17 November 2021

This week in PVD

Low birth weight raises PH risk in premature infants needing oxygen

Low birth weight has been linked to an increased risk of pulmonary hypertension (PH) in premature infants needing oxygen therapy for at least 28 days, an analysis revealed.

Additionally, the failure, after birth, of the blood vessels of the heart to close — before birth, they’re normally open to allow blood flow to bypass the lungs — also was associated with a greater PH risk among these premature infants, according to researchers.

Noting that “the diagnosis of PH depended entirely on echocardiography” — a non-invasive heart scan not done until “at least 28 days after birth” among the more than 80 infants in this study — the investigators said implementing additional screening could help in treating premature babies with PH.

“We suggest that a more active screening echocardiogram may be needed for diagnosing PH” in very low birth-weight, premature infants with blood vessel problems, the team wrote.

The study, “Risk factors and clinical characteristics for bronchopulmonary dysplasia associated pulmonary hypertension in very-low-birth-weight infants,” was published in the journal BMC Cardiovascular Disorders.

Due to advances in oxygen therapy and other treatment approaches for premature babies, their survival rate — especially among those with very low or extremely low birth weights — has increased.

Bronchopulmonary dysplasia or BPD, characterized by damage to the airways and the tiny air sacs (alveoli) of the lung, is a chronic lung disease that can affect these newborns. In some cases, BPD can thicken the arteries that supply the lungs, resulting in high blood pressure or pulmonary hypertension.

While women ages 20–40 are most at risk for pulmonary hypertension, the disease can occur at any age, even among newborns.

Study identifies potential noninvasive biomarkers for PAH severity

Researchers in Japan identified 2 potential biomarkers for severity of pulmonary arterial hypertension (PAH) that can be measured without invasive procedures.

Results of a retrospective study showed serum total plasminogen activator inhibitor-1 (tPAI-1) and thrombomodulin (TM) levels may be useful predictors of pulmonary arterial hypertension (PAH) severity, similar to mean pulmonary artery pressure (mPAP). Findings, published in Thrombosis Journal, also indicated these levels could be beneficial in predicting PAH in individuals in the early stage of the disease, researchers wrote.

Currently, severity of PAH is based on mPAP levels evaluated by right heart catheterization (RHC), which is an invasive procedure. However, fibrinolytic markers such as tPAI-1 and TM are known to reflect arterial endothelial function.

In an effort to identify noninvasive and alternative predictors for prognosis, researchers investigated the relationship between serum tPAI-1, TM, and pulmonary circulation in patients with PAH using electronic medical records.

All individuals who underwent RHC to assess cardiac function at a university hospital in Japan between January 2012 and March 2018 were assessed for inclusion. Individuals on hemodialysis, with hepatic failure, or with other conditions that could affect serum tPAI-1 and TM levels were excluded from analyses.

Blood samples were also taken from all patients prior to RHC and the final sample included 100 patients. Mean (SD) patient age was 68.9 (12) years, and 38% were male. Of these patients, 30% had underlying heart failure, 21% had collagen diseases, and 11% had vascular diseases. In addition, average mPAP value was 25.1 (13.1) mm Hg.

KER-012 prevents heart damage in PH mice

Treatment with the experimental medication KER-012 helped to prevent heart damage in a mouse model of pulmonary hypertension, new research shows.

The findings were showcased by KER-012’s developer, Keros Therapeutics, at the American Heart Association (AHA) 2021 Scientific Sessions, held Nov. 13–15, according to a company press release.

KER-012 is designed to increase the activity of a molecular signaling cascade called the bone morphogenic protein (BMP) pathway. As its name suggests, this pathway is important for bone growth, but it also helps to coordinate the development and function of blood cells.

According to Keros, reduced BMP signaling has been implicated in the development of pulmonary arterial hypertension (PAH). The company is developing KER-012 as a potential treatment for PAH, and also for conditions related to bone loss.

Pulmonary hypertension broadly refers to increased blood pressure in the vessels of the lungs. This puts strain on the right ventricle, which is the portion of the heart that pumps blood through the lungs to pick up oxygen. The oxygen-rich blood then travels to the other side of the heart, where the left ventricle pumps it to the rest of the body.

