Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension

Hjalmarsson, Clara; Rådegran, Göran; Kylhammar, David; Rundqvist, Bengt; Multing, Jonas; Nisell, Margret; Kjellström, Barbro

doi:10.1183/13993003.02310-2017

Cited by 96 publications

(154 citation statements)

References 36 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…Registry data show that PAH drugs are widely used in older patients with multiple comorbidities, but little is known about their safety and efficacy in these patients. The present paper by HJALMARSSON et al [6] reinforces this notion by demonstrating absence of substantial clinical improvements in the majority of older IPAH patients receiving PAH therapies. Registry data help to better characterise and understand these patients, but eventually, adequate representation in randomised trials is necessary to determine the best possible care for this increasingly relevant group of patients.…”

Section: Treatment and Treatment Responsesupporting

confidence: 66%

“…Perhaps the most important clue to the findings by HJALMARSSON et al [6] is a better understanding of how older patients respond to PAH targeted therapies. Such patients were not well represented in PAH studies.…”

Section: Treatment and Treatment Responsementioning

confidence: 99%

“…In this issue of the European Respiratory Journal, HJALMARSSON et al [6] present data from the Swedish PH registry showing that the likelihood that IPAH patients meet a low risk profile with targeted therapies diminishes with increasing age. Almost 80% of patients aged between 18 and 45 years reached the low risk category with PAH treatment, compared with approximately 20% of patients aged ⩾65 years and less than 10% of patients aged ⩾75 years.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Age, risk and outcomes in idiopathic pulmonary arterial hypertension

2018

View full text Add to dashboard Cite

The current European pulmonary hypertension (PH) guidelines recommend a risk-based therapeutic approach to patients with idiopathic pulmonary arterial hypertension (IPAH) [1,2]. The goal is reaching and maintaining a low risk profile. Recent studies from the French PH registry and from the European PH registry COMPERA have confirmed that IPAH patients who meet 3-4 distinct low risk criteria with targeted therapies have 5-year survival rates of 95% or higher [3,4]. Unfortunately, this was accomplished only in 19% of the patients in the French series and 9% of the patients in COMPERA [4,5]. The reasons why the majority of patients fail to reach a low risk profile with targeted therapies have not been fully explored.In this issue of the European Respiratory Journal, HJALMARSSON et al.[6] present data from the Swedish PH registry showing that the likelihood that IPAH patients meet a low risk profile with targeted therapies diminishes with increasing age. Almost 80% of patients aged between 18 and 45 years reached the low risk category with PAH treatment, compared with approximately 20% of patients aged ⩾65 years and less than 10% of patients aged ⩾75 years. Improvements in risk category were rarely observed in patients aged ⩾65 years. Similar data have been recently reported from COMPERA [3]. In the present Swedish series, the 5-year transplantation-free survival decreased from 88% in patients aged 18-45 years to 36% in patients aged ⩾75 years.The high mortality risk of older IPAH patients is probably due to various reasons including comorbidities, unique disease phenotypes, different treatment patterns, and a diminished response to PAH targeted therapies. These factors are tightly interconnected but can be assessed separately. Increasing age and mortality in IPAHThe mean age of patients enrolled between 1981 and 1985 in the US National Institutes of Health (NIH) registry was 36 years at the time of diagnosis; only 9% of the patients were more than 60 years of age [7]. Since then, the age of IPAH patients has increased considerably, at least in Western countries [4,[8][9][10][11]. In Germany, the mean age of patients newly diagnosed with IPAH in 2014 was 65 years [12]. In a recent Swedish registry, the mean age at diagnosis was 69 years [13]. Naturally, older patients have a higher mortality risk in general, but it has already been shown that older patients (>65 years) diagnosed with IPAH have a significantly higher mortality risk than younger patients (18-65 years), even when adjusted for their respective statistical life expectancies [14].

show abstract

Section: Treatment and Treatment Responsesupporting

confidence: 66%

Section: Treatment and Treatment Responsementioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Age, risk and outcomes in idiopathic pulmonary arterial hypertension

2018

View full text Add to dashboard Cite

show abstract

“…The aging process itself predisposes to vitamin D deficiency due to a progressive decline in the cutaneous capacity to synthetize vitD and reduced exposure to sunlight [56]. This bias may have influenced the results because the five-year survival was reported to be higher in PAH patients aged 18-45 years (88%), while the survival rates were 63%, 56%, and 36% for patients in the groups 46-64, 65-74, and ≥75 years, respectively [57]. However, after adjusting for age, survival still remained significantly different for those with high vs. low levels of total 25(OH)vitD.…”

Section: Discussionmentioning

confidence: 99%

Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension

Callejo

Mondéjar-Parreño

Esquivel-Ruiz

et al. 2020

JCM

View full text Add to dashboard Cite

Introduction: Epidemiological studies suggest a relationship between vitamin D deficiency and cardiovascular and respiratory diseases. However, whether total, bioavailable, and/or free vitamin D levels have a prognostic role in pulmonary arterial hypertension (PAH) is unknown. We aimed to determine total, bioavailable, and free 25-hydroxy-vitamin D (25(OH)vitD) plasma levels and their prognostic value in PAH patients. Methods: In total, 67 samples of plasma from Spanish patients with idiopathic, heritable, or drug-induced PAH were obtained from the Spanish PH Biobank and compared to a cohort of 100 healthy subjects. Clinical parameters were obtained from the Spanish Registry of PAH (REHAP). Results: Seventy percent of PAH patients had severe vitamin D deficiency (total 25(OH)vitD < 10 ng/mL) and secondary hyperparathyroidism. PAH patients with total 25(OH)vitD plasma above the median of this cohort (7.17 ng/mL) had better functional class and higher 6-min walking distance and TAPSE (tricuspid annular plane systolic excursion). The main outcome measure of survival was significantly increased in these patients (age-adjusted hazard ratio: 5.40 (95% confidence interval: 2.88 to 10.12)). Vitamin D-binding protein (DBP) and albumin plasma levels were downregulated in PAH. Bioavailable 25(OH)vitD was decreased in PAH patients compared to the control cohort. Lower levels of bioavailable 25(OH)vitD (<0.91 ng/mL) were associated with more advanced functional class, lower exercise capacity, and higher risk of mortality. Free 25(OH)vitD did not change in PAH; however, lower free 25(OH)vitD (<1.53 pg/mL) values were also associated with high risk of mortality. Conclusions: Vitamin D deficiency is highly prevalent in PAH, and low levels of total 25(OH)vitD were associated with poor prognosis.

show abstract

“…The 2015 European pulmonary hypertension guidelines propose a multidimensional risk assessment strategy based on nine items and 13 distinct variables in order to predict the estimated 1-year mortality [1,2]. Recently, several large registry studies have shown that simplified tools can be used to predict outcomes and guide treatment decisions [3][4][5][6]. These studies have focused largely on 6-min walking distance (6MWD), World Health Organization (WHO) functional class (FC), right atrial pressure (RAP), cardiac index (CI) and brain natriuretic peptides (BNP or NT-proBNP).…”

mentioning

confidence: 99%