Mens! MEDI Atherosclerosis vs arteriosclerosis "2 tha atar is more on thickening ot te nner anc central wall of artery. © TheAtherosclersiu Major cause of death and promt ly involves ip formation (deadly in developed (© Coronary aterles Mi & angina pectoris (© CNS strokes and Transient cerebral acer (TIA) S _Pergheral circulation ~cludiaton and gangrene ‘© Splanonie culation ~ masentare cherie © idneys~ renal artery stenosis Tha proximal lof anterior descending coronary artery axis particular predilection for developing atherosleretie ieaee (arson) ‘heroslerosis alo affects the proximal portions af the renal arteries ang, i the extracanial culation of the bran, he ‘arate bfurston (Harrisons) INTERNAL MEDICINE II (15 SEMESTER) | ATHEROSCLEROSIS |Dr. Daet Extracranial elzeulation tothe brain Cicie of pteral carovic ommen carote 1 Athorseeratie lestons often form at branch pins of arteries, ‘eglons characterized dsurbed hydrodynaris (hts) Nt al manifestations of stherozclerasi result from steno occlusive dieses Ectasa andthe davalopment of aneurysmal iaaee, for example, feoquently ecurin the aor iol?Mens! INTERNAL MEDICINE II (15 SEMESTER) | ATHEROSCLEROSIS |Dr. Daet cana dare Siem engn > win 030% of vesee' sien) ‘Aneurysm: ameter >1.5n, widm > length (<50% of vessels length) + ptherogenesis in humans typically occurs over period of many vests. 1+ Afar a generally prolonged “sent” pelo, atherosclerosis may became crically manifest 1+ Cinta expression of therosclross may he: Aeute oF Chronic (5 Chronie= dovslopment of table, efor nducad pectorsor predictable ae represen ‘leudiation 2 Aewte china avant suchas Ml stroke, or sucden cardiac dost herald the prosonce af thororlraxe) A. FATTY STREAK (precursor of atberoslerotiep © Roprosets the nial lesion of thororlerose © tariss from fcaincrese inthe content of Kpoprotine within the regions of he intima ‘1 Inparticuar LDL thet bears Ape B appear causal ‘elated to atheroslrosa (9 Accumulation oflipoproteins pars may not simply ru ‘rom increased permesblityo “leakness" ofthe everying ‘endothelium ‘thet this Hpoprotel, cll ine intima of atelas because they bind to conmituents ofthe extracelilar ‘atric Ineeasing the residence time of the pick partie within the arterial w Key saps in the formation ofthe fate streak 4. Moneyte attachment to the endothelium 2. Mieration nt the intima 3. Maturation form pt laden macoph {LL LECHOW De LECHE (aaD CHOLESTEROL) HDL = HINDI DAW LECHON (6000 CHOLESTEROL) 8. LEUKOCYTE RECRUTTMENT © Accumulation af leukocytes charactorias the formation of caty atherosclerotic lesion (Haron) (2 Involves elements of INFLAMMATION ‘1 proces that now prowdes 2 unifying theme inthe pathogenesis of te dase (© Inflammstary eal typeall found in the evolving atheroma 1 Monoeyte-derived macrophages + Oandsi als + Tana mphocytes + gst calle 2 LAMINAR SHEAR FORCES ‘1 Can also suppress the expression of leukocyte adhesion molecules 1 SUmulatesendothetal cel to produce superoxide emtaze lntondantensimel + Low shear strats and/or disturbed flow —stes of prediection for atherosclerotic lesions (example: distal torow dvisers) ‘the production of NITRIC OXIDE by endothelial els ‘+ Vasodilator propetis + NO‘ctas local ant inflammatory autocad (iting local achesion molecle expressions) *eskocyt adhesion molecles provide an edttonal nk between arterial ccumulation of fpoprotens (HARRISON) laminar flow turbulent flow ee ee ee MEDI Bot?Mens! ‘emo i of ede © erToKINes Induce or augment the expression ofaukocyte ‘anesion molecules on endothelial celle om oN