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DYSLIPIDEMIAS: TYPES I-V. Thomas F. Whayne, Jr, MD, PhD, FACC Professor of Medicine (Cardiology) University of Kentucky March 2011. E-Mail: twhayn0@uky.edu . No conflicts to declare. THE MAJOR LIPOPROTEINS. CHYLOMICRONS. VERY LOW DENS. LIPOPROT. (VLDL).

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dyslipidemias types i v
DYSLIPIDEMIAS:TYPES I-V

Thomas F. Whayne, Jr, MD, PhD, FACC

Professor of Medicine (Cardiology)

University of Kentucky

March 2011.

E-Mail: twhayn0@uky.edu.

No conflicts to declare.

the major lipoproteins
THE MAJOR LIPOPROTEINS
  • CHYLOMICRONS.
  • VERY LOW DENS. LIPOPROT. (VLDL).
  • LOW DENS. LIPOPROT. (LDL) .
  • HIGH DENS. LIPOPROT. (HDL) .
slide4

Type I

Type IIA

Type IIB

Type III

Type IV

Type V

Normal

slide7

Before UC

After UC

VLDL

Tube Plain

LDL

HDL

slide8

VLDL

Tube with KB

LDL

HDL

type i
TYPE I
  • RARE GENETIC DISORDER.
  • HYPERCHYLOMICRONEMIA.
  • LIPOPROTEIN LIPASE DEFICIENCY.
type i treatment
TYPE I: TREATMENT
  • RESTRICTION OF FATS.
  • PANCREATITIS: NPO.
  • MEDIUM CHAIN FATTY ACID TRIGLYCERIDES.
type ii a hyperlipoproteinemia
TYPE II-A HYPERLIPOPROTEINEMIA

AUTOSOMAL DOMINANT.

  • HETEROZYGOTES: 1 IN 500.
  • HOMOZYGOTES: 1 IN 1,000,000.
type ii a is also
TYPE II-A IS ALSO:
  • POLYGENIC.
  • SPORADIC.
  • POSSIBLY ACQUIRED
type ii a
TYPE II-A
  • ACCELERATED ATHEROSCLEROSIS, ESPECIALLY CORONARY.
  • TENDON XANTHOMAS.
  • TUBEROUS XANTHOMAS.
  • XANTHELASMA.
  • CORNEAL ARCUS.
type ii b
TYPE II-B

ACCELERATED ATHEROSCLEROSIS: CORONARY AND PERIPHERAL

types iia iib treatment
TYPES IIA/IIB: TREATMENT
  • STATINS ESPECIALLY.
  • BILE ACID BINDING RESINS, ESPECIALLY COLESEVELAM.
  • NICOTINIC ACID (NIASPAN®).
  • ZETIA.
  • POLICOSANOL.
  • LDL APHERESIS.
type iii
TYPE III
  • ACCELERATED ATHEROSCLEROSIS, ESPECIALLY PERIPHERAL.
  • PALMAR XANTHOMAS.
  • TUBEROUS XANTHOMAS.
type iii1
TYPE III

APO E IN LIVER RECEPTORS IS ABNORMAL OR DEFICIENT FOR:

