by Phyllis Hanlon, Contributing Writer

WHO Group 1 PH (PAH, pulmonary arterial hypertension) can affect people of all ages. But, in recent years, there has been a noted increase in the number people being diagnosed with the disease at an older age. To better understand how age is related to PAH development and how the disease responds to treatment, a team of researchers evaluated data from previous clinical trials.

Adriano R. Tonelli, MD, from the Respiratory Institute at the Cleveland Clinic, led the team in reviewing data from all previously published treatment studies for PAH conducted by United Therapeutics Corporation. This included seven randomized, placebo-controlled trials and one extension study. These results were compared with data from the National Institutes of Health (NIH) registry ; the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) and the European registry, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA).

After combining the data, the researchers examined data on 2,627 patients; 1,438 (54.7%) were 50 years old or younger; 780 (29.7%) were between the ages of 51 and 64; and 409 (15.6%) were 65 or older. Most patients were women and white.

The researchers found some fundamental differences between older and younger patients. Idiopathic PAH is less frequent in the older group. When compared to the group of patients who were 50 or younger, those who were 65 and older had a higher proportion with connective disease (CTD) associated with PAH. PH associated with left ventricular diastolic dysfunction, a type of heart failure, is the most common cause of PH in people over the age of 65.  The authors note that this may suggest that “older patients who do meet criteria for PAH may have some degree of left ventricular diastolic dysfunction and compose a unique phenotype of  ’mixed’ pulmonary hypertension.”

Clinically speaking, older patients have less severe hemodynamic measurements in the heart and lungs, which may suggest a different mechanism of disease or a more pronounced functional impairment for less severe hemodynamic abnormalities. The researchers noted that there was no difference in pulmonary artery wedge pressure (PWP), a measure used to monitor left ventricular function, in the clinical trials studied.

These older patients also did not respond as favorably to treatment as the younger patients. Dr. Tonelli and his team noted smaller changes in the six-minute walk test (6MWD), regardless of gender, origin of the disease, functional class, baseline score and hemodynamic  measures following therapy. Noting that further research will be required, the authors suggest that this could mean that traditional PH measures may not fit older patients with PAH and changes may need to be made to better assess illness in this age group, possibly including more quality of life measures.

The researchers cited some limitations to their study, which was a post-hoc analysis (meaning that the data were taken and analyzed from already completed studies – in this case from one company). Additionally, all of the studies Dr. Tonelli’s team examined included only patients younger than 70 years of age, suggesting possible bias, however, the authors speculated that including older patients would have magnified these findings.

In spite of these limits, the authors noted that their findings could have many positive implications for managing PAH in this particular group of patients. Additional studies could produce results that might help explain how the disease develops and progresses in older patients and how to establish age-appropriate outcome measures for this population. They emphasized the importance of “…setting reasonable expectations…” for treatment goals. “In addition, these data could be used to plan and design future treatment trials to best evaluate a therapy’s efficacy in certain age groups,” they noted.