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Araujo-Castro M, Paja Fano M, González-Boillos M, Pascual-Corrales E, Parra Ramírez P, Martín Rojas-Marcos P, García-Cano A, Ruiz-Sanchez JG, Vicente A, Gómez-Hoyos E, Casterás A, Puig-Perez A, García Sanz I, Recasens M, Barahona San Millan R, Picón César MJ, Díaz Guardiola P, Perdomo C, Manjón-Miguélez L, Rebollo Román Á, Robles Lázaro C, María Recio J, Morales-Ruiz M, Calatayud M, Jiménez López N, Meneses D, Sampedro Nuñez M, Ribas EM, Sanmartín Sánchez A, Gonzalvo Diaz C, Lamas C, Del Castillo Tous M, Serrano J, Michalopoulou T, Tenes Rodrigo S, Roa Chamorro R, Jaén Aguila F, Moya Mateo EM, Gutiérrez-Medina S, Hanzu FA. Influence of smoking on cardiometabolic profile and surgical outcomes in patients with primary aldosteronism: a cohort study. Eur J Endocrinol 2024; 191:579-587. [PMID: 39556770 DOI: 10.1093/ejendo/lvae143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 08/29/2024] [Accepted: 11/15/2024] [Indexed: 11/20/2024]
Abstract
AIM To evaluate the influence of smoking on cardiometabolic profile and surgical outcomes in patients with primary aldosteronism (PA). METHODS Multicentre retrospective study of patients with PA evaluated in 36 Spanish tertiary hospitals with available information on smoking habits [smokers and non-smokers (never smokers and ex-smokers)]. RESULTS A total of 881 patients were included, of whom 180 (20.4%) were classified as smokers and 701 as non-smokers. At diagnosis, smokers and non-smokers did not differ in blood pressure or serum potassium levels between. However, smokers had a higher prevalence of left ventricular hypertrophy (LVH) than non-smokers [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.23-3.25], and smokers were more likely to have severe LVH than non-smokers (12.5% vs 6.6%, P = .164). A larger mean tumour size of the adrenal nodule/s was observed in the smoking group (18.6 ± 9.66 vs 15.8 ± 8.66 mm, P = .002). In addition, the odds of mild autonomous cortisol secretion (MACS) was greater in smokers than in non-smokers (OR 2.1, 95% CI 1.14-4.06), but these differences disappeared when adjusted for the size of the adrenal nodule/s (adjusted OR 1.6, 95% CI 0.76-3.37). The rate of biochemical and hypertension cure was similar in both groups; however, hypertension cure tended to be more frequent in the non-smoker group (41.2% vs 29.9%, P = .076). CONCLUSIONS Patients with PA who smoke have a higher prevalence of LVH and MACS and larger adrenal nodule/s than non-smokers. Smoking has no significant effect on the probability of hypertension response after adrenalectomy in patients with PA; however, a tendency to a lower probability of hypertension cure is observed in smokers compared to non-smokers.
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Affiliation(s)
- Marta Araujo-Castro
- Endocrinology & Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid 28034, Spain
- Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid 28034, Spain
| | - Miguel Paja Fano
- Endocrinology & Nutrition Department, OSI Bilbao-Basurto, Hospital Universitario de Basurto, Bilbao 48013, Spain
- University of the Basque Country UPV/EHU, Bilbao 48013, Spain
| | - Marga González-Boillos
- Endocrinology & Nutrition Department, Hospital Universitario de Castellón, Castellón 12004, Spain
| | - Eider Pascual-Corrales
- Endocrinology & Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid 28034, Spain
- Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid 28034, Spain
| | - Paola Parra Ramírez
- Endocrinology & Nutrition Department, Hospital Universitario La Paz, Madrid 28046, Spain
| | | | - Ana García-Cano
- Biochemistry Department, Hospital Universitario Ramón y Cajal, Madrid 28034, Spain
| | - Jorge Gabriel Ruiz-Sanchez
- Endocrinology & Nutrition Department, Hospital Universitario Fundación Jiménez Díaz, Madrid 28040, Spain
| | - Almudena Vicente
- Endocrinology & Nutrition Department, Hospital Universitario de Toledo, Toledo 45007, Spain
| | - Emilia Gómez-Hoyos
- Endocrinology & Nutrition Department, Hospital Universitario de Valladolid, Valladolid 47003, Spain
| | - Ana Casterás
- Endocrinology & Nutrition Department, Hospital Val de Hebrón, Barcelona 08035, Spain
| | - Albert Puig-Perez
- Endocrinology & Nutrition Department, Hospital Val de Hebrón, Barcelona 08035, Spain
| | - Iñigo García Sanz
- General & Digestive Surgery Department, Hospital Universitario de La Princesa, Madrid 28006, Spain
| | - Mònica Recasens
- Endocrinology & Nutrition Department, Hospital De Girona Doctor Josep Trueta, Girona 17007, Spain
| | | | - María José Picón César
- Endocrinology & Nutrition Department, Hospital Universitario Virgen de la Victoria de Málaga, IBIMA, Malaga 29010, Spain
- CIBEROBN, Madrid 29010, Spain
| | - Patricia Díaz Guardiola
- Endocrinology & Nutrition Department, Hospital Universitario Infanta Sofía, Madrid 28702, Spain
| | - Carolina Perdomo
- Endocrinology & Nutrition Department, Clínica Universidad de Navarra, Pamplona 28027, Spain
| | - Laura Manjón-Miguélez
- Endocrinology & Nutrition Department, Hospital Universitario Central de Asturias, Oviedo 33011, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias 33011, Spain
| | - Ángel Rebollo Román
- Endocrinology & Nutrition Department, Hospital Reina Sofía, Córdoba 14004, Spain
| | - Cristina Robles Lázaro
- Endocrinology & Nutrition Department, Hospital Clínico Universitario de Salamanca, Salamanca 37007, Spain
| | - José María Recio
- Endocrinology & Nutrition Department, Hospital Clínico Universitario de Salamanca, Salamanca 37007, Spain
| | - Manuel Morales-Ruiz
- Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona 08036, Spain
| | - María Calatayud
- Endocrinology & Nutrition Department, Hospital Doce de Octubre, Madrid 28041, Spain
| | - Noemi Jiménez López
- Endocrinology & Nutrition Department, Hospital Doce de Octubre, Madrid 28041, Spain
| | - Diego Meneses
- Endocrinology & Nutrition Department, Hospital Universitario Fundación Jiménez Díaz, Madrid 28040, Spain
| | - Miguel Sampedro Nuñez
- Endocrinology & Nutrition Department, Hospital Universitario La Princesa, Madrid 28006, Spain
| | - Elena Mena Ribas
- Endocrinology & Nutrition Department, Hospital Universitario Son Espases, Islas Baleares 07120, Spain
| | - Alicia Sanmartín Sánchez
- Endocrinology & Nutrition Department, Hospital Universitario Son Espases, Islas Baleares 07120, Spain
| | - Cesar Gonzalvo Diaz
- Endocrinology & Nutrition Department, Complejo Hospitalario Universitario de Albacete, Albacete 02008, Spain
| | - Cristina Lamas
- Endocrinology & Nutrition Department, Complejo Hospitalario Universitario de Albacete, Albacete 02008, Spain
| | - María Del Castillo Tous
- Endocrinology & Nutrition Department, Hospital Universitario Virgen Macarena, Seville 41009, Spain
| | - Joaquín Serrano
- Endocrinology & Nutrition Department, Hospital General Universitario de Alicante, Alicante 03010, Spain
| | | | | | - Ricardo Roa Chamorro
- Internal Medicine Department, Hospital Universitario Virgen de las Nieves, Granada 18014, Spain
| | - Fernando Jaén Aguila
- Internal Medicine Department, Hospital Universitario Virgen de las Nieves, Granada 18014, Spain
| | | | | | - Felicia Alexandra Hanzu
- Endocrinology & Nutrition Department, Hospital Clinic, University of Barcelona, IDIPAS, Barcelona 08036, Spain
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Yun Z, Shen Y, Yan X, Tian S, Wang J, Teo CS, Zhao H, Xue C, Dong Q, Hou L. Association between 19 medication use and risk of common cancers: A cross-sectional and Mendelian randomisation study. J Glob Health 2024; 14:04057. [PMID: 38487860 PMCID: PMC10940964 DOI: 10.7189/jogh.14.04057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2024] Open
Abstract
Background Previous studies have yielded inconsistent results concerning drug use and the risk of cancers. We conducted a large-scale cross-sectional study and a two-sample Mendelian randomisation (MR) study to reveal the causal effect between the use of 19 medications and the risk of four common cancers (breast, lung, colorectal, and prostate). Methods We obtained information on medication use and cancer diagnosis from National Health and Nutrition Examination Survey participants. After propensity score matching, we conducted survey-weighted multivariate logistic regression and restricted cubic spline analysis to assess the observed correlation between medication use and cancer while adjusting for multiple covariates. We also performed MR analysis to investigate causality based on summary data from genome-wide association studies on medication use and cancers. We performed sensitivity analyses, replication analysis, genetic correlation analysis, and reverse MR analysis to improve the reliability of MR findings. Results We found that the use of agents acting on the renin-angiotensin system was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.42; 95% confidence interval (CI) = 0.27-0.63, P < 0.001), and there was a nonlinear association of 'decrease-to-increase-to-decrease' (P < 0.0001). The random-effects inverse variance weighted (IVW) model-based primary MR analysis (OR = 0.94, 95% CI = 0.91-0.97, P = 0.0007) and replication MR analysis (OR = 0.90, 95% CI = 0.85-0.96, P = 0.0006) both provided robust evidence of the causality of genetic liability for the use of agents acting on the renin-angiotensin system on a decreased risk of prostate cancer. Conclusions Our study provides robust evidence that the use of drugs acting on the renin-angiotensin system can reduce prostate cancer risk. Given the high prevalence of prostate cancer, these findings have important implications for drug selection and prostate cancer prevention in patients with cardiovascular disease.
