Sex-Related Differences in Oxidative, Platelet, and Vascular Function in Chronic Users of Heat-not-Burn vs. Traditional Combustion Cigarettes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Design
2.2. Flow-Mediated Dilation
2.3. Laboratory Analyses
2.3.1. Plasma Soluble CD40 Ligand Assay
2.3.2. Plasma Soluble P-Selectin
2.3.3. Platelet Preparation and Aggregation
2.3.4. Serum Cotinine
2.3.5. Serum Nitric Oxide Bioavailability
2.3.6. Serum Hydrogen Peroxide Production
2.3.7. Serum Soluble Nox2-Derived Peptide Assay
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Beaglehole, R.; Bonita, R.; Yach, D.; Mackay, J.; Reddy, K.S. A tobacco-free world: A call to action to phase out the sale of tobacco products by 2040. Lancet 2015, 385, 1011–1018. [Google Scholar] [CrossRef]
- Saglietto, A.; Manfredi, R.; Elia, E.; D’Ascenzo, F.; De Ferrari, G.M.; Biondi-Zoccai, G.; Munzel, T. Cardiovascular disease burden: Italian and global perspectives. Minerva Cardiol. Angiol. 2021, 69, 231–240. [Google Scholar] [CrossRef] [PubMed]
- Frati, G.; Carnevale, R.; Nocella, C.; Peruzzi, M.; Marullo, A.G.M.; De Falco, E.; Chimenti, I.; Cammisotto, V.; Valenti, V.; Cavarretta, E.; et al. Profiling the Acute Effects of Modified Risk Products: Evidence from the SUR-VAPES (Sapienza University of Rome-Vascular Assessment of Proatherosclerotic Effects of Smoking) Cluster Study. Curr. Atheroscler. Rep. 2020, 22, 8. [Google Scholar] [CrossRef] [PubMed]
- Hartmann-Boyce, J.; Livingstone-Banks, J.; Ordóñez-Mena, J.M.; Fanshawe, T.R.; Lindson, N.; Freeman, S.C.; Sutton, A.J.; Theodoulou, A.; Aveyard, P. Behavioural interventions for smoking cessation: An overview and network meta-analysis. Cochrane Database Syst. Rev. 2021, 1, Cd013229. [Google Scholar] [CrossRef]
- Quigley, J.M.; Walsh, C.; Lee, C.; Long, J.; Kennelly, H.; McCarthy, A.; Kavanagh, P. Efficacy and safety of electronic cigarettes as a smoking cessation intervention: A systematic review and network meta-analysis. Tob. Prev. Cessat. 2021, 7, 69. [Google Scholar] [CrossRef]
- Suissa, K.; Larivière, J.; Eisenberg, M.J.; Eberg, M.; Gore, G.C.; Grad, R.; Joseph, L.; Reynier, P.M.; Filion, K.B. Efficacy and Safety of Smoking Cessation Interventions in Patients With Cardiovascular Disease: A Network Meta-Analysis of Randomized Controlled Trials. Circulation. Cardiovasc. Qual. Outcomes 2017, 10, e002458. [Google Scholar] [CrossRef]
