Really important if you have arterial plaque!
HDL: Why it's so important
By Dr Davis
Q: What is the most common lipid abnormality that causes heart attack?
A: Low HDL cholesterol
That's right—it's not high LDL cholesterol. Look at the HDL levels in people with heart attacks. More than likely, people with heart attacks have low HDL of 40 mg/dl or less, and LDL will be in the 100–160 mg/dl range (i.e., in the middle range, neither high nor low). Should these people be treated with an LDL-lowering agent alone? Will lowering LDL eliminate the risk posed by low HDL?
The evidence suggests that both abnormalities need to be treated. And in the patients who already have a low LDL, strategies to raise HDL should be initiated. The combined strategy of lowering LDL and raising HDL can, in fact, be a powerful means of preventing future coronary events and achieving plaque regression. In this report, we discuss the very important findings of Dr. Greg Brown's "HATS" Trial, conducted at the University of Washington.
The HDL-Atherosclerosis Treatment Study (HATS) trial enrolled 160 patients (149 males), all of whom had documented coronary disease. Coronary plaque was measured with heart catheterization. There were four treatment arms: simvastatin (Zocor) + niacin, placebo, simvastatin + niacin +anti-oxidant vitamins, and anti-oxidant vitamins alone.
The anti-oxidant treatment arms proved of no value in lowering coronary events or achieving plaque regression. Let's focus on the HDL observations. This boils down to a comparison of two groups: the placebo group vs. the simvastatin + niacin. Simvastatin therapy was adjusted to achieve an LDL of 90 mg/dl or lower; niacin was adjusted to achieve an increase in HDL of 10 mg/dl. As expected, the treatment arm patients achieved a mildly greater reduction in plaque progression.
But what is eye-opening in this study is the magnitude of reduction of events comparing the simvastatin + niacin group to the placebo group: There was a 90% reduction in death and myocardial infarction (12 events placebo;1 event simvastatin + niacin) over three years. In other words, coronary events were nearly shut off.
To put this into perspective, recall that all the major clinical trials of lipid therapy, such as 4S, LIPID, AFCAPS/TEXCAPS, Heart Protection Study, etc. achieved event reductions of 25-35% over approximately 3 to 5 years when LDL cholesterol was lowered by statin therapy. Trials such as VA-HIT and the Helsinki Heart Study demonstrated similar magnitudes of event reduction with raising HDL. The 90% achieved in the HATS Trial is therefore truly phenomenal, perhaps unprecedented.
Placebo Simvastatin + niacin
Total cholesterol (mg/dl) 188 139
VLDL 37 23
LDL 116 75
IDL 11 6
HDL 34 40
HDL2 3.8 6.1
Total Triglycerides 196 26
IDL 7.0 6.2
Lipoprotein(a) 29 23
Apoprotein B 104 73
Figure 1. Lipoprotein levels on treatment
Rarely do we see a treatment effect as powerful as the reduction in events seen in the HATS Trial with patients on combination therapy. As seen in table 1, the HDL level that achieved this marked reduction in events was only 40 mg/dl (average HDL at the start was 31 mg/dl). Also note the substantial increase in the HDL2 ("large") fraction of HDL, which correlated well with the reduction in coronary events.
Dr. Brown and colleagues propose that the larger than expected benefits of combination therapy are due to a dual therapeutic pathway: statin therapy reduces LDL cholesterol and the number of LDL particles (apoprotein B); and niacin, which increases HDL and HDL2 and increases LDL particle size.
At what level of HDL should we begin HDL-raising strategies? This is not entirely clear. The Adult Treatment Panel guidelines call for consideration for LDL-lowering if HDL is less than 40 mg/dl, but they are not specific regarding HDL-raising. We believe that the HATS Trial and related evidence very powerfully suggests that raising HDL is very important and can lead to a profound reduction in coronary events. We certainly should not tolerate HDL's of less than 40 in men, 45 in women, particularly when atherosclerotic vascular disease is present in any form.
From the Track Your Plaque viewpoint, where plaque shrinkage and inactivation is our goal, we aim to raise HDL to 60 mg/dl or greater. We should be able to match or exceed the 90% reduction in events of the HATS experience.
References
Simvastatin and Niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. B. Greg Brown, Zhao et al, N Engl J Med, 345:15831591, 2001. |
