from Uffe Ravsnkovís The Cholesterol Myths:
@LDL has the strongest and most
consistent relationship to individual and population risk of CHD,
and LDL‑cholesterol is centrally and causally important in the pathogenetic chain leading to atherosclerosis and CHD@. These words you will find in the
large review Diet and Health (NRC. Diet and health.
Implications for reducing chronic disease risk. Washington
Academy Press, 1989, p. 166).
by distinguished scientific bodies are supposed to meet high standards.
Therefore, you are probably wondering how the authors of Diet and Health, an
official, most authoritative and supposedly reliable review from the National
Research Council in Washington, had reached their conclusion about LDL‑cholesterol.
Four publications were mentioned.
1973 Dr. Jack Medalie and his coworkers published a
five‑year follow‑up study of 10,000 Israeli male government and
municipal employees (Medalie JH et al. Five‑year
myocardial infarction incidence‑II. Association of
single variables to age and birthplace. J Chronic Diseases 1973;26:325‑349). But the Israeli study did not support
the words of Diet and Health, because total cholesterol, not LDL‑cholesterol,
had the strongest relationship to risk of coronary disease.
second paper claimed by the Diet and Health‑authors was a 1977 report
from the Framingham Study by Dr. Tavia Gordon and her
colleagues (Gordon T et al. HDL as a protective factor against CHD. Am J Med
1977;62:707‑714.). This study concerned HDL
cholesterol, however. Only logistic regression coefficients (a statistical
concept unknown to most doctors) for coronary disease on LDL‑cholesterol
were given, and one of the conclusions of the paper
was that @LDL‑cholesterol
...is a marginal risk factor for people of these age groups@ (men and women above 50 years). Some
of the coefficients were indeed low. For women above the age of 70 it was
negative, which means that women at that age ran a greater risk of having a
heart attack if their LDL‑cholesterol was low than if it was high. Thus,
there was no support either from Gordon's paper.
the third paper concerned HDL‑cholesterol only. No support again.† (Watkins LO et al.† Racial differences in HDL and CHD incidence
in the usual‑care group of the MRFIT. Am J Cardiology† 1987;57:538‑545)
fourth reference was to the National Cholesterol Education Program, which
produced another large review without original data (The Expert Panel.† Report of the NCEP expert
panel on detection, evaluation, and treatment of high blood cholesterol in
adults.† Arch Int Med 1988;148:36‑69).
One of its conclusions was that @a
large body of epidemiologic evidence supports a direct relationship between the
level of serum total and LDL‑cholesterol and the rate of CHD.@ The large body of evidence was to be
found in three references. The first one was another large review without
original data, Optimal resources for primary
prevention of atherosclerotic disease (Kannel WB et
al.† Optimal resources
for primary prevention of atherosclerotic diseases. Atherosclerosis
study group.† Circulation† 1984;70:157A‑205A).† I shall return to their review below.
next reference was yet another large review (Grundy SM. Cholesterol and
coronary heart disease: a new era. JAMA 1986;256:2849‑2858),
but nothing in that review was said about the connection between the LDL‑level
and the incidence of coronary heart disease.
last reference was an analysis of various lipoproteins as risk factors in the
Honolulu Heart Study (Hulley SB et al. The plasma
lipoproteins as risk factors: comparison of electrophoretic
and ultracentrifugation results. Metabolism 1982;31:773‑777).
The conclusion of that paper was that @both
measures of LDL‑cholesterol were related to CHD prevalence, but neither
appeared to be superior to total cholesterol@.
I discuss Kannel's review I shall mention another
conclusion in the National Cholesterol Education Program: @The issue of whether lowering LDL‑cholesterol
levels by dietary and drug interventions can reduce the incidence of CHD has
been addressed in more than a dozen randomized clinical trials@. This is a most misleading statement
because at that time, in 1988, only four randomized trials including LDL‑cholesterol
analysis had previously been published (The Multiple Risk Factor Intervention
Trial (MRFIT), the Newcastle trial, the Lipid Research Clinic's trial, and the
Helsinki Heart Study), and only in one of them the number of heart attacks was
me now return to the review by Kannel and colleagues,
the one used as evidence by the authors of The Cholesterol Education Program,
which in turn was used as evidence by the authors of Diet and Health. Almost
nothing was written about LDL‑cholesterol in Kannel's
review except for the following (page 164A): @Longitudinal
studies within populations show a consistent rise in the risk of CHD in
relation to serum total cholesterol and LDL‑cholesterol at least until
little more cautious conclusion than in Diet and Health, it may seem, but even
for this prudent statement the evidence was weak. References to six studies
were given. In two of them LDL‑cholesterol was not analysed
or mentioned at all (Yaari S et al.† Associations of serum HDL
and total cholesterol with total, cardiovascular, and cancer mortality in a 7‑year
prospective study of 10000 men. The Lancet 1981;1:1011‑1015,
Ancel Keys. Seven Countries. A multivariate analysis of death and coronary heart disease.
Harvard University Press 1980.); in two reports LDL‑cholesterol was only
correlated to the prevalence of heart disease (Rhoads GG et al.† Serum lipoproteins and CHD in a population
study of Hawaii Japanese men. NEJM 1976;294:293
298, and The Pooling Project Research Group. Relationship of blood pressure,
serum cholesterol, smoking habit, relative weight and ECG abnormalities to
incidence of major coronary events: final report of the pooling project. Journal
of Chronic Diseases 1978;31:201‑306.); in
one report two tables was aimed at the subject (tables 8 and 9) and showed that
the predictive power of LDL‑cholesterol was statistically nonsignificant (Conference on the health effects of blood
lipids: Optimal distributions for populations. Workshop report: Epidemiological
section. Preventive Medicine† 1979;8:612. No LDL data
were presented in that report either); in one study LDL‑cholesterol was
predictive for heart disease, but only for men between 35 and 49 and for women
between 40 and 44 (Kannel WB, Castelli
WP, Gordon T. Cholesterol in the prediction of atherosclerotic disease. New
perspectives based on the Framingham
study. Annals of Internal Medicine 1979;90:85
conclusion, the @large
body of evidence@ was
cooked down to one single study, which showed a predictive value for LDL‑cholesterol
but for a few age groups only. LDL‑cholesterol is neither centrally nor
causally important, it has not the strongest and most consistent relationship
to risk of CHD, it has not a direct relationship to the rate of CHD, and it has
not been studied in more than a dozen randomized trials.