Publications by authors named "Veronique L Roger"

343 Publications

Prevalence of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction.

JAMA Cardiol 2021 08 25. Epub 2021 Aug 25.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

Importance: Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized.

Objective: To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening.

Design, Setting, And Participants: This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening. Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort).

Exposures: Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis.

Main Outcomes And Measures: The ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex.

Results: A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 150 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 150 men (10.0%; 95% CI, 5.7%-16.1%) and 3 of 136 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002).

Conclusions And Relevance: In this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.
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http://dx.doi.org/10.1001/jamacardio.2021.3070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387947PMC
August 2021

Advanced Heart Failure Epidemiology and Outcomes: A Population-Based Study.

JACC Heart Fail 2021 Oct 11;9(10):722-732. Epub 2021 Aug 11.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Objectives: The goal of this study was to evaluate the prevalence, characteristics, and outcomes of patients with advanced heart failure (HF) in a geographically defined population.

Background: Some patients with HF progress to advanced HF, characterized by debilitating HF symptoms refractory to therapy. Limited data are available on the epidemiology and outcomes of patients with advanced HF.

Methods: This was a population-based cohort study of all Olmsted County, Minnesota, adults with and without HF from 2007 to 2017. The 2018 European Society of Cardiology advanced HF diagnostic criteria were operationalized and applied to all patients with HF. Hospitalization and mortality in advanced HF, overall and according to ejection fraction (EF) type (reduced EF <40% [HFrEF], mid-range EF 40%-49% [HFmrEF], and preserved EF ≥50% [HFpEF]) were examined using Andersen-Gill and Cox models.

Results: Of 6,836 adults with HF, 936 (13.7%) met criteria for advanced HF. The prevalence of advanced HF increased with age and was higher in men. At advanced HF diagnosis, 396 (42.3%) patients had HFrEF, 134 (14.3%) had HFmrEF, and 406 (43.4%) had HFpEF. The median (interquartile range) time from advanced HF diagnosis to death was 12.2 months (3.7-29.9 months). The mean rate of hospitalization was 2.91 (95% CI: 2.78-3.06) per person-year in the first year after advanced HF diagnosis. There were no differences in risks of all-cause mortality or hospitalization by EF. Patients with advanced HFpEF were at lower risk for cardiovascular mortality compared with advanced HFrEF (HR: 0.79; 95% CI: 0.65-0.97).

Conclusions: In this population-based study, more than one-half of patients with advanced HF had mid-range or preserved EF, and survival was poor regardless of EF.
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http://dx.doi.org/10.1016/j.jchf.2021.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487916PMC
October 2021

The Reply.

Am J Med 2021 07;134(7):e443-e444

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn; Department of Health Sciences Research, Mayo Clinic, Rochester, Minn. Electronic address:

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http://dx.doi.org/10.1016/j.amjmed.2021.03.020DOI Listing
July 2021

Longitudinal cohorts for harnessing the electronic health record for disease prediction in a US population.

BMJ Open 2021 06 8;11(6):e044353. Epub 2021 Jun 8.

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA

Purpose: The depth and breadth of clinical data within electronic health record (EHR) systems paired with innovative machine learning methods can be leveraged to identify novel risk factors for complex diseases. However, analysing the EHR is challenging due to complexity and quality of the data. Therefore, we developed large electronic population-based cohorts with comprehensive harmonised and processed EHR data.

Participants: All individuals 30 years of age or older who resided in Olmsted County, Minnesota on 1 January 2006 were identified for the discovery cohort. Algorithms to define a variety of patient characteristics were developed and validated, thus building a comprehensive risk profile for each patient. Patients are followed for incident diseases and ageing-related outcomes. Using the same methods, an independent validation cohort was assembled by identifying all individuals 30 years of age or older who resided in the largely rural 26-county area of southern Minnesota and western Wisconsin on 1 January 2013.

Findings To Date: For the discovery cohort, 76 255 individuals (median age 49; 53% women) were identified from which a total of 9 644 221 laboratory results; 9 513 840 diagnosis codes; 10 924 291 procedure codes; 1 277 231 outpatient drug prescriptions; 966 136 heart rate measurements and 1 159 836 blood pressure (BP) measurements were retrieved during the baseline time period. The most prevalent conditions in this cohort were hyperlipidaemia, hypertension and arthritis. For the validation cohort, 333 460 individuals (median age 54; 52% women) were identified and to date, a total of 19 926 750 diagnosis codes, 10 527 444 heart rate measurements and 7 356 344 BP measurements were retrieved during baseline.

Future Plans: Using advanced machine learning approaches, these electronic cohorts will be used to identify novel sex-specific risk factors for complex diseases. These approaches will allow us to address several challenges with the use of EHR.
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http://dx.doi.org/10.1136/bmjopen-2020-044353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190051PMC
June 2021

Recent trends in cardiovascular disease deaths: a state specific perspective.

BMC Public Health 2021 06 1;21(1):1031. Epub 2021 Jun 1.

Department of Quantitative Health Sciences, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.

Background: The rate of decline in cardiovascular disease (CVD) mortality has lessened nationally. How these findings apply to specific states or causes of CVD deaths is not known. Examining these trends at the state level is important to plan local interventions.

Methods: We analyzed CVD mortality trends in Minnesota (MN) using the U.S. Centers for Disease Control and Prevention (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Trends were analyzed by age, sex, type of CVD and location of death.

