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Chemical Pathology of CV Disease - Coggle Diagram
Chemical Pathology of CV Disease
Cardiovascular Disease (CVD)
Epidemiology
CVD leading cause of premature death worldwide
35% of all deaths attributed to CVD
20% of which are under 65 yrs
Atherosclerosis major cause of CVD morbidity and mortality
Coronary Heart Disease (CHD)
Clinical presentation
Angina
Acute coronary syndrome ACS:
Unstable angina
MI
Symptoms
Severe crushing central chest pain
Dyspnoae
Cold sweat
Pallor
Nausea
Heart Failure
State of reduced myocardial performance
Mainly affects LV
Aetiology
Coronary heart disease
Hypertension
Valvular defects
Cardiomyopaties
Classifications
Systolic HF
Reduced systolic ejection
Diastolic HF
Impaired diastolic filling of L ventricle
Consequences
Water and Na retention
Activation of RAAS
ADH release
LHF
Pulmonary odeama
PAroxysmal noctural dyspnoae (PND)
RHF
Peripheral Odema
Lower limbs
Sacral Odema
Atherosclerotic CVD Risk Factors and Assessment Tools
Clinical manifestations of Atherosclerosis
Coronary Heart Disease (CHD)
Angine -> MI
Peripheral vascular disease (PVD)
Intermittent clausication -> Limb amputation
Cerebrovascular disease
TIA -> Stoke (CVA)
Risk factors fo ASCVD
Dyslididpaemia
Hypertension
Obesity / T2DM
Smoking
Lack of excercise
Age
Sex
Family hx
Ethnicity
Premature menopause
Lipoprotein a
Low birth weight
Socioeconomic
Geographic
Depressive illness
Erectile dysfunction
HIV status
Rheumatoid arthritis
Stress / personality type a
Homocysteine
Prevention
Primary CVD prevention
Preventing onset
Secondary CVD prevention
Aimed at preventing recurrence of CVD events
Mi, strok
Assesment
Framingam risk scor
SCORE : systematic coronary risk estimation
ASSIGN
QRISK3
PROCAM
WHO
ESC guidelines
SCORE2
Risk factors
Systolic BP
Non-HDL cholesterol
Smoking
Sex
Age
Dyslipidemias
A disorder of lipoprotein metabolism, including lipoprotein overproduction (hyperlidpidaemia) or deficiency (hypolipidaemia)
Serum Lipid Profile
Total cholesterol
Low density lipoprotein (LDL) cholesterol
High density lipoprotein (HDL) cholesterol
Non-HDL cholesterol (Total cholesterol - HDL cholesterol )
Surrogae for LDL chol
Triglycerides
Serum Lipids and CHD
Raised Total Chol
LDL chol
Non HDL-chol
∝
CHD
HDL chol
1/ ∝
CHD
Triglyceride
∝
CHD
Causes of 2ndary Displipidaemias
Hyperthyroidism
Nephrotic syndrome
Chronic renal failure
Cholestasis
Diabetes mellitus
Obesity
Alcohol abuse
PCOS
Drugs
Investigations
BMI and waist circum
Medication hx
Dietary habits
Labs
LFTs
Renal Fx
TFTs
Glycaemic status
Primary Dyslipidaemias
Predominantly elevated plasma cholesterol
Polygenic hypercholesterolaemia
Monogenic hypercholesterolaemias
eg. Familial
Predominantly elevated plasma triglyceride
Lipoprotein lipase (LPL) deficiency
ApoC-II deficiency
FAmilial hypertriglyceridaemia
Mixed (Combined eleved Chol + Trigs)
Familial combined hyperlipidaemia (FCH)
Dybetalipoproteinamia (Type III HPLA)
Very Rare Dyslipidaemiae
Low LDL syndromes
abeta, hypobet lipoproteinaemia
Low HDL syndromes
ApoA-I mutations
Tangiers disease
LCAT deficiency
Misc
Lp(a)
Hyperalphalipoproteinamia
Biomarkers for Acute Coronary Syndrome (ACS) and Heart Failure
Diagnosis of ACS
Clinical hx
ECG
STEMI or NSTEMI
Q waves appear later
Lab diagnosis
Cardiac Biomarkers of MI
Creatin Kinase (CK)
Muscle enzyme
Nonspecific - may originate from skeletal or cardiac muscle
Starts to increase at 3-8h
Peak level at 18-24h
Returns to normal 3-4 days port MI
Aspartate transaminase AST
Found in liver and muscl
Nonspecific
Increase 6-10hr post MI
Peak level 24 hr
Return to normal 3-5 days post MI
Lactate dehydrogenase (LDH)
Nonspecific
Peak at 72 hrs
Return to normal 8-14 days post MI
CK-MB
CK more specific for hear
Similar kinetics to total CK
CK-MB > 6% of total CK indicated mycoardial origin
CK-MB mass >5
Troponin T or I
Regulatory complex in muscle
Increased are very specific for cardiac muscle damage
ACS TnT / TnI increase at 3-6hrs
Peak 18-24 hrs
Can remain elevated for 7-10 days
TnT /TnI at 12hrs post onset of chest pain is very sensitive
High sensitivity Troponin T (hsTnT) better marker than previous TnT assays
However can detect elevated levels due to non-ACS causes
Serial measurements are recommended
Future Markers
Ischaemia modified albumin
Heart-fatty acid binding protein (H-FABP)
Copeptin (C-eminal part of pro-AVP)
Biomarkers of Cardiac FAilure
Biochemical abnormality
Hyponatraemia
Hypokalamia
Renal failure
BNP (B-type natriuretic peptide) increase
NT-proBNP
Cleavage product of BNP
Pathophysiology
Diuretics - increased AVP
2ndary hyperaldosteronism
Reduced perfusion
Familial Hypercholesterolemia (FH): Diagnosis and Cascade Screening
Pathogenesis
All known defective genes causing FH are involved in receptor mediated uptake of LDL
Clinical Features
Tendon Xanthomata
Corneal arcus
Xanthelasmata
Diagnosis
Dutch Lipid Clinic NEtwork (DLCN)
The Simon Broome FH Register
US MEDPED Program
Differential Diagnosis of FH
Polygenic hypercholesterolaemia
Familial combined hyperlipidaemia
Other monogenic hypercholesterolaemia
eg sitosterolaemia
Management
High dose statins
combo with Ezetimibe
Consider PCSK9 inhibitor
Clinical Follow Up
Regular non-invasive testing for silent ischaemia
Family screening
Obesity and Metabolic Syndrome
Obesity
BMI =>35
Metabolic syndrome ID
Abdominal obesity
Elevated fasting Triglyceride
Reduced HLD cholesterol
Elevated BP
Elevated Fasting glucose
Hypertension
140/09
Associations
CVD risk
Target organ damage
Left ventricular hypertrophy - Cardiac failure
Hypertensive renal disease - chronic kidey disease
Hypertensive retinopathy
Cognitive impairement/ vascular dementai
Secondary hypertension
Renal
CRF
Renal artery stenosis
Atheroma in older
Fibromuscular dysplasia in younger
Renal tubular genetic defects
Liddle's syndrome
CV
Coartation of Aorta
Endocrine
Primary hyperaldosteronism
Conn's syndrome
Cushing's syndrome
Phaechromocytoma - adrenal medulla tumour
Hypothyroidism
Hyperparthyroidism
Drugs
Steroids
OCP
Tyrosine-kinase inhibitors
