Mini Lecture 2 Module: Effects of Tobacco on the Cardiovascular System

1. SMOKING AND CARDIOVASCULAR DISEASES: THE MECHANISMS Mini Lecture 2 Module:Effects of Tobacco on the Cardiovascular System

2. Objectives of the Mini Lecture GOAL OF MINI-LECTURE: Provide students with knowledge about the risks of cardiovascular disease among tobacco users. LEARNING OBJECTIVES Students will be able to: • Discuss how smoking can cause cardiovascular diseases. • Understandthe mechanisms underlying the hazardous effects of smoking on cardiovascular diseases. • Describe the impacts of secondhand smoking on cardiovascular diseases.

3. Contents Core Slides: Optional Slides: Smoking and CVD: Causation Pathophysiology of CigaretteSmoking and CVD (1) Pathophysiology of CigaretteSmoking and CVD (2) Secondhand Smoke and CVD: the Underlying Mechanism Pathophysiology of Cigarette Smoking and CVD: Hemodynamic Effects Pathophysiology of Cigarette Smoking and CVD: Endothelial Injury and/or Dysfunction Pathophysiology of Cigarette Smoking and CVD: Thrombosis Pathophysiology of Cigarette Smoking and CVD: Inflammation Gene–Environment Interaction in the Causation of CHD

4. CORE SLIDES Smoking and Cardiovascular Diseases: The Mechanisms Mini Lecture 2 Module: Effects of Tobacco on the Cardiovascular System

5. Smoking and CVD: Causation • Cigarette smoking is a cause of peripheral vascular disease (PVD), aortic aneurysm, coronary heart disease (CHD), and cerebrovascular disease (stroke). • Smoking contributes to the development and progression of atherosclerosis plaque, which leads to an increased risk of thrombosis of the narrowed vessels. • Smoking induces a localized inflammatory response in the lungs. • Smoking induces a systemic inflammatory response  elevations in inflammatory markers, which is a risk marker (and potentially a risk factor) of CVD USDHHS 2004; Burns 2003

6. Pathophysiology of CigaretteSmoking and CVD (1) • Mechanisms by which smoking causes acute cardiovascular disease: • Thrombosis • Endothelial dysfunction • Inflammation • Hemodynamic changes • Smoking-mediated thrombosis appears to be a major factor in the pathogenesis of acute cardiovascular events. Benowitz 2003

7. Pathophysiology of CigaretteSmoking and CVD (2) Overview of mechanisms by which cigarette smoking causes acute cardiovascular event. 1. Benowitz 2003

8. Secondhand Smoke and CVD: the Underlying Mechanism • Secondhand smoke increases platelet aggregation that leads to thrombosis, endothelial dysfunction, and inflammation.1 • Exposure of non-smoker to secondhand smoke increases white blood cells, C-reactive protein, homocysteine, fibrinogen, and oxidized low density lipoprotein cholesterol – value similar to active smokers.2 • In animal experiments, there was evidence of a cause-effect vascular toxicity.1 1. Law and Wald 2003; 2. Pechacek and Babb 2004

9. OPTIONAL SLIDES Smoking and Cardiovascular Diseases: The Mechanisms Mini Lecture 2 Module: Effects of Tobacco on the Cardiovascular System

10. Pathophysiology of Cigarette Smokingand CVD: Hemodynamic Effects • Mainly mediated by nicotine. • Related to coronary ischemia due to imbalance of myocardial oxygen demand and blood supply. • The mechanisms are: • Stimulation of sympathetic nervous system  increases myocardial oxygen demand. • Constriction of coronary artery  decreases coronary blood flow. 1. Benowitz 2003; 2. Ford and Zlabek 2005

11. Pathophysiology of CigaretteSmoking and CVD: EndothelialInjury and/or Dysfunction • Mainly related to oxidant chemicals. • Oxidant chemicals lead to constriction of blood vessels and inhibition of platelet aggregation. • Changes in the structure and function of vascular smooth muscle and endothelial cells  vascular thickening. • Releases of basic fibroblast growth factor lead to DNA synthesis, mitogenic activity, and endothelial proliferation. Benowitz 2003

12. Pathophysiology of Cigarette Smokingand CVD: Thrombosis • Mainly related to increased platelet aggregation. • Several mechanisms: • Lack of inhibition of platelet activation by nitric oxide • Impaired fibrinolysis (low tPA and high PAI-1) • Higher levels of tissue factor • Increased blood viscocity related to compensation for relative hypoxemia 1. Benowitz 2003; 2. Ford and Zlabek 2005

13. Pathophysiology of Cigarette Smokingand CVD: Inflammation • The inflammation mechanisms are unclear. • Oxidant stress appears to play a major role. • Nicotine as a chemotactic agent for neutrophil migration. • Nicotine acts on human monocyte-derived dendritic cells. • Inflammation is believed to contribute to atherogenesis. Benowitz 2003

14. Gene–Environment Interactionin the Causation of Chronic Heart Disease (CHD) • A prospective study in Great Britain found: • Smokers have 1.94 times higher risk (95% CI = 1.25– 3.01) for CHD compared to non-smokers. • Smoking interacts with genetic factors (carrier of allele ApoE 4) and increases risk by 197% (OR 2.97; 95% CI = 1.59–4.91).1 • Possible mechanisms: • ApoE 4 is more suspectible to LDL oxidation. • A high level of ApoE inhibits migration of invitro vascular smooth cells – patients with ApoE 4 have higher risk of lesion development on vascular bed.2 1. Talmud 2004; 2. Humphries et al. 2001

15. The most important health message a doctor can give to patients is to quit smoking.