DISLIPEMIAS UN FACTOR DE RIESGO SIEMPRE VIGENTE

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DISLIPEMIASUN FACTOR DE RIESGO SIEMPRE VIGENTE
Dr Marcos Baroni Dpto de Prevención Cardiovascular (Instituto Modelo de Cardiología Córdoba)
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INTERHEART Risk of AMI Associated With Risk Factors

Risk Factors Control () Cases () OR (99 CI)Adjusted forAge, Sex,and Smoking OR (99 CI)Adjusted forAll OtherRisk Factors
Apo B/ Apo A 20 33.5 3.87 (3.39 -4.42) 3.25 (2.82 3.76)
Current smoking 26.8 45.2 2.95 (2.72 -3.20) 2.87 (2.58-3.19)
Diabetes 7.5 18.5 3.08 (2.77-3.72) 2.37 (2.07-2.71)
Hypertension 21.9 39.0 2.48 (2.30-2.68) 1.91 (1.74-2.10)
Abdominal obesity (3 vs 1) 33.3 46.3 2.22 (2.03-2.42) 1.62 (1.45-1.80)
Lancet. 2004364937-952 Lancet. 2004364937-952 Lancet. 2004364937-952 Lancet. 2004364937-952 Lancet. 2004364937-952
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LDL cholesterol

• Strongly associated with atherosclerosis and CVD
  events
• 10 increase results in an approximate 20
  increase in CHD risk
• Most of the cholesterol in plasma is found in LDL
  particles
• Smaller denser LDL are more atherogenic than
  larger, less dense particles
• Risk associated with LDL-C is increased by other
  risk factorslow HDL
• smoking
• hypertension
• diabetes

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                          Incidence of
recurrent MI
                          Incidence of
recurrent MI
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HDL cholesterol

• HDL-C has a protective effect for risk of
  atherosclerosis and CHD
• Epidemiological studies show the lower the HDL-C
  level, the higher the risk for atherosclerosis
  and CHD
• low level (lt40 mg/dL, 1 mmol/L) increases risk
• HDL-C tends to be low when triglycerides are high
• HDL-C is lowered by smoking, obesity and physical
  inactivity

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Rol de la apolipoproteínas de las HDL en la
remoción de las LDL oxidadas

• Transferencia CETP de las LDL oxidada a las HDL
• Las LDL oxidadas son reducidas por las
  apolipoproteínas de las HDL
• Hígado capta los lípidos reducidos por las HDL
  más rápidamente que las LDL

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Low HDL-C is an IndependentPredictor of CHD Risk
even when LDL-C is Low
Risk of CHD
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65
85 mg/l
HDL-C
100 mg/l
160 mg/l
220 mg/l
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COLESTEROL HDL
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Factores Modificadores de las HDL

• Efectos Antiinflamatorios
• Apo A1 mimetizada
• Ejercicio
• Dieta baja en grasas
• Grasas Poliinsaturadas
• Estatinas

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Factores Modificadores de las HDL

• Efectos Proinflamatorios
• Ateroesclerosis coronaria
• DBT
• Hemodiálisis
• Grasas saturadas
• Infecciones
• Artritis Reumatoidea
• Cirugías
• LES

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Por Qué Pro inflamatorias?

• Disminución Apo A1
• Daño de Apo A1 por la mieloperoxidasa
• Inflamación asociada a estrés oxidativo
• (puede llevar a la alteración y reducción de las
  enzimas antioxidantes)

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Nuevos Tests evaluando función HDL

• Determinación Quimiotaxis de Monocitos
• Moléculas de Adhesión
• Estimulación por el Cobre
• ( todos en fase experimental)

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CETP
                                                                                                                                                          
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ILLUMINATE Major results
HDL (mg/dl) 3 meses Torcetrabip Radio para muerte CV
lt 60 1.00
60 - 70 0.67
71 - 80 0.47
81 - 93 0.57
gt 93 0.43
N Engl J Med 20073561304-1316
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ILLUMINATE Major results
End point Atorvastatin (n 7534) Atorvatatin Torcetrabip (n7533) Hazard Ratio (95 CI) P
Eventos Mayores 373 464 1.25 (1.09- 1.44) 0.001
Muertes 59 93 1.58 (1.14 2.19) 0.006
N Engl J Med 20073561304-1316
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Riesgo de EC segun Trigliceridos( Framingham
Heart Study)
N5127
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Hipertrigliceridemia HDL bajo

