EHR519 Week 1 Lecture 2B: Cardiovascular Disease Prevention PDF

WARNING THIS MATERIAL HAS BEEN PRODUCED AND COMMUNICATED TO YOU BY OR ON BEHALF OF CHARLES STURT UNIVERSITY IN ACCORDANCE WITH SECTION 113P OF THE COPYRIGHT ACT (ACT). THE MATERIAL IN THIS COMMUNICATION MAY BY SUBJECT TO COPYRIGHT UNDER THE ACT. ANY FURTHER RE...

WARNING THIS MATERIAL HAS BEEN PRODUCED AND COMMUNICATED TO YOU BY OR ON BEHALF OF CHARLES STURT UNIVERSITY IN ACCORDANCE WITH SECTION 113P OF THE COPYRIGHT ACT (ACT). THE MATERIAL IN THIS COMMUNICATION MAY BY SUBJECT TO COPYRIGHT UNDER THE ACT. ANY FURTHER REPRODUCTION OR COMMUNICATION OF THIS MATERIAL BY YOU MAY BE THE SUBJECT OF COPYRIGHT PROTECTION UNDER THIS ACT. DO NOT REMOVE THIS NOTICE EHR519 week 1 lecture 2B * Prevalence of cardiovascular disease in Australia * Role of Exercise for clients with cardiovascular conditions * Endothelial dysfunction and cardiovascular disease 2  Cardiovascular disease Cardiovascular disease (CVD) describes many different conditions affecting the heart and blood vessels The most common and serious types include coronary heart disease, stroke and heart failure Despite declining mortality and hospitalisation rates, CVD remains a major health problem in Australia Greater impact on males, elderly, Indigenous Australians and people living in remote and socioeconomically disadvantaged areas  Australia – the scary stats from ABS and AIHW In 2022, ~1.3 million (5.3%) of Australians had 1 or more conditions related to heart, stroke or vascular disease. 5.9% males, 4.6% females Age related 0-44 yrs 0.6% 75yrs and over 27.7% Adults >18 yrs- Increases with increased waist circumference (8.3% compared to 3.3%), ex-smokers to smokers (10.3% - 7.6%) and never smoked (10.3% compared to 4.7%), and self-reported health (49.2% compared to 17.2%) (>15 yrs) Socioeconomically disadvantaged 8.2 compared to 3.6 (gap increasing) Indigenous Australians, (adjusted for age) the prevalence of heart, stroke and vascular disease is 2.1 times higher than non-indigenous. Higher 2.1 times higher in Indigenous men than women. Australia – the scary stats  Coronary heart disease In 2020–21 ~ 3% of the adult population had CHD prevalence increases rapidly with age (~11% >75 yrs) In 2020, CHD was the leading single cause of death in Australia, accounting for 10% of all deaths, and 41% of CVD related deaths. 39% of CHD deaths from resulted from MI In 2019 ~ 60,000 ≥ 25 had an acute coronary event (MI or unstable angina) with 13% fatal However, the age-standardised rate of acute coronary events fell by nearly 60% between 2001 and 2019, slightly more for women than men Attributed to reductions in some risk factor levels, better treatment and care, and improved secondary prevention 2018-19 cost ~ $2.4 billion (PBS $156.3 million) Population groups: 2019-20 1.5 x higher in remote and very remote areas 1.3 x higher in lowest socioeconomic areas 2 x higher in aboriginal and Torres Straight islander people  Hypertension High blood pressure (hypertension) = major risk factor for chronic conditions including stroke, coronary heart disease, heart failure and chronic kidney disease 2022, 11.6% of Australians self-reported HT (significantly lower than the actual number. Evidence - as 23.3% of adults having a high blood pressure reading when checked (nurse/doctor) 92.3% (18-44 yrs) of those with measured HT did not report having HT. Age is a risk factor: 4.5% in 18-24 yrs and 42.9% in 75 yrs and over  Covid-19 and CHD People with pre-existing chronic conditions e.g. CHD > risk of contracting COVID- 19, experiencing complications or more severe illnesses 2020–21, of ~ 5k hospitalisations in Australia that involved a COVID-19 diagnosis, CVD accounted for 20% of the comorbid conditions associated with COVID-19 Of those hospitalisations with comorbid diagnosis of CVD 18% spent in an Intensive Care Unit, 12% involved continuous ventilatory support and 20% died in hospital Among COVID-19 deaths that occurred by 30 April 2022, chronic cardiac conditions including coronary atherosclerosis, cardiomyopathies and atrial fibrillation were the most certified comorbidities, present in 37% of deaths. While CHD deaths during 2021 were below the 2015–19 average they were higher than the number certified in 2020  National health survey 2022 Alcohol: 26.8% of adults exceeded the Australian Adult Alcohol Guideline Males 35.8% females 18.1% 36.1% of young