FTR, low carbing typically causes a significant rise in HDL, while
causing CVD predictive TGLs to plummet.

Susan

Low HDL cholesterol, even when LDL levels are low, is cardiovascular
dynamite, new TNT analysis shows

September 26, 2007        Michael O'Riordan

Sydney, Australia - Among patients treated with statins, including those
who achieved very low levels of cholesterol with high-dose statin
therapy, HDL-cholesterol levels are still predictive of major
cardiovascular events [1]. These are the new findings from the Treating
to New Targets (TNT) study, a trial previously covered by heartwire.

"In this post hoc analysis from the TNT trial, HDL cholesterol was a
significant predictor of major cardiovascular events across the entire
study cohort, even after all other baseline risk factors, including
baseline LDL-cholesterol level, had been taken into account," writes Dr
Philip Barter (Heart Research Institute, Sydney, Australia) on behalf of
the TNT investigators in the September 27, 2007 issue of the New England
Journal of Medicine.

Discussing the rationale of the study, the authors note that while low
levels of HDL cholesterol are known to be a strong predictor of
increased cardiovascular risk, it is unknown whether low HDL cholesterol
remained a significant risk factor in subjects treated to very low
LDL-cholesterol levels. Some have argued, Barter and colleagues point
out, that if LDL levels were reduced sufficiently, "the level of HDL
cholesterol might be irrelevant."

TNT: Part of the lower-is-better posse

The TNT trial was one of several studies that made the "lower-is-better"
case for lowering LDL cholesterol beyond the then-current recommended
guidelines. TNT, first presented at the American College of Cardiology
(ACC) 2005 Scientific Sessions and published in the New England Journal
of Medicine, showed that lowering LDL-cholesterol levels in stable
coronary heart disease (CHD) patients substantially below the current
targets resulted in better clinical outcomes [2].

Intensive lipid lowering with atorvastatin (Lipitor, Pfizer) 80 mg daily
provided greater protection from major cardiovascular events compared
with low-dose atorvastatin in stable CHD patients. High-dose
atorvastatin reduced the primary composite end point of death from CHD,
nonfatal MI, resuscitation after cardiac arrest, and fatal or nonfatal
stroke 22% compared with patients treated with atorvastatin 10 mg.

In this newest post hoc analysis, the investigators assessed the
predictive value of HDL cholesterol in 9770 patients, with the primary
outcome measure being the time to a first major cardiovascular event.
All subjects were stratified into quintiles based on their
HDL-cholesterol levels determined at month 3 of the double-blind
treatment phase.

In the determination of the five-year risk of major cardiovascular
events across the different quintiles, univariate analysis showed the
event rate to be reduced by 40% in the highest quintile when compared
with subjects with the lowest HDL-cholesterol levels. After adjustment
for covariates, HDL cholesterol remained a significant predictor of
cardiovascular events; there was a 25% reduction in risk when those in
the highest quintile were compared with those in the lowest. When the
analysis was stratified according to LDL-cholesterol levels in patients
receiving statins, the relationship between HDL-cholesterol levels and
major cardiovascular events was of borderline significance (p=0.05).
Multivariate analysis of the relationship between HDL-cholesterol levels
at month 3 and risk of major cardiovascular events

Comparison with HDL quintiles
    Q5 (HDL cholesterol >55 mg/dL)
    Q4 (HDL cholesterol 47 to <55 mg/dL)
    Q3 (HDL cholesterol 42 to <47 mg/dL)
    Q2 (HDL cholesterol 37 to <42 mg/dL)
Hazard ratio (95% CI) vs Q1 (HDL <37 mg/dL)
    0.75 (0.60-0.95)
    0.92 (0.74-1.13)
    0.80 (0.65-0.99)
    1.00 (0.82-1.21)

To download table as a slide, click on slide logo below

The TNT investigators also report that when they examined subjects who
achieved very low levels of cholesterol, less than 70 mg/dL, those with
HDL-cholesterol levels 55 mg/dL or greater were still at significantly
less risk for a major cardiovascular events than those in the lowest
quintile.

Commenting on the results of the study for heartwire, Dr Monty Krieger
(Massachusetts Institute of Technology, Cambridge, MA) said that this is
yet another study showing that HDL cholesterol is protective, this time
at various LDL levels, and will reinforce the concept that doing
something to treat low levels of HDL cholesterol may be beneficial,
regardless of the LDL-cholesterol numbers.