Black people disproportionately experience cardiovascular disease in the United States.[1] Research on allostatic load and stress finds discrimination—resulting from internalized, interpersonal, institutional, and structural racism—to be an arbiter for poor cardiac health among Black people in the United States.[2] Health disparities are consistent across multiple outcomes known to be markers for cardiovascular disease: hypertension, subclinical carotid disease, coronary artery calcification, coronary artery obstruction, elevated cholesterol, visceral abdominal fat deposits, and increased C-reactive protein.[3]

However, despite this research, clinical guidelines for diagnosis and treatment of cardiac disease do not take discrimination or structural factors into account. Instead, they attribute the cause of disproportionate outcomes to one’s race alone. For example, the following guideline is from the Eighth Joint National Committee, which sets national recommendations on treatment thresholds, goals, and medications in the management of hypertension in adults: “Initial antihypertensive treatment should include a thiazide diuretic, calcium channel blocker, ACE inhibitor, or ARB in the general nonblack population or a thiazide diuretic or calcium channel blocker in the general black population.”[4] Furthermore, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are recommended as first-line agents only in Black people with comorbid chronic kidney disease.[5]

Here, Black or African American racial identity is treated as a proxy or a unique numeric variable for diagnostic equations and treatment indications. The use of Black racial identity as a proxy appears in claims ranging from increased “salt sensitivity” contributing to hypertension and the supposed need for specialized pharmaceutical treatments (e.g., BiDil). Use of racial identities as sole determinants of health outcomes frames Black people as having “inherently” poor cardiovascular health.

Framing racial disparities in cardiovascular disease as a product of the social category of race itself is harmful because it falsely attributes racial disparities to genetics and other underlying biological characteristics and it ignores the contributions of internal, interpersonal, institutional, and structural racism to these disparities.

Hypertension—Salt Sensitivity Hypothesis

Many clinical researchers and medical providers today are aware of the Black health disparities in hypertension, oftentimes with many thinking that such disparities are a result of genetic or biological predisposition. However, few clinicians are aware that these assumptions are erroneous and originated in misguided assertions of the “African gene” hypothesis, in which Black people are more likely to have salt sensitivity as a by-product of the slave trade.[6] This assertion is further misguided as critical theorists have pointed out that no current or contemporary West African populations suffer rampant hypertension. Despite this, the American Heart Association website declares: “Researchers have also found that there may be a gene that makes African Americans much more salt sensitive.”

On Medscape and WebMD, two popular publishers of medical information for the general public, cursory searches on the intersections of salt sensitivity and Black race argue that “high rates of high blood pressure in African Americans may be due to the genetic makeup of people of African descent. Researchers have uncovered some facts: In the United States, Blacks respond differently to high blood pressure drugs than do other groups of people.”[7] Claims of biological racial differences in salt sensitivity have unclear origins. In a recent paper by Lujan and DiCarlo (2018), the authors note that “Wilson and Grim…published only a single peer-reviewed scientific paper on the Slavery Hypertension Hypothesis in 1991. As noted by Kaufman and Hall…the majority of the written work on the slavery hypertension hypothesis is limited to conference reports and nonreviewed abstracts and book chapters.”[8]

In 2005, media attention praising Harvard economist Ronald Fryer’s work on salt sensitivity began to influence clinical researchers of racial difference today. It was during this time when changes to clinical guidelines associating Black racial identity with salt sensitivity popularized in clinical medicine. In the seminal paper entitled “Racial Differences in Life Expectancy: The Impact of Salt, Slavery, and Selection,” Fryer et al. hypothesizes how specific factors in the slave trade experience could explain the hypertension disparities among Black people in the United States.[9] They use a Darwinistic “bottleneck theory” of evolution, in other words claiming that the catastrophic population-wide effect of slavery led to the evolutionary selection of a trait that improved survival during the Atlantic Slave Trade. In making this claim, they cite data sources, such as precipitation data and historic images of “a slave trader licking a slave’s face to assess his fitness for the voyage across the Atlantic”:

As T. Buxton writes, “…nobody suffered more intensely from thirst than the poor little slaves, who were crying for water…Perspiration is one source of dehydration….”

In a setting of profuse water loss, the ability to retain salt and hence water substantially increased the chances of survival. Contemporary accounts indicate that at least some slave traders were aware of this, and selected slaves on the basis of the salt on their skin. Figure 2 captures a slave trader licking a slave’s face to assess his fitness for the voyage across the Atlantic. Most of the selection on the basis of salt sensitivity was likely unintentional, however. Salt depleting environments and diseases were ubiquitous throughout the slave trade, favoring individuals able to retain salt.[10]

Despite Fryer et al.’s false and limited arguments to support the slavery hypothesis, this work attracted popular media attention, such as forming the basis of the New York Time’s 2005 article, “To a Unified Theory of Black America.”[11] In 2007, Dr. Oz appeared on the Oprah Winfrey Show and asked the audience, “Do you know why African Americans have high blood pressure?” to which Winfrey studiously replied, “African Americans who survived [the slave trade’s Middle Passage] were those who could hold more salt in their body,” with Dr. Oz’s enthusiastic agreement.[12]

With the widespread blind acceptance of the salt sensitivity hypothesis among clinicians, hypertension disparities faced by Black people are seen not as a consequence of stressful environments and situations caused by social and structural determinants but rather by false notions of biological differences in salt retention. As noted by critical race theory scholar Osagie Obasogie, perhaps the most important rebuttal to the hypothesized link of salt retention and racial difference is the fact that “no contemporary West African population suffers from rampant hypertension. Historical records suggest that Africans’ overall mortality during the Middle Passage was about 13 percent. For a bottleneck theory to hold up, the alleged ‘salt sensitive gene’ would have had to play a significant role for the roughly 87 percent that survived, implying that this gene was relatively common among enslaved West Africans.”[13]

False notions of salt sensitivity that are currently present in clinical medicine and practice will continue to inflict harm on Black communities, as such bad science deflects from attention to social, structural, and environmental stressors that are linked to susceptibility and exacerbation of hypertension.

