High risk for cardiovascular disease in patients with alpha-1 antitrypsin deficiency

Key takeaways:

• Patients with alpha-1 antitrypsin deficiency (AATD) faced an increased risk for cardiovascular disease based on aortic pulse wave velocity.
• In AATD, this measure was linked to proteinase 3 activity.

Aortic stiffness, a known risk factor for cardiovascular disease, was raised among patients with alpha-1 antitrypsin deficiency vs. patients with COPD or healthy individuals, according to study results.

Louise E. Crowley

“We have found that traditional cardiovascular disease risk factors, such as smoking, may not account for all cardiovascular disease risk in patients with the condition, alpha-1 antitrypsin deficiency,” Louise E. Crowley, MBChB, clinical research fellow and PhD researcher at University of Birmingham, told Healio. “This suggests that the everyday clinician should be cautious in using solely assessment tools such as QRISK2 in patients with alpha-1 antitrypsin deficiency, as they may underestimate the cardiovascular disease risk.”

In an observational study published in Orphanet Journal of Rare Diseases, Crowley and colleagues evaluated 228 patients (median age, 58 years) with alpha-1 antitrypsin deficiency (AATD) against 50 patients (median age, 71 years) with non-AATD COPD and 51 healthy individuals/controls (median age, 68 years) to see if this patient population faces a higher risk for cardiovascular disease (CVD).

In this study cohort, more patients with AATD reported never smoking than patients with COPD and healthy controls (25.4% vs. 0% vs. 17.6%). These patients also had the lowest proportion of current smokers (2.2% vs. 20% vs. 7.8%).

Use of aortic pulse wave velocity (aPWV), a measure of aortic stiffness, and the QRISK2 score (including age, sex, ethnicity, zip/postcode, smoking status, BMI, presence of key comorbidities related to CVD and CVD in a first degree relative) allowed researchers to measure an individual’s risk for CVD. A past CVD diagnosis was found in 17 patients with AATD, nine patients with COPD and four controls, so they did not receive a QRISK2 score.

Both CVD risk measures were “highly concordant” among controls and those with COPD, whereas 45% of patients with AATD had discordant measures, according to researchers.

Between patients with AATD and patients with COPD/healthy controls, researchers found the highest measure of aPWV among those with AATD following adjustment for age and smoking history. These patients also had the lowest QRISK2 score in the aPWV adjusted model.

“This discrepancy really highlights that there must be something, independent of traditional cardiovascular risk factors, that is increasing vascular stiffness in patients with AATD,” Crowley told Healio. “Here we have proposed that the enzyme proteinase 3 may be the link between heart and lung disease in AATD.”

Researchers further studied how CVD risk is linked to lung physiology, as well as neutrophil proteinase activity in patients with AATD in a model that accounted for age, smoking status and traditional CVD risk factors (QRISK2 scores).

In this model, having a heightened aPWV was significantly linked to three factors in patients with AATD: lung physiology impairments (carbon monoxide transfer coefficient percent predicted and FEV₁ percent predicted), emphysema on CT scan and proteinase 3 activity.

Researchers did not find these associations when assessing QRISK2 in AATD.

During 4-year follow-up visits, a new CVD diagnosis was found in 23 patients with AATD, 18 patients with COPD and seven healthy controls. Patients who developed CVD had higher aPWV and QRISK2 scores at baseline than patients who did not develop CVD in each of the three patient groups.

Among those with new CVD, the group with the lowest median QRISK2 baseline score was the AATD group at 19.4 vs. the COPD group (31.8) and the healthy control group (33.9).

Reference:

• Lung disease puts patients at risk of developing heart conditions regardless of other risk factors. https://www.birmingham.ac.uk/news/2024/lung-disease-puts-patients-at-risk-of-developing-heart-conditions-regardless-of-other-risk-factors. Published March 22, 2024. Accessed March 26, 2024.