Epidemiology of Cigarette Smoking and Cardiovascular Disease

Environmental Toxicology Assignment

Abstract

1.1 billion people smoke in today’s world. These people knowingly increase their risk of premature death every day. Thy are also putting everyone else around them at risk. Over 7 million people die worldwide every year due to cigarette smoke. Cigarettes can exert their effects both directly and in-directly. 6 million of these people die as a direct result of tobacco use while almost 1 million of these people are non-smokers and die due to inhalation of second-hand smoke. Cardiovascular disease is the leading cause of death in the world and cigarette smoking is the leading risk factor of cardiovascular disease. The thousands of chemicals in cigarette smoke cause severe damage to the heart and the arteries which carry blood around the body. Many studies have been conducted throughout the world on every aspect of cigarette smoking, from the damage it causes to organs to whether men and women react differently to cigarette smoke. Cigarettes have been studied in depth, the dangers associated with them are endless, their devastating effects are advertised worldwide yet the addictive chemical nicotine keeps driving people back to them. Cigarettes can have varying effects on human’s dependant on certain genotypes, this adds an unpredictability to cigarettes which makes it even more difficult to provide early diagnosis and treatment to those affected by them (World Health Organization, 2017). Cigarette smoke has been shown to cause severe damage to humans from a molecular and cellular level to damage to vital organs and even influencing behavioural characteristics. Cigarettes are popular throughout the world, regardless of the damage they cause the worldwide population continues to embrace them and many of these people will pay the ultimate consequence for doing so.

Introduction

Cardiovascular disease is the leading cause of death in the world. Cardiovascular diseases such as coronary heart disease (including myocardial infarction and sudden death), cerebrovascular disease (stroke), peripheral artery disease (PAD), abdominal aortic aneurysm, and hypertension are identified to be directly related to smoking. According to data published by the World Health Organization (WHO) in 2012, 46.2% (17.5 million) of all deaths globally were the result of cardiovascular diseases. 7.4 million of these deaths were ischemic cardiac diseases. Cardiovascular diseases are responsible for 37% of deaths below the age of 70 years. Deaths due to cardiovascular diseases are estimated to be 22.2 million in 2030, 8 million of which are related directly to smoking. 37% of deaths worldwide below the age of 70 are caused by cardiovascular diseases. 22.2 million people are estimated to die from cardiovascular diseases in 2030, 8 million of these deaths are expected to be directly caused by cigarette smoking. Strangely however, most of the deaths from cardiovascular diseases are ‘preventable’ (Akcay, M., et al. 2017). Cigarette smoking is thought to be the leading preventable cause of death in the world. Cigarette smoking is an important risk factor for cardiovascular disease. Smoking has an effect on every organ in the body. It is detrimental to the heart and blood vessels. Tobacco smoke contains over 4000 chemicals including nicotine and carbon monoxide which are known to have harmful effects on cardiovascular function (Papathanasiou, G., et al. 2014). 60 of the chemicals found in cigarette smoke are known to be carcinogenic (Sopori, M., et al. 2002).

Original Implications of Cigarette Smoking in Cardiovascular Disease

The first cohort studies indicating that death from cardiovascular disease is more prevalent in smokers than non-smokers were published in the 1950’s. Before this time cigarettes were enjoyed without much concern for any potential repercussion. Cigarettes became popularized by manufacturers in the early 1900’s and this seen a major increase in the amount of people who were smoking throughout the world (Michael Pittilo, R., et al. 2000), (Doll, R., et al. 1956), (Hammond, E.C., et al. 1958). Cigarettes were now being produced on a large scale thanks to new technology at the turn of the 20^th century and cigarettes were being glamourized by manufacturing companies through advertising. It really was the fashionable trend to be associated with smoking cigarettes at the time. The US military were even supplying free cigarettes to their soldiers during World War I and II (Hammond, E.C., et al. 1958).

