Race and Cancer-Associated Venous Thromboembolism in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: Venous thromboembolism (VTE) is classified as provoked (associated with surgery, hospitalization, trauma, or cancer) and unprovoked events.  Whether provoked, unprovoked or cancer-associated VTE differs by age, sex, race, or region in the United States is poorly understood.

Methods: VTE events were ascertained in 30,183 individuals in the REGARDS cohort enrolled between 2003-2007 in the contiguous United States.  Participants were enrolled in their homes, with a goal of 50% of the cohort being black, female, and living in the southeastern US.  VTE events were identified by telephone interviews, review of hospitalizations and deaths and validated by physician review of medical records.  Cancer-associated VTE (CA-VTE) was defined as a VTE associated with active cancer or chemotherapy in the last 90 days. Non-cancer, provoked VTE was defined as a VTE that was preceded within 90 days by major trauma, surgery, or hospitalization.  Unprovoked VTE was defined as having none of the above risk factors. The associations of age, sex, race and region with cancer-associated, provoked, and unprovoked VTE were analyzed by chi square analyses and Cox proportional hazard ratios that were adjusted for age, sex, race, region and obesity.

Results: Overall, 332 VTE events occurred over a mean of 4.7 years follow up.  Of these, 163 events (49.1%) were provoked, 47 (14.2%) were CA-VTE.  The proportion of unprovoked to provoked VTE did not differ by age (120 to 104 in those older than 65,  49 to 59 for those under 65, p=0.16) sex (98 to 90 in men, 71 to 73 in women, p=0.61), race (61 to 62 in blacks, 108 to 101 in whites, p=0.71) or region (89 to 88 in the Southeast, 80 to 75 for the rest of the country p=0.81); however CA-VTE was significantly less common in blacks (11 of 123, 8.9%) than whites (36 of 209, 17.2%) (p=0.04).  While the overall risk of VTE was similar in blacks and whites, blacks had a lower risk of CA-VTE than whites (Hazard Ratio (HR) 0.38, 95% Confidence Interval (CI) 0.18-0.77).  Increased age and male sex were associated with an increased risk for all-cause VTE and unprovoked VTE with a trend for male sex and increased risk for provoked VTE (Table).  However, men had no increased risk of CA-VTE compared to women (0.85 95% CI 0.46-1.55).

Discussion:  The proportion of provoked versus unprovoked VTE events did not differ by age, sex, race or region in REGARDS, though blacks had a lower proportion of CA-VTE than whites.  Men overall had a higher risk of VTE than women, but there was no increased risk for CA-VTE in men.  Blacks and whites had a similar risk of VTE overall, however blacks had a lower incidence of CA-VTE than whites.  Possible reasons for our findings include shorter survival after a diagnosis of cancer, different cancer types or treatments, or differential ascertainment of VTE by race or sex.  These findings highlight the need to understand how sex and race impact VTE incidence so we can best prevent VTE in everyone.

Table:

Hazard Ratios for different  VTE subtypes by Age, Sex, and Race (95% Confidence Interval)
	All VTE	Unprovoked VTE	Provoked VTE	Cancer-Associated VTE
Age (per SD, 9.4 years)	1.61 (1.43-1.80)	1.70 (1.44-1.99)	1.52 (1.29-1.79)	1.48 (1.09-2.02)
Male Sex	1.42 (1.13-1.78)	1.52 (1.11-2.09)	1.32 (0.96-1.82)	0.85 (0.47-1.55)
Black versus White Race	0.90 (0.71-1.13)	0.84 (0.61-1.16)	0.96 (0.69-1.34)	0.38 (0.18-0.77)