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Affiliation(s)
- Zhangjun Yun
- Department of Oncology and Haematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yang Shen
- Department of Oncology and Haematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xiang Yan
- Department of Oncology and Haematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Shaodan Tian
- Department of Oncology and Haematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jing Wang
- Department of Oncology and Haematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Chiah Shean Teo
- School of Traditional and Complementary Medicine, Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur, Malaysia
| | - Hongbin Zhao
- Department of Oncology and Haematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Chengyuan Xue
- Department of Oncology and Haematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Qing Dong
- Department of Oncology and Haematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Li Hou
- Department of Oncology and Haematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Pince CL, Whiting KE, Wang T, Lékó AH, Farinelli LA, Cooper D, Farokhnia M, Vendruscolo LF, Leggio L. Role of aldosterone and mineralocorticoid receptor (MR) in addiction: A scoping review. Neurosci Biobehav Rev 2023; 154:105427. [PMID: 37858908 PMCID: PMC10865927 DOI: 10.1016/j.neubiorev.2023.105427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 09/24/2023] [Accepted: 10/13/2023] [Indexed: 10/21/2023]
Abstract
Preclinical and human studies suggest a role of aldosterone and mineralocorticoid receptor (MR) in addiction. This scoping review aimed to summarize (1) the relationship between alcohol and other substance use disorders (ASUDs) and dysfunctions of the aldosterone and MR, and (2) how pharmacological manipulations of MR may affect ASUD-related outcomes. Our search in four databases (MEDLINE, Embase, Web of Science, and Cochrane Library) indicated that most studies focused on the relationship between aldosterone, MR, and alcohol (n = 30), with the rest focused on opioids (n = 5), nicotine (n = 9), and other addictive substances (n = 9). Despite some inconsistencies, the overall results suggest peripheral and central dysregulations of aldosterone and MR in several species and that these dysregulations depended on the pattern of drug exposure and genetic factors. We conclude that MR antagonism may be a promising target in ASUD, yet future studies are warranted.
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Affiliation(s)
- Claire L Pince
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA; Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA; Stress & Addiction Neuroscience Unit, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA
| | - Kimberly E Whiting
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA; Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA
| | - Tammy Wang
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA
| | - András H Lékó
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA; Center on Compulsive Behaviors, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA
| | - Lisa A Farinelli
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA
| | - Diane Cooper
- Office of Research Services, Division of Library Services, National Institutes of Health, Building 10, Bethesda, MD 20892, USA
| | - Mehdi Farokhnia
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA
| | - Leandro F Vendruscolo
- Stress & Addiction Neuroscience Unit, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA.
| | - Lorenzo Leggio
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA.
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Papadopoulos KI, Papadopoulou A, Aw TC. Live to die another day: novel insights may explain the pathophysiology behind smoker's paradox in SARS-CoV-2 infection. Mol Cell Biochem 2023; 478:2517-2526. [PMID: 36867341 PMCID: PMC9983545 DOI: 10.1007/s11010-023-04681-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 02/17/2023] [Indexed: 03/04/2023]
Abstract
The severe acute respiratory coronavirus 2 (SARS-CoV-2) infection demonstrates a highly variable and unpredictable course. Several reports have claimed a smoker's paradox in coronavirus disease 2019 (COVID-19), in line with previous suggestions that smoking is associated with better survival after acute myocardial infarction and appears protective in preeclampsia. Several plausible physiological explanations exist accounting for the paradoxical observation of smoking engendering protection against SARS-CoV-2 infection. In this review, we delineate novel mechanisms whereby smoking habits and smokers' genetic polymorphism status affecting various nitric oxide (NO) pathways (endothelial NO synthase, cytochrome P450 (CYP450), erythropoietin receptor (EPOR); β-common receptor (βcR)), along with tobacco smoke modulation of microRNA-155 and aryl-hydrocarbon receptor (AHR) effects, may be important determinators of SARS-CoV-2 infection and COVID-19 course. While transient NO bioavailability increase and beneficial immunoregulatory modulations through the above-mentioned pathways using exogenous, endogenous, genetic and/or therapeutic modalities may have direct and specific, viricidal SARS-CoV-2 effects, employing tobacco smoke inhalation to achieve protection equals self-harm. Tobacco smoking remains the leading cause of death, illness, and impoverishment.
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Affiliation(s)
- K. I. Papadopoulos
- THAI StemLife, 566/3 Soi Ramkhamhaeng 39 (Thepleela 1), Prachaouthit Rd., Wangthonglang, Wangthonglang, 10310 Bangkok Thailand
| | - A. Papadopoulou
- Occupational and Environmental Health Services, Feelgood Lund, Ideon Science Park, Scheelevägen 17, 223 63 Lund, Sweden
| | - T. C. Aw
- Department of Laboratory Medicine, Changi General Hospital, 2 Simei Street 3, Singapore, 529889 Singapore
- Department of Medicine, National University of Singapore, Singapore, 119228 Singapore
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Freeman MW, Halvorsen YD, Brown MJ. Baxdrostat for Treatment-Resistant Hypertension. Reply. N Engl J Med 2023; 388:1821-1822. [PMID: 37163635 DOI: 10.1056/nejmc2302673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
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Kluwe B, Pohlman N, Kesireddy V, Zhao S, Tan Y, Kline D, Brock G, Odei JB, Effoe VS, Tcheugui JBE, Kalyani RR, Sims M, Taylor HA, Mongraw-Chaffin M, Akhabue E, Joseph JJ. The Role of Aldosterone and Ideal Cardiovascular Health in Incident Cardiovascular Disease: The Jackson Heart Study. Am J Prev Cardiol 2023; 14:100494. [PMID: 37114212 PMCID: PMC10126856 DOI: 10.1016/j.ajpc.2023.100494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 03/31/2023] [Accepted: 04/01/2023] [Indexed: 04/05/2023] Open
Abstract
Background Higher levels of ideal cardiovascular health (ICH) are associated with lower levels of aldosterone and incidence of cardiovascular disease (CVD). However, the degree to which aldosterone mediates the association between ICH and CVD incidence has not been explored. Thus, we investigated the mediational role of aldosterone in the association of 5 components of ICH (cholesterol, body mass index (BMI), physical activity, diet and smoking) with incident CVD and the mediational role of blood pressure (BP) and glucose in the association of aldosterone with incident CVD in a cohort of African Americans (AA). Methods The Jackson Heart Study is a prospective cohort of AAs adults with data on CVD outcomes. Aldosterone, ICH metrics and baseline characteristics were collected at exam 1 (2000-2004). ICH score was developed by summing 5 ICH metrics (smoking, dietary intake, physical activity, BMI, and total cholesterol) and grouped into two categories (0-2 and ≥3 metrics). Incident CVD was defined as stroke, coronary heart disease, or heart failure. Cox proportional hazard regression models were used to model the association of categorical ICH score with incident CVD. The R Package Mediation was utilized to examine: 1) The mediational role of aldosterone in the association of ICH with incident CVD and 2) The mediational role of blood pressure and glucose in the association of aldosterone with incident CVD. Results Among 3,274 individuals (mean age: 54±12.4 years, 65% female), there were 368 cases of incident CVD over a median of 12.7 years. The risk of incident CVD was 46% lower (HR: 0.54; 95%CI 0.36, 0.80) in those with ≥3 ICH metrics at baseline compared to 0-2. Aldosterone mediated 5.4% (p = 0.006) of the effect of ICH on incident CVD. A 1-unit increase in log-aldosterone was associated with a 38% higher risk of incident CVD (HR 1.38, 95%CI: 1.19, 1.61) with BP and glucose mediating 25.6% (p<0.001) and 4.8% (p = 0.048), respectively. Conclusion Aldosterone partially mediates the association of ICH with incident CVD and both blood pressure and glucose partially mediate the association of aldosterone with incident CVD, emphasizing the potential importance of aldosterone and ICH in risk of CVD among AAs.
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Silva H. Tobacco Use and Periodontal Disease-The Role of Microvascular Dysfunction. BIOLOGY 2021; 10:441. [PMID: 34067557 PMCID: PMC8156280 DOI: 10.3390/biology10050441] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/05/2021] [Accepted: 05/07/2021] [Indexed: 12/30/2022]
Abstract
Periodontal disease consists in highly prevalent wide-ranging inflammatory conditions that affect the supporting apparatus of teeth. Tobacco use is the most important risk factor for periodontal disease as it increases disease severity and periodontal surgery complications. Tobacco use is harmful for the vasculature by causing microvascular dysfunction, which is known to negatively affect periodontal disease. To the author's knowledge this paper is the first comprehensive review on the mechanisms by which tobacco use affects oral microcirculation and impacts the pathophysiology of periodontal disease. In healthy subjects, acute nicotine administration or tobacco use (smoking/smokeless forms) increases the blood flow in the oral mucosa due to local irritation and increased blood pressure, which overcome neural- and endocrine-mediated vasoconstriction. Chronic tobacco smokers display an increased gingival microvascular density, which is attributed to an increased capillary recruitment, however, these microcirculatory units show higher tortuosity and lower caliber. These morphological changes, together with the repetitive vasoconstrictive insults, contribute to lower gingival perfusion in chronic smokers and do not completely regress upon smoking cessation. In periodontal disease there is considerable gingival inflammation and angiogenesis in non-smokers which, in chronic smokers, are considerably suppressed, in part due to local immune suppression and oxidative stress. Tobacco exposure, irrespective of the form of use, causes long-term microvascular dysfunction that increases the risk of complications due to the natural disease course or secondary therapeutic strategies.
