B.   Obtain History.  Assess Risk Factors for Atherosclerotic Cardiovascular Disease (ASCVD)

OBJECTIVE

To identify clinical markers that predict an increased risk for developing ASCVD, thereby changing the interpretation of LDL levels.

ANNOTATION

A high low-density lipoprotein (LDL) cholesterol level is a strong predictor of cardiovascular (CV) risk, although in the absence of other CV risk factors the absolute risk for developing ASCVD is still relatively low. Conversely, the presence of other recognized CHD risk factors magnify the risk associated with any level of LDL. Proven, independent, clinical predictors of increased risk for ASCVD (in addition to elevated LDL cholesterol) include:

  1. Age (males > 45 years, females > 55 years or menopause < age 40?)
  2. Family history of premature coronary artery disease; definite myocardial infarction (MI) or sudden death before age 55 in father or other male first-degree relative, or before age 65 in mother or other female first-degree relative
  3. Current cigarette smoker
  4. Hypertension (systolic blood pressure equal or greater140 mmHg or diastolic blood pressure equal or greater 90 mmHg confirmed on more than one occasion, or current therapy with antihypertensive medications)
  5. Diabetes mellitus (DM)
  6. High-density lipoprotein (HDL)-cholesterol < 40 mg/dL

"Negative" Risk Factor

Elevated HDL cholesterol, > 60 mg/dL, is a well-established independent, clinical predictor of decreased risk for ASCVD. It has been suggested that an HDL > 60 mg/dL negates one ASCVD risk factor for individual risk calculation.

DISCUSSION

Several large trials, including the Framingham Heart Study (Castelli, 1984) and the Multiple Risk Factor Intervention Trial Research Group (MRFIT, 1982; Neaton & Wentworth, 1992), have identified non-LDL cholesterol risk factors that predict a person's risk for developing ASCVD. Importantly, these risk factors are more than additive to one another. The single most important risk factor for having a myocardial infarction is established cardiovascular disease. Approximately 50 percent of all myocardial infarctions occur in people with known cardiovascular disease. Further discussion of non-cholesterol risk factors for IHD is in the VHA/DoD Guideline for Ischemic Heart Disease (IHD).

Multiple epidemiologic studies including the Framingham Study have observed an inverse relation between HDL levels and risk for coronary heart disease, where a difference of one mg/dL is associated with a 2-3 percent change in risk (Gordon et al., 1989). In the Framingham Study, for instance, men with an HDL lower than 25 mg/dL had an incidence of coronary heart disease of 176.5/1000, whereas men with an HDL of 25 to 34 mg/dL had an incidence of coronary heart disease of 100.0/1000. Likewise, women with an HDL of 25 to 34 mg/dL had an incidence of coronary heart disease of 164.2/1000, whereas women with an HDL of 35 to 44 mg/dL had an incidence of 54.5/1000. The importance of low HDL as a risk factor for developing coronary heart disease was borne out in the AFCAPS/TexCAPS trial, in which the most significant benefit was seen in patients treated with an entry HDL lower than 35 mg/dL (Downs et al., 1998). Just as a low HDL level is inversely linked to an increased risk for developing coronary heart disease, so a high HDL level is inversely linked to a decreased risk for developing coronary heart disease (Wilson et al., 1988). It has been established that the protective effect of a high HDL is present even in the setting of a high LDL (Kannel, 1978).

EVIDENCE

LDL. (QE=I, SR=A). MRFIT, 1982; Neaton & Wentworth, 1992; Castelli, 1984

HDL. (QE=II-2, SR=A). Gordon et al., 1989; Downs et al., 1998; Wilson et al., 1988; Kannel, 1978