• Es usual en síndrome metabólico
• Es un patrón muy común en aterosclerosis temprana
• Asociada a la tríada de ?ILDL y VLDL con LDL
  pequeña-densa
• Tríada lipídica dislipidemia aterogénica

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TRIGLICERIDOS POSPRANDIALES FACTOR DE RIESGO CV
La trigliceridemia posprandial (2 hs.)es un FR
independiente para aterosclerosis temprana
Enfermedad coronaria Enfermedad carotídea (IMT)
Boquist S et al. Circulation 17723,1999

• Aumento de triglicéridos posprandiales causan
  disfunción endotelial.
• El bloqueo del SRA (IECA y Ant. At1) previenen
  esta disfunción

Wilmink HW et al. JACC 34140,1999
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TRIGLICÉRIDOS Y GLUCOSA POST PRANDIALES
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Dislipemia en el Síndrome Metabólico
Hipertrigliceridemia por sobreproducción de VLDL Disminución de las HDL Cambios cualitativos de las LDL
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COLESTEROL NO HDL
COLESTEROL NO HDL COL TOTAL COL HDL
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Therapeutic Targets for Low-Density Lipoprotein
(LDL) Cholesterol and Non-High-Density
Lipoprotein (non-HDL) Cholesterol as Recommended
by the National Cholesterol Education Program
Adult Treatment Panel III
Risk Level LDL Cholesterol Goal Non-HDL Cholesterol Goal
CHD and CHD risk equivalents lt100 mg/dL lt130 mg/dL
Multiple (2) risk factors (10-year CHD risk lt/20) lt130 mg/dL lt160 mg/dL
0-1 Risk factor lt160 mg/dL lt190 mg/dL

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Effect of lipid-modifying therapies on lipids
Therapy Bile acid sequestrants Nicotinic acid
Fibrates Probucol Statins Ezetimibe
TC Down 20 Down 25 Down 15 Down
25 Down 1937 -
LDL Down 1530 Down 25 Down 515 Down
1015 Down 2550 Down 18
HDL Up 35 Up 1530 Up 20 Down 2030
Up 412 Up 1
TG Neutral or up Down 2050 Down
2050 Neutral Down 14-29 Down 8
Patient tolerability Poor Poor
to reasonable Good Reasonable Good Good
TCtotal cholesterol, LDLlow density
lipoprotein, HDLhigh density lipoprotein,
TGtriglyceride. Daily dose of 40 mg of
atorvastatin, simvastatin, pravastatin and
fluvastatin.
Yeshurun D, Gotto AM. Southern Med J
199588(4)379391. Knopp RH. N Engl J Med
1999341498511. Product Prescribing
Information. Gupta EK, Ito MK. Heart Dis
20024399-409. ,
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NCEP ATP III LDL-C Goal (2004 proposed
modifications)
Therapeutic option 70 mg/dL 1.8 mmol/L 100
mg/dL 2.6 mmol/L 130 mg/dL 3.4 mmol/L 160
mg/dL 4.1 mmol/L
Grundy SM et al. Circulation 2004110227-239.
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ESTATINAS ? ? HMG CoA reductasa ? ?Niveles intrahepatocitarios de colesterol ? ? Expresión del receptor de LDL ? ?LDL circulante ? ? Colesterol Plasmático
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Efecto Adverso Efecto
General Pérdida de apetito, pérdida de peso
Piel Rásh cutáneo
Sistema Nervioso Pérdida de concentración, cefalea
Gastrointestinal Dolor abdominal, naúseas, diarrea
Hígado Hepatitis, aumento de transaminasas
Músculos Dolor muscular, ? CPK , miositis, rabdomiólisis
Sistema Inmune Síndrome simil lupus
Unión Proteica Disminución de unión a proteínas de warfarina
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Is Lower Better? Relationship between LDL-C and
CV Event Rate
                                                                                                                                                          
                          Cholesterol balance
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Is Lower Better? Relationship between LDL-C and
CV Event Rate
Ballantyne CM et al. Am J Cardiol 1998823Q12Q.
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The Anglo-Scandinavian Cardiac Outcomes Trial Lipid Lowering Arm Extended Observations 2 Years After Trial

Eur Heart J.  200829(4)499-508.  2008 
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Qué Podemos Hacer con las HDL?

