Era to Action: 40 Years of Health Disparity Research in Cardiovascular Disease and the Path to Equity

A recent report by Islek and colleagues in this issue of the Journal of the American Heart Association (JAHA) describes racial differences in the outcomes of acute myocardial infarction (AMI) from the ARIC (Atherosclerosis Risk in Communities) study. ¹ Although the data are intriguing, particularly with respect to inpatient mortality, this is a persistent and well‐known inequity of cardiovascular disease (CVD) care in the United States. For >4 decades, investigators have shown disparities in access, acute management, and long‐term treatment for several interventions for Black Americans. The Heckler Report of 1985, a pivotal observation of racial disparities in CVD health, likely inspired efforts to initiate further studies, such as ARIC and the JHS (Jackson Heart Study), evaluating real‐world observation as a means of verifying the undeniable adversity the Heckler Report documented. ¹ , ² , ³ , ⁴ , ⁵ This federal, bipartisan initiative was the first of its kind to call attention to an excess of ~60 000 deaths per year for Black Americans. These data were thought to be related to the historical disenfranchisement of Black Americans, particularly those descendants of enslaved people, commonly from biased policies of health care access, racism, and government. Despite the efforts of many to address these worrisome inequities observed in 1985, data from the current era demonstrate persistent and expanding CVD mortality racial disparity. ⁶ Thus, decades of extensively documented racial and ethnic disparities in CVD outcomes of the United States have made little substantial progress beyond demographic narratives characterizing a persistent problem. ⁶ The intent and purpose of the health equity mission are essential, but reducing disparate CVD outcomes is ultimately the goal.

Although often minimized, this history is profoundly vital in understanding the power dynamics and other factors that are associated with ongoing racial and ethnic disparities in CVD health. As the United States gradually evolved in tandem with the emergence of global commerce, so did the diversity of its population. However, imbalanced or heavy‐handed policies that perpetuate systemic discrimination have led to many state and federal laws, strategically designed to disenfranchise minoritized communities without agency to effect change. This study by Islek and colleagues, particularly in the current landscape, lends an opportunity for the medical society to ask ourselves, “Have we made the strides in reducing racial disparities in CVD for the US population as we might have hoped?”

Within the time frame of the data collected for the recent ARIC analysis by Islek and colleagues, significant advances in the management of AMI care occurred, yielding proven and efficacious interventions from randomized controlled trials (RCTs). Yet, as the pace of proven evidence‐based therapies for AMI was driven by the RCT enterprise, there was little attention to the recruitment of representative populations. Much of the early data limited retrospective analyses by the imbalanced recruitment of women and people of color. When RCTs enrolled a reasonable number of underrepresented groups, the data began to shift in nuance, although health disparity in CVD remains. At some point, one must reflect on the unconscionable duality that, despite our advances, we have an insurmountable systemic failure that impedes equitable CVD care in the United States. Have we, as a Western civilization, failed to implement and integrate the necessary changes to optimize population health for all? Understanding CVD racial disparities within a historical context is essential for younger health disparity researchers (eg, Dr Makawi), as data collection has made strides to move beyond passive observation.

Islek and colleagues evaluated the racial differences in recurrent AMI from the ARIC cohort, in which investigators followed 422 Black and 1245 White survivors of a first nonfatal MI from 1987 to 2017. ⁷ Baseline risk factors were skewed: hypertension (77.2% versus 55.7%), diabetes (42.9% versus 25.7%), and body mass index (median 29.9 versus 27.8 kg/m²) were higher in Black survivors, who also had lower income and education. Although hazard ratios (HRs) shifted markedly with adjustment, a persistent difference was observed over a median follow‐up of 8 years. Black patients had higher recurrent nonfatal MI (32.4 versus 22.8 per 1000 person‐years) and fatal coronary heart disease (34.2 versus 17.9 per 1000 person‐years), compared with the White patients of the cohort. Notably, all Black participants in ARIC were from Jackson, Mississippi, whereas White participants were from Maryland and Minnesota. Although differences narrowed after adjusting for income, education, and cardiovascular risk factors, the in‐hospital fatal coronary heart disease gap remained. Lastly, the Black survivors had twice the risk of dying in the hospital compared with White survivors (HR, 2.01), which emphasizes care disparities that occur in a relatively short inpatient duration.

Unfortunately, the results from this current ARIC analysis do not provide significant nuance to what is known about modern‐day CVD disparities, as the United States continues to intermingle cultures and societies with the potential to be marginalized. Thus, disparities research must continue to evolve beyond the discussion of 2 races, particularly as changes in ethnic communities are emphasized. However, the current study exemplifies a type of research design addressing health disparity in AMI that appears to fall within 4 relatively distinct areas: observational, trial cohort analysis, quality improvement, and policy‐driven design (Figure). ¹ , ² , ⁷ , ⁸ This consideration facilitates a deeper understanding of analyses, such as those of Islek and colleagues, which may help investigators progress towards less passive observations of racial differences in a significantly more complex social and therapeutic landscape.

