Blood Pressure Is a Major Modifiable Risk Factor Implicated in Pathogenesis of Intraplaque Hemorrhage

Abstract

Objective Effective prevention and management strategies of intraplaque hemorrhage (IPH) remain elusive due to our limited knowledge regarding its etiology and contributing factors. This hypothesis-generating study aimed to investigate associations between cardiovascular risk factors and IPH for improved understanding of the pathogenesis of IPH. Approach and Results Asymptomatic subjects with 16–79% stenosis on ultrasound underwent carotid magnetic resonance imaging (MRI) using a large-coverage, three-dimensional MRI protocol. Individual plaques (maximum thickness>1.5 mm) in bilateral carotid arteries were identified and presence of IPH was determined. From 80 subjects, 176 de novo plaques were measured, of which 38 (21.6%) contained IPH. Blood pressure (BP), primarily low diastolic BP, was associated with IPH in multivariate analysis adjusted for age, sex, and plaque size (odds ratio [OR with 95% confidence interval] per 10 mmHg ↑: 0.51 [0.30–0.88]), which was little changed after adjusting for antihypertensive use and systemic atherosclerosis. Antiplatelet use was associated with IPH in age and sex-adjusted models (p=0.018), for which a trend remained after considering plaque size and past medical history (OR for aspirin alone vs. none: 3.1 [0.66–14.8]; OR for clopidogrel or dual therapy vs. none: 5.3 [0.80–35.0]; p=0.083). Conclusions Low diastolic BP was independently associated with IPH, which was unlikely due to treatment difference or BP changes from systemic atherosclerosis. Hemodynamic changes from lowering diastolic BP may be the pathophysiological link. Prospective serial studies are needed to assess whether BP and antiplatelet use are associated with the development of new or repeated IPH.

Ipsilateral plaques display higher T1 signals than contralateral plaques in recently symptomatic patients with bilateral carotid intraplaque hemorrhage

“…Haptoglobin genotype, which is considered to lead to different tissue responses to IPH, was found to be associated with iron deposition in atherosclerotic plaques [33]. Furthermore, blood pressure fluctuation was recently indicated as an unrecognized risk factor in the pathogenesis of IPH [22,34]. These traditional and novel risk factors could have unique influences on the natural history of IPH+ plaques that is different from their effects on IPH-plaques.…”

“…Plaque length was defined as the number of slices with distinct plaque (maximum wall thickness ≥1.5 mm) multiplied by slice thickness. Previous studies indicate that IPH+ plaques are longer than IPH- plaques and frequently extend across the flow divider of the common carotid artery [22]. Therefore, plaque location was recorded as above or below the flow divider by comparing the slice with largest plaque burden (maximum percent wall area) relative to the flow divider.…”

Simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) imaging: Comparison with contrast‐enhanced MR angiography for measuring carotid stenosis

“…Written informed consent was obtained prior to study for all subjects. Subjects were recruited as part of an ongoing prospective cohort study that examines the natural history of carotid atherosclerosis (17). Patients aged 50–85 years, free from cerebrovascular events within the past 6 months, and with 16–79% stenosis by duplex ultrasound in at least one carotid artery were recruited.…”

Atherosclerotic Plaque Rupture

“…An interesting connection between blood pressure and prevalence of intraplaque hemorrhage in carotid plaques in patients (up to ≈22%) was recently reported. 75 The stiffer the arterial system, the more intraplaque hemorrhages were found. 76 The latter 2 reports indicate the relevance of intraplaque hemorrhage in human plaque instability.…”

“…A recent human study provides evidence that treating blood pressure has the potential to reduce intraplaque hemorrhage as seen in MRI in carotid plaques in patients. 75 DNA/RNA therapeutics hold great promise and initial promising approaches toward plaque stabilization have been published. These include micro-RNA, 118 anti-micro-RNA, 119,120 and a type B CpG oligodeoxynucleotide TLR9 agonist.…”