- Salman, R.; Talih, S.; El-Hage, R.; Haddad, C.; Karaoghlanian, N.; El-Hellani, A.; Saliba, N.A.; Shihadeh, A. Free-Base and Total Nicotine, Reactive Oxygen Species, and Carbonyl Emissions From IQOS, a Heated Tobacco Product. Nicotine Tob. Res. Off. J. Soc. Res. Nicotine Tob. 2019, 21, 1285–1288. [Google Scholar] [CrossRef]
- Auer, R.; Concha-Lozano, N.; Jacot-Sadowski, I.; Cornuz, J.; Berthet, A. Heat-Not-Burn Tobacco Cigarettes: Smoke by Any Other Name. JAMA Intern. Med. 2017, 177, 1050–1052. [Google Scholar] [CrossRef] [Green Version]
- Bekki, K.; Inaba, Y.; Uchiyama, S.; Kunugita, N. Comparison of Chemicals in Mainstream Smoke in Heat-not-burn Tobacco and Combustion Cigarettes. J. UOEH 2017, 39, 201–207. [Google Scholar] [CrossRef] [Green Version]
- Carnevale, R.; Sciarretta, S.; Violi, F.; Nocella, C.; Loffredo, L.; Perri, L.; Peruzzi, M.; Marullo, A.G.; De Falco, E.; Chimenti, I.; et al. Acute Impact of Tobacco vs Electronic Cigarette Smoking on Oxidative Stress and Vascular Function. Chest 2016, 150, 606–612. [Google Scholar] [CrossRef]
- West, R. Tobacco smoking: Health impact, prevalence, correlates and interventions. Psychol. Health 2017, 32, 1018–1036. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ikonomidis, I.; Marinou, M.; Vlastos, D.; Kourea, K.; Andreadou, I.; Liarakos, N.; Triantafyllidi, H.; Pavlidis, G.; Tsougos, E.; Parissis, J.; et al. Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program. Atherosclerosis 2017, 262, 123–130. [Google Scholar] [CrossRef] [PubMed]
- Peruzzi, M.; Biondi-Zoccai, G.; Carnevale, R.; Cavarretta, E.; Frati, G.; Versaci, F. Vaping Cardiovascular Health Risks: An Updated Umbrella Review. Curr. Emerg. Hosp. Med. Rep. 2020, 8, 103–109. [Google Scholar] [CrossRef]
- Farsalinos, K.E.; Yannovits, N.; Sarri, T.; Voudris, V.; Poulas, K.; Leischow, S.J. Carbonyl emissions from a novel heated tobacco product (IQOS): Comparison with an e-cigarette and a tobacco cigarette. Addiction 2018, 113, 2099–2106. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Luo, Y.; Jiang, X.; Zhang, H.; Zhu, F.; Hu, S.; Hou, H.; Hu, Q.; Pang, Y. Chemical Analysis and Simulated Pyrolysis of Tobacco Heating System 2.2 Compared to Conventional Cigarettes. Nicotine Tob. Res. Off. J. Soc. Res. Nicotine Tob. 2019, 21, 111–118. [Google Scholar] [CrossRef]
- Archie, S.R.; Sharma, S.; Burks, E.; Abbruscato, T. Biological determinants impact the neurovascular toxicity of nicotine and tobacco smoke: A pharmacokinetic and pharmacodynamics perspective. Neurotoxicology 2022, 89, 140–160. [Google Scholar] [CrossRef]
- Khan, N.A.; Sundar, I.K.; Rahman, I. Strain- and sex-dependent pulmonary toxicity of waterpipe smoke in mouse. Physiol. Rep. 2018, 6, e13579. [Google Scholar] [CrossRef] [Green Version]
