Iningi lezinhliziyo ze-cardiologists kanye nezazi ze-lipid sezibhalisele isikhathi eside "kwi-cholesterol hypothesis." I-cholesterol hypothesis, echazwe ngokusobala ukuthi i-elevated blood level ye- LDL cholesterol iyimbangela eqondile ye- atherosclerosis . Ngakho-ke, ukuthatha isinyathelo ukunciphisa amazinga wethu we-LDL ye-cholesterol yisinyathelo esibalulekile ekunciphiseni izingozi zethu zokuthuthukisa isifo se-atherosclerotic cardiovascular.
Sekungamashumi eminyaka, ochwepheshe basikhuthaze ukuba sishintshe ukudla kwethu ngezindlela ezenzelwe ukunciphisa amazinga ethu e-cholesterol, futhi izinkampani ezithatha imithi ziye zachitha izigidigidi zamaRandi ezakhela izidakamizwa ekunciphiseni i-cholesterol. I-hypothesis ye-cholesterol ayihlanganisiwe nje kuphela odokotela nasezindlini zezokwelapha-ezimbonini, kodwa futhi phakathi kwabantu abaningi.
Ngakho-ke, kungase kumangalise ukuzwa ukuthi ochwepheshe abaningi be-lipid kanye ne-cardiologists manje sebebuza ukuthi ngabe i-cholesterol hypothesis iqinisile ngemva kwakho konke. Ngenkathi ingxabano phakathi kwabachwepheli phezu kwe-cholesterol hypothesis iye yenzeke ikakhulukazi emaceleni futhi hhayi emkhakheni womphakathi, lokho akunciphisi amandla kanye nesifiso sempikiswano. Ngakho-ke, naphezu kwezimemezelo zomphakathi zabanye abachwepheshe abavelele, i-cholesterol hypothesis ngokucacile ayizange "ihlelwe isayensi."
I-Hypothesis ye-Cholesterol
I-hypothesis ye-cholesterol isekelwe kokubheka okubili okubalulekile.
Okokuqala, i-pathologists yabonisa esikhathini eside esidlule ukuthi i-cholesterol deposits iyinxenye enkulu yama-atherosclerotic plaques. Okwesibili, izifundo ze-epidemiological-ikakhulukazi, i-Framingham Heart Study-yabonisa ukuthi abantu abanezinga eliphezulu legazi le-cholesterol banomngcipheko omkhulu kakhulu wezifo zenhliziyo ezilandelayo.
Khona-ke, ngawo-1990, ukuhlolwa kwemitholampilo okungahleliwe kwabonisa ukuthi amaqembu akhethiwe abantu abanezinga eliphezulu le-cholesterol baphumelela imiphumela yomtholampilo lapho amazinga abo e-LDL cholesterol encishiswa ngemithi yesimiso . Kuchwepheshe abaningi, lezi zilingo zafakazela i-cholesterol hypothesis njalo.
Imibuzo emisha mayelana ne-Chopotterol Hypothesis
Phakathi neminyaka edlule, noma kunjalo, i-cholesterol hypothesis iye yafakwa embuzweni omkhulu. Nakuba izilingo eziningana zokwelapha ngezidakamizwa ezinemithi yesimanje ziyaqhubeka zibolekisa ngokuqinile i-cholesterol hypothesis, ezinye izilingo eziningana zokunciphisa i-cholesterol, zisebenzisa izidakamizwa ngaphandle kwezimo zokunciphisa amazinga e-cholesterol, ziye zahluleka ukubonisa inzuzo yomtholampilo.
Inkinga yukuthi, uma i-hypothesis ye-cholesterol empeleni yayiyiqiniso, ngakho-ke akufanele ukuthi ngabe yimuphi umuthi osetshenziselwa ukunciphisa i-cholesterol; noma iyiphi indlela yokunciphisa i-cholesterol kufanele ithuthukise imiphumela yomtholampilo.
Kodwa lokho akusona okuye kwabonwa. Izifundo lapho amazinga e-LDL ama-cholesterol ayehlaselwa kakhulu nge- niacin , ezetimibe , i- bile acid sequestrants , i- fibrates , i- CETP inhibitors , ukwelapha ama-hormone esikhundleni sabantu besifazane abanesifo samadoda, kanye nokudla okunamafutha aphansi, ngokuvamile abazange bakwazi ukukhombisa imiphumela enhle ye-cardiovascular .
