Methamphetamine and the risk of pulmonary arterial hypertension

Abstract

Purpose of review: Methamphetamine is a highly addictive drug originally developed for the treatment of neuropsychiatric disorders. At present, the epidemic rise of illicit methamphetamine use has increased the number of patients living with medical complications. Our group has recently identified a definite association between methamphetamine use and pulmonary arterial hypertension (PAH), a life-threatening disease characterized by occlusive vasculopathy and progressive right heart failure. This review will discuss the evidence that links methamphetamine with PAH and how to approach the diagnosis and management of methamphetamine-associated pulmonary arterial hypertension (Meth-APAH) patients in clinic.

Recent findings: Compared with idiopathic (I) PAH, Meth-APAH patients present with worse functional status, right ventricular dysfunction, and exercise tolerance. Despite therapy, the 5-year survival of Meth-APAH patients is significantly lower compared with IPAH. Genetic studies suggest that loss of function variants in genes involved in drug detoxification can increase susceptibility for methamphetamine-related vascular injury and trigger occlusive vasculopathy.

Summary: PAH patients undergoing diagnostic evaluation should be screened for a history of current or past methamphetamine use. Pharmacovigilance should be implemented to monitor patients being treated with methamphetamine for neuropsychiatric disorders (e.g., attention-deficit hyperactivity disorder). More studies will be needed to identify which susceptibility factors increase risk of PAH in methamphetamine users.

FIGURE 1.

Histopathology of Meth-APAH and IPAH. Panel A: normal muscular pulmonary artery. Panel B: plexiform lesion in patient with IPAH who underwent lung transplantation. Panel C: plexiform arteriopathy in Meth-APAH involving muscular artery. Panel D: high-power magnification showing proliferation of slit-like vascular channels within artery. Panel E: pulmonary microvasculopathy in Meth-APAH. Panel F: high-power magnification showing proliferation of capillaries within the pulmonary interstitium. Panel G: angiomatoid lesion in Meth-APAH composed of dilated, thin-walled vascular spaces surrounding a plexiform lesion. Panel H: the patient in panel G also exhibited scattered intravascular collections of microcrystalline cellulose (a filler commonly used to “cut” amphetamines), causing an intimal proliferative response within the muscular artery. IPAH, idiopathic pulmonary arterial hypertension; Meth-APAH, methamphetamine-associated pulmonary arterial hypertension. Reproduced with permission [29^■■].

FIGURE 2.

Kaplan–Meier plot comparing event-free survival in Meth-APAH patients vs. iPAH patients. Kaplan–;Meier estimated event-free survival demonstrates worse outcomes for patients presenting with Meth-APAH (dashed line) as compared to those with iPAH (solid line). iPAH, idiopathic pulmonary arterial hypertension; Meth-APAH, methamphetamine associated pulmonary arterial hypertension. Reproduced with permission [29^■■].

FIGURE 3.

Whole body images of radiolabeled methamphetamine in an African-American and in a White. Note the higher accumulation of radiolabeled methamphetamine in the lungs of the African-American. The hot spot on the abdomen of the White study participant represents the stomach, where radiolabeled methamphetamine accumulation was high but variable across study participants (may reflect the acidic environment of the stomach that favors trapping methamphetamine, which is a weak base). Reproduced with permission [30].

FIGURE 4.

CES1 expression is reduced in vascular lesions of METH-PAH. Representative immunofluorescence studies of lung sections stained for CES1 (red) obtained from a healthy donor (top) and four METH-PAH patients. CD31 (green) stains for endothelial cells. CES1, carboxylesterase 1; METH-PAH, methamphetamine-associated pulmonary arterial hypertension. Reproduced with permission [32^■].