Results: CVD mortality rates in MN declined in 2000-2009 and then leveled off in 2010-2018, paralleling national rates. Age- and sex-adjusted CVD mortality decreased by 3.7% per year in 2000-2009 (average annual percent changes [AAPC]: -3.7; 95% CI: - 4.8, - 2.6) with no change observed in 2010-2018. Those aged 65-84 years had the most rapid early decline in CVD mortality (AAPC: -5.9, 95% CI: - 6.2, - 5.7) and had less improvement in 2010-2018 (AAPC: -1.8, 95% CI: - 2.2, - 1.5), and the younger age group (25-64 years) now experiences the most adverse trends (AAPC: 1.2, 95% CI: 0.7-1.8). Coronary heart disease (CHD) and cerebrovascular disease had the largest relative decreases in mortality in 2000-2009 (CHD AAPC: -5.2; 95% CI: - 6.5,-3.9; cerebrovascular disease AAPC: -4.4, 95% CI: - 5.2, - 3.6) with no change 2010-2018. Heart failure (HF)/cardiomyopathy followed similar trends with a 2.5% decrease (AAPC 95% CI: - 3.5, - 1.5) per year in 2000-2009 and no change in 2010-2018. Deaths from other CVD also decreased in the early time period (AAPC: -1.6, 95% CI: - 2.7, - 0.5) but increased in 2010-2018 (AAPC: 1.9, 95% CI: 0.5, 3.3). In- and out-of-hospital death rates improved in 2000-2009 with a slowing in improvement for in-hospital death and no further improvement for out-of-hospital death in 2010-2018.

Conclusion: Concerning CVD mortality trends occurred in MN. In the most recent decade (2010-2018) mortality from all CVD subtypes plateaued or even increased. CVD mortality among the younger age groups increased as well. These data are congruent with adverse national trends supporting their generalizability. These adverse trends underscore the urgent need for CVD prevention and treatment, as well as continued surveillance to assess progress at the state and national level.
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http://dx.doi.org/10.1186/s12889-021-11072-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169395PMC
June 2021

Recommendations for Statistical Reporting in Cardiovascular Medicine: A Special Report From the American Heart Association.

Circulation 2021 Jul 25;144(4):e70-e91. Epub 2021 May 25.

Department of Cardiovascular Diseases Medicine, Mayo Clinic College of Medicine, Rochester, MN (V.L.R.).

Statistical analyses are a crucial component of the biomedical research process and are necessary to draw inferences from biomedical research data. The application of sound statistical methodology is a prerequisite for publication in the American Heart Association (AHA) journal portfolio. The objective of this document is to summarize key aspects of statistical reporting that might be most relevant to the authors, reviewers, and readership of AHA journals. The AHA Scientific Publication Committee convened a task force to inventory existing statistical standards for publication in biomedical journals and to identify approaches suitable for the AHA journal portfolio. The experts on the task force were selected by the AHA Scientific Publication Committee, who identified 12 key topics that serve as the section headers for this document. For each topic, the members of the writing group identified relevant references and evaluated them as a resource to make the standards summarized herein. Each section was independently reviewed by an expert reviewer who was not part of the task force. Expert reviewers were also permitted to comment on other sections if they chose. Differences of opinion were adjudicated by consensus. The standards presented in this report are intended to serve as a guide for high-quality reporting of statistical analyses methods and results.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055393DOI Listing
July 2021

Patient perceptions and use of non-statin lipid lowering therapy among patients with or at risk for atherosclerotic cardiovascular disease: Insights from the PALM registry.

Clin Cardiol 2021 Jun 18;44(6):863-870. Epub 2021 May 18.

Duke Clinical Research Institute, Durham, North Carolina, USA.

Background: Non-statin lipid lowering therapies (LLTs) provide additional treatment options for patients. Use patterns and patient perceptions of non-statin LLT remain incompletely described.

Hypothesis: The guideline-recommended statin intensity remains underutilized in patients treated with and without non-statin LLT.

Methods: The PALM Registry collected LLT information on patients with or at risk of ASCVD treated at 125 US clinics in 2015. We compared patient perceptions, lipid levels and statin use among patients treated with and without non-statin LLT.

Results: Among 7720 patients, 1930 (25.0%) were treated with a non-statin LLT (1249 fish oil, 417 fibrates, 329 ezetimibe, 196 niacin). Concurrent statin treatment occurred in 73.7%, of which 45.4% were dosed under the guideline-recommended intensity. Compared with patients on statin alone, patients receiving both a statin and non-statin LLT (n = 1423) were more likely to be male, white race and to perceive themselves as higher risk of ASCVD compared with their peers (38.5% vs. 34.9%, p = .047). Only 27.4% of patients treated with non-statin LLT alone perceived themselves at higher risk. Most (75.7%) patients treated with a non-statin LLT alone reported never being treated with a statin, despite ASCVD in 30.8% of these patients. Among those previously treated with a statin, 59.3% reported being willing to try a statin again.

Conclusions: Non-statin LLT is used in one in four patients with or at risk for ASCVD; its use is frequently in place of statin therapy or in the absence of guideline-recommended statin intensity. More work is needed to establish statins as first line therapy.
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http://dx.doi.org/10.1002/clc.23625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207979PMC
June 2021

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

N Engl J Med 2021 05 15;384(21):1981-1990. Epub 2021 May 15.