- Rerkpattanapipat, P.; Stanek, M.S.; Kotler, M.N. Sex and the heart: What is the role of the cardiologist? Eur. Heart J. 2001, 22, 201–208. [Google Scholar] [CrossRef] [Green Version]
- Loffredo, L.; Carnevale, R.; Battaglia, S.; Marti, R.; Pizzolo, S.; Bartimoccia, S.; Nocella, C.; Cammisotto, V.; Sciarretta, S.; Chimenti, I.; et al. Impact of chronic use of heat-not-burn cigarettes on oxidative stress, endothelial dysfunction and platelet activation: The SUR-VAPES Chronic Study. Thorax 2021, 76, 618–620. [Google Scholar] [CrossRef]
- Violi, F.; Sanguigni, V.; Loffredo, L.; Carnevale, R.; Buchetti, B.; Finocchi, A.; Tesauro, M.; Rossi, P.; Pignatelli, P. Nox2 is determinant for ischemia-induced oxidative stress and arterial vasodilatation: A pilot study in patients with hereditary Nox2 deficiency. Arterioscler. Thromb. Vasc. Biol. 2006, 26, e131–e132. [Google Scholar] [CrossRef] [Green Version]
- Fried, N.D.; Gardner, J.D. Heat-not-burn tobacco products: An emerging threat to cardiovascular health. Am. J. Physiol. Heart Circ. Physiol. 2020, 319, H1234–H1239. [Google Scholar] [CrossRef] [PubMed]
- Sakaguchi, C.; Nagata, Y.; Kikuchi, A.; Takeshige, Y.; Minami, N. Differences in Levels of Biomarkers of Potential Harm Among Users of a Heat-Not-Burn Tobacco Product, Cigarette Smokers, and Never-Smokers in Japan: A Post-Marketing Observational Study. Nicotine Tob. Res. Off. J. Soc. Res. Nicotine Tob. 2021, 23, 1143–1152. [Google Scholar] [CrossRef] [PubMed]
- Ikonomidis, I.; Vlastos, D.; Kostelli, G.; Kourea, K.; Katogiannis, K.; Tsoumani, M.; Parissis, J.; Andreadou, I.; Alexopoulos, D. Differential effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function. Sci. Rep. 2021, 11, 11808. [Google Scholar] [CrossRef] [PubMed]
- Connett, J.E.; Murray, R.P.; Buist, A.S.; Wise, R.A.; Bailey, W.C.; Lindgren, P.G.; Owens, G.R. Changes in smoking status affect women more than men: Results of the Lung Health Study. Am. J. Epidemiol. 2003, 157, 973–979. [Google Scholar] [CrossRef] [Green Version]
- Haghani, A.; Arpawong, T.E.; Kim, J.K.; Lewinger, J.P.; Finch, C.E.; Crimmins, E. Female vulnerability to the effects of smoking on health outcomes in older people. PLoS ONE 2020, 15, e0234015. [Google Scholar] [CrossRef]
- Howe, M.; Leidal, A.; Montgomery, D.; Jackson, E. Role of cigarette smoking and gender in acute coronary syndrome events. Am. J. Cardiol. 2011, 108, 1382–1386. [Google Scholar] [CrossRef]
