G. TG >400 mg/dL, Apply Diet and Exercise to Reduce TG; Consider Direct Measurement of LDL-C

objective

Identify patients whose LDL-C is confounded by secondary /modifiable causes of hypertriglyceridemia.

background

When TG levels are very high (over 400 mg/dL), the estimation of LDL-C using the Friedewald formula is not accurate.  A direct measurement of the LDL-C can be performed using specialized laboratories.  In addition, patients with significant elevated TG need further evaluation (see Annotation T).

In the management of dyslipidemia, therapy targeted at lowering LDL-C levels is the first priority to lower CVD risk.  However, since many institutions continue to rely upon the calculated LDL value, and LDL-C can be affected by conditions which raise TGs, it is important to address the common, easily modifiable causes of hypertriglyceridemia with simple interventions (e.g., diet and exercise).

recommendations

1. If TG levels can be brought to <400 mg/dL by dietary or other interventions, then Friedewald’s formula can be used to calculate a more exact LDL-C level.  [C]
2. If TGs cannot be brought to levels less than 400 mg/dL, then consider measuring LDL-C directly, or estimate the LDL-C using the following equation:  [I]

Estimated LDL-C = (TC – HDL) – 30

3. Screen and treat common causes of elevated TGs: fatty diet, high carbohydrate diets, alcohol use, hypothyroidism, and hyperglycemia.  [B]
4. In the absence of secondary causes, the first-line therapy for elevated TGs should be therapeutic life-style changes.  [C]

discussion

The Friedewald calculation [LDL-C = total cholesterol - (HDL-C + TG/5] yields an unacceptable inaccurate estimation of the LDL-C in patients with TGs >400.  Also, simple reversible processes, which raise triglycerides, also raise LDL-C.  When resolutions of these causes of hypertriglyceridemia are addressed, the LDL-C may also be modified.  In the absence of reversible causes of hypertriglyceridemia there are three options to obtain an accurate LDL-C measurement: 1) Perform a direct LDL-C measurement using a specialized laboratory, 2) Estimate the LDL-C using the adjusted non-HDL equation, or 3) Attempt to modify the triglycerides using therapeutic lifestyle changes (TLC) and estimate the LDL-C when the triglyceride level is <400.

Since non-HDL-C levels tend to be approximately 30 mg/dL greater than estimated LDL levels, the estimated LDL from this equation will be approximately 30 points lower and LDL goals need to be interpreted accordingly.  Estimated LDL-C = (TC – HDL) – 30 mg/dL.

Hypertriglyceridemia can be caused by or exacerbated by an underlying medical disorder.  When secondary disorders of hyperlipidemia are appropriately treated, TG levels can greatly improve or, in some cases, even return to the normal range.  For other conditions associated with high level of TG see Annotation L1, Table 1.