With all the research and drug development surrounding LDL (“bad”) cholesterol (not to mention all the advertising) you would think that high LDL cholesterol is easily the most common factor contributing to heart disease and heart attacks. 

It is not. Low HDL (“good”) cholesterol is.

In the now-famous HDL-Atherosclerosis Treatment Study (HATS) trial, where coronary plaque was directly measured using heart catheterizations (we owe a debt of gratitude to the trial participants for the pain, inconvenience and risk), four treatments were tested to determine which had the greatest plaque fighting power. The tested agents included a statin plus niacin (the most well-known HDL-increasing agent), a statin plus niacin and antioxidant vitamins, antioxidant vitamins alone, and, of course, a placebo.

The placebo and “antioxidant only” groups showed no reduction in coronary events or plaque regression. However, the groups using a statin plus niacin did. The statin dose was adjusted to achieve an LDL cholesterol of 90 mg/dl, while the niacin was adjusted to achieve an increase in HDL cholesterol of 10 mg/dl. Over a three-year trial period, those receiving the statin plus niacin treatment experienced a whopping 90 percent reduction in heart attack and death. Seems to me that this is a result we would all like to experience.

One might ask, “How can you tell if it was the statin or the niacin that made the difference?” The study produced a far greater reduction in cardiac events than what was achieved in multiple other studies where the participants received only statin therapy to reduce LDL cholesterol (e.g. 4S, LIPID, AFCAPS/TEXCAPS, Heart Protection Study). Conversely, similar trials such as VA-HIT and the Helsinki Heart Study also demonstrated similar magnitudes of event reduction when raising HDL. 

Let’s take a look at the various measures of heart health monitored in this study for those in the statin plus niacin and placebo arms.

TABLE 1: HATS Results

Lipoproteins                                Placebo            Statin plus 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

Note that just a small increase in HDL from 34 to 40 mg/dl yielded exceptional results as compared to trials where the only treatment was for LDL reduction. Next, look at the “HDL2” numbers. HDL2 is the portion or “sub-fraction” HDL known as “large HDL.” It is theorized that this sub-fraction does most of the work of “reverse cholesterol transport” which is the process of actually removing cholesterol from the artery wall. This important sub-fraction nearly doubled.

As I look back on my battle against heart disease, perhaps the most frustrating aspect is that for years I had low HDL cholesterol, yet my doctor never mentioned it to me. All he ever remarked about was my low LDL cholesterol and how it meant I was unlikely to have heart disease. Boy, was he ever wrong! 

I believe the takeaway message from both the HATS trial and my personal experience is that you can have heart disease even with low LDL cholesterol if your HDL cholesterol is low as well.