dyslipidemia
DYSLIPIDEMIA
Dyslipidemia is having an abnormal amount of lipids or fats in the blood.
Lipid profile is obtained from an individual with diabetes mellitus, coronary heart disease, cerebrovascular disease, peripheral arterial disease or other coronary heart disease risk factors or from an individual with family history or clinical evidence of familial hypercholesterolemia.
Plasma lipids are total cholesterol, high-density lipoprotein cholesterol, trigylcerides, and low-density lipoprotein cholesterol.
Evaluation of lipid profile must be performed in parallel with the risk assessment of coronary heart disease.
  • Lipid profile is obtained from an individual with diabetes mellitus (DM), cardiovascular disease (CVD), cerebrovascular disease, or other CVD risk factor(s) or from an individual with family history or clinical evidence of familial hypercholesterolemia
    • Cardiovascular diseases include coronary heart disease (CHD), myocardial infarction (MI), coronary insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack, peripheral artery disease (PAD), and heart failure

Measure Plasma Lipids

  • Total cholesterol (TC)
  • High-density lipoprotein cholesterol (HDL-C)
  • Triglycerides (TG)
  • Low-density lipoprotein cholesterol (LDL-C) is derived by Friedewald formula: LDL-C (mmol/L) = TC - HDL-C - [TG/2.2] or LDL-C (mg/dL) = TC - HDL-C - [TG/5 ]

Considerations

  • TC and HDL-C can be measured accurately at any time of the day
    • Triglycerides (TG) and estimated LDL-C levels must be obtained after 10-12 hours of fasting
    • TG levels are influenced by alcohol intake within 24 hours prior to measurement and by smoking during the fasting state
  • Friedewald formula can only be used if TG <4.5 mmol/L (<400 mg/dL) but is only recommended for use during fasting states
  • In patients with TG >4.5 mmol/L (400 mg/dL), non HDL-C should be the alternative primary target of treatment
  • If TG is >2.3 mmol/L (200 mg/dL), non HDL-C is a better indicator of total atherogenic burden
  • Plasma measurement of cholesterol is 3% lower than serum measurements
  • Levels will be affected by recent acute illness (eg fever, surgery, stroke) and drugs (eg beta-blockers, steroids, thiazides)
  • Cholesterol level is low 24 hours-3 months after MI 
    • If possible, measure lipids within 24 hours of myocardial infarction
  • ≥1 measurement is needed to make hyperlipidemic diagnosis because of biological variability

Dyslipidemia Screening

  • More frequent assessments are needed for all patients with coronary artery disease (CAD) risk factors and those with a family history of premature CAD (definite MI or sudden death prior to age 55 years in father or other male 1st-degree relative, or before age 65 years in mother or other female 1st-degree relative)
  • Women should be screened in the same way as men

Young Adults (Men 20-45 years of age; Women 20-55 years of age)

  • Evaluate for dyslipidemia every 5 years

Middle-aged Adults (Men 45-65 years of age; Women 55-65 years of age)

  • Evaluate at least every 1-2 years in the absence of CAD risk factors
  • Evaluate more frequently in the presence of multiple global CAD risk factors

Adults >65 years of age

  • Evaluate annually those with 0-1 CAD risk factor

Adult with Diabetes Mellitus (DM)

  • All adult patients with DM should be screened annually for dyslipidemia

Pediatric Screening

  • Children >2 years of age should be screened every 3-5 years if they have CAD risk factors, family history of dyslipidemia or premature CAD, obese or overweight, have other elements of insulin resistance syndrome, or have no available family history
  • Adolescents >16 years of age should be screened every 5 years
  • If with CAD risk factors, with family history of dyslipidemia or premature CAD, obese or overweight, or with other elements of insulin resistance syndrome, screen patient more frequently

Dyslipidemia Screening Tests

Fasting Lipid Profile

  • Fasting lipid profile is used to ensure that the most accurate lipid assessment is achieved
  • Includes TC, LDL-C, HDL-C and TG

LDL-C

  • Direct measurement of LDL-C in certain high-risk patients (eg patients with DM, vascular disease, fasting TG level >250 mg/dL or >2.9 mmol/L) is recommended
    • Estimation by Friedewald equation is valid only for values obtained in the fasting state, and is largely inaccurate in TG levels >200 mg/dL (>2.3 mmol/L) and is invalid when TG levels are >400 mg/dL (4.5 mmol/L)

HDL-C

  • HDL-C >60 mg/dL (>1.6 mmol/L) is an independent negative risk factor for dyslipidemia in both sexes
  • In women, very low HDL-C (<40 mg/dL or 1.03 mmol/L) is an independent risk factor for development of CVD and mortality, even in the presence of normal LDL-C and/or triglyceride levels or TC level <200 mg/dL (<2.3 mmol/L)
    • Women with low HDL-C have a CVD risk elevated to almost 3-fold (as compared with women with high HDL-C)
  • Considered as an alternative risk marker, especially in combined hyperlipidemias, diabetes, metabolic syndrome or chronic kidney disease

Non-HDL-C (total cholesterol minus HDL-C)

