Posted on 01/24/2009 12:22:25 AM PST by neverdem
Age, sex, body mass index, smoking status, hypertension, diabetes, family history, and cholesterol levels are the heavy hitters of risk assessment for coronary heart disease, especially in patients of a certain age. Combined, these risk factors explain a considerable amount of population risk; but in isolation, each is merely a weak predictor of risk, so that making risk predictions at the individual level is a complex and risky process.
Recently, biomarkers such as homocysteine levels and C-reactive protein (CRP) have been added as considerations in predicting individual risk. Their inclusion has sparked considerable debate, and things could heat up yet, given that, as of last month—December 2008—genome-wide association studies have identified at least 22 new genetic markers for coronary heart disease (CHD) risk.
These markers provide novel insights on pathways and mechanisms for cardiovascular disease pathogenesis and will prove invaluable over time in developing new approaches for the prevention and treatment (think “statins”) of the disease. Many of these associations are related to lipid profiles and other known and already measurable risk factors. Some may eventually prove useful in clinical care, given that your DNA sequence is not much affected by transient factors such as diet or the presence of a cold. And at least some of the markers seem to be independent of all currently measurable markers of cardiovascular disease risk.
The markers are those near the 9p21 locus. The presence of certain variants at this locus increases an individual's risk for CHD by about 1.3 fold over the average individual, whereas protective variants at the locus will diminish risk for the disease.
Can these genetic risk markers for coronary heart disease be used to improve the prediction of disease risk and health outcomes? In our attempts to answer this question we cannot lose sight of our goal: We consider using new risk markers in clinical medicine to improve health outcomes, not to refine current models for predicting risk.
Remember, too, that the process of analyzing the usefulness of these markers is occurring within the context of a health care system in which cost consciousness is mandatory and cost savings would be a huge benefit. It may turn out that adding markers to existing risk models makes little sense unless the new markers dramatically improve risk discrimination.
Consider a recent area under the curve (AUC) analysis of the potential for improved risk prediction for CHD: Adding 22 genetic cardiovascular risk markers to the conventional risk factors increases the AUC from 63% to 66%. Although this small change is significant, it is not transformative for the individual patient.
An incremental improvement on CHD risk assessment could conceivably drive up health care costs with little return on the investment. Transformation would therefore best be achieved by discovering additional genetic contributors to risk as well as rethinking the way in which we use the information to care for individual patients and populations.
For example, it is possible that those identified as having increased risk by virtue of these genetic markers at 9p21 may be subject to more-intense management. Using the information this way may improve health outcomes and is a hypothesis that should be tested. Alternatively, health benefits and cost savings may be achieved if those individuals shown to be at reduced risk had less-aggressive management with expensive drugs and laboratory tests.
Most scientists and providers agree that it is too early to recommend using the new CHD risk markers in routine care. However, CHD risk evaluation is rapidly evolving, and you can expect that future guidelines will incorporate at least some elements of genetic risk assessment. The big question is whether such guidelines will transform or simply tweak cardiovascular health care.
He speaks of transient factors, diet and colds not having much effect. What is his stance on pharmaceuticals? Something is not quite stirring the kool-aid to me. What about epigenesis, whereby environmental influences switch genes off and on? This, btw is my favorite thing, epigenesis. It might explain why institutionalizing kids and prisoners cause very predictive changes in many of their brains.
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