by Yt as © Themonenuclear phagocytes mature Inco macrophages and bbesomelipis-aden foam happans within the nema] ‘This conversion requires uptake ef lipoprozein parties by receptor mediated endoeyosts © Theexogenous choestero| Suppresses the expression of the LDL receptor decreasing the lovl of el-surface receptor for LOL Under condition of cholesterol ease ‘© Exogenous cholesterol “suppresses ‘expression of the LDL receptor decrease lipid uptake + Scavenger” neceptrs 2 Aternatve receptors that can mediate pd loading of foam cals ‘+ Iepreferentaly endocytoses modifi poproceins INTERNAL MEDICINE II (15 SEMESTER) | ATHEROSCLEROSIS |Dr. Daet et W.. bs = wer So 5G): ‘s =e st a Ao teem ‘otal fatty streaks progress oferm complex theromata arson: ‘© Lipa ccumultion ensues ifthe amount of oid entering the ortery wall exceed that removed by mononuclear phagocytes. ‘+ Mocrophogespoiferates nthe plagues response 19 roach octrs overexgressed in esions, another aspect of the dynamic egulation an flu of ell cing ‘+ Expar by phogocytes constitute one response to fea pd cvericod in the evovng lesions + Transportof cholesterol from the cll tothe HDL particle reverse cholaeroltranspor} 2 Mediated by ATP binding cnrette (ABC) ransporter Spaciled cel surface molecules + Beample: ABCAL transporter se pene mutstedin Tangier dense, characterized by ‘ery oer HO pares, ‘+ Tranferschoostora ram eal onascant HOL aries and ABCGL to mature HDL partes (© This process alows HDL loaded with cholesterol to deliver ito epatcyt by binding to eavenger receptor BE (aritons) + Moerophages (© Playsa vitalrole inthe dynamic economy of ipkd accumulation inthe arterial wal during atherogenesis + Apoptosis Programmed eal death (2 Results inthe formation of the Kpd-ich center called NecRoTic cone om ove MEDI aot?Mens! INTERNAL MEDICINE II (15 SEMESTER) | ATHEROSCLEROSIS |Dr. Daet ‘© Oytoknes inthe pave TL-Land TNF found within the Plaque Can induce cal production f growth actors, incuding forme of PDGF, FGF which may contribute ta plaque aelution and complistion IFNy dared from Tells within lesions it the _ythasi of nterttia forms of cllagan by smooth ruse calls POG stimulate the migration of smooth muscle celle Into the intima + TGEB~ stimulates iteratitial cllagen production by smooth muse calle + peherathrombose 15 Products of blood coagulation and thrombosis that contibute toathacma evaliton and complication ‘Smooth muse calle + Asthe atherosclerotic lesion advance, abundant ple of mie \ezrele develop in connection withthe artany= vas aearumy 1+ These bood vesels provide an abundant surface are or leukocyte twafcing + temay serveas the prtl for enty and ext of white blood eal from the establlenes atheroma teeay also furish oc for itraplaque hemortage ‘There ao rable and prone to rp proce focal hhemorthage Hartson ‘© Vosculr lok provokes thrembosis yeing local thrombin generation which a tarm activote smooth muscle ond endothelial cts 1+ Atherosleroieploques often contin iin and hnemesideri en inaiation that eisodes of nroploque hemorhage contribute oploavefrmarion #Athersceratle plagues also accumulate ealéum 4 oxeccsin,osoporin and bone morphogenetpretes A. Arterial remodeling during atherogenesis (© Compensatory enlargement, atheroma s growing nar preverving the caer ofthe kamen 8, Rupture ofthe plaques fibrous eapeule cousss thrombosis (Sites of plaque rupture ram the rides, the normal rtry tend to esl this tvomnboss by flaoyte mechanism or antithrombotic ‘echaneme Thrombelyie molecules 2. Thrombomoduln D. Tiesue and Urokinasesype