The Doctor Weighs In

The recent posting by Dr. Salber describing the ostensible superiority of wine drinking over beer or spirits reminded me that I actually saw with my own eyes one of the confounding factors of the study, namely, lifestyle differences.

In the mid-80's, I was a visiting scholar at the University of Turku (also called Oulu ) where the study was done.
OuluOn weekend nights the streets were littered with drunks asleep (comatose is a more apt description of their state) on the sidewalks, the gutters, and the roads. It was a sobering sight to behold: well-dressed, seemingly upright citizens, mostly men, wallowing in the mud. I asked my colleague, a surgeon at the University hospital, what was the drink of choice. It was vodka, he said. What about beer? That’s for kids. And wine? Only women and intellectuals drink wine; and they rarely get drunk.

I remember thinking at the time: these people are not going to live very long. In fact, the three most common causes of their demise were heart disease, liver disease, and accidents (like being run over by a car while sleeping on the road). So, anybody who has been to Oulu would tell you—this is not a good study, and scientists who live in Oulu should have known better.

Wine is good for you

True, but up to a point. Studies have shown that men who drink up to 2 glasses of wine a day, and women 1 glass a day (sorry, life is not fair) are less prone to coronary disease and cardiac events.

The mechanism of such a blessed effect of wine is not really understood. Several studies have shown that wine (especially red, some claim) causes elevation of HDL, the “good” cholesterol.

But don’t forget a big caveat: Our eagerness to believe in something can color our judgment. The facts however, cannot be changed by beliefs, however ardent.

Is all “good” cholesterol the same?

In March of last year Pfizer withdrew the experimental drug torcetrapib from clinical trials because it caused excess mortality due to cardiovascular events over the placebo. That was quite a shock, because the drug was designed to elevate HDL (good cholesterol) levels. Why the drug caused higher mortality we do not know yet, but one theory is gaining prominence: not all HDL is born equal.

There are most likely variants of HDL that are actually “bad” cholesterol. Ansell and his coworkers (Circulation, vol.108, pp. 2751-2756, 2003) studied people who had very high HDL levels, but still developed heart disease. In lab assays they found that these people’s form of HDL promoted deposition rather than removal of cholesterol from the artery walls. Could it be that Pfizer’s ill-fated drug promoted the wrong kind of HDL? Quite likely.

HDL is actually a family of particles, varying in their protein components, size, and other parameters. In the heart of Tuscany (the wine country of Italy ) there is a village where people were found to have very low levels of HDL, but were not prone to heart disease. Aha! The protective effect of wine, you might eagerly conclude. But what about other villages in the area? They too drink, but have “normal” levels of cardiovascular disease (and normal levels of HDL). So what gives?

A toast to Milano

It turns out that the people in this village have a variant of a protein that is part of the HDL particle, called Apo A-1. The variant, Apo A-1 Milano is apparently responsible for the protective effect, despite the low levels of HDL in the blood. In fact, Nissen and his colleagues from the Cleveland Clinic showed that five infusions of this protein shrank plaques in the arteries (Nissen et al. J. Am. Med. Assoc. vol. 290, pp. 2292-2300, 2003).

What this study shows us is that our classification of HDL as “good cholesterol” should be reconsidered. There is probably “good” and “bad” HDL cholesterol. As scientists almost invariably say at the end of a paper: more work needs to be done.

Nothing is simple…

Dov Michaeli MD, Ph.D