Clinical Medicine Insights Received 15 Sep 2021 | Revised 20 Oct 2020 | Accepted 25 Nov 2020| Published Online 15 Dec 2020 DOI: https://doi.org/10.52845/CMI/2020-1-1-06 CMI JOURNAL 1 (1), 34−49 (2020) ISSN (O) 2694-4626 REVIEW ARTICLE Smoking and Non-Communicable Diseases: Part I Cardiovascular Diseases, Respiratory Diseases, Obesity, Depression, Liver Diseases Shashi K. Agarwal, MD ∗ 12227 US Highway 1, #309 North Brunswick, NJ 08902, USA Abstract Smoking tobacco is popular all over the world. It is however full of toxic chemicals, with many of them being carcinogenic. These chemicals affect every organ in the human body, leading to a wide array of disorders. This results in considerable suffering. frequent disability, and premature mortality. It is estimated that smokers lose several years of healthy life. Smoking hookah or e-cigarettes is also harmful. Smoking remains the number one preventable cause of several non- communicable diseases. Keywords: smoking, non-communicable diseases, cardiovascular dis- eases, respiratory diseases, obesity, depression, liver diseases Copyright : © 2021 The Authors. Published by Medical Editor and Educational Research Publishers Ltd. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 INTRODUCTION Tobacco smoking is a major modifiable risk factor for a wide array of diseases1. Besides nicotine, tobacco smoke also contains sev- eral thousand chemical compounds, either gaseous or particulate, and many of these are toxic2. In addition to the major non-communicable diseases discussed in this two-partmanuscript, tobacco smoke has been associated with complications of pregnancy and sudden infant death syndrome3. Infants exposed to cigarette smoke either prenatal or after birth also increase their risk of orofacial clefts, periodontal disease, and dental caries4. Smoking increases the risk of dental implant failure5. It also enhances aging, causing premature wrinkles6. It is estimated that 16 million adults are currently living with smoking- related diseases in the United States7. Smoking cessation reduces the risk of major chronic diseases8. Cessation also helps reduce the severity of Supplementary information The online version of this article (10.52845/CMI/2020-1-1-06) contains supplementary material, which is available to autho- rized users. Corresponding Author: Shashi K. Agarwal, MD Shashi K. Agarwal, MD 2227 US Highway 1, #309 North Brunswick, NJ 08902, USA Email: usacardiologist@gmail.com CMI JOURNAL 1 (1), 34−49 (2020) MEERP LTD 34 Open Access Journal https://doi.org/10.52845/CMI/2021-2-3-12 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ mailto:usacardiologist@gmail.com https://medicineinsights.info/index.php/cmi/index MEERP LTD SHASHI K. AGARWAL, MD the disease9, improves the quality of life10, increases disease-free life11, and augments life expectancy12. Smoking is the leading preventable cause of death worldwide13. 2 DISCUSSION CDC defines chronic diseases as “conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both”14. Most chronic diseases are noncommunicable. The five major diseases discussed in this part are cardio- vascular diseases (CVD), respiratory diseases, obe- sity, depression, and liver diseases. CVDs include coronary heart disease, high blood pressure (BP), stroke, heart failure, cardiac arrhythmias (includ- ing sudden cardiac death), peripheral arterial dis- ease, deep vein thrombosis, and vasculogenic erec- tile dysfunction. They are a leading cause of mor- bidity and mortality, globally15. Smoking remains the main modifiable lifestyle factor responsible for most of these diseases16. Even low-tar cigarettes and smokeless tobacco have been shown to increase the risk of cardiovascular events in comparison to non- smokers17. The main respiratory diseases are chronic obstructive pulmonary disease (COPD), asthma, res- piratory infections, and cancer. COPD is a progres- sive and debilitating disease that causes a decline in lung function leading to cor-pulmonale, respiratory failure, and premature death18. It is responsible for over 3 million deaths annually19. The World Health Organization (WHO) predicts that COPD will be the third leading cause of death, worldwide, in 203020. Obesity is a pandemic and is associated with in- creased morbidity and mortality21. Bodyweight clas- sification is generally based on the calculation of body mass index (BMI)22. Normal BMI is 18.5– 24.9 kg/m2, overweight is a BMI 25 to 29.9 kg/m2, and obesity is a BMI >30 kg/m223. Central obesity (visceral or abdominal obesity) often confers worse health effects, even with a normal BMI24. This type of obesity can be determined by waist circumfer- ence, waist hip-ratio, or waist-height ratio25,26. De- pression is characterized by sadness, loss of interest and pleasure, feelings of guilt, feeling of worthless- ness, low appetite, fatigue, and poor concentration27. It is estimated that it affects 350 million people worldwide28. Depression increases the risk of phys- ical ailments, especially cardiovascular diseases29. The Global Burden of Disease Study 2016 reported that depression is a major cause of disability30. It also increases suicide and all-cause mortality31. Liver diseases are on the rise worldwide and are respon- sible for a considerable amount of morbidity and mortality32. They include non-alcoholic fatty liver (NAFLD), alcoholic liver disease, cirrhosis, and liver cancer33. Hepatocellular carcinoma is highly lethal, with less than 10% living beyond 5 years34. Cardiovascular Diseases