Publications by authors named "Amit K Dey"

88 Publications

Prevalence of cardiovascular risk factors in a nationally representative adult population with inflammatory bowel disease without atherosclerotic cardiovascular disease.

Am J Prev Cardiol 2021 Jun 16;6:100171. Epub 2021 Mar 16.

Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, United States.

Background And Aims: Chronic inflammation is associated with premature atherosclerotic cardiovascular disease (ASCVD). We studied the prevalence of cardiovascular risk factors (CRFs) amongst individuals with IBD who have not developed ASCVD.

Methods: Our study population was derived from the 2015 - 2016 National Health Interview Survey. Those with ASCVD (defined as myocardial infarction, angina or stroke) were excluded. The prevalence of CRFs among individuals with IBD was compared with those without IBD. The odds CRFs among adults with IBD was assessed using logistic regression models.

Results: In our study population of 60,155 individuals, 786 (1.3%) had IBD. IBD was associated with increased odds hypertension (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.39-2.09), diabetes (OR 1.68, 95% CI 1.22-2.32), hypercholesterolemia (OR 1.62, 95% CI 1.32-2.99) and insufficient physical activity (OR 1.38, 95% CI 1.16-1.66).

Conclusion: IBD is associated with higher prevalence of CRFs. Early screening and risk mitigation strategies are warranted.
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http://dx.doi.org/10.1016/j.ajpc.2021.100171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315477PMC
June 2021

GlycA measured by NMR spectroscopy is associated with disease activity and cardiovascular disease risk in chronic inflammatory diseases.

Am J Prev Cardiol 2020 Dec 7;4:100120. Epub 2020 Nov 7.

Division of Rheumatology and Immunology, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27701, USA.

GlycA is a biomarker of systemic inflammation, quantifying both the protein concentrations and glycosylation states of several acute phase proteins. GlycA has been shown to be associated with both subclinical atherosclerosis and with cardiovascular disease (CVD). GlycA levels are higher in acute and chronic inflammation. During ongoing systemic inflammatory processes, GlycA specific acute phase reactants and proteins undergo circulating concentration and glycosylation pattern changes, and these alterations are reflected in the GlycA NMR signal. Additionally, levels associate with ongoing disease severity in individuals with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis thus capturing active inflammation. Furthermore, in these disease states, GlycA is associated with cardiovascular disease (CVD) independent of traditional risk factors including C-reactive protein (CRP). Finally, GlycA levels decrease with exercise, weight loss, and systemic anti-inflammatory agents. Therefore, GlycA appears to be a promising new composite biomarker of active systemic inflammation including assessing CVD risk in patients with inflammatory diseases.
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http://dx.doi.org/10.1016/j.ajpc.2020.100120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315361PMC
December 2020

Subclinical Liver Disease is Associated with Subclinical Atherosclerosis in Psoriasis: Results from Two Observational Studies.

J Invest Dermatol 2021 Jul 19. Epub 2021 Jul 19.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n=76 psoriasis participants and 76 controls), non-alcoholic fatty liver disease (NAFLD), assessed by the sonographic hepatorenal index (SHRI), was more prevalent in psoriasis than controls (61% vs 45%; p=.04). Psoriasis participants with NAFLD had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than psoriasis without NAFLD (61% vs 23%; p=.006) and controls with NAFLD (61% vs 32%; p<.05). SHRI was a determinant of subclinical atherosclerosis in psoriasis (OR, 3.5; p=.01). In the United States cohort, (n=162 psoriasis participants who underwent positron emission tomography and coronary CT angiography), those with high hepatic F-FDG uptake had higher noncalcified (1.3 (0.49 mm) vs 1.0 (0.40 mm)), fibrofatty (0.23 (0.15 mm) vs 0.11 (0.087 mm)), and lipid rich necrotic core (4.3 (2.3 mm) vs 3.0 (1.7 mm)) coronary burden (all p<.001,). Hepatic F-FDG uptake associated with noncalcified (β=0.28; p<.001), fibrofatty (β=0.49; p<.001) and lipid rich necrotic core (β=0.28; p=.003) burden. These results demonstrate the downstream cardiovascular effects of subclinical liver disease in psoriasis.
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http://dx.doi.org/10.1016/j.jid.2021.05.034DOI Listing
July 2021

Chronic inflammatory diseases and coronary heart disease: Insights from cardiovascular CT.