  • LOW DENS. LIPOPROTEINS (LDL).
  • INTERMED. DENS. LIPOPROTEINS (IDL).
  • CHYLOMICRON REMNANTS.
type iii treatment
TYPE III TREATMENT
  • LOW CHOLESTEROL UNSATURATED FAT DIET.
  • SOME CARBOHYDRATE (SIMPLE SUGARS) RESTRICTION.
  • CLOFIBRATE (ATROMID).
  • GEMFIBROZIL (LOPID).
  • FENOFIBRATE (TRICOR).
  • STATIN.
type iv hyperlipoproteinemia
TYPE IV HYPERLIPOPROTEINEMIA
  • ALSO CALLED FAMILIAL HYPERTRIGLYCERIDEMIA.
  • ACCELERATED ATHEROSCLEROSIS, ESPECIALLY PERIPHERAL.
type iv treatment
TYPE IV: TREATMENT
  • FENOFIBRATE.
  • NICOTINIC ACID (NIASPAN®).
  • OMEGA FATTY ACIDS (LOVAZA®).
  • METFORMIN.
  • PIOGLITAZONE.
  • STATINS.
  • EZETIMIBE.
  • INSULIN.
type v
TYPE V
  • INCREASED CHYLOMICRONS AND VLDL.
  • CAN BE RARE GENETIC DISORDER.
  • CAN BE MORE FREQUENTLY SEEN IN DIABETES, EVEN WITH MILD INCREASE IN PLASMA GLUCOSE.
type v treatment
TYPE V: TREATMENT
  • CONTROL DIABETES.
  • FENOFIBRATE.
  • NICOTINIC ACID (NIASPAN®).
  • OMEGA FATTY ACIDS (LOVAZA®).
  • METFORMIN.
  • PIOGLITAZONE.
  • INSULIN.
dyslilpidemia in diabetes typical pattern
DYSLILPIDEMIA IN DIABETES:TYPICAL PATTERN
  • HIGH LEVELS OF TRIGLYCERIDES.
  • LOW LEVELS OF HDL.
  • PREPONDERANCE OF SMALL DENSE LDL.
small dense ldl
SMALL, DENSE LDL
  • ASSOCIATED WITH 3X  RISK OF CHD.
  • INCREASED ATHEROGENICITY:
    • FASTER ENTRY INTO BLD. VESSEL WALL.
    •  BINDING TO LDL RECEPTOR.
    • INCREASED SUSCEPTIBILITY TO OXIDATION.
triglycerides in diabetes
TRIGLYCERIDES IN DIABETES
  • HIGH TRIGLYCERIDE LEVELS OCCUR MAINLY IN VLDL BUT ALSO IN CHYLOMICRONS.
  • ELEVATED TRIGLYCERIDE LEVELS RESULT FROM:
    • OVERPRODUCTION OF VLDL.
    • IMPAIRED LIPOLYSIS OF TRIGLYCERIDES (INSULIN IS AN LPL COFACTOR).
ada rationale for rx of dyslipidemia in diabetes
ADA RATIONALE FOR Rx OF DYSLIPIDEMIA IN DIABETES
  • THERE IS  RISK OF CHD BECAUSE OF DYSLIPIDEMIA.
  • DIABETIC DYSLIPIDEMIA FREQUENTLY CHARACTERIZED BY  TRIGLYCERIDES,  HDL AND  SMALL, DENSE LDL.
  • Rx OF DIABETIC DYSLIPIDEMIA MAY REDUCE RISK OF CHD.
improved control of hyperglycemia
IMPROVED CONTROL OF HYPERGLYCEMIA
  • CAN REDUCE DYSLIPIDEMIA.
  • MAY RESULT IN  ATHEROGENIC DENSE LDL.
  • COMPLETE REVERSAL OF DYSLIPIDEMIA USUALLY NOT ACHIEVABLE.
response of dense ldl to medication
RESPONSE OF DENSE LDL TO MEDICATION
  • FIBRATES AND NICOTINIC ACID (NIASPAN®) SHIFT THESE DENSE LDL TO A LARGER SIZE LDL PARTICLE.
  • STATINS ARE NOT EFFECTIVE IN FAVORABLE SHIFT OF DENSE LDL TO LARGER, LESS DENSE LDL PARTICLE.
syndrome x metabolic syndrome or cardiovascular dysmetabolic syndrome
Syndrome X, Metabolic Syndrome or Cardiovascular Dysmetabolic Syndrome
  • Obesity.
  • Hypertriglyceridemia.
  • Low HDL.
  • Increased Dense LDL.
  • Hypertension.
  • Insulin Resistance.
  • Hyperuricemia.
  • Increased PAI-1.
slide44

METABOLIC SYNDROME, SYNDROME X

or CV DYSMETABOLIC SYNDROME

AT LEAST 3 OF THE FOLLOWING 5 PRESENT†:

TG  150 mg/dl.

HDL < 40 mg/dl in men and < 50 mg/dl in women .

BP  130/85 mm/Hg.

Waist girth > 102 cm (men) and > 88 cm (women).

Fasting glucose  100 mg/dl.

OTHER COMPONENTS:

 dense LDL, Insulin resistance, Hyperuricemia,  PAI-1,  hsCRP,  Tissue necrosis factor-α Interleukin-6,  Resistin, and  Adiponectin.

†Grundy SM, et al. Circulation 2005;112:2735-2752.

metabolic syndrome prevalence increases with age
Metabolic Syndrome: Prevalence Increases with Age

47 million or 23% of US adults have the metabolic syndrome

Adapted from: Ford ES, et al. JAMA2002;287:356-359.

thiazides
Thiazides:
  • Marked elevation of triglycerides and VLDL can occur.
  • Increased total cholesterol and LDL.
  • Little effect on HDL.
estrogen
ESTROGEN

SPORADICALLY AND UNPREDICTABLY, ESTROGEN MAY CAUSE A MARKED ELEVATION IN TRIGLYCERIDES.

beta blockers
BETA BLOCKERS
  • Increase triglycerides and VLDL.
  • Decrease HDL.
  • Less significant increase in Total Cholesterol and LDL.
  • Beta Blockers with ISA may have a less pronounced effect.
conclusion
CONCLUSION

MULTIPLE APPROACHES AVAILABLE TO ACHIEVE GOOD BLOOD LIPID CONTROL AND THEREBY AVOID MULTIPLE CLINICAL PROBLEMS INCLUDING SEQUELAE OF CORONARY ATHEROSCLEROSIS.