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Affiliation(s)
- Henrique Silva
- Informetrics Research Group, Ton Duc Thang University, Ho Chi Minh City 758307, Vietnam;
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 758307, Vietnam
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Nadalin S, Flego V, Pavlić SD, Volarić D, Radojčić Badovinac A, Kapović M, Ristić S. Association between the ACE-I/D polymorphism and nicotine dependence amongst patients with lung cancer. Biomed Rep 2020; 13:58. [PMID: 33123372 DOI: 10.3892/br.2020.1365] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 09/14/2020] [Indexed: 11/06/2022] Open
Abstract
The biologically active peptide angiotensin II is cleaved from angiotensinogen by the renin and the angiotensin-converting enzyme (ACE), an enzymatic cascade known as the renin-angiotensin system (RAS). RAS may be important in the etiology of nicotine dependence by influencing dopaminergic signaling. In the present study, the association between an insertion/deletion (I/D) polymorphism of ACE and nicotine dependence amongst patients with lung cancer was assessed. To date, several studies have shown the relevance of this polymorphic variant in both nicotine dependence and lung cancer. However, the present study is the first to address the potential role of the ACE-I/D polymorphism in nicotine dependence among patients with lung cancer. Genotyping was performed in 305 patients with lung cancer (males/females, 214/91). Significantly more male smokers had the ACE-I allele compared with male non-smokers (44.9 vs. 20.0%; P<0.05). The risk of smoking was ~5-fold higher for males with the ACE-I allele (ACE-II homozygous and ACE-ID heterozygous) vs. ACE-DD homozygous (odds ratio, 5.47; 95% confidence interval, 1.4-21.9; P=0.016). The pack-year smoking history in a subgroup of females with squamous cell carcinoma carrying the ACE-I allele was significantly lower compared with ACE-DD (37.1±14.1 vs. 57.0±29.1; F=4.5; P=0.046). The ACE-I/D polymorphism accounted for 17.6% of the smoking severity in this patient group (β, -0.42; multiple R2 change, 0.176; P=0.046). These results suggest that the ACE-I/D polymorphism contributes to the risk of nicotine dependence and smoking severity in lung cancer patients in a sex-specific manner.
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Affiliation(s)
- Sergej Nadalin
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
| | - Veljko Flego
- Department of Pulmonology, Clinical Hospital Center Rijeka, University of Rijeka, 51000 Rijeka, Croatia
| | - Sanja Dević Pavlić
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
| | - Darian Volarić
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
| | - Anđelka Radojčić Badovinac
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.,Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia
| | - Miljenko Kapović
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
| | - Smiljana Ristić
- Department of Medical Biology and Genetics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
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Jian J, Zhang P, Li Y, Liu B, Zhang Y, Zhang L, Shao XM, Zhuang J, Xiao D. Reprogramming of miR-181a/DNA methylation patterns contribute to the maternal nicotine exposure-induced fetal programming of cardiac ischemia-sensitive phenotype in postnatal life. Theranostics 2020; 10:11820-11836. [PMID: 33052248 PMCID: PMC7546014 DOI: 10.7150/thno.48297] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Accepted: 09/16/2020] [Indexed: 02/07/2023] Open
Abstract
Background: E-cigarette and other novel electronic nicotine delivery systems (ENDS) have recently entered the market at a rapid pace. The community desperately needs answers about the health effects of ENDS. The present study tested the hypothesis that perinatal nicotine exposure (PNE) causes a gender-dependent increase in vulnerability of the heart to ischemia-reperfusion (I/R) injury and cardiac dysfunction in male rat offspring via reprogramming of the miRNA-181a (miR-181a)-mediated signaling pathway and that miR-181a antisense could rescue this phenotype. Methods: Nicotine or saline was administered to pregnant rats via subcutaneous osmotic minipumps from gestational day 4 until postnatal day 10. Cardiac function and molecular biological experiments were conducted in ~3- month-old offspring. Results: PNE enhanced I/R-induced cardiac dysfunction and infarction in adult male but not in female offspring, which was associated with miR-181a over-expression in left ventricle tissues. In addition, PNE enhanced offspring cardiac angiotensin receptor (ATR) expressions via specific CpG hypomethylation of AT1R/AT2R promoter. Furthermore, PNE attenuated cardiac lncRNA H19 levels, but up-regulated cardiac TGF-β/Smads family proteins and consequently up-regulated autophagy-related protein (Atg-5, beclin-1, LC3 II, p62) expression in the male offspring. Of importance, treatment with miR-181a antisense eliminated the PNE's effect on miR-181a expression/H19 levels and reversed PNE-mediated I/R-induced cardiac infarction and dysfunction in male offspring. Furthermore, miR-181a antisense also attenuated the effect of PNE on AT1R/AT2R/TGF-β/Smads/autophagy-related biomarkers in the male offspring. Conclusion: Our data suggest that PNE could induce a reprogramming of cardiac miR-181a expression/DNA methylation pattern, which epigenetically modulates ATR/TGF-β/autophagy signaling pathways, leading to gender-dependent development of ischemia-sensitive phenotype in postnatal life. Furthermore, miR-181a could severe as a potential therapeutic target for rescuing this phenotype.
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McAlinden KD, Eapen MS, Lu W, Sharma P, Sohal SS. The rise of electronic nicotine delivery systems and the emergence of electronic-cigarette-driven disease. Am J Physiol Lung Cell Mol Physiol 2020; 319:L585-L595. [PMID: 32726146 DOI: 10.1152/ajplung.00160.2020] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
In 2019, the United States experienced the emergence of the vaping-associated lung injury (VALI) epidemic. Vaping is now known to result in the development and progression of severe lung disease in the young and healthy. Lack of regulation on electronic cigarettes in the United States has resulted in over 2,000 patients and 68 deaths. We examine the clinical representation of VALI and the delve into the scientific evidence of how deadly exposure to electronic cigarettes can be. E-cigarette vapor is shown to affect numerous cellular processes, cellular metabolism, and cause DNA damage (which has implications for cancer). E-cigarette use is associated with a higher risk of developing crippling lung conditions such as chronic obstructive pulmonary disease (COPD), which would develop several years from now, increasing the already existent smoking-related burden. The role of vaping and virus susceptibility is yet to be determined; however, vaping can increase the virulence and inflammatory potential of several lung pathogens and is also linked to an increased risk of pneumonia. As it has emerged for cigarette smoking, great caution should also be given to vaping in relation to SARS-CoV-2 infection and the COVID-19 pandemic. Sadly, e-cigarettes are continually promoted and perceived as a safer alternative to cigarette smoking. E-cigarettes and their modifiable nature are harmful, as the lungs are not designed for the chronic inhalation of e-cigarette vapor. It is of interest that e-cigarettes have been shown to be of no help with smoking cessation. A true danger lies in vaping, which, if ignored, will lead to disastrous future costs.
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Affiliation(s)
- Kielan Darcy McAlinden
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia
| | - Mathew Suji Eapen
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia
| | - Wenying Lu
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia
| | - Pawan Sharma
- Center for Translational Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Sukhwinder Singh Sohal
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia
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Cora N, Ghandour J, Pollard CM, Desimine VL, Ferraino KE, Pereyra JM, Valiente R, Lymperopoulos A. Nicotine-induced adrenal beta-arrestin1 upregulation mediates tobacco-related hyperaldosteronism leading to cardiac dysfunction. World J Cardiol 2020; 12:192-202. [PMID: 32547713 PMCID: PMC7283997 DOI: 10.4330/wjc.v12.i5.192] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/27/2020] [Accepted: 05/12/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Tobacco-related products, containing the highly addictive nicotine together with numerous other harmful toxicants and carcinogens, have been clearly associated with coronary artery disease, heart failure, stroke, and other heart diseases. Among the mechanisms by which nicotine contributes to heart disease is elevation of the renin-angiotensin-aldosterone system (RAAS) activity. Nicotine, and its major metabolite in humans cotinine, have been reported to induce RAAS activation, resulting in aldosterone elevation in smokers. Aldosterone has various direct and indirect adverse cardiac effects. It is produced by the adrenal cortex in response to angiotensin II (AngII) activating AngII type 1 receptors. RAAS activity increases in chronic smokers, causing raised aldosterone levels (nicotine exposure causes the same in rats). AngII receptors exert their cellular effects via either G proteins or the two βarrestins (βarrestin1 and-2). AIM Since adrenal ßarrestin1 is essential for adrenal aldosterone production and nicotine/cotinine elevate circulating aldosterone levels in humans, we hypothesized that nicotine activates adrenal ßarrestin1, which contributes to RAAS activation and heart disease development. METHODS We studied human adrenocortical zona glomerulosa H295R cells and found that nicotine and cotinine upregulate βarrestin1 mRNA and protein levels, thereby enhancing AngII-dependent aldosterone synthesis and secretion. RESULTS In contrast, siRNA-mediated βarrestin1 knockdown reversed the effects of nicotine on AngII-induced aldosterone production in H295R cells. Importantly, nicotine promotes hyperaldosteronism via adrenal βarrestin1, thereby precipitating cardiac dysfunction, also in vivo, since nicotine-exposed experimental rats with adrenal-specific βarrestin1 knockdown display lower circulating aldosterone levels and better cardiac function than nicotine-exposed control animals with normal adrenal βarrestin1 expression. CONCLUSION Adrenal βarrestin1 upregulation is one of the mechanisms by which tobacco compounds, like nicotine, promote cardio-toxic hyperaldosteronism in vitro and in vivo. Thus, adrenal βarrestin1 represents a novel therapeutic target for tobacco-related heart disease prevention or mitigation.
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Affiliation(s)
- Natalie Cora
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, United States
| | - Jennifer Ghandour
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, United States
| | - Celina Marie Pollard
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, United States
| | - Victoria Lynn Desimine
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, United States
| | - Krysten Elaine Ferraino
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, United States
| | - Janelle Marie Pereyra
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, United States
| | - Rachel Valiente
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, United States
| | - Anastasios Lymperopoulos
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, United States.