From Duke Clinical Research Institute, Duke University, Durham (W.S.J., H.M., L.M.W., M.J.P., M.T.R., H.R.R., L.H.C., A.G.S., L.G.B., B.G.H., D.F.H., L.G.Q., G.M.-G., A.F.H.), University of North Carolina at Chapel Hill, Chapel Hill (D.A.D.), and Wake Forest University School of Medicine, Winston-Salem (L.Z.) - all in North Carolina; Vanderbilt University Medical Center, Nashville (S.K., D.M., D.L.C., R.L.R.); Ochsner Health (M.B.E., R.N.R.) and Louisiana Public Health Institute (T.W.C., E.N.) - both in New Orleans; University of Kansas Medical Center, Kansas City (K.G.); University of Florida, Gainesville (R.D.A., C.J.P., E.M.H., B.R.M., E.A.S.); University of Pittsburgh Medical Center, Pittsburgh (S.K.J., K.M.M.), Penn State College of Medicine, Hershey (J.L.K.), and Temple University, Philadelphia (A.P.) - all in Pennsylvania; University of Iowa, Iowa City (S.G., D.R.); Medical College of Wisconsin, Milwaukee (J.W.), and Marshfield Clinic Research Institute, Marshfield (J.J.V.) - both in Wisconsin; Albert Einstein College of Medicine, Bronx (Y.H.G.), and Weill Cornell Medicine and New York-Presbyterian Hospital, New York (R.K.) - both in New York; Mayo Clinic, Rochester (V.L.R.), Essentia Health Heart and Vascular Center, Duluth (C.P.B.), and Allina Health and Minneapolis Heart Institute, Minneapolis (S.M.B.) - all in Minnesota; University of Utah School of Medicine (R.H.) and Intermountain Medical Center Heart Institute (K.U.K.) - both in Salt Lake City; University of Michigan, Ann Arbor (P.F.); Johns Hopkins University School of Medicine, Baltimore (D.E.F.); HealthCore, Wilmington, DE (K.H.); University of Chicago Medicine (T.S.P.) and Northwestern University Feinberg School of Medicine (D.J.F., F.S.A., A.M.K.) - both in Chicago; University of Nebraska Medical Center, Omaha (J.C.M., J.R.C.); University of California, Los Angeles, Los Angeles (D.S.B., G.C.F.), University of California, San Francisco, San Francisco (M.F.M., G.M.M.), and Stanford University School of Medicine, Stanford (R.A.H.) - all in California; University of Missouri School of Medicine, Columbia (L.R.W.); University of Colorado School of Medicine, Anschutz Medical Campus, Aurora (F.A.M.); Brigham and Women's Hospital, Harvard Medical School, Boston (E.M.A.); Chicago (D.R.D.); St. Joseph, MO (K.E.); Brighton, MI (J.G.M.); Columbia, TN (L.S.B.); Alachua, FL (D.N.Z.); Columbia, MD (T.E.M.); North Hills, CA (J.D.A.); and Metairie, LA (K.C.G.).

Background: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.

Methods: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis.

Results: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]).

Conclusions: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).
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http://dx.doi.org/10.1056/NEJMoa2102137DOI Listing
May 2021

Premature Myocardial Infarction: A Community Study.

Mayo Clin Proc Innov Qual Outcomes 2021 Apr 16;5(2):413-422. Epub 2021 Apr 16.

Departments of Health Sciences Research, Mayo Clinic, Rochester, MN.

Objective: To evaluate the trends in incident premature myocardial infarction (MI) and prevalence of cardiac risk factors in a population-based cohort.

Methods: We studied a population-based cohort of incident premature MIs among residents (MI in men aged 18-55 years and women aged 18-65 years) in Olmsted County, Minnesota, during a 26-year period from January 1, 1987 through December 31, 2012. Recurrent MI and death after incident premature MI were enumerated through September 30, 2018.

Results: Of 3276 MI cases, 850 were premature events (37.9% [322/850] women). Age-adjusted premature MI incidence rates (2012 vs 1987) declined by 39% in men (rate ratio, 0.61; 95% CI, 0.46 to 0.81]) and 61% in women (rate ratio, 0.39; 95% CI, 0.27 to 0.57). Among men with premature MI, the prevalence of hypertension, diabetes, and hyperlipidemia increased over time, whereas in women, only the prevalence of hyperlipidemia increased. During a mean follow-up of 13.3 years, there was no temporal decline in recurrent MI in men and women. Women showed 66% decreased risk for mortality (hazard ratio, 0.34; 95% CI, 0.17 to 0.68) over time, whereas men showed no change.

Conclusion: The incidence of premature MI declined over a 26-year period for both men and women. The risk factor profile of persons presenting with MI worsened over time, especially in men. Death following incident MI declined only in women. These results underscore the importance of primary prevention in young adults and of sex-specific approaches.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105506PMC
April 2021

Epidemiology of Heart Failure: A Contemporary Perspective.

Circ Res 2021 May 13;128(10):1421-1434. Epub 2021 May 13.

Department of Quantitative Health Sciences and Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN. Now at Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health. Véronique L Roger, MD, MPH is now at Chief, Epidemiology and Community Health Branch National Heart, Lung and Blood Institute, National Institutes of Health.

Designated as an emerging epidemic in 1997, heart failure (HF) remains a major clinical and public health problem. This review focuses on the most recent studies identified by searching the Medline database for publications with the subject headings HF, epidemiology, prevalence, incidence, trends between 2010 and present. Publications relevant to epidemiology and population sciences were retained for discussion in this review after reviewing abstracts for relevance to these topics. Studies of the epidemiology of HF over the past decade have improved our understanding of the HF syndrome and of its complexity. Data suggest that the incidence of HF is mostly flat or declining but that the burden of mortality and hospitalization remains mostly unabated despite significant ongoing efforts to treat and manage HF. The evolution of the case mix of HF continues to be characterized by an increasing proportion of cases with preserved ejection fraction, for which established effective treatments are mostly lacking. Major disparities in the occurrence, presentation, and outcome of HF persist particularly among younger Black men and women. These disturbing trends reflect the complexity of the HF syndrome, the insufficient mechanistic understanding of its various manifestations and presentations and the challenges of its management as a chronic disease, often integrated within a context of aging and multimorbidity. Emerging risk factors including omics science offer the promise of discovering new mechanistic pathways that lead to HF. Holistic management approaches must recognize HF as a syndemic and foster the implementation of multidisciplinary approaches to address major contributors to the persisting burden of HF including multimorbidity, aging, and social determinants of health.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.318172DOI Listing
May 2021

Biomarkers and indoor air quality: A translational research review.

J Clin Transl Sci 2020 Sep 4;5(1):e39. Epub 2020 Sep 4.

