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The exact mechanism by which the risk factors produce PH has not been established. Given the fact that the absolute risk is generally low, factors of individual susceptibility are likely to play an important role. Risk factors and associated conditions for PAH are presented in the table below [1].

A “definite” association is defined as an epidemic, such as occurred with appetite suppressants in the 1960s, or large, multicenter epidemiologic studies demonstrating an association between a drug and PAH.

A “likely” association is defined as a single-center, case-control study demonstrating an association or a multiple-case series. “Possible” is defined as drugs with similar mechanisms of action as those in the “definite” or “likely” categories but which have not yet been studied (e.g., drugs used to treat attention-deficit disorder).

An “unlikely” association is defined as one in which a drug has been studied in epidemiologic studies and an association with PAH has not been demonstrated.


Table: Updated risk factors for and associated conditions of PAH

Definite	Possible
Aminorex Fenfluramine Dexfenfluramine Toxic rapeseed oil	Cocaine Phenylpropanolamine St. John's Wort Chemotherapeutic agents SSRI
Likely	Unlikely
Amphetamines L-tryptophan Methamphetamines	Oral contraceptives Estrogen Cigarette smoking

 

 

PAH = pulmonary arterial hypertension; SSRI = selective serotonin reuptake inhibitor

Ref. Simmoneau G et al. JACC 2009; 54: Suppl S, S43-54