1. Mini Lecture 1 Module: Effects of Tobacco on the Cardiovascular System
EPIDEMIOLOGY OF CVD AND SMOKING
Mini Lecture 1
Module: Effects of Tobacco on the
Cardiovascular System
Key References:
Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to PLoS Med. 2006; 3(11):e442.
Benowitz NL. Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis. 2003; 46(1) : 91–111.
Tonstad S, Johnston JA. Cardiovascular risks associated with smoking: a review for clinicians. Eur J Cardiovasc Prev Rehabil. 2006; 13:507–14.
He J, Vupputuri S, Allen K, Prerost MR, Hughes J, Whelton PK. Passive smoking and the risk of coronary heart disease--a meta-analysis of epidemiologic studies. N Engl J Med. 1999;340(12):920–6.

2. Objectives of the Mini Lecture
GOAL OF MINI LECTURE: Provide students with knowledge about the burden of smoking and tobacco use among patients with cardiovascular diseases (CVD).
LEARNING OBJECTIVES
Students will be able to:
Understand the global burden of CVD and smoking
Discuss the burden of smoking in CVD patients
Describe the association between active and passive smoking and CVD
Module Description:
This module is intended to provide students with knowledge of the global burden of CVD and smoking, and the burden of smoking behavior in CVD patients. Students will discuss the association between smoking and CVD, as well as the risk of second hand smoke exposure to CVD.

3. Contents Core Slides: Optional Slides:
Cardiovascular Diseases (CVDs) as a Leading Cause of Global Death
Smoking-attributable Deaths: The Global Context
Smoking-attributable Deaths in the Asia Pacific Region
Mortality from CVD in India
Smoking as a CVD Risk Factor
Smoking Attributable CVD Deaths in India
Cost-effectiveness of Smoking Cessation for CVD Prevention
Cardiovascular Risks of Secondhand Smoke
Constituents of Cigarette Smoke that Contribute to CVD
Smoking and Acute Myocardial Infarction (AMI)
Factors Associated with Risk of AMI

4. CORE SLIDES Epidemiology of CVD and Smoking Mini Lecture 1
Module: Effects of Tobacco on the
Cardiovascular System
There are five core generic slides:
Cardiovascular Diseases (CVDs) as a Leading Cause of Global Death
Smoking-attributable Deaths: The Global Context
Smoking-attributable Deaths in the Asia Pacific Region
Mortality from CVD in India
Smoking as CVD Risk Factor
Smoking Attributable CVD Deaths in India
Cost-effectiveness of Smoking Cessation for CVD Prevention
Cardiovascular Risks of Secondhand Smoke

5. Cardiovascular Diseases (CVDs) as a Leading Cause of Global Death
Globally, non-communicable diseases (NCD) accounted for 58% and 62% of deaths in men and women, respectively, in 2004.
Cardiovascular disease (CVD) deaths in 2004: 26.8 million in men and 31.5 million in women.
Two leading causes of death: ischemic heart disease (12.2% of all deaths) and cerebrovascular disease (9.7%).
Both diseases were the leading causes of death globally, in middle- and high-income countries.
In low income countries, ischemic heart disease was 2nd cause of death (9%) and cerebrovascular disease was 5th (6%).
Notes:
In 2004, the World Health Organization updated their Global Burden of Disease work, which originated in 1990:
The 2004 estimate showed that 60% of global deaths were caused by non-communicable diseases (NCD), 30% by communicable diseases, and 10% by injury.
Deaths were more common in young age groups in low-income countries in Africa, the Eastern Mediterranean, and South East Asia, and were more common in older age groups in high-income countries in America and Europe, mainly related to NCD.
Cardiovascular disease is the leading cause of global death, and accounted for 26.8 million deaths in men and 31.5 million deaths in women in 2004.
The two leading causes of death were ischemic heart disease (estimated 7.2 million deaths in 2004, or 12.2% of global death) and cerebrovascular disease (5.7 million or 9.7%). In high income countries, ischemic heart disease accounted for 1.3 million deaths (16.3% of total deaths) and cerebrovascular diseases accounted for 0.8 million death (9.3% of total deaths).
In middle-income countries, the leading causes of death were cerebrovascular disease (3.5 million deaths or 14.2%) and ischemic heart disease (3.4 million deaths or 13.9%).
Reference:
World Health Organization. The Global Burden of Disease. Geneva: World Health Organization; Update, 2008.
World Health Organization 2008

