ĐIỀU TRỊ RỐI LOẠN LIPID MÁU

gold coast gardenersI. Những đặc điểm chính trong chẩn đoán:

- Cholesterol toàn phần > 200mg/dL trong 2 lần thử cách nhau 2 tuần.
- LDL-c > 100mg/dL.
- HDL-c < 40mg/dL.
- Triglycerid > 200mg/dL

Vai trò của Lipid đối với VXĐM được tổng kết thành tam chứng Lipid:

- Tăng LDL-cholesterol.
- Tăng Triglycerid.
- Giảm HDL-cholesterol

Những cận lâm sàng khác:

    1. Soi đáy mắt: Từng đoạn xơ nhỏ cứng vữa xơ với những tổn thương đáy mắt khác nếu có phối hợp tăng huyết áp.
    2. Chụp động mạch cản quang chọn lọc.
    3. Siêu âm Doppler.
    4. Lưu huyết não EEG ECG
II. Thành phần Lipoprotein: (% trọng lượng)

   Lipoprotein
                       
   Tỷ trọng  CholesterolTriglyceridePhospholipidProteinApoprotein chính
Chylomicrons0 94
5
85-90
1
1-2
B48 E C11
VLDL0 94-1 006
20
60-70
15
5-10
B100 E C11
Chylomicrons remnant1 006-1 019
30
30
 
15-20
B48 E
VLDL remnant1 006-1 019
30
30
 
15-20
B100 E
LDL1 006-1 019
50-60
4-8
25
20
B100
HDL1 063-1 21
15-20
2-7
25
45-55
A1 A11

- Lipid trong cơ thể người gồm 3 nhóm chính:
    + Triglyceride (mỡ trung tính).
    + Phospholipid.
    + Cholesterol.

- Dạng Cholesterol tuần hoàn chủ yếu trong cơ thể là Cholesterol ester và Triglycerid đều không tan trong nước. Để tuần hoàn trong môi trường nước Cholesterol kết hợp với Phospholipid và Protein gọi là Lipoprotein. Thành phần Protein của phức hợp này gọi là Apoprotein đóng vai trò quan trọng trong sự tương tác giữa các Lipase trên bề mặt tế bào và các thụ thể Lipoprotein cần thiết cho quá trình dị hóa Lipid.

- Chức năng của Lipoprotein là vân chuyển các loại Lipid đi khắp cơ thể. Triglycerid được sản xuất ở gan từ Glucid và ra khỏi gan dưới dạng VLDL để tới mô mỡ sau khi trao phần lớn Triglycerid cho mô mỡ thì tỷ trọng tăng lên và biến thành IDL rồi LDL gồm đa số là Cholesterol Phospholipid. Sau khi trao Cholesterol cho các tế bào LDL biến thành HDL.

- VLDL và LDL vận chuyển Cholesterol vào tế bào HDL chuyển Cholesterol từ trong tế bào ra ngoài tế bào vì vậy HDL là yếu tố chống vữa xơ động mạch.

III. Phân loại FREDRICKSON về tăng Lipid máu:

Kiểu hình
Lipoprotein gia tăng
Hậu quả
Tính sinh VXĐM
I
ChylomicronsTG rất cao
?
IIa
LDLTăng Cholesterol
+++
IIb
LDL và VLDLTăng Cholesterol và TG
+++
III
IDLTăng Cholesterol và TG
+++
IV
VLDLTăng TG Cholesterol bình thường hay tăng nhẹ
+
V
VLDL và ChylomicronsTG rất cao Cholesterol bình thường hay tăng nhẹ
+

* Triglyceride máu > 150mg/dL: 1 yếu tố của hội chứng chuyển hóa.

IV. Phân loại của ATP về LDL Cholesterol toàn phần và HDL (mg/dL):

1. LDL-c:

- < 100: Tối ưu.
- 100 – 129: Giới hạn tối ưu.
- 130 – 159: Giới hạn cao.
- 160 – 189: Cao.
- >= 190: rất cao.