- Gemmati, D.; Varani, K.; Bramanti, B.; Piva, R.; Bonaccorsi, G.; Trentini, A.; Manfrinato, M.C.; Tisato, V.; Carè, A.; Bellini, T. “Bridging the Gap” Everything that Could Have Been Avoided if We Had Applied Gender Medicine, Pharmacogenetics and Personalized Medicine in the Gender-Omics and Sex-Omics Era. Int. J. Mol. Sci. 2019, 21, 296. [Google Scholar] [CrossRef] [Green Version]
Characteristic | Male | Female | p |
---|---|---|---|
Subjects | 27 | 33 | - |
Age (years) | 30.2 ± 8.5 | 30.8 ± 7.7 | 0.763 |
Height (cm) | 178.3 ± 6.4 | 165.9 ± 7.5 | <0.001 |
Weight (kg) | 77.4 ± 8.9 | 58.4 ± 7.1 | <0.001 |
Body mass index (kg/m2) | 24.4 ± 2.7 | 21.3 ± 2.5 | <0.001 |
Systolic blood pressure (mmHg) | 123.2 ± 14.3 | 112.4 ± 8.9 | <0.001 |
Diastolic blood pressure (mmHg) | 77.5 ± 7.2 | 71.4 ± 9.4 | 0.007 |
Mean blood pressure (mmHg) | 92.7 ± 6.6 | 85.1 ± 8.4 | <0.001 |
Total cholesterol (mg/dL) | 180.0 ± 14.2 | 174.7 ± 14.5 | 0.163 |
Smoking status | 0.946 | ||
Non-smoker | 9 (33.3%) | 11 (33.3%) | |
Traditional combustion cigarette smoker | 10 (37.0%) | 10 (30.3%) | |
Heat-not-burn cigarette smoker | 8 (29.6%) | 12 (36.4%) | |
Years of smoking | 2.2 ± 2.2 | 3.0 ± 4.0 | 0.349 |
Cigarettes per day | 9.8 ± 9.3 | 8.0 ± 6.6 | 0.390 |
Flow-mediated dilation (%) | 4.0 ± 3.6 | 5.5 ± 5.0 | 0.198 |
Nitric oxide (µmol/L) | 20.8 ± 15.8 | 22.1 ± 18.6 | 0.767 |
sNox2-dp (ng/mL) | 34.3 ± 13.0 | 33.9 ± 12.9 | 0.887 |
H2O2 (µmol/L) | 25.6 ± 15.7 | 22.8 ± 16.7 | 0.519 |
sCD40L (ng/mL) | 2.5 ± 1.1 | 2.7 ± 1.2 | 0.322 |
sP-selectin (ng/mL) | 6.4 ± 3.2 | 7.0 ± 3.9 | 0.584 |
Platelet aggregation (%) | 71.3 ± 12.4 | 73.4 ± 10.4 | 0.465 |
Cotinine (ng/mL) | 95.5 ± 78.5 | 94.2 ± 72.0 | 0.949 |
Characteristic | Male | Female | p |
---|---|---|---|
Subjects | 9 | 11 | - |
Age (years) | 30.0 ± 6.5 | 27.6 ± 5.2 | 0.380 |
Height (cm) | 175 ± 6.6 | 161 ± 6.8 | <0.001 |
Weight (kg) | 76.3 ± 5.9 | 57.6 ± 8.1 | <0.001 |
Body mass index (kg/m2) | 25.0 ± 2.4 | 22.1 ± 2.3 | <0.05 |
Systolic blood pressure (mmHg) | 130 ± 20.9 | 111.2 ± 7.2 | <0.05 |
Diastolic blood pressure (mmHg) | 78.9 ± 8.2 | 68.2 ± 10.6 | <0.05 |
Mean blood pressure (mmHg) | 95.9 ± 8.2 | 82.5 ± 9.0 | <0.01 |
Total cholesterol (mg/dL) | 181.1 ± 9.4 | 176.4 ± 16.7 | <0.459 |
Flow-mediated dilation (%) | 6.3 ± 4.4 | 9.1 ± 5.7 | 0.244 |
Nitric oxide (µmol/L) | 41.4 ± 8.3 | 46.1 ± 11.8 | 0.333 |
sNox2-dp (ng/mL) | 18.2 ± 5.3 | 20.4 ± 9.4 | 0.550 |
H2O2 (µmol/L) | 9.7 ± 3.8 | 8.4 ± 3.6 | 0.434 |
sCD40L (ng/mL) | 1.4 ± 0.5 | 1.6 ± 0.6 | 0.465 |
sP-selectin (ng/mL) | 3.2 ± 1.0 | 2.7 ± 1.4 | 0.335 |
Platelet aggregation (%) | 59.3 ± 8.6 | 64.0 ± 7.5 | 0.209 |
