cholesterol
    (John Wiley and Sons Inc., 2017) Lawler, Patrick R.; Akinkuolie, Akintunde; Chu, Audrey Y.; Shah, Svati H.; Kraus, William E.; Craig, Damian; Padmanabhan, Latha; Glynn, Robert; Ridker, Paul; Chasman, Daniel; Mora, Samia
    Background: Levels of LDL (low‐density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid‐related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (<130 mg/dL) LDL cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations. Methods and Results: We performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of LDL and VLDL (very low‐density lipoprotein) particle subclasses in 11 984 JUPITER trial participants (NCT00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%CI] per SD increment) among placebo‐allocated participants was associated with total LDL particles (1.19 [1.02, 1.38]) and total VLDL particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non–high‐density lipoprotein cholesterol, and triglycerides, but not LDL‐c. Rosuvastatin reduced LDL measures but had variable effects on triglyceride and VLDL measures. On‐statin levels of the smallest VLDL particle subclass were associated with a 68% per‐SD (adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk—this risk was related to VLDL cholesterol and not triglyceride or larger VLDL particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key VLDL measures (Harrell C‐index 0.780 versus 0.712; P<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (CATHGEN), similar patterns of lipoprotein‐related risk were observed. Conclusions: Atherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when LDL cholesterol was low. VLDL lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
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    Prediction Score for Anticoagulation Control Quality Among Older Adults
    (John Wiley and Sons Inc., 2017) Lin, Kueiyu Joshua; Singer, Daniel; Glynn, Robert; Blackley, Suzanne; Zhou, Li; Liu, Jun; Dube, Gina; Oertel, Lynn B.; Schneeweiss, Sebastian
    Background: Time in the therapeutic range (TTR) is associated with the effectiveness and safety of vitamin K antagonist (VKA) therapy. To optimize prescribing of VKA, we aimed to develop and validate a prediction model for TTR in older adults taking VKA for nonvalvular atrial fibrillation and venous thromboembolism. Methods and Results: The study cohort comprised patients aged ≥65 years who were taking VKA for atrial fibrillation or venous thromboembolism and who were identified in the 2 US electronic health record databases linked with Medicare claims data from 2007 through 2014. With the predictors identified from a systematic review and clinical knowledge, we built a prediction model for TTR, using one electronic health record system as the training set and the other as the validation set. We compared the performance of the new models to that of a published prediction score for TTR, SAMe‐TT 2R2. Based on 1663 patients in the training set and 1181 in the validation set, our optimized score included 42 variables and the simplified model included 7 variables, abbreviated as PROSPER (Pneumonia, Renal dysfunction, Oozing blood [prior bleeding], Staying in hospital ≥7 days, Pain medication use, no Enhanced [structured] anticoagulation services, Rx for antibiotics). The PROSPER score outperformed SAMe‐TT 2R2 when predicting both TTR ≥70% (area under the receiver operating characteristic curve 0.67 versus 0.55) and the thromboembolic and bleeding outcomes (area under the receiver operating characteristic curve 0.62 versus 0.52). Conclusions: Our geriatric TTR score can be used as a clinical decision aid to select appropriate candidates to receive VKA therapy and as a research tool to address confounding and treatment effect heterogeneity by anticoagulation quality.