Figure 1. From observation to actionable equity in cardiovascular health.

This figure traces the evolution of cardiovascular disparity research from observational cohorts to implementation. A, compares trial data (SYNERGY) and real‐world ARIC outcomes, showing that although trials reveal what equitable care can achieve, cohorts expose persistent gaps, especially in Black patients. Historical eras (Heckler Report, clinical trials, quality improvement registries, and policy integration) illustrate progress towards equity‐centered systems. B, displays ARIC findings: higher recurrent MI and fatal CHD incidence and hazard ratios among Black vs White participants, even after adjustment. The sidebar highlights the translation pathway, which includes an equity‐centered redesign, sustained monitoring, and the expected impact on inpatient and preventive outcomes. Bottom prompts guide data translation into action: confirm relevance (using the “So What?” test), assess novelty, ensure adequate subgroup analysis, and identify actionable next steps. ACA indicates Affordable Care Act; ACS, acute coronary syndrome; ARIC, Atherosclerosis Risk in Communities Study; CHD, coronary heart disease; CMS, Centers for Medicare & Medicaid Services; FHS, Framingham Heart Study; GRACE, Global Registry of Acute Coronary Events; GWTG, Get With The Guidelines Registry; HD, health disparity; HR/OR, hazard ratio/odds ratio; JHS, Jackson Heart Study; MI, myocardial infarction; NCDR, National Cardiovascular Data Registry; NSTE‐ACS, non–ST‐elevation acute coronary syndrome; QI, quality improvement; SDOH, social determinants of health; SYNERGY, Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors Study; and TIMI, Thrombolysis in Myocardial Infarction.

OBSERVATIONAL RACIAL DISPARITY ANALYSIS: THE ARIC COHORT

The authors present a well‐described and persistent racial disparity of AMI in the ARIC cohort. In fact, observational or registry data only partly describe the narrative, raising the question of whether equitable care is possible in this space. ⁹ , ¹⁰ , ¹¹ Yet, researchers in this environment must address the comprehensive scope of contemporary health disparity research to understand the totality of a modern‐day report of racial disparities. The era of observational cohort development in the late 1980s, with current‐day follow‐up, has afforded insight into the real‐world care of patients with AMI. Notwithstanding, data from studies such as ARIC and the JHS provide only an intermittent cross‐sectional snapshot of a population, which is inferred to be representative. ² , ⁷

The “So What Test” is the initial jolt that compels many passionate researchers to understand the utility of the work they produce as aspiring investigators. However, being passionate about your results is not enough. Does the article provide nuances and insight for a topic that is well documented? Are there studies or comparable data available to validate the author’s findings? Has the adjudicated outcome definition stood the test of time? These were all important questions that require further thought‐provoking hypotheses. In this phase, understanding what researchers communicate is crucial to the research question, which should also prompt investigators to ask, “Is this the right question right now?”

In the context of the current study, several observational studies have revealed similar racial disparities in care over the past 4 decades. However, in the various observational cohorts, several factors consistently diminish the generalizability of the findings, including those relevant to the current analysis. Often, additional factors suggested the presence of selection bias that exacerbates the disparities demonstrated by the investigators in the current analysis. First, the selective geographic location limits access to insurance, routine, and specialty medical treatment for most Black individuals. The location in Jackson, Mississippi, for the majority of the Black participants in the ARIC cohort had the highest adverse risk rates. Compared with the overall ARIC population, patients in Jackson also underwent fewer invasive interventions for AMI, which is consistent with the results of the current analysis. Second, Medicaid expansion, community health infrastructure investment, mobile cardiac rehabilitation, and telehealth are necessary to close treatment gaps that may not have been readily accessible in Jackson. ¹² Real‐world observational data are critical to track the slow path to equity. However, we must also use clinical trial data to develop hypothesis‐driven interventions to standardize quality and eliminate disparities in outcomes. As for current‐day management, the study falls short due to its broad definition of the AMI outcome. Consequently, deriving actionable concepts from health disparity research necessitates the ongoing evolution of research design to remain relevant and thought‐provoking.

