Pulmonary Arterial Hypertension (PAH)


Patients with pulmonary arterial hypertension (PAH) may have many comorbid conditions. PAH comorbidities include systemic hypertension, ischemic cardiovascular events, obesity, thyroid disease, sleep apnea, obstructive airway disease, diabetes mellitus, clinical depression, anemia, frailty, chronic kidney disease, chronic liver disease, chronic muscle disease, chronic pain, peripheral vascular disease, cancer, and dementia.1

The presence of PAH comorbidities can make it difficult to differentiate the disease from other identified groups (Groups 2 to 5) classified under pulmonary hypertension (PH). Further, comorbidities can mask the symptoms of PAH, delaying diagnosis and making it difficult to evaluate disease progression and therapy outcome.1

Systemic Hypertension and Ischemic Cardiovascular Events

Systemic hypertension increases the risk of cardiovascular conditions, including coronary events and stroke.2 Almost 75% of patients who experience a stroke or myocardial infarction have concomitant systemic hypertension. Concomitant use of antihypertensive medications with PAH-specific therapies should be done cautiously due to the risk of systemic hypotension. In PAH patients, the use of beta-blockers as a first-line antihypertensive drug should be avoided.1

Obesity

Among PAH patients, the prevalence of obesity is between 30% and 40%. PAH patients with BMI ≥40 kg/m2 and aged less than 65 years have higher mortality. High BMI (≥30 kg/m2) has been linked to worse functional class. Obese PAH patients also have significantly lower 6-minute walk distances and worse quality of life than patients without obesity. Obesity is associated with other illnesses that lead to the development of PH, including sleep apnea, insulin resistance, and obesity hypoventilation syndrome.1

Sleep Apnea and Obstructive Airway Disease

Obstructive airway disease includes obstructive lung disease (asthma and bronchiectasis), reactive airways disease, and chronic obstructive pulmonary disease (COPD). These conditions along with sleep apnea occur in approximately 25% of PAH patients. Sleep apnea is associated with increased pulmonary artery pressure and together with hypoxemia-inducing comorbidities results in even more severe PH. PAH patients with sleep apnea have lower arterial oxygen and higher arterial carbon dioxide tension during the day, in comparison to those without PAH, and may require supplemental oxygen therapy.1,3

Clinical Depression

Clinical depression was observed in a study in more than 25% of patients with idiopathic PAH.4 Diagnosis of depression can be missed due to the overlapping symptoms of fatigue and apathy in PAH.5

Thyroid Disease

Thyroid disease is commonly seen in PAH patients. Both hypothyroidism and hyperthyroidism lead to increased cardiac output and pulmonary vascular resistance (PVR), which eventually lead to PH. Thyroid function tests should be included at the diagnosis of PAH. In cases where PAH is confirmed, thyroid testing should be performed at least annually.1

Diabetes

PAH cases with concomitant diabetes have considerably lesser 10-year survival as compared with PAH cases without diabetes. Diabetes as a comorbid condition reduces right ventricular function. Diabetes treatment may delay PAH progression and improving quality of life as well.1,6

Anemia

The prevalence of anemia, likely linked to interleukin-6, is significantly higher in idiopathic PAH than in chronic thromboembolic pulmonary hypertension(CTEPH).7

Chronic Kidney Disease

Kidney dysfunction is a common comorbidity and a significant predictor of mortality in PAH. Some of the abnormalities of PAH that can potentially affect kidneys are decreased cardiac output, increased venous congestion, and neurohormonal hypertension.8

Chronic Liver Disease

Around 2%-6% of patients with decompensated liver disease develop PH, called portopulmonary hypertension (PoPH). A study of PoPH patients showed a 5-year survival rate of 40%. The development of PoPH is not related to the severity of liver disease and is more common in females and those with autoimmune hepatitis.9

Chronic Muscle Disease

Abnormalities in the skeletal and respiratory muscles contribute to exercise intolerance and decreased quality of life in PAH patients. Skeletal muscles in PAH patients show a wide range of cellular abnormalities that finally lead to muscle atrophy and reduced contractility. Exercise training in PAH patients improves muscle function and clinical outcome.10

References

  1. Lang IM, Palazzini M. The burden of comorbidities in pulmonary arterial hypertension. Eur Heart J Suppl. 2019;21(Suppl K):K21-K28. doi:10.1093/eurheartj/suz205
  2. Aronow WS. Treatment of systemic hypertension. Am J Cardiovasc Dis. 2012;2(3):160-170.
  3. Sajkov D, McEvoy RD. Obstructive sleep apnea and pulmonary hypertension. Prog Cardiovasc Dis. 2009;51(5):363-370. doi:10.1016/j.pcad.2008.06.001
  4. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL registry. Chest. 2010;137(2):376-387. doi:10.1378/chest.09-1140
  5. Verma S, Sahni S, Vijayan VK, Talwar A. Depression in pulmonary arterial hypertension: an undertreated comorbidity. Lung India. 2016;33(1):58-63. doi:10.4103/0970-2113.173072
  6. Whitaker ME, Nair V, Sinari S, et al. Diabetes mellitus associates with increased right ventricular afterload and remodeling in pulmonary arterial hypertension. Am J Med. 2018;131(6):702.e7-702.e13. doi:10.1016/j.amjmed.2017.12.046
  7. Soon E, Treacy CM, Toshner MR, et al. Unexplained iron deficiency in idiopathic and heritable pulmonary arterial hypertension. Thorax. 2011;66(4):326-332. doi:10.1136/thx.2010.147272
  8. Nickel NP, O’Leary JM, Brittain EL, et al. Kidney dysfunction in patients with pulmonary arterial hypertension. Pulm Circ. 2017;7(1):38-54. doi:10.1086/690018
  9. Bartolome SD. Portopulmonary hypertension: diagnosis, clinical features, and medical therapy. Clin Liver Dis (Hoboken). 2014;4(2):42-45. doi:10.1002/cld.401
  10. Marra AM, Arcopinto M, Bossone E, Ehlken N, Cittadini A, Grünig E. Pulmonary arterial hypertension-related myopathy: an overview of current data and future perspectives. Nutr Metab Cardiovasc Dis. 2015;25(2):131-139. doi:10.1016/j.numecd.2014.10.005

Reviewed by Harshi Dhingra, MD, on 7/1/2021.

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