Chapter 2-7: Cholesterol Screening

What is the burden of disease?

1. Coronary heart disease (CHD) is the leading cause of death in the United States.

2. Overall costs of CHD and stroke estimated to be $317 billion in 2011–2012.

3. Lifetime risk of a CHD event, calculated at age 40 years, is 49% for men and 32% for women; nearly one-third of CHD events are attributable to total cholesterol > 200 mg/dL.

Is it possible to identify a high-risk group that might especially benefit from screening?

1. High low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) levels themselves are independent risk factors for CHD, with the increased risk being continuous and linear.

   1. For every 38 mg/dL increase in LDL above 118 mg/dL, the relative risk for CHD is 1.42 in men and 1.37 in women.

   2. For every 15.5 mg/dL increase in HDL above 40 mg/dL in men, the relative risk for CHD is 0.64.

   3. For every 15.5 mg/dL increase in HDL above 51 mg/dL in women, the relative risk for CHD is 0.69.

   4. Total cholesterol–HDL ratio

      1. In men, a ratio ≥ 6.4 was associated with a 2–14% greater risk than predicted from total cholesterol or LDL alone.

      2. In women, a ratio ≥ 5.6 was associated with a 25–45% greater risk than predicted from total cholesterol or LDL alone.

2. Patients with established atherosclerotic cardiovascular disease (ASCVD), defined as acute coronary syndrome, a history of myocardial infarction, stable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease, are in the highest risk category.

3. Patients without established ASCVD should have a global risk score calculated.

   1. The American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines recommend the Pooled Cohort Equations, a risk assessment tool that estimates the 10-year risk of a first ASCVD event, defined as nonfatal myocardial infarction or coronary heart disease death or fatal or nonfatal stroke.

      1. Derived and validated in non-Hispanic whites and non-Hispanic blacks

      2. Can use the equations developed for non-Hispanic whites in other populations, although risk assessments may not be as accurate

      3. Found at http://clincalc.com/cardiology/ascvd/pooledcohort.aspx

      4. Some studies suggest it overestimates risk; other studies show that, compared to other calculators, it more accurately predicts cardiovascular events

   2. The Framingham Risk Score is another commonly used calculator available at https://www.mdcalc.com/framingham-coronary-heart-disease-risk-score.

      1. Validated in populations over age 40

      2. Not validated with the 2013 ACC/AHA guidelines described below.

What is the quality of the screening test?

1. Total cholesterol and HDL are minimally affected by eating and can be measured in fasting or nonfasting individuals.

2. Triglycerides may be increased 20–30% by eating and must be measured in the fasting state.

3. LDL can be directly measured but is most commonly estimated using the following equation, which is valid only when the fasting triglycerides are < 400 mg/dL: LDL = total cholesterol – (triglycerides/5 + HDL).

4. Total cholesterol may vary by 6% in day-to-day measurements, with HDL varying as much as 7.5%; clinicians should obtain 2 measurements before starting therapy.

Does screening reduce morbidity or mortality?

1. In meta-analyses of primary prevention studies of statin drug therapy, including ...