The Actual Cause of Coronary Heart Disease?

There are plenty of risk factors for coronary heart disease – high blood pressure, high cholesterol, smoking, and lack of exercise – but none of these are a ‘proximate cause’ of the atherosclerosis that can precipitate a heart attack.  Blood C-reactive protein (CRP), which is associated with inflammation in the body, has come under suspicion as a cause of coronary artery disease, but this has recently been discounted in a Lancet publication.  Now there’s a new candidate: lipoprotein(a), or Lp(a); supporting evidence is to be found in a New England Journal of Medicine article.    

Lp(a) is really a third type of cholesterol (after low-density lipoprotein [LDL] cholesterol and high-density lipoprotein cholesterol).  However, the increased risk to people from a raised Lp(a) is significantly less than that from a high LDL-cholesterol.  The evidence for Lp(a)’s role came from a search for relatively rare genetic variants in the population – in 5% to 10% of people – in association with a measurable increase in coronary heart disease.  Over 3,000 subjects with coronary disease and more than 3,000 control subjects from 4 European countries were tested initially; the findings were then substantiated in an additional 4,500 patients and 4,500 controls.

Among three chromosomal regions strongly associated with the risk for coronary disease, one (the LPA locus) had the strongest association.  Two variants at this locus were linked to an overall increase in Lp(a), but decreased Lp(a) size.  And, as ‘proof’ that Lp(a) – in some form – has a causal role in coronary disease, the researchers found that after adjustment for the Lp(a) levels, the association between these two variants and coronary disease was abolished. 

Many questions still remain, but a role for Lp(a) in causation of coronary disease is pretty certain; so much so, that this discovery may well open the way to research projects looking for new drugs to interfere with the Lp(a) role.