In the late 1920’s to the late 1940’s researches soon began to question the effects cigarettes may be having on human health due to a major increase in numbers of heart and lung diseases. These studies were insufficient from an evidence point of view and could not reach the impact level which would highlight the damaging effects cigarettes were having to the world. Hammond and Horn’s was a major stepping-stone in terms of highlighting the damaging effects smoking has on the cardiovascular disease. Hammond and Horn took on the task of conducting an in depth cohort study, the results of which would be impossible for cigarette manufacturers to debate like they had been doing for the previous half century or so. Hammond and Horn were able to get 22,000 volunteers to help recruit American males from the ages 50 to 69 across 10 states and question these men on their smoking habits. Hammond and Horn were able to include 188,000 men in their study and follow these men for almost four years. Eleven months after the study began the volunteers conducted the first follow up, indicating whether the men they were checking up on were dead or alive. If the men had deceased Hammond and Horn obtained a copy of their death certificates. After almost two years Hammond and Horn published their preliminary findings, they found that men who smoked had a significantly higher death rate than men who did not. A few months later, the two men felt that they had enough evidence to show the damaging effects of cigarette smoking. They published their paper and ended it stating, “… we are of the opinion that the associations found between regular cigarette smoking and death rates from diseases of the coronary arteries and between regular cigarette smoking and death rates from lung cancer reflect cause and effect relationships” (Hammond, E.C., et al. 1958).

Epidemiology studies, cellular pathology studies, chemical analytics and experimentation with animals soon pointed towards cigarette smoking as the cause for respiratory and cardiovascular diseases. Many reports have been published indicating that cardiovascular disease is the highest cause of smoking-related premature death. It took time for people to fully consider the effects of cigarettes to their health (Michael Pittilo, R., et al. 2000). Even in the late 1960’s only one-third of all doctors in the USA believed that there was a case against cigarettes (Proctor, R.N., et al. 2012).

Mechanisms of Exposure to Cigarette Smoke

Cigarette smoke is divided into two phases, the gas phase and the tar phase. The tar phase (particulate phase) is the material particles that are trapped when the smoke passes through the filter. The filter retains 99.9% of all particles of >0.1 μm in size. The gas phase is simply the material that passes through the filter. There is then mainstream smoke that is made up of 8% tar and 92% gaseous components, and side stream smoke that contains a higher concentration of toxic gaseous components than mainstream smoke. Mainstream smoke is the smoke which is passed through the tobacco directly into the smokers’ mouth. Side stream smoke is the smoke which is emitted from the cigarette as it burns. People can be affected by cigarette smoke directly (by smoking a cigarette) or passively (by inhaling cigarette smoke from another smoker). Second-hand smoke (environmental smoke) which can be inhaled passively is made up of 85% side stream smoke and 15% exhaled mainstream smoke. Once cigarette smoke enters the human body through the mouth, it can have adverse effects on the body in many ways (Ambrose, J.A., et al. 2004).

Although cigarette smoking is a risk for developing cardiovascular disease, many factors can influence the level of this risk and even the intensity to which a person may develop a disease. The number of cigarettes smoked per day one of these factors. However, it is important to note that there has been a series of studies attempting to link the risk of cardiovascular disease to the number of cigarettes smoked per day, but results are inconsistent around this. It would be the natural assumption that the more cigarettes smoked per day the greater risk of developing cardiovascular disease, and for the most part this is the case but there are many studies which show little correlation between the two. If anything, this is an indication of how lethal cigarettes are even at a low level of use. The duration of smoking increases the likelihood of developing cardiovascular disease, the longer a person has been smoking the greater that person’s chances are of developing cardiovascular disease. Understandably, the risk of cardiovascular disease is found to be much lower in those who have quit smoking than those who continue to smoke (Centers for Disease Control and Prevention (US), 2010).

Studies Used to Implicate Cigarette Smoking in Cardiovascular Disease

Countless studies have been conducted over the last number of decades in order to assess the effects of cigarettes on every part of the body from organelle to mental health. Studies involving the effects of smoking cigarettes unanimously outline the damaging effects cigarettes have on the human body. Both cohort and case-control studies have outlined how cigarettes affect the body and increase the risk of cardiovascular disease and hence death. Interestingly however there are many questions left to be answered regarding the effects of cigarettes and people across the world continue to develop studies to answer these questions. For example, there is no debate that cigarettes damage the human body and risk lower life expectancy, but there is no clear data whether smoking heavily over a short period of time is more dangerous than smoking less regularly over a long period of time. Similar to whether smoking is more harmful to men than women, many studies contradict each other.

Outlined are some interesting studies surrounding cigarette smoking and cardiovascular disease (Lubin, J.H., et al. 2016). One study conducted in Bosnia and Herzegovina looks at the effects of cigarette smoke on haematological parameters in healthy humans and how this causes cardiovascular diseases. In this particular study 156 people participated. 56 were smokers and 100 were non-smokers. The 56 smokers were regularly consuming 10-20 cigarettes per day for at least three years. Blood cell counts were then analysed to compare the differences between the smokers and non-smokers. The results of the study showed that the smokers had significantly higher levels of white and red blood cells, haemoglobin, mean corpuscular volume and mean corpuscular haemoglobin concentrations. Increased levels of each is highly linked with being a major cause of cardiovascular diseases. This study demonstrated how haematological parameters can be influenced by cigarette smoking, an influence which leads to increased risk of developing life threatening diseases (Malenica, M., et al. 2017).

