HEART ATTACKAMI

??

Denotes abnormallyLEVELS of any or all LIPIDS &/or LIPOPROTEINS [LP] in blood

HYPERLIPIDEMIA ???

Is the most common form of dyslipidemia

HypertriglyceridemiaHyper-cholesterolemia Mixed

Hyperlipoprotienemia* Denotes usually LDL

* Unless specified in the familial types

TGs & C

CM, VLDL, IDL, LDL, HDL

LProteinemia

LP Lipids Risk

Type I CM TGs -

Type IIa LDL C

Type IIb VLDL & LDL TG & C Type III IDL TGs & C

Type IV VLDL TGs

Type V VLDL & CM TGs & C _

TGs < 220 mg/dlC < 200 mg/dlLDL < 130 mg/dlHDL > 50 mg/dl

NORMAL Levels

If Above Hyperlipidemia

Familial Hyperlipoproteinemia

Very low Density lipoprotein

[VLDL]

Low Density lipoprotein

[LDL]

Chylomicrons[CM]

High Density lipoproteins

[HDL]

% LipidComposition

Protein CholesterolTriglycerides Phospholipids

LP

OUTER Coat INNER CorePhospholipids

CholesterolTriglyceridesCholesterol esters

Hydrophilic Gps. Lipophylic Gps.

APOPROTEINS

C

TGs

LP

Very low Density lipoprotein

[VLDL]

Low Density lipoprotein

[LDL]

Chylomicrons[CM]

High Density lipoproteins

[HDL]DENSIT

Y

[IDL]

TYPE of Apoprotein

B 48 B100 AI&II

Beta LP Alpha LPNon-HDL Cholesterol HDL

CholesterolATHEROGENIC ATHEROPROTECTIVE

LP REMODELING

Begins as INFLAMMATORY REACTION triggered by;Endothelial dysfunction + Dyslipidemia

THE STORY OF ATHEROGENESIS

MC

Dysfunction

RollingScrolling

Diapedesis

Expression

LDL leak

Trapping

SR-A

SR-A

Engulf Ox -LDLNo efflux

Progress as FIBRO-PROLIFERATIVE DISORDERLumen

LipidCore

Fibrous cap

Shoulder

Intima

MediaElasticlaminæ

InternalExternal

Rapidity of lipid accumulation & apoptosis

Proliferative (fibrous) vs Inflammatory (proteolysis)

Atheromatus Plaque

Divide into

> Lipid core< fibrous cap (thin)> Inflammatory cells

THE STORY OF ATHEROGENESIS

THE STORY OF ATHEROGENESISSwitch into ATHER-THROMBOTIC INSULT at any stage of progression

= ACSs, Stroke, …etc.

ATHEROGENESIS PROGRESSION ALONG AGE

DYSLIPEDEMIA

ENDOTHELIAL DYSFUNCTION

MORBIDITY & MORTALITY OUTCOMES

PREVENTED or DECREASEDBy CONTROLLING DYSLIPIDYMIA

ATHEROGENESIS & CLINICAL EVENTS

Coronary SUPPLY Pumping Cardiac Work

DEMAND (O2)

O

2O

2

O

2

O

2 FFAFFA

GFFAG

GG

O

2

O2

ATP

ATP

O2

O

2ATP

IMPAIRED SUPPLY

INCREASED DEMAND

ISCHEMIC HEART DISEASE [IHD]

Coronary SUPPLY Pumping Cardiac Work

DEMAND (O2)

Coronary Filling (in diastole) bydiastolic timediastolic pressure …etc

Coronary Narrowing bySpasm Atherosclerosis lesion

IMPAIRED

Cardiac Work Heart Rate Load; i.e BP…etc. Force; Hypertrophy

INCREASED

ISCHEMIC HEART DISEASE [IHD]

CORONARY HEART DISEASES [CHD]

???

FUNCTIONAL STRUCTURAL

SPASM ATHEROSCLEROTIC PLAQUE

+ THROMBOSIS

Vulnerable

Stabilized

CORONARY HEART DISEASES [CHD]

Fissure at Classifications

FUNCTIONAL STRUCTURAL

SPASM ATHEROSCLEROTIC PLAQUE

+ THROMBOSIS

Vulnerable

Stabilized

CORONARY HEART DISEASES [CHD]

ISCHEMIC HEART DISEASE [IHD]

SPASTIC ANGINAPrinzmetal’s Angina

STABLE ANGINA

UNSTABLE ANGINA

MYOCARDIAL INFARCTION [AMI]

Acute ~Subtotal / Total OCCLUSION

ANGINA

ACUTE CORONARY SYNDROME [ACS]

Sustained Spasm

ANGINA PectorisChest pain (varying in severity) due to ischemia of heart muscle caused by obstruction or spasm of coronary arteriesConstricting & tight, oppressive, crushingStarts in the centre behind the sternum or on left side of the front of chest & spread out to shoulder arm…..

Weak relationship between severity of pain & degree of O2 deprivation in the heart muscle (i.e., severe pain can occur with little or no risk of a heart attack, and a heart attack can occur without pain).

Stable Angina

Pain is due to (accumulation of metabolites K+, PGs, Kinins, Adenosine….) 2ndry to the ischemia

EFFORT ANGINA

Prinzmetal’s AnginaVARIANT ANGINA Occurs at rest Cyclic (vasospasm) due to contraction of VSMC>in younger women

Develops by exertionResolves at restLasts ~5 minInsidious onset

Unstable AnginaCRESCENDO ANGINA

Occurs at rest / minimal exertionSevere / Lasting >10 min; Either of;* New onset (nothing for last 4–6 w) * Crescendo pattern; getting > severe / prolonged / frequent than previous

By a Spasm or Stabilized Plaque

Vulnerable

Plaque

ATP, Ion PumpsCa

Proteolysis, Membrane damage…. Necrosis

~~Action Potention, elect. Activities & functions

Acute ~Subtotal /

Total OCCLUSION

ST – Elevation

Non ST – Elevation

Inflam. Mediators, ROS TNFa, NFkB, ….

Apoptosis

ACUTE CORONARY SYNDROMES [ACS]

ECG CHANGES

AMI

Cardiac Enzymes (Markers)

+ve

AMI

-ve

STEMINSTEMI

Unstable

Angina

Umbrella term that covers a spectrum of acute clinical conditions ranging from

Unstable angina (38%) NSTEMI (25%) STEMI (30%)

A heart Attack