CHD+Overview+%282024%29.pdf

WEEK 9 MPharm Programme CHD Overview Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA222 CHD Overview WEEK 9 CVD LECTURE SERIES...

WEEK 9 MPharm Programme CHD Overview Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA222 CHD Overview WEEK 9 CVD LECTURE SERIES Ischaemic / Coronary Heart Disease Heart Failure Systemic Arterial Hypertension Cardiac Arrhythmias Slide 2 of 32 MPharm PHA222 CHD Overview WEEK 9 OUTLINE OF LECTURES Definitions Epidemiology & natural history Pathogenesis & pathophysiology Clinical management & therapeutics Slide 3 of 32 MPharm PHA222 CHD Overview WEEK 9 Coronary Heart Disease An Overview Brief introduction to Myocardial Ischaemia CHD – definitions, aetiology, manifestations Pathogenesis of IHD / CHD Atherosclerosis Coronary thrombosis Coronary artery spasm Coronary microvascular dysfunction Slide 4 of 32 MPharm PHA222 CHD Overview WEEK 9 Learning Outcomes At the end of this overview lecture, you should be able to: Define myocardial ischaemia & describe its consequences Describe the major clinical manifestations of coronary heart disease Describe the major obstructive & constrictive processes in coronary arteries that may predispose to coronary heart disease Slide 5 of 32 MPharm PHA222 CHD Overview WEEK 9 Please note! You will need a thorough knowledge and understanding of the ‘Physiology & Functional Anatomy of the Heart’ & ‘Haemostasis’, which were covered in great detail in last year’s PHA112 lectures on the circulatory system. Please make sure you have reviewed that lecture material before the start of this series of lectures. Slide 6 of 32 MPharm PHA222 CHD Overview  Myocardial Ischaemia & WEEK 9 Aetiology of CHD blood to had back What is “tissue ischaemia”? reduced blood flow to an organ or tissueenough not south od in out  lack of O2 & nutrient supply n table  lack of washout of metabolic waste el can durationcolls ase do substant. recover ba > - they're danag dead reversible & irreversible tissue damage but not ~any factors that can determing which Garage determinants of extent of tissue damage Slide 7 of 32 MPharm PHA222 CHD Overview  Myocardial Ischaemia & WEEK 9 Aetiology of CHD Myocardial ischaemia reduced regional blood flow to the heart ischaemia as an imbalance between myocardial demand & supply concept of exertional demand ischaemia & when non-exertional supply ischaemia it's inkal d exercise umpassphami an that at supply↑ during Aft Slide 8 of 32 MPharm PHA222 CHD Overview WEEK 9 Determinants of Myocardial Oxygen Demand & Supply Slide 9 of 32 MPharm PHA222 CHD Overview WEEK 9 CORONARY HEART DISEASE Definition pathological conditions characterised by a reduced or inadequate blood flow to the heart usually due to an obstructive (or constrictive) disease of coronary arteries hence ‘coronary heart disease’; ‘coronary artery disease’ or ‘ischaemic heart disease’ Slide 10 of 32 MPharm PHA222 CHD Overview WEEK 9 CORONARY HEART DISEASE Epidemiology & natural history the single leading cause of death worldwide one of the leading causes of death & most common cause of premature death in the UK associated with high morbidity & social cost Slide 11 of 32 MPharm PHA222 CHD Overview WEEK 9 2024 BHF HeartStats Report CHD – The Killer Statistics CHD accounts for 68,000 UK deaths a year ~ 190 people die from CHD each day – ~1 in every 8 minutes! Accounts for ~1 in 8 deaths (men) & 1 in 14 deaths (women) ~2.3 million people currently living with CHD in the UK – ~1.5 million men & 830,000 women ~1.4 million people have survived a heart attack – ~1 million men and 400,000 women >1.3 million suffer from angina Slide 12 of 32 MPharm PHA222 CHD Overview WEEK 9 2024 BHF HeartStats Report CHD – The Killer Statistics 100,000 hospital admissions each year due to heart attack ~290 heart attack admissions each day, i.e. someone is admitted to hospital with a heart attack in UK every 5 minutes ~30% don’t surviveGet years Overall, someone in UK dies from CHD every 8 minutes! In total, CHD cost the UK economy ~£12.7 billion in 2018 [Landeiro, F et al. (2024). The Lancet Healthy Longevity 5:e514 - e523] Slide 13 of 32 MPharm PHA222 CHD Overview WEEK 9 CHD – the disease process CORONARY ARTERY OBSTRUCTION OR CONSTRICTION REDUCED REGIONAL BLOOD FLOW TO THE HEART OXYGEN & NUTRIENT DEPRIVATION AND ACCUMULATION OF TOXIC WASTES METABOLIC DYSFUNCTION S usual CONTRACTILE DYSFUNCTION A ELECTRICAL INSTABILITY cherers as > change in - the conduct irrussalMYOCARDIAL CELL DEATH (INFARCTION) => Slide 14 of 32 MPharm PHA222 CHD Overview  CORONARY HEART DISEASE WEEK 9 Clinical manifestations chestersonally when there physical activity - pain in Angina Pectoris (‘Stable’, ‘Variant’, ‘Microvascular’) Immediate or Sudden Cardiac Death - dies of Shod 1st Acute Coronary Syndromes (ACS) – Unstable Angina, Acute Myocardial Infarction (NSTEMI, STEMI) Pathological factors atherosclerosis coronary thrombosis coronary artery spasm coronary microvascular dysfunction Slide 15 of 32 MPharm PHA222 CHD Overview WEEK 9 ATHEROSCLEROSIS Definition ‘a progressive, degenerative arterial disease characterized by asymmetric deposition of lipids and fibrous