For years, cardiologists have revered high-density lipoproteins – the so-called “good cholesterol” – for their work ferrying fats along the bloodstream and out through the liver. Having high levels of these fat-moving molecules has been long considered key for a smooth-humming heart and blood vessel network.
Until recently, at least.
New research published in last week’s The Lancet is “compelling and disturbing,” according to a number of high-profile clinician-scientists cited by the New York Times. The research findings, which looked at the DNA from tens of thousands of Americans, show that “good genes” known to raise HDL levels actually had no bearing on an individual’s risk for heart disease.
Could the recent trial’s results shake up cholesterol science as we know it? We spoke to preventive cardiologist Dr. Robert Block to find out.
Scripts: Can you back up and explain, briefly, the difference between HDL and LDL?
Block: Happily. HDL, as you’ve noted, is the high-density lipoprotein (historically dubbed “good” cholesterol); LDL is low-density lipoprotein (or “bad” cholesterol). Here’s a simple analogy: We often refer to LDL as the “garbage” that clogs up arteries, and HDL as the “garbage trucks” that collect it. In other words, LDL causes blood vessel disease, heart attacks and strokes, whereas HDL actively helps avert it by keeping the circulatory system free and clear.
Besides being “good,” HDL also has been considered “smart”; it has many characteristics that help to regulate overall cholesterol metabolism. Remember, cholesterol is an essential ingredient in building cell membranes, human hormones, and more.
Scripts: For many years we’ve accepted, almost as fact, that high HDL levels are protective. What’s propped up this theory?
Block: The Framingham Heart Study, for starters. It’s a landmark, longitudinal heart-health research project. Initially launched in 1948, it continues to follow participants in an effort to better understand heart disease risk factors. Repeatedly, the Framingham study has shown HDL levels to be better predictors of heart attacks than LDL levels, or other types of cholesterol levels (triglycerides, etc.)
You could also look at the gender argument. As a group, women tend to have higher HDL levels than men, and also a lower risk of cardiovascular disease events to boot. So the two appear connected. Other studies, such as the 1990s Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT), showed that an increase in HDL (thanks to gemfibrozil, a medication that boosts HDL levels) was tied to a significant risk reduction for cardiovascular disease.
On the other hand, as the Times recently pointed out, another prominent HDL project – the AIM-HIGH study – showed little promise and was halted early.
AIM-HIGH set out to test whether a double-punch – raising HDL levels and lowering triglycerides – could reduce the likelihood of repeat heart and vascular problems in people with well-controlled LDL levels. On a cursory glance, the mere fact that the study closed early might seem to deflate the “high-HDL-helps” theory a bit, but it’s worth looking at the study design. In AIM-HIGH participants, the LDL (“bad” cholesterol) levels already were rather low. Going back to our garbage analogy, you can think of it this way: If you have little in the way of trash, amping up your fleet of garbage removal trucks won’t matter much. This goes to show that all findings need to be taken in context of the trial’s design, its inherent limits, and of course, other parallel studies.
Scripts: Well said. Still, researchers say that this may be a perfect example of two factors having an associative, but not causative, relationship. Can you explain this idea to us?
Block: Certainly. And it’s a very good point. “Associative,” in this case, means that having a high or low level of a given molecule correlates with either high or low risk for a linked disease. “Causative,” just like it sounds, would go a step further, attributing credit (or blame!) and implying that the molecule actually causes the disease.
For the HDL saga, if only an association exists between HDL levels and heart disease risk, then raising or lowering HDL blood content would have little power to fend off heart disease and stroke. And that’s not impossible; it’s at least conceivable that HDL is merely a marker (associated and predictive, but not actually causative) of heart disease risk. Current data from many studies, however, have strongly suggested that HDL actually is protective (causative) in preventing the arterial hardening that leads to heart attacks and strokes. That’s why I’m taking the Lancet study’s results with a grain of salt. In large part, it’s a step removed from the real issue: Genetics is just one of a whole host of factors that shape a person’s overall blood HDL level. So to jump right from genes to heart disease risk is a bit of an oversimplification. So many other things work together to influence HDL levels.
Scripts: Even so, the Lancet study seems to have shaken up some big players in the field of HDL research. Do you think this will have major implications for current investigations and clinical care?
Block: I doubt this one study will change the game much. It certainly will (and should) stimulate more research regarding HDL function and metabolism.
It’s interesting to note that a less-talked-about measure, known as the “non-HDL” cholesterol level (this is, simply subtracting HDL from total cholesterol), has been shown in some very large, reputable studies to be a far better predictor of cardiovascular disease risk than LDL and some other blood cholesterol molecules. This is important, as it nods to HDL as an important part of the equation. Another perk of this “non-HDL” measure is that it’s highly practical – it’s valid in the fasting and non-fasting states.
Dr. Block specializes in the care of patients with high blood cholesterol levels. If you’ve been diagnosed with unhealthy cholesterol levels, and are you looking for help getting them under control, call URMC’s Lipid Clinic at URMC at (585) 341-7700.