6. Smoking-attributable Deaths: The Global Context
In 2030, smoking will account for 10% of global deaths.
Between 2002 and 2030, tobacco-related deaths are projected to:
Decrease by 9% in high-income countries.
Double in low-and middle-income countries (from 3.4 million to 6.8 million).
Leading causes of tobacco-attributable deaths are: cancer (33%), cardiovascular diseases (29%), and chronic respiratory diseases (29%).
Notes:
The Comparative Risk Assessment (CRA) project estimated tobacco-related deaths using past and current age-specific smoking prevalence adjusted to regional characteristics of the tobacco epidemic in different WHO sub-regions. Using the recent World Bank data on adult per capita consumption of cigarettes and patterns of age-sex specific lung cancer mortality, the country specific-estimate was developed from the regional projections.
The CRA projected an increase of tobacco-attributable deaths from 5.4 million in 2005 to 8.3 million in 2030 (the estimates in 2030 range from 7.4 million in the optimistic scenario to 9.7 millions in the pessimistic scenario). This burden was projected to decrease in many high-income countries by 9%, in contrast to a doubling burden estimated in low-and middle-income countries (from 3.4 million to 6.8 million). The leading cause of tobacco-attributable deaths are:
Cancer (33%), mainly trachea, bronchus, and lung cancer (18%)
Cardiovascular disease (29%), including ischemic heart disease (14%), cerebrovascular disease (8%), and other cardiovascular disease (4%)
Chronic respiratory disease (29%), mainly related to chronic obstructive pulmonary diseases (27%)
Other diseases: diabetes mellitus (2%), tuberculosis (1%), lower respiratory infection (2%), digestive diseases (3%).1
By analyzing the available data from 600,000 adult subjects in the Asia Pacific Cohort Studies Collaboration (APCSC), Martiniuk et al. quantified the direct burden of smoking for cardiovascular diseases (CVD) by calculating the population attributable fractions (PAF) for fatal ischaemic heart disease (IHD) and stroke (haemorrhagic and ischaemic) for all 38 countries in the World Health Organization Western Pacific and South East Asian regions.
The results showed that the prevalence of smoking in the 33 countries ranged from 28–82% in males and from 1–65% in females. The portion of IHD attributable to smoking ranged from 13–33% in males and from <1–28% in females. The percentage of haemorrhagic stroke attributable to smoking ranged from 4–12% in males and from <1–9% in females. Corresponding figures for ischemic stroke were 11–27% in males and <1–22% in females. Up to 30% of some cardiovascular fatalities can be attributed to smoking, which might have grown since the study was conducted.2
References:
Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to PLoS Med. 2006; 3(11):e442.
Martiniuk AL, Lee CM, Lam TH, Huxley R, Suh I, Jamrozik K, et al. The fraction of ischaemic heart disease and stroke attributable to smoking in the WHO Western Pacific and South-East Asian regions. Tob Control ; 15(3):181–8.

7. Smoking-attributable Deaths in the Asia-Pacific Region
Smoking contributes to 30% of cardiovascular deaths in Pacific and South-East Asia regions.1
Smoking causes:
10–33% of heart diseases among men (10% in Australia and 33% in Kiribati).
3–12% of hemorrhagic stroke among men (3% in Australia and Palau, and 12% in Kiribati).
8–27% of ischemic stroke among men (8% in Australia and 27% in Kiribati).
1. Martiniuk et al., 2006
Notes:
By analyzing the available data from 600,000 adult subjects in the Asia Pacific Cohort Studies Collaboration (APCSC), Martiniuk et al. quantified the direct burden of smoking for cardiovascular diseases (CVD) by calculating the population attributable fractions (PAF) for fatal ischaemic heart disease (IHD) and stroke (haemorrhagic and ischaemic) for all 38 countries in the World Health Organization Western Pacific and South East Asian regions.
The results showed that the prevalence of smoking in the 33 countries ranged from 28% to 82% in males and from 1% to 65% in females. The fraction of IHD attributable to smoking ranged from 13% to 33% in males and from <1% to 28% in females. The percentage of haemorrhagic stroke attributable to smoking ranged from 4% to 12% in males and from <1% to 9% in females. Corresponding figures for ischemic stroke were 11% to 27% in males and <1% to 22% in females. Up to 30% of some cardiovascular fatalities can be attributed to smoking, which might have been grown since the study was conducted.
References:
Martiniuk AL, Lee CM, Lam TH, Huxley R, Suh I, Jamrozik K, et al. The fraction of ischaemic heart disease and stroke attributable to smoking in the WHO Western Pacific and South-East Asian regions. Tob Control. 2006; 15(3):181–8.
Ministry of Health Indonesia. The Tobacco Source Book—Data to support a National Tobacco Control Strategy. Jakarta: Ministry of Health Indonesia, 2004.

