David Q. Rich, ScD Departments of Public Health Sciences and - PowerPoint Presentation

1. David Q. Rich, ScDDepartments of Public Health Sciences and Environmental MedicineDoes ambient wood smoke in Rochester, NY increase levels of cardiovascular biomarkers or trigger myocardial infarction?

2. OutlineBackgroundStudy A: Delta-C and Cardiovascular BiomarkersStudy Population and MethodsResults - Hourly concentrations from NYSDEC siteStudy B: Delta-C and Myocardial InfarctionStudy Population and MethodsResultsHourly concentrations from NYSDEC siteDaily concentrations from Land Use Regression ModelConclusions and Next Directions

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4. Odds of STEMI and NSTEMI associated with lagged PM2.5 concentrationsGardner et al, Part & Fibre Toxicol 2014;11:1

5. Potential Air Pollution & Cardiorespiratory Mechanisms ?AMBIENT AIR POLLUTIONPulmonaryReflexesAutonomic Nervous SystemAutomaticityConductionRepolarizationHeart rateRhythmPulmonary InflammationEndothelialDysfunctionAcute PhaseResponse &CoagulationFactorsLeukocyte & PlateletActivationOxidantStressPlaque RuptureSystemic InflammationAtherosclerosis Progression & Plaque InstabilityThrombosisMYOCARDIAL INFARCTION, STROKE& OTHER CV EVENTS?

6. Change in rMSSD associated with each IQR increase in pollutant concentration

7. Pre-Olympic PeriodJune 6, 2008

8. During-Olympic PeriodAugust 16, 2008

9. sCD62pImprovements in most biomarkers34% reduction in CD62p (marker of platelet activation)CD62p also impacted by ambient PM

10. HypothesesStudy A: Short term increases in the concentration of Wood Smoke (Delta-C) and other pollutants will be associated with increased levels of cardiovascular biomarkers Study B: Short term increases in the concentration of Wood Smoke (Delta-C) and other pollutants will be associated with an increased risk of myocardial infarction.

11. Air PollutionHourly measurements at New York State Department of Environmental Conservation site in RochesterPM2.5Black carbon Delta-CUFP (<100 nm)AMP (100-500nm)CO, O3, SO2, NO2TemperatureRelative humidityLand Use Regression ModelWinter (November – April Only)

12. Study A – CV Biomarkers:Study Population, Outcomes, Air pollutionAre increased ambient concentrations of wood smoke and other PM pollutants associated with increases in markers of inflammation, coagulation, and hemostasis in cardiac patients?N=135 Adult (≥ 18 years) patients treated at URMC Cardiac Catheterization laboratoryFor either:Myocardial InfarctionCAD requiring catheterizationWinters (November 1 to April 30) of 2011-2013Blood sample collected upon arrival at Cath LabFibrinogen hs-C-reactive protein Platelet factor 4 P-selectinMyeloperoxidase D-dimerUse NYSDEC Air pollution data only

13. Study A: Statistical AnalysisLinear regressionIndependent variable = Delta-C concentration in previous 24 hoursDependent variable = FibrinogenCovariates = Temperature, Relative Humidity (3df natural spline), age, smoking, year, hour of the day, dyslipidemia, prior MIChange in Fibrinogen associated with each 0.13 µg/m3 increase in Delta-C concentration in previous 24 hours Repeated for each combination of outcome and lagged pollutant concentration

14. Percent change in fibrinogen associated with each IQR increase in lagged pollutant concentration

15. Percent change in CRP associated with each IQR increase in lagged pollutant concentration

16. Percent change in MPO associated with each IQR increase in lagged pollutant concentration

17. Percent change in fibrinogen associated with each IQR increase in black carbon in the previous 24 hours, by tertile of fatty acidPlease see Poster by Daniel Croft, MD, MPH* p<0.05- comparison to HIGH tertile