CLINICAL TRIAL RACIAL DISPARITY ANALYSIS: LESSONS FROM SUPERIOR YIELD OF THE NEW STRATEGY OF ENOXAPARIN, REVASCULARIZATION, AND GLYCOPROTEIN IIB/IIIA INHIBITORS‐ACUTE CORONARY SYNDROMES

The simultaneous discovery of persistent CVD disparities in real‐world observational cohorts led to parallel advancements in therapeutic interventions for AMI through several large global clinical trials. With the approval of the first intravascular coronary stent by the Food and Drug Administration in 1994 also came the opportunity to improve clinical therapeutics through clinical trial investigation. Consequently, retrospective analyses of other RCT data became a viable means of health disparity assessment, assisting young investigators in establishing a platform of known evidence. For example, as a resident, I (Echols) was particularly interested in understanding whether racial disparities existed when various aspects of access were equalized. I was fortunate to have actively assisted in the enrollment of patients in the SYNERGY Trial (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) in patients with non–ST‐elevation acute coronary syndromes (NSTE ACS). ⁸ Unlike the ARIC study, a large number of patients ultimately received very similar care, which included the use of an early invasive catheterization strategy for NSTE ACS. For me, this trial represented a game changer but caused invasive coronary catheterization, which was inherently used disparately among races in the care of ACS. There was difficulty even knowing whether Black and White patients had a similar burden of disease. Thus, the SYNERGY analysis provided some possible hints as to whether equity is possible if a regimen or protocol is followed. At that moment, I closely associated the work of well‐conducted RCTs with a level of “quality” that could mitigate the differences between Black and White patients, analyzing a portion of a large, randomized data set assigned to a therapy. When we performed the SYNERGY analysis >20 years ago, several larger observational studies of patients with NSTE‐ACS demonstrated similar findings to those reported by Islek in the most recent study.

The racial analysis of SYNERGY was undoubtedly not the inaugural examination of its kind based on clinical trial data; yet several intriguing aspects of the adjudicated trial process and its outcomes were primed for furthering disparities in AMI care. Distinctive from observational studies, our racial differences analysis of the SYNERGY trial (2007) explored outcomes for high‐risk patients with NSTE ACS, with >98% of all patients receiving an early invasive intervention, such as angiography. Second, the North American cohort was segmented for analysis specifically due to the persistent disparate outcomes between races in acute CVD care for this region, which also included North American Hispanic participants for broader comparisons. Remarkably, Black patients had a 27% lower relative risk of 30‐day death or MI compared with White patients (adjusted odds ratio [OR], 0.73 [95% CI, 0.55–0.98]). However, by 6 months, outcomes equalized, suggesting a slight loss of benefit for the Black patients of the cohort. These results indicate that when access, at least in relation to inpatient care, is regimented in NSTE ACS, short‐term mortality and overall disparate outcomes are eliminated in association with race and ethnicity. Although the mitigated morbidity seems to be lessened in the North American cohort of Black patients with NSTE ACS, the advantage was lost over the next 180 days, where structural barriers gained strong influence.

Whereas ARIC provides a historical observational perspective, SYNERGY offers a counterpoint an RCT. ¹³ The contrasting findings emphasize the potential of structured, equitable care to mitigate disparities stemming from social determinants of health. Our retrospective analysis of SYNERGY demonstrated that among patients with NSTE ACS, Black patients who received standardized care, including early equitable access to angiography, had a 27% lower adjusted risk of death or MI at 30‐day outcomes than White patients, even after statistical adjustments for social and clinical factors. ⁸ Among other differences, the cohort of both Black and White patients was larger for SYNERGY compared with ARIC, providing more data to evaluate the effects of the inpatient care pathway (See Table). ¹ , ⁸ Questions of whether the burden of macrovascular disease was the same between races were also seemingly understood, as sub hoc analysis demonstrated that even with Black patients demonstrating less macrovascular coronary disease per vessel when compared with White patients, the external social systemic factors that limit those with less social means indeed become powerful historical neutralizers, and the ultimate villains of equitable care in the United States.

Table 1.

Comparison of the SYNERGY Randomized Trial and ARIC Observational Cohort in Evaluating Racial Disparities in AMI Outcomes

Feature	SYNERGY trial 8 (acute coronary syndromes)	ARIC cohort study 1 (community‐based epidemiology)
Study design and scope	Randomized controlled trial Compared enoxaparin vs heparin in high‐risk non–ST‐elevation acute coronary syndrome‐ACS Protocol‐driven, invasive care	Long‐term observational cohort Tracked natural history of atherosclerosis and cardiovascular disease Real‐world clinical setting
Patient population	N=6077 White, 586 Black, 344 Hispanic patients High‐risk patients with ACS from North America	N=1245 White, 422 Black patients Survivors of initial nonfatal MI
Baseline characteristics	Higher hypertension in Black patients (83% vs 66%, P<0.001) Higher diabetes (43% vs 28%, P<0.001) Less extensive coronary artery disease	Higher hypertension in Black patients (77.2% vs 55.7%) Higher diabetes (42.9% vs 25.7%) Lower socioeconomic status
Key findings on disparities	Equal care yielded better outcomes for Black patients 30‐d death/MI: 10% Black vs 14% White (P=0.034) Equalized by 6 mo.	Worse long‐term outcomes for Black patients Recurrent MI: 32.4 vs 22.8 per 1000 person‐y Fatal coronary heart disease: 34.2 vs 17.9
Impact of adjustment	Favorable outcomes remained after adjustment Suggests protocolized care can overcome acute disparities	HR for recurrent MI attenuated (1.70→1.28) after adjustment In‐hospital mortality remained doubled (HR, 2.01)
Key insight	Standardized, protocol‐driven care equalized short‐term outcomes for Black patients, despite baseline disparities.	Real‐world inequities in access and care sustain long‐term disparities in AMI outcomes.