8. Mortality from CVD in India
CVD accounted for 29% of all deaths in India in
Nearly 10 million deaths are predicted to occur in the year 2015; CVD will account for one third of these deaths.2
CVD death toll is projected to rise from 3 million in 2000 to 4.8 million in 2020, and will account for 42% of total deaths.
Between 2000 and 2020, about 35% deaths will occur among year olds, mostly attributable to tobacco use.3
Notes:
The relative risk for death due to tobacco use in cohort studies from rural India is
40% to 80% higher for any type of tobacco use;
50% to.60% higher for smoking;
90% higher for reverse smoking;
15% and 30% higher for tobacco chewing in men and women, respectively;
40% higher for chewing and smoking combined.
An urban cohort study in Mumbai found that the relative risk of dying was more than 50% higher for smokers and about 15% higher for smokeless tobacco users.
An urban case control study in Chennai found that the relative risk of dying for smokers was slightly higher than two-fold.
Overall, smoking currently causes about 700,000 deaths per year in India.
In addition, there are excess deaths due to smokeless tobacco use, which is common among men as well as women and also deaths due to exposure to second-hand smoke. These deaths have not been quantified, but it appears reasonable to assume that these will add at least another 100,000 deaths. Thus, a conservative estimate of tobacco-attributable mortality in India would be about 800,000.
References:
Reddy KS. India wakes up to the threat of cardiovascular diseases, J. Am. Coll. Cardiol, 2007; 50:1370–2.
Indrayan A. Forecasting vascular disease cases and associated mortality in India. Reports of the National Commission on Macroeconomics and Health. Ministry of Health and Family Welfare, India Available at: Accessed February 18, 2008.
Reddy KS, Gupta PC, editors. Report on tobacco control in India. Ministry of Health and Family Welfare, Government of India, Centers for Disease Control and Prevention, USA, World Health Organization 2004.
Reddy 2007; 2. Indrayan et al. 2008; 3. Reddy and Gupta 2004

9. Smoking as a CVD Risk Factor
Smoking is an established risk factor for many cardiovascular diseases such as: peripheral vascular disease (PVD), aortic aneurysm, coronary heart disease (CHD), and cerebrovascular disease (stroke).1
12% of deaths in China were attributable to smoking (22% to respiratory disease, 16% to neoplastic disease, and 9% to vascular disease).2
30% of cardiovascular deaths in the Pacific and Southeast Asia regions are attributable to smoking.
Notes:
Seven of the 10 leading risk factors attributable to death are risk factors for NCD. Tobacco is a risk factor to several NCDs, such as lung cancer and almost all other cancers, chronic obstructive pulmonary diseases, and all vascular diseases (WHO, 2002).
References:
World Health Organization. The World Health Report Reducing risks, promoting healthy life. Geneva: World Health Organization, 2002.
Niu SR, Yang GH, Chen ZM, Wang JL, Wang GH, He XZ, et al. Emerging tobacco hazards in China: 2. Early mortality results from a prospective study. BMJ. 1998; 317(7170):1423–4.
1. World Health Organization 2002; 2. Niu et al. 1998

10. Smoking Attributable CVD Deaths in India
Smoking causes a large and growing number of premature deaths.1
Overall, smoking in India accounts for 20% of deaths from stroke and 24% of deaths from cardiac and other vascular diseases.2
Notes:
In India, the excess number of deaths among adult smokers in 2010 will be about 930,000, including 580,000 deaths among men and 90,000 deaths among women between the ages of 30 and 69 years. Because of population growth, the annual number of smoking-associated deaths among adults will be about 1 million during
In the rural as in the urban study area, heart and other vascular disease again accounted for about one third of all smoking-associated mortality at ages 25–69 years, for although the relative risk for vascular disease (odds ratio (OR) 1.7; CI = 1.6–1.9) is less extreme than that for respiratory disease, vascular disease is the most common cause of death at these ages.2
References:
Jha P, Jacob B, Gajalakshmi V, Gupta PC, Dhingra N, Kumar R, et al., for the RGI–CGHR Investigators. A nationally representative case–control study of smoking and death in India, N Engl J Med. 2008; 358:1137–47.
Gajalakshmi V, Peto R, Kanaka TS, Jha P. Smoking and mortality from tuberculosis and other diseases in India: retrospective study of adult male deaths and controls. Lancet. 2003; 362:507–15.
1. Jha et al. 2008; 2. Gajalakshmi et al. 2003

