2023
Distinguishing features of long COVID identified through immune profiling
Klein J, Wood J, Jaycox J, Dhodapkar R, Lu P, Gehlhausen J, Tabachnikova A, Greene K, Tabacof L, Malik A, Silva Monteiro V, Silva J, Kamath K, Zhang M, Dhal A, Ott I, Valle G, Peña-Hernández M, Mao T, Bhattacharjee B, Takahashi T, Lucas C, Song E, McCarthy D, Breyman E, Tosto-Mancuso J, Dai Y, Perotti E, Akduman K, Tzeng T, Xu L, Geraghty A, Monje M, Yildirim I, Shon J, Medzhitov R, Lutchmansingh D, Possick J, Kaminski N, Omer S, Krumholz H, Guan L, Dela Cruz C, van Dijk D, Ring A, Putrino D, Iwasaki A. Distinguishing features of long COVID identified through immune profiling. Nature 2023, 623: 139-148. PMID: 37748514, PMCID: PMC10620090, DOI: 10.1038/s41586-023-06651-y.Peer-Reviewed Original ResearchConceptsLong COVIDSARS-CoV-2Infection syndromeExaggerated humoral responseSoluble immune mediatorsEpstein-Barr virusPost-exertional malaiseCross-sectional studyHigher antibody responseImmune mediatorsImmune phenotypingImmune profilingHumoral responseAntibody responseLymphocyte populationsCOVID statusUnbiased machineCortisol levelsLC statusRelevant biomarkersViral pathogensSyndromeCOVIDFuture studiesBiological features
2021
Contemporary National Patterns of Eligibility and Utilization of Novel Cardioprotective Anti‐hyperglycemic agents in Type 2 Diabetes
Nargesi AA, Jeyashanmugaraja GP, Desai N, Lipska K, Krumholz H, Khera R. Contemporary National Patterns of Eligibility and Utilization of Novel Cardioprotective Anti‐hyperglycemic agents in Type 2 Diabetes. Journal Of The American Heart Association 2021, 10: e021084. PMID: 33998258, PMCID: PMC8403287, DOI: 10.1161/jaha.121.021084.Peer-Reviewed Original ResearchMeSH KeywordsAgedBiomarkersBlood GlucoseCardiovascular DiseasesDiabetes Mellitus, Type 2Drug UtilizationEligibility DeterminationFemaleGlucagon-Like Peptide-1 ReceptorGuideline AdherenceHeart Disease Risk FactorsHumansIncretinsMaleMiddle AgedNutrition SurveysPractice Guidelines as TopicPractice Patterns, Physicians'Risk AssessmentSodium-Glucose Transporter 2 InhibitorsTime FactorsTreatment OutcomeUnited StatesConceptsSGLT-2 inhibitorsType 2 diabetes mellitusAtherosclerotic cardiovascular diseaseChronic kidney diseaseLarge clinical trialsGLP-1RAsDiabetes mellitusCardiovascular diseaseHeart failureKidney diseaseClinical trialsHigh-risk atherosclerotic cardiovascular diseaseGLP-1RA useAmerican Diabetes AssociationNutrition Examination SurveyAnti-hyperglycemic agentsPublic health benefitsComplex survey designCardiovascular riskGuideline recommendationsDiabetes AssociationExamination SurveyProtective therapyNational HealthAmerican College
2020
Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials
Bikdeli B, Caraballo C, Welsh J, Ross JS, Kaul S, Stone GW, Krumholz HM. Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials. Clinical Trials 2020, 17: 723-728. PMID: 32838556, PMCID: PMC8088773, DOI: 10.1177/1740774520949157.Peer-Reviewed Original ResearchConceptsNon-inferiority trialPrimary endpointClinical outcome trialsNon-inferiority marginSurrogate markerNon-inferiority designCardiovascular trialsOutcome trialsClinical outcomesDefinitive clinical outcome trialsNon-inferiority criteriaStudy protocolSurrogate outcomesBACKGROUND/Median numberSurrogate endpointsPrimary analysisCardiovascular interventionsCardiovascular medicineTrialsEndpointClinical interpretationOutcomesMarkersIntervention
