Are apolipoproteins the key to heart attack risk?
When it comes to your risk of heart attack, cholesterol is one of the major factors of concern. Current clinical guidelines rely on blood tests of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides to determine your risk of heart disease. However, a recent study published in The Lancet suggests that cholesterol-carrying molecules called apolipoproteins may also play an important role in predicting heart disease.
About the study
Researchers in Sweden and Norway enrolled 175,553 healthy Swedish men and women in a study to measure their blood levels of cholesterol, triglycerides, and apolipoproteins B and A-1. All participants were enrolled and had their blood tested between 1985 and 1989 or between 1990 and 1996. The study population included 98,722 men with an average age of 47 and 76,831 women with an average age of 49.
After approximately five years of follow-up for each participant, researchers used death certificates to determine which participants died of heart attacks and then analyzed their cholesterol, triglyceride, and apolipoprotein levels. They were trying to determine if levels of apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) are better predictors of fatal heart attack than high LDL cholesterol, high triglycerides, and low HDL cholesterol.
Analysis of the data suggests that high levels of apoB indicate increased risk of fatal heart attack regardless of whether a person has high levels of LDL cholesterol. According to current clinical guidelines, high LDL is a predictor of heart attack risk, but in this study, even people with low or normal LDL levels were at increased risk of heart attack if their apoB levels were high. These results suggest that high apoB levels may be the stronger indicator of heart attack risk.
The data also showed that higher apoA-1 levels were protective against heart attack, similar to the way that higher HDL levels are protective. Again, current clinical guidelines for cholesterol abnormalities are based on low HDL levels, not low apoA-1 levels.
The researchers also found that the ratio of apoB to apoA-1 is strongly related to risk of fatal heart attack. Dr. Goran Walldius, the study's lead author, calls this relationship between apoB and apoA-1 statistically stronger as a predictor of fatal heart attack risk than LDL and HDL cholesterol.
Unlike many studies of this kind, this study did not attempt to factor in all possible risk factors for heart disease, such as high blood pressure, diabetes, smoking, and so on. No information was collected regarding such risk factors or any treatment participants may have received. Rather, every eligible person was allowed to participate in the study and no exclusions were made based on risk factors or therapies. Although this may be considered a limitation because we do not know what role, if any, these factors played in the participants' heart health, the study population was quite large, and without the usual exclusions, probably very representative of a large population of apparently healthy people.
How does this affect you?
The findings of this study are not likely to immediately change the cholesterol testing practices of your primary care physician. There is no consensus within the medical community as to whether the measurement of apoB and apoA-1 is a valuable tool in predicting heart disease risk. This study is one of the largest to study these factors.
Current international guidelines recommend treatment for high cholesterol based on LDL and HDL cholesterol measurements. The authors of this study suggest that our ability to predict who is at risk for fatal heart attack could be improved by including measurements of apoB, apoA-1, and the apoB/apoA-1 ratio. In their accompanying editorial, independent reviewers Sathanur Srinivasan and Gerald Berenson caution that before such measurements become part of clinical practice, measurement methods must be standardized and threshold and target values must be set.
Although your next cholesterol test may not be any different from the last, the day may come when you'll be tracking your apolipoprotein levels the way you track your HDL and LDL levels.
Walldius G, et al. High apolipoprotein B, low apolipoprotein A-1, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study.
The Lancet . December 15, 2001. 358: 2026-2033.
Srinivasan SR and Berenson GS. Apolipoproteins B and A-1 as predictors of risk of coronary artery disease.
The Lancet . December 15, 2001. 358: 2012-2013.
Last reviewed Dec 31, 2001 by ]]>Richard Glickman-Simon, MD]]>
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