11. Cost-effectiveness of Smoking Cessation for CVD Prevention
Compared to other CVD prevention strategies (such as lowering blood pressure, blood glucose, LDL cholesterol, BMI), smoking cessation is the most cost-effective intervention for CVD prevention.
Notes:
Kahn et al.1 simulated effects of different prevention activities for CVD prevention using the National Health and Nutrition Education Survey in US adults aged years old. The study compared health outcomes, quality of life, and direct medical costs to current levels of prevention and care. The study estimated the cost-effectiveness of various CVD prevention activities, including: provision of low dose aspirin (81 mg daily aspirin); lowering LDL cholesterol to <160 mg/dl in low-risk individuals, to <130 mg/dl in high-risk individuals, or to <100 mg/dl in people with CAD or diabetes; lowering blood pressure to 140/90 mmHg in non-diabetic individuals or 130/80 mmHg in diabetic individuals; lowering A1C to <7% in diabetic individuals; lowering FPG to <110 mg/dl; reducing weight to BMI<30kg/m2; and smoking cessation. Of all these tested interventions, smoking cessation is the only cost-saving intervention over a 30 year period. Smoking cessation will cost $1,755/Quality-Adjusted Life Year (QALY), as compared to $2,779/QALY for low-dose aspirin, $17,500 for lowering FPG<110 mg/dl, $ for lowering BMI, and at the other extreme, $272,000 for lowering cholesterol <160 mg/dl among CAD patients. This cost-effectiveness analysis depends a lot on the cost of each unit of prevention activity themselves, which can range from $597 for smoking cessation up to $106,906 for lowering A1C <7% among diabetes. patients
Quality-Adjusted Life Year (QALY) measures quality and quantity of life lived. QALY is used to measure disease burden, mainly to assess the value for money of an intervention. The QALY estimates the number of years of life that would be gained by an intervention. More detailed information can be obtained from
Reference:
Kahn R, Robertson RM, Smith R, Eddy D. The impact of prevention on reducing the burden of cardiovascular disease. Diabetes Care. 2008; 31(8):1686–96.
Kahn et al. 2008

12. Cardiovascular Risks of Secondhand Smoke
Secondhand smoke (SHS) exposure in the home and workplace increases the risk of coronary heart disease among nonsmokers by 25%-30% among both men and women.1
A significant dose-response relationship exists between intensity and duration of exposure to SHS and CVD risks:
Risk increases sharply with low doses of SHS (< 5 cigs/day).
Risk increases more slowly and linearly with higher level of exposure (5-20 cigs/day).2
Notes:
He et al.1 conducted meta-analysis to assess the risk of coronary heart disease related to secondhand some (SHS) among non-smokers. The meta-analysis was done on 10 cohort and 8 case-control studies, mainly in the US and UK, and from other countries including Japan, New Zealand, China, Argentina, Australia, and Italy. The researchers found that a non-smoker exposed to SHS had a 25% higher risk (relative risk/RR=1.25; 95% CI = 1.17–1.32) of developing coronary heart disease than a non-smoker who was not exposed to SHS.
He et al.1 also identified a significant dose-response relationship in this meta-analysis. The risk increased with the number of cigarettes an individual was exposed to (23% higher risk/RR=1.23; 95% CI = 1.13–1.34 for those exposed to 1–19 cigarettes, and 31% higher risk/ RR=1.31; 95% CI = 1.21–1.42 for those exposed to more than 20 cigarettes). Pechachek and Babb2 established that the association between duration of exposure and CVD risk was not linear. The longer the duration of exposure to second hand smoke, the higher the risk of CVD (18% higher risk/RR= 1.18; 95% CI = 0.98–1.42 for those exposed for less than 10 years vs. 31% higher risk/ RR=1.31; 95% CI = 1.11–1.55 for those exposed for 10–19 years vs. 29% higher risk/ RR=1.29; 95% CI = 1.16–1.43 for those exposed 20 years or more). Pechacek and Babb demonstrated that the risk increased significantly with low doses of exposure, and it increased more linearly with a higher level of exposure.
References:
He J, Vupputuri S, Allen K, Prerost MR, Hughes J, Whelton PK. Passive smoking and the risk of coronary heart disease—a meta-analysis of epidemiologic studies. N Engl J Med. 1999; 340(12):920–6.
Pechacek TF, Babb S. How acute and reversible are the cardiovascular risks of secondhand smoke? BMJ. 2004; 328(7446):980–3.
1. He et al. 1999; 2. Pechacek et al. 2004