tissue on the inside wall of arteries’ most common cause of CHD ( 90%)Sea Disease process E an inflammatory process wall in corocity begins early in life as a ‘fatty streak’ of astries Slide 16 of 32 MPharm PHA222 CHD Overview WEEK 9 Atherosclerosis - the disease process Garago Chesical or chomic LDL deposition in sub-endothelial space to the endothelias spat + high cholestic specially (DL will get caricay modified t LDL oxidation + Monocyte recruitment into - sub-endothelial space the monecute will differentiate in macrophage Macrophage differentiation + uptake of oxidised LDL cell look bloated because they to Foam cell formation filled mit LAh attat sooth musch SMC migration, proliferation & de-differentiation in well Sitting gar Fibrous plaque or atheroma and how no partial ocusin Slide 17 of 32 MPharm PHA222 CHD Overview WEEK 9 Atherosclerosis – consequences Impact on coronary function partial coronary occlusion  stable angina endothelial / vascular dysfunction  coronary artery spasm lads somatio most Seas Place of dot a Eulceration / rupture  coronary thrombosis atte Slide 18 of 32 MPharm PHA222 CHD Overview WEEK 9 Atheroma plaque in a coronary artery Slide 19 of 32 MPharm PHA222 CHD Overview WEEK 9 Atheroma plaque in a coronary artery Slide 20 of 32 MPharm PHA222 CHD Overview WEEK 9 Coronary Thrombosis Definition intreeskular ‘unwanted formation of ahaemostatic plug or clotsattentthrombus or blood clot within coronary arteries’ to seen in ~30-90% of ACS (unstable angina & evolving acute myocardial infarction, AMI) Disease process usually occurs on top of ruptured atheroma involves platelet aggregation & the coagulation cascade Slide 21 of 32 MPharm PHA222 CHD Overview WEEK 9 Coronary thrombosis - the disease process Rupture or ulceration of atherosclerotic plaque Contact of blood elements with collagen & tissue factor Platelet adhesion Activation of coagulation & activation cascade   platelet aggregation fibrin formation & deposition Thrombus / clot Slide 22 of 32 MPharm PHA222 CHD Overview  Coronary Thrombosis – consequences WEEK 9 Impact on coronary function complete & permanent occlusion of coronary artery  ACS (STEMI) subtotal or intermittent occlusion of coronary artery  ACS (UA / NSTEMI) thromboembolism in a distal artery Slide 23 of 32 MPharm PHA222 CHD Overview WEEK 9 Coronary thrombus on top of ruptured atheroma Thrombus Ruptured plaque Slide 24 of 32 MPharm PHA222 CHD Overview  Coronary Artery Spasm WEEK 9 Definition block blood flow to ht ‘a transient, spontaneous coronary vasoconstriction’ may occur in ‘normal’ coronary arteries may occur at ‘mildly’ atherosclerotic sites or during ongoing coronary thrombosis the underlying cause of variant angina Slide 25 of 32 MPharm PHA222 CHD Overview WEEK 9 Coronary Artery Spasm Disease mechanisms local endothelial injury   reactivity to vasoconstrictors abnormal release of vasoconstrictors or local imbalance orlatos robally constricts versity in release of vasodilators & constrictors smooth muscle cell hypercontraction/hyper-reactivity Impact on coronary function subtotal or intermittent occlusion of coronary artery complete focal occlusion of coronary artery Slide 26 of 32 MPharm PHA222 CHD Overview WEEK 9 Coronary Artery Spasm in LAD in patient with Variant Angina complete occulision of e of tho Worsening store · vertical Clas v ↳ min later after gini , After GTN gTM? Slide 27 of 32 MPharm PHA222 CHD Overview WEEK 9 Coronary Microvascular Dysfunction Definition ‘damage to the inner walls of the small surface coronary blood breache of left and righttom or nott vessels (coronary microvasculature) of the heart, leading to page microvascular spasms, decreased blood flow to the heart muscle and reduced coronary flow reserve’ coronary microvasculature – network of small coronary blood vessels (arterioles) that branch off the large epicardial coronary arteries damage may be structural (microvascular remodelling) or functional (endothelial dysfunction) the underlying cause of microvascular angina Slide 28 of 32 MPharm PHA222 CHD Overview WEEK 9 Coronary Microvascular Dysfunction Slide 29 of 32 MPharm PHA222 CHD Overview WEEK 9 Coronary Microvascular Dysfunction Disease mechanisms microvascular remodelling  luminal narrowing of the intramural arterioles and capillaries  microvascular obstruction endothelial dysfunction  impaired vasodilator response & reduced coronary blood during exercise or stress functional abnormalities of smooth muscle cells that regulate arteriolar tone Impact on coronary function reduced coronary flow reserve & increased risk of myocardial ischaemia  INOCA (e.g. microvascular angina) or MINOCA (myocardial infarction with no obstructive coronary artery disease) Slide 30 of 32 MPharm PHA222 CHD Overview  Atherosclerosis: A Progressive Process WEEK 9 Slide 31 of 32 MPharm PHA222 CHD Overview WEEK 9 Atherosclerosis: A Progressive Process Main Medical & Modifiable Risk Factors for Coronary Atheroma & CHD high blood cholesterol (hypercholesterolaemia) hypertension diabetes obesity poor diet cigarette smoking physical inactivity https://youtu.be/5BwrX-tbWIg Slide 32 of 32 MPharm PHA222 CHD Overview