Using newer lipid markers to either replace or supplement conventional cholesterol measurements doesn’t improve cardiovascular risk prediction, according to a report from the Emerging Risk Factors Collaboration in the June 20 issue of JAMA.
Some experts have advocated simplifying and perhaps improving cardiovascular disease risk prediction by replacing the currently accepted measurements of total and HDL cholesterol with other measurements (such as the ratio of total:HDL cholesterol, or the difference of total minus HDL cholesterol) because these are believed to better reflect the underlying atherosclerotic process. Others have proposed adding measures of apolipoprotein B, apolipoprotein A-I, lipoprotein (a), or lipoprotein-associated phospholipase A2 to the current risk prediction formulas to improve risk prediction.
To examine whether any of these alternative methods of risk prediction would improve on the currently accepted method, researchers in the Emerging Risk Factors Collaboration reviewed the literature from 1968 through 2007 for prospective cohort studies that obtained numerous lipid measures and reported CVD outcomes, said Dr. Emanuele Di Angelantonio, head of the collaboration’s writing group, and his colleagues.
To assess the accuracy of each method of risk prediction, the researchers selected 37 studies involving 165,544 subjects in 15 countries who had no CVD at baseline and were followed for a median of 10 years. There were 15,126 incident fatal and nonfatal cardiovascular events, including 10,132 coronary heart disease and 4,994 stroke events.
Replacing total and HDL cholesterol measures with any other lipid markers did not improve CVD risk prediction in the study population as a whole, or in clinically relevant subgroups such as diabetes patients or people with elevated triglycerides. In fact, using apolipoprotein B and A-I measures instead of total and HDL cholesterol measures significantly worsened risk discrimination, said Dr. Di Angelantonio of the department of public health and primary care at the University of Cambridge (England), and his associates.
Adding information on various "emerging" lipid markers to existing risk assessments only improved prediction slightly. And none of the newer lipid markers significantly changed classification of subjects "across the clinical risk cutoff levels that are currently used to inform treatment decisions," the investigators said (JAMA 2012;307:2499-506).
The researchers then created a statistical model that assessed various lipid markers specifically in 13,622 patients who were judged to be at intermediate risk after screening by conventional risk factors alone. Such patients would not be recommended for statin therapy according to Adult Treatment Panel III guidelines.
Using lipoprotein (a) measures would reclassify only 555 of these subjects (4.1%) to a higher-risk group, using lipoprotein-associated phospholipase A2 would reclassify only 365 subjects (2.7%) to a higher-risk group, and using a combination of apolipoprotein B and A-I would reclassify only 154 subjects (1.1%) to a higher-risk group. "In other words, such targeted assessment of [and initiation of statin therapy in] individuals at intermediate CVD risk could help prevent [one] extra CVD outcome over 10 years for every 801 assessed for lipoprotein (a), every 973 assessed for lipoprotein-associated phospholipase A2, and every 4,541 assessed for the combination of apolipoprotein B and A-I," Dr. Di Angelantonio and his associates said.
This study was funded by the British Heart Foundation, the U.K. Medical Research Council, and the U.K. National Institute of Health Research, Cambridge Biomedical Research Centre. Dr. Di Angelantonio reported ties to Merck Sharp and Dohme, John Wiley & Sons, and Pfizer, and his associates reported ties to numerous industry sources.