Well Living Lab, Inc., Mayo Clinic, Rochester, MN 55902, USA.

Introduction: Air pollution is linked to mortality and morbidity. Since humans spend nearly all their time indoors, improving indoor air quality (IAQ) is a compelling approach to mitigate air pollutant exposure. To assess interventions, relying on clinical outcomes may require prolonged follow-up, which hinders feasibility. Thus, identifying biomarkers that respond to changes in IAQ may be useful to assess the effectiveness of interventions.

Methods: We conducted a narrative review by searching several databases to identify studies published over the last decade that measured the response of blood, urine, and/or salivary biomarkers to variations (natural and intervention-induced) of changes in indoor air pollutant exposure.

Results: Numerous studies reported on associations between IAQ exposures and biomarkers with heterogeneity across study designs and methods. This review summarizes the responses of 113 biomarkers described in 30 articles. The biomarkers which most frequently responded to variations in indoor air pollutant exposures were high sensitivity C-reactive protein (hsCRP), von Willebrand Factor (vWF), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 1-hydroxypyrene (1-OHP).

Conclusions: This review will guide the selection of biomarkers for translational studies evaluating the impact of indoor air pollutants on human health.
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http://dx.doi.org/10.1017/cts.2020.532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057458PMC
September 2020

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

medRxiv 2021 Mar 20. Epub 2021 Mar 20.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.
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http://dx.doi.org/10.1101/2021.03.19.21253986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987050PMC
March 2021

Natural Language Processing and Machine Learning for Identifying Incident Stroke From Electronic Health Records: Algorithm Development and Validation.

J Med Internet Res 2021 03 8;23(3):e22951. Epub 2021 Mar 8.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States.

Background: Stroke is an important clinical outcome in cardiovascular research. However, the ascertainment of incident stroke is typically accomplished via time-consuming manual chart abstraction. Current phenotyping efforts using electronic health records for stroke focus on case ascertainment rather than incident disease, which requires knowledge of the temporal sequence of events.

Objective: The aim of this study was to develop a machine learning-based phenotyping algorithm for incident stroke ascertainment based on diagnosis codes, procedure codes, and clinical concepts extracted from clinical notes using natural language processing.

Methods: The algorithm was trained and validated using an existing epidemiology cohort consisting of 4914 patients with atrial fibrillation (AF) with manually curated incident stroke events. Various combinations of feature sets and machine learning classifiers were compared. Using a heuristic rule based on the composition of concepts and codes, we further detected the stroke subtype (ischemic stroke/transient ischemic attack or hemorrhagic stroke) of each identified stroke. The algorithm was further validated using a cohort (n=150) stratified sampled from a population in Olmsted County, Minnesota (N=74,314).

Results: Among the 4914 patients with AF, 740 had validated incident stroke events. The best-performing stroke phenotyping algorithm used clinical concepts, diagnosis codes, and procedure codes as features in a random forest classifier. Among patients with stroke codes in the general population sample, the best-performing model achieved a positive predictive value of 86% (43/50; 95% CI 0.74-0.93) and a negative predictive value of 96% (96/100). For subtype identification, we achieved an accuracy of 83% in the AF cohort and 80% in the general population sample.

Conclusions: We developed and validated a machine learning-based algorithm that performed well for identifying incident stroke and for determining type of stroke. The algorithm also performed well on a sample from a general population, further demonstrating its generalizability and potential for adoption by other institutions.
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http://dx.doi.org/10.2196/22951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985804PMC
March 2021

Improved Incidence of Cardiovascular Disease in Patients With Incident Rheumatoid Arthritis in the 2000s: A Population-based Cohort Study.

J Rheumatol 2021 Sep 15;48(9):1379-1387. Epub 2021 Feb 15.

C.S. Crowson, PhD, Division of Rheumatology, Department of Internal Medicine, and Division of Medical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

Objective: To assess trends in incidence of cardiovascular disease (CVD) and mortality following incident CVD events in patients with rheumatoid arthritis (RA) onset in 1980-2009 vs non-RA subjects.

Methods: We studied Olmsted County, Minnesota residents with incident RA (aged > 18 yrs, 1987 American College of Rheumatology criteria met in 1980-2009) and non-RA subjects from the same source population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2016. Incident CVD events included myocardial infarction and stroke. Patients with CVD before RA incidence/index date were excluded. Cox models were used to compare incident CVD events by decade, adjusting for age, sex, and CVD risk factors.

Results: The study included 905 patients with RA and 904 non-RA subjects. Cumulative incidence of any CVD event was lower in patients with incident RA in the 2000s vs the 1980s. The HR for any incident CVD in the 2000s vs 1980s was 0.53 (95% CI 0.31-0.93). The strength of association attenuated after adjustment for anti-rheumatic medication use (HR 0.64, 95% CI 0.34-1.22). Patients with RA in the 2000s had no excess in CVD over non-RA subjects (HR 0.71, 95% CI 0.42-1.19). Risk of death after a CVD event was somewhat lower in patients with RA after the 1980s with an HR of 0.54 (95% CI 0.33-0.90) in the 1990s vs 1980s and 0.68 (95% CI 0.33-1.41) in the 2000s vs 1980s.

Conclusion: The incidence of major CVD events in RA has declined in recent decades. The gap in CVD occurrence between patients with RA and the general population is closing. Mortality after CVD events in RA may be improving.
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http://dx.doi.org/10.3899/jrheum.200842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364571PMC
September 2021

Rurality, Death, and Healthcare Utilization in Heart Failure in the Community.

J Am Heart Assoc 2021 02 3;10(4):e018026. Epub 2021 Feb 3.

Department of Health Sciences Research Mayo Clinic Rochester MN.