psrinogen activator . Heparan sulfate proteogiyean 1. prastacyels and nite ude When the elt overwhelm the endogenous fibrinalytic machanis, Ieimay propagate and lead to arterial eclusion . The subsequent thrombin-indueed fibrosis and healing causes 2 ‘broproliferatve response that can lead toa more lsrous lesions ‘that can prodce an ascent plague that causes a hemodynamically signiicane stenosis + Acomplex and highly regulated balance betveen ent and eeress of tpoprotens and leukocytes, call proliferation and ell death, ‘exvactlar mavik production and remodeling, 25 well 5 ‘lection and neovaecvlarzation contrite lesion formation Most atheromata produce no symptoms, and many never cause nial manifestations + Arterial remodeling ‘5 Account for some ofvarabity ia the nial expression of stherorclratle disease + Compenzatory enlargement © Vesels atfacta by atherogenesis tend toneresse in iometer © Growing atheroma doesnot encroach onthe arterial lien Lun the burden af atherosceroieplaque excaod “sof ‘the area ancompatead by tha intrna last lina MEDI ot?Mens! INTERNAL MEDICINE II (15 SEMESTER) | ATHEROSCLEROSIS |Dr. Daet + Hypone Stimulus Induce formation of collateral veces in the myocardum, rmtgating the consequence ofan acute occlusion ofan pcan coronary attry Lesions thot cause arate or unstable atherosclerotic syndromes parculry in the coroneryeeulation, may arise from atherosclerotic plaques that do not produce @ Flwrlimiting stenosz ‘+ "Thromb ovsing rom nanoccisv stenoses explain the “Fremiency of Mi 2 an inal manfestation of CAD in pottents whe report no prior history of ongina pects, syndrome usualy caused by fow-limting stenoses ‘orzo + Acuperico erosion of the endothe ora ploase rupture er fissure usual produce the thembus that ‘ovses ends of unstable ongina pectoris or the teclonv and relatively persistant thrombus tha couece “© Plaques that have caused thromboses tend ta have (2 Thin fibrous cape © Relatively age ipl cores 5 High content of macrophage Oulward remodeling 12 Spotty (rater than dense] clelcation Calpe eons show that at ses of plaque rupture, Macrophage tnd Lymphocytes predominate and contain relatively few THIN-CAP FIBROATHEROMAS(TICRA} = A oh -MACROPHAGE-POOR TCFA [MACROPHAGE RICH TCFA — © FIBROATHEROMA ECTITETTEE sor aise ractons ron arwenoscienosis High Dt cholesteo CGigarete smoking Hypertension @P 2140/00 mg or on artihypertensve meciation) Low HO cholesero (c1.0 mmolt (40 a/c) Diabetes mets Family hisory of premature CD ‘age (men 245 years women 255 yeas) ese risk ac besty 230 ka) Physical nacivty ‘therogenc det Emerging ik ctor. Lpoprcein | Prothrombotc factors Proifiammato Iga fastng glucose Subcines sterols 11 chlo molt 40 ef has ben vw 3s ease {Write a ans psi: 0, oy pd Disorders (52013 cholesterol aiden: focused on S-hyron 3 ‘ethyllutary!eeerayme | HMG-Cal eductars inhibitors (statins) © Fourstatin benef groups 1. Allindviuals rho have cinical atherosclerotic arlorascularelsease(ASCVD) “secondary prevention! 2. Those with LDL cholesterol 2180 mglel without secondary cause such 35a high intake of saturated or tran ats, various hues or certain diseases 4. Individuals with abet without extablzhed cardiovascular Asease who ae 40-75 years old and have LOL cholesterol 70-189 e/a 4. Those without esabiichod ASCUD without diabetes who are {40-75 years old and who have LDL cholesterol ef 72-189 mg/d apd a calculated ASCVD tsk 2755, MEDI Sot?AAscrss" INTERNAL MEDICINE II (15 SEMESTER) | ATHEROSCLEROSIS |Dr. Daet (©The 2012 guidtine oes not advocate any specific