• Considerar que los pacientes con disminución de
  HDL tienen riesgo incrementado para enfermedad
  cardiovascular
• Conocer que las enfermedades crónicas alteran la
  calidad de las HDL (proinflamatorias) aumentando
  el riesgo CV (a pesar de valores elevados de HDL)
• El uso de estatinas, fibratos, niacinas y medidas
  no farmacológicas pueden reducir el riesgo CV
• Anacetrapib ???

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FIBRATOS

• Modo de Acción
• ? actividad de lipoprotein lipasa (lipolisis de
  trigliceridos, ? clearance)
• ? lipolisis en el tejido adiposo, ? liberación
  AGL
• ? secrecion de VLDL por el hígado
• ? captación de AGL por el hígado
• ? HDL moderadamente

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FIBRATOS

• Efectos Adversos
• Cálculos Biliares (disconfort epigástrico,
  intolerancia a CCK, meteorismo)
• Usar con precaución en ptes c/ patolog biliar,
  mujeres, obesos
• Miopatia (injuria muscular)
• Debilidad, o dolor muscular inusual
• Puede aumentar risgo de miopatia inducida por
  estatinas cuando se usan conjuntamente
  (rabdomiolisis ha ocurrido raramente)
• Desplaza warfarina y ciclosporina de la albúmina
• plasmática. Necesidad de disminuir dosis de
  warfarina. Chequear RIN

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TERAPEÚTICA INSUFICIENTE ??
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FISH OILS AND STATINS

• Marine fish oil rich in omega 3 fatty acids lower
  trigliceride levels and may be effective in
  combination with statins to treat patients with
  combined hyperlipidemia
• Fish oils plus statin may often be an alternative
  to fibrate plus statin
• Fish oils may have other cardiovascular effects
  complementary to those of statins, such as
• - Reduction in malignant ventricular
  dysrithmias
• - Antithrombotic effects
• - Improved endothelial reactivity
  /relaxation
• - Antiinflammatory effects
• Bays HE et al Expert Opin Pharmacother 2003 -4
  -1901 -1938
• Kris Etherton Circulation 2002 106 -2747 -
  2757

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PPAR- y AGONIST AND STATINS

• Statins are commonly used to reduce CHD risk in
  patients
• with type 2 diabetes and the metabolic
  syndrome
• PPAR y agonist, improved glucose control and may
  have lipid effects complementary to those of
  statins
• LDL particle size may be increased with PPAR y
• Trigliceride levels are decreased with PPAR y
• HDL are increased with PPAR y
• The metabolic effects of PPAR y agonist may be
  complementary to the lipid effects of statins in
  patients with type 2 diabetes and metabolic
  syndrome
• 
  Bays HE- Brithis Journal of
  Diabetes and Vascular Disease 2003 -3 356-360
• insberg
  HN Am J of Cardiol 2003 91 29E-39E

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Benefits of Intensive Lifestyle Changes on TG
Levels
Benefits of Intensive Lifestyle Changes on TG
Levels
Benefits of Intensive Lifestyle Changes on TG
Levels
180

• Within DPP, TG levels fell significantly more
  in the group with intensive lifestyle
  intervention than in the metformin group
• Aimed to reduce weight by 7 with a low-fat diet
• 150 minutes of moderate exercise per week

Baseline
180

• Within DPP, TG levels fell significantly more
  in the group with intensive lifestyle
  intervention than in the metformin group
• Aimed to reduce weight by 7 with a low-fat diet
• 150 minutes of moderate exercise per week

Year 1
Year 2
Year 3
160
160
160
160
TG (mg/dL)
140
140
TG (mg/dL)
140
120
120
100
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Lifestyle
DPPDiabetes Prevention Program.
Lifestyle
National Institute of Diabetes Digestive
Kidney Diseases of the NIH. Accessed at
http//www.niddk.nih.gov/welcome/releases/8_8_01.h
tm.Ratner R et al. Diabetes Care.
200528888-894.
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ACTIVIDAD FISICA AEROBICA
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MUCHAS GRACIAS