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Atherosclerosis Coronary heart disease Angina pectoris Myocardial infarction.

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Presentation on theme: "Atherosclerosis Coronary heart disease Angina pectoris Myocardial infarction."— Presentation transcript:

1 Atherosclerosis Coronary heart disease Angina pectoris Myocardial infarction

2 Causes of death in Europe men –coronary heart disease (MI)21% –trauma and poisoning12% –stroke11% –pulmonary carcinoma 6% –carcinomas in GIT 4% women –coronary heart disease21% –stroke18% –other CVS diseases15% –trauma and poisoning 5% –breast carcinoma 3%

3 Atherosclerosis syndrome affecting large and medium-sized arteries artery wall thickenings – lipid infiltration - atheroma creation chronic inflammatory response in the walls of arteries hardening of the artery wall (loss of elasticity) Result - insufficient blood supply to the heart – myocardial infarction (heart attack) to the brain – stroke to the legs – claudicatio

4 Tunica intima Endothelial cells Tunica media Smooth muscle cells Tunica adventicia

5 Atherosclerosis

6 Atherosclerotic plague Endothelial cells Thrombus Rupture of fibrous cap Smooth muscles cells Lipid core Platellets Foam cells

7 Stages of atherosclerotic plaque development Type I – isolated foam cells –macrophages with a droplet of fat in intima Type II – fatty streaks –foam cells layer Type III –higher amount of lipids under the foam cells layer Type IV – atheroma –lipid core, fibrous cap Type V –more collagen and smooth muscle cells in fibrous cap Type VI –atheroma with complications - thrombosis

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9 Coronary heart (artery) disease result of the ateromatous plaques within the walls of the coronary arteries limitation of blood flow to the heart → ischaemia Result Angina pectoris Myocardial infarction

10 Coronary heart disease physical acitivy (emotional stress) activation of sympathicus  heart rate and contraction  demand after oxygen supply coronary artery obstruction due to atherosclerosis lack of blood (oxygen) supply PAIN

11 Risk factors (CHD, IM) Basic biological –age, gender, family history (= genes) Biochemical, classical –cholesterol, LDL-CH, TAG,  HDL-CH, apoproteins, Lp(a), indexes Biochemical, new –fibrinogen, homocysteine, ferritin –small dense LDL, oxidized LDL Nutrition and life style –too much fat, sugar, antioxidant and fiber deficiency –SMOKING, SEDENTARY LIFE STYLE Diseases –obesity, diabetes (IR!), hypertension, kidney failure Genetic RF –LDL receptor (FH), apo E variants and many others

12 Basic biological factors age –men > 45 years –women after menopause gender –men > women

13 Obesity obesity hyperinsulinaemia dyslipidaemia central typ

14 Hypertension endothelium damage

15 Smoking nicotine –effect on lipid metabolism –vasoconstriction CO –carboxyhaemoglobin increased coagulation cascade activity

16 Endothel Intelligent interface between blood and vessel wall/tissues 1500 g, football field (1000 m 2 ) Endocrine, paracrine and autocrine functions –vessel tonus, coagulation, adhesion, cell replication Organ specificity, differences in arteries, capillaries a venes Dysfunction in hypertension, diabetes, dyslipidemia...

17 Lipoproteins

18 Cholesterol, free and esters with fatty acids 275 mmol in the body –50 mmol LP, GIT, liver –25 mmol fat tissue –90 mmol muscles & vessel wall –110 mmol nervous system 3 mmol/d exchange Cholesterol –In: food and synthesis in cells (from CoA) –Breakdown: no –Out: bile (enterohepatal circuit); stool LDL cholesterol –The normal level (3,1 – 3,9 mmol/l) is not normal for the endothel –Newborns & atherosclerosis resistant animals only  0,8 mmol/l

19 Triacylglycerols & fatty acids TAG & FFA 15 kg in nonobese subjects kJ; enough for 3 months Thermal isolation, fertility, body shape Intake & synthesis: 80 – 170 mmol/d Different fatty acids – saturated, unsaturated, polyunsaturated (eikosanoids), shorter and longer chain Rapid turnover dependent on diet and alcohol intake, breakdown through physical activity (FFA – minutes )

20 water-soluble particles, that transport water-insoluble lipids in the blood Lipoproteins Phospholipids Apolipoproteins Triacylglycerols Cholesterol esters lipids proteins Free cholesterol

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22 Apoproteins

23 3 lipoprotein families (LP) spherical or discoid particles synthesised in guts or liver –Hydrophilic surface (phospholipids, cholesterol esters and apoproteins) –Hydrophobic inner part (TAG, CH) –Dynamic interaction with vessel wall and each other Chylomicrons  chylomicron remnants VLDL  IDL  LDL (heterogenous group) HDL nascent  HDL 3  HDL 2

24 Chylomicrons Enterocytes apoB48, others from HDL TAG into fat and other tissues, LPL CH into liver (from bile and food) Peak 3 – 6 h after meal, t 1/2 30 min, after 9 h Ø Remnants into liver through receptor cytotoxic and atherogenic

25 VLDL – LDL family Liver, endogeneous TAG, CH B100 and others functions and metabolism similar to CHY VLDL t 1/2 2 – 4 hod, transformation to IDL, LDL LDL has a slow turnover, can be modified – oxidation, glycation small dense LDL Receptor and scavenger receptor

26 LDL classes LDL classdensity, g/mldiameter, nm% of LDL I1,02527,5 – 26,03 II1,02826,0 – 25,516 III1,03425,5 – 24,250 IV1,04824,2 – 21,822 V> 1,048< 21,89