adults aged 18–24 Dietary: Just 4.2% and 4.3% of adults and children respectively meet both fruit and vegetable recommendations However, 44.1% of adults and 63.9% children met the fruit recommendation Physical activity: 23.9% aged 15 years and over met the physical activity guidelines but 46.9% of employed aged 18–64 yrs spend most of their work-day sitting. Smoking / vaping: One in ten (10.6%) adults were current daily smokers, declining from 22.4% in 2001 58.3% of adults have never smoked 14.4% adults have used e-cigarette or vaping devices Role of Exercise for clients with cardiovascular conditions 10  Insufficient physical activity Low levels of physical activity (PA) increases risk for chronic conditions e.g. CVD, T2D, osteoporosis and dementia. Self-reported 2022 data: 56.4% of adults 18-64 yrs, completed 30 minutes of activity 5 days or more 26.6% undertaking strength or toning exercises 2+ days previous week 24.9% of males meet the PA guidelines compared to 19.9% female While 77.6% aged 18–64 years did not meet the guidelines, the majority were active in the week prior to interview: 67.4%) undertook at least some physical activity on five or more days 74.2% did at least 150 minutes of physical activity in the week Aged 65+: 33.4% met the physical activity guidelines in 2022. 43.4%) did at least 30 minutes of physical activity on five or more days and 30.8% completed at least 30 minutes of physical activity daily 37.6% did more than 300 minutes of physical activity in the last week 40.7% engaged in daily physical activity.  Exercise is Medicine “If we had a pill that gave all those benefits and was readily available, we would find a way to make sure every patient took it.”-Robert E. Sallis, M.D. Why isn’t this happening with exercise? – Lack of media advocacy. – Minimal tangible success measures. – Doctors are lacking the time and proper training to effectively counsel patients on the importance of exercise. Minimal side effects: – Overuse injuries – start low and go slow.  CV Disease and exercise as a viable intervention Meta-analysis including 47 studies & 10,794 participants reported exercise-based cardiac rehabilitation: Reduced overall and cardiovascular mortality (12 months or more follow-up) Hospital admissions in short term patients (30min reduces LDL particle size 30-60min of moderate-intense exercise 3-5x/week Significant increase in HDL concentration and decrease in triglycerides Systemic Inflammation (CRP, ILs, leukocytes and fibrinogen) Relationship between systemic inflammation and atherosclerosis Skeletal muscle contraction (acute) – ↑ circulatory IL-6 – Inhibit TNF-α – Decrease insulin resistance – Stimulate lipolysis Long term-training = ↓ resting IL-6 due to lower glycogen content, improved oxidative capacity and insulin resistance (Ahmed et al. 2012; Leal et al. 2018) Endothelial dysfunction and cardiovascular disease 17  Endothelial dysfunction Endothelial cells (EC) important constituents of blood vessels which playing critical roles in cardiovascular homeostasis by: Regulating blood flow, vascular tone, angiogenesis and monocyte/leukocyte adhesion, and platelet aggregation Imbalance between vasodilators and vasoconstrictors = oxidative stress & reactive oxygen species (ROS) then endothelial dysfunction (ED) Specifically, an impaired ability of the endothelium to vasodilate is a hallmark of endothelial dysfunction EC maintain a relaxed vascular tone and low levels of oxidative stress by releasing mediators such as nitric oxide (NO) “MAIN DRIVER”, prostacyclin (PGI2) and endothelin (ET-1), + control local angiotensin-II activity. eNOS increase from sheer stress (exercise) increasing relaxing factors and inhibiting platelet and WBC activation Lee et al., 2018. Regulation of Vascular Tone and eNOS bioavailability used to determine atherosclerosis Ischemia-Induced Arteriogenesis development 18  Endothelial dysfunction Endothelial dysfunction occurs early in the process of atherogenesis Contributes to the formation, progression, and complications of atherosclerotic plaque Resulting in CV disorders including hypertension, atherosclerosis and heart failure. Causes: inactivity, ageing, HT, infections and some medications Results: disrupt vascular tone and redox balance; increased inflammatory reactions in blood vessel & wall Sun et al., 2020. Role of Endothelial Dysfunction in Cardiovascular Diseases: = prothrombotic and