This weeks
Question:
What combination presents more of a risk factor:
1.
Having a high total cholesterol and a high high-density lipoprotein
(HDL) cholesterol?
2. Having a low total cholesterol and a low HDL cholesterol?
3. Having a high total cholesterol when all of the other parameters
are normal?
The answer to this
question depends on the value of the calculated LDL cholesterol. In
most cases, assuming a normal serum triglyceride value, a patient with
an elevated total and HDL cholesterol would have an elevated LDL cholesterol,
whereas the patient with a low total and HDL cholesterol would have
a low LDL cholesterol. The lower risk would exist in the latter patient.
For the former patient, the decision to begin lipid-lowering therapy
would be based on the LDL cholesterol and the response to nonpharmacologic
therapy, including diet and exercise. If the patient met criteria for
lipid-lowering therapy, based on the ATP III guidelines, clinicians
should follow LDL cholesterol as the primary evidence for successful
therapy, and need not be concerned in the rare situation where the HDL
cholesterol values also fall as a result of therapy. The total cholesterol
would never be elevated if all the component lipid values were normal,
as it is a weighted sum of the various components.
Discussion
The Adult Treatment Panel III (ATP III) on the Detection, Evaluation,
and Treatment of High Blood Cholesterol in Adults from the National
Cholesterol Education Program of the NHBLI[1] provides the current consensus
on the treatment of abnormal components of the total cholesterol. The
current version of this guideline simplifies clinician assessment of
risk due to various components of the total serum cholesterol. In this
guideline, the focus is on the low-density lipoprotein (LDL) cholesterol,
among the components of total cholesterol, as the primary risk factor
for coronary artery disease (CAD). Clinicians need not be concerned
about the influence of total cholesterol on the risk for CAD when interpreting
baseline or posttreatment lipid values. The calculated LDL cholesterol,
obtained from a fasting serum sample, is the total serum cholesterol
minus the HDL cholesterol minus one fifth of the triglyceride level.
The ATP III guideline considers HDL cholesterol < 40 mg/dL to be
a risk factor for the development of CAD.
While the primary
effect of the "statin" class of lipid-lowering medications
is to reduce the LDL cholesterol, HDL cholesterol may occasionally be
reduced by such medications. More commonly, statin class medications
lead to a modest increase in HDL cholesterol values.
Treatment trials
of statins for primary and secondary prevention of cardiac events have
focused on the degree of reduction of LDL cholesterol. While a low HDL
is an independent risk factor for the development of CAD, the ATP III
considers this to be a minor risk factor when compared with the importance
of elevated LDL cholesterol. The causal relationship between low HDL
cholesterol and the development of CAD is not well established and it
is possible that a low HDL may serve primarily as a marker of CAD risk
rather than as a strong etiologic factor. For example, in multivariate
analyses that control for comorbidities, HDL cholesterol has a weaker
relationship to the risk of CAD events. Patients with a low HDL level
benefit from statin therapy to lower LDL to the same extent as patients
with a baseline high HDL. It has not been definitely established that
drug therapy specifically to raise HDL lowers the risk of CAD events.
Therefore, the answer
to this question depends on the value of the calculated LDL cholesterol.
In most cases, assuming a normal serum triglyceride value, a patient
with an elevated total and HDL cholesterol would have an elevated LDL
cholesterol, whereas the patient with a low total and HDL cholesterol
would have a low LDL cholesterol. The lower risk would exist in the
latter patient. For the former patient, the decision to begin lipid-lowering
therapy would be based on the LDL cholesterol and the response to nonpharmacologic
therapy, including diet and exercise. If the patient met criteria for
lipid-lowering therapy, based on the ATP III guidelines, clinicians
should follow LDL cholesterol as the primary evidence for successful
therapy, and need not be concerned in the rare situation where the HDL
cholesterol values also fall as a result of therapy. The total cholesterol
would never be elevated if all the component lipid values were normal,
as it is a weighted sum of the various components.
References
1. National Cholesterol Education Program. Third Report of the Expert
Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol
in Adults (Adult Treatment Panel III) Full Report. 2002. Available at:
http://www.nhlbi.nih.gov/guidelines/cholesterol/
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