In order to test KER-012’s effect on heart damage, researchers at Keros used a mouse model called pulmonary arterial banding (PAB). This involves a surgical procedure to put a “band” around the main blood vessel that goes from the right ventricle to the lungs — the pulmonary artery.

Comparisons with mice given a sham operation demonstrated this procedure resulted in elevated pressure in the lung’s blood vessels, starting a day after the operation and lasting for at least three weeks. The PAB mice also had diminished heart function and signs of physical changes to heart tissue, consistent with right ventricle stress.

Posters provide evidence on COPD treatment considerations, exacerbation risk assessment

Chronic obstructive pulmonary disease (COPD) management should take into account patients’ comorbidities, according to a poster presented at the Academy of Managed Care Pharmacy Nexus 2021 meeting. Another poster validated the use of the COPD Treatment Ratio as a measure of exacerbation risk.

Chronic obstructive pulmonary disease (COPD) management should balance reducing the number and severity of exacerbations and the likelihood of treatment failure with the health risks of systemic corticosteroids (SCS), according to a poster presented at the Academy of Managed Care Pharmacy Nexus 2021 meeting, which occurred October 21-28 in Denver, Colorado. Another poster presented at the conference validated the use of the COPD treatment ratio (CTR) as a measure of exacerbation risk within a large commercial and Medicare population.

The first poster examined comorbidities of COPD in a Medicare patient sample and the use patterns of SCS.1 SCS are often prescribed for COPD exacerbations and are sometimes prescribed in chronic maintenance therapy for COPD. However, SCS use has many known complications, including osteoporosis and diabetes, the poster authors wrote.

Utilizing the 2013-2019 Medicare 100% fee-for-service (FFS) database, the researchers examined all FFS patients 40 years and older who received a new diagnosis of COPD in 2015. The patients had no history of SCS use within 24 months prior to the COPD diagnosis.

The results were compared with members with continuous Medicare Part A, B, and D enrollment from 2013-2015.

They identified 183,637 newly diagnosed COPD patients with no recent history of SCS use in 2015. Twenty-eight percent had cardiovascular disease, 15% had peripheral arterial disease, and 32% had depression/anxiety.

Within 4 years of their COPD diagnosis, 36% were treated with oral SCS.

FFS patients with incident COPD had a variety of comorbidities at the time of their COPD diagnoses, the presenters said. Compared with the sample of FFS beneficiaries, the COPD patients were younger with higher rates of select comorbidities, and many were prescribed oral SCS after their COPD diagnosis.

Secondhand smoke leads to respiratory disease, even in adulthood

As many as 4% of population-level asthma cases could be attributed to secondhand smoke, the study suggests.

Exposure to secondhand smoke increases a person’s risk of respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) regardless of whether the person is exposed as a child, an adult, or both.

The new report helps unify existing knowledge about links between “passive smoking” and the health consequences associated with personal use of cigarettes and other tobacco products.

Corresponding author Morten Dahl, MD, PhD, of Zealand University Hospital, in Denmark, and colleagues said second-hand smoking has been the topic of considerable research in children, because a child’s lungs are still in development and therefore could be particularly harmed by exposure to smoke. However, research has also suggested that adults who are regularly exposed to cigarette smoke are also at risk. In an attempt to better understand how secondhand smoke affects people at different ages in their lives, the investigators pulled data from a cohort of more than 20,000 adults who participated in the Danish General Suburban Population Study, a cross-sectional study performed in a Danish city between 2010 and 2013. Their findings were published in the Journal of Asthma and Allergy.

The database yielded 2551 patients (12%) who had been exposed to secondhand smoke for their entire lives, 459 patients (2%) who had only been exposed to secondhand smoke as adults, and 13,998 (69%) who were exposed in childhood only. At the time of the study, all 3 groups of patients had mean ages in the mid-50s.

A minority of members of each age cohort were reported to be current smokers: 25% of those in the lifelong secondhand smoke exposure group, 20% in the adulthood-only group, and 18% in the childhood-only group. For comparison, among 3413 people in the database who had never been exposed to secondhand smoke, just 12% were current smokers.


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