ABO RISK AND RISK OF VASCULAR EVENTS

COPENHAGEN, DENMARK — Patients with non-O blood types are at significantly increased risk for venous thromboembolic and cardiovascular events, a study of 1.1 million blood donors confirms^[1].

ABO blood groups accounted for a striking 30% to 40% of the risk of venous events in this healthy population of blood donors.

"That's huge," senior author Dr Gustaf Edgren (Karolinska Institute, Stockholm, Sweden) told heartwire from Medscape. "We rarely come across risk factors where one individual risk factor can explain this much of the risk in the general population. That's what surprised me the most."

Risks on the individual level were comparatively modest and certainly far from the 40% to 80% chance of developing breast cancer reported for carriers of BRCA1/2 germline mutations. These mutations, however, are found in a small fraction of women, whereas 60% to 70% of the population has a non-O blood type, Edgren observed.

"This might not be all that important on the individual level, but it certainly is an important risk factor or risk marker on a wider population level," he added.

Thus, ABO blood group could have a role in thrombosis risk assessment and be added to existing prediction models. While further comparison with other risk markers is warranted to determine the clinical utility of this information, the greater challenge may be in getting blood type on the radar of cardiologists and vascular specialists.

While the public has a "huge interest" in blood groups, among physicians, "there is a general disinterest in risk factors you can't affect," Edgren observed. "I would think most cardiologists are not aware of this."

The current study—involving 1,112,072 blood donors in the SCANDAT database from 1987 through 2012 in Denmark and Sweden—is the largest ever to investigate the association between ABO blood groups and venous and arterial events.

Prior, smaller studies have also shown an association, but a large chunk were done in hospital settings where important comorbidities and other risk factors, such as smoking, obesity, and those for Factor VIII and von Willebrand factor, are more prevalent. Using data from a cohort of essentially all healthy blood donors allowed the investigators to better tease out the effect driven by blood type alone, Edgren said.

At entry, the blood donors' mean age was 33 years, 51.4% were female, 665,952 had blood types A, B, or AB, and 446,120 had blood type O. In all, 9170 venous and 24,653 arterial events occurred during 13.6 million person-years of follow-up.

Incidence rate ratios (IRRs) were highest for venous events, with venous thromboembolism (VTE) in all age groups combined having an incidence rate of 1.80 (95% CI 1.71–1.88) in the non-O blood group vs blood group O, after adjustment for age, sex, calendar period, country, and comorbidity.

Risk patterns were similar for pulmonary embolism (IRR 1.75; 95% CI 1.64–1.86) and deep vein thrombosis (IRR 1.92; 95% CI 1.80–2.05) but were slightly higher for pregnancy/abortion-related VTE (IRR 2.22; 95% CI 1.76–2.78).

Although relative risks were generally lower for arterial events, risks were still significantly elevated for MI (IRR 1.10 95% CI 1.05–1.14) and stroke (IRR 1.07; 95% CI 1.02–1.12) in the non-O blood groups than in blood group O.

When the investigators subclassified the non-O blood group and compared them with blood group O, risk elevations for VTE were similar for donors with blood types A and B, who may be carriers of an O allele, and consistently higher for donors with blood type AB, who do not carry any O alleles.

Overall, the findings suggest that ABO blood groups act independently of other risk factors for thromboembolic and vascular events.

"The conclusion is that this is not driven by comorbidity, for example," Edgren said. "It might be linked to other genetic risk factors, but it is not linked to the occurrence of other diseases."

The SCANDAT database was created through grants from the Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Society for Medical Research, and Danish Research Council. The authors reported no relevant financial disclosures.