PAPi Blood Pressure Test Predicts Mortality in Asian Patients

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by Steve Bryson PhD |

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The PAPi blood pressure test was able to accurately predict mortality in Asian people with pulmonary arterial hypertension (PAH), a 14-year study revealed.

Despite that finding, the multi-factor REVEAL score was found to still be the best predictor for mortality risk in PAH.

“In our analysis, low PAPi was found to be a significant but modest independent predictor for death and time to death,” the researchers wrote. “The REVEAL score stands out as the strongest risk prediction tool still.”

The study, ”Does pulmonary artery pulsatility index predict mortality in pulmonary arterial hypertension?,” was published in the journal ESC Heart Failure.

In PAH, blood vessels in the lungs narrow, slowing blood flow and causing blood pressure to rise. This makes the heart work harder to pump blood through the lungs and eventually causes the right ventricle heart muscle to become weak and fail. As PAH becomes worse, it can increase the risk of mortality.

PAH has many potential causes, including heart abnormalities, viral infections, connective tissue disorders, certain medicines, and liver disease. In addition, PAH can be inherited in up to 20% of cases, but it also can occur due to unknown causes (idiopathic).

Advances in PAH therapy have improved survival; that’s why comprehensive and accurate risk prediction is essential to guide treatment.

The Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator uses multiple clinically relevant factors to predict survival in PAH populations. REVEAL includes the World Health Organization (WHO) functional classification of PAH, demographics, co-existing conditions, and vital signs, as well as other functional, blood marker, and blood pressure tests. A higher REVEAL score reflects a higher risk of mortality.

The pulmonary artery pulsatility index (PAPi) is a composite measure of blood flow defined as the pulmonary artery systolic pressure minus the pulmonary artery diastolic pressure, divided by the mean right atrial (one of heart’s chambers) blood pressure. Systolic blood pressure is measured during a heartbeat when the pressure is high, whereas diastolic pressure is assessed between heartbeats when the heart is relaxed, and pressure is lower.

PAPi has emerged as a valuable predictor of right ventricular heart failure in people who have experienced a heart attack. However, studies investigating PAPi as a predictor of heart failure in people with PAH have been limited to a few underlying causes. Also, none have evaluated PAPi in multi-ethnic Asian people with PAH with a wide range of different causes.

This study analyzed whether PAPi was associated with mortality risk over a 14-year follow-up period to determine if it could be used to predict mortality. The study was conducted by researchers based at the National University Heart Centre in Singapore.

“To our knowledge, this is the first study to evaluate the prognostic [outcome] utility of PAPi in a multi-ethnic Asian cohort [group] of patients with PAH,” the team wrote.

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Of the 102 participants with confirmed PAH, 65 (63.7%) were ethnic Chinese, 23 were Malay (22.5%), 10 Indians (9.8%), and four (3.9%) were classified as others. Overall, the mean age was 52.6 years, 77% were women, and the median follow-up time was 3.8 years (maximum was almost 14). During this time, 41 (40.2%) deaths occurred.

Idiopathic PAH was diagnosed in 34 (33%) participants, connective tissue disease-associated PAH in 32 (31%), followed by congenital heart disease-associated PAH in 24 (24%), and other forms in 12 (12%). Treatment with a single medication (monotherapy) was the most common in 66.7%, and 25.5% were receiving combination therapies, while 7.8% were untreated.

Most patients (75.8%) were in the WHO functional class of I or II, which refers to those who either did not experience any symptoms with ordinary physical activity or had symptoms such as shortness of breath during regular activities.

A PAPi cut-off was chosen to categorize participants into two groups: those with a PAPi below 5.3 versus 5.3 or higher. A lower PAPi indicates worse heart function.

Overall, the low PAPi group was older (56 vs. 49 years) but similar in ethnicity, sex, underlying cause, clinical parameters, and body mass index (body fat measure). Between the two groups, there was no difference in WHO functional class or the distance walked in six minutes.

As expected, the low PAPi group had a higher mean right atrial blood pressure (14 mmHg vs. 6 mmHg) but also a lower pulmonary artery systolic pressure. Further, the low PAPi group tended to have higher REVEAL scores and higher NT-proBNP values — a measure of heart disease severity.

Compared to the low PAPi group, those with a greater PAPi had higher survival rates at one year (95.7 vs. 77.2%), at three years (86.2 vs. 58.6%), at five years (80.4 vs. 50.4%), and at 10 years (53.4 vs. 31.7%). The differences were statistically significant across all time points.

The results remained when assessing by age, with those 53 years of age and younger and a high PAPi had the best survival outcome while patients older than 53 years with low PAPi had the worst outcome.

A risk assessment calculation found PAPi was a useful predictor of mortality, similar to age as a predictor. However, the calculated REVEAL score was found to be the most reliable predictor of mortality risk. Of the blood flow parameters included in the PAPi calculation, pulmonary artery systolic and diastolic pressure were weak predictors individually. In contrast, the mean right atrial pressure was the greatest predictor of survival.

“The composite PAPi does not have better discriminatory ability compared with using measured [mean right atrial pressure] alone in predicting mortality,” the scientists wrote.

The most statistically significant factors for the occurrence of death as well as time-to-death were the distance walked in six minutes, NT-proBNP values, REVEAL score, mean right atrial pressure, and PAPi.

Finally, after adjusting for demographics, clinical characteristics, underlying cause, WHO functional class, and treatments, participants with a low PAPi had a significantly higher death rate and shorter time-to-death.

“In PAH, accurate clinical prognostication can lead to an actionable outcome, but risk prediction is best improved when a combination of risk markers is considered,” the investigators concluded. “PAPi should be examined rigorously in further studies for its possibility of adding incremental value to current models of clinical risk prediction.”

According to the team, the findings warrant validation in larger studies that reflect the latest advances in PAH therapy and their impact on survival.