Background Prior reports indicate that living in a rural area may be associated with worse health outcomes. However, data on rurality and heart failure (HF) outcomes are scarce. Methods and Results Residents from 6 southeastern Minnesota counties with a first-ever code for HF ( [], code 428, and [] code I50) between January 1, 2013 and December 31, 2016, were identified. Resident address was classified according to the rural-urban commuting area codes. Rurality was defined as living in a nonmetropolitan area. Cox regression was used to analyze the association between living in a rural versus urban area and death; Andersen-Gill models were used for hospitalization and emergency department visits. Among 6003 patients with HF (mean age 74 years, 48% women), 43% lived in a rural area. Rural patients were older and had a lower educational attainment and less comorbidity compared with patients living in urban areas (<0.001). After a mean (SD) follow-up of 2.8 (1.7) years, 2440 deaths, 20 506 emergency department visits, and 11 311 hospitalizations occurred. After adjustment, rurality was independently associated with an increased risk of death (hazard ratio [HR], 1.18; 95% CI, 1.09-1.29) and a reduced risk of emergency department visits (HR, 0.89; 95% CI, 0.82-0.97) and hospitalizations (HR, 0.78; 95% CI, 0.73-0.84). Conclusions Among patients with HF, living in a rural area is associated with an increased risk of death and fewer emergency department visits and hospitalizations. Further study to identify and address the mechanisms through which rural residence influences mortality and healthcare utilization in HF is needed in order to reduce disparities in rural health.
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http://dx.doi.org/10.1161/JAHA.120.018026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955348PMC
February 2021

Accelerated aging: A marker for social factors resulting in cardiovascular events?

SSM Popul Health 2021 Mar 12;13:100733. Epub 2021 Jan 12.

University of Massachusetts Medical School, Department of Population and Quantitative Health Sciences, USA.

Background: Medicine and public health are shifting away from a purely "personal responsibility" model of cardiovascular disease (CVD) prevention towards a societal view targeting social and environmental conditions and how these result in disease. Given the strong association between social conditions and CVD outcomes, we hypothesize that accelerated aging, measuring earlier health decline associated with chronological aging through a combination of biomarkers, may be a marker for the association between social conditions and CVD.

Methods: We used data from the Coronary Artery Risk Development in Young Adults study (CARDIA). Accelerated aging was defined as the difference between biological and chronological age. Biological age was derived as a combination of 7 biomarkers (total cholesterol, HDL, glucose, BMI, CRP, FEV1/h, MAP), representing the physiological effect of "wear and tear" usually associated with chronological aging. We studied accelerated aging measured in 2005-06 as a mediator of the association between social factors measured in 2000-01 and 1) any incident CVD event; 2) stroke; and 3) all-cause mortality occurring from 2007 through 18.

Results: Among 2978 middle-aged participants, mean (SD) accelerated aging was 3.6 (11.6) years, i.e., the CARDIA cohort appeared to be, on average, 3 years older than its chronological age. Accelerated aging partially mediated the association between social factors and CVD (N=219), stroke (N=36), and mortality (N=59). Accelerated aging mediated 41% of the total effects of racial discrimination on stroke after adjustment for covariates. Accelerated aging also mediated other relationships but to lesser degrees.

Conclusion: We provide new evidence that accelerated aging based on easily measurable biomarkers may be a viable marker to partially explain how social factors can lead to cardiovascular outcomes and death.
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http://dx.doi.org/10.1016/j.ssmph.2021.100733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823205PMC
March 2021

Bi-directional association between depression and HF: An electronic health records-based cohort study.

J Comorb 2020 Jan-Dec;10:2235042X20984059. Epub 2020 Dec 24.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Objective: To determine whether a bi-directional relationship exists between depression and HF within a single population of individuals receiving primary care services, using longitudinal electronic health records (EHRs).

Methods: This retrospective cohort study utilized EHRs for adults who received primary care services within a large healthcare system in 2006. Validated EHR-based algorithms identified 10,649 people with depression (depression cohort) and 5,911 people with HF (HF cohort) between January 1, 2006 and December 31, 2018. Each person with depression or HF was matched 1:1 with an unaffected referent on age, sex, and outpatient service use. Each cohort (with their matched referents) was followed up electronically to identify newly diagnosed HF (in the depression cohort) and depression (in the HF cohort) that occurred after the index diagnosis of depression or HF, respectively. The risks of these outcomes were compared (vs. referents) using marginal Cox proportional hazard models adjusted for 16 comorbid chronic conditions.

Results: 2,024 occurrences of newly diagnosed HF were observed in the depression cohort and 944 occurrences of newly diagnosed depression were observed in the HF cohort over approximately 4-6 years of follow-up. People with depression had significantly increased risk for developing newly diagnosed HF (HR 2.08, 95% CI 1.89-2.28) and people with HF had a significantly increased risk of newly diagnosed depression (HR 1.34, 95% CI 1.17-1.54) after adjusting for all 16 comorbid chronic conditions.

Conclusion: These results provide evidence of a bi-directional relationship between depression and HF independently of age, sex, and multimorbidity from chronic illnesses.
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http://dx.doi.org/10.1177/2235042X20984059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768856PMC
December 2020

Achieving Optimal Population Cardiovascular Health Requires an Interdisciplinary Team and a Learning Healthcare System: A Scientific Statement From the American Heart Association.

Circulation 2021 Jan 3;143(2):e9-e18. Epub 2020 Dec 3.

Population cardiovascular health, or improving cardiovascular health among patients and the population at large, requires a redoubling of primordial and primary prevention efforts as declines in cardiovascular disease mortality have decelerated over the past decade. Great potential exists for healthcare systems-based approaches to aid in reversing these trends. A learning healthcare system, in which population cardiovascular health metrics are measured, evaluated, intervened on, and re-evaluated, can serve as a model for developing the evidence base for developing, deploying, and disseminating interventions. This scientific statement on optimizing population cardiovascular health summarizes the current evidence for such an approach; reviews contemporary sources for relevant performance and clinical metrics; highlights the role of implementation science strategies; and advocates for an interdisciplinary team approach to enhance the impact of this work.
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http://dx.doi.org/10.1161/CIR.0000000000000913DOI Listing
January 2021

Racial differences in the association of accelerated aging with future cardiovascular events and all-cause mortality: the coronary artery risk development in young adults study, 2007-2018.