J Cardiovasc Comput Tomogr 2021 Jun 24. Epub 2021 Jun 24.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Epidemiological and clinical studies have demonstrated a consistent relationship between increased systemic inflammation and increased risk of cardiovascular events. In chronic inflammatory states, traditional risk factors only partially account for the development of coronary artery disease (CAD) but underestimate total cardiovascular risk likely due to the residual risk of inflammation. Computed coronary tomography angiography (CCTA) may aid in risk stratification by noninvasively capturing early CAD, identifying high risk plaque morphology and quantifying plaque at baseline and in response to treatment. In this review, we focus on reviewing studies on subclinical atherosclerosis by CCTA in individuals with chronic inflammatory conditions including rheumatoid arthritis (RA), systemic lupus erythematous (SLE), human immunodeficiency virus (HIV) infection and psoriasis. We start with a brief review on the role of inflammation in atherosclerosis, highlight the utility of using CCTA to delineate vessel wall and plaque characteristics and discuss combining CCTA with laboratory studies and emerging technologies to complement traditional risk stratification in chronic inflammatory states.
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http://dx.doi.org/10.1016/j.jcct.2021.06.003DOI Listing
June 2021

Spontaneous Rupture of Pheochromocytoma Presenting as Acute Retroperitoneal Hemorrhage.

Am J Med Sci 2021 08 26;362(2):e15-e16. Epub 2020 Nov 26.

Professor and Unit Head, Department of Surgery, Seth GS Medical college and KEM Hospital, Mumbai, Maharashtra, India.

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http://dx.doi.org/10.1016/j.amjms.2020.11.022DOI Listing
August 2021

New Frontiers in Psoriatic Disease Research, Part II: Comorbidities and Targeted Therapies.

J Invest Dermatol 2021 Apr 19. Epub 2021 Apr 19.

Department of Dermatology, University of California San Francisco, San Francisco, California. Electronic address:

Although psoriasis and psoriatic arthritis (PsA) have been classically considered to be diseases of the skin and joints, respectively, emerging evidence suggests that a combination of innate and environmental factors creates widespread immune dysfunction, affecting multiple organ systems. A greater understanding of the pathogenesis of psoriasis and the systemic effects of psoriatic inflammation has allowed for the development of new, more effective treatments. The second portion of this two-part review series examines the comorbidities associated with psoriasis and PsA as well as the most recent advances in targeted systemic therapies for these conditions.
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http://dx.doi.org/10.1016/j.jid.2021.02.743DOI Listing
April 2021

The evolving role of coronary CT angiography in Acute Coronary Syndromes.

J Cardiovasc Comput Tomogr 2021 Sep-Oct;15(5):384-393. Epub 2021 Feb 23.

Division of Cardiology, The George Washington University School of Medicine & Health Sciences, Washington, DC, USA; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

In the United States, non-obstructive coronary disease has been on the rise, and each year, nearly one million adults suffer myocardial infarction, 70% of which are non-ST-segment elevation myocardial infarction (NSTEMI). In addition, approximately 15% of patients suffering NSTEMI will have subsequent readmission for a recurrent acute coronary syndrome (ACS). While invasive angiography remains the standard of care in the diagnostic and therapeutic approach to these patients, these methods have limitations that include procedural complications, uncertain specificity in diagnosis of the culprit lesion in patients with multi-vessel coronary artery disease (CAD), and challenges in following coronary disease over time. The role of coronary computed tomography angiography (CCTA) for evaluating patients with both stable and acute chest pain has seen a paramount upshift in the last decade. This paper reviews the established role of CCTA for the rapid exclusion of obstructive plaque in troponin negative acute chest pain, while exploring opportunities to address challenges in the current approach to evaluating NSTEMI.
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http://dx.doi.org/10.1016/j.jcct.2021.02.002DOI Listing
February 2021

Outcomes of patients hospitalized for acute pulmonary embolism by obstructive sleep apnea status.