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    Risk of Ischemic Cerebrovascular and Coronary Events in Adult Users of Anticonvulsant Medications in Routine Care Settings
    (Blackwell Publishing Ltd, 2013) Patorno, Elisabetta; Glynn, Robert; Hernandez‐Diaz, Sonia; Avorn, Jerome; Wahl, Peter M.; Bohn, Rhonda L.; Mines, Daniel; Liu, Jun; Schneeweiss, Sebastian
    Background: Older‐generation anticonvulsants that highly induce cytochrome P450 enzyme system activity produce metabolic abnormalities that may increase cardiovascular risk. The objective of this study was to evaluate the risk of ischemic cerebrovascular and coronary events in adult new users of anticonvulsants that highly induce cytochrome P450 activity compared with other anticonvulsant agents, as observed in a routine care setting. Methods and Results: This was a cohort study of patients 40 to 64 years old from the HealthCore Integrated Research Database who had initiated an anticonvulsant medication between 2001 and 2006 and had no recorded major coronary or cerebrovascular condition in the 6 months before treatment initiation. Propensity score (PS) matching was used to evaluate ischemic cerebrovascular and coronary risk among anticonvulsant new users. High‐dimensional propensity score (hdPS)–matched analyses were used to confirm adjusted findings. The study identified 913 events in 166 031 unmatched new treatment episodes with anticonvulsant drugs. In a PS‐matched population of 22 864 treatment episodes, the rate ratio (RR) for ischemic coronary or cerebrovascular events associated with highly inducing agents versus other agents was 1.22 (95% CI, 0.90‐1.65). The RR moved to 0.99 (95% CI, 0.73‐1.33) with adjustment for hdPS matching (RR, 1.47; 95% CI, 0.95‐2.28 for cerebrovascular events; RR, 0.70; 95% CI, 0.47‐1.05 for coronary events). Conclusions: In this exploratory analysis, there was no evidence of a consistent and statistically significant effect of initiating anticonvulsants that highly induce cytochrome P450 activity on ischemic coronary or cerebrovascular outcomes compared with other agents, given routine care utilization patterns.
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    Association between adiponectin and heart failure risk in the Physicians' Health Study
    (2012) Djousse, Luc; Wilk, Jemma; Hanson, Naomi Q.; Glynn, Robert; Tsai, Michael Y.; Gaziano, J. Michael
    Limited data are available on the association between adiponectin and incident heart failure. In the current ancillary study to the Physicians' Health Study, we used a prospective nested-case control design to examine whether plasma adiponectin concentration was related to the risk of heart failure. We selected 787 incident heart failure cases and 787 matched controls for the current analysis. Each control was selected using a risk set sampling technique at the time of the occurrence of the index case and matched on year of birth, age at blood collection, and race. Adiponectin was measured using ELISA. Heart failure occurrence was self-reported in annual follow-up questionnaire. Validation of self-reported heart failure in this cohort has been published. The mean age was 58.7 years. In a conditional logistic regression adjusting for age, race, time of blood collection, year of birth, hypertension, atrial fibrillation, smoking, alcohol intake, and exercise, estimates of the relative risk (95% confidence interval) were 1.0 (ref), 0.74 (0.53–1.04), 0.67 (0.48–0.94), 0.70 (0.50–0.99), and 0.92 (0.65–1.30) from the lowest to the highest quintile of adiponectin, respectively, p for quadratic trend 0.004. Additional adjustment for potential mediating factors including diabetes, C-reactive protein, and body mass index led to the attenuation of the estimate of effect [1.0 (ref), 0.81 (0.57–1.15), 0.75 (0.53–1.06), 0.83 (0.58–1.18), and 1.26 (0.87–1.81) across consecutive quintiles of adiponectin]. Our data are consistent with a J-shaped association between total adiponectin and the risk of heart failure among US male physicians.
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    Time-Dependent Propensity Score for Assessing the Effect of Vaccine Exposure on Pregnancy Outcomes through Pregnancy Exposure Cohort Studies
    (Molecular Diversity Preservation International (MDPI), 2014) Xu, Ronghui; Luo, Yunjun; Glynn, Robert; Johnson, Diana; Jones, Kenneth L.; Chambers, Christina
    Women are advised to be vaccinated for influenza during pregnancy and may receive vaccine at any time during their pregnancy. In observational studies evaluating vaccine safety in pregnancy, to account for such time-varying vaccine exposure, a time-dependent predictor can be used in a proportional hazards model setting for outcomes such as spontaneous abortion or preterm delivery. Also, due to the observational nature of pregnancy exposure cohort studies and relatively low event rates, propensity score (PS) methods are often used to adjust for potential confounders. Using Monte Carlo simulation experiments, we compare two different ways to model the PS for vaccine exposure: (1) logistic regression treating the exposure status as binary yes or no; (2) Cox regression treating time to exposure as time-to-event. Coverage probability of the nominal 95% confidence interval for the exposure effect is used as the main measure of performance. The performance of the logistic regression PS depends largely on how the exposure data is generated. In contrast, the Cox regression PS consistently performs well across the different data generating mechanisms that we have considered. In addition, the Cox regression PS allows adjusting for potential time-varying confounders such as season of the year or exposure to additional vaccines. The application of the Cox regression PS is illustrated using data from a recent study of the safety of pandemic H1N1 influenza vaccine during pregnancy.
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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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    Baseline Characteristics of Participants in the JUPITER Trial, A Randomized Placebo-Controlled Primary Prevention Trial of Statin Therapy Among Individuals With Low Low-Density Lipoprotein Cholesterol and Elevated High-Sensitivity C-Reactive Protein
    (Elsevier BV, 2007) Ridker, Paul; Fonseca, Francisco A.H.; Genest, Jacques; Gotto, Antonio M.; Kastelein, John J.P.; Khurmi, Nardev S.; Koenig, Wolfgang; Libby, Peter; Lorenzatti, Alberto J.; Nordestgaard, Borge G.; Shepherd, James; Willerson, James T.; Glynn, Robert
    The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a randomized, double-blind, placebo-controlled primary prevention trial of statin therapy among persons with average to low levels of low-density lipoprotein (LDL) cholesterol who are at increased cardiovascular risk due to elevated plasma concentrations of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP). A total of 17,802 persons with LDL cholesterol <130 mg/dl (3.36 mmol/L) and hs-CRP ≥2 mg/L were recruited from 26 countries and randomly allocated to 20 mg/day rosuvastatin or placebo. In contrast to previous studies of statin therapy in primary prevention, JUPITER is evaluating a group with modest plasma concentrations of LDL cholesterol (median 108 mg/dl, interquartile range 94 to 119). Further, the trial includes 6,801 women (38.2%) and 5,577 participants with metabolic syndrome (32.1%). Thus, in addition to broadening our understanding of statin therapy and inflammation, the JUPITER trial will provide important and clinically relevant information on primary prevention among patients who do not currently qualify for lipid-lowering therapy. In conclusion, as 20 mg of rosuvastatin can reduce LDL cholesterol by up to 50%, JUPITER will also provide crucial safety data for several thousand patients who should achieve LDL cholesterol levels <50 mg/dl on a long-term basis.
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    Relation of Baseline High-Sensitivity C-Reactive Protein Level to Cardiovascular Outcomes With Rosuvastatin in the Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)
    (Elsevier BV, 2010) Ridker, Paul; MacFadyen, Jean; Libby, Peter; Glynn, Robert
    In the Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), random allocation of rosuvastatin compared to placebo among primary prevention patients with a low-density lipoprotein cholesterol level of <130 mg/dl and a high-sensitivity C-reactive protein (hs-CRP) level of ≥2 mg/L resulted in a highly significant 44% reduction in major vascular events. However, the relation of baseline hs-CRP levels to risk within JUPITER has not previously been described and has been an area of controversy for study interpretation. As reported in the present study for the first time, despite enrolling patients with a constrained range of values, increasing baseline hs-CRP levels within JUPITER were nonetheless associated with increasing vascular risk in analyses treating hs-CRP as a continuous variable, as an ordinal variable, and as a threshold variable. As anticipated, the relative risk reduction associated with rosuvastatin was similar in magnitude across the tertile and threshold levels of entry hs-CRP. In conclusion, as the absolute risk increased with increasing hs-CRP, the absolute risk reduction associated with rosuvastatin within JUPITER was also greatest among those with the greatest entry hs-CRP levels.