Cigarette smoking is a major cause of CVDs35. Most CVDs are due to atherosclerosis36. Smoking accel- erates this process by several mechanisms, including activation of inflammatory factors, dysregulation of the lipid metabolism, an increase in oxidative stress, and causing endothelial dysfunction37−39. Smoking acutely elevates blood pressure40 through the stim- ulation of the sympathetic nervous system41. It also increases the risk of renovascular42, malignant43, and masked hypertension44. The causal impact of smok- ing on chronic hypertension is however unclear45. Passive smoking has been associated with an in- creased risk of hypertension among adults46. Several epidemiologic studies have indicated that there is an increase in the incidence of myocardial infarction and fatal coronary artery disease with smoking47,48. Smoking raises the risk of coronary plaque rup- ture47, and this generates thrombosis at the site48. Smoking is also associated with an increase in coro- nary spasms49,50. Passive smoking also increases the risk of coronary artery disease51. In a meta- analysis of 29 prospective cohort studies, Aune et al. found that smoking increased the relative risk of heart failure by 44%52. Lu et al. confirmed this increased propensity in a recent Mendelian ran- domization analysis study53. Cigarette smoking is causally connected with 12.4% of acute strokes54. Pre-stroke smoking also appears to worsen its prog- nosis when compared to never smokers55. Smoking is also directly associated with a more than a two- fold increased risk of atrial fibrillation56. Smoking cessation lowers this risk56. Sudden cardiac death MEERP LTD CMI JOURNAL 1 (1), 34−49 (2020) 35 SMOKING AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, OBESITY, DEPRESSION, LIVER DISEASES is usually due to ventricular arrhythmias57, and this is also increased in smokers58. Smoking has been linked with an increase in the risk of peripheral artery disease59,60 and abdominal aortic aneurysms61,62. Smoking cessation is associated with a reduced rate of aneurysmal growth63. Smoking can induce erec- tile dysfunction64 through multiple pathways, with disturbed nitric oxide signal transduction pathway being the main one65−68. Smokers are also at an increased risk of venous thromboembolism69. This risk is partially increased by physical inactivity70 and the occurrence of smoking-related diseases in these patients71. Smoking cessation reduces cardiovascular events72. It reduces these risks and mortality even if cessa- tion happens after the development of a CVD73. Smoking promotes atherosclerosis via vasomotor dysfunction, increased inflammation, and modifica- tion of lipids74. It also enhances thrombosis, via prothrombotic alterations in platelet function, an- tithrombotic/prothrombotic activity, and fibrinolytic factors75. Respiratory Diseases Cigarette smoking is a major cause of COPD76,77. COPD is one of the most common and dangerous noncommunicable health disorders78. The lifetime risk for smokers getting COPD is estimated to be over 20%79, with one recent study estimating the risk to be as high as 50%80. Passive smokers are also at an increased risk of developing COPD81. COPD smokers, both current and past, exhibit an increased risk for lung cancer, CVDs, and diabetes mellitus82−84. Smoking cessation, especially at an early age, greatly helps reduce the symptoms and the rate of pulmonary function decline in these patients85,86. Their quality of life also improves87, and mortality is reduced88. Besides COPD, asthma is also a major disease affecting the respiratory tract89. Smoking increases the risk of developing asthma by 33% to 81%, when compared to nonsmokers90. Continued smoking also increases the incidence of exacerbations and poor control in these patients91. It can also lead to a more severe pulmonary disease like COPD92. Second-hand smoke exposure, espe- cially in children, also exacerbates asthma-related hospitalizations93,94. Smoking has also been associ- ated with chronic bronchitis and several interstitial lung diseases85,96. It is estimated that almost 90% of lung cancers are related to smoking97. Secondhand smoke exposure also increases the risk of lung cancer in non-smokers98. Smokers are alsomore susceptible to bacterial and viral pulmonary infections99−101. These include viral influenza and tuberculosis99,100. Smoking also increases the risk of acute respiratory distress syndrome in COVID infections101. Tobacco smoke affects the lungs in several ways – it induces oxidative stress and apoptosis102−104, increases secretions from mucous glands105,106, and alters the histologic alveolar histology107,108. Epige- netic factors may also be involved109. Obesity The relationship between smoking and obesity is complex and published reports provide conflicting results110−112. While some studies have shown no significant association between smoking status and BMI110, others have suggested that smoking may be associated with lower BMI111 and smoking cessation with an increased BMI112. Most individuals believe that smoking helps weight loss113−115, and fear of weight gain is often a cause of relapse among former smokers116. Both smokers and nonsmokers believe that smoking is an efficient way to control body weight117. Most scientific studies confirm that lower adiposity is common among active smokers118,119. Nicotine acutely increases energy expenditure120 and may also help reduce appetite121,122. Further, scien- tific studies find that former smokers have a higher