18. Study B:Study Population, Outcomes, Air PollutionAre increased ambient concentrations of wood smoke and other pollutants associated with the triggering of myocardial infarction?N=366 adult ST-elevation myocardial infarction (STEMI) patients treated at the University of Rochester Medical Center from January 2007 – September 2012Hourly Delta-C, BC, PM2.5, UFP, AMP, CO, O3, SO2, NO2 measured at NYSDEC site in RochesterDaily Delta-C and BC concentrations estimated at subject residences using Land Use Regression ModelN=246 STEMI in Winter time only (November to April)Case-crossover study designConditional Logistic Regression

19. Risk of MI associated with each IQR increase in pollutant concentrations, by lag hours: NYSDEC site

20. Risk of MI associated with each IQR increase in pollutant concentrations, by lag hours: NYSDEC site

21. Risk of MI associated with each IQR increase in pollutant concentrations, by lag hours and season: NYSDEC site

22. Strengths & LimitationsWe can examine risk of STEMI associated with air pollution levels in few hours before MIHowever, exposure error and bias is present when using pollutant concentrations from fixed monitoring station for all study subjectsMay be different for different pollutants

23. Risk of MI associated with each IQR increase in pollutant concentrations, by lag days: Land Use Regression Estimates

24. Strengths & LimitationsWe cannot examine risk of STEMI associated with air pollution levels in few hours before MIHowever, exposure error and bias is reduced when using LUR estimated pollutant concentrations at each subject’s residence instead of concentrations measured at fixed monitoring station

25. Temporal misalignmentProblems with use of daily LUR concentrationsCannot examine time period of greatest interest (Lag hour 0)Mean PM2.5 from Lag Day 0 does ≠ Mean PM2.5 from Lag hours 0-23MI Onset10:00am March, 2016 Lag Day 2 Lag Day 1 Lag Day 014th 15th 16th Daily PM2.5 Concentrations Hourly PM2.5 ConcentrationsLag hour 0Lag hours 23-47 Lag hours 0-23

26. ConclusionsAmbient wood smoke associated with markers of systemic inflammation in susceptible subjectsIncreased fibrinogen, CRP, and decreased MPO associated with Delta-C, PM2.5, BC, and UFP concentrations in previous 1-24 hoursNot clear that Delta-C is any more toxic than other PMNo clear association between wood smoke and the triggering of MIHowever issues of spatial and temporal misalignment make this unclearRisk of myocardial infarction NOT associated with Delta-C concentrations from NYSDEC site in previous 72 hoursRisk of myocardial infarction IS associated with PM2.5, O3, and CO concentrations from NYSDEC site in previous 1-48 hours

27. Conclusions (continued)Risk of myocardial infarction MAY BE associated with BC or Delta-C concentrations estimated using LUR in previous 2 or 3 daysNeed to study health events with acute responses to air pollution (e.g. Myocardial Infarction, Stroke, Asthma Exacerbation, etc.)Need to examine responses to air pollution in time intervals < 1 day, and even as short as a few hoursLUR models needed that can estimate PM concentrations at individual locations for individual hours, for all year long

28. Thank You!Daniel CroftRobert BlockScott Cameron Charles LowensteinFrederick LingWojciech ZarebaPhilip HopkeMark UtellSally ThurstonKelly Thevenet-MorrisonKristin EvansPing ZhuDuncan ThomasScott DiehlShou-En LuMark FramptonDavid OakesScott CameronCraig MorrellJason SuWilliam BeckettJunfeng ZhangHoward KipenTong Zhu Wei HuangGuangfa WangYuedan WangMin HuPamela Ohman-StricklandJicheng Gong

29. Thank You!This work supported by:New York State Energy Research and Development Authority Contract #’s 32971 and 8650Electric Power Research Institute Agreement#W06325Health Effects Institute 4750-RFPA05-4NIEHS Grant #P30-ES001247, T32-HL066988-1, 1R01-ES015864, P30-ES005022, P30-ES007048Bruce and Marsha Moskowitz FoundationBeijing Environmental Protection BureauBeijing Council of Science and Technology