2019
Effects of Mobile Text Messaging on Glycemic Control in Patients With Coronary Heart Disease and Diabetes Mellitus
Huo X, Krumholz HM, Bai X, Spatz ES, Ding Q, Horak P, Zhao W, Gong Q, Zhang H, Yan X, Sun Y, Liu J, Wu X, Guan W, Wang X, Li J, Li X, Spertus JA, Masoudi FA, Zheng X. Effects of Mobile Text Messaging on Glycemic Control in Patients With Coronary Heart Disease and Diabetes Mellitus. Circulation Cardiovascular Quality And Outcomes 2019, 12: e005805. PMID: 31474119, DOI: 10.1161/circoutcomes.119.005805.Peer-Reviewed Original ResearchMeSH KeywordsAgedAsian PeopleBiomarkersBlood GlucoseChinaCoronary DiseaseCulturally Competent CareDiabetes MellitusExerciseFemaleGlycated HemoglobinHealth CommunicationHealthy LifestyleHumansHypoglycemic AgentsMaleMedication AdherenceMiddle AgedMotivationPatient Education as TopicRisk Reduction BehaviorSelf CareSingle-Blind MethodTelemedicineText MessagingTime FactorsTreatment OutcomeConceptsCoronary heart diseaseHeart diseaseGlycemic controlIntervention groupUsual careDiabetes mellitusBlood glucosePhysical activityControl groupText message-based interventionBlood pressure controlProportion of patientsRisk factor managementGood glycemic controlSystolic blood pressureBody mass indexText messaging programsText message interventionMobile health interventionsSecondary outcomesBlood pressurePrimary outcomeLDL cholesterolMass indexMedication adherence
2018
Implications of coronary artery calcium testing on risk stratification for lipid-lowering therapy according to the 2016 European Society of Cardiology recommendations: The MESA study
Bittencourt MS, Blankstein R, Blaha MJ, Sandfort V, Agatston AS, Budoff MJ, Blumenthal RS, Krumholz HM, Nasir K. Implications of coronary artery calcium testing on risk stratification for lipid-lowering therapy according to the 2016 European Society of Cardiology recommendations: The MESA study. European Journal Of Preventive Cardiology 2018, 25: 1887-1898. PMID: 30043629, DOI: 10.1177/2047487318788930.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overBiomarkersClinical Decision-MakingCoronary AngiographyCoronary Artery DiseaseDyslipidemiasFemaleHumansHypolipidemic AgentsIncidenceLipidsMaleMiddle AgedPractice Guidelines as TopicPredictive Value of TestsPrognosisProspective StudiesRisk AssessmentRisk FactorsUnited StatesVascular CalcificationConceptsLipid-lowering treatmentCoronary artery calciumLipid-lowering therapyArtery calciumHigher cardiovascular mortalityCardiovascular mortalityUncontrolled groupCoronary Artery Calcium TestingCoronary heart disease eventsEuropean SocietyHeart disease eventsCardiovascular mortality ratesCardiovascular risk assessmentLow-risk groupCardiology recommendationsCardiology guidelinesCardiovascular riskESC recommendationsRisk stratificationMESA participantsCalcium testingRisk groupsGroup 31Lower incidenceMESA studyIs Posthospital Syndrome a Result of Hospitalization-Induced Allostatic Overload?