Ethn Health 2020 Nov 21:1-13. Epub 2020 Nov 21.

Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA.

Objective: Variability of Cardiovascular disease (CVD) risk, including racial difference, is not fully accounted for by the variability of traditional CVD risk factors. We used a multiple biomarker model as a framework to explore known racial differences in CVD burden.

Design: We measured associations between accelerated aging (AccA) measured by a combination of biomarkers, and cardiovascular morbidity and all-cause mortality using data from the Coronary Artery Risk Development in Young Adults study (CARDIA). AccA was defined as the difference between biological age, calculated using biomarkers with the Klemera and Doubal method, and chronological age. Using logistic regression, we assessed overall and race-specific associations between AccA, CVD, and all-cause mortality.

Results: Among our cohort of 2959 Black or White middle-aged adults, after adjustment, a one-year increase in AccA was associated with increased odds of CVD (Odds Ratio (OR) = 1.04; 95% CI: 1.02, 1.06), stroke (OR = 1.12; 95% CI: 1.07, 1.17), and all-cause mortality (OR = 1.05; 95% CI: 1.02, 1.08). We did not find significant overall racial differences, but we did find race by sex differences where Black men differed markedly from White men in the strength of association with CVD (OR = 1.06, 95% CI: 1.01, 1.12).

Conclusions: We provide evidence that AccA is associated with future CVD.
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http://dx.doi.org/10.1080/13557858.2020.1839021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137718PMC
November 2020

Evaluation of claims-based computable phenotypes to identify heart failure patients with preserved ejection fraction.

Pharmacol Res Perspect 2020 12;8(6):e00676

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

The purpose of this analysis was to develop and validate computable phenotypes for heart failure (HF) with preserved ejection fraction (HFpEF) using claims-type measures using the Rochester Epidemiology Project. This retrospective study utilized an existing cohort of Olmsted County, Minnesota residents aged ≥ 20 years diagnosed with HF between 2007 and 2015. The gold standard definition of HFpEF included meeting the validated Framingham criteria for HF and having an LVEF ≥ 50%. Computable phenotypes of claims-type data elements (including ICD-9/ICD-10 diagnostic codes and lab test codes) both individually and in combinations were assessed via sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with respect to the gold standard. In the Framingham-validated cohort, 2,035 patients had HF; 1,172 (58%) had HFpEF. One in-patient or two out-patient diagnosis codes of ICD-9 428.3X or ICD-10 I50.3X had 46% sensitivity, 88% specificity, 84% PPV, and 54% NPV. The addition of a BNP/NT-proBNP test code reduced sensitivity to 35% while increasing specificity to 91% (PPV = 84%, NPV = 51%). Broadening the diagnostic codes to ICD-9 428.0, 428.3X, and 428.9/ICD-10 I50.3X and I50.9 increased sensitivity at the expense of decreasing specificity (diagnostic code-only model: 87% sensitivity, 8% specificity, 56% PPV, 30% NPV; diagnostic code and BNP lab code model: 61% sensitivity, 43% specificity, 60% PPV, 45% NPV). In an analysis conducted to mimic real-world use of the computable phenotypes, any one in-patient or out-patient code of ICD-9 428/ICD-10 150 among the broader population (N = 3,755) resulted in lower PPV values compared with the Framingham cohort. However, one in-patient or two out-patient instances of ICD-9 428.0, 428.9, or 428.3X/ICD-10 150.3X or 150.9 brought the PPV values from the two cohorts closer together. While some misclassification remains, the computable phenotypes defined here may be used in claims databases to identify HFpEF patients and to gain a greater understanding of the characteristics of patients with HFpEF.
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http://dx.doi.org/10.1002/prp2.676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596663PMC
December 2020

Patient-centered communication and outcomes in heart failure.

Am J Manag Care 2020 10;26(10):425-430

Department of Health Sciences Research, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Email:

Objectives: To measure the impact of patient-centered communication on mortality and hospitalization among patients with heart failure (HF).

Study Design: This was a survey study of 6208 residents of 11 counties in southeast Minnesota with incident HF (first-ever International Classification of Diseases, Ninth Revision code 428 or International Classification of Diseases, Tenth Revision code I50) between January 1, 2013, and March 31, 2016.

Methods: Perceived patient-centered communication was assessed with the health care subscale of the Chronic Illness Resources Survey and measured as a composite score on three 5-point scales. We divided our cohort into tertiles and defined them as having fair/poor (score < 12), good (score of 12 or 13), and excellent (score ≥ 14) patient-centered communication. The survey was returned by 2868 participants (response rate: 45%), and those with complete data were retained for analysis (N = 2398). Cox and Andersen-Gill models were used to determine the association of patient-centered communication with death and hospitalization, respectively.

Results: Among 2398 participants (median age, 75 years; 54% men), 233 deaths and 1194 hospitalizations occurred after a mean (SD) follow-up of 1.3 (0.6) years. Compared with patients with fair/poor patient-centered communication, those with good (HR, 0.70; 95% CI, 0.51-0.97) and excellent (HR, 0.70; 95% CI, 0.51-0.96) patient-centered communication experienced lower risks of death after adjustment for various confounders (Ptrend = .020). Patient-centered communication was not associated with hospitalization.