Ngempela, kwezinye zezilingo, umphumela omubi kakhulu we-cardiovascular wasebonakala ngokuphathwa, naphezu kwamazinga e-cholesterol akhuphukile.
Njengengqungquthela evamile yomzimba wokuhlolwa kwe-cholesterol-ukwehliswa okwenziwe kuze kube manje, kungcono ukusho ukuthi ukunciphisa amazinga e-cholesterol ne-statins kubonakala sengathi kuthuthukisa imiphumela yezinhliziyo, kodwa ukunciphisa nokunye ukungenelela akusho. Lo mphumela ubonisa ngokuqinile ukuthi izinzuzo ze-cholesterol ukwehla okubonwa nge-statin therapy ziqondile ezitatimendeni ngokwazo, futhi azikwazi ukuchazwa ngokuphelele ngokululaza i-cholesterol ye-LDL. Ngenxa yalesi sizathu, i-cholesterol hypothesis, okungenani kwifomu yayo yakudala, manje isabaza kakhulu.
Ukungaqiniseki okukhulayo mayelana ne-cholesterol hypothesis yaba ngumphakathi kakhulu ngo-2013, ngokushicilelwa kwemihlahlandlela emisha ekwelapheni kwe-cholesterol. Esikhathini esikhulu sokuphumula nemikhombandlela yangaphambili ye-cholesterol, inguqulo ka-2013 ishiye izincomo ukunciphisa i-cholestolol ye-LDL kumazinga athile ahlosiwe. Esikhundleni salokho, iziqondiso zigxile ekunqumeni ukuthi yiziphi abantu okufanele baphathwe ngama-statins. Empeleni, ngenxa yeziguli eziningi, lezi ziqondiso ngokuvamile zinconywa ngokumelene nokusebenzisa izidakamizwa ezingekho komthetho ukunciphisa i-cholesterol. Okungenani tacitly, le mihlahlandlela yashiya i-classic cholesterol hypothesis, futhi ngaleyo ndlela badala ukungqubuzana okukhulu emphakathini wezinhliziyo.
Icala Lokushiya Ngokuphelele I-Cholesterol Hypothesis
Icala lokumemezela ukuthi i-cholesterol hypothesis ifile ihamba kanje: Uma i-LDL ephezulu i-cholesterol ingumphumela oqondile we-atherosclerosis, futhi ukwehlisa amazinga e-LDL ama-cholesterol nganoma iyiphi indlela kufanele ithuthukise imiphumela ye-cardiovascular. Kodwa, emva kokuhlolwa okuningi kwe-cholesterol ekunciphiseni ukuhlolwa kwemitholampilo usebenzisa amanxusa amaningi okunciphisa ama-cholesterol, lokhu okulindelekile akukona okwakubonwe. Ngakho-ke, i-hypothesis ye-cholesterol kumele ibe yiphutha.
Izitatimende zimelela icala elikhethekile uma kuziwa ekwelashweni kwe-cholesterol. Izitatimende zinemiphumela eminingi ohlelweni lwe-cardiovascular ngaphezu kokunciphisa amazinga e-cholesterol, kanti leminye imiphumela (eyathathwa ndawonye ukuze kuqinisekiswe ama-atherosclerotic plaques) ingachaza okuningi, uma kungenjalo, inzuzo yabo yomtholampilo yangempela. Izidakamizwa ukuthi i-cholesterol encane ngaphandle kokuba nalezi zici, izici ezibeka ukubekezela zibonakala zingabangeli lolu hlobo lwenzuzo. Ngakho-ke, kunengqondo ukubeka ukuthi izitembu azikhombisi ngempela ingozi yegazi ngokunciphisa amazinga e-cholesterol, kodwa kunalokho, kungenzeka ukuthi wenze kanjalo ngalezi ezinye, imiphumela engeyona ye-cholesterol.
Iningi labodokotela, kanye nenani elilinganayo lochwepheshe be-cholesterol, kubonakala sengathi lilungele ukwamukela lo mkhakha wokucabanga nokushiya i-cholesterol hypothesis ngokuphelele.
I-Case for Ukubukeza Ngokubukeka I-Cholesterol Hypothesis
Olunye ochwepheshe-mhlawumbe iningi-namanje abavumelani kakhulu nomqondo wokuthi amazinga e-cholesterol awabalulekile. Babambe lo mbono ngoba iqiniso elilula lokuthi, kungakhathaliseki ukuthi uyayinqamula kanjani, uma kuziwa ezifweni ze-heart atherosclerotic, i-cholesterol ayinandaba.