Pulm Circ 2021 Apr-Jun;11(2):2045894021996224. Epub 2021 Mar 27.

Institute of Cardiovascular Medicine, Section of Advanced Heart Failure/Transplant/MCS and Pulmonary Hypertension, Allegheny General Hospital, Pittsburgh, PA, USA.

Pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) is increasingly recognized in the aging population, especially with the rising obesity epidemic. The impact of OSA on inpatient mortality in PE is not well understood. We used the Nationwide Inpatient Sample databases from 2005 to 2016 to identify 755,532 acute PE patients (age≥18 years). Among these, 61,050 (8.1%) were OSA+. Temporal trends in length of stay, inpatient mortality, and its association with OSA in PE patients were analyzed. The proportion of PE patients who were OSA+ increased from 2005 to 2016. OSA+ PE patients were younger and predominantly men. Despite a higher prevalence of traditional risk factors for inpatient mortality in OSA+ patients, OSA was associated with a lower risk of mortality in PE patients (odds ratio, 95% confidence interval; : unadjusted 0.56, 0.53-0.58;  < 0.0001 and adjusted 0.55, 0.52-0.58;  < 0.0001). Overall mortality and length of stay in PE patients decreased over time. Relative to OSA- patients, there was a slight increase in mortality among OSA+ PE patients over time, although the length of stay remained unchanged between the two groups. In conclusion, OSA+ PE patients had a lower inpatient mortality compared to OSA- patients despite a higher prevalence of traditional mortality risk factors. Secondary pulmonary hypertension related to OSA with preconditioning of the right ventricle to elevated afterload may potentially explain the protective effect of OSA on mortality in PE. However, mechanistic studies need to further elucidate the links behind this association.
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http://dx.doi.org/10.1177/2045894021996224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013707PMC
March 2021

Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in a Community-Based Cohort: Data From the Washington, D.C. Cardiovascular Health and Needs Assessment.

Front Cardiovasc Med 2021 10;8:599341. Epub 2021 Mar 10.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, United States.

Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar Fluorodeoxyglucose (FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort. Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity. AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (β = 0.41, = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity. AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.
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http://dx.doi.org/10.3389/fcvm.2021.599341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988194PMC
March 2021

Application of machine learning in understanding atherosclerosis: Emerging insights.

APL Bioeng 2021 Mar 16;5(1):011505. Epub 2021 Feb 16.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Biological processes are incredibly complex-integrating molecular signaling networks involved in multicellular communication and function, thus maintaining homeostasis. Dysfunction of these processes can result in the disruption of homeostasis, leading to the development of several disease processes including atherosclerosis. We have significantly advanced our understanding of bioprocesses in atherosclerosis, and in doing so, we are beginning to appreciate the complexities, intricacies, and heterogeneity atherosclerosi. We are also now better equipped to acquire, store, and process the vast amount of biological data needed to shed light on the biological circuitry involved. Such data can be analyzed within machine learning frameworks to better tease out such complex relationships. Indeed, there has been an increasing number of studies applying machine learning methods for patient risk stratification based on comorbidities, multi-modality image processing, and biomarker discovery pertaining to atherosclerotic plaque formation. Here, we focus on current applications of machine learning to provide insight into atherosclerotic plaque formation and better understand atherosclerotic plaque progression in patients with cardiovascular disease.
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http://dx.doi.org/10.1063/5.0028986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889295PMC
March 2021

Underperformance of clinical risk scores in identifying imaging-based high cardiovascular risk in psoriasis: results from two observational cohorts.

