Tobacco and

Cardiovascular
Diseases the
Mechanisms
Mini Lecture 2
Module: Tobacco effects on
cardiovascular system

Objectives of the Mini Lecture

GOAL OF MINI-LECTURE: Provide students with
knowledge on the mechanisms of hazardous effects of
smoking and tobacco use to cardiovascular diseases
LEARNING OBJECTIVES
Learners will be able to:
Discuss how smoking can cause cardiovascular diseases
Discuss the mechanisms underlying the hazardous
effects of smoking on cardiovascular diseases
List the impacts of passive smoking on cardiovascular
diseases

CORE SLIDES
Tobacco and Cardiovascular
Diseases: the Mechanisms
Mini Lecture 2
Module: Tobacco effects on
cardiovascular system

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 lead to the increase 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)

Pathophysiology of Cigarette
Smoking and CVD
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)

Pathophysiology of Cigarette
Smoking and CVD

Overview of mechanisms by which cigarette smoking causes acute cardiovascular event.

(Benowitz, 2003)

Secondhand smoke and CVD:

the underlying mechanism
Secondhand smoke increases platelet aggregation that
leads to thrombosis, endothelial dysfunction,
inflammation (Law and Wald, 2003)
Exposure of secondhand smoke to non-smoker
increases white blood cells, C-reactive protein,
homocysteine, fibrinogen, and oxidized low density
lipoprotein cholesterol value similar to active smokers
(Pechacek and Babb, 2004)

A cause-effect evidence of vascular toxicity in animal

experimentation (Law and Wald, 2003)

OPTIONAL SLIDES
Tobacco and Cardiovascular
Diseases: the Mechanisms
Mini Lecture 2
Module: Tobacco effects on
cardiovascular system

Pathophysiology of Cigarette Smoking

and 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 increase
myocardial oxygen demand.
Constriction of coronary artery decreases coronary
blood flow.

(Benowitz, 2003; Ford and Zlabek, 2005)

Pathophysiology of Cigarette Smoking

and CVD: endothelial injury 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)

Pathophysiology of Cigarette Smoking

and 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

(Benowitz, 2003; Ford and Zlabek, 2005)

Pathophysiology of Cigarette Smoking

and 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)

Gene-environmental interaction in the

causation of CVD
A prospective study in the Great Britain:
Smoker has 1.94 times higher risk (95% CI=1,25 3,01) to experience CHD compared to non-smoker
Smoking interacts with genetic factor (carrier of alel
ApoE 4 allel) and increases the risk to 197% higher
risk (OR=2.97; 95% CI=1,59 4,91).
Possible mechanisms:
APOE 4 is more suspectible to LDL oxidation
A high level of ApoE inhibit invitro vascular smooth
cells migration patients with APOE 4 has higher risk
of lesion development on vascular bed
(Talmud, 2004; Humphries et al., 2001)