Conclusions: Among community patients living with HF, excellent and good patient-centered communication is associated with a reduced risk of death. Patient-centered communication can be easily assessed, and consideration should be given toward implementation in clinical practice.
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http://dx.doi.org/10.37765/ajmc.2020.88500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587036PMC
October 2020

Association of New-Onset Atrial Fibrillation After Noncardiac Surgery With Subsequent Stroke and Transient Ischemic Attack.

JAMA 2020 09;324(9):871-878

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

Importance: Outcomes of postoperative atrial fibrillation (AF) after noncardiac surgery are not well defined.

Objective: To determine the association of new-onset postoperative AF vs no AF after noncardiac surgery with risk of nonfatal and fatal outcomes.

Design, Setting, And Participants: Retrospective cohort study in Olmsted County, Minnesota, involving 550 patients who had their first-ever documented AF within 30 days after undergoing a noncardiac surgery (postoperative AF) between 2000 and 2013. Of these patients, 452 were matched 1:1 on age, sex, year of surgery, and type of surgery to patients with noncardiac surgery who were not diagnosed with AF within 30 days following the surgery (no AF). The last date of follow-up was December 31, 2018.

Exposures: Postoperative AF vs no AF after noncardiac surgery.

Main Outcomes And Measures: The primary outcome was ischemic stroke or transient ischemic attack (TIA). Secondary outcomes included subsequent documented AF, all-cause mortality, and cardiovascular mortality.

Results: The median age of the 452 matched patients was 75 years (IQR, 67-82 years) and 51.8% of patients were men. Patients with postoperative AF had significantly higher CHA2DS2-VASc scores than those in the no AF group (median, 4 [IQR, 2-5] vs 3 [IQR, 2-5]; P < .001). Over a median follow-up of 5.4 years (IQR, 1.4-9.2 years), there were 71 ischemic strokes or TIAs, 266 subsequent documented AF episodes, and 571 deaths, of which 172 were cardiovascular related. Patients with postoperative AF exhibited a statistically significantly higher risk of ischemic stroke or TIA (incidence rate, 18.9 vs 10.0 per 1000 person-years; absolute risk difference [RD] at 5 years, 4.7%; 95% CI, 1.0%-8.4%; HR, 2.69; 95% CI, 1.35-5.37) compared with those with no AF. Patients with postoperative AF had statistically significantly higher risks of subsequent documented AF (incidence rate 136.4 vs 21.6 per 1000 person-years; absolute RD at 5 years, 39.3%; 95% CI, 33.6%-45.0%; HR, 7.94; 95% CI, 4.85-12.98), and all-cause death (incidence rate, 133.2 vs 86.8 per 1000 person-years; absolute RD at 5 years, 9.4%; 95% CI, 4.9%-13.7%; HR, 1.66; 95% CI, 1.32-2.09). No significant difference in the risk of cardiovascular death was observed for patients with and without postoperative AF (incidence rate, 42.5 vs 25.0 per 1000 person-years; absolute RD at 5 years, 6.2%; 95% CI, 2.2%-10.4%; HR, 1.51; 95% CI, 0.97-2.34).

Conclusions And Relevance: Among patients undergoing noncardiac surgery, new-onset postoperative AF compared with no AF was associated with a significant increased risk of stroke or TIA. However, the implications of these findings for the management of postoperative AF, such as the need for anticoagulation therapy, require investigation in randomized trials.
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http://dx.doi.org/10.1001/jama.2020.12518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489856PMC
September 2020

Poor quality of life in patients with and without frailty: Co-prevalence and prognostic implications in patients undergoing percutaneous coronary interventions and cardiac catheterization.

Eur Heart J Qual Care Clin Outcomes 2020 08 21. Epub 2020 Aug 21.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.

Background: We hypothesize that poor QOL is highly prevalent in frail older adults and is associated with worse prognosis.

Methods And Results: Predismissal standardized tests for frailty and QOL were prospectively administered to patients included in 2 cohorts. In cohort 1, 629 patients ≥ 65 years who underwent percutaneous coronary intervention (PCI) from 2005-2008, frailty (Fried criteria) and QOL [SF-36 and Seattle Angina Questionnaires (SAQ)] were ascertained. Cohort 2 included 921 patients ≥55 years who underwent cardiac catheterization (535 had PCI) from 2014-18 and frailty was determined by Rockwood criteria and QOL by single-item, self-reported health questionnaire. In cohort 1, 19% were frail and 20% patients in cohort 2 were frail with a frailty index>0.30. The median SAQ for physical limitation (58.9 vs. 82.2, p < 0.001); physical (29.5 vs. 43.9, p < 0.001) and mental (49.2 vs. 57.4, p < 0.001) component scores of SF-36 in cohort 1 were lower and self-rating of fair/poor health (56% vs 18%, p < 0.001) in cohort 2 was significantly higher in frail patients. As compared to patients without frailty, frail patients were 5 times more likely (59% vs. 11%, p < 0.001) in cohort 1 and 7 times more likely (56% vs. 8%) in cohort 2 to be classified with poor QOL. Age- and gender-adjusted three year all-cause death and death or myocardial infarction (MI) was significantly higher for patients undergoing PCI with frailty; [HR (95% CI) death, 4.20 (2.63, 6.68, p < 0.001) and death or MI HR 2.72 (1.91, 3.87, p < 0.001)] and with poor QOL [HR death 2.47 (1.59, 3.84, p < 0.001) and death or MI 1.61 (1.16, 2.24, p < 0.001). There was no significant interaction between frailty and QOL (p = 0.64) and only modest attenuation was observed when considered together indicating their independent prognostic influence.

Conclusions: In elderly patients undergoing cardiac catheterization or PCI, poor QOL is seen more frequently in frail patients. Both frailty and poor QOL had significant and independent association with long-term survival.
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http://dx.doi.org/10.1093/ehjqcco/qcaa065DOI Listing
August 2020

Indoor Environment and Viral Infections.

