Hyperlipidemia

General Principles

• • Plasma lipids are transported by lipoprotein molecules composed of proteins called aplipoproteins, and phospholipids, cholesterol esters, and triglycerides.

  • 5 major classes of human plasma lipoproteins based on their density:

    • Chylomicrons (least dense)

    • VLDLs

    • IDLs

    • LDLs

    • HDLs

    • Lp(a) a sixth class. Looks like LDL, and behaves somwhere inbetween LDL and HDL.

History: 

• • Risk factors for CAD: Nearly 90% of patients with coronary heart disease (CHD) have some form of dyslipidemia. Increased levels of LDL, Lp(a), remanant lipoproteins, decreased level of HDL have been associated with premature vascular disease. Other risk factors that should be investigated in history:

    • HTN

    • DM

    • obesity, BMI: 30 or above

    • dyslipidemia, HDL <40 (HDL >60 is protective), elevated LDL >130

    • physical inactivity

    • cigarette smoking

    • microalbuminuria (urine albumin/cr ratio of 30 - 300 mg/g), GFR: 60 ml/min or less, renal insufficiency (Sr. Cr 1.5 or more)

    • age: >45 in males, and >55 in females.

    • If FH/o of CVD is positive in males relatives: <55 yrs and female relatives: <65 years

    • Carotid artery disease, PAD, AAA

    • hyperhomocystinemia, high CRP and circulating fibrinogen.

  • Individuals with hyperlipidemia should be evaluated for potential secondary causes: Hypothyroidism, DM, obstructive liver disease, chronic renal disease or nephrotic syndrome, or medications such as estrogens, progestins, anabolic steroids, and corticosteroids.

Dx:

• • Obtain fasting TC, LDL, HDL, and TG. Obtained after a 12 hour fast.

  • If fasting is not possible, do total and HDL cholesterol. If these come back as total chol >200 mg/dL or above, or HDL-C is <40 mg/dL or lower, check for fasting lipids.

  • According to USPSTF and ACP:

    • Screening in men 35  years or above without any risk factors for CAD 

    • Screening in women 45 years or above without any risk factors for CAD

    • Adults 20 years or older who have normal fasting lipids and no risk factors for CAD should have screening done at least once every five years (NCEP-ATP III).

    • Patients who have been hospitalized for an ACS or coronary revascularization should have a lipid panel obtained within 24 hours of admission if lipid levels are unknown.

    • Insufficient evidence exists to screen patients >65 years of age unless there are multiple cardiovascular risk factors present.

DDx:

Table: Three categories of risk that modify LDL cholesterol goals

Metabolic syndrome

3/5 criteria must be met.

• Waist circumference greater than or equal to 102 cm in men and greater than or equal to 88 cm in women

• Triglycerides greater than or equal to 150 mg/dL

• HDL-C less than or equal to 40 mg/dL in women and less than or equal to 50 mg/dL in men

• Blood pressure greater than or equal to 130/85 mm Hg

• Fasting glucose greater than or equal to 100 mg/d

The effect of the metabolic syndrome on stroke risk is greater among women than men and greater among

Hispanics than African Americans and whites.

Familial hypercholesterolemia (FH): 

• • Autosomal dominant

    • Due to mutations of the LDL receptor that leads to defective uptake and degradation of LDL

  • Total cholesterol >300 mg/dL, LDL >250 mg/dL 

  • The homozygous form which is rare can have total cholesterol >600 mg/dL, and LDL >550 mg/dL

  • Premature CAD, tendon xanthomas, xanthelasmata, premature arcus conrneae

Familial combined hyperlipidemia (FCH): 

• • Autosomal dominant

    • Genetic and metabolic defects are not known

  • High levels of VLDL, LDL, or both

  • LDL apo B-100 level >130 mg/dL

  • Premature CAD, no tendon xanthomas