2. Cholesterol toàn phần:

- < 200: Mong muốn.
- 200 – 239: Giới hạn cao.
- >= 240: Cao.

3. HDL-c:

- < 40: thấp.
- >= 60: cao.

V. Rối loạn chuyển hóa Lipid:

1. Những nguyên nhân chính làm giảm HDL-c:

- Hút thuốc lá.
- Béo phì.
- Ít vận động.
- Steroide và Hormon nam hóa: Andrrogen Progesteron Steroide đồng hóa.
- Thuốc ức chế beta.
- Tăng Triglyceride.
- Yếu tố di truyền.
- Giảm alpha Lipoprotein máu nguyên phát.

2. Tăng Lipid máu:

- Sinh lý: Sau bữa ăn.
- Do huy động: Hầu hết các trường hợp có vai trò của hormon như ưu năng tuyến yên tuyến giáp thượng thận hoặc khi tiêm Adrenalin Corticoid. Còn gặp trong sốt đói tiểu đường…
- Do giảm sử dụng và chuyển hóa: Viêm gan cấp vàng da tắc mật ngộ độc rượu thuốc mê…
- Tăng Lipid máu gia đình: Do một gen trội.

4. Tăng Lipoprotein:

a. Mắc phải:

- Tăng chung: Suy giáp thận hư nhiễm mỡ suy thượng thận chế độ ăn…
- Tăng từng loại:
    + Thiếu Lipoprotein lipase: người già cơ địa vữa xơ tiểu đường.
    + Tăng riêng lẻ các thành phần Lipoprotein:
· Tăng beta-Lipoprotein kèm theo tăng Cholesterol (tăng LDL): Bệnh u vàng (Xanthoma) vữa xơ động mạch.
· Tăng beta-Lipoprotein và tiền beta-Lipoprotein kèm theo tăng Glycerid và Cholesterol (tăng LDL): Bệnh u vàng vữa xơ động mạch.
· Tăng tiền beta-Lipoprotein nhưng giảm alpha và beta-Lipoprotein (tăng LDL và giảm HDL): Bệnh tiểu đường vữa xơ động mạch béo phì.
· Tăng tiền beta-Lipoprotein tăng dưỡng chấp tăng Triglycerid và Cholesterol: bệnh tiểu đường và béo phì.

b. Di truyền: Xem thêm bảng Phân loại FREDRICKSON về tăng Lipid máu ở trên.

Kiểu hình
Tên chung
LP tăng
Lipid tăng
       RL di truyền nguyên phát
I
Tăng LP ngoại sinhChyloM

TG

Giảm hoạt tính Lipase. Thiếu Apoprotein

IIa
Tăng CholesterolLDLCholesterol

Tăng Cholesterol gia đình. Tăng Cholesterol đa gen

IIb
Tăng LP hỗn hợpLDL và VLDLCholesterol và TGTăng LP hỗn hợp có tính chất gia đình
III
Tăng LP RemnantBeta-VLDLTG và CholesterolRối loạn beta-LP có tính gia đình
IV
Tăng LP nội sinhVLDLTGTăng TG gia đình. Tăng LP hỗn hợp. Tăng LP không thường xuyên. Bệnh Tangier
V
Tăng LP hỗn hợpVLDL và ChyloMTG và CholesterolTăng LP trầm trọng. Suy LP-lipase. Thiếu Apoprotein CII gia đình

VI. HƯỚNG DẪN ĐIỀU TRỊ:

       NCEP khuyến cáo tiếp cận bệnh nhân người lớn dựa vào mức LDL-c. Điều trị bắt đầu với điều chỉnh lối sống và chế độ ăn. Nếu không đáp ứng đầy đủ phối hợp thuốc.

