Photo Credit: Rasi Bhadramani

Research suggests the systemic inflammatory response index may be able to independently predict the severity of idiopathic pulmonary arterial hypertension.

Past studies have demonstrated a connection between the systemic inflammatory response index (SIRI) and the prognosis of heart failure. However, SIRI’s connection to idiopathic pulmonary arterial hypertension (IPAH) is not well understood.

In a new paper from the Journal of Inflammation Research, Luyang Gao, MD, from the Beijing Fuwai Hospital and coinvestigators assessed the relationship between SIRI and IPAH, analyzing how SIRI scores related to variables such as echocardiography results, long-term patient outcomes, hemodynamic measures, and functional ability.

Undetermined Link Between SIRI & IPAH

For many cardiopulmonary conditions, IPAH is an end-stage condition marked by right-sided heart failure.

Questions remain about how to predict IPAH severity. Since previous research has established a link between SIRI and the development and outcomes of conditions that lead to IPAH, such as congestive heart failure and acute coronary syndrome, SIRI may be able to predict IPAH as well, the investigators explained.

Gao and researchers conducted a retrospective cohort study of 426 patients with IPAH who underwent right heart catheterization (RHC) between January 2013 and December 2020. Patients were at least 18 years of age, with a IPAH diagnosis and had hemodynamic characteristics of PAH and/or RHC.

The researchers excluded patients who also had cancer, inflammatory conditions, or an ongoing infection, as well as those who did not have available data on platelet, monocyte, neutrophil, and lymphocyte counts.

The investigators collected venous blood samples and information related to medication use, comorbidities, World Health Organization functional class (WHO-FC), demographics, and alcohol and smoking habits. Within 48 hours of blood sample collection, each patient underwent an echocardiogram. Once patients were in stable condition, they also performed a 6-minute walking test.

To calculate SIRI, the researchers used composite inflammation indicators from blood tests, looking for clinical deterioration as an outcome measure.

Calculating SIRI

In the paper, the researchers shared their calculation formulas for the following measures:

• SIRI = (neutrophil count × monocyte count) / lymphocyte count
• neutrophil-to-lymphocyte ratio= neutrophil count / lymphocyte count
• platelet-to-lymphocyte ratio = platelet count / lymphocyte count
• systemic immune inflammation index = (neutrophil count × platelet count) / lymphocyte count.

With this SIRI calculation, the researchers classified patients based on their risk level (low, intermediate, or high). Every 3-6 months, the researchers conducted two follow-ups via telephone to ask about clinical outcomes.

Patients experiencing clinical deterioration during follow-up exhibited lower WHO-FC ratings and higher SIRI values. Those with SIRI scores above 0.741 had significantly worse pulmonary hemodynamic markers compared to patients with scores of 0.741 or less (P<0.001).

“SIRI showed positive associations with indicators such as N-terminal pro-brain natriuretic peptide, right ventricular end-diastolic diameter, pericardial effusion, mean pulmonary arterial pressure, and pulmonary vascular resistance. Conversely, SIRI had inverse relationships with 6-minute walking distance and left ventricular end-diastolic diameter,” Gao and colleagues explained.

SIRI May Predict Prognosis

The researchers followed up with patients for over 3 years. About 31% (132 patients) experienced clinical deterioration. Deterioration outcomes included death, lung transplant, and hospital readmission due to heart failure.

Gao and colleagues used three Cox regression models to establish SIRI’s ability to predict IPAH outcomes. All three models suggested that a high SIRI category indicated someone was twice as likely to experience clinical deterioration (HR, 1.366; 95% CI, 1.073-1.738, P=0.011).

Of note, this study does not establish causation between SIRI and clinical deterioration, only a consistent correlation. While this may indicate SIRI could be an independent prognosis of IPAH, the researchers emphasized that echocardiographic and hemodynamic factors should be used alongside SIRI for the most accurate outcome predictions.

“The findings showed that the SIRI has the ability to autonomously anticipate clinical decline in individuals suffering from IPAH and offers additional benefits when used alongside the concise ESC/ERS risk score,” Gao and colleagues concluded.