proinflammatory damage to the The Link Between Inflammation and Hydrogen Sulfide endothelium Damaged ED: Decreases production and release of NO = oxidative stress Inflammatory response and leukocyte adhesion Increased permeability Altered angiogenesis 19  Inflammation and Endothelial dysfunction Chronic inflammation and immune dysregulation play a role in the development of atherosclerosis Cells of injured tissue undergo morphological and functional modifications = inflammation Stimulation of EC receptors by damage- associated molecular patterns = Inflammatory cytokines (TFN-α, ILs, oxLDL) promotes nuclear factor-κB signalling Results in: upregulation of adhesion molecules + monocyte adhesion. Monocytes differentiate into macrophages that phagocytose oxLDL to become foam cells Injured ED cells release inflammatory mediators and TF which: Promotes inflammation and coagulation Theofilis et al., 2021. Inflammatory mechanisms contributing to endothelial dysfunction Other chemicals cause platelet adhesion and aggregation following the binding with platelet glycoprotein 20  Inflammation and Endothelial dysfunction Chronic inflammation and immune dysregulation play a role in the development of atherosclerosis Cells of injured tissue undergo morphological and functional modifications = inflammation Stimulation of EC receptors by damage- associated molecular patterns = Inflammatory cytokines (TFN-α, ILs, oxLDL) promotes nuclear factor-κB signalling Results in: upregulation of adhesion molecules + monocyte adhesion. Monocytes differentiate into macrophages that phagocytose oxLDL to become foam cells Injured ED cells release inflammatory mediators and TF which: Promotes inflammation and coagulation Theofilis et al., 2021. Inflammatory mechanisms contributing to endothelial dysfunction Other chemicals cause platelet adhesion and aggregation following the binding with platelet glycoprotein 21  Inflammation and Endothelial dysfunction Chronic inflammation and immune dysregulation play a role in the development of atherosclerosis Cells of injured tissue undergo morphological and functional modifications = inflammation Stimulation of EC receptors by damage- associated molecular patterns = Inflammatory cytokines (TFN-α, ILs, oxLDL) promotes nuclear factor-κB signalling Results in: upregulation of adhesion molecules + monocyte adhesion. Monocytes differentiate into macrophages that phagocytose oxLDL to become foam cells Injured ED cells release inflammatory mediators and TF which: Promotes inflammation and coagulation Theofilis et al., 2021. Inflammatory mechanisms contributing to endothelial dysfunction Other chemicals cause platelet adhesion and aggregation following the binding with platelet glycoprotein 22  Inflammation and Endothelial dysfunction Chronic inflammation and immune dysregulation play a role in the development of atherosclerosis Cells of injured tissue undergo morphological and functional modifications = inflammation Stimulation of EC receptors by damage- associated molecular patterns = Inflammatory cytokines (TFN-α, ILs, oxLDL) promotes nuclear factor-κB signalling Results in: upregulation of adhesion molecules + monocyte adhesion. Monocytes differentiate into macrophages that phagocytose oxLDL to become foam cells Injured ED cells release inflammatory mediators and TF which: Promotes inflammation and coagulation Theofilis et al., 2021. Inflammatory mechanisms contributing to endothelial dysfunction Other chemicals cause platelet adhesion and aggregation following the binding with platelet glycoprotein 23  Inflammation and Endothelial dysfunction Chronic inflammation and immune dysregulation play a role in the development of atherosclerosis Cells of injured tissue undergo morphological and functional modifications = inflammation Stimulation of EC receptors by damage- associated molecular patterns = Inflammatory cytokines (TFN-α, ILs, oxLDL) promotes nuclear factor-κB signalling Results in: upregulation of adhesion molecules + monocyte adhesion. Monocytes differentiate into macrophages that phagocytose oxLDL to become foam cells Injured ED cells release inflammatory mediators and TF which: Promotes inflammation and coagulation Theofilis et al., 2021. Inflammatory mechanisms contributing to endothelial dysfunction Other chemicals cause platelet adhesion and aggregation following the binding with platelet glycoprotein 24  Endothelial Dysfunction (ED) Is an important factor in the progression of atherosclerotic CVD Progression of ED is related to the intensity and duration of the patient’s risk factors and total amount of risk Vascular endothelium is a monolayer of cells covering the lumen of the vessels Plays a complex role Highly sensitive and is metabolically active Maintenance of homeostasis by keeping a balance between vasodilation and vasoconstriction Dilation: nitric oxide (NO) and endothelium derived hyperpolarising factor (EDHF) Constriction: endothelin-1 (ET-1), angiotensin II etc. However, chronic exposure to CV risk factors and oxidative stress overwhelms the defence mechanisms of the vascular endothelium = ED, loss of integrity, leukocyte adhesion Park and Park, 2015. Endothelial Dysfunction: Clinical implications in cardiovascular disease and therapeutic approaches 25 Nitric oxide (NO) NO is considered to be the most potent endogenous vasodilator in the body Maintains homeostasis by inhibiting Platelet aggregation Inflammation Oxidative stress Vascular smooth muscle cell migration and proliferation Leukocyte adhesion. Produced and released from L-arginine through activity of the endothelial NO synthase (eNOS) Park and Park, 2015. Endothelial Dysfunction: Clinical implications in cardiovascular disease and therapeutic approaches 26 Park and Park, 2015. Endothelial Dysfunction: Clinical implications in cardiovascular disease and therapeutic approaches  Oxidative stress deteriorates endothelial function Impaired homeostasis Reduced anti-oxidant and anti-inflammatory effects Increased vascular permeability to lipoproteins Increased expression of inflammatory cytokines and adhesion molecules Oxidative stress is the most common underlying mechanism for the development of ED Up-regulation of reactive oxygen species (ROS) In healthy endothelium, eNOS is responsible for most of the vascular NO production…… however…. eNOS becomes a potential ROS generator when in a pathological uncoupled state. Park and Park, 2015. Endothelial Dysfunction: Clinical implications in cardiovascular disease and therapeutic approaches 28  Chronic inflammation Another common underlying mechanism for ED Endothelium controls vascular inflammation by releasing NO Dysfunctional endothelium will promote ROS generation and aggravate inflammation Amplification of inflammation signalling pathways C-reactive protein (CRP) – protein present in the acute inflammatory response Direct effects of NO bioavailability → oxidative stress → endothelial dysfunction Over expression of tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) Promote leukocyte adherence and migration Due to associated macrophages, facilitate the uptake and accumulation of lipids Transformation of macrophages into foam cells Park and Park, 2015. Endothelial Dysfunction: Clinical implications in cardiovascular disease and therapeutic approaches 29  C-reactive protein Schuler, Adams and Goto, Eur Heart J 2013  Shear stress Entire vascular tree is exposed to the risk factors of ED, atherosclerotic lesions usually generate at specific arterial regions Bifurcations Branching points Inner aspect of a curved segment of the coronary artery Locally disturbed shear stress by pulsatile blood flow is one the modulators of the atherogenic process Local endothelial shear stress (ESS) Low ESS = ↑ plaque progression and vulnerability High ESS = upregulation of eNOS Increases in vascular blood flow and shear rate are considered the main mechanisms of the beneficial effects on the CV system during exercise Park and Park, 2015. Endothelial Dysfunction: Clinical implications in cardiovascular disease and therapeutic approaches 31 Week 1 WATCH (available on Interact2) Lecture 1 Introduction Lecture 2A Introduction to the CV system READ (available on Interact) Park, K. H., & Park, W. J. (2015). Endothelial dysfunction: clinical implications in cardiovascular disease and therapeutic approaches. Journal of Korean medical science, 30(9), 1213-1225. Petersen, A. M. W., & Pedersen, B. K. (2005). The anti-inflammatory effect of exercise. Journal of applied physiology, 98(4), 1154-1162. Schuett, K. A., Lehrke, M., Marx, N., & Burgmaier, M. (2015). High-risk cardiovascular patients: clinical features, comorbidities, and interconnecting mechanisms. Frontiers in immunology, 6, 591. ENGAGE (Zoom tutorials) It is expected that you make time to attend these sessions in person 32