Cotinine (ng/mL) | 2.2 ± 0.7 | 2.2 ± 0.8 | 0.898 |
Characteristic | Male | Female | p |
---|---|---|---|
Subjects | 10 | 10 | |
Age (years) | 24.7 ± 2.9 | 29.8 ± 5.0 | 0.012 |
Height (cm) | 179.7 ± 7.0 | 164.3 ± 6.8 | <0.001 |
Weight (kg) | 78.6 ± 11.9 | 58.4 ± 6.4 | <0.001 |
Body mass index (kg/m2) | 24.3 ± 3.5 | 21.6 ± 2.0 | 0.046 |
Systolic blood pressure (mmHg) | 121.5 ± 8.8 | 115 ± 9.7 | 0.135 |
Diastolic blood pressure (mmHg) | 79.2 ± 5.8 | 71 ± 9.1 | 0.027 |
Mean blood pressure (mmHg) | 93.3 ± 2.8 | 85.7 ± 8.5 | 0.015 |
Total cholesterol (mg/dL) | 180.1 ± 15.4 | 183.1 ± 10.3 | 0.615 |
Years of smoking | 4.5 ± 1.8 | 8.2 ± 3.5 | 0.009 |
Cigarettes per day | 13.4 ± 8.0 | 12.8 ± 2.66 | 0.824 |
Flow-mediated dilation (%) | 2.1 ± 2.9 | 3.5 ± 4.2 | 0.380 |
Nitric oxide (µmol/L) | 11.7 ± 3.0 | 9.2 ± 2.5 | 0.060 |
sNox2-dp (ng/mL) | 46.4 ± 4.2 | 41.7 ± 11.4 | 0.236 |
H2O2 (µmol/L) | 36.1 ± 15.0 | 32.9 ± 22.9 | 0.720 |
sCD40L (ng/mL) | 3.1 ± 1.0 | 3.5 ± 1.0 | 0.388 |
sP-selectin (ng/mL) | 8.8 ± 2.8 | 9.9 ± 2.7 | 0.366 |
Platelet aggregation (%) | 78 ± 9.9 | 81.2 ± 7.5 | 0.426 |
Cotinine (ng/mL) | 147.6 ± 63.2 | 145.1 ± 24.9 | 0.909 |
Characteristic | Male | Female | p |
---|---|---|---|
Subjects | 8 | 12 | |
Age (years) | 37.3 ± 10.5 | 34.6 ± 10.0 | 0.573 |
Height (cm) | 180.1 ± 4.0 | 171.7 ± 4.9 | 0.000 |
Weight (kg) | 77.3 ± 8.5 | 59.2 ± 7.3 | 0.000 |
Body mass index (kg/m2) | 23.8 ± 2.1 | 20.1 ± 2.9 | 0.006 |
Systolic blood pressure (mmHg) | 117.5 ± 7.6 | 111.3 ± 9.8 | 0.145 |
Diastolic blood pressure (mmHg) | 73.9 ± 7.0 | 74.8 ± 8.1 | 0.806 |
Mean blood pressure (mmHg) | 88.4 ± 6.1 | 86.9 ± 7.9 | 0.656 |
Total cholesterol (mg/dL) | 178.5 ± 18.4 | 166.2 ± 11.2 | 0.077 |
Smoking status | |||
Non-smoker | 0 | 0 | |
Combustion cigarette smoker | 0 | 0 | |
Heat-not-burn cigarette smoker | 8 | 12 | |
Years of smoking | 1.6 ± 0.4 | 1.3 ± 0.5 | 0.185 |
Cigarettes per day | 16.3 ± 6.9 | 11.3 ± 4.8 | 0.077 |
Flow-mediated dilation (%) | 3.9 ± 1.8 | 3.9 ± 3.0 | 0.999 |
Nitric oxide (µmol/L) | 8.9 ± 3.3 | 10.9 ± 3.2 | 0.187 |
sNox2-dp (ng/mL) | 37.4 ± 4.2 | 39.7 ± 5.1 | 0.305 |
H2O2 (µmol/L) | 30.3 ± 10.2 | 27.7 ± 6.5 | 0.493 |
sCD40L (ng/mL) | 2.8 ± 0.6 | 3.1 ± 0.9 | 0.318 |
sP-selectin (ng/mL) | 7.1 ± 2.3 | 8.4 ± 3.0 | 0.326 |
Platelet aggregation (%) | 76.3 ± 9.2 | 75.6 ± 8.3 | 0.868 |
Cotinine (ng/mL) | 135.3 ± 29.6 | 136.2 ± 42.8 | 0.959 |
Characteristic | Main Effects | Interactions | |||||
---|---|---|---|---|---|---|---|
TCC vs. NS | HNBC vs. NS | HNBC vs. TCC | Female Sex | TCC vs. NS | HNBC vs. NS | HNBC vs. TCC | |
