Improving the use of “race” in clinical decisions: Learn more about racism or ancestry?

Suppose you are a doctor seeing a patient with hypertension.  The patient is a 54 year-old black man.  What should you do?  What more do you want to know before deciding what to do?

Perhaps you already know more along the following lines:

Regardless of region, blacks were less likely than whites to achieve treatment success with atenolol (P = .02) or prazosin (P = .03) and more likely with diltiazem (P = .05).  ( Cushman et al., 2000)

(Atenolol is a beta blocker; prazosin lowers blood pressure by relaxing blood vessels ; diltiazem is a calcium channel blocker).

You might say to yourself, “I know that not all black men with hypertension do better with calcium channel blocker and worse with beta blockers, but on average they do.  So I’ll prescribe diltiazem and see what happens.  If it doesn’t work well, I’ll change the medication.”

But you might also say, “I want to know more about this black man and learn to make decisions not simply based on averages.”  If so, let me trace two paths of learning more that you might follow, first around racism and second around ancestry.

“This is a 54 y.o. black man, or, at least, that is how he appears to me…”  You may know that not every man that looks black identifies as African-American, so you might first ask that.  Even if he doesn’t self-identify that way, you might think, “Given his skin color, he may have experienced racial discrimination.  Let me ask him whether he has.”  You may know that self-reports of experience of racism are conditioned by class, so you might look for a survey that is better at probing beyond self-reports.  You might, however, think, “Having someone answer questions on a survey and then interpreting the results takes time and the insurance company doesn’t reimburse me for that time.  What would I do with what I learn, anyway?”  Yet, if enough doctors collected the survey data—or even the self-reports of experiences of discrimination—then researchers could assess whether there was an association with that and the responses to the alternative hypertension medications.  After all, it’s implausible that experiences of discrimination have no physical effect on our bodies and it’s plausible that these effects might add up over time to produce differences in ways that bodies are hypertensive.  “OK,” you might say, “I’m interested in this line of inquiry, but I won’t start asking my patients about experiences of racial discrimination until researchers have shown clear associations with what anti-hypertension medicine works best.”  Understandable, but you might do some reading after hours about the positive effects of acknowledging the topic of discrimination and, conversely, of pride in one’s identity.

Now to the ancestry line of inquiry: “This is a 54 y.o. black man, or, at least, that is how he appears to me…”  You may know that not every man that looks black identifies as African-American, so you might first ask that.  You might discover that he is an immigrant from Africa, not a descendant of slaves in the United States.  Either way, you might know that genomic studies are starting to identify some genetic variants of biomedical significance that are more common in people of specific areas of Africa (e.g., Genovese etal. 2010).   You might ask, “Does your ancestry trace back to region X?”  There is a good chance that African-Americans won’t know this, or won’t know their places of ancestry with enough precision to be helpful, or will have multiple places of origin in Africa.  Moreover, if he is a descendant of slaves, you know he has probably has a lot of European ancestry.  “OK, we need to do a genetic test to see if he has the genetic variant in question.  But, on second thoughts, doing the test is expensive and the insurance company doesn’t reimburse me for that.  In any case, what would I do with what I learn?  Has any genetic variant been associated with what anti-hypertensive medication is appropriate, or is it simply telling us that the population of African-American men as a whole (meaning the population on average) has higher risk when they possess that variant?”  Yet, if researchers collected more data about ancestry (which would probably require genetic markers given people’s imperfect knowledge of their ancestors) then researchers could assess whether there was an association between ancestry and responses to the alternative hypertension medications.  But you might ask, “how plausible is it that such associations will be useful for clinical decisions, or even for further research?” You might ask this because you know that Genome-Wide Association studies “have not found common genes with a big impact on heart health” (Couzin-Frankel 2010).  There is heated debate about whether to “hope that the low-effect genes they are finding will help identify pathways and drug targets.”  (“Low effect” here means much smaller relative risk than between modifiable aspects of diet and behavior.)  “OK,” you might say, “I wonder if I should be interested in this line of inquiry?  Let me see if anyone can show me what considerations I’m overlooking.”

