Dyslipidemia

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Dyslipidemia

• Dr FCJ Bester
• 082 5542 799
• www.bestgib.co.za

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Hoofgedagtes

• Hipercholesterolemie is skadelik
• Cholesterol word nie getoets
• Hipercholesterolemie word onderbehandel.
• DIE BEHANDELINGSGAPING

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Many High-Risk Patients Are Not Reaching NCEP
LDL-C Goals
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7

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63 of patients with ?2 risk factors and no CHD
did not reach NCEP goal
82 of CHD patients did not reach NCEP goal
Data from a survey of 901 primary care providers
in the USA. Data were collected from 4888
patients being treated for hypercholesterolemia. P
earson T et al. Arch Int Med 1999In press.
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Small Increases in Cholesterol Lead to Dramatic
Increases in CAD Death

• (Adapted from Neaton et al.)

Neaton JD et al, Arch Intern Med, 1992.
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Indeling van Lipoproteiene
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Siektes van Dislipiedemie

• Hipercholesterolemie
• Familieel (heterosigote, Homosigote)
• Defektiewe ApoB100
• Poligenies
• Hipertrigliseriedemie
• Familieel
• LPL tekort
• Apo CII tekort

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Siektes (vervolg)

• Kombinasie van TG en Cholesterol
• Gemengde hiperlipiedemie
• Disbetalipoproteienemie

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Sekondêre dislipiedemie

• Diabetes
• Hipotireose
• Niersiektes - nefrose
• Alkohol
• Lewersiektes

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Endoteel disfunksie

• LDL, HTS, DM, rook
• Verhoogde deurlatendheid
• Adhesie molekules
• WBT en plaatjies
• migrasie
• vashegting

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Vetterige streep

• Gladde spier migrasie
• Skuimselle
• T-sel aktivering
• Plaatjie vashegting
• Leukosiet vashegting

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Gevorderde gekompliseerde letsel

• Makrofaag akkumulasie
• Nekrotiese kern
• Fibrotiese kap

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Plaak ruptuur (disaster)

• Verdunning van fibreuse kap
• Bloeding in letsel
• Trombose met afsluiting van lumen

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Navorsing

• POSH (Ileale omleiding)
• FATS (Lovastatien, Niasien)
• EXCEL (Lovastatien)
• MAAS (Simvastatien)
• 4S (Simvastatien)
• PLAC I EN II (Pravastatien)
• WOSCOPS (Pravastatien)
• REGRESS (Pravastatien)
• CARE(Pravastatien)

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Belangrike syfers
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Behandelings modaliteite

• Lewensstyl veranderinge
• Dieet
• Medikasie
• Galsoutbinders
• Nikotiensuur
• Fibrate
• Statiene -gt superstatiene
• Selektiewe cholesterol opname inhibeerders
• Aferese

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Dieet

• Gemiddelde westerse dieet
• 400-500 mg cholesterol per dag
• 35 kalorie van vet
• Stap 1 dieet (AHA)
• lt 300 mg cholesterol per dag
• 30 kalorie van vet
• Stap 2 dieet (AHA)
• lt200 mg Cholesterol

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Geskiedenis van cholesterolRx

• 1988 NCEP ATP I
• Eksklusiewe fokus op op LDL-C verlaging
• Sterk klem op harse en niasien
• Statiene en fibrate nie eerste linie nie
• 1993 NCEP ATP II
• Risiko faktore belangrik in teiken waardes
• Teiken LDL vir CHD verminder na 2,5 mmol/l
• Statiene die major middel, fibrate vir gemengde
  HPL

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Geskiedenis van Cholesterol Rx

• NCEP ATP III - 2001
• Verlaag die drempel vir terapie in hoe risiko
  persone
• LDL-C teiken reduksie na 2,5 mmol/l ook vir CHD
  ekwivalentes
• Non HDL-C as n teiken (IDL ook ingesluit)

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Medikasie

• Nikotiensuur
• 1-2.5 g tds
• Slegte newe effekte
• Galsoutbinders
• Questran 9g tds
• Veral gebruik in kombinasie terapie.

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Medikasie - Fibrate

• Verhoogde LPL en TG hidrolise
• Verhoogde LDL afbraak
• Fibrate
• Klofibraat (Atromid S, Lipaten)
• Bezafibraat (Bezalip, Rolab-bezafibraat)
• Fenofibraat (Lipsin)
• Gemfibrocil (Lopid)

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Statiene (HMG-KoA reduktase inhibitor)

• Simvastatien (Zocor)
• Pravastatien (Prava)
• Fluvastatien
• Atorvastatien (Lipitor)
• Lovastatien (Lescol)
• Cerivastatien (Baycol - onttrek)

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Statiene - newe effekte

• Mialgie
• Miositis - selde
• Spiernekrose - in kombinasie met fibrate
• Leweraantasting - staak by verhoogde
  lewerensieme.

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LDL aksievlakke
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NCEP Guidelines for LDL-C

• CHD status LDL-C goal
• No CHD and lt160 mg/dL (4.1 mmol/L) lt2 CHD risk
  factors
• No CHD and lt130 mg/dL (3.4 mmol/L) ?2 CHD risk
  factors
• Established CHD ?100 mg/dL (2.6 mmol/L)

The NCEP recommends lowering LDL-C even further
than these goals if possible
NCEP. Circulation 19948913291445.
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Teikenwaardes
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Joint European Recommendations on Coronary
Prevention

• Lipoprotein marker Goal of therapy
• LDL-C lt3.0 mmol/L (115 mg/dL)
• Total-C lt5.0 mmol/L (190 mg/dL)

Wood D et al. Eur Heart J 19981914341503.
Atherosclerosis 1998140199270. J Hypertens
19981614071414.
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Risikofaktore vir IHS
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The Undertreatment of Hypercholesterolemia is
Widespread

• Undertreatment is emerging as a major problem in
  the management of hypercholesterolemia
• Data from Europe and the USA consistently show
  that a large proportion of patients do not reach
  their LDL-C goal
• Of particular concern is that the problem is
  greatest in patients with existing CHD

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Total-C Levels in CHD Patients Receiving
Lipid-Lowering Therapy
gt6.5(gt250)
gt5.5(gt215)
gt4.5(gt175)
At the time of the study EAS recommended a
Total-C goal of 4.55 mmol/L for patients with
existing CHD. EUROASPIRE Study Group. Eur Heart J
19971815691582.
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Reasons for the Current Under-Use of Treatment
Guidelines

• Lack of awareness of current guidelines
• Difficulty in extrapolating clinical trial data
  to complex patients in practice
• Disagreement with guidelines due to
• lack of involvement in the consensus process
• lack of opportunity to evaluate and adapt
  guidelines critically to local practice
• Mixed messages resulting from multiple sets of
  guidelines