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Background: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH. Objective: We explored the biomarker potential of plasma BLVRB through (1) its correlation with IPH in carotid plaques assessed by magnetic resonance imaging (MRI), and with recurrent ischemic stroke, and (2) its use for monitoring pharmacotherapy targeting IPH in a preclinical setting. Methods: Plasma BLVRB levels were measured in patients with symptomatic carotid atherosclerosis from the PARISK study (n = 177, 5 year follow-up) with and without IPH as indicated by MRI. Plasma BLVRB levels were also measured in a mouse vein graft model of IPH at baseline and following antiangiogenic therapy targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Results: Plasma BLVRB levels were significantly higher in patients with IPH (737.32 ± 693.21 vs. 520.94 ± 499.43 mean fluorescent intensity (MFI), p = 0.033), but had no association with baseline clinical and biological parameters. Plasma BLVRB levels were also significantly higher in patients who developed recurrent ischemic stroke (1099.34 ± 928.49 vs. 582.07 ± 545.34 MFI, HR = 1.600, CI [1.092–2.344]; p = 0.016). Plasma BLVRB levels were significantly reduced following prevention of IPH by anti-VEGFR-2 therapy in mouse vein grafts (1189 ± 258.73 vs. 1752 ± 366.84 MFI; p = 0.004). Conclusions: Plasma BLVRB was associated with IPH and increased risk of recurrent ischemic stroke in patients with symptomatic low- to moderate-grade carotid stenosis, indicating the capacity to monitor the efficacy of IPH-preventive pharmacotherapy in an animal model. Together, these results suggest the utility of plasma BLVRB as a biomarker for atherosclerotic plaque instability. [ABSTRACT FROM AUTHOR]

Preeclampsia is a maternal hypertensive disease, complicating 2–8% of all pregnancies. It has been linked to a 2–7-fold increased risk for the development of cardiovascular disease, including heart failure, later in life. A total of 40% of formerly preeclamptic women develop preclinical heart failure, which may further deteriorate into clinical heart failure. Noninvasive cardiac imaging could assist in the early detection of myocardial abnormalities, especially in the preclinical stage, when these changes are likely to be reversible. Moreover, imaging studies can improve our insights into the relationship between preeclampsia and heart failure and can be used for monitoring. Cardiac ultrasound is used to assess quantitative changes, including the left ventricular cavity volume and wall thickness, myocardial mass, systolic and diastolic function, and strain. Cardiac magnetic resonance imaging may be of additional diagnostic value to assess diffuse and focal fibrosis and perfusion. After preeclampsia, sustained elevated myocardial mass along with reduced myocardial circumferential and longitudinal strain and decreased diastolic function is reported. These findings are consistent with the early phases of heart failure, referred to as preclinical (asymptomatic) or B-stage heart failure. In this review, we will provide an up-to-date overview of the potential of cardiac magnetic resonance imaging and echocardiography in identifying formerly preeclamptic women who are at high risk for developing heart failure. The potential contribution to early cardiac screening of women with a history of preeclampsia and the pros and cons of these imaging modalities are outlined. Finally, recommendations for future research are presented. [ABSTRACT FROM AUTHOR]

INTRICATE is a prospective double-blind placebo-controlled feasibility study, assessing the influence of combined vitamin K2 and vitamin D3 supplementation on micro-calcification in carotid artery disease as imaged by hybrid Sodium [18F]Fluoride (Na[18F]F) positron emission tomography (PET)/ magnetic resonance imaging (MRI). Arterial calcification is an actively regulated process and results from the imbalance between calcification promoting and inhibiting factors. Considering the recent advancements in medical imaging, ultrasound (US), PET/MRI, and computed tomography (CT) can be used for the selection and stratification of patients with atherosclerosis. Fifty-two subjects with asymptomatic carotid artery disease on at least one side of the neck will be included in the study. At baseline, an Na[18F]F PET/MRI and CT examination will be performed. Afterwards, subjects will be randomized (1:1) to a vitamin K (400 µg MK-7/day) and vitamin D3 (80 µg/day) or to placebo. At the 3-month follow-up, subjects will undergo a second Na[18F]F PET/MRI and CT scan. The primary endpoint is the change in Na[18F]F PET/MRI (baseline vs. after 3 months) in the treatment group as compared to the placebo arm. Secondary endpoints are changes in plaque composition and in blood-biomarkers. The INTRICATE trial bears the potential to open novel avenues for future large scale randomized controlled trials to intervene in the plaque development and micro-calcification progression. [ABSTRACT FROM AUTHOR]