Progression of coronary calcium burden and carotid stiffness in patients with essential thrombocythemia associated with JAK2 V617F mutation

Atherosclerosis. 2020 Mar:296:25-31. doi: 10.1016/j.atherosclerosis.2020.01.001. Epub 2020 Jan 11.

Abstract

Background and aims: Patients with myeloproliferative neoplasms often succumb to cardiovascular events, but little is known on the early stages of their vascular disease. We studied how patients with JAK2 V617F positive essential thrombocythemia (ET) without overt atherosclerotic disease differed from control subjects in the progression of carotid artery stiffness and preclinical atherosclerosis.

Methods: Thirty-six patients with JAK2 V617F positive ET and 38 age-, gender- and Framingham coronary heart disease (CHD) -matched control subjects were examined twice within 4 years. Clinical and laboratory testing, echo-tracking ultrasound of carotid arteries, coronary calcium measurement and digital plethysmography were performed (ClinTrials.gov NCT03828422).

Results: Coronary calcium correlated with the Framingham CHD risk score at the first examination in the control group (rs = 0.410), but not among the ET patients (rs = 0.116). Both groups progressed in coronary calcium, but the outliers were more prominent among ET patients. Carotid artery stiffness increased with time in the ET patients much more than in the control group: the increase in β-index 1.95 (SD 2.18) vs. 0.22 (SD 1.99), p < 0.001, and the increase in carotid pulse wave velocity 0.72 (SD 0.92) vs. 0.08 (SD 0.72) m/s, p = 0.001. There was no correlation between carotid stiffness and Framingham CHD risk in either group. Digital endothelial function did not change.

Conclusion: Carotid artery stiffness progressed faster in patients with JAK2 V617F positive ET than in control subjects. Coronary calcium correlated with the Framingham CHD risk only in control subjects. This indicates that JAK2 V617F positive ET acted as a non-classical risk factor for vascular disease.

Keywords: Arterial stiffness; Cardiovascular risk; Coronary calcium; Essential thrombocythemia; JAK2 V617F mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asymptomatic Diseases
  • Calcium / analysis*
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / etiology*
  • Carotid Intima-Media Thickness
  • Coronary Disease / diagnostic imaging
  • Coronary Disease / etiology*
  • Coronary Disease / metabolism
  • Disease Progression
  • Female
  • Humans
  • Hyperemia / diagnostic imaging
  • Hyperemia / etiology
  • Janus Kinase 2 / genetics
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plethysmography
  • Positron Emission Tomography Computed Tomography
  • Pulse Wave Analysis
  • Surveys and Questionnaires
  • Thrombocythemia, Essential / blood
  • Thrombocythemia, Essential / complications*
  • Thrombocythemia, Essential / genetics
  • Ultrasonography
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / etiology*
  • Vascular Stiffness

Substances

  • JAK2 protein, human
  • Janus Kinase 2
  • Calcium

Associated data

  • ClinicalTrials.gov/NCT03828422