Clinical Context

Cerebral venous thrombosis is a relatively uncommon but important etiology of stroke that may confer significant morbidity and mortality. Older studies of the annual incidence of CVT likely failed to detect many cases, as they predated the widespread use of modern noninvasive imaging techniques. More recent studies suggest that incidence may be higher than previously estimated, but population-based data are still limited regarding trends in CVT incidence and hospitalizations, particularly in multi-ethnic populations.

 The goal of this retrospective cohort study by Otite and colleagues was to test the hypothesis that race-, age- and sex-specific incidences of CVT have increased in the United States over the last decade.

Study Synopsis and Perspective

The US incidence of CVT, an uncommon but important cause of stroke, is more than 3 times greater than previously reported, new research suggests; however, whether this is a real increase or simply an artifact of better detection is unclear.

Results of a large population-based study that included data for inpatient hospital stays throughout New York and Florida showed the incidence of CVT, which is associated with significant morbidity and mortality, increased from 13.9 cases/million in 2006 to 20.2 cases/million in 2014. Most of the increased CVT incidence over time resulted from increases among men of all ages and women age 45 years and older.

"CVT is considered to be a disease that predominantly affects young women. Part of the message to neurologists is that the demographic characteristics of CVT may be changing. More men and older women are now developing CVT, and in the appropriate clinical scenario, [neurologists] should have a high index of suspicion for CVT," study investigator Fadar Oliver Otite, MD, State University of New York (SUNY) Upstate Medical University in Syracuse, New York, told Medscape Medical News.

The findings were published online August 26 in Neurology.

Unique Study

Previous research examining the incidence of CVT relied on data that predated the widespread use of modern noninvasive diagnostic technologies, introducing the possibility that the condition has been underdetected in the past.

More recent research from other countries suggested CVT incidence may be higher than previously thought, but there is still a lack of population-based data examining incidence trends and hospitalizations, particularly in ethnic populations, the investigators noted.

"Population-based studies are very rare. This is one of a few studies to evaluate CVT incidence using the entire population of multiple states in the US," said Otite. He also noted this is the first study to evaluate CVT incidence by race. 

The study had 3 primary aims: quantify current racial, age, and sex-specific CVT incidence in the United States; investigate trends in the incidence and the overall burden of CVT hospitalizations; and describe trends in the prevalence of CVT over the past decade.

To identify all new cases of CVT between 2006 and 2016, the researchers used nationally representative retrospective administrative claims data from the acute care hospitals participating in the State Inpatients Databases (SIDs) of New York and Florida.

The investigators chose these 2 states because they are large, demographically diverse, and together represent > 10% of the US population, so are likely nationally representative.

A Doubling in the Elderly

Researchers identified all hospitalizations of patients age 18 years or older with a first diagnosis of CVT using International Classification of Diseases (ICD) codes.

To determine national generalizability, they used ICD codes to identify all adult stroke hospitalizations in the National Inpatient Sample, which is a database of a 20% stratified sample of all hospital discharges in the United States during the study period.

Finally, the researchers used ICD codes to identify established risk factors for CVT such as pregnancy/puerperium, prothrombotic conditions, inflammatory diseases, and contraceptive use.

They identified a total of 57,315 weighted CVT admissions from 2005 through 2016. These admissions accounted for 0.66% of all adult hospitalizations for any cerebrovascular disease during that period. The proportion of CVT stroke admissions increased from 0.47% in 2005 to 0.8% in 2016.

Two-thirds (66.7%) of CVT hospitalizations in the United States were in women, but this decreased during the period. Hospitalizations in men increased from 22.9% in 2005 to 43.1% in 2016: an increase of 88.6%. The mean age was 49.6 years among men and 42.1 years among women; the mean age increased steadily among women during the entire study period.

Women ages 18 to 44 years accounted for 56.5% of all CVT hospitalizations in the United States in 2005 and 27.6% of all CVT hospitalizations in 2016. In contrast, CVT incidence in elderly adults more than doubled from 11.2% in 2005 to 24.7% in 2016.

