Reductions in mobility and cognitive function linked to accrual of brain microvascular disease related white-matter hyperintensities(WMH) on magnetic resonance imaging (MRI) canoccur in older hypertensive patients in as little as 2 years. We have designed a trial evaluating two levels of ambulatory BP control in individuals with normal or mildly impaired mobility and cognition who have detectable cerebrovascular disease (>0.5% WMH fraction of intracranial volume) on functional outcomes. The study is a prospective randomized, open-label trial with blinded endpoints, inpatients ages 75 and older with elevated 24-h systolic BP (≥145 mmHg in the untreated state) who do not have unstable cardiovascular disease, heart failure or stroke. The primary and key secondary outcomes in the trial are: change from baseline in mobility and cognitive function and damage to brain white matter as demonstrated by accrual of WMH volume and changes indiffusion tensor imaging.Approximately 300 patients will be enrolled and 200 randomized to one of two levels of ambulatory BP control (intensive to achieve a goal 24-hour systolic BP of ≤ 130 mmHg or standard to achieve a goal 24-hour systolic BP of ≤ 145 mmHg) for a total of 36 months using similar antihypertensive regimens. The analytical approach provides 85% power to show a clinically meaningful effect in differences in mobility accompanied by quantitative differences in WMH between treatment groups. The INFINITY trial is the first to guide antihypertensive therapy using ambulatory BP monitoring rather than clinic BP to reduce cerebrovascular disease.

Objective-To establish and validate early noninvasive imaging of matrix metalloproteinase (MMP) activation for monitoring the progression of vascular remodeling and response to dietary modification. Methods and Results-Apolipoprotein E Ϫ/Ϫ mice that were fed a high-fat diet underwent left common carotid artery wire injury. One week after surgery, a group of animals were withdrawn from the high-fat diet. The other group of animals continued that diet throughout the study. Micro single-photon emission computed tomographic (microSPECT)/CT imaging with RP805 (a 99m Tc-labeled tracer targeting activated MMPs) was repeatedly performed at 2 and 4 weeks after surgery. Histological analysis at 4 weeks showed significant left carotid neointima formation, monocyte/macrophage infiltration, and upregulation of several MMPs, which were ameliorated by withdrawal from the high-fat diet. In vivo microSPECT/CT images visualized significant RP805 uptake, reflecting MMP activation, in the injured carotid arteries. MMP activation was reduced as early as 1 week after withdrawal from the high-fat diet and significantly correlated with neointimal area at 4 weeks after surgery. Key Words: carotid arteries Ⅲ imaging agents Ⅲ metalloproteinases Ⅲ vascular biology D espite recent preventive, diagnostic, and therapeutic advances, cardiovascular diseases remain a major cause of mortality worldwide. Vascular remodeling (ie, changes in the vessel wall geometry and structure) contributes to the pathogenesis of many vascular diseases, including atherosclerosis, postangioplasty restenosis, and aneurysm. Several preventive and therapeutic measures (eg, smoking cessation and hypertension and hyperlipidemia control) aim at changing the natural course of vascular remodeling. 1 Early monitoring of the effects of these measures may potentially enhance their effectiveness by providing the opportunity to personalize interventions. Conventional imaging modalities (eg, angiography, MRI, and perfusion imaging) provide valuable anatomic and physiological information for patient care. However, they cannot detect early biological processes that precede the development of advanced vascular diseases. Molecular imaging is a potentially powerful strategy for early detection of vascular remodeling that may also help predict the natural course of the disease and its response to therapy. Conclusion-MMPMatrix metalloproteinases (MMPs) contribute to a variety of physiological and pathological processes, including wound healing, inflammation, angiogenesis, cancer metastasis, and vascular remodeling. 2,3 MMP activity is delicately controlled at transcriptional and posttranscriptional (activation) levels and by the presence of inhibitors, such as tissue inhibitors of MMPs. 4,5 Several MMPs, including MMP-2 and MMP-9, are upregulated in remodeling arteries and play key roles in the remodeling process. 2 The recent development of indium 111-labeled RP782 and its homologue, 99m Tc-labeled RP805, which specifically target the MMP activation epitope, have provided an opportuni...

Objective Inflammation plays a key role in the development of vascular diseases. Monocytes and macrophages express αvβ3 integrin. We used an αv integrin-specific tracer, 99mTc-NC100692, to investigate integrin-targeted imaging for detection vessel wall inflammation. Methods and Results The binding of a fluorescent homologue of NC100692 to αvβ3 on human monocytes and macrophages was shown by flow cytometry. Vessel wall inflammation and remodeling was induced in murine carotid arteries through adventitial exposure to CaCl2. NC100692 microSPECT-CT imaging was performed after 2 and 4 weeks and showed significantly higher uptake of the tracer in CaCl2-exposed left carotids compared to sham-operated contra-lateral arteries. Histological analysis at 4 weeks demonstrated significant remodeling of left carotid arteries and considerable macrophage infiltration which was confirmed by real-time polymerase chain reaction. There was no significant difference in normalized αv, β3 or β5 mRNA expression between right and left carotid arteries. Finally, NC100692 uptake strongly correlated with macrophage marker expression in carotid arteries. Conclusions NC100692 imaging can detect vessel wall inflammation in vivo. If further validated, αv-targeted imaging may provide a non-invasive approach for identifying patients who are at high risk for vascular events and tracking the effect of anti-inflammatory treatments.

Background Cardiac injury is common in COVID‐19 patients and is associated with increased mortality. However, it remains unclear if reduced cardiac function is associated with cardiac injury, and additionally if mortality risk is increased among those with reduced cardiac function in COVID‐19 patients. Hypothesis The aim of this study was to assess cardiac function among COVID‐19 patients with and without biomarkers of cardiac injury and to determine the mortality risk associated with reduced cardiac function. Methods/Results This retrospective cohort study analyzed 143 consecutive COVID‐19 patients who had an echocardiogram during hospitalization between March 1, 2020 and May 5, 2020. The mean age was 67 ± 16 years. Cardiac troponin‐I was available in 131 patients and an increased value (>0.03 ng/dL) was found in 59 patients (45%). Reduced cardiac function, which included reduced left or right ventricular systolic function, was found in 40 patients (28%). Reduced cardiac function was found in 18% of patients without troponin‐I elevation, 42% with mild troponin increase (0.04‐5.00 ng/dL) and 67% with significant troponin increase (>5 ng/dL). Reduced cardiac function was also present in more than half of the patients on mechanical ventilation or those deceased. The in‐hospital mortality of this cohort was 28% (N = 40). Using logistic regression analysis, we found that reduced cardiac function was associated with increased mortality with adjusted odds ratio (95% confidence interval) of 2.65 (1.18 to 5.96). Conclusions Reduced cardiac function is highly prevalent among hospitalized COVID‐19 patients with biomarkers of myocardial injury and is independently associated with mortality.