1. Các bước điều trị thay đổi lối sống:
Khám lần 1 → 6 tuần → Khám lần 2 → 6 tuần → Khám lần 3 → 6 tuần → Khám lần 4
       ↓                            ↓                              ↓                              ↓
     Bắt đầu                     Đánh giá đáp ứng            Đánh giá đáp ứng           Theo dõi tuân thủ chế
  điều chỉnh                   LDL nếu chưa đạt           LDL nếu chưa đạt          độ điều chỉnh lối sống
    lối sống                     LDL mục tiêu                    LDL mục tiêu xem
                                       tăng cường điều trị          xét phối hợp thuốc
                                       giảm LDL
           ↓                                          ↓                                            ↓
- Giảm ăn mỡ bão       - Tăng cường giảm ăn mỡ      - Khởi đầu điều trị hội chứng
  hòa và Cholesteril.     bão hòa và Cholesterol         chuyển hóa.
- Tập luyện thể           - Xem xét việc thêm chất       - Tăng cường giảm cân
  dục trung bình.            Stanol và Sterol thực vật.     và tập luyện thể chất
- Tham khảo                - Ăn nhiều chất xơ.                 - Tham khảo chuyên gia
 chuyên gia dinh        - Tham khảo chuyên gia          dinh dưỡng.
 dưỡng.                          dinh dưỡng


2. Các nhóm thuốc:

Nhóm thuốc
Cơ chế tác dụng
Tác dụng chuyển hóa
VLDL
LDL
HDL

Nhóm Resin:

Questran (Cholestyramine) Cholestid (Cholestipol)

Gắn với acid mật ngăn cản chu trình gan-ruột của muối mật dẫn đến tăng tổng hợp acid mật trong gan và tăng hoạt tính thụ thể LDL­↑đào thải LDL qua thụ thể LDL 
→↑
 
↓↓↓

Nhóm acid nicotinic:

Niacin Niaspan

Ức chế thủy phân mô mỡ và ↓dòng acid béo tự do vào gan↓tổng hợp VLDL và LDL ↓đào thải HDL 
↓↓↓↓
 
↓↓↓
 
↑↑↑↑

Nhóm Fibrrate:

Fenofibrate (Lipanthyl) Clofibrate (Atromid Slipavlon) Bezafibrate (Bezalip) Gemfibrozil (Lopid) Ciprosibrate (Lipanor)

↑hoạt tính Lipoprotein Lipase  ↓sản xuất VLDL và Apoprotein ở gan ­↑hoạt tính thụ thể LDL.­↑dị hóa VLDL ­↑tổng hợp HDL. 
↓↓↓↓
 
 
↑↑

Nhóm Statin; (HMG-CoA reductase inhibitor):

Simvastatin Travastatin (Zocor) Atorvastatin (Rahor Lipitor) Fluvastatin (Lescol) Lovastatin (Mevacor) Pravastatin (Elisor) Rosuvastatin

Ức chế cạnh tranh trong giai đoạn đầu của quá trình tổng hợp Cholesterol ở gan-ruột bằng cách ức chế enzyme HMG-CoA  ↑hoạt tính thụ thể LDL↑đào thải LDL qua thụ thể LDL.

 
↓↓↓↓
 

3. Điều trị rối loạn Lipid máu nguyên phát:

Pheno-typ
Tên chung
Rối loạn Lipoprotein và Lipid
Ưu tiên 1
Ưu tiên 2
Phối hợp thuốc
I
Tăng LP ngoại sinh↑ChyM và TGKhôngKhôngKhông
IIa
Tăng Cholesterol↑Cholesterol máu gia đình dị hợp tử (↑LDL và Cholesterol)Statin Resin
Nicotinic acid
FibrateResin + Statin
Resin + Fibrate
Statin + Resin
IIb
Tăng LP hỗn hợp

↑Lipid máu gia đình
(tăng LDL VLDL Cholesterol và TG)

Fibrate
Nicotinic acid

StatinStatin +
Nicotinic acid
Statin + Fibrate
Statin + Resin
III
Tăng LP RemnantBệnh thành phần remnant (↑VLDL TG và Cholesterol)

