Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery Disease

NEJM -- Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery Disease:
Sotirios Tsimikas, M.D. et al.
"Background Lp(a) lipoprotein binds proinflammatory oxidized phospholipids. We investigated whether levels of oxidized low-density lipoprotein (LDL) measured with use of monoclonal antibody E06 reflect the presence and extent of obstructive coronary artery disease, defined as a stenosis of more than 50 percent of the luminal diameter"
(From Daily Headlines)
SAN DIEGO, July 6-The connection between levels of oxidized low-density lipoprotein (LDL) and the risk of coronary artery disease has been strengthened, a finding that may one day lead to the era of oxidized phospholipids as a diagnostic marker or even a therapeutic target.

Oxidized LDL levels showed a "strong and graded association (P <0.001) with the presence and extent of coronary artery disease," reported Sotirios Tsimikas, M.D., of the University of San Diego and colleagues in the July 7 issue of the New England Journal of Medicine.

Although phospholipids such as LDL are important to the structural integrity of cells, when oxidized they can promote inflammation, which in turn can lead to coronary artery disease, the researchers said.

To evaluate the relationship between circulating oxidized LDL and coronary artery disease, Dr. Tsimikas measured oxidized LDL levels in 504 patients 18 to 75 years old before they underwent clinically indicated coronary angiography.

The researchers also measured the levels of another molecule, Lp(a) lipoprotein, which many believe binds to oxidized LDL and helps degrade it. But this molecule can also contribute to coronary artery disease when its levels are chronically high.

Statistical analysis showed that, in the entire study group, the predictive value of oxidized LDL for coronary artery disease was similar to that of traditional risk factors such as age, hypertension, and LDL cholesterol levels.

However, the association between oxidized LDL and coronary artery disease was much stronger for patients less than 60 years old compared with older patients.

Among patients 60 or younger, those in the highest quartile for oxidized LDL had more than three times the risk for coronary artery disease compared with those in the lowest quartile (P <0.001).

Also among patients 60 or younger, those in the highest quartile for Lp(a) had more than 3.5 times the disease risk compared to those in the lowest quartile (P <0.001).

The researchers speculated that the strength of the association between oxidized LDL and coronary artery disease decreased for those older than 60 because of the cumulative contributions of additional risk factors as people grow older.

In an Perspectives article, Judith A. Berliner, Ph.D., and Andrew D. Watson, Ph.D., of UCLA welcomed the new findings, going as far as to state they established a causal connection -- a claim the researchers themselves did not make.

"This study is the first to establish a causal connection between the levels of oxidized phospholipids and the risk of coronary artery disease," they wrote. "Thus, oxidized phospholipids may be a diagnostic marker of coronary artery disease or may represent a potential target for therapeutic intervention."

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Primary source: New England Journal of Medicine
Source reference:
Tsimikas S et al. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. NEJM. 2005; 353(1): 46-57.

Additional source: New England Journal of Medicine
Source reference:
Berliner JA et al. A role for oxidized phospholipids in atherosclerosis. NEJM. 2005; 353(1): 9-11.