Splenic Metabolic Activity Predicts Risk of Future Cardiovascular Events

Emami, Hamed; Singh, Parmanand; MacNabb, Megan H.; Vucic, Esad; Lavender, Zachary; Rudd, James H.F.; Fayad, Zahi A.; Lehrer‐Graiwer, Joshua; Korsgren, Magnus; Figueroa, Amparo L.; Fredrickson, Jill; Rubin, Barry B.; Hoffmann, Udo; Truong, Quynh A.; Min, James K.; Baruch, Amos; Nasir, Khurram; Nahrendorf, Matthias; Tawakol, Ahmed

doi:10.1016/j.jcmg.2014.10.009

Cited by 221 publications

(230 citation statements)

References 26 publications

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“…While invading leukocytes are essential for the removal of debris and dead tissue, an excessive production of myeloid cells is associated with an impaired development of cardiac function and outcome (12,29,30). And as shown recently, an acute event like MI additionally accelerates established atherosclerosis due to a burst of acute systemic inflammation (31,32).…”

Section: Discussionmentioning

confidence: 97%

Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest

Dufner

André

Stiepak³

et al. 2016

Cardiovasc. Diagn. Ther.

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Background: Patients admitted to the hospital after primarily successful cardiopulmonary resuscitation (CPR) are at a very high risk for neurologic deficits and death. Targeted temperature management (TTM) for mild therapeutic hypothermia has been shown to improve survival compared to standard treatment.Acute cardiovascular events, such as myocardial infarction (MI), are a major cause for cardiac arrest (CA) in patients who undergo CPR. Recent findings have demonstrated the importance and impact of the leukocyte response following acute MI.Methods: In this retrospective, single center study we enrolled 169 patients with CA due to non-traumatic causes and primarily successful CPR. A total of 111 subjects (66%) underwent TTM aiming for a target temperature of 32-34 ℃.Results: Analysis of 30 day follow up showed a significantly improved survival of all patients who received TTM compared to patients without hypothermia (P=0.0001). Furthermore TTM was an independent variable of good neurological outcome after 6 months (P=0.0030). Therapeutic hypothermia was found to be beneficial independent of differences in age and sex between both groups. While a higher rate of pneumonia was observed with TTM, this diagnosis had no additional impact on survival or neurological outcome. The beneficial effect on mortality remained significant in patients with the diagnosis of an acute cardiac event (P=0.0145). Next, we evaluated the kinetics of leukocytes in this group over the course of 7 days after CA.At presentation, patients showed a mean level of 16.5±6.7 of leukocytes per microliter. While this level stayed stable in the group of patients without hypothermia, patients who received TTM showed a significant decline of leukocyte levels resulting in significantly lower numbers of leukocytes on days 3 and 5 after CPR. Interestingly, these differences in leukocyte counts remained beyond the time period of TTM while C-reactive protein (CRP) levels were suppressed only during ongoing cooling, but differences between the groups were diminished after TTM was terminated (from day 3 on, P>0.2). Finally, patients who received TTM and showed a leukocyte count of less than 12.7/μL on day 3 had an improved survival (P=0.0214) and neurological outcome (P=0.0049) compared to patients above that level.Conclusions: Our data underline the beneficial effects of TTM and demonstrate an impact of hypothermia on leukocyte counts after CA.

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Section: Discussionmentioning

confidence: 97%

Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest

Dufner

André

Stiepak³

et al. 2016

Cardiovasc. Diagn. Ther.

