Only slight improvements in cardiovascular risk prediction were gained by adding more blood lipid-related markers to conventional factors, researchers said.
Fewer than 5% of individuals would have their risk classifications changed by including such markers as apolipoprotein A-I, apolipoprotein B, lipoprotein(a), or lipoprotein-associated phospholipase A2 (LpA-PLA2) in gauging the likelihood of major cardiovascular events, reported John Danesh, FRCP, of the University of Cambridge in England, and colleagues belonging to the Emerging Risk Factors Collaboration.
At best, adding more lipid markers to the risk prediction equation brought "slight improvement," the researchers wrote in the June 20 issue of the Journal of the American Medical Association. Replacing the standard markers with the other lipoprotein-associated factors reduced the accuracy of risk prediction.
"These findings applied to clinically relevant subpopulations, including people with diabetes and people with elevated triglyceride levels," Danesh and colleagues noted.
Earlier studies have gone back and forth on whether blood lipid measurements besides total and HDL cholesterol contribute significantly to the accuracy of risk prediction. Some research groups have proposed supplementing or even replacing standard cholesterol markers with various other lipid components that appear to be associated with cardiovascular event risk.
But other research has failed to confirm the value of additional lipid parameters, leading Danesh and colleagues to perform a meta-analysis of data from 37 prospective cohorts in which blood lipids were measured and cardiovascular events systematically recorded.
Overall, these cohorts comprised more than 165,000 individuals experiencing some 15,000 cardiovascular deaths and nonfatal MIs and strokes over a median of 10.4 years of follow-up.
Measurements of apolipoprotein A-I and B and lipoprotein(a) were available in more than 130,000 of the study participants. Information on LpA-PLA2 was obtained for about 32,000 participants.
The pooled data showed that each of these factors, except for apolipoprotein A-I, was significantly associated with increased event risk after adjusting for age, smoking status, systolic blood pressure, and history of diabetes. Hazard ratios ranged from 1.13 to 1.24 for each standard deviation of higher age and systolic blood pressure (P<0 .05=".05" a="a" and="and" apolipoprotein="apolipoprotein" b="b" for="for" lipoprotein="lipoprotein" span="span">LpA-PLA0>2.
But adding these factors to total and HDL cholesterol only rarely altered participants' classifications into low-, medium-, or high-risk groups.
Adding each marker individually changed risk classifications in fewer than 1% of participants, Danesh and colleagues found.
The researchers also looked more narrowly at the effect on the number of participants estimated to have at least a 20% 10-year risk of major events, which would qualify them for statin treatment.
The most influential additional marker in this respect was lipoprotein(a). Adding it to conventional risk factors boosted the number of participants in this risk group by 4.1%.
Adding a combination of apolipoproteins B and A-I to conventional risk factors would boost the number qualifying for statins by 1.1%, and LpA-PLA2 would increase it by 2.7%.
Danesh and colleagues estimated that, on the basis of these calculations, it would be necessary to test from 800 to 4,500 individuals for these markers in order to prevent one major cardiovascular event over 10 years.
In an accompanying editorial, Scott Grundy, MD, PhD, of the University of Texas Southwestern Medical Center in Dallas, suggested that the study's implicit basic assumption -- that accurate risk classification as currently defined is important -- can be questioned.
"These [low-medium-high] risk categories were designated more than a decade ago to guide in the use of cholesterol-lowering drugs (e.g., statins) in primary prevention, and were defined to reduce use of expensive drugs for lower-risk persons," he wrote.
Now that statins are available in cheap generic form and their safety is "well established," the need for risk categories in deciding who should get them is "less compelling," Grundy suggested.
Instead, it makes more sense to identify patients now classified as low-risk who may benefit from statins, he argued. Recent research has suggested that this may be a sizable population.
Grundy wrote that imaging methods for detecting early, sub-clinical atherosclerosis or simple risk prediction algorithms based on age, sex, LDL cholesterol, "and perhaps another major risk factor" may be the best way to select such patients.
POSTED BY: Steven Almany M.D.