Ama-plaque atherosclerotic amane alayishwe nge-cholesterol. Siphinde sibe nobufakazi obuqinile bokuthi i-cholesterol ephelela emaceleni ihanjiswa lapho ngezinhlayiya ze-LDL. Ngaphezu kwalokho, okungenani kukhona ubufakazi obuthi, uma unciphisa i-cholesterol ye-LDL egazini emazingeni aphansi kakhulu, ungaqala ngisho nokuguqula inqubo ye-atherosclerotic-futhi wenze ama-plaque ahlehlise. Njengoba kunikezwe lobufakazi obubonakalayo, kubonakala sengathi kusengakapheli ukufakazela ukuthi amazinga e-cholesterol awunandaba.
Nakuba i-cholesterol yokuqala ye-hypothesis ecacile ngokucacile idinga ukubuyekezwa, yilokho uhlobo lokucabanga. I-hypothesis ayifani nje kuphela njengesibonelo sokusebenza. Njengoba ufunda kabanzi, ushintsha imodeli. Ngalokhu kucabangela, sekuyisikhathi sokuba i-cholesterol hypothesis ibuyekezwe, ingashiywa.
Kubuyekezwe ku-Yini?
Kubonakala sengathi i-cholesterol ibalulekile ekubunjweni kwamacwecwe e-atherosclerotic. Kuyabonakala nakakhulu ukuthi, ngenkathi ukwandisa i-LDL cholesterol e-correlates yegazi kakhulu engozini yokuphefumula kwe-atherosclerosis, kuningi endabeni kunamazinga egazi kuphela.
Kungani abanye abantu abanezinga eliphezulu le-LDL le-cholesterol bengakhulumi neze-atherosclerosis ephawulekayo? Kungani abanye abantu abanamazinga "ejwayelekile" e-LDL ama-cholesterol anezigcawu ezise-atherosclerotic ezigcwele yi-cholesterol? Kungani ukunciphisa amazinga e-LDL we-cholesterol ngomuthi owodwa kuthuthukisa imiphumela, kanti ukwehlisa amazinga e-LDL nomunye umuthi akusho?
Manje sekusobala ukuthi akuyona nje amazinga wegazi we-cholesterol yedwa ebalulekile-futhi futhi uhlobo nokuziphatha kwe- lipoprotein izinhlayiyana ezithwala i-cholesterol. Ngokuyinhloko, yilapho futhi i-lipoprotein izinhlayiyana ezihlukahlukene zihlangana kanjani ne- endothelium yemithwalo yegazi yokukhuthaza (noma ibuyise) ukubunjwa kweplate. Isibonelo, manje siyazi ukuthi izinhlayiya ze-LDL ze-cholesterol ziza "ngama-flavour" ahlukene. Ezinye ziyingcosana, izinhlayiya ezincane futhi ezinye zikhulu, izinhlayiya "eziwu-fluffy", okwakungase kube khona amathuba okukhiqiza i-atherosclerosis kunalokho. Ngaphezu kwalokho, izinhlayiya ze-LDL eziba ne-oxidized zinesifo sobuthi kuya empilweni yempilo, futhi kungenzeka kakhulu ukuthi zibhebhetheke kakhulu kwe-atherosclerosis. I-makeup kanye "nokuziphatha" kwezinhlayiya zethu ze-LDL kubonakala sengathi zithonywa amazinga ethu omsebenzi, uhlobo lokudla esikudlayo, amazinga ethu we-hormone, iziphi izidakamizwa esizibekiwe, futhi mhlawumbe ezinye izinto ezingakaze zichazwe okwamanje.
Ososayensi bafunda ngokusheshisa okuningi mayelana nezinhlobo ezihlukahlukene ze-lipoprotein, futhi yini eyenza baziphatha ngendlela ehlukahlukene, futhi ngaphansi kwezimo ezihlukahlukene.
