Achieving LDL-Cholesterol Targets on Statins May Not Negate CVD Risk

Patients who achieve target LDL-cholesterol levels on statin therapy may still be at risk for cardiovascular disease due to elevated levels of low-density lipoprotein particle number or apoprotein B, Robert A. Kreisberg, MD, said Sunday in a General Session at the American Association of Clinical Endocrinologists 19th Annual Meeting and Clinical Congress.

Apoprotein B is increasingly being recognized as a significant risk factor for cardiovascular disease. The differences in the response of LDL-cholesterol and apoprotein B to statin therapy is something that has largely flown under the radar, said Kreisberg, Professor of Medicine at the University of Alabama, Birmingham, Alabama.

“We make the assumption that anything that lowers LDL cholesterol lowers apoprotein B, but the reduction is not equivalent,” he said. “There is a much greater reduction in LDL cholesterol than there is in apoprotein B with statins. When we achieve a 40-plus percent reduction in the LDL-cholesterol concentration with statin therapy, the apoprotein B concentration only decreases by 30%, so there is a relative excess of apoprotein B in most statin-treated patients.”

A substantial number of otherwise healthy-appearing individuals have elevated apoprotein B in relation to their LDL-cholesterol concentrations. Forty percent of individuals with LDL-C below 70 mg/dL will have disproportionately high apoprotein B levels.

“If particle number determines atherogenicity, then the LDL-cholesterol is only a surrogate for particle number, it is not accurately reflecting particle number in patients who we think we’ve gotten to goal by treating them with statins and reducing their LDL-cholesterol concentration,” he said.

In one study, Kreisberg noted, women with metabolic syndrome whose LDL-C was controlled at around 130 mg/dL were found to have higher relative levels of apoprotein B, “indicating that patients with this particular disorder have small dense LDL particles, and just identifying the LDL-cholesterol or thinking that the LDL-cholesterol concentration is acceptable, gives very misleading information because they are at very high atherogenic risk.”

This was true for women with metabolic syndrome being treated with statins, “but the exact same data can be demonstrated in men,” he added. “We can identify these at risk individuals by measuring apoprotein B.”

Kreisberg advised using apoprotein B selectively. “Do not use it for screening and do not use it in every patient. I use it in a number of physicians who are on statins and who still have coronary calcification and they are very happy to have me do so,” he said.