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Association between preterm birth and the renin-angiotensin system in adolescence: influence of sex and obesity. J Hypertens 2019; 36:2092-2101. [PMID: 29846325 DOI: 10.1097/hjh.0000000000001801] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Preterm birth appears to contribute to early development of cardiovascular disease, but the mechanisms are unknown. Prematurity may result in programming events that alter the renin-angiotensin system. We hypothesized that prematurity is associated with lower angiotensin-(1-7) in adolescence and that sex and obesity modify this relationship. METHODS We quantified angiotensin II and angiotensin-(1-7) in the plasma and urine of 175 adolescents born preterm and 51 term-born controls. We used generalized linear models to estimate the association between prematurity and the peptides, controlling for confounding factors and stratifying by sex and overweight/obesity. RESULTS Prematurity was associated with lower plasma angiotensin II (β: -5.2 pmol/l, 95% CI: -10.3 to -0.04) and angiotensin-(1-7) (-5.2 pmol/l, 95% CI: -8.4 to -2.0) but overall higher angiotensin II:angiotensin-(1-7) (3.0, 95% CI: 0.9-5.0). The preterm-term difference in plasma angiotensin-(1-7) was greater in women (-6.9 pmol/l, 95% CI: -10.7 to -3.1) and individuals with overweight/obesity (-8.0 pmol/l, 95% CI: -12.2 to -3.8). The preterm-term difference in angiotensin II:angiotensin-(1-7) was greater among those with overweight/obesity (4.4, 95% CI: 0.6-8.1). On multivariate analysis, prematurity was associated with lower urinary angiotensin II:angiotensin-(1-7) (-0.13, 95% CI: -0.26 to -0.003), especially among the overweight/obesity group (-0.38, 95% CI: -0.72 to -0.04). CONCLUSION Circulating angiotensin-(1-7) was diminished whereas urinary angiotensin-(1-7) was increased relative to angiotensin II in adolescents born preterm, suggesting prematurity may increase the risk of cardiovascular disease by altering the renin-angiotensin system. Perinatal renin-angiotensin system programming was more pronounced in women and individuals with overweight/obesity, thus potentially augmenting their risk of developing early cardiovascular disease.
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Solesio ME, Mitaishvili E, Lymperopoulos A. Adrenal βarrestin1 targeting for tobacco-associated cardiac dysfunction treatment: Aldosterone production as the mechanistic link. Pharmacol Res Perspect 2019; 7:e00497. [PMID: 31236278 PMCID: PMC6581946 DOI: 10.1002/prp2.497] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 05/23/2019] [Accepted: 05/25/2019] [Indexed: 12/13/2022] Open
Abstract
Tobacco kills 6 million people annually and its global health costs are continuously rising. The main addictive component of every tobacco product is nicotine. Among the mechanisms by which nicotine, and its major metabolite, cotinine, contribute to heart disease is the renin-angiotensin-aldosterone system (RAAS) activation. This increases aldosterone production from the adrenals and circulating aldosterone levels. Aldosterone is a mineralocorticoid hormone with various direct harmful effects on the myocardium, including increased reactive oxygen species (ROS) generation, which contributes significantly to cardiac mitochondrial dysfunction and cardiac aging. Aldosterone is produced in the adrenocortical zona glomerulosa (AZG) cells in response to angiotensin II (AngII), activating its type 1 receptor (AT1R). The AT1R is a G protein-coupled receptor (GPCR) that leads to aldosterone biosynthesis and secretion, via signaling from both Gq/11 proteins and the GPCR adapter protein βarrestin1, in AZG cells. Adrenal βarrestin1 is essential for AngII-dependent adrenal aldosterone production, which aggravates heart disease. Since adrenal βarrestin1 is essential for raising circulating aldosterone in the body and tobacco compounds are also known to elevate aldosterone levels in smokers, accelerating heart disease progression, our central hypothesis is that nicotine and cotinine increase aldosterone levels to induce cardiac injury by stimulating adrenal βarrestin1. In the present review, we provide an overview of the current literature of the physiology and pharmacology of adrenal aldosterone production regulation, of the effects of tobacco on this process and, finally, of the effects of tobacco and aldosterone on cardiac structure and function, with a particular focus on cardiac mitochondrial function. We conclude our literature account with a brief experimental outline, as well as with some therapeutic perspectives of our pharmacological hypothesis, that is that adrenal βarrestin1 is a novel molecular target for preventing tobacco-induced hyperaldosteronism, thereby also ameliorating tobacco-related heart disease development.
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Affiliation(s)
- Maria E Solesio
- Department of Basic SciencesNew York UniversityNew YorkNew York
| | | | - Anastasios Lymperopoulos
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical SciencesNova Southeastern University College of PharmacyFort Lauderdale, Florida
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Muller PDT, Barbosa GW, O'Donnell DE, Neder JA. Cardiopulmonary and Muscular Interactions: Potential Implications for Exercise (In)tolerance in Symptomatic Smokers Without Chronic Obstructive Pulmonary Disease. Front Physiol 2019; 10:859. [PMID: 31354517 PMCID: PMC6635481 DOI: 10.3389/fphys.2019.00859] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 06/20/2019] [Indexed: 12/15/2022] Open
Abstract
Smoking and physical inactivity are important preventable causes of disability and early death worldwide. Reduced exercise tolerance has been described in smokers, even in those who do not fulfill the extant physiological criteria for chronic obstructive pulmonary disease (COPD) and are not particularly sedentary. In this context, it is widely accepted that exercise capacity depends on complex cardio-pulmonary interactions which support oxygen (O2) delivery to muscle mitochondria. Although peripheral muscular factors, O2 transport disturbances (including the effects of increased carboxyhemoglobin) and autonomic nervous system unbalance have been emphasized, other derangements have been more recently described, including early microscopic emphysema, pulmonary microvascular disease, ventilatory and gas exchange inefficiency, and left ventricular diastolic dysfunction. Using an integrative physiological approach, the present review summarizes the recent advances in knowledge on the effects of smoking on the lung-heart-muscle axis under the stress of exercise. Special attention is given to the mechanisms connecting physiological abnormalities such as early cardio-pulmonary derangements, inadequate oxygen delivery and utilization, and generalized bioenergetic disturbances at the muscular level with the negative sensations (sense of heightened muscle effort and breathlessness) that may decrease the tolerance of smokers to physical exercise. A deeper understanding of the systemic effects of smoking in subjects who did not (yet) show evidences of COPD and ischemic heart disease - two devastating smoking related diseases - might prove instrumental to fight their ever-growing burden.
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Affiliation(s)
- Paulo de Tarso Muller
- Laboratory of Respiratory Pathophysiology, Respiratory Division, Department of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, Brazil
| | - Gisele Walter Barbosa
- Laboratory of Respiratory Pathophysiology, Respiratory Division, Department of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, Brazil
| | - Denis E O'Donnell
- Laboratory of Clinical Exercise Physiology, Respiratory Investigation Unit, Division of Respiratory and Critical Care Medicine, Department of Medicine, Queen's University, Kingston, ON, Canada
| | - J Alberto Neder
- Laboratory of Clinical Exercise Physiology, Respiratory Investigation Unit, Division of Respiratory and Critical Care Medicine, Department of Medicine, Queen's University, Kingston, ON, Canada
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The Association of Life's Simple 7 with Aldosterone among African Americans in the Jackson Heart Study. Nutrients 2019; 11:nu11050955. [PMID: 31035479 PMCID: PMC6566676 DOI: 10.3390/nu11050955] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 04/19/2019] [Accepted: 04/22/2019] [Indexed: 01/21/2023] Open
Abstract
Background: Among African Americans (AAs), attaining higher levels of American Heart Association (AHA) ideal cardiovascular health (Life’s Simple 7 [LS7]) is associated with lower risk of diabetes and cardiovascular disease (CVD). We previously showed that aldosterone is associated with higher risk of diabetes and CVD in AAs. Thus, we investigated the association of LS7 metrics with aldosterone in the Jackson Heart Study (JHS). Methods: Ideal metrics were defined by AHA 2020 goals for health behaviors (smoking, dietary intake, physical activity, and body mass index) and health factors (total cholesterol, blood pressure, and fasting glucose). The number of ideal LS7 metrics attained at baseline were summed into a continuous score (0–7) and categorical groups (Poor: 0–1, Intermediate: 2–3, and Ideal: ≥4 ideal LS7 metrics). Multivariable linear regression was used. Results: Among 4,095 JHS participants (mean age 55 ± 13 years, 65% female), median serum aldosterone was 4.90, 4.30, and 3.70 ng/dL in the poor (n = 1132), intermediate (n = 2288) and ideal (n = 675) categories respectively. Aldosterone was 15% [0.85 (0.80, 0.90)] and 33% [0.67 (0.61, 0.75)] lower in the intermediate and ideal LS7 categories compared to the poor LS7 category. Each additional LS7 metric attained on continuous LS7 score (0–7) was associated with an 11% [0.89 (0.86, 0.91)] lower aldosterone level with variation by sex with women having a 15% lower aldosterone vs. 5% in men. Conclusions: Higher attainment of ideal LS7 metrics was associated with lower serum aldosterone among AAs with a greater magnitude of association among women compared to men.
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Oakes JM, Fuchs RM, Gardner JD, Lazartigues E, Yue X. Nicotine and the renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol 2018; 315:R895-R906. [PMID: 30088946 DOI: 10.1152/ajpregu.00099.2018] [Citation(s) in RCA: 207] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases (CVPD). Although cigarette smoking has been in constant decline since the 1950s, the introduction of e-cigarettes or electronic nicotine delivery systems 10 yr ago has attracted former smokers as well as a new generation of consumers. Nicotine is a highly addictive substance, and it is currently unclear whether e-cigarettes are "safer" than regular cigarettes or whether they have the potential to reverse the health benefits, notably on the cardiopulmonary system, acquired with the decline of tobacco smoking. Of great concern, nicotine inhalation devices are becoming popular among young adults and youths, emphasizing the need for awareness and further study of the potential cardiopulmonary risks of nicotine and associated products. This review focuses on the interaction between nicotine and the renin-angiotensin system (RAS), one of the most important regulatory systems on autonomic, cardiovascular, and pulmonary functions in both health and disease. The literature presented in this review strongly suggests that nicotine alters the homeostasis of the RAS by upregulating the detrimental angiotensin-converting enzyme (ACE)/angiotensin (ANG)-II/ANG II type 1 receptor axis and downregulating the compensatory ACE2/ANG-(1-7)/Mas receptor axis, contributing to the development of CVPD.