Fibrate
Nicotinic acid

StatinStatin +
Nicotinic acid
Statin + Fibrate
IV
Tăng LP nội sinh­↑Triglyceride gia đình (tăng VLDL TG)

Fibrate
Nicotinic acid

StatinFibrate + Nicotinic acid/Statin
V
Tăng LP hỗn hợp­↑Cholesterol đa gen (tăng VLDL ChyloM TG rất cao và Cholesterol bình thường hay tăng nhẹ)Resin StatinFibrate 

4. Một số ứng dụng điều trị:

- Điều trị rối loạn Lipid ở trẻ em:

  1. Dinh dưỡng: Ăn mhiều rau trái cây.
  2. Cholestyramine (Questran) Cholestipol (Cholestid).
  3. Pravastatin: FDA đồng ý cho sử dụng ở trẻ em.
  4. Ezetimibe.

- Tăng Cholesterol toàn phần tăng LDL-c Triglycerid bình thường:

    1.   Statin.
    2.   Statin + chất ngưng kết mật.
    3.   Statin + acid nicotinic.
    4.   Statin + Ezetimibe.

- Tăng Triglycerid rất cao > 500mg/dL:

    1.   Giảm cân tăng vận động ít mỡ.
    2.   Fenofibrate hoặc Gemfibrozil liều cao (mục tiêu phòng viêm tụy cấp).

VII. TIÊN LƯỢNG VÀ BIẾN CHỨNG:

- Suy tim.
- Nhồi máu cơ tim.
- Đột tử do phình động mạch bóc tách.
- Thiếu máu não tai biến mạch máu não.
- Giảm thị lực.
- Xơ thận suy thận.
- Hoại tử chi do tắt mạch máu.
- Thủng dạ dày – tá tràng hoại tử ruột viêm tụy.
- Tiểu đường.

* Bài này chỉ có tính chất tham khảo không thể thay thế cho BS điều trị của bạn. Không tự ý chẩn đoán và điều trị. Mọi vấn đề có liên quan đến sức khỏe phải tham khảo với BS điều trị.
—–&—–

Từ viết tắt:

NCEP: Natinal Cholesterol Education Program.
ATP III: Aldult Treatment Panel III.
VLDL-c: Very Low Density Lipoprotein cholesterol.
LDL-c: Low Density Lipoprotein cholesterol.
HDL-c: High Density Lipoprotein cholesterol.
IDL-c: Intermediate Density Lipoprotein cholesterol (VLDL remnant).
TG: Triglycerid.
HMG-CoA: Hydroxylmethylglutamin-Coenzyme A.
FFA: Free Fat Acide – acid béo tự do.
NEFA: Non-EsterifiedÈat acide – Acid béo không ester hóa.
LP: Lipoprotein.
ChyloM: Chylomicron.
VXĐM: Vỡ xơ động mạch.

Tài liệu tham khảo

  1. PGS. TS. Phạm Nguyễn Vinh – Điều trị rối loạn Lipid máu: Chiến lược điều trị sau NCEP-ATP III (Treatment of Dyslipidemia Strategic Management after the NCEP-ATP III guidelines) Báo cáo chuyên đề.
  2. PGS. TS Nguyễn Phú Kháng – Vữa xơ động mạch Lâm sàng Tim Mạch tr. 488-502 NXB Y học 2001.
  3. GS. Đặng Vạn Phước – Hướng dẫn điều trị rối loạn Lipid máu tài liệu chuyên đề.
  4. Rối loạn Lipid máu – Thời sự chẩn đoán và điều trị bệnh tim Vol. 1 tr. 21-40 NXB Y học 2005.
  5. Rối loạn chuyển hóa Lipid máu – Sinh lý bệnh họỏct. 81-94 Nhà Xuất bản Y học 2002.
  6. Henry N. Ginsberg Ira J. Goldberg – Disorder of Lipoprotein Metabolism Harrison’s Principles of Internal Medicine 15th Edition (CD Disk).

—–¯—–

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