Effect of Switching From Cigarette Smoking to THS on Systemic Endothelial Function in Subjects With Established Atherosclerotic Disease

Main Inclusion Criteria: * History of coronary artery disease, defined as documented CAD (stable) with coronary artery stenosis on coronary angiogram ≥50% (incl. Percutaneous Coronary Intervention (PCI) / Coronary artery bypass graft surgery (CABG)) in the medical history or previously documented acute coronary syndrome (ACS) / myocardial infarction occurring more than 1 month prior to V1. AND / OR, History of peripheral artery disease (PAD) defined as ABI \<0.9 or TBI \<0.6 or clinical diagnosis of chronic, symptomatic lower limb ischemia as defined by Fontaine's stages I, IIa and IIb. * Body mass index (BMI) 17.6-40.0 kg/m2 and body weight \> 50 kg (male) or 40 kg (female). * Subject has a smoking history of at least 10 years. * Subject has not used other tobacco and nicotine products apart from cigarettes on a daily basis over the past year prior to V1. * Subject has been smoking ≥ 10 commercially available cigarettes/day on average (no brand restriction) for at least 1 year prior to V1 (based on self-reporting). * For subjects not willing to quit smoking only: have been advised to quit smoking and informed of smoking risks and of cessation programs and is still not willing to quit during the study duration. * Subjects willing to quit smoking only: willing to and set a target quit date (TQD) within the next 28 days at V1 as assessed by self-reported questions Main Exclusion Criteria: * Planned peripheral or coronary intervention or surgical procedure. * Unstable angina pectoris. * Critical limb ischemia (absolute peripheral pressures \<50mmHg). * Recent (\< 30 days) PAD revascularization therapy prior to V1. * Recent ACS / myocardial infarction or stroke / TIA \<30 days prior to V1. * Pre-existing symptomatic heart failure with reduced ejection fraction (EF\<35%). * Planned peripheral or coronary intervention or surgical procedure related to CAD or PAD. * Subjects with spirometry values indicating chronic obstructive pulmonary disease (COPD) GOLD\* Stage 3 or 4 (FEV1/FVC \<0.7 \& FEV1 \<50% predicted \[post-BD\]) * Existing known serious infection or chronic inflammatory systemic disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, uncontrolled diabetes (HbA1c ≥ 7.0 % \[or ≥ 53.0 mmol/mol\]) or uncontrolled hypertension (systolic blood pressure≥140 mmHg and / or diastolic blood pressure ≥90 mmHg., stage 4 and 5 chronic kidney disease, etc…). * Currently active cancer or history of cancer within the last 5 years prior to V1. * History of alcohol and / or drug abuse (other than tetrahydrocannabinol \[THC\]). * Positive serology test (human immunodeficiency virus (HIV) 1/2), hepatitis B and / or C). * Female subject is pregnant or breastfeeding, (a urine pregnancy test will be performed at V1 and V2) * Previous participation in this study, or participation in an investigational study (drug or medical device) within 4 weeks before V1 (participation in observational studies/registries allowed) * For women of childbearing potential, female subject who does not agree to using an acceptable method of effective contraception during the entire study. \[\*Global Initiative for Obstructive Lung Disease\]