  • In patients with moderately increased TG (200-500 mg/dL or 2.3-5.6 mmol/L), DM and/or established CAD, or if insulin resistance is suspected, measure non-HDL-C
  • Provides a better risk assessment than LDL-C alone in patients with moderately elevated TG

Triglycerides

  • TG levels ≥150 mg/dL (>1.7 mmol/L) may help identify those at risk for insulin resistance syndrome
  • TG levels ≥200 mg/dL (≥2.3 mmol/L) may point to a significant increase in the risk for CVD

Apolipoprotein B

  • Target apo B level to <90 mg/dL (<0.9 g/L) for those at risk of CVD (including those with DM)
  • Target apo B level to <80 mg/dL (<0.8 g/L) for those with established CVD or those with DM who have ≥1 additional risk factors
  • May help evaluate the success of LDL-C lowering therapy
  • Considered as an alternative risk marker, especially in combined hyperlipidemias, diabetes, metabolic syndrome or chronic kidney disease
  • Apo B and/or Apo B/Apo A1 ratio calculation and evaluation in patients with (TG ≥150, HDL-C <40, prior atherosclerotic CVD (ASCVD) event, type 2 DM, and/or insulin resistance syndrome may help in determining the best treatment strategy
  • Apo B reflects LDL particle number and is considered a more potent measure of CVD risk as compared with LDL-C and LDL particle size

Classification

Hypercholesterolemia

  • Increased LDL, TC, and LDL-C

Hypertriglyceridemia

  • A state where VLDL and triglycerides are significantly increased
    • Mild hypertriglyceridemia: TG >1.7 mmol/L (>150 mg/dL)
    • Moderate hypertriglyceridemia: TG <10 mmol/L (<880 mg/dL)
    • Severe hypertriglyceridemia: TG >10 mmol/L (>900 mg/dL)
  • Etiologic factors include heredity, obesity, type 2 DM, high carbohydrate diet, renal disease, medications (eg corticosteroids, Tamoxifen, Ciclosporin, estrogens, protease inhibitors, Isotretinoin)

Severe Hypertriglyceridemia

  • Increased chylomicrons and TG (≥4.5 mmol/L or 400 mg/dL)

Combined Dyslipidemia

  • Increased LDL, VLDL, TC, LDL-C, and TG

Lipid Profile Evaluation

 

IDEAL LIPID LEVELS
  Optimal/Near-Optimal Serum Concentration Borderline High Serum Concentration High-Risk/Very High-Risk Serum Concentration
LDL-C Optimal: <100 mg/dL (<2.6 mmol/L) optimal
Near-optimal: 100-129 mg/dL (2.6-3.3 mmol/L) near-optimal
130-159 mg/dL (3.4-4.1 mmol/L) 160-189 mg/dL (4.1-4.9 mmol/L) (high)
≥190 mg/dL (4.9 mmol/L) (very high)
TG <150 mg/dL (<1.7 mmol/L) 150-199 mg/dL (1.7-2.3 mmol/L) 200-499 mg/dL (2.3-5.6 mmol/L) (high)*
≥500 mg/dL (>5.6 mmol/L) (very high)*
HDL-C ≥60 mg/dL (1.6 mmol/L) Male: 40-59 mg/dL (1-1.3 mmol/L)
Female: 50-59 mg/dL (1.3-1.5 mmol/L)
Male: <40 mg/dL (<1 mmol/L)
Female: <50 mg/dL (<1.3 mmol/L)
Non-HDL-C  30 mg/dL above LDL-C goal  30 mg/dL above LDL-C goal 250 mg/dL above LDL-C goal (extreme risk patients)
TC <200 mg/dL (5.2 mmol/L) 200-239 mg/dL (5.2-6.2 mmol/L) >240 mg/dL (6.2 mmol/L)
Apo B Not recommended  <90 mg/dL (patients at risk of coronary heart disease) <80 mg/dL (patients with coronary heart disease/diabetes mellitus plus ≥1 risk factor)
<70 mg/dL (patients at extreme risk)
Modified from: Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and AmericanCollege of Endocrinology guidelines for management of dyslipidemia and prevention of atherosclerosis. Endocr Pract. 2017 Feb 3.
*The Endocrine Society (2010) classifies TG levels of >200 mg/dL as moderate hypertriglyceridemia (200-999 mg/dL), severe hypertriglyceridemia (1000-1999 mg/dL) and very severe hypertriglyceridemia (>2000 mg/dL); the levels corresponding to risk levels for premature CVD and pancreatitis

 

Lipid Treatment Goals Based on Cardiovasular Disease Risk
 Risk Categories LDL-C Non-HDL-C Apolipoprotein B
Extreme Risk <55 mg/dL   <80 mg/dL <70 mg/dL 
Very High Risk  <70 mg/dL  <100 mg/dL <80 mg/dL
High Risk <100 mg/dL  <130 mg/dL  <90 mg/dL 
Moderate Risk <100 mg/dL1   <130 mg/dL  <90 mg/dL
Low Risk  <130 mg/dL1  <160 mg/dL  Not recommended
1LDL-C levels for low to moderate risk patients average 115 mg/dL as per the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS).
Modified from: Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of atherosclerosis. Endocr Pract. 2017.

