iTTP remission may still carry higher stroke risk, study finds

People in remission from immune-mediated thrombotic thrombocytopenic purpura (iTTP) may have a higher risk of certain major cardiovascular events, particularly stroke, according to a study out of Italy.

Compared with the overall Italian population, people who had reached clinical remission after recovering from an iTTP attack had higher-than-expected rates of certain cardiovascular events. Standard cardiovascular risk factors, such as obesity or high blood pressure, did not appear to fully explain this discrepancy. The research team suggested that the buildup of damage in the body’s network of small blood vessels, called the microvasculature, and in organs could contribute to cardiovascular vulnerability in this group.

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“These preliminary results underline the urgent need of a multidisciplinary scientific effort aimed at understanding the role of microvascular cumulative organ damage in iTTP patients during remission,” the researchers wrote.

The study, “Major adverse cardiovascular events in immune-mediated thrombotic thrombocytopenic purpura during clinical remission,” was published in Haematologica.

In thrombotic thrombocytopenic purpura (TTP), small blood clots form in the microvasculature. Over time, this can block blood flow and lead to organ damage. In iTTP, an autoimmune form of the disease, self-directed immune attacks interfere with proteins that help regulate blood clotting.

iTTP attacks can occur suddenly, but with appropriate treatment, patients may recover and enter remission. Previous work has suggested high rates of major adverse cardiovascular events (MACE), such as stroke, in iTTP. However, “data on MACE incidence during clinical remission in iTTP patients are still scarce,” the team wrote.

To help illuminate this, the scientists examined medical records for 232 eligible iTTP outpatients who were referred at least once to a specialist treatment center in Milan. Participants had no history of MACE before TTP onset and had at least six months of follow-up data. The researchers defined MACE as a composite outcome of clot-related stroke (ischemic stroke) or acute coronary syndrome, which could include heart attack and sudden or worsening chest pain (unstable angina).

Stroke rates higher than in general population

Over a median of 6.3 years of follow-up, 3.4% of participants had at least one MACE. This corresponded to an estimated 10-year incidence rate of 4.8%. The median time between participants’ first iTTP episode and their MACE was 95 months, or nearly eight years. Two participants had multiple events.

Ischemic strokes were the most common type of MACE, occurring in 3% of participants. “These rates are higher than those observed in the general population and are consistent with a population at high cardiovascular risk,” the researchers wrote. For comparison, a large Italian study with a similar age and sex distribution found a 0.8% incidence of stroke.

Acute coronary syndrome, which includes heart attack and unstable angina, was less common in the iTTP group than in the larger Italian population. However, the team noted the shorter follow-up period in their study and the low number of participants with MACE as factors that limit conclusions.

Breaking down participants by age at iTTP onset, older participants tended to be at the highest risk of MACE. Among the five participants whose iTTP began at age 70 or older, the estimated 10-year incidence was 41%. Researchers often consider a rate higher than 15% to indicate very high cardiovascular risk in this age range, so “in our cohort patients with elderly-onset iTTP … appear to be at much higher risk of developing MACE during remission,” the scientists wrote.

Usual risk factors may not fully explain findings

Next, the team tested whether standard cardiovascular risk factors were common in iTTP participants who experienced MACE. Smoking, which can elevate cardiovascular risk, was common among many of these individuals. However, taken together, the prevalence of traditional cardiometabolic risk factors, such as overweight or obesity, type 2 diabetes, high blood pressure, and high cholesterol or other blood fats, was low to moderate.

“This finding is consistent with a previous study showing that standard cardiovascular risk models do not properly predict MACE risk in iTTP survivors,” the researchers wrote. “Therefore, iTTP itself appears to be the major independent risk factor for MACE during remission.”

The team proposed that an accumulation of damage in small blood vessels could increase the chance of MACE during iTTP remission. This could include damage from active iTTP attacks. The disease might also continue to cause subtle blood vessel and organ damage during remission without causing symptoms.

“These preliminary results underline the urgent need of a multidisciplinary scientific effort aimed at understanding the role of microvascular cumulative organ damage in iTTP patients during remission,” the investigators concluded.