Let me note one thing that has been put aside in this exposition of the two paths.  The Cushman study showing differential response to medication between blacks and whites was actually a study of differential responses to medication inside versus outside the “stroke belt,”  that is, the “12 states with stroke mortality rates more than 10% above the mean rate for the rest of the United States: 10 of these states are in the south- eastern region.”  The authors conclude:

Hypertension in patients residing inside the Stroke Belt responded less to the use of several antihypertensive medications [even after controlling for race] and important differences were shown in a number of characteristics that may affect the control of blood pressure, compared with patients residing outside the Stroke belt.

Perhaps the first questions a doctor might ask is “Do you come from the Stroke belt? Do your parents?”  In their spare time the doctor might learn about the competing theories for the existence of this belt (e.g., Howard et al. 2010, Kuzawa and Sweet 2009).

Reference
Couzin-Frankel , J.: 2010, Major Heart Disease Genes Prove Elusive. Science 328(5983),1220-1221.

Cushman, W; D.J. Reda; H. M. Perry; D. Williams; M. Abdellatif; B. J. Materson, Regional and Racial Differences in Response to Antihypertensive Medication Use in a Randomized Controlled Trial of Men With Hypertension in the United States, Arch Intern Med. 2000;160:825-831.

Genovese, G. et al. (2010), Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans, Science 13 August 2010: 329 (5993), 841-845.

Howard, V. et al. (2010) Prevalence of hypertension by duration and age at exposure to the stroke belt, J Am Soc Hypertens. 2010 Jan–Feb; 4(1): 32–41.

Kuzawa C. and E. Sweet (2009), Epigenetics and the Embodiment of Race: Developmental Origins of US Racial Disparities in Cardiovascular Health. AMERICAN JOURNAL OF HUMAN BIOLOGY, 21(1); 2-15.

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3 thoughts on “Improving the use of “race” in clinical decisions: Learn more about racism or ancestry?

  1. Chuck

    In case you missed it, Nature Genetics had an issue on this (Nature Genetics v. 36, 2004). Many of the concerns that you noted were mentioned but it was generally thought that knowledge of ancestry had value and that, to the extent ‘race’ was a proxy for ancestry, knowledge of that also had value — at least, given the current state of knowledge. You might find the argument made by Tate and Goldstein in “Will tomorrow’s medicines work for everyone?” interesting. In that article, the authors argued that, for the sake of “social justice,” more consideration of ancestry in medical research is needed. The article brings to mind some problematic ethical issues that run reverse to your concerns. In that regards, it’s worth considering that pharmaceutical and other companies market their products internationally and yet their experimental populations are not always globally representative. Usually opposition to the idea of “race based medicine” hangs on images of handing out different pills to “X people” than “Y people,” but you can look at the issue in reverse. Globally, medicine is used yet the efficacy, it could be argued, is judged by unrepresentative samples. I guess, though, that would only be a concern if you think that there could be medical relevant genetic differences between historic regional populations.

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  2. Chuck

    To continue with what I was saying, one problem that I have with critiques of “race based medicine” is that often overly provincial views are taken. Take your following point:

    “You might ask, “Does your ancestry trace back to region X?” There is a good chance that African-Americans won’t know this, or won’t know their places of ancestry with enough precision to be helpful, or will have multiple places of origin in Africa. Moreover, if he is a descendant of slaves, you know he has probably has a lot of European ancestry. “OK, we need to do a genetic test to see if he has the genetic variant in question.”

    Your implicit reasoning about race based medicine seems to be, basically: is it good for Africans Americans? The question “Do calcium channel blockers treat hypertension worse than beta blockers?” has relevance, though, not just for African-Americans but for the billions of non-Europeans who were likely underrepresented in the study samples. (Or were the samples globally representative? — I don’t know; it’s something to look into,) Perhaps considerations of ‘race’ has questionable relevance for African-Americans and other hybrid groups, but what about West Africans, Oceanians, and East Asians? Presumably, much of the West African medical knowledge is based on research conducted on non-African populations. (I don’t know, but again it might be worth looking into). Does this have relevance? Should medical practitioners outside the US be alerted that there could be medicine x population genotype interactions? Those, to my mind, are the important questions. The exclusive focus on ‘race’ in context to the US or West is somewhat myopic especially given the global demographics and projected growth.

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