Coronary microvascular dysfunction due to essential thrombocythemia and policythemia vera: the missing piece in the puzzle of their increased cardiovascular risk?

Myeloproliferative neoplasms are most commonly associated with venous thrombosis. Up to 60% of patients experience a thrombotic event in their lifetimes, including stroke or myocardial infarction. It is unclear whether pathogenetic factors linking essential thrombocythemia (ET) and polycythemia vera (PV) to thrombotic complications do play a role in the risk of coronary artery disease (CAD). We aimed to assess coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic patients with ET and PV. Fifty-two patients with ET (M/F 13/39, age 61 ± 7 years) and 22 patients with PV (M/F 13/9, age 60.4 ± 13 years) without clinical evidence of heart disease, and 50 controls matched for age and gender were studied. None had CAD. All control subjects were asymptomatic with no history of heart disease. CFR in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. In patients with ET and PV, CFR was lower than in controls (2.9 ± 0.94 and 2.2 ± 0.7 vs. 3.8 ± 0.7, P < 0.004 and P < 0.0001 respectively). The prevalence of CFR ≤ 2.5 was higher in patients with ET (20 cases, 38.5%) and PV (15 cases, 68.2%) compared with controls (4.1%) (P < 0.0001). Severe CFR (CFR < 2) impairment was found in eight patients with ET (15.4%), in nine patients with PV (40.9%), and in none of control subjects. The mutation of JAK2 gene was associated with abnormal CFR. Asymptomatic patients with ET and PV have coronary microvascular dysfunction in the absence of clinical conditions suggesting CAD.