Mayo Clin Proc 2020 08;95(8):1581-1583

Well Living Lab, Rochester, Minnesota; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. Electronic address:

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http://dx.doi.org/10.1016/j.mayocp.2020.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395586PMC
August 2020

Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics.

Cardiovasc Drugs Ther 2021 06;35(3):549-559

Department of Cardiovascular Medicine, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.

Purpose: Describe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic variation detected by next-generation sequencing (NGS) with comprehensive annotation and functional studies.

Methods: Seventy ST cases on clopidogrel identified from the PLATO trial (n = 58) and Mayo Clinic biorepository (n = 12) were matched 1:1 with controls for age, race, sex, diabetes mellitus, presentation, and stent type. NGS was performed to cover the entire CYP2C19 gene. Assessment of exonic variants involved measuring in vitro protein expression levels. Intronic variants were evaluated for potential splicing motif variations.

Results: Poor metabolizers (n = 4) and rare CYP2C19*8, CYP2C19*15, and CYP2C19*11 alleles were identified only in ST cases. CYP2C19*17 heterozygote carriers were observed more frequently in cases (n = 29) than controls (n = 18). Functional studies of CYP2C19 exonic variants (n = 11) revealed 3 cases and only 1 control carrying a deleterious variant as determined by in vitro protein expression studies. Greater intronic variation unique to ST cases (n = 169) compared with controls (n = 84) was observed with predictions revealing 13 allele candidates that may lead to a potential disruption of splicing and a loss-of-function effect of CYP2C19 in ST cases.

Conclusion: NGS detected CYP2C19 poor metabolizers and paradoxically greater number of so-called rapid metabolizers in ST cases. Rare deleterious exonic variation occurs in 4%, and potentially disruptive intronic alleles occur in 16% of ST cases. Additional studies are required to evaluate the role of these variants in platelet aggregation and clopidogrel metabolism.
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http://dx.doi.org/10.1007/s10557-020-06988-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779664PMC
June 2021

Sex Differences in Outcomes After Myocardial Infarction in the Community.

Am J Med 2021 01 3;134(1):114-121. Epub 2020 Jul 3.

Department of Cardiovascular Diseases; Department of Health Sciences Research, Mayo Clinic, Rochester, Minn. Electronic address:

Purpose: Prior studies observed that women experienced worse outcomes than men after myocardial infarction but did not convincingly establish an independent effect of female sex on outcomes, thus failing to impact clinical practice. Current data remain sparse and information on long-term nonfatal outcomes is lacking. To address these gaps in knowledge, we examined outcomes after incident myocardial infarction for women compared with men.

Methods: We studied a population-based myocardial infarction incidence cohort in Olmsted County, Minnesota, between 2000 and 2012. Patients were followed for recurrent myocardial infarction, heart failure, and death. A propensity score was constructed to balance the clinical characteristics between men and women; Cox models were weighted using inverse probabilities of the propensity scores.

Results: Among 1959 patients with incident myocardial infarction (39% women; mean age 73.8 and 64.2 for women and men, respectively), 347 recurrent myocardial infarctions, 464 heart failure episodes, 836 deaths, and 367 cardiovascular deaths occurred over a mean follow-up of 6.5 years. Women experienced a higher occurrence of each adverse event (all P <0.01). After propensity score weighting, women had a 28% increased risk of recurrent myocardial infarction (hazard ratio: 1.28, 95% confidence interval: 1.03-1.59), and there was no difference in risk for any other outcomes (all P >0.05).

Conclusion: After myocardial infarction, women experience a large excess risk of recurrent myocardial infarction but not of heart failure or death independently of clinical characteristics. Future studies are needed to understand the mechanisms driving this association.
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http://dx.doi.org/10.1016/j.amjmed.2020.05.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752831PMC
January 2021

Outcomes of incident atrial fibrillation in heart failure with preserved or reduced ejection fraction: A community-based study.

J Cardiovasc Electrophysiol 2020 09 16;31(9):2275-2283. Epub 2020 Jul 16.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: The best management strategy for patients with atrial fibrillation (AF) with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) is unknown.

Methods And Results: This cohort study was conducted in Olmsted County, Minnesota, with resources of the Rochester Epidemiology Project. Patients with incident AF occurring between 2000 and 2014 with a prior or concurrent HF were included. Patients with LVEF ≥ 50% were designated as HF and preserved ejection fraction (HFpEF) and those with LVEF < 50% were designated as HF and reduced ejection fraction (HFrEF). Rhythm control in the first year after AF diagnosis was defined as prescriptions for an antiarrhythmic drug, catheter ablation, or maze procedure. The primary endpoint was all-cause mortality. The secondary endpoints were cardiovascular death, cardiovascular hospitalization, and stroke or transient ischemic attack. Of 859 patients (age, 77.2 ± 12.1 years; 49.2%, female), 447 had HFpEF-AF, and 412 had HFrEF-AF. There was no difference in all-cause mortality (10-year mortality, 83% vs 79%; p = .54) or secondary endpoints between the HFpEF-AF and HFrEF-AF, respectively. Compared with the rate control strategy, rhythm control in HFpEF-AF patients (n = 40, 15.9%) offered no survival benefits (adjusted HR, 0.70; 95% CI, 0.42-1.16; p = .16), whereas rhythm control in HFrEF-AF patients (n = 52, 22.5%) decrease cardiovascular mortality (HR, 0.38; 95% CI, 0.17-0.86; p = .02).

Conclusions: Patients with HFpEF-AF and HFrEF-AF had similar poor prognoses. Rhythm control strategy was seldom adopted in community care in patients with HF and AF. A rhythm control strategy may provide survival benefit for patients with HFrEF-AF and the benefit of rhythm control in patients with HFpEF-AF warrants further study.
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http://dx.doi.org/10.1111/jce.14632DOI Listing
September 2020
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