Risk Stratification

  • Evaluation of lipid profile must be performed in parallel with risk assessment for CHD
    • LDL-C is used as primary lipid analysis for screening and risk estimation
  • Risk assessment tools (eg Framingham risk score, Reynold’s risk score, Systemic Coronary Risk Estimation (SCORE), Multi-Ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk with coronary artery calcification calculator, United Kingdom Prospective Diabetes Study (UKPDS) risk engine in individuals with type 2 DM, etc) are commonly used to assess a patient’s risk for CVD
    • Point system for CVD risk differs by gender
    • Framingham risk score:
      • Predictors include age, sex, smoker/non-smoker, total cholesterol level, HDL cholesterol, systolic BP and if the patient is being treated with antihypertensive drugs
      • High systolic BP, age, total cholesterol and smoking are more significant in women
      • 130-139 mmHg systolic BP has more points in women (untreated - 2; treated - 4) than in men (untreated - 1; treated - 2) but overall points have lower threshold for men than in women (10 total points = 6% 10-year risk in men vs 1% in women)
  • Identify patients with established CVD or with CVD risk equivalents: DM, atherosclerotic CV disease, PAD or abdominal aortic aneurysm
  • Major independent risk factors for CVD
    • Cigarette smoking
    • Hypertension (BP >140/90 mmHg or on antihypertensive medication)
      • History of preeclampsia or pregnancy-induced hypertension in women
    • Low HDL cholesterol (<40 mg/dL)
    • Increased total serum cholesterol level
    • Increased non-HDL-cholesterol levels
    • Increased LDL-cholesterol levels (≥190 mg/dL)
    • Family history of premature CVD (male 1st-degree relative <55 years; female 1st-degree relative <65 years)
    • Age (men ≥45 years; women ≥55 years)
    • Chronic kidney disease (CKD)
    • Diabetes mellitus
      • For individuals with high HDL cholesterol (>60 mg/dL), subtract 1 risk factor from the total
      • History of gestational diabetes in women
  • Additional risk factors:
    • Dyslipidemic triad (hypertriglyceridemia, low HDL-C, small dense LDL-C)
    • Obesity, abdominal obesity
    • Elevated apo B
    • Elevated LDL particle number
    • Fasting/postprandial hypertriglyceridemia
    • Family history of hyperlipidemia
    • Polycystic ovarian syndrome (PCOS) in women
    • Small dense LDL-C
    • Microalbuminuria/proteinuria
  • Nontraditional risk factors:
    • Elevated lipoprotein
    • Elevated clotting factors
    • Elevated inflammation markers
    • Elevated triglyceride-rich remnants
    • Elevated homocysteine levels
    • Apo E4 isoform
    • Elevated uric acid

Cardiovascular Disease Risk Categories

    Risk Category Risk Factors/10-year Risk
    Extreme Risk Progressive atherosclerotic CVD including unstable angina after reduction of LDL-C to <70 mg/dL or
    Established clinical CVD in patients with DM, CKD, or heterozygous familial hypercholesterolemia or
    History of premature atherosclerotic CVD at <55 years of age in males; <65 years of age in females
    Very High Risk History of recent hospitalization for ACS, coronary, carotid, or peripheral vascular disease and 10-year risk >20% or diabetes or CKD ¾ plus ≥1 additional risk factor(s) or heterozygous familial hypercholesterolemia
    High Risk ≥2 risk factors and 10-year risk 10-20% or cardiovascular disease risk equivalents, including diabetes or moderate chronic kidney disease with no other risk factors
    Moderate Risk ≤2 risk factors and <10% 10-year cardiovascular disease risk 
    Low Risk 0 risk factor (<1% 10-year cardiovascular disease risk)

Metabolic Syndrome

  • Secondary target of therapy (LDL-C lowering is primary)

Clinical Identification

  • Any 3 or more of the following (including those on treatment):
    • Increased waist circumference (Asian cut off: ≥80 cm for females; ≥90 cm for males)
    • Raised TG level ≥1.7 mmol/L (150 mg/dL) or specific treatment for this lipid abnormality
    • Reduced HDL cholesterol <1 mmol/L (40 mg/dL) in males and <1.3 mmol/L (50 mg/dL) in females or specific treatment for this lipid abnormality
    • Raised BP (SBP ≥130 mmHg or DBP ≥85 mmHg) or treatment of previously diagnosed hypertension
    • Disorders of glycemia:
      • Type 2 DM, or
      • Impaired glucose tolerance (IGT): fasting plasma sugar <7 mmol/L (<125 mg/dL) and 2 hrs post-75 g glucose load 7.8-11.1 mmol/L (140-200 mg/dL), or
      • Impaired fasting glucose (IFG): fasting plasma sugar 6.1-7.0 mmol/L (110-125 mg/dL)

Manage the Underlying Causes

  • Obesity and physical activity
    • Weight loss and increased physical activity will reduce all of the above risk factors
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