Flow-mediated dilation | p < 0.001 (−4.9 [−7.4; −2.5]) | p = 0.002 (−4.0 [−6.5; −1.5]) | p = 0.453 (0.9 [−1.5; 3.4]) | p = 0.166 (1.4 [−0.6; 3.5] | p = 0.594 | p = 0.273 | p = 0.566 |
Nitric oxide | p < 0.001 (−33.3 [−37.6; −29.3]) | p < 0.001 (−34.0 [−38.1; −29.8]) | p = 0.816 (−0.5 [−4.7; 3.7]) | p = 0.424 (1.4 [−2.0; 4.8] | p = 0.088 | p = 0.534 | p = 0.279 |
sNox2-dp | p < 0.001 (24.6 [20.0; 29.3]) | p < 0.001 (19.3 [14.7; 24.0]) | p = 0.026 (−5.3 [−9.9; −0.7]) | p = 0.949 (−0.1 [−3.9; 3.7]) | p = 0.142 | p = 0.971 | p = 0.136 |
H2O2 | p < 0.001 (25.4 [17.7; 33.1]) | p < 0.001 (19.9 [12.2; 27.5]) | p = 0.154 (−5.5 [−13.2; 2.1]) | p = 0.456 (−2.4 [−8.7; 3.9]) | p = 0.817 | p = 0.873 | p = 0.945 |
sCD40L | p < 0.001 (1.8 [1.3; 2.3]) | p < 0.001 (1.5 [1.0; 2.0]) | p = 0.147 (−0.4 [−0.9; 0.1]) | p = 0.130 (0.3 [−0.1; 0.7]) | p = 0.665 | p = 0.730 | p = 0.932 |
sP-selectin | p < 0.001 (6.4 [4.9; 7.9]) | p < 0.001 (4.9 [3.5; 6.4]) | p = 0.050 (−1.5 [−3.0; 0.0]) | p = 0.316 (0.6 [−0.6; 1.8]) | p = 0.268 | p = 0.232 | p = 0.919 |
Platelet aggregation | p < 0.001 (17.8 [12.5; 23.1]) | p < 0.001 (13.8 [8.5; 19.2]) | p = 0.140 (−4.0 [−9.3; 1.3]) | p = 0.270 (2.4 [−1.9; 6.8]) | p = 0.786 | p = 0.330 | p = 0.478 |
Cotinine | p < 0.001 (144.1 [122.1; 166.2]) | p < 0.001 (133.7 [111.6; 155.7]) | p = 0.346 (−10.5 [−32.6; 11.6]) | p = 0.953 (−0.5 [−18.7; 17.6]) | p = 0.910 | p = 0.969 | p = 0.881 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Schirone, L.; Loffredo, L.; Carnevale, R.; Battaglia, S.; Marti, R.; Pizzolo, S.; Bartimoccia, S.; Nocella, C.; Cammisotto, V.; Saade, W.; et al. Sex-Related Differences in Oxidative, Platelet, and Vascular Function in Chronic Users of Heat-not-Burn vs. Traditional Combustion Cigarettes. Antioxidants 2022, 11, 1237. https://doi.org/10.3390/antiox11071237
Schirone L, Loffredo L, Carnevale R, Battaglia S, Marti R, Pizzolo S, Bartimoccia S, Nocella C, Cammisotto V, Saade W, et al. Sex-Related Differences in Oxidative, Platelet, and Vascular Function in Chronic Users of Heat-not-Burn vs. Traditional Combustion Cigarettes. Antioxidants. 2022; 11(7):1237. https://doi.org/10.3390/antiox11071237
Chicago/Turabian StyleSchirone, Leonardo, Lorenzo Loffredo, Roberto Carnevale, Simona Battaglia, Roberta Marti, Stefano Pizzolo, Simona Bartimoccia, Cristina Nocella, Vittoria Cammisotto, Wael Saade, and et al. 2022. "Sex-Related Differences in Oxidative, Platelet, and Vascular Function in Chronic Users of Heat-not-Burn vs. Traditional Combustion Cigarettes" Antioxidants 11, no. 7: 1237. https://doi.org/10.3390/antiox11071237