Racial Differences

CVT incidence also differed by race. Results showed the incidence was disproportionately higher in Black individuals in New York and Florida, where it jumped from 18.6 cases/million population in 2010 to 21.2 cases/million in 2016. In contrast, CVT incidence in Asian people increased from 5.1 cases/million in 2010 to 13.8 cases/million in 2016; and for White persons, the incidence rose from 14.3 cases/million to 18.4 cases/million.

The exact reasons for the racial disparity in CVT incidence is unknown, the investigators noted; however, they added, it is possible that Black people may have an underlying predisposition to thrombosis.

They pointed out that fibrinogen levels, an essential component of blood clots and an "established marker" of coronary artery disease and stroke, are known to be higher in people of African descent vs European Americans.

Furthermore, they pointed out that systemic lupus erythematosus (SLE), sarcoidosis, and other inflammatory conditions associated with CVT incidence are more prevalent and more severe in Black individuals vs White individuals.

Finally, they noted, race may be a proxy for socioeconomic and lifestyle risk factors that increase CVT risk.

"Studies evaluating the role of access to healthcare, neighborhood factors and other social determinants of health that separate across racial lines and may possibly influence CVT risk are lacking. Further studies are needed to address these and other potential explanatory factors," the investigators wrote. 

In the United States, most hospitalized patients (57.4% of men and 63.6% of women) had at least 1 CVT risk factor. The most common associated conditions in women were pregnancy and puerperium (21.7%), cancer (11.8%), and inflammatory conditions (11.4%). In men, the most common conditions were cancer (19.5%), central nervous system (CNS) trauma (11.3%), and CNS infection (11.2%).

The proportion of women hospitalized with comorbid codes for pregnancy and puerperium decreased by more than 50% during the study period; however, the proportion of hospitalizations with comorbid cancer and comorbid CNS trauma increased significantly in both sexes.

The exact reasons for these changes in CVT risk factors are unclear and require further research, said Otite.

A Much-Needed Update

Commenting on the findings for Medscape Medical News, Shashank Shekhar, MD, assistant professor of vascular neurology at the University of Mississippi Medical Center in Jackson, Mississippi, said the study provides much needed up-to-date information on the incidence and prevalence of CVT.

"Representative and up-to-date information on the incidence and prevalence of CVT has been lacking in the US population," Shekhar told Medscape Medical News. "This study gives us the latest trends from a representative sample from the US and sheds light on the evolving racial and sex disparity of the disease."

The results will improve neurologists' understanding of CVT and ultimately improve patient care, Shekhar added.

Nevertheless, he added, the study has limitations. The community-level incidence of CVT may be underreported because of missing data for asymptomatic or mild cases, said Shekhar. On initial presentation, some patients may have received a misdiagnosis.

"In addition, CVT risk factor prevalence should be interpreted with caution, as improved patient care risk category may have modified the temporal association between risk factors and CVT."

The database that the investigators used also did not include information about all CVT risk factors.

Increased prevalence of known CVT risk factors, and the emergence of unknown CVT risk factors, could explain the increasing incidence of CVT, said Shekhar.

Like the investigators, Shekhar pointed out the potential genetic, socioeconomic, and lifestyle risk factors that may make Black individuals more vulnerable to CVT and called for more research into prevention and treatment.

"Future research should focus on replicating similar multiethnic studies in different parts of the country to better understand the etiological reasons for the trend," he said. "Future studies should also focus on an individualized and optimal treatment regimen for CVT patients and develop new risk modification and preventive therapies."

The study had no specific funding. Otite and Shekhar have disclosed no relevant financial relationships.

 Neurology. Published online August 26, 2020.^[1]

Clinical Implications

• US incidence of CVT appears to have risen in the past decade, more so in Black and male individuals, according to a retrospective cohort study by Otite and colleagues.
• The findings may reflect an actual increase caused by changing risk factors, or an artifactual increase from better detection by improved imaging tests and increased clinician awareness of CVT.
• Implications for the Healthcare Team: Whether actual or artifactual, rising CVT incidence suggests that it is either a growing or previously unrecognized problem in men and older women and no longer limited to only young women.

Earn Credit