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“…All subjects fasted for at least 8 h before intravenous 18 F-FDG injection (;370 MBq for a 70-kg patient). PET/CT images were acquired approximately 60-90 min after 18 F-FDG injection, on a Biograph 64 scanner (Siemens Healthcare).…”

Section: F-fdg Pet/ct Imagingmentioning

confidence: 99%

“…The combination of PET and CT (PET/CT) allows for the identification of BAT, because BAT demonstrates high 18 F-FDG uptake on PET and CT allows for the identification of fat tissue using Hounsfield units (HU) (11,12). Moreover, 18 F-FDG uptake in the aortic wall can be used as a reliable imaging biomarker of inflammation in atherosclerotic plaques (13).…”

mentioning

confidence: 99%

“…Moreover, 18 F-FDG uptake in the aortic wall can be used as a reliable imaging biomarker of inflammation in atherosclerotic plaques (13). Hence, the aim of this study was to evaluate the relation between 18 F-FDG uptake in supraclavicular BAT and arterial inflammation in humans using PET/CT imaging. As a secondary aim, we sought to evaluate the relation between supraclavicular BAT uptake and subsequent cardiovascular events.…”

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confidence: 99%

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Supraclavicular Brown Adipose Tissue ¹⁸F-FDG Uptake and Cardiovascular Disease

et al. 2016

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Preclinical data suggest a negative correlation between brown adipose tissue (BAT) and the degree of coronary atherosclerosis. We sought to evaluate the relationship between 18 F-FDG uptake in supraclavicular BAT in relation to arterial inflammation and subsequent cardiovascular disease (CVD) events in humans. Methods: Individuals who underwent 18 F-FDG PET/CT for clinical indications but who did not have either cancer or known atherosclerotic disease at the time of imaging were included. A radiologist masked to clinical data measured 18 F-FDG uptake within BAT (in the supraclavicular region) as well as in subcutaneous adipose tissues. Tissue density was evaluated using CT (Hounsfield units). Arterial inflammation was assessed by measuring arterial 18 F-FDG uptake and calculating target-to-background ratio. CVD events were independently adjudicated by masked cardiologists. Thereafter, the relationship between BAT activity and CVD events was evaluated. Results: A total of 443 patients (age, 55 y [44-66 y]; 44% men; body mass index [BMI], 26 [range, 23-31]) were included, and 30 patients experienced a cardiovascular event during a median follow-up of 4 y. BAT activity negatively correlated with arterial inflammation (r 5 −0.178, P , 0.01), a relationship that persisted after correcting for age and BMI (r 5 −0.147, P , 0.01). When either high sensitivity or high accuracy thresholds (from receiver-operating curve analyses) were used to define elevated BAT, high BAT was associated with a reduced risk of CVD events (P 5 0.048), even after correcting for age (P 5 0.037). Conclusion: Our results suggest that increased supraclavicular BAT activity is inversely associated with arterial inflammation, independently of age and BMI. Additionally, increased BAT may be associated with fewer cardiovascular events.

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“…For example, inflammatory conditions, such as atherosclerosistriggered ischemic events, can activate splenic hematopoiesis and result in overproduction and deployment of splenic inflammatory monocytes into the circulation [172]. Hence, imaging splenic activity in such pathological conditions, for example by 18 F-FDG-PET, can be useful to monitor therapeutic response and has been shown to serve as a good predictor of future complications by Tawakol and colleagues [174]. The accelerated hematopoiesis and rapid egress of inflammatory monocytes from splenic niches rely in part on CCL-2/CCR-2 interaction and angiotensin II (Ang II)-Ang type I and II receptors [14,175,176].…”

Section: Monocyte Mobilization and Recruitmentmentioning

confidence: 99%

Targeted therapeutics in inflammatory atherosclerosis

Alaarg¹

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Splenic Metabolic Activity Predicts Risk of Future Cardiovascular Events

Cited by 221 publications

References 26 publications

Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest

Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest

Supraclavicular Brown Adipose Tissue ¹⁸F-FDG Uptake and Cardiovascular Disease

Targeted therapeutics in inflammatory atherosclerosis

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Splenic Metabolic Activity Predicts Risk of Future Cardiovascular Events

Cited by 221 publications

References 26 publications

Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest

Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest

Supraclavicular Brown Adipose Tissue 18F-FDG Uptake and Cardiovascular Disease

Targeted therapeutics in inflammatory atherosclerosis

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Supraclavicular Brown Adipose Tissue ¹⁸F-FDG Uptake and Cardiovascular Disease