Cholesterol-Carrying Particle Tied To 70 Percent Increase In Heart Attack Risk

In the first large-scale study of this topic so far, scientists at Oxford University found a "clear association" between elevated Lp(a) levels and increased coronary heart disease risk in the general population. Their findings are based on reviews of 27 smaller studies that involved more than 5,200 individuals who had heart disease or had survived a heart attack.

"For more than a decade, there has been controversy about whether Lp(a) concentrations can predict increased risk of heart disease," says John Danesh, MBChB, MSc, DPhil., of Oxford's Clinical Trials Unit. "Our analysis indicates that high Lp(a) values are a definite risk factor, but there is still much we don't know, particularly whether reducing Lp(a) levels can help prevent heart attacks."

Lp(a) was first discovered in Norway in the 1960s, Danesh notes, but its exact function in the bloodstream remains a mystery. It consists of two main attached components: a molecule of "bad" low-density lipoprotein (LDL) cholesterol and a large protein resembling plasminogen, which aids the blood's natural clot-preventing activity.

"It has been suggested that Lp(a) might either mimic or block plasminogen," Danesh says, "but that still remains to be proven. In the general population, Lp(a) values are highly skewed, and they appear to be determined mainly by genetic factors. People tend to have either very high or very low concentrations, and blacks generally have higher values than whites."

In the Oxford study, the number of heart attacks suffered by individuals with the highest Lp(a) concentrations was compared to the number of attacks among those with the lowest levels of Lp(a). During a decade of follow-up, the highest group had 70 percent more heart attacks than the lowest group.

So far, there are no readily available drugs for lowering Lp(a), Danesh points out, and those that do exist have many undesirable side-effects.

Also, he says there are no standardized blood tests at present to measure Lp(a). "Special tests are required and are used mainly for research purposes, but efforts are being made to make testing more available."

Danesh says the Oxford study provides the most reliable assessment so far of Lp(a)'s association with coronary disease, but many important questions remain unanswered.

He says two main types of research are needed: (1) large observational studies to demonstrate the strength of the association between Lp(a) and heart disease in a range of different circumstances ­ at different ages, different levels of classical risk factors, in men and women, etc.; (2) clinical trials of treatments to reduce Lp(a) and their effectiveness in preventing heart disease.

"Currently, the lack of a practical Lp(a)-lowering drug makes the second type of study difficult," Danesh says. "Overall, it will take much further study to determine the relevance of Lp(a) in the causation of coronary heart disease, but at least we have clearly established a moderately strong association between the two, independent of the standard risk factors."

Other researchers participating in this study include Rory Collins, MBBS, MSc., and Richard Peto, FRS.