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Affiliation(s)
- Joshua M Oakes
- Department of Physiology, Louisiana State University Health Sciences Center , New Orleans, Louisiana
| | - Robert M Fuchs
- Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, Louisiana
| | - Jason D Gardner
- Department of Physiology, Louisiana State University Health Sciences Center , New Orleans, Louisiana
| | - Eric Lazartigues
- Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, Louisiana
| | - Xinping Yue
- Department of Physiology, Louisiana State University Health Sciences Center , New Orleans, Louisiana
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The Renin-Angiotensin-Aldosterone System in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 935:75-82. [PMID: 27334735 DOI: 10.1007/5584_2016_39] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
High concentrations of renin and aldosterone are risk factors for cardiovascular diseases (CVD) which are the leading cause of morbidity and mortality worldwide. Enhanced activation of the renin-angiotensin-aldosterone system (RAAS) by cigarette smoking has been reported. The aim of our study was to analyze the effect of cigarette smoking on parameters of the RAAS in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study as well as the utility of RAAS parameter for risk prediction. We determined the concentration of aldosterone, renin, angiotensin-I and angiotensin-II in participants of the LURIC study. Smoking status was assessed by a questionnaire and the measurement of plasma cotinine concentration. Parameters were log transformed before entering analyses, where appropriate. We used a multivariate Cox regression analysis to assess the effect of parameters on mortality. From the 3316 LURIC participants 777 were AS and 1178 NS. Within a median observation period of 10 years 221 (28.4 %) AS and 302 (25.6 %) NS died. After adjustment for age, gender, and the use of anti-hypertensive medication, only angiotensin-I was significantly different in AS compared to NS with an estimated marginal mean (95 % CI) of 1607 (1541-1673) ng/L and 1719 (1667-1772) ng/L, respectively. For both NS and AS renin and angiotensin-II were directly associated with mortality in the multivariate Cox regression analysis. Angiotensin-I was only associated with increased risk for mortality in NS (HR (95 % CI) of 0.69 (0.53-0.89)). We conclude that increased renin and angiotensin-II are independent predictors of mortality in AS and NS, while angiotensin-I was associated with reduced risk of death in NS only.
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Liu X, Zhu T, Manojlovich M, Cohen HW, Tsilimingras D. Racial/ethnic disparity in the associations of smoking status with uncontrolled hypertension subtypes among hypertensive subjects. PLoS One 2017; 12:e0182807. [PMID: 28793323 PMCID: PMC5549965 DOI: 10.1371/journal.pone.0182807] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 07/25/2017] [Indexed: 01/13/2023] Open
Abstract
Background Racial/ethnic differences in the associations of smoking with uncontrolled blood pressure (BP) and its subtypes (isolated uncontrolled systolic BP (SBP), uncontrolled systolic-diastolic BP, and isolated uncontrolled diastolic BP (DBP)) have not been investigated among diagnosed hypertensive subjects. Methods A sample of 7,586 hypertensive patients aged ≥18 years were selected from the National Health and Nutrition Examination Survey 1999–2010. Race/ethnicity was classified into Hispanic, non-Hispanic white, and non-Hispanic black. Smoking was categorized as never smoking, ex-smoking, and current smoking. Uncontrolled BP was determined as SBP≥140 or DBP≥90 mm Hg. Isolated uncontrolled SBP was defined as SBP≥140 and DBP<90 mm Hg, uncontrolled SDBP as SBP≥140 and DBP≥90 mm Hg, and isolated uncontrolled DBP as SBP<140 and DBP≥90 mm Hg. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of uncontrolled BP and its subtypes were calculated using weighted logistic regression models. Results The interaction effect of race and smoking was significant after adjustment for the full potential confounding covariates (Adjusted p = 0.0412). Compared to never smokers, current smokers were 29% less likely to have uncontrolled BP in non-Hispanic whites (OR = 0.71, 95% CI = 0.56–0.90), although the likelihood for uncontrolled BP is the same for smokers and never smokers in Hispanics and non-Hispanic blacks. Current smokers were 26% less likely than never smokers to have isolated uncontrolled SBP in non-Hispanic whites (OR = 0.74, 95% CI = 0.58–0.95). However, current smoking is associated with an increased likelihood of uncontrolled systolic-diastolic BP in non-Hispanic blacks, and current smokers in this group were 70% more likely to have uncontrolled systolic-diastolic BP than never smokers (OR = 1.70, 95% CI = 1.10–2.65). Conclusion The associations between current smoking and uncontrolled BP differed over race/ethnicity. Health practitioners may need to be especially vigilant with non-Hispanic black smokers with diagnosed hypertension.
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Affiliation(s)
- Xuefeng Liu
- Department of Systems, Population, and Leadership, University of Michigan School of Nursing, Ann Arbor, MI, United States of America
- Frankel Cardiovascular Center, University of Michigan School of Medicine, Ann Arbor, MI, United States of America
- * E-mail:
| | - Tinghui Zhu
- Department of Systems, Population, and Leadership, University of Michigan School of Nursing, Ann Arbor, MI, United States of America
| | - Milisa Manojlovich
- Department of Systems, Population, and Leadership, University of Michigan School of Nursing, Ann Arbor, MI, United States of America
| | - Hillel W. Cohen
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States of America
| | - Dennis Tsilimingras
- Department of Family Medicine & Public Health Sciences, Wayne State University School of Medicine, Detroit, MI, United States of America
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Nadalin S, Buretić-Tomljanović A, Lavtar P, Starčević Čizmarević N, Hodžić A, Sepčić J, Kapović M, Peterlin B, Ristić S. The lack of association between angiotensin-converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis. Brain Behav 2017; 7:e00600. [PMID: 28127518 PMCID: PMC5256183 DOI: 10.1002/brb3.600] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 09/14/2016] [Accepted: 10/03/2016] [Indexed: 11/09/2022] Open
Abstract
OBJECTIVE Blood-borne angiotensin II is generated from angiotensinogen via cleavage by renin and angiotensin-converting enzyme (ACE), an enzymatic cascade known as the renin-angiotensin system (RAS). Several lines of evidence indicate that ACE, beyond its classical role of mediating blood pressure regulation, might contribute to the etiology of substance addictions by influencing dopaminergic signaling. A functional insertion/deletion (I/D) polymorphism of the ACE gene was associated with risk for being a smoker among individuals with depression and with smoking severity in studies comprising patients with depression and healthy controls. Several reports have described significantly increased ACE activity in cerebrospinal fluid and serum among MS patients. Furthermore, in our previous work with MS patients from Croatian and Slovenian populations, we demonstrated that the ACE-I/D polymorphism contributes to an elevated MS risk among male patients. Here we investigated whether the ACE-I/D polymorphism might influence smoking behavior among patients with MS. PATIENTS AND METHODS Genotyping was performed in 521 patients (males/females: 139/382) using polymerase chain reaction. RESULTS We revealed no significant differences in ACE genotype and allele frequencies between smokers and nonsmokers and no significant association between the ACE-I/D polymorphism and either pack-year smoking history or number of cigarettes smoked daily (p > .05, respectively). CONCLUSION The ACE-I/D polymorphism does not contribute either to risk for nicotine dependence or to smoking severity among MS patients. In the context of reports on the ACE-I/D polymorphism and nicotine dependence among healthy controls and patients with depression, we may speculate that the mechanism by which this polymorphism influences nicotine dependence risk differs in MS compared to depression, although not compared to a healthy population. In addition to angiotensin II, other potential ACE substrates, such as substance P and neurotensin, which also influence dopaminergic neurotransmission (and are proposed to be associated with MS), may deserve study in future.
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Affiliation(s)
- Sergej Nadalin
- Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia
| | | | - Polona Lavtar
- Clinical Institute of Medical Genetics University Medical Centre Ljubljana Slovenia
| | | | - Alenka Hodžić
- Clinical Institute of Medical Genetics University Medical Centre Ljubljana Slovenia
| | - Juraj Sepčić
- Postgraduate Studies School of Medicine University of Rijeka Rijeka Croatia
| | - Miljenko Kapović
- Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia
| | - Borut Peterlin
- Clinical Institute of Medical Genetics University Medical Centre Ljubljana Slovenia
| | - Smiljana Ristić
- Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia
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Wang W, Shen G, Shahar E, Bidulescu A, Kimberly WT, Sheth KN, Campbell BW, Horbal S, Correa A, Griswold ME. Forced Expiratory Volume in the First Second and Aldosterone as Mediators of Smoking Effect on Stroke in African Americans: The Jackson Heart Study. J Am Heart Assoc 2016; 5:e002689. [PMID: 26819252 PMCID: PMC4859388 DOI: 10.1161/jaha.115.002689] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2015] [Accepted: 10/25/2015] [Indexed: 11/16/2022]
Abstract
BACKGROUND Cigarette smoking is a risk factor for stroke, but the mechanisms by which smoking contributes to stroke are not well understood. This study aimed to evaluate the roles of lung function (represented by forced expiratory volume in the first second (FEV1)) and aldosterone as potential mediators of the association of smoking with stroke. METHODS AND RESULTS The data were derived from 5010 Jackson Heart Study participants who had mean follow-up of 97.9 months. Using the Cox proportional hazards model, we estimated the hazard ratios of smoking for total stroke with and without adjustment for FEV1 and/or aldosterone at baseline after controlling for the confounders. The hazard ratio for current smoking (versus never smoking) was 2.70 (95% CI 1.71 to 4.25) for total stroke after adjustment for the confounders. Additional adjustment for FEV1 and aldosterone reduced the hazard ratio to 2.32 (95% CI 1.42 to 3.79), suggesting that 22.4% of the excess risk of current smoking for total stroke is mediated by these factors. FEV1 and aldosterone account for 13.1% and 12.1%, respectively, of the excess risk. The hazard ratio for FEV1 increased (0.61 versus 0.65) after including systemic inflammatory marker C-reactive protein, and the hazard ratios for aldosterone were comparable for the models that included all confounders and smoking status with or without different blood pressure measurements. CONCLUSIONS Our findings suggest that the difference in stroke risk between current and never smokers may develop partially through pathways involving lung function and aldosterone and that the mediation effect through aldosterone is independent of blood pressure.