level of obesity123, mainly due to an increase in BMI following smoking cessation124−126, thereby validat- ing the smokers’ bias. However, current smokers tend to have a higher visceral (abdominal) obesity than non-smokers127−129. CAT scans reveal higher levels of visceral adiposity to subcutaneous adipose tissue ratio in smokers130. Second-hand smoke expo- sure also increases obesity, with adolescents having an increased 1.19 odds of obesity than those with no exposure to secondhand smoke131. In a study includingmore than 10million participants from 239 prospective studies, all-cause mortality was minimal for persons with BMI between 20 and 25; however, each 5-unit increase in BMI above 25 was associated with a 49%, 38%, and 19% higher risk of mortality, respectively132. Therefore, there is a concern that CMI JOURNAL 1 (1), 34−49 (2020) MEERP LTD 36 MEERP LTD SHASHI K. AGARWAL, MD weight gain after smoking cessation could increase the risk of chronic diseases and potentially attenuate the benefits of quitting smoking133. However, given the serious deterioration of health from smoking, the net effect is still better health outcomes after smoking cessation134. Depression Individuals with mental health conditions smoke more heavily135 and experience up to 18 years of reduced life expectancy when compared with the general population136. This major decrease in longevity is primarily due to premature mortal- ity from smoking-related diseases137. Depression is strongly linked with smoking – and this relation- ship is bidirectional138. In the National Longitudi- nal Study of Adolescent Health from the United States, Goodman and Capitman found that smoking in adolescents resulted in a higher risk of develop- ing depressive symptoms139. In an Australian case- control study, the age-adjusted odds ratio (OR) for smoking more than 20 cigarettes per day and de- veloping depression, was 2.18140. In a multinational study (WHO’s Study on Global Ageing and Adult Health), the OR for smoking associated with incident depression was 2.06141. In another study, current smokers who smokedmore than 20 cigarettes per day had the highest risk of developing depression142. A more recent systematic review of 148 studies, also found a positive association between smoking and depression143. Another recent large study involving 10,036 individuals (Gutenberg Health Study), found that current smoking was predictive of new-onset de- pression, with an OR of 1.35144. Secondhand smoke also increases the risk of depression, in children145, adolescents146, and adults147−149. This relationship is dose dependent150. Depressed people also smoke more151−154. It is estimated that in the United Kingdom, up to 31% of individuals with depression smoke151 while only 14% of the general population does152. Depressed patients are more likely to increase their smoking over time153, and those who continue to smoke expe- rience worse depressive symptoms compared to their abstinent counterparts154. Liver Diseases Smoking is associated with worse outcomes in patients with NAFLD155,156. They are more apt to develop liver fibrosis155 and primary biliary cirrhosis156. Patients with Hepatitis B (HBV) who smoke increase their risk for hepatocellular cancer (HCC)157. Smoking is also harmful to individu- als with hepatitis C (HCV), increasing the risk of steatosis, fibrosis, and HCC158,159.Tobacco smoking has been shown to delay wound healing post-liver transplant160 and to significantly increase vascular complications in these patients161. HCC is also more common in smokers162. Lee et al. calculated that the relative risk ratio was 1.51 for this increased incidence, after conducting a meta- analysis of 38 cohort studies and 58 case-control studies, and after adjusting for HBV infection, HCV infection, and alcohol consumption163. Smoking also increases HCC related mortality164. Besides the mul- titude of carcinogens found in cigarette smoke, one chemical, 4-Aminobiphenyl, has been specifically shown to increase the risk of HCC165. Tobacco smoking has also been implicated in the reduction of p53, a tumor-suppressing gene and a common pathway of oncogenesis for many neoplasms166. Al- cohol is extremely harmful to the liver167. Almost 90% of alcoholics smoke and most of them smoke at least one pack of cigarettes per day168. Chronic smokers are also more likely to consume alcohol in excess169. Smoking is also harmful in patients needing liver transplantation – a poor lung function often precludes liver transplantation170. Following transplantation, smoking increases the risk of de novo malignancy171, vascular complications172, and non-graft-associated mortality173. 3 CONCLUSION Tobacco is highly addictive and extremely harmful. It increases the risk of developing and worsening the progression of several non-communicable diseases, including cardiovascular, respiratory, and liver dis- eases. It is also detrimentally associated with obesity and depression. There is no safe level of tobacco exposure including second-hand and third-hand ex- posure. Smoking cessation can be achieved and is associated with alleviation of symptoms, decrease in MEERP LTD CMI JOURNAL 1 (1), 34−49 (2020)) 37 SMOKING AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, OBESITY, DEPRESSION, LIVER DISEASES disease progression, a better quality of life, and an increased life expectancy. Acknowledgment: None Funding: None Conflict of interest: None References 1. Samet JM. 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