Goldwater DS, Dharmarajan K, McEwan BS, Krumholz HM. Is Posthospital Syndrome a Result of Hospitalization-Induced Allostatic Overload? Journal Of Hospital Medicine 2018, 13 PMID: 29813141, DOI: 10.12788/jhm.2986.Peer-Reviewed Original ResearchConceptsPosthospital syndromeAllostatic overloadAutonomic nervous systemMultiple organ systemsHospital dischargeInflammatory markersAdverse eventsHospital readmissionAdrenal axisAdverse outcomesPlausible etiologyPathophysiologic consequencesElevated riskNervous systemNarrative reviewOrgan systemsEnhanced vulnerabilityElevated levelsHospital environmentTraditional hospital environmentSyndromeMaladaptive statesOverloadOutcomesPossible mechanismSex Differences in Omega‐3 and ‐6 Fatty Acids and Health Status Among Young Adults With Acute Myocardial Infarction: Results From the VIRGO Study
Lu Y, Ding Q, Xu X, Spatz ES, Dreyer RP, D'Onofrio G, Caulfield M, Nasir K, Spertus JA, Krumholz HM. Sex Differences in Omega‐3 and ‐6 Fatty Acids and Health Status Among Young Adults With Acute Myocardial Infarction: Results From the VIRGO Study. Journal Of The American Heart Association 2018, 7: e008189. PMID: 29848494, PMCID: PMC6015388, DOI: 10.1161/jaha.117.008189.Peer-Reviewed Original ResearchConceptsAcute myocardial infarctionHealth status scoresArachidonic acidVIRGO StudyStatus scoreMyocardial infarctionHealth statusPoorer health status outcomesYoung menPatient-reported health statusYoung womenOmega-3 fatty acidsSex differencesPatient-reported outcomesFatty acidsHealth status outcomesCardiovascular outcomesClinical characteristicsAdjusted analysisAMI patientsRisk factorsUS adultsStatus outcomesOmega-3Women 1Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study
Wallach JD, Ciani O, Pease AM, Gonsalves GS, Krumholz HM, Taylor RS, Ross JS. Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study. BMC Medicine 2018, 16: 45. PMID: 29562926, PMCID: PMC5863466, DOI: 10.1186/s12916-018-1023-9.Peer-Reviewed Original ResearchConceptsPostapproval trialsPivotal trialsActual clinical effectSurrogate markerTrial endpointsLarge treatment effectsPrimary endpointNovel therapeuticsNovel drugsTreatment effectsFDA approvalPatient-relevant outcomesMeta-epidemiological studyStandardized mean differenceTreatment effect sizeClinical effectsResultsBetween 2005Odds ratioDrug trialsSame indicationDrug AdministrationEvidence of differencesMean differenceU.S. FoodDisease
2017
Are non-ST-segment elevation myocardial infarctions missing in China?
Murugiah K, Wang Y, Nuti SV, Li X, Li J, Zheng X, Downing NS, Desai NR, Masoudi FA, Spertus JA, Jiang L, Krumholz HM, Group F. Are non-ST-segment elevation myocardial infarctions missing in China? European Heart Journal - Quality Of Care And Clinical Outcomes 2017, 3: 319-327. PMID: 28950309, DOI: 10.1093/ehjqcco/qcx025.Peer-Reviewed Original ResearchTwo Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011
Bikdeli B, Punnanithinont N, Akram Y, Lee I, Desai NR, Ross JS, Krumholz HM. Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011. Journal Of The American Heart Association 2017, 6: e005285. PMID: 28325713, PMCID: PMC5524035, DOI: 10.1161/jaha.116.005285.Peer-Reviewed Original ResearchConceptsClinical outcome trialsOutcome trialsEndpoint trialsPrimary endpointCardiovascular trialsClinical outcome studiesClinical outcomesSurrogate markerPatient's perspectiveSurrogate endpointsOutcome studiesNew England JournalSample cohortTrial resultsTrialsSurrogate trialsEndpointPositive resultsAmerican MedicalInterventionHigh-impact journalsCohortIs Hemoglobin A1c the Right Outcome for Studies of Diabetes?