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Affiliation(s)
- Wei Wang
- Center of Biostatistics and BioinformaticsUniversity of Mississippi Medical CenterJacksonMS
| | - Gui Shen
- Department of Mathematics and StatisticsMississippi State UniversityMississippi StateMS
| | - Eyal Shahar
- Department of Epidemiology and BiostatisticsMel and Enid Zuckerman College of Public HealthUniversity of ArizonaTucsonAZ
| | - Aurelian Bidulescu
- Department of Epidemiology and BiostatisticsIndiana University School of Public HealthBloomingtonIN
| | | | - Kevin N. Sheth
- Division of Neurocritical Care & Emergency NeurologySchool of MedicineYale UniversityNew HavenCT
| | | | - Steven Horbal
- Department of Epidemiology and BiostatisticsIndiana University School of Public HealthBloomingtonIN
| | - Adolfo Correa
- Jackson Heart StudyDepartment of MedicineUniversity of Mississippi Medical CenterJacksonMS
| | - Michael E. Griswold
- Center of Biostatistics and BioinformaticsUniversity of Mississippi Medical CenterJacksonMS
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Correale J, Farez MF. Smoking worsens multiple sclerosis prognosis: Two different pathways are involved. J Neuroimmunol 2015; 281:23-34. [DOI: 10.1016/j.jneuroim.2015.03.006] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 03/03/2015] [Accepted: 03/04/2015] [Indexed: 12/13/2022]
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Yoon C, Yang HS, Jeon I, Chang Y, Park SM. Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies. CMAJ 2011; 183:E1073-84. [PMID: 21876027 DOI: 10.1503/cmaj.101497] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Epidemiologic studies have reported inconsistent findings regarding the association between the use of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers and the risk of cancer. We performed a meta-analysis of observational studies to assess the association. METHODS We searched MEDLINE, EMBASE and the Cochrane Library to identify studies through January 2011. Two evaluators independently reviewed and selected articles of cohort and case-control studies on the basis of predetermined selection criteria. RESULTS Of 3970 screened articles, 12 cohort studies and 16 case-control studies were selected for analysis. We found no significant association between the use of ACE inhibitors or angiotensin-receptor blockers and the overall risk of cancer (relative risk [RR] 0.96, 95% confidence interval [CI] 0.90-1.03). We found a decreased risk of cancer associated with use of either medication when we restricted the analyses to cohort and nested case-control studies (RR 0.90, 95% CI 0.83-0.97) or to studies with long-term follow-up of more than five years (RR 0.89, 95% CI 0.83-0.96). In the subgroup meta-analyses by cancer site, a decreased risk was identified for esophageal cancer, whereas an increased risk was found for melanoma and kidney cancer. INTERPRETATION No significant association was found between the use of ACE inhibitors or angiotensin-receptor blockers and overall risk of cancer. A possible beneficial effect associated with use of either medication was suggested in sensitivity analyses, including those of studies with long-term follow-up. Large randomized controlled trials with long-term follow-up are needed to specifically test the effect of each of these medications on the risk of cancer.
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Affiliation(s)
- Chan Yoon
- Seoul National University College of Medicine, Seoul, Republic of Korea
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Shah AM, Pfeffer MA, Hartley LH, Moyé LA, Gersh BJ, Rutherford JD, Lamas GA, Rouleau JL, Braunwald E, Solomon SD. Risk of all-cause mortality, recurrent myocardial infarction, and heart failure hospitalization associated with smoking status following myocardial infarction with left ventricular dysfunction. Am J Cardiol 2010; 106:911-6. [PMID: 20854949 DOI: 10.1016/j.amjcard.2010.05.021] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2010] [Revised: 05/11/2010] [Accepted: 05/11/2010] [Indexed: 10/19/2022]
Abstract
Patients with left ventricular (LV) systolic dysfunction after myocardial infarction (MI) are at particularly high risk for recurrent adverse outcomes. The magnitude of the decrease in risk associated with smoking cessation after MI has not been well described in patients with LV dysfunction after MI. We aimed to quantify the risk decrease associated with smoking cessation in subjects with LV dysfunction after MI. The Survival and Ventricular Enlargement (SAVE) trial randomized 2,231 subjects with LV dysfunction 3 to 16 days after MI. Smoking status was assessed at randomization and at regular intervals during a median follow-up of 42 months. Propensity score-adjusted Cox proportional hazard models were used to quantify the decrease in risk of all-cause mortality, death or recurrent MI, and death or heart failure (HF) hospitalization associated with smoking cessation. In baseline smokers who survived to 6 months without interval events, smoking cessation at 6-month follow-up was associated with a significantly lower adjusted risk of all-cause mortality (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.31 to 0.91), death or recurrent MI (HR 0.68, 95% CI 0.47 to 0.99), and death or HF hospitalization (HR 0.65, 95% CI 0.46 to 0.92). In conclusion, in patients with LV dysfunction after MI, smoking cessation is associated with a 40% lower hazard of all-cause mortality and a 30% lower hazard of death or recurrent MI or death or HF hospitalization. These findings indicate that smoking cessation is beneficial after high-risk MI and highlight the importance of smoking cessation as a therapeutic target in patients with LV dysfunction after MI.
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Renin and aldosterone but not the natriuretic peptide correlate with obsessive craving in medium-term abstinent alcohol-dependent patients: a longitudinal study. Alcohol 2008; 42:375-81. [PMID: 18486430 DOI: 10.1016/j.alcohol.2008.03.128] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2008] [Revised: 02/26/2008] [Accepted: 03/06/2008] [Indexed: 01/02/2023]
Abstract
Both animal and human studies suggest that volume-regulating hormones could play a role in alcohol dependence as well as in alcohol craving. The role of the volume-regulating hormones, renin, aldosterone, and the N-terminal pro B-type natriuretic peptide (NT-proBNP) in alcohol craving was therefore evaluated in the present study. Twenty-five actively drinking alcohol-dependent patients satisfied the inclusion criteria and were enrolled into the study. The volume-regulating hormones, renin, aldosterone, and the NT-proBNP, and craving measurements--Obsessive-Compulsive Drinking Scale (OCDS) and Penn Alcohol Craving Scale (PACS)--were performed at baseline and after 12 weeks. Sixteen patients remained totally abstinent for the entire 12 weeks and were available for the second assessments. At baseline, no correlations between hormones and craving scores were found with either the 25 patients initially enrolled or the 16 abstinent patients. At 12 weeks, a significant increase of renin and a significant decrease of aldosterone were observed. Aldosterone showed a significant direct correlation with the obsessive OCDS subscore (r=0.59, P=.016) and a trend toward a significant direct correlation with the PACS score (r=0.48, P=.057). Renin demonstrated a significant direct correlation with the obsessive OCDS subscore (r=0.51, P=.041) and with the PACS score (r=0.56, P=.025). The NT-proBNP never correlated with craving measurements. In conclusion, the renin-aldosterone axis could play a role in craving in medium-term abstinent patients and thereby leading to the hypothesis that alcohol craving could be influenced by the fluid volume intake.
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Pureza DYD, Sargentini L, Laterza R, Flores LJF, Irigoyen MC, Angelis KD. Efeitos cardiovasculares da abstinência do fumo no repouso e durante o exercício submáximo em mulheres jovens fumantes. REV BRAS MED ESPORTE 2007. [DOI: 10.1590/s1517-86922007000500003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJETIVO: O objetivo do presente estudo foi verificar o efeito da abstinência do fumo nas respostas cardiovasculares ao exercício físico progressivo submáximo em mulheres sedentárias fumantes. MÉTODOS: A pressão arterial sistólica (PAS) e diastólica (PAD) e a freqüência cardíaca (FC) foram medidas de forma não invasiva em mulheres jovens não fumantes (MNF, n = 7) e fumantes (MF, n = 7), sem e com abstinência do fumo por 24 horas, em repouso, durante a realização do teste submáximo em bicicleta ergométrica e na recuperação. RESULTADOS: Em repouso, a PAD e a FC foram maiores nas MF (76 ± 1mmHg e 86 ± 5bpm) quando comparadas com as MNF (68 ± 2mmHg e 72 ± 2bpm). Após 24 horas sem o tabaco essas medidas foram normalizadas. Durante o exercício, a PAS e a FC aumentaram nos grupos estudados. A PAD foi maior nas MF (~15%) em relação às MNF em todos os estágios do exercício. Na situação de abstinência, a PAD aumentou somente no último estágio de exercício. Na recuperação tanto a PAD quanto a FC foram maiores nas MF, na situação basal e com abstinência de 24h, quando comparadas as MNF. CONCLUSÃO: Estes resultados demonstram que mulheres jovens fumantes apresentam prejuízo em parâmetros hemodinâmicos em repouso e em resposta ao exercício submáximo, os quais, podem ser em parte revertidos pela abstinência em curto prazo do uso do tabaco.
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Arima H, Kiyohara Y, Tanizaki Y, Nakabeppu Y, Kubo M, Kato I, Sueishi K, Tsuneyoshi M, Fujishima M, Iida M. Angiotensin I-converting enzyme gene polymorphism modifies the smoking-cancer association: the Hisayama Study. Eur J Cancer Prev 2006; 15:196-201. [PMID: 16679861 DOI: 10.1097/01.cej.0000199506.15571.37] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
We examined the long-term contribution of smoking and angiotensin I-converting enzyme (ACE) gene I/D polymorphism to total cancer deaths in a prospective study of a general Japanese population. A total of 937 subjects aged 40 years or older were selected from an original cohort of 1621 subjects and were followed up for 32 years. During the follow-up period, 176 subjects died of cancer. Cancer mortality increased significantly with increasing current smoking levels. Although no clear relationship was observed between ACE genotypes and fatal cancer, the interaction term between current smoking and ACE genotype DD was found to be significant. In stratified analysis by ACE genotype after controlling for age, sex, alcohol intake, body mass index, glucose intolerance, serum total cholesterol and systolic blood pressure, the risk of fatal cancer in currently smoking subjects with genotype DD was twofold greater than that in subjects with genotypes II and ID. Among current smokers, subjects with genotype DD also showed a significantly greater risk of death due to cancer compared with those with genotypes II and ID combined (hazard ratio 1.77; 95% confidence interval 1.04-3.00; P=0.03). In conclusion, our findings suggest that ACE genotype DD enhances the association between smoking and cancer death in the general population.