This table compares key design features, patient characteristics, and findings on racial disparities from the SYNERGY randomized trial and the ARIC community‐based observational study. Although SYNERGY demonstrated that protocol‐driven care may eliminate short‐term racial disparities in cardiovascular outcomes, ARIC findings highlight persistent long‐term disparities in real‐world practice.

ACS indicates acute coronary syndrome; AMI, acute myocardial infarction; ARIC, Atherosclerosis Risk in Communities; R, hazard ratio; MI, myocardial infarction; and SYNERGY, Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors.

This approach contradicted the idea that discrepancies were biologically predetermined, providing relevance from a country‐level international RCT. If removing a universal access barrier can accomplish equity in a clinical trial, shouldn’t it be possible in real life? Even so, no amount of statistical adjustment can bring forth the benefits of hindsight and retrospective design. As a result, the advancement of clinical trials and the refinement of protocol‐driven analyses, combined with observational data, led to the development of a more actionable protocol driven by quality initiatives for standardizing the care of AMI, marking the beginning of the era of quality improvement registries.

AMI QUALITY REGISTRY ANALYSIS: AN UNDENIABLE DUALITY

In theory, given the known disparities and the ability to develop effective protocol‐driven care, one might assume that moving forward with quality improvement registries would afford a better chance of equitable outcomes for all patients who suffer from AMI. Yet registry‐based analyses such as the National Cardiovascular Data Registry, Get With The Guidelines, and many others continue to show persistent racial and ethnic disparities across hospital systems, states, and territories. ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ Despite decades of registry participation and reporting, disparities remain visible in door‐to‐balloon times, discharge prescriptions of guideline‐directed therapy, referral to cardiac rehabilitation, and 30‐day mortality. ¹⁵ , ¹⁶ , ¹⁹ So then, are we doomed to repeat history, along with the same old story of disparity among patients with AMI, but just in a different framing or design? What will propel us from passive to equitable interventions that mitigate these persistent disparities?

POLICY, IMPLEMENTATION, INCENTIVIZATION: THE WAY FORWARD

Although policy research and payment reform analyses yield varying findings on the impacts of US financial reform and the health care system, it is apparent that CVD disparities in the United States are sustained through the financing of health care. Regarded as a common challenge, variations in service reimbursement, often dictated by federal policy, disrupt the standardization of incentivized health care. Yet, the Affordable Care Act narrowed gaps in CVD disparities in states that chose to expand Medicaid, demonstrating that even a reduced structure of incentivization was still more beneficial in providing more equitable outcomes. ¹² , ¹⁵ , ²⁰ A future, mature infrastructure that has the capacity to drive incentivized interventions based on equitable metrics and risk‐adjusted outcomes can help reduce disparities in practice. Hospitals that serve those with greater social disadvantages operate on thinner margins compared with other private health systems, often with fewer specialists and less access to advanced coronary revascularization programs. The states without Medicaid expansion continue to report the highest rates of hypertension, diabetes, and premature heart failure in the United States, where the US Black and Hispanic populations tend to be disproportionately affected. ²⁰ , ²¹ Federal payment programs that penalize readmissions or “excess cost” without adjusting for social risk only deepen the disparities gap. Thus, policies that progress the financing of health care toward standards of incentivization and redefined value will pave the way towards equitable care for all (Figure).

CONCLUSION: FROM ERA TO ACTION

Four decades after the Heckler Report, the United States still struggles to translate discovery into equitable care. Observational cohorts, such as ARIC, can tell only a crude story. The translations of real‐world outcomes should incorporate the contextual factors that exist, providing greater insight to mitigate inequities. Analysis of clinical trials and quality improvement registries provides avenues for protocol‐managed care with potential to scale in the United States. These efforts of understanding CVD racial and ethnic disparities, although essential, continue to tell a fragmented story of the US health care system and its ability, or lack thereof, to provide equitable care. Yet the data prove systems can neutralize acute disparities. Thus, it is not for lack of knowledge that CVD disparities exist in the United States but resistance to developing an equitable system that works.

Disclosures

ME serves as a consultant for Medtronic (Advisory Board), Bayer (Advisory Board), and receives research funding from the American Heart Association (Strategically Focused Research Network). ME also serves as the Chief Health Equity Officer for the American College of Cardiology.