BiDil

The implications of the erroneous correlation of Black racial identity with hypertension have not only affected clinicians’ perception of disease and pathophysiology, but also treatment for Black people. In 2005, BiDil, a combination pill of two standard therapies—hydralazine and isosorbide dinitrate—for heart failure, became the first drug to receive approval from the US Food and Drug Administration (FDA) to treat a specific racial group—African Americans.[14] However, the clinical development of BiDil was never intended for an explicitly racialized purpose—it was simply another drug to treat heart failure. In this section, we will reveal how the drug development of BiDil is an example of bad science and epidemiology. Moreover, we will explain how the development of BiDil predicated on the use of ideas of the biological inferiority of Black people in order to gain commercial and market success.

In the 1980s, cardiologist Jay Cohn led two clinical trials—V-HeFT 1 and V-HeFT II—to study the drug. The investigators of these trials, however, “did not build the trials around race or ethnicity. They enrolled both Black and white patients and in the published reports of the trials’ successes, they did not break down the data by race. Rather, they presented BiDil as generally efficacious in the population at large, without regard to race and filed a patent.”[15] However, despite these assertions, the FDA rejected BiDil’s approval due to statistical design flaws in these trials in 1997.[16]

The FDA rejection did not restrict use of data from the V-HeFT trials. In an attempt to reconsider how to best market the drug to the FDA and public, Cohn, along with his coinvestigators, returned to the V-HeFT data and recategorized the results by race. There was no scientific reason for this reanalysis, for Cohn and his coinvestigators only turned to race after the initial application to market failed for commercial purposes. In 1999, nearly fifteen years after the first V-HeFT 1 data was collected, the investigators claimed they had discovered a race-based differential response to BiDil treatment.[17] Then, Cohn “filed for and was granted a patent identical to the first one, except that the use was now for African Americans suffering from heart failure, which had the financial and commercial benefit of extending his patent rights an additional thirteen years.”[18]

A company named NitroMed gained the license for BiDil from Cohn and conducted a new clinical trial, the African American Heart Failure Trial (A-HeFT), in order to test BiDil’s race-specific benefit. However, this new trial only included participants that self-identified as African American and did not include a comparison group. Therefore, the trial could not have demonstrated that BiDil works better in African Americans than in any other group. As a result, this specious “reanalysis” opened the door for an epidemiologically flawed race-based trial. Despite this fundamental design flaw, the A-HeFT trial produced data “demonstrating a 43 percent reduction in mortality, leading the FDA to approve a race-specific indication for use by Blacks with heart failure.”[19] Neither Cohn nor any of his collaborators have been able to identify the biological markers responsible for Blacks’ receptiveness to BiDil. Cohn himself states that the drug is effective in non-Black patients as well. The same year that BiDil gained FDA approval, Cohn admitted to prescribing the generic drugs constituting BiDil to 25 percent of his white patients.[20] He directly stated, “I actually think everybody should be using it.”[21]

Ever since its FDA approval, BiDil has been widely prescribed in a race-specific manner, based on the prevailing yet unfounded assumption that “self-identified race mirrored some underlying ‘real’ biological difference that shapes health disparities and drug reaction.”[22] As medical students, we are implicitly taught the same assumption through uncritical textbooks and precepting clinicians. A widely used pharmacology textbook directly states, “A fixed combination of hydralazine and isosorbide dinitrate is available as isosorbide dinitrate/hydralazine (BiDil), and this is currently recommended for use in African Americans.”[23]    

The race specificity of BiDil is unsubstantiated and commercially motivated, yet “it has come to reflect the legal, regulatory, and economic sanctioning of race as a biologically significant category of human difference that meaningfully affects human health” [Obasogie]. This framing falsely leads social categories of race to be perceived as the causes of disease and for structural causes of disease being ignored. Critical race legal scholar Dorothy Roberts powerfully summarizes,

While the racial gap in life expectancy widens, owing largely to the government’s failure to address structural inequities, the poor health of African Americans opens new markets for pharmaceutical companies. The claim that race-based biotechnologies will shrink the gap based on genetic difference is a powerful way to deflect concerns about their unjust social impact and the social inequality that actually drives poor minority health. We should be against an approach that promotes individual health through technological cures as a way of ignoring larger social inequities. This view sets up a false dichotomy between health and social justice: it treats health and justice as opposing values, weighs them against each other, and declares health the winner. It hides the social factors that determine health not only for individuals but for the entire nation. Letting health trump social justice does not really improve the welfare of most people; it supports the interests of big business and the most privileged members of society.

The promotion of race-based medicine misrepresents the relationship between genes, drugs, and health disparities. Of course, pharmaceuticals can help improve sick people’s health, and effective pharmaceuticals should be available to people who would benefit from them. But health inequities are not caused by genes and cannot be eliminated with drugs. Promoting race-based medicine with the myth that poor minority health is caused by genetic difference will only widen the gap, diverting us from the real solution. It makes no sense to put aside social justice concerns in order to improve minority health. A more just society would be a healthier one.[24]