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Affiliation(s)
- Hisatomi Arima
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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Iida H, Iida M, Takenaka M, Fujiwara H, Dohi S. Angiotensin II type 1 (AT1)-receptor blocker prevents impairment of endothelium-dependent cerebral vasodilation by acute cigarette smoking in rats. Life Sci 2005; 78:1310-6. [PMID: 16213531 DOI: 10.1016/j.lfs.2005.07.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2005] [Accepted: 07/04/2005] [Indexed: 11/18/2022]
Abstract
Our aim was to test for smoking-induced endothelial dysfunction in rat cerebral vessels, then to evaluate the effect of valsartan [angiotensin II type I (AT1)-receptor blocker] on that impairment. In pentobarbital-anesthetized, mechanically ventilated Sprague-Dawley rats, we used a cranial window preparation to measure changes in pial vessel diameters following topical applications of acetylcholine (Ach) (before and after smoking or intravenous nicotine infusion; n = 6 in each group), and adenosine (n = 6 for before and after smoking). Then, after intravenous valsartan pretreatment we reexamined the pial vasodilator response to topical Ach (before and after cigarette smoking). Under control conditions, cerebral arterioles were dilated by 6.9 +/- 4.2% and 13.6 +/- 4.8% by topical Ach (10(-6) M and 10(-5) M, respectively) and by 6.4 +/- 2.5% and 12.2 +/- 3.1% by topical adenosine (10(-5) M and 10(-4) M, respectively). One hour after a 1-min inhalation of mainstream smoke (1-mg nicotine cigarette), 10(-5) M Ach constricted cerebral arterioles (-4.4 +/- 4.1%), while 10(-4) M adenosine dilated them by 13.4 +/- 3.4%. One hour after a 1-min nicotine infusion (0.05 mg), 10(-5) M Ach dilated cerebral arterioles by 9.9 +/- 2.4%. Thus, vasodilator response to topical Ach was impaired after smoking, whereas that to adenosine was unaffected. However, the vasodilator response to Ach was unaffected by intravenous nicotine. Valsartan prevented smoking from impairing Ach-induced vasodilation. In conclusion, acute single-cigarette smoking causes a dysfunction of endothelium-dependent, but not endothelium-independent, vasodilation of rat cerebral vessels in vivo, and the effect was not mimicked by intravenous nicotine. AT1-receptor blockade prevented the above smoking-induced impairment of endothelium-dependent vasodilation.
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Affiliation(s)
- Hiroki Iida
- Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu-City, Gifu 501-1194, Japan.
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Saijonmaa O, Nyman T, Fyhrquist F. Regulation of angiotensin-converting enzyme production by nicotine in human endothelial cells. Am J Physiol Heart Circ Physiol 2005; 289:H2000-4. [PMID: 15964916 DOI: 10.1152/ajpheart.01238.2004] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Nicotine, a component of cigarette smoke, has been implicated in the pathogenesis of cardiovascular disease. We examined whether nicotine regulates angiotensin-converting enzyme (ACE), an enzyme that plays an important role in the pathophysiology of atherosclerosis and hypertension. Human umbilical cord vein endothelial cells were treated with nicotine (0.1-1 microM) alone or in combination with vascular endothelial growth factor (VEGF; 0.5 nM) or GF-109203X (GFX; 2.5 microM). The amount of ACE in intact endothelial cells was measured by an inhibitor-binding assay method, and ACE mRNA levels were quantified using LightCycler technology. Phosphorylated PKC levels were measured by Western immunoblotting. Nicotine did not modulate basal ACE production but significantly potentiated VEGF-induced ACE upregulation. Treatment of endothelial cells with the PKC inhibitor GFX totally blocked VEGF- and nicotine-induced ACE upregulation. VEGF induced PKC phosphorylation, which was potentiated by cotreatment with nicotine. We conclude that nicotine significantly potentiated VEGF-induced ACE upregulation. This effect was probably mediated by PKC phosphorylation. The interaction of nicotine with VEGF in ACE induction may contribute to the pathogenesis of smoking-related cardiovascular disease.
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Affiliation(s)
- Outi Saijonmaa
- Minerva Institute for Medical Research, Biomedicum Helsinki, Haartmaninkatu 8, FIN-00290, Helsinki, Finland.
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Abstract
Smoking has multiple effects on hormone secretion, some of which are associated with important clinical implications. These effects are mainly mediated by the pharmacological action of nicotine and also by toxins such as thiocyanate. Smoking affects pituitary, thyroid, adrenal, testicular and ovarian function, calcium metabolism and the action of insulin. The major salient clinical effects are the increased risk and severity of Graves' hyperthyroidism and opthalmopathy, osteoporosis and reduced fertility. Smoking also contributes to the development of insulin resistance and hence type 2 diabetes mellitus. An important concern is also the effect of smoking on the foetus and young children. Passive transfer of thiocyanate can cause disturbance of thyroid size and function. Furthermore, maternal smoking causes increased catecholamine production, which may contribute to under perfusion of the foetoplacental unit.
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Affiliation(s)
- D Kapoor
- Centre for Diabetes and Endocrinology, Barnsley District General Hospital, Barnsley, UK
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Payne JR, Dhamrait SS, Toor IS, Cooper J, Jones A, Miller GJ, Humphries SE, Montgomery HE. The −344T>C promoter variant of the gene for aldosterone synthase (CYP11B2) is not associated with cardiovascular risk in a prospective study of UK healthy men. Atherosclerosis 2004; 174:81-6. [PMID: 15135254 DOI: 10.1016/j.atherosclerosis.2004.01.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2003] [Revised: 12/30/2003] [Accepted: 01/21/2004] [Indexed: 10/26/2022]
Abstract
INTRODUCTION The tissue renin-angiotensin system is implicated in the pathogenesis of coronary artery disease (CAD). As locally synthesised aldosterone is a potential mediator of CAD, we have sought an association of the -344T>C variant of the aldosterone synthase (CYP11B2) gene with CAD events. METHODS Subjects comprised of the Second Northwick Park Heart Study (NPHSII), a prospective study of unrelated, healthy middle-aged Caucasian males. CAD events were recorded in 2490 subjects, and defined as a sudden cardiac death, myocardial infarction or coronary artery revascularisation procedure. Mean follow-up was 10.8 years. Aldosterone synthase genotype was determined in 2490 subjects. Power calculation suggests that we have 80% power (at a significance level of 0.05) to detect a difference in hazard ratio (HR) between homozygote groups of 0.45. RESULTS One hundred and eighty-seven CAD events were recorded in 2490 subjects. In the group overall, CAD events were independent of genotype with adjusted hazard ratios being 1.00 versus 1.25 versus 0.80 for TT versus TC versus CC genotypes, respectively, P = 0.07. Genotype interactions with smoking and blood pressure were sought. Whilst CAD events were independent of genotype amongst non-smokers, CC genotype in smokers was associated with a reduced risk HR 2.02 versus 2.28 versus 0.82 for TT versus TC versus CC genotypes, P = 0.05 (HR for TT + TC versus CC were 1.77 versus 0.67, P = 0.02). This apparent interaction remained after adjustment for conventional risk factors. No such interaction was found with blood pressure. CONCLUSIONS Aldosterone synthase genotype is unrelated to overall CAD events risk. A possible interaction with smoking requires confirmation.
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Affiliation(s)
- J R Payne
- British Heart Foundation Laboratories, Centre for Cardiovascular Genetics, Royal Free & University College Medical School, Rayne Building, 5 University Street, London WC1E 6JF, UK
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Paganelli MO, Tanus-Santos JE, Toledo JC, do Prado JF, Calegari V, Moreno H. Acute administration of nicotine impairs the hypotensive responses to bradykinin in rats. Eur J Pharmacol 2001; 413:241-6. [PMID: 11226399 DOI: 10.1016/s0014-2999(01)00744-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Nicotine may contribute to smoking-induced endothelial dysfunction because of its ability to impair endothelium-dependent vasodilatation. We investigated whether the acute administration of nicotine changes the hypotensive responses to bradykinin in rats. The effects of pre-treatment with losartan or enalapril on the nicotine-induced changes in the responses to bradykinin were also evaluated. In study 1, anesthetized rats were cannulated via carotid artery for the measurement of mean arterial pressure. Dose-response curves to bradykinin (0.1, 0.4, 1.6, 6.4, 25 and 100 microg/kg) were generated before and 10 min after the injection of nicotine (200 microg/kg, i.v.) or saline. The individual dose-response curves were fitted to a four-parameter logistic equation using the ALLFIT program, which provided an estimate of the maximal response (E(max)) and of the dose of bradykinin producing the half-maximal response (ED(50)). In study 2, rats were pre-treated orally with losartan (10 mg/kg/day) or enalapril maleate (25 mg/kg/day) for 2 weeks. Control rats received tap water alone. After pre-treatment, the rats were anesthetized and used as described in study 1. Nicotine decreased the E(max) (from 73.0+/-7.5 to 65.7+/-3.3 mm Hg; P<0.05) but did not affect the ED(50). In study 2, losartan or enalapril did not affect nicotine-induced decrease in responses to bradykinin; E(max) decreased in both groups (from 68.7+/-6.3 to 62.8+/-4.2 mm Hg, and from 53.8+/-13.0 to 43.1+/-7.1 mm Hg, respectively; P<0.05) without significantly changing the ED(50). These results suggest that nicotine impairs the endothelium-dependent hypotensive responses to bradykinin. This effect is not influenced by inhibition of the angiotensin-converting enzyme or by blockade of the angiotensin AT(1) receptors.
