Blood levels of oxidized phospholipids strongly predict the degree of narrowing seen in coronary arteries affected by atherosclerosis, according to an article in the July 7 issue of the New England Journal of Medicine.

The current work represents development of a new test, as well as key findings associated with clinical research on its significance. The new test detects and measures oxidized phospholipids: The researchers found that levels strongly predict extent of coronary narrowing, especially in people younger than 60 years old who have elevated blood cholesterol levels. The researchers also discovered that the oxidized phospholipid particles are strongly attached to lipoprotein a, Lp (a), which might explain why the lipoprotein may be atherogenic.

Lp (a), discovered in the 1960s, has received little attention by researchers for the last decade due to the lack of understanding of its role in atherosclerosis. This study suggests that Lp (a), which has a strong affinity for binding to the blood vessel wall, may play a key role in development of atherosclerosis with oxidized phospholipids. Both are known to be highly pro-inflammatory.

“We’ve known about other lipid risk factors for years, such as elevated Low Density Lipoprotein (LDL) cholesterol, low levels of High Density Lipoprotein (HDL) cholesterol, and elevated triglycerides,” said lead author Soritios Tsimikas, MD. “Lp(a) appears to be another risk predictor, particularly in patients with abnormal cholesterol levels, but it has not been determined how it actually causes arterial blockages.

“This study provides a potential explanation, and shows that high levels of oxidized phospholipids and Lp (a) are tightly associated with coronary heart disease, indicating that they could be useful tests to determine risk in patients,” he said. “It also demonstrates that these molecules could be promising targets for pharmaceutical research, particularly in developing new drugs to reduce their levels in the bloodstream and in the vessel wall.”

The team analyzed blood samples from 500 patients being treated for heart problems at the Mayo Clinic in Rochester, MN, including the clinical and laboratory risk factors associated with atherosclerosis and heart disease in patients who were referred for coronary angiography. They found that levels of oxidized phospholipids could predict the presence of coronary blockages even after taking into account all other known risk factors such as abnormal cholesterol levels, high blood pressure, smoking and gender.

Interestingly, said Tsimikas, the risk attributable to oxidized phospholipids was nearly identical to the risk attributable to Lp (a) in the overall group, but in patients under 60 years old, oxidized phospholipid measure was a strong indicator independent of Lp (a). This suggests that oxidized phospholipids may be more powerful determinants of risk for coronary artery disease in patients younger than 60 years old compared with those older than 60 years old.

“These results suggest that Lp (a) and oxidized phospholipid levels are very tightly linked and each helps the other contribute toward atherosclerosis when found at high levels in the blood,” Tsimikas said. “These two molecules may be working differently in younger patients, so that oxidized phospholipids may generate additional risk above and beyond Lp (a). As this is the first study to show this, further confirmation will be required in other studies.”

He noted that while elevated LDL cholesterol levels alone were very strong predictors of coronary artery disease, the combination of oxidized phospholipids with elevated cholesterol levels was the highest predictor for determining the presence of coronary blockages, showing a 16-fold higher risk for coronary blockages in those with the highest levels of both compared to the lowest levels of both. This suggests that these biomarkers may provide improved diagnostic accuracy in patients, above and beyond knowing the cholesterol levels.