Ngesinye isikhathi, cishe sizoba ne-cholesterol entsha yokuhlola i-cholesterol eyenza ukucabangela ukufunda kwethu okusha mayelana nokuziphatha kwe-LDL, i- HDL , nezinye izinkinga ze-lipoproteins ezithatha ukuthi, futhi zingakanani, i-cholesterol ethwalayo ifakwe emaceleni . Futhi i-hypothesis enjalo ebuyekeziwe (ezoba usizo) izophakamisa izindlela ezintsha zokushintsha ukuziphatha kwalezi lipoprotein ukunciphisa isifo senhliziyo.
Kuthiwani Nge-PCSK9 Inhibitors?
Abanye ochwepheshe baye bathi imiphumela yomtholampilo manje ebikwe nge- PCSK9 inhibitors iye yasindisa i-cholesterol hypothesis, futhi ikakhulukazi, ukuthi akukho ukubuyekezwa kwanoma iyiphi i-cholesterol hypothesis edingekayo ngenxa yale miphumela.
Lezi zilingo zibonise ukuthi uma i-PCSK9 inhibitor ingeziwe ekwenzeni imithi ephakeme kakhulu, amazinga e-ultra-low LDL ama-cholesterol ayefinyeleleka, futhi ngalezi zizinga ezincane ze-cholesterol ukuthuthukiswa okukhulu emiphumeleni yomtholampilo kubonwe.
Kodwa lokhu okushiwo akusho ukuthi i-cholesterol ye-classic hypothesis yabuye yasungulwa kabusha. Abantu abafundela kulezi zivivinyo, ngemuva kwalokho, babesayithola imithi yokwelapha ephezulu, futhi ngenxa yalokho babezuza zonke izinzuzo "ezengeziwe" zokubeka izilonda ezinikezwa izidakamizwa ze-statin. Ngakho, impendulo yabo yomtholampilo yayingeyona ngenxa yokuthi "ukwehla" kwe-cholesterol kwehla. Ngaphezu kwalokho, imiphumela emihle etholakala nge-PCSK9 izidakamizwa + izitembu azihambisani nokuthi ukwehla kwe-cholesterol nezinye izidakamizwa nezinye izindlela kuye kwahluleka ukubonisa inzuzo.
Naphezu kwemiphumela manje ebonwe nge-PCSK9 inhibitors, i-cholesterol hypothesis ayichazi ngokwanele lokho okuye kwabonwa ekuvivinyweni kwemitholampilo.
Okubalulekile
Yini ebonakala ecacile ukuthi i-cholesterol ye-classic hypothesis-ephansi yezinga le-cholesterol ezingeni eliphansi engozini yakho-lilula kakhulu ukuchaza noma yikuphi uhla lwemiphumela esiyibonile ngokuhlolwa kwe-cholesterol-ukwehlisa noma izindlela ezifanele zokunciphisa ukuhlobene ne-cholesterol yethu ingozi yenhliziyo.
Phakathi naleso sikhathi, ochwepheshe bashiywe endaweni engakhululekile lapho ukucabanga okwenziwe khona emashumini eminyaka kubonakala kungasasebenzi-kodwa bengakakulungeli ukushintshwa.
Ngalokho engqondweni, kubalulekile ukuthi ukhumbule ukuthi ukuguqula indlela yokuphila kanye nemithi enqunyelwe ukwelapha izifo ze-coronary, okufaka phakathi izidakamizwa ezihlambulula i-lipid, zinezinzuzo ezibonisiwe. Ungalokothi uyeke ukwelashwa ngaphandle kokukhuluma nodokotela wakho kuqala.
> Imithombo:
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> Ray KK, Seshasai SR, Erqou S, et al. Izitatimende kanye nokufa kwe-All-cause ku-High-Risk Prevention Prevention: Ukuhlaziywa kwe-Meta kwezingu-11 ezilinganiselwe izivivinyo ezilawulwayo ezibandakanya abangu-65 229 abahlanganyeli. I-Arch Intern Med 2010; 170: 1024-31.
> Sabatine MS, Giugliano RP, Keech AC, et al. I-Evolocumab kanye Nemiphumela Yomtholampilo Ezigulini ezinezifo Zezinhliziyo. N Engl J Med 2017; I-DOI: 10.1056 / NEJMoa1615664.
> Stone NJ, uRobinson J, uLichtenstein AH, et al. Umhlahlandlela we-ACC / AHA ka-2013 ekuPhileni kwegazi le-Cholesterol ukunciphisa ingozi ye-Atherosclerotic Inhliziyo kubantu abadala: Umbiko we-American College of Cardiology / American Heart Association. J Am Coll Cardiol 2013.