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Affiliation(s)
- M O Paganelli
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), P.O. Box 6111, 13081-970, Campinas, São Paulo, Brazil
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Hibi K, Ishigami T, Kimura K, Nakao M, Iwamoto T, Tamura K, Nemoto T, Shimizu T, Mochida Y, Ochiai H, Umemura S, Ishii M. Angiotensin-converting enzyme gene polymorphism adds risk for the severity of coronary atherosclerosis in smokers. Hypertension 1997; 30:574-9. [PMID: 9322984 DOI: 10.1161/01.hyp.30.3.574] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
To investigate the relation between the angiotensin-converting enzyme (ACE) gene polymorphism and acute coronary syndromes with respect to environmental factors, we analyzed the association of genotype with the coronary angiographic findings of patients with acute myocardial infarction or unstable angina pectoris, and we examined the linkage of each genotype with established risk factors for coronary artery disease. We determined the ACE genotype in 152 Japanese patients with acute coronary syndromes and 399 healthy individuals. The genotype distributions were not different between the two groups (P=.74, chi2 test). In the former group, coronary angiograms were evaluated by criteria based on the number of diseased vessels, the number of stenotic lesions (> or = 50%), and the relative abnormal arterial portion (extent index). Although the number of stenotic lesions was higher in patients with the DD genotype than in those with the ID or II genotype (P=.006), there were no differences in the number of diseased vessels or the extent index. When only smokers were analyzed, the number of diseased vessels (P=.032), number of stenotic lesions (P=.003), and extent index (P=.019) were all higher in patients with the DD genotype than in those with the ID or II genotype. In contrast, these differences in the respective parameters did not exist in nonsmokers. The results indicate smoking-associated effects of the ACE genotype on the severity of coronary atherosclerosis.
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Affiliation(s)
- K Hibi
- Second Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan
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Kotamäki M. Smoking induced differences in autonomic responses in military pilot candidates. Clin Auton Res 1995; 5:31-6. [PMID: 7780288 DOI: 10.1007/bf01845496] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The effects of smoking on autonomic function, the renin-angiotensin-aldosterone system, plasma catecholamine and 11-dehydro-thromboxane B2 values were studied in 37 young male military pilot candidates, 19 smokers and 18 non-smokers. There was a higher diastolic blood pressure at rest and higher systolic blood pressure after 5 min during the orthostatic test in smokers. Smokers also had higher diastolic blood pressure levels after exercise in the hand-grip test. Smokers had a lower Valsalva ratio and higher tachycardia ratio in the modified Valsalva manoeuvre, suggesting a degree of autonomic dysfunction. Plasma renin levels at rest and plasma noradrenaline levels after hand-grip test were significantly higher in smokers, implying increased sympathetic activity and enhanced activation of the renin-angiotensin system. Our findings indicate that smoking in fit young men increases sympathetic activity and changes physiological responses to autonomic tests.
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Affiliation(s)
- M Kotamäki
- Wihuri Research Institute, Helsinki, Finland
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Virokannas H, Anttonen H. Dose-response relationship between smoking and impairment of hearing acuity in workers exposed to noise. SCANDINAVIAN AUDIOLOGY 1995; 24:211-6. [PMID: 8750748 DOI: 10.3109/01050399509047538] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The study included an inquiry and clinical examination of 443 reindeer herders (mean age 43 years) who frequently used noisy tools and vehicles, in particular snowmobiles and chain-saws. Age-adjusted hearing thresholds at 3 and 4 kHz deteriorated significantly with increased exposure to noise. There was the dose-response relationship between the amount of smoking and the impairment of hearing acuity when exposure time to noise was used as covariance. The amount of smoking was not significant until very heavy smoking (more than 144,000 cigarettes, i.e. 20 cigarettes/day for more than 20 years), and no smoking effect could be seen using the classification of current smoking habits. The results support the practice that screening of hearing acuity should be repeated more often in smokers than in non-smokers in noisy work so that hearing damage can be found in an incipient stage and noise-induced hearing loss effectively prevented.
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Affiliation(s)
- H Virokannas
- Department of Public Health Science and General Practice, University of Oulu, Finland
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Ekberg G, Sjöfors G, Grefberg N, Larsson LO, Vaara I. Protein intake and glomerular hyperfiltration in insulin--treated diabetics without manifest nephropathy. SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY 1993; 27:441-6. [PMID: 8159915 DOI: 10.3109/00365599309182275] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Protein intake in relation to glomerular filtration rate (GFR) and urinary albumin excretion (UAE) has been studied in 96 insulin-treated diabetic patients, 20-40 years of age and without nephropathy. They had diastolic blood pressure (DBP) not exceeding 90 mmHg and a GFR exceeding -2 SD of the age-related value. They were without medications except for insulin. There were no significant differences in protein intake between diabetic patients with and without hyperfiltration (1.18 +/- 0.26 g/kg/d vs 1.21 +/- 0.42 g/kg/d, p = 0.75) or between diabetic patients with or without increased UAE (1.16 +/- 0.41 g/kg/d vs 1.24 +/- 0.37 g/kg/d, p = 0.37). No relations were found between protein intake and GFR or UAE in the whole sample, but a positive relation was found between UAE and protein intake in patients with increased UAE. Protein intake correlated with UAE in hyperfiltrators who use tobacco (n = 8, r = 0.85, p = 0.01), but not in non-users (n = 11, r = 0.24, p = 0.48). In conclusion our findings give no support for a relation between high protein intake and glomerular hyperfiltration in insulin-treated-diabetic patients. However, in contrast to non-users of tobacco, a positive relation was found between UAE and protein intake in tobacco users with hyperfiltration.
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Affiliation(s)
- G Ekberg
- Department of Medicine, Central Hospital, Växjö, Sweden
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Kotamäki M, Manninen V, Laustiola KE. Enalapril versus atenolol in the treatment of hypertensive smokers. Eur J Clin Pharmacol 1993; 44:13-7. [PMID: 8436148 DOI: 10.1007/bf00315273] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
A randomised crossover study has been done to compare the antihypertensive efficacy of enalapril and atenolol in 45 smoking, hypertensive men. Treatment was started with enalapril 20 mg/d or atenolol 50 mg/d and, if necessary, the doses were doubled after 4 weeks to achieve a sitting diastolic blood pressure < or = 95 mm Hg, after which hydrochlorothiazide was added, if necessary. Both drugs lowered blood pressure significantly. However, enalapril was more efficient in lowering both systolic and diastolic blood pressure; the mean difference was significant after both 4 and 8 weeks in the sitting systolic (11.6 mm Hg and 7.9 mm Hg) and diastolic (3.3 mm Hg and 3.0 mm Hg) pressures and in the erect systolic pressures (8.2 mm Hg and 7.2 mm Hg), and after 8 weeks in the supine systolic pressure, too (8.9 mm Hg). The effect on enalapril was especially marked in moderate (< 20 cigarettes/day) smokers. The need for diuretics was also significantly less in the enalapril group. It appears that angiotensin-converting enzyme inhibitors may be superior to beta-adrenoceptor blockers in the treatment of hypertensive smoking patients.
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Affiliation(s)
- M Kotamäki
- Wihuri Research Institute, Helsinki, Finland
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Affiliation(s)
- R Lassila
- Wihuri Research Institute, Helsinki, Finland
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38
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Abstract
BACKGROUND Washington State birth certificates were used to conduct a population-based case-control study to assess the possible association of maternal smoking with polyhydramnios. METHODS All singleton births complicated by polyhydramnios (n = 557) were identified from the vital records for the years 1984 to 1987. For comparison, 1671 records were randomly selected for the same years from singleton births uncomplicated by polyhydramnios. RESULTS Women who reportedly smoked prenatally were found to be at increased risk for polyhydramnios (relative risk [RR] = 1.7, 95% confidence interval [CI] = 1.5-2.1, adjusted for marital status, maternal age, and parity). When women with conditions known to be associated with polyhydramnios were excluded, the risk for those who smoked prenatally remained elevated (RR = 1.8, 95% CI = 1.1-2.3). CONCLUSION Overdistention of the uterus from polyhydramnios may cause a variety of pregnancy complications. The observed association of smoking with polyhydramnios may be a further indication for public health interventions aimed at preventing smoking during pregnancy.
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Affiliation(s)
- W Myhra
- Department of Epidemiology, University of Washington, Seattle
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Kaprio J, Koskenvuo M. Cigarette smoking as a cause of lung cancer and coronary heart disease. A study of smoking-discordant twin pairs. ACTA GENETICAE MEDICAE ET GEMELLOLOGIAE 1990; 39:25-34. [PMID: 2392891 DOI: 10.1017/s0001566000005560] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Despite increasing scientific evidence for a causal role of tobacco smoking in lung cancer and coronary heart disease, an alternative hypothesis was put forward several decades ago. The constitutional hypothesis has stated that there are genetic or other common factors, which predispose both to smoking and disease. A critical test of this hypothesis was considered the pattern of occurrence of disease in monozygotic (MZ) twin pairs in which one is a smoker and the other never has been a smoker. Initial twin studies found only small differences in the mortality of smoking and nonsmoking twins of discordant pairs. In the Finnish Twin Cohort, a population-based panel of adult like-sexed twin pairs, a questionnaire study carried out in 1975 permitted identification of 2488 twin pairs discordant for cigarette smoking. Analyses of total mortality and mortality due to coronary heart disease and lung cancer indicate that the smoking members of discordant MZ pairs are at higher risk than their nonsmoking cotwins; increased mortality of smoking cotwins was also found on 21-year follow-up of smoking-discordant pairs in Sweden. Incidence data and noninvasive studies of atherosclerosis in the Finnish sample provide confirmatory evidence for the causal role of smoking in the etiology of coronary heart disease and lung cancer.
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Affiliation(s)
- J Kaprio
- Department of Public Health, University of Helsinki, Finland
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