Lipska KJ, Krumholz HM. Is Hemoglobin A1c the Right Outcome for Studies of Diabetes? JAMA 2017, 317: 1017-1018. PMID: 28125758, PMCID: PMC5350060, DOI: 10.1001/jama.2017.0029.Commentaries, Editorials and LettersSex Differences in Inflammatory Markers and Health Status Among Young Adults With Acute Myocardial Infarction
Lu Y, Zhou S, Dreyer RP, Spatz ES, Geda M, Lorenze NP, D'Onofrio G, Lichtman JH, Spertus JA, Ridker PM, Krumholz HM. Sex Differences in Inflammatory Markers and Health Status Among Young Adults With Acute Myocardial Infarction. Circulation Cardiovascular Quality And Outcomes 2017, 10: e003470. PMID: 28228461, PMCID: PMC5459381, DOI: 10.1161/circoutcomes.116.003470.Peer-Reviewed Original ResearchMeSH Keywords1-Alkyl-2-acetylglycerophosphocholine EsteraseAdolescentAdultAge of OnsetBiomarkersChi-Square DistributionComorbidityC-Reactive ProteinFemaleHealth Status DisparitiesHumansInflammation MediatorsLinear ModelsMaleMiddle AgedMultivariate AnalysisMyocardial InfarctionProspective StudiesRisk AssessmentRisk FactorsSex FactorsSocioeconomic FactorsUnited StatesUp-RegulationYoung AdultConceptsHigh-sensitivity C-reactive proteinAcute myocardial infarctionHigher inflammatory levelsInflammatory markersPoor health statusHealth statusYoung womenMyocardial infarctionInflammatory levelsTargeted anti-inflammatory treatmentsElevated inflammatory markersResidual cholesterol riskResidual inflammatory riskSex differencesAnti-inflammatory treatmentAnti-inflammatory therapyC-reactive proteinHigher mortality riskYoung menPhospholipase A2Years of ageCardiovascular outcomesMultivariable adjustmentPatient characteristicsSecondary prevention
2016
Troponin Testing for Clinicians
Brush JE, Kaul S, Krumholz HM. Troponin Testing for Clinicians. Journal Of The American College Of Cardiology 2016, 68: 2365-2375. PMID: 27884254, DOI: 10.1016/j.jacc.2016.08.066.Peer-Reviewed Original Research
2015
Biomarkers, Risk Factors, and Risk
Krumholz HM. Biomarkers, Risk Factors, and Risk. Circulation Cardiovascular Quality And Outcomes 2015, 8: 457-459. PMID: 26349839, PMCID: PMC5322983, DOI: 10.1161/circoutcomes.115.002245.Peer-Reviewed Original ResearchTrends in Cardiac Biomarker Testing in China for Patients with Acute Myocardial Infarction, 2001 to 2011: China PEACE-Retrospective AMI Study
Zhan L, Masoudi FA, Li X, Hu S, Venkatesh AK, Spertus JA, Lin Z, Desai NR, Li J, Krumholz HM, Jiang L, . Trends in Cardiac Biomarker Testing in China for Patients with Acute Myocardial Infarction, 2001 to 2011: China PEACE-Retrospective AMI Study. PLOS ONE 2015, 10: e0122237. PMID: 25893247, PMCID: PMC4404305, DOI: 10.1371/journal.pone.0122237.Peer-Reviewed Original ResearchConceptsAcute myocardial infarctionCardiac biomarker testingProportion of hospitalsBiomarker testingChinese hospitalsDiagnosis of AMIChina PEACE-Retrospective AMI StudyRate of useMiddle-income countriesMyocardial infarctionPractice compliesHigh-income countriesAMI admissionsBiomarker testsUrban hospitalBiomarker use
2014
Hospital Variation in the Use of Noninvasive Cardiac Imaging and Its Association With Downstream Testing, Interventions, and Outcomes