Two studies conducted in China indicate clearly how cigarette smoking is a cause of cardiovascular disease. These studies are not linked. The first study aimed to assess the effects cigarette smoking have on a human’s chances of having an ischemic stroke (form of cardiovascular disease). This case-control study analysed data from many previously conducted studies. The study took many factors into consideration such as age and BMI. 1037 cases and 1205 controls were included in this study. The study indicated that smokers had a much higher incidence of ischemic stroke than non-smokers with OR=2.158, 95% CI 2.29-3.60. These results showed that cigarette smoking greatly increases your risk of ischemic stroke. (Ma, X., et al. 2014). The second study in China analysed the effects of smoking on the elderly population of China. A population based perspective cohort of 65,510 people enrolled in this study over a period of three years. This study took place over a period of eleven years. The results of the study show that half of all deaths in Chinese smokers over the age of 65 and a quarter of all deaths in Chinese smokers over the age of 85 were due to smoking related diseases such as cardiovascular disease and cancer. The study did not provide the exact mortality numbers. 4,024 people who died in this study did so as a result of cardiovascular disease. This study highlighted the dangers of smoking and the increased risk of developing cardiovascular disease due to smoking. Studies like these are vital in trying to increase levels of smoking cessation (Lam, T.H., et al. 2015).

An in depth study which took place in Spain aimed to highlight the effects of cigarette smoking in terms of total coronary risk in a cohort of 35-74 year olds over a period of ten years. The study followed 1011 patients in a primary care practice with no history of cardiovascular disease. 29% of these people were smokers. During the follow up the smokers had a higher mortality rate than the non-smokers and a higher rate of coronary events. The exact mortality figures were not listed in the report. The results over ten years indicated that smoking doubles the risk of coronary events (Lubin, J.H., et al. 2016).

Mechanisms by which Cigarette Smoke Exerts its Effect

Smoking is harmful to almost every organ in the body. Many of the thousands of chemicals in cigarette smoke harm the blood cells, disrupt the function of the heart and damage the structure of blood vessels which interferes with their function. Smoking causes the build-up of plaque in the arteries which is called atherosclerosis, one of the leading causes of cardiovascular disease. This plaque solidifies over time and gradually narrows the arteries. The amount of oxygen-rich blood which can flow throughout the body is reduced and the risk of blood clots is increased. If this plaque builds up in the coronary arteries, coronary heart disease can ensue, this can lead to many cardiovascular diseases such as heart attack, heart failure, arrhythmias which may all lead to death. Second-hand smoke contains a large portion of the harmful chemicals that people inhale when they smoke. Smoking also thickens the blood and makes it much more difficult to be transported around the body. Second-hand smoke can damage the heart and blood vessels in the same way that active smoking harms people who do smoke, in turn exposure to second-hand smoke greatly increases the risk of cardiovascular disease. Children and teens who are exposed to second-hand smoke have an increased risk of developing cardiovascular disease in the future as it lowers LDL (good) cholesterol, raises blood pressure and damages the tissue in the heart (NHLBI, 2018).

Cigarettes cause serious damage at a cellular and molecular level also. Tissues directly exposed to cigarette smoke are at high risk of misreplication of DNA. One study which compared the tissue of 2,490 smokers and 1,063 non-smokers showed that on average smokers had 150 extra mutations in each lung cell, 97 in each larynx cell, 23 in each mouth cell, 18 in each bladder cell and 6 in each liver cell. Cells are damaged by cigarette smoke in the form of covalent bonding of metabolically activated re-active species of carcinogens to DNA adducts (Alexandrov, L.B., et al. 2018).

The three main constituents of cigarette smoke that cause cardiovascular disease are nicotine, carbon monoxide (CO) and oxidant gases. Nicotine is a sympathomimetic drug; it is the addictive chemical in cigarettes which leaves many people unable to cease smoking. Nicotine has been found to elevate the heart rate and make it work at a much higher capacity than it should need to. CO binds to haemoglobin, which reduces the amount of haemoglobin available to carry oxygen and interferes with the release of oxygen by haemoglobin. High levels of CO have also been linked with greater mass of red blood cells which reduces the oxygen carrying capabilities of red blood cells, in turn this leads to higher blood viscosity making it much more difficult to pump around the body. The oxidant gases delivered to smokers include oxides of nitrogen and many free radicals from the gas and tar phases of cigarette smoke. Exposure to high levels of these oxidant chemicals has been linked with the depletion of antioxidants. Lipid peroxidation products in plasma and urine were also found to be elevated due to the oxidant gases. Cigarette smoke is also full of metals such as aluminium, cadmium, copper, lead, mercury, nickel and zinc. Cadmium accumulates in the aortic walls of smokers and can be a large contributing factor to cardiovascular disease (Centers for Disease Control and Prevention (US), 2010).