therapy for © Weight os and physical activity can raise HOL + Disbetos Melts (3 Abnormal ipproten profs associated with inca rsitance, known as dabetic dslgidenia © Accounts for part ofthe elevated cerdovascle skin patients with spe 2 diabetes + Diabet indole (© UDl cholesterol evels ner the average 5 LDL particles tend te besmaller and denser > more atherogeni + Metabolic some ‘Table 1. Cincalidemteabonct te metabote synarome any tee isk factors) jominal obesity Tien (waiatcveunference) | >i0Zem 40m) ‘Women 388 em (°35 in) Traiyeonds SET mmol (150 mglaLy HDL chotestereh Ten 6.1 mmol/L (>110 mg/dL) Mnemonic + nasiosr ‘+ Men was circumference: “red ano gusto mong regalo sa sradvation?” ISANG AUTO (L02= 102 cm) 1+ Women waist ckeumference: mehiig daw isayaw ng baba —OTSO (0730 (ase) 4+ _Tiehoerder: 150 vised by (TR Fasting glucose: "Gt" rom glucosestooks ke "Sand 2" ETESSPEY icant HEALTHY NUTRITION AKDPAYSICALACTIITY 'BENAVIORS RECOMMENDED INTHE2013ACCABA IDCLINE ON UIFESTYL€ MANAGEMENT TO REDUCE CARDIOVASCULAR RISK “The au poplaton shuld be encouraged to pra ese behaars nab ‘Cons a etry pate tat emphases intake oF vegetables [ras and wae granu owt dy proc legumes nortopieal vegetabe ol and ‘vets sogrSametned Beverage, ees ‘Ast iis detwry pee to aproptatecaloreequreents penal ‘acuta fod preferences and rasion Uap footer medal Achieve ei pt mb folowing ene uch 3 the OASH stay ater, ero" he RAD ngage 2h and 30 ia week of modeatenensy or 1h and TS mn 7 me) a week ovigorourinensty able ples acy. oan ‘ahalere crane mae roar wi act Aart cvs petra icyncci of To mn prteby send thoughout tbe meek. Ache and rina 2 eaty wor Ree tothe 2013 Pino Report for sy x00 fmmendatons on weight los a3 marsrance ‘To determine whether ts vigorous or moderate intensity, you must get the hear rate Maximum HR (100%) = 220—oge Moderoteeersity~ 50.70% of maximur HR Vigorous itensty— 70858 of maximum HA Male Sex/Postmencpausl State (© Excess coronary sk in men compared with premenopausal © Ahormenopaute coronary rk scoleraterin women (© Estrogen therapy lowers LDL cholesterol and aise HDL cholesterol > relies coronary rise Dyseequlated Coagulation of Feinolysis Thrombosis provoked by atheroma rupture and subsequent healing may promote plaque growth © ibvinagenevel coreate with coranary sk and provide Information ahovt coronary nt independant ofthe ipoprotln profile © Balance between Mina factors (plasmin and inhibitors of the forinolce system iplasminegen aethvator inhibitor 1 (PAI) (© Aplin radices CHD events in several contents omonytsine! accumulation covalatauith wombs a wth coronary risk Inflammation 1D Plasma levels of CRP, as measured bya high-sensitivity aesny (sch) + Also coreclate with the outzome in patents with acute coronary smdromes + Validate biomarker of sk but probably not asa rect contributor to pathogenesis (© Evidence fom the JUPITER study that both LDLJowering and ant= Inflammatory actions contibuta tothe benefit af eatin therapy Lifestyle Medieston 12 Optimise rick actor profles lng before atheroxcortic doace aniests (2 Rese and minim earcovascular ise © Counsel patients about the health isk ftbacco use and plese guidance and resources reqang smoking cessation (© Prucent etary and phyla actty habit for malntlring ies! body weigh (2 Atleast 20 minutes of madersteetensty physical activity pr day MEDI Got?AAeo's' INTERNAL MEDICINE II (15 SEMESTER) | ATHEROSCLEROSIS |Dr. Daet In incinaduais not recom Tecalculate estimated 10 ASCYD risk every 4-6 Witndividusie aged 30-75 7 without ASETE's soveey MEDI Tot?