Safavi KC, Li SX, Dharmarajan K, Venkatesh AK, Strait KM, Lin H, Lowe TJ, Fazel R, Nallamothu BK, Krumholz HM. Hospital Variation in the Use of Noninvasive Cardiac Imaging and Its Association With Downstream Testing, Interventions, and Outcomes. JAMA Internal Medicine 2014, 174: 546-553. PMID: 24515551, PMCID: PMC5459406, DOI: 10.1001/jamainternmed.2013.14407.Peer-Reviewed Original ResearchConceptsAcute myocardial infarctionNoninvasive cardiac imagingDownstream testingReadmission ratesRevascularization proceduresCardiac imagingHospital variationCardiac ischemiaProportion of patientsNoninvasive imagingLower readmission ratesPrincipal discharge diagnosisCross-sectional studyCardiac biomarker testsQ4 hospitalsChest discomfortCoronary angiographyCoronary diseaseDischarge diagnosisCoronary angiogramEmergency departmentMyocardial infarctionSame hospitalCurrent guidelinesInpatient wardsClinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005-2012
Downing NS, Aminawung JA, Shah ND, Krumholz HM, Ross JS. Clinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005-2012. JAMA 2014, 311: 368-377. PMID: 24449315, PMCID: PMC4144867, DOI: 10.1001/jama.2013.282034.Peer-Reviewed Original ResearchConceptsPivotal efficacy trialsNovel therapeutic agentsClinical trial evidencePivotal trialsEfficacy trialsTherapeutic agentsEnd pointTrial evidenceMedian numberAvailable FDA documentsSingle pivotal trialTrial end pointsSurrogate end pointsNumber of patientsLength of treatmentCross-sectional analysisPrimary outcomeClinical outcomesTrial completion ratesClinical benefitPlacebo comparatorSurrogate outcomesMAIN OUTCOMEDrug AdministrationUS Food
2013
Urinary Biomarkers of AKI and Mortality 3 Years after Cardiac Surgery
Coca SG, Garg AX, Thiessen-Philbrook H, Koyner JL, Patel UD, Krumholz HM, Shlipak MG, Parikh CR. Urinary Biomarkers of AKI and Mortality 3 Years after Cardiac Surgery. Journal Of The American Society Of Nephrology 2013, 25: 1063-1071. PMID: 24357673, PMCID: PMC4005309, DOI: 10.1681/asn.2013070742.Peer-Reviewed Original ResearchConceptsKidney injury molecule-1Long-term mortalityIL-18Urinary biomarkersClinical AKICardiac surgeryHighest tertileUrinary neutrophil gelatinase-associated lipocalinProspective long-term followNeutrophil gelatinase-associated lipocalinContinuous net reclassification improvementInjury molecule-1Kidney injury biomarkersPostoperative day 1Gelatinase-associated lipocalinImmediate postoperative periodAdditional prognostic informationLong-term followNet reclassification improvementMortality 3 yearsLiver fatty acidAKI cohortCause mortalityHospital outcomesKidney injuryTarget cardiovascular risk rather than cholesterol concentration
Krumholz HM. Target cardiovascular risk rather than cholesterol concentration. The BMJ 2013, 347: f7110. PMID: 24284344, DOI: 10.1136/bmj.f7110.Peer-Reviewed Original Research
2012
Preoperative Serum Brain Natriuretic Peptide and Risk of Acute Kidney Injury After Cardiac Surgery
Patel UD, Garg AX, Krumholz HM, Shlipak MG, Coca SG, Sint K, Thiessen-Philbrook H, Koyner JL, Swaminathan M, Passik CS, Parikh CR. Preoperative Serum Brain Natriuretic Peptide and Risk of Acute Kidney Injury After Cardiac Surgery. Circulation 2012, 125: 1347-1355. PMID: 22322531, PMCID: PMC3312808, DOI: 10.1161/circulationaha.111.029686.Peer-Reviewed Original ResearchConceptsSevere acute kidney injuryMild acute kidney injuryAcute kidney injuryPostoperative acute kidney injuryCardiac surgeryPreoperative BNPKidney injuryHigh riskAcute Kidney Injury Network definitionPreoperative brain natriuretic peptide levelsBrain natriuretic peptide levelsSerum brain natriuretic peptideAcute renal replacement therapyAcute Kidney Injury studyDoubling of creatinineHigher AKI riskPreoperative BNP levelsNatriuretic peptide levelsHigh-risk patientsRenal replacement therapyBrain natriuretic peptidePreoperative risk stratificationTypes of patientsAddition of BNPAKI cases