04 March 2021

Pulmonary Hypertension: a newly recognised complication of obesity?

October 25, 2019 (11).jpg

By Anna R. Hemnes, on behalf of the Pulmonary Vascular Research Institute

Pulmonary hypertension refers to elevated blood pressure in the lungs and can result in right heart failure and death. There are several forms of pulmonary hypertension including a rare and deadly disease termed pulmonary arterial hypertension (PAH) and pulmonary hypertension due to left heart disease and lung disease. PAH primarily affects young women and even with the best treatment commonly results in death within 8 years of the diagnosis.

In the past decade, it has become increasingly clear that obesity and its sequalae can promote both PAH and also the development of right heart failure. Insulin resistance, particularly related to lipid metabolism, is common in patients with PAH and when manifest as diabetes mellitus is associated with worse outcomes in PAH. The right heart appears particularly susceptible to this altered lipid metabolism with deposition of toxic fat within the cardiomyocytes. New basic research is beginning to understand how altered lipid metabolism may also promote development of the complex pulmonary vascular lesions found in PAH, plexiform lesions. The Pulmonary Vascular Research Institute (PVRI) has been a leading forum for presentation of these data in conferences and in manuscripts through the journal Pulmonary Circulation. It is presently unknown if reversal of metabolic disease through drugs or weight loss can improve PAH outcomes. It is also unknown if patients with diabetes mellitus are at increased risk for PAH.

Patients with pulmonary hypertension due to left heart disease have obesity in many, if not most, cases. There is emerging literature that insulin resistance and altered fat metabolism also promote development of pulmonary vascular disease and right heart failure in pulmonary hypertension due to left heart failure. At the bedside, it is clear that features of the metabolic syndrome are highly prevalent in this most common form of pulmonary hypertension and physicians routinely counsel patients with this condition to lose weight.

The field of pulmonary hypertension has recognised that obesity is increasingly common in our patients and nearly every epidemiologic study of pulmonary hypertension over the past 30 years has shown a gradual but steady increase in BMI. There is a growing literature that obesity plays a role in promoting pulmonary vascular disease and is not a benign process. The global impact of obesity on pulmonary vascular disease may be quite large and is an active area of discussion at the PVRI.  Our field is actively researching how obesity affects the pulmonary vasculature and the right heart and whether reversal of obesity and its consequences can improve survival and quality of life in these conditions.

References

1. Obokata M, Reddy YNV, Pislaru SV, Melenovsky V and Borlaug BA. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Circulation. 2017;136:6-19.

2. Hemnes AR, Luther JM, Rhodes CJ, Burgess JP, Carlson J, Fan R, Fessel JP, Fortune N, Gerszten RE, Halliday SJ, Hekmat R, Howard L, Newman JH, Niswender KD, Pugh ME, Robbins IM, Sheng Q, Shibao CA, Shyr Y, Sumner S, Talati M, Wharton J, Wilkins MR, Ye F, Yu C, West J and Brittain EL. Human PAH is characterized by a pattern of lipid-related insulin resistance. JCI Insight. 2019;4.

3. Weatherald J, Huertas A, Boucly A, Guignabert C, Taniguchi Y, Adir Y, Jevnikar M, Savale L, Jais X, Peng M, Simonneau G, Montani D, Humbert M and Sitbon O. Association Between BMI and Obesity With Survival in Pulmonary Arterial Hypertension. Chest. 2018;154:872-881.


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