Disparities in cardiovascular care: Past, present, and solutions

Disparities and heart transplant

For patients with end-stage heart failure, orthotopic heart transplant is the most definitive and durable option for long-term survival. According to data from the United Network for Organ Sharing, 62,508 heart transplants were performed from January 1, 1988 to December 31, 2015. Compared with transplants of other solid organs, heart transplant occurs in significantly infrequent rates.

Barriers to transplant include lack of health insurance, considered a surrogate for low socioeconomic status. Hispanics and African Americans are less likely to have private health insurance than non-Hispanic whites, and this difference is magnified among the working poor.

Despite these perceived barriers, Kilic et al⁷⁵ found that African Americans comprised 16.4% of heart transplant recipients, although they make up only approximately 13% of the US population. They also had significantly shorter wait-list times than whites. On the negative side, African Americans had a higher unadjusted mortality rate than whites (15% vs 12% P = .002). African Americans also tended to receive their transplants at centers with lower transplant volumes and higher transplant mortality rates.

Several other studies also showed that African Americans compared to whites have significantly worse outcomes after transplant.^76–79 What accounts for this difference? Kilic et al⁷⁵ showed that African Americans had the lowest proportion of blood type matching and lowest human leukocyte antigen matching, were younger (because African Americans develop more advanced heart failure at younger ages), had higher serum creatinine levels, and were more often bridged to transplant with an LVAD.

DISPARITIES IN CARDIOVASCULAR RESEARCH

Although the United States has the most sophisticated and robust medical system in the world, select groups have significant differences in delivery and healthcare outcomes. There are many explanations for these differences, but a contributing factor may be the paucity of research dedicated to understand racial and ethnic differences.⁸⁰

Differences observed in epidemiologic studies may be secondary to pathophysiology, genetic differences, environment, and lifestyle choices. Historically, clinical trials were conducted in homogeneous populations with respect to age (middle-aged), sex (male), and race (white), and the results were generalized to heterogeneous populations.⁸⁰

Disparities in research have implications in clinical practice. Overall, the primary cause of heart failure is ischemia; however, in African Americans, the primary cause is hypertensive heart disease.⁸¹ Studies in hypertension have shown that African Americans have less of a response to neurohormonal blockade with ACE inhibitors and beta-blockers than non-African Americans.⁸² Nevertheless, neurohormonal blockade has become the cornerstone of heart failure treatment.

Retrospective analysis of the Vasodilator-Heart Failure trials⁸³ showed that treatment with isosorbide dinitrate plus hydralazine, compared with placebo, conferred a survival benefit for African Americans but not whites.⁸⁰ No survival advantage was noted when isosorbide dinitrate/hydralazine was compared to enalapril in African Americans, although enalapril was superior to isosorbide dinitrate in whites.⁴⁵ These observations were recognized 10 to 15 years after trial completion, and were only possible because the trials included sufficient numbers of African American patients to complete analysis.

In 1993, the US Congress passed the National Institutes of Health (NIH) Revitalization Act, which established guidelines requiring NIH grant applicants to include minorities in human subject research, as they were historically underrepresented in clinical research trials.^84,85

In 2001, the Beta-Blocker Evaluation of Survival Trial⁸⁶ reported its results investigating whether bucindolol, a nonselective beta-blocker, would reduce mortality in patients with advanced heart failure (New York Heart Association class III or IV). This was one of the first trials to prospectively investigate racial and ethnic differences in response to treatment. Though it showed no overall benefit in the use of bucindolol in the treatment of advanced heart failure, subgroup analysis showed that whites did enjoy a benefit in terms of lower mortality, whereas African Americans did not.

Results of the Vasodilator-Heart Failure trials led to further population-directed research, most notably the African American Heart Failure Trial,⁸⁷ a double-blind, placebo-controlled, randomized trial in patients who identified as African American. Patients who were randomized to receive a fixed dose of hydralazine and isosorbide dinitrate had a 43% lower mortality rate, a 33% lower hospitalization rate for heart failure, and better quality of life than patients in the placebo group, leading to early termination of the trial. The outcomes suggested that the combination of isosorbide dinitrate and hydralazine treats heart failure in a manner independent of pure neurohormonal blockade.

CHALLENGES IN STUDY PARTICIPATION

Recruitment of minority participants in biomedical research is a challenging task for clinical investigators.^88,89 Some of the factors thought to pose potential barriers for racial and ethnic minority participation in health research include poor access to primary medical care, failure of researchers to recruit minority populations actively, and language and cultural barriers.⁹⁰

Further, it is widely claimed that African Americans are less willing than nonminority individuals to participate in clinical research trials due to general distrust of the medical community as a result of the Tuskegee Syphilis Experiment.⁹¹ That infamous study, conducted by the US Public Health Service between 1932 and 1972, sought to record the natural progression of untreated syphilis in poor African American men in Alabama. The participants were not informed of the true purpose of the study, and they were under the impression that they were simply receiving free healthcare from the US government. Further, they were denied appropriate treatment even after it became readily available, in order for researchers to observe the progression of the disease.

While the 1993 mandate did in fact increase pressure on researchers to develop strategies to overcome participation barriers, the issue of underrepresentation of racial minorities in clinical research, including cardiovascular research, has not been resolved and continues to be a problem today.

The overall goal of clinical research is to determine the best strategies to prevent and treat disease. But if the study population is not representative of the affected population at large, the results cannot be generalized to underrepresented subgroups. The implications of underrepresentation in research are far-reaching, and can further contribute to disparate care of minority patients such as African Americans, who have a higher prevalence of cardiovascular risk factors and greater burden of heart failure.