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Endothelial dysfunction, biomarkers and lung function

- Lung. Endothelial dysfunction, biomarkers and lung function. R Graham Barr, MD DrPH Departments of Medicine and Epidemiology Columbia University Medical Center Funding: NHLBI R01: HL077612, HL075476 N01: HC95159 to HC95165, HC95169 Conflict of Interest: None. - Lung II.

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Endothelial dysfunction, biomarkers and lung function

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  1. - Lung Endothelial dysfunction, biomarkers and lung function R Graham Barr, MD DrPH Departments of Medicine and Epidemiology Columbia University Medical Center Funding: NHLBI R01: HL077612, HL075476 N01: HC95159 to HC95165, HC95169 Conflict of Interest: None

  2. - Lung II Cardiopulmonary Structure and Function in the Multi-Ethnic Study of Atherosclerosis R Graham Barr, MD DrPH Departments of Medicine and Epidemiology Columbia University Medical Center Funding: National HEART-LUNG-BLOOD Institute R01… N01: HC95159 to HC95165, HC95169 Conflict of Interest: None

  3. - Lung Endothelial Hypothesis of COPD Smoking Endothelial apoptosis and dysfunction Microvascular damage Systemic circulation End-organ damage

  4. - Lung Endothelial Hypothesis of COPD Smoking Endothelial apoptosis and dysfunction Microvascular damage Systemic circulation Alveolar destruction (%emphysema) Airflow obstruction Pulmonary circulation ↓ Pulmonary blood flow ↓LV-EDV ↓CO ↑RV mass PA dilation (TPVV)

  5. - Lung CT Percent Emphysema and the LV Stroke Volume (ml) CT % emphysema Adjusted for age, sex, race/ethnicity, education, smoking status, packyears, BSA, height, DM, FPG, HTN, SBP, DBP, CRP, site, wt>220 lbs

  6. - Lung MESA-Lung II – Hypotheses • TPVV is linearly related to lower LV end-diastolic volume • TPVV is increased in a linear fashion with reduced post-bronchodilator FEV1/FVC ratio and emphysema • Impaired FMD predicts decline in lung function, increased CT percent emphysema, and incident COPD

  7. Proposed Sample and Components • All MESA-Lung participants active in Ex 5 • 3,250 MESA-Classic (~2,550 selected for CAC) • 225 MESA Air “new recruits” • Components • Replace one CAC scan with full-lung scan • Oxygen saturation • Pre/post bronchodilator spirometry • One-page questionnaire/completion form • Cotinine

  8. Additional Measures on Full-lung Scans • Total Pulmonary Vascular Volume (TPVV) • Non-contrast CT scan • 154 ml vs. 125 ml, P<0.05 • Reproducible • Total lung volumes • Airway dimensions • Apical emphysema

  9. - Lung Burden of Full-lung CT Scan • Participant • ~0 min if selected for CAC; ~15 min otherwise • Additional 1-2 mSv above CAC scan • Field Center • Consent, transmission, reporting • CT RC burden • Transmission to Iowa Lung CT RC • CC burden

  10. - Lung Complements Aims of MESA II • Increased pulmonary vascular resistance may be major determinant of impaired LV filling • Examines potential mechanisms • Loss of lung vasculature + parenchyma • Hyperinflation • Hypoxemia • Hypercoagulability and increased viscosity • Endothelial dysfunction • Uniquely testable in the MESA cohort

  11. - Lung MESA-COPD Study HL093081 MR Pulmonary Angiography

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