Publication: Yüksek dansiteli lipoprotein ve alt gruplarıyla koroner arter hastalığı arasındaki ilişki
Abstract
1.ÖZET Koroner arter hastalığı (KAH) genellikle, organ tutulumunun gerçekleştiği ve tam bir iyileşmenin sağlanamayacağı bir aşamada teşhis edilebilmektedir. Günümüzde çoğunlukla, LDL-C’yi düşürmeyi hedefleyen tedavi uygulanmaktadır. Oysa AMI geçiren hastaların en az 1/ 3’ünde serum LDL-C < 130 mg/ dl’dir. O halde sadece bu hedef yeterli değildir, yeni hedefler belirlenmelidir. Tanı gücü yüksek belirteçler ve spesifik risk faktörleri bulunabilse, primer tedaviyle tam bir iyileşme şansı doğabilir. Bu tezde, anjiyografik yöntemle KAH (+) ve (-) olarak belirlenmiş ve en az üç haftadır antihiperlipidemi tedavisi almayan toplam 291 olgu incelendi. KAH(+) olanlar hastalığın ciddiyet ve yaygınlığına göre, Gensini Skoruna göre hafif ve şiddetli olarak ayrıldı. Bu olgularda, poliakrilamid jel elektroforeziyle büyük, orta ve küçük ana grupları olmak üzere HDL alt grupları ayrıldı. Bunun yanında bir çok biyokimyasal parametre ölçüldü. KAH(-), hafif KAH(+) ve şiddetli KAH(+) olan kadın ve erkekler arasında yapılan karşılaştırmada, hem HDL-C hem de HDL alt gruplarının dağılımı anlamlı fark göstermedi. KAH(-) erkekler ve kadınlarda, mg/ dl olarak ortalama değerler sırasıyla şöyleydi; HDL L: 13,7 ± 5,8 ve 17,4 ± 5,7, HDL M: 22,6 ± 4,8 ve 25,8 ± 5,3, HDL S: 5,8 ± 2,2 ve 6,4 ± 2,4. KAH(-) ve KAH(+) olgularda cinsiyete göre ayırım yapılmadığında, serum büyük HDL (HDL L) alt fraksiyonunda, KAH(-) olanlara göre anlamlı bir azalma saptandı (p = 0,038). Serum HDL-C ortalama değerleri KAH(-) olan erkek ve kadında sırayla, 42 ± 8,1 ve 50 ± 10,3 mg/ dl’dı. Bu düzeyler, TEKHARF ve TKÇ’ında bildirilenlere göre daha yüksekti. KAH(-) ve KAH(+) olguların ayrımında, lipid parametresi olarak en iyi belirteç apolipoprotein A-I/ B oranıydı; rutin risk faktörleri arasında yer almayan HbAıc, BUN, vücut yüzey alanına göre oranlanmış kreatinin düzeyleri, iki grubu ayırmada çok daha iyi bir ayırım belirteci gibi görülmektedir. Daha fazla sayıda vakayla ve destekleyici parametrelerle yapılacak yeni araştırmalara ihtiyaç vardır. Koroner arter hastalığı, ateroskleroz, lipoproteinler, HDL alt grupları, PAGE, HbAıc 2.
Coronary Artery Disease (CAD) is generally diagnosed at a stage when the organ is affected and a total recovery can not be achieved. Currently, usually a treatment targeted to reduce the LDL-C is being carried out. Whereas, at least one third of the patients who suffered from AMI have LDL-C levels less than 130 mg/ dl. So this target level is not sufficient by itself and new targets should be defined. If some markers with high diagnostic power and specific risk factors are found then a total recovery could be achieved with primary treatment. In this thesis total of 291 cases, each were defined as CAD(-) and (+) by angiographic methods and none had any antihiperlipidemic treatment at least for the last 3 weeks, were investigated. CAD(+) cases were divided as mild and severe according to their severity and extent using Gensini Score. The HDL subclasses in these cases were also separated as large, intermediate and small using polyacrylamide gel electrophoresis (PAGE). Additionally many biochemical parameters were measured. The comparison between the female and male with CAD(-), mild CAD(+) and severe CAD(+) showed no significant differences at the distribution of HDL-C and HDL subclasses. Mean levels in mg/ dl at CAD(-) male and female patients were determined, respectively; HDL L: 13,7 ± 5,8 and 17,4 ± 5,7, HDL M: 22,6 ± 4,8 and 25,8 ± 5,3, HDL S: 5,8 ± 2,2 and 6,4 ± 2,4. Significant reduction at large HDL (HDL L) subclasses compared to CAD(-) cases was observed only when no sex distinction were made for CAD (-) and CAD(+) cases (p = 0,038). Mean HDL-C levels at CAD(-) male and female patients were 42 ± 8,1 and 50 ± 10,3 mg/ dl, respectively. These findings were higher compared to TEKHARF and TKÇ results. Apolipoprotein A-I/ B ratio was the best diagonistic marker between the lipid parameters to differentiate between the CAD(-) and CAD(+) cases; HbAıc, BUN and body surface area adjusted creatinine which are not in the routine risk factors seemed also to be a better diagnostic marker to separate the two groups. The subject needs to be investigated further with new studies with more cases and other supporting parameters. Key words: Atherosclerosis, Coronary Artery Diseases, lipoproteins, HDL subclasses, PAGE, HbAıc
Coronary Artery Disease (CAD) is generally diagnosed at a stage when the organ is affected and a total recovery can not be achieved. Currently, usually a treatment targeted to reduce the LDL-C is being carried out. Whereas, at least one third of the patients who suffered from AMI have LDL-C levels less than 130 mg/ dl. So this target level is not sufficient by itself and new targets should be defined. If some markers with high diagnostic power and specific risk factors are found then a total recovery could be achieved with primary treatment. In this thesis total of 291 cases, each were defined as CAD(-) and (+) by angiographic methods and none had any antihiperlipidemic treatment at least for the last 3 weeks, were investigated. CAD(+) cases were divided as mild and severe according to their severity and extent using Gensini Score. The HDL subclasses in these cases were also separated as large, intermediate and small using polyacrylamide gel electrophoresis (PAGE). Additionally many biochemical parameters were measured. The comparison between the female and male with CAD(-), mild CAD(+) and severe CAD(+) showed no significant differences at the distribution of HDL-C and HDL subclasses. Mean levels in mg/ dl at CAD(-) male and female patients were determined, respectively; HDL L: 13,7 ± 5,8 and 17,4 ± 5,7, HDL M: 22,6 ± 4,8 and 25,8 ± 5,3, HDL S: 5,8 ± 2,2 and 6,4 ± 2,4. Significant reduction at large HDL (HDL L) subclasses compared to CAD(-) cases was observed only when no sex distinction were made for CAD (-) and CAD(+) cases (p = 0,038). Mean HDL-C levels at CAD(-) male and female patients were 42 ± 8,1 and 50 ± 10,3 mg/ dl, respectively. These findings were higher compared to TEKHARF and TKÇ results. Apolipoprotein A-I/ B ratio was the best diagonistic marker between the lipid parameters to differentiate between the CAD(-) and CAD(+) cases; HbAıc, BUN and body surface area adjusted creatinine which are not in the routine risk factors seemed also to be a better diagnostic marker to separate the two groups. The subject needs to be investigated further with new studies with more cases and other supporting parameters. Key words: Atherosclerosis, Coronary Artery Diseases, lipoproteins, HDL subclasses, PAGE, HbAıc