27 Small dense LDL small –easy transport to intima of vessels higher density higher TAG concentration easy oxidation Lipoprotein(a) LDL with apoproteine(a) – glykoprotein very similar to plasminogen higher risk of thrombosis Oxidized LDL (oxLDL) high atherogenity higher macrophage afinity x higher than to LDL

28 Reverse transport of cholesterol by HDL Liver, enterocytes and fromCHY as nascent „disc“ Lot of apoproteins LCAT and CEPT –lecitin-cholesterol acyltransferase, esterifies CH –cholesterol ester transfer protein transprots CH-E from HDL into other LPs Takes out cholesterol from tissues, disc is filled to HDL 3 Exchanges CH-E for TAG with other LPs transforms to HDL 2 Binds through AI to specific receptor in liver

29 HDL 3 HDL 2 nascent HDL liver vessel tissues

30 Apolipoprotein E  3 allels - APOE2, APOE3, APOE4  APOE4 - high cholesterol and LDL-chol, high risk of complications of atherosclerosis E3 = 112 Cys, 158 Arg E2 = 112 Arg, 158 Arg E4 = 112 Cys, 158 Cys

31 Normal (desired) values T-CH < 5,0 mmol/l4,55 – 5,45 HDL-CH> 1,0 mmol/l0,87 – 1,13 LDL-CH< 3,0 mmol/l2,65 – 3,35 TAG< 2,0 mmol/l1,70 – 2,30 INDEXES T-CH/HDL-CH< 5,0 NONHDL-CH < 3,8 LDL-CH/HDL-CH< 3,0 Klimov (T-CH – HDL-CH)/HDL-CH< 4,2 APO AI/APO B> 1,3

32 Other laboratory methods Special –Apo B, Apo AI, Lp(a) –homocysteine, coagulation and fibrinolytic factors. Very special –LDL receptors –Apo C, E, LPL, CETP, LCAT –classes of LDL, HDL Yesterday –total lipids, phospholipids, fatty acid esters –elektrophoresis Tomorrow - genomics

33 Hyperlipoproteinemias

34 Classifications Fredrickson 1967, WHO 1970 –I, IIa, IIb, III, IV, V, VI - partly history Therapeutical 1992, European task force –CH, TAG, both Etiological – future –primary and secondary DLP is not sufficient! –most primary DLP are not exactly characterized

35 “Primary DLP” Familiar hypercholesterolemia (LDL rec.) Familiar defect of ApoB100 (FDB) ?Polygenous hypercholesterolemia ?Polygeneous hypertriglcyceridemia ?Dysbetalipoproteinemia (IDL) ?Familiar type V hyperlipidemia

36 “Secondary DLP” Nutrition and lifestyle –including smoking, alcohol and micronutrient deficiency Obesity Diabetes mellitus –type 2 usually, decompensated type 1 (BG 20 – extreme TAG) Kidney failure Liver disease Endocrine diseases –  thyroid function Drugs Hormones – anticonception, gravidity, postmenopausal, anabolics

37 Familial hypercholesterolaemia AD inherited defect of LDL receptor (> 300 mutations of LDLR) Symptoms increased LDL-chol concentration atherosclerosis (high risk of MI, homozygouts in decenium) LDL LDL receptor

38 Symptoms and signs xantomas arcus lipoides corneae xantelasma palpebrarum atherosclerosis and CHD

39 Angina pectoris severe chest pain due to ischaemia of the heart muscle, due to obstruction of the coronary arteria Symptoms –after exertion, emotional stress, in the rest –chest pain (or discomfort) –lasting several minutes –referred pain to the arms, shoulders, neck, chin –exacerbated by full stomach or cold temperature –breathlessness, sweating, nausea –pain relieved by nitroglycerin

40 Types of angina pectoris Stable AP –stable atherosclerotic plaque –retrosternal pain precipitaded by activity (walking, running) –no pain in rest –3 – 5 min –referred pain to the arms, shoulders, back... Unstable AP –„crescendo“ angina –unstable atherosclerotic plaque –at rest –> 10 min. –more serious symptoms Variant (Prinzmetal´s, vasospastic) AP –caused by vasospasm –unknown mechanism (dysfunction of endothelium?) –atherosclerotic changes – not necessary –at rest (at night, early morning)

41 Myocardial infarction Acute myocardial infarction Heart attack Necrosis of the heart cells due to interruption of blood supply to the part of the heart Causes rupture of the ustable atherosclerotic plaque → trombosis coronary artery obstruction by the stable plaque

42 Signs and symptoms –sudden chest pain radiating to the left arm, shoulder, neck, chin... –pain not relieved by nitroglycerin –anxiety –nausea, vomiting, sweating –dyspnea –pale, cold skin –cardiogenic shock symptoms arterial pressure decrease tachycardia –sometimes silent ischaemia – without pain (e.g. diabetic neuropathy)

43 Pain left shoulder right shoulder arm neck epigastrium chest

44 T wave inverion ST segment elevation patological Q wave ECG diagnosis

45 Complication of MI –dysrhythmias –heart failure –shock and hypotension –myocardial rupture –valve defects –embolisation –pericarditis

46 Cardiac markers myoglobin (Mb) troponin I (TnI), T (TnT) creatine kinase (CK) heart MB subtype (CK-MB) lactate dehydrogenase (LD) aspartate aminotranspherase (AST)

47 serum concentration time (days) myoglobin CK-MB troponin I

48 activity time (days) CK-MB AST LD

49 Complication of MI –dysrhythmias –heart failure –shock and hypotension –myocardial rupture –valve defects –embolisation –pericarditis


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