How Cigarette Smoking Interacts with the Human Genome and Factors that Increase the Risk of Cardiovascular Disease

Cigarette smoke not only causes damage to organs in the body, but it also has the ability to interact with various genotypes in different ways. The chemicals in cigarette smoke can affect people in different ways, depending on their genetic make-up. This is one possible explanation as to why some people live into old age while smoking heavily and others develop diseases such as cardiovascular disease and can die from smoking at a much younger age. The extent of the damage cigarette smoking has on DNA and different genotypes in the human genome is not fully comprehended to date. Different genotypes are influenced by cigarette smoking in different ways and this is not always consistent. While studies involving the damage cigarette smoking has on the heart and the lungs are in abundance, the study of the damage cigarettes have on DNA and human genes is a relatively modern topic and is somewhat lacking in terms of level of discovery. Advances in the technologies and methods used to analyse the damage caused to the human genome are popular at the moment. A new study conducted by Dr. Aziz Sancar in the Department of Biochemistry and Biophysics in the University of North Carolina has gained global recognition. Dr. Sancar developed a new method for mapping damage caused to DNA by cigarette smoking. The technology maps the sites on the genome that are being repaired following DNA damage by cigarette smoking. For the first time it is possible to see exactly what damage is caused to the DNA because of cigarette smoking. Mutations to genes caused by smoking can lead to many types of cancers throughout the body such as lung, stomach and larynx cancer. Benzo[a]pyrene (BaP), is a polycyclic aromatic hydrocarbon, it is a potent carcinogen found in cigarette smoke. It is the leading cause of lung cancer found in cigarettes. BaP forms covalent DNA adducts after metabolic activation which causes mutation. This technology may be able to help diagnose disease earlier and potentially repair gene sequences (Li, W., et al. 2017).

The damage caused by cigarettes to DNA may be life threatening due to potential diseases while may result from the alterations to DNA. A recent study using the blood of over 16,000 smokers and non-smokers discovered that cigarette smoking could lead to disease-causing DNA damage, which can last for over 30 years even after a person quits smoking. Gene expression is regulated by DNA methylation. Methylation was consistent in genes linked to smoking related diseases such as cardiovascular disease. Gene analysis indicated that one third of known genes in smokers were damaged. TIAM2 is a gene linked to lymphoma. This gene encodes a guanine nucleotide exchange factor when exposed to cigarette smoke. This study found that damage to this gene could potentially last up to 30 years due to smoking (Joehanes, R., et al. 2016).

As previously mentioned, cigarette smoking greatly increases the risk of developing cardiovascular disease; however, several studies have found that gender plays quite a large role in the probability of developing cardiovascular diseases from smoking. Women who smoke have been found at 25% higher risk of coronary heart disease than males. The factors responsible for this increased likelihood in women are unknown to this day, but it is thought that sex hormones may play a major role. In some cases, the damaging effects of cigarette smoking can be enhanced with alcohol consumption (Allen, A.M., et al. 2014). A study carried out to assess the effect of prenatal smoking on dopaminergic genotypes found that smoking during pregnancy is heavily linked with ADHD in children who are genetically susceptible. Children exposed to cigarette smoke with the DAT1 (mediates the reuptake of dopamine) and DRD4 (dopamine receptor) genes were found to be at greater risk of having ADHD than children who didn’t.  Cigarette smoking accompanied by alcohol consumption can also increase the risk of ADHD in these genetically susceptible children. This study is not only an indication of the dangers of smoking during pregnancy, but also an indication of how cigarette smoking can react differently depending on the genetic make-up of those at risk (Neuman, R.J., et al. 2007).

Lifestyle plays a huge role in the effects cigarettes have on a humans well-being. Accompanied with excessive alcohol intake and drug use, cigarettes are proven to become even more lethal. Along with these factors, poor diet, nutrition and obesity are also extremely influential to the extent of the damaging effects of cigarettes. Factors such as race, age, education and socioeconomic status are all seen as risk factors when it comes to cigarette smoking and in turn increase chances of developing cardiovascular disease.

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