Ischemic Heart Disease I Flashcards
Treatable risk factors for development of coronary atherosclerosis (with consequent reduced risk)
- smoking
- HTN
- dyslipidemia
unique features of coronary circulation
- myocardium operates ONLY on aerobic metabolism
- @ rest: near maximal O2 extraction occurs @ coronary arteries –> must INCREASE FLOW in order to increase O2 delivery
- LV is perfused during DIASTOLE only
major determinants of myocardial O2 supply
- coronary blood flow rate: perfusion pressure, perfusion time(=1/HR), vascular resistance
- O2 content of blood
- O2 delivery (mmol/min) = CBF rate (ml/min) x O2 content (mmol/ml)
pathophysiology of stable coronary artery disease
- obstructive coronary lesion –> limited coronary blood flow –> myocardial ischemia
- myocardial ischemia = imbalance btwn coronary O2 delivery and myocardial O2 demand
- ischemia occurs more frequently when cardiac work/O2 demand increase
- major sx: angina pectoris (chest pain)
pathophysiology of unstable coronary artery disease
- inflammation of arterial wall
- weak cap –> plaque rupture/fissure
- rupture –> thrombosis + complete/partial vessel occlusion
- vessel occlusion –> myocardial injury and/or necrosis –> cardiac dysfxn, arrythmias, death
Major categories of treatment of stable coronary artery disease
- increase oxygen delivery to myocardium
- decrease oxygen demand of myocardium
Progressive process of atherosclerosis
- endothelial injury –> lipid deposition + WBC recruit
- WBCs + smooth muscle –> fibrous plaque
- progressive lipid accumulation at core of plaque –> occlusive atherosclerotic plaque and sx: angina, claudication
- plaque disruption –> acute vascular events
Major acute vascular events resulting from artherosclerotic plaque disruption
- unstable angina
- MI
- stroke
- critical leg ischemia
Treatable risk factors for development of coronary atherosclerosis (with unclear/possible reduced risk)
- diabetes
- obesity
- sedentary lifestyle
- inflammation
- psychological stress
Untreatable risk factors for development of coronary atherosclerosis
- male gender
- age
- genetic factors
Smoking impact on CAD risk
- 50% increase in risk; cessation can normalize risk
- mechanisms:
- clot formation
- aryl hydrocarbons
- CO decreases myocardial O2 delivery
- decreases HDL
HTN impact on CAD risk
- graded risk based on BP; tx reduces risk
- mechanisms:
- direct endothelial cell injury
- pathologic cell signaling
- circulating hormones increase
- LVH
Diabetes/insulin resistance impact on CAD risk
- both dx diabetes and insulin resistance have similar increased CV risk
- mechanisms:
- inflammation
- oxidative stress
- dyslipidemia
Dyslipidemia definiton and impact on CAD risk
- dyslipidemia = high LDL (low-density lipoprotein) cholesterol + low HDL (high-density lipoprotein) cholester + high triglycerides
- each aspect = independent risk factors
LDL impact on CAD risk
- LDL oxidized –> pro-inflammatory and atherogenic
- mechanisms:
- injury to vascular endothelium
- deposited in arterial wall –> macrophages take up –> progressive increase in plaque volume
- activated inflammatory cells
- activates platelets –> pro-thrombotic
HDL impact on CAD risk
- low HDLs are bad b/c HDL = anti-atherosclerotic
- mechanism:
- inhibits oxidation of LDLs
- inhibits tissue factor (clot formation)
- inhibits endothelial adhesion mlx
- stimulates NO production
- enhances reverse cholesterol transports
Inflammation impact on CAD risk
- inflammation contributes to progression of atherosclerosis
- lipid-laden macrophages = pro-inflammatory
- extravascular inflammation –> increase risk of CV events
- inflammatory markers (e.g. IL-6, CRP)–> info about future CAD risk
major determinants of myocardial O2 demand
- heart rate
- wall tension: determined by BP and chamber dimensions (Law of LaPlace)
- inotropic state
Characteristics of autoregulation of blood flow to myocardium (and impact of CAD)
- autoregulation allows vessels to adapt to changes in perfusion pressure/protect from moderate pressure changes
- occurs @ level of arterioles
- w/CAD: autoregulation may become exhausted when pressure drops across an epicardial coronary stenosis
Impact of tachycardia on coronary flow
- tachycardia can compromise coronary flow b/c LV is perfused predominately during diastole
- intramural coronary vessels are compressed during systole
- increased HR –> shortened cardiac cycle via shortening of diastole
Treatments that help increase oxygen delivery to myocardium
- prevent coronary hypotension
- rate-slowing drugs (beta-blockers)
- decrease coronary resistance via vasodilators, coronary angioplasty or bypass surgery
- treat anemia or hypoxemia
Treatments that help reduce myocardial oxygen demand
- antihypertensive drugs
- rate-slowing drugs (beta-blockers, calcium channel blockers)
- limit LV size via limiting preload (diuretics, nitrates)
- negative inotropes
unstable angina vs. acute MI
- unstable angina=near-complete occlusion, negative biomarkers, “threatened” heart attack
- acute MI=usually complete occlusion, severe and constant chest pain @ rest, positive biomarkers –> cardiac dysfxn and failure
Common biomarkers of vascular inflammation/myocardial injury
- inflamed vessel: CRP, other inflammatory markers
- injury: troponin, creatine kinase
