Estimates of Daily Mortality Effects of Increases in PM: 60 studies in 35 cities Cause of deathPercent of total deaths Cause-specific % increase / 50mcg inc in PM2.5 % of excess deaths due to PM exposure All Causes1007.0100 Respiratory 825.028 Cardiovascular 4511.069 Other Disease 470.4 3
Particles and MI MI risk increased with PM2.5 elevations in 2 hours preceding onset of symptoms. Multivariate OR= 1.48 (1.09-2.02) for 25 mcg/m3 increase in PM 2.5. (Peters, 2001) OR=2.9 1-2 h after exposure to traffic (Peters, 2004) UF particles increase thrombosis within one hour of instillation by platelet activation Effects not explained by a mechanism dependent on lung inflammation because they occur too quickly for inflammation to manifest
Endothelial Dysfunction Physiological dysfunction of normal biochemical processes carried out by endothelial cells lining inner surface of all blood vessels, arteries and veins. May compromise coagulation, platelet adhesion, immune function, control of volume and electrolyte content of the intravascular and extravascular spaces. Characteristic of smokers, diabetics, heart disease
Endothelial Function and ASCVD Endothelial dysfunction precedes plaque formation and may acutely promote abnormal reactions between vessel walls, platelets & WBC Can be assessed noninvasively by USG: brachial artery reactivity (flow mediated dilation) following ischemia Acutely responds to ascorbic acid, tea, ETS, or 150mcg/m3 PM2.5 + 120ppb ozone
Genetic Endothelial Susceptibility ? Low concentrations of the intercellular messenger NO are important to endothelial function Directly Inhibits platelet aggregation Variant eNOS (Glu298Asp) variably increases risk of ASCVD; +/- decreases FMD 10% homozygous SNP prevalence in UK and Italy
Schematic drawing of ultrasound imaging of the brachial artery with upper versus lower cuff placement and transducer position above the antecubital fossa. BP = blood pressure; FMD = flow-mediated vasodilation. Journal of the American College of Cardiology, Jan 2002.
Ultrasound image of the brachial artery at (A) baseline and (B) 1 min after hyperemic stimulus. Journal of the American College of Cardiology, Jan 2002.
Specific Aims of 4 Year EPA Study 50 healthy, young, non-smoking volunteers Two hour exposure to freshly generated aerosols (200 mcg/m3) Measure endothelial function as brachial artery reactivity change Measure platelet activation markers independent of pulmonary inflammation Determine if individuals with genetically increased risk for ASCVD and endothelial dysfunction exhibit enhanced sensitivity for above endpoints
Costs of Myocardial Infarction 2003: 22,439 inpatient MIs (NJ CHS) 1997: cost per MI (752 US Hospitals) $15,631* (excludes MD fees, inflation, indirect) $350,744,000 1% is $3,507,440 *Azoulay et al. Cardiovasc Rev Rep 24:555-560 2003
EOHSI Studies of Diesel Health Effects DE and Stress on Acute Phase Response: Fiedler & Laumbach (DOD) DE Vessels, Coagulation: Kipen (EPA) DE Biomarkers Validation: Zhang (EPA) PM2.5, Crossing Guards, and HRV: Fan (EOHSI) Nasal Resp to DE Particles: Laumbach (EOHSI) Strong support from Debra Laskin, Emmy Gordon, Alexander Kusnecov, Terri Kinzy, Omowunmi Osinubi, Kathy Kelly-McNeil, Kelechi Olejeme, Pamela Ohman-Strickland, Claire Philipp, Daniel Shindler