13. OPTIONAL SLIDES Epidemiology of CVD and Smoking Mini Lecture 1
Module: Effects of Tobacco on the
Cardiovascular System
The optional supplementary slides include three slides:
Constituents of Cigarette Smoke that Contribute to CVD
Smoking and Acute Myocardial Infarction (AMI)
Factors Associated with Risk of AMI

14. Constituents of Cigarette Smoke that Contribute to CVD
Main contributors:
Nicotine
Carbon monoxide
Oxidant (chemical) gases: oxides of nitrogen and free-radicals
Other contributors promote atherogenesis:
Polycyclic aromatic hydrocarbons
Other constituents
Notes:
Tobacco contains more than 4000 chemical substances, most of which are toxic for the human body. There are three main constituents that were identified as main contributors to CVD:
Nicotine—a sympthatomimetic agent that can lead to endothelial dysfunction, lipid abnormalities, and insulin resistance.
Carbon monoxide—CO competes with haemoglobin in oxygen binding, and can influence oxygen release by hemoglobin. CO reduces the oxygen carrying capacity of haemoglobin, leading to increasing red blood cell mass and increased blood viscosity (hypercoagulable state).
Oxidant (chemical) gases—oxides of nitrogen and free radicals in cigarette smoke deplete endogenous levels of antioxidants. Exposure to cigarette smoke also increases level of lipid peroxidation products. Oxidant stress can lead to endothelial dysfunction, inflammation, lipid abnormalities (LDL oxidation), and platelet oxidation.
Several other constituents can also promote atherogenesis in smokers. Exposure to polycyclic aromatic hydrocarbons (PAHs) and inhaled butadiene accelerate atherosclerosis in animals. Mutation of smooth muscle or other cells was hypothesized to become the source of an atherosclerotic plaque.
Reference:
Benowitz NL. Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis. 2003; 46(1):
Benowitz 2003

15. Smoking and Acute Myocardial Infarction (AMI)
A current smoker has a 3x higher risk of experiencing non-fatal MI compared with a never smoker.
Dose response relationship between number of cigarettes smoked per day and risk of AMI is independent of age.
The risk of AMI increases even with low levels of smoking.
Risk increases by 5.6% for every additional cigarette smoked.
Notes:
Current smoking was associated with a nearly 200% greater risk of non-fatal AMI (odds ratio OR 2.95; 95% CI = 2.77–3.14, p< 0·0001) compared with never smoking. Three years after quitting, the OR for former smoking fell to 1.87 (95% CI = 1.55–2.24). Residual risk remained 20 or more years after quitting (OR 1.22, 95% CI = 1.09–1.37).
Given the evidence that the risk of acute myocardial infarction halves significantly following quitting, doctors should inform patients of the benefits of quitting, regardless of the number of years they have been smoking. Doctors should inform patients that their risk of AMI quickly starts to decrease if they quit smoking, and should strongly advise patients to quit smoking.
Reference:
Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006; 368:647–58.
Teo et al. 2006

16. Factors Associated with Risk of AMI
Young smokers are at higher risk of AMI compared to older smokers
Higher prevalence of smoking
Higher numbers of cigarettes smoked per day
Risk of acute myocardial infarction (AMI) from:
Smoking beedies: 2.89
Chewing tobacco: 2.23
Smoking and chewing: 4.09
Low doses of exposure (1–7 hour/week)=1.24
High doses of exposure (>21 hour/week)=1.62
Notes:
Smoking beedies alone (indigenous to South Asia) was associated with an increased risk of 189% (OR 2.89; 95% CI = 2.11–3.96), similar to that associated with cigarette smoking. Chewing tobacco alone was associated with a 120% higher risk (OR 2.23; 95% CI = 1.41–3.52), and smokers who also chewed tobacco had a 300% higher risk of AMI (OR 4.09; 95% CI = 2.98–5.61).
SHS was associated with a graded increase in risk related to exposure; the risk increased by 24% (OR 1.24; 95% CI = 1.17–1.32) in individuals who were least exposed (1–7 h per week) and by 62% (OR 1.62; 95% CI = 1.45–1.81) in people who were most exposed (>21 h per week).
Given the higher risk of AMI among young smokers compared to older smokers, particularly observed in any form of tobacco use, and increasing risk related to higher exposure, doctors should advise any young smokers to quit smoking as soon as possible. Doctors should also advise patients to prevent their children from smoking initiation, as studies have shown that smokers who start early tend to develop higher dependence to tobacco uses.
Reference:
Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006; 368:647–58.
Teo et al. 2006

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