Pulmonary embolism in Black Americans

Venous thromboembolism (VTE) constitutes one of the three leading cardiovascular illnesses, along with myocardial infarction and stroke. Advances in VTE epidemiology have sharpened our awareness of VTE’s steep impact on mortality, morbidity, hospitalization, and cost. The Surgeon General has estimated that pulmonary embolism (PE) causes 100,000–180,000 deaths annually in the United States [1]. He has labeled PE as the most common cause of preventable death among hospitalized patients. For those of us who evaluate a lot of VTE patients in an urban setting, it is usually apparent that Black Americans are over-represented relative to their population. In a tertiary care hospital in Detroit, African Americans had a higher incidence of PE than Caucasians [2]. In a much broader population, the California Discharge Data Set in 1996 identified a cohort of patients with VTE. Black Americans were most frequently affected. The standardized incidence of VTE per 100,000 adults in California was: 138 in African-Americans, 103 in Caucasians, 61 in Hispanics, and 29 in Asian-Pacific Islanders. Of special concern was that the case-fatality rate for VTE was more than twice as high for African Americans,4.1%, than for Caucasians, 1.8% [3]. With respect to temporal trends in PE in the U.S. from 1998 to 2005, the proportion of African American patients remained nearly constant, whereas the proportion of White patients decreased [4]. The Genetic Attributes and Thrombosis Epidemiology (GATE) study was designed to examine racial differences in VTE etiology and pathogenesis. Clinical characteristics varied between Blacks and Whites when the two races were compared. Cancer, recent surgery and immobilization were more common among Caucasians, whereas hypertension, diabetes, and kidney disease were more prevalent among African Americans [5]. The observation that African Americans bear a disproportionate burden of PE goes against the grain of conventional thinking. After all, the best known genetic predispositions for PE are factor V Leiden and the prothrombin gene mutation. Both abnormalities occur predominantly in White Americans, and both are rare in Blacks. How does one resolve this apparent incongruity? Though the finding is paradoxical with respect to these two genetic mutations, the most likely explanation is that most genetic predispositions to VTE among Black Americans have not yet been discovered or have not been described in detail. Factor V Leiden and the prothrombin gene mutation simply don’t tell the whole story. For example, a variety of new single-nucleotide polymorphisms (SNPs) have been reported to be associated with VTE in population-based case-control studies. Dutch investigators identified seven SNPs in three large, well characterized populations that were combined and that had 3,155 cases and 5,087 controls. Evidence was strongest for three SNPs in the CYP4V2, SERPINC1, and GP6 genes [6]. In the U.S. Physicians Health Study cohort among patients with an initial idiopathic VTE, an N291S lipoprotein lipase gene polymorphism and a Q27E b-2-adrenergic receptor gene polymorphism were associated with increased risk [7]. For recurrent VTE in the same population cohort, additional genetic variants were identified that were associated with both increased risk and reduced risk [8]. Thus, we have barely scratched the surface in cataloging genetic findings in those at risk for VTE. And, so far, most of the cohorts created to investigate genetic predisposition have included very few Blacks. In this context, publication of the Heit manuscript in this issue of the American Journal of Hematology is a landmark that will stand the test of time and be cited frequency whenever the epidemiology of VTE in the U.S. is studied or discussed [9]. Heit worked in conjunction with investigators from seven Centers for Disease Control (CDC) Thrombosis and Hemostasis Research and Prevention Network Centers to compare demographic and baseline characteristics among White and Black Americans with VTE. Those of us advocating for more government support of VTE research owe a debt of gratitude to the CDC for its backing of these epidemiologic initiatives. The Heit’s article is filled with major findings that contrast differences between Blacks and Whites. A higher proportion of Blacks were female (71% versus 61%). Blacks had a higher proportion of PEs, and fewer had DVT alone. Blacks had a higher proportion of HIV and sickle cell disease, whereas Whites had a higher proportion of surgery, trauma, or infection. Blacks also had a higher proportion of idiopathic DVT and idiopathic PE compared with Whites, who more often had secondary, provoked VTE. This finding is ominous for Blacks because after discontinuing anticoagulation, those with idiopathic VTE have a much higher rate of recurrent events than those with provoked VTE [10]. In the Heit analysis, some of the risk factors for both coronary heart disease and VTE were more common in Blacks, including hypertension, diabetes mellitus, and chronic kidney disease. The average body mass index (BMI) was higher among Blacks: 33 kg/m versus 30 kg/ m. These findings lead us to speculate about racial disparities in health care delivery, preventive medicine, and access to primary care. With respect to obesity, both Blacks and Whites were overweight. High BMIs in both groups remind us that it is expensive for economically disadvantaged individuals to follow a heart healthy nutrition regimen. Carbohydrates from ‘‘fast food’’ are the least expensive food option. Fresh fruit, fresh vegetables, and protein-filled foods are far more costly, as calculated on a per calorie basis. From an epidemiologic perspective, we are learning that the same risk factors that apply to coronary heart disease, such as cigarette smoking, hypertension, and lipid abnormalities, also affect VTE. Therefore, the ‘‘silo thinking’’ that had previously placed ‘‘red clot’’ of VTE and ‘‘white clot’’ of coronary heart disease into two separate bins has been