Eur J Prev Cardiol 2020 Nov 9. Epub 2020 Nov 9.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Clinical Research Center, Room 5-5140, Bethesda, MD 20892, USA.

Aims: We aimed to evaluate whether traditional risk scores [short-term, 'psoriasis-modified' (multiplied by 1.5) and lifetime] were able to capture high cardiovascular disease (CVD) risk as defined by the presence of atherosclerotic plaques in coronary, femoral, or carotid arteries in psoriasis.

Methods And Results: We used two prospectives obseravational cohorts. European cohort: femoral and carotid atherosclerotic plaques were evaluated by ultrasound in 73 psoriasis patients. Lifetime CVD risk (LTCVR) was evaluated with QRISK-LT; short-term CVD risk was evaluated with SCORE and psoriasis-modified SCORE. American cohort: 165 patients underwent coronary computed tomography angiography to assess presence of coronary plaques. LTCVR was evaluated with atherosclerotic cardiovascular disease (ASCVD-LT) lifetime; short-term CVD risk was evaluated with ASCVD and psoriasis-modified ASCVD. European cohort: subclinical atherosclerosis was present in 51% of patients. QRISK-LT identified 64% of patients with atherosclerosis missing a high proportion (35%) with atheroma plaque (P < 0.05). The percentage of patients with atherosclerosis identified by QRISK-LT was significantly higher than those detected by SCORE (0%) and modified SCORE (10%). American cohort: subclinical atherosclerosis was present in 54% of patients. ASCVD-LT captured 54% of patients with coronary plaques missing a high proportion (46%) with coronary plaque (P < 0.05). The percentage of patients with atheroma plaques detected with ASCVD and modified ASCVD were only 20% and 45%, respectively.

Conclusions: Application of lifetime, short-term and 'psoriasis-modified' risk scores did not accurately capture psoriasis patients at high CVD risk.
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http://dx.doi.org/10.1093/eurjpc/zwaa033DOI Listing
November 2020

Etiology and pathophysiology of heart failure in people with HIV.

Heart Fail Rev 2021 May 22;26(3):497-505. Epub 2021 Feb 22.

Section of Cardiology, Baylor College of Medicine and the Michael E. DeBakey VA Hospital, Houston, TX, 77030, USA.

HIV-associated cardiomyopathy is a well-established sequela in people infected with HIV (PHIV). Despite significant advances in HIV management through the use of highly active anti-retroviral therapy (HAART), PHIV on HAART continue to have elevated risk of cardiomyopathy and heart failure, even when accounting for known cardiovascular risk factors. This review article will explore the proposed mechanisms by which chronic HIV infection induces cardiomyopathy and heart failure in the setting of HAART. Evaluation, work-up, and management of cardiomyopathy in PHIV will also be briefly discussed. The advent of HAART has altered the pathophysiology HIV-associated cardiomyopathy from a rapidly progressive cardiomyopathy, often with pericardial involvement, into a chronic process involving inflammation and persistent immune dysregulation. With the significant decrease in AIDS-related deaths, the prevalence of cardiomyopathy and the mortality associated with heart failure in PHIV have increased. Multiple immune-related and inflammatory mechanisms have been proposed, which may provide insight into evaluation and management of cardiomyopathy in PHIV.
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http://dx.doi.org/10.1007/s10741-020-10048-8DOI Listing
May 2021

Nanotomography of lesional skin using electron microscopy reveals cytosolic release of nuclear DNA in psoriasis.

JAAD Case Rep 2021 Mar 6;9:9-14. Epub 2021 Jan 6.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.

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http://dx.doi.org/10.1016/j.jdcr.2020.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868746PMC
March 2021

The neutrophil-lymphocyte ratio and incident atherosclