NEJM Volume 357:1301-1310  September 27, 2007  Number 13

HDL Cholesterol, Very Low Levels of LDL Cholesterol, and
Cardiovascular Events

Philip Barter, M.D., Ph.D., Antonio M. Gotto, M.D., D.Phil., John C.
LaRosa, M.D., Jaman Maroni, M.D., Michael Szarek, M.S., Scott M.
Grundy, M.D., Ph.D., John J.P. Kastelein, M.D., Ph.D., Vera Bittner,
M.D., M.S.P.H., Jean-Charles Fruchart, Pharm.D., Ph.D., for the
Treating to New Targets Investigators

ABSTRACT

Background High-density lipoprotein (HDL) cholesterol levels are a
strong inverse predictor of cardiovascular events. However, it is not
clear whether this association is maintained at very low levels of low-
density lipoprotein (LDL) cholesterol.

Methods A post hoc analysis of the recently completed Treating to New
Targets (TNT) study assessed the predictive value of HDL cholesterol
levels in 9770 patients. The primary outcome measure was the time to a
first major cardiovascular event, defined as death from coronary heart
disease, nonfatal non-procedure-related myocardial infarction,
resuscitation after cardiac arrest, or fatal or nonfatal stroke. The
predictive relationship between HDL cholesterol levels at the third
month of treatment with statins and the time to the first major
cardiovascular event was assessed in univariate and multivariate
analyses and was also assessed for specific LDL cholesterol strata,
including subjects with LDL cholesterol levels below 70 mg per
deciliter (1.8 mmol per liter).

Results The HDL cholesterol level in patients receiving statins was
predictive of major cardiovascular events across the TNT study cohort,
both when HDL cholesterol was considered as a continuous variable and
when subjects were stratified according to quintiles of HDL
cholesterol level. When the analysis was stratified according to LDL
cholesterol level in patients receiving statins, the relationship
between HDL cholesterol level and major cardiovascular events was of
borderline significance (P=0.05). Even among study subjects with LDL
cholesterol levels below 70 mg per deciliter, those in the highest
quintile of HDL cholesterol level were at less risk for major
cardiovascular events than those in the lowest quintile (P=0.03).

Conclusions In this post hoc analysis, HDL cholesterol levels were
predictive of major cardiovascular events in patients treated with
statins. This relationship was also observed among patients with LDL
cholesterol levels below 70 mg per deciliter. (ClinicalTrials.gov
number, NCT00327691 [ClinicalTrials.gov] .)

Source Information

I. Weill Medical College of Cornell University, New York (A.M.G.); the
State University of New York Downstate Medical Center, Brooklyn
(J.C.L.); Pfizer, New York (J.M., M.S.); the Center for Human
Nutrition, University of Texas Southwestern Medical Center, Dallas
(S.M.G.); the Academic Medical Center, University of Amsterdam,
Amsterdam (J.J.P.K.); the Division of Cardiovascular Disease,
University of Alabama, Birmingham (V.B.); and the Institut Pasteur,
Lille, France (J.-C.F.).

Address reprint requests to Dr. Barter at the Heart Research
Institute, 145 Missenden Rd., Camperdown, NSW 2050, Australia, or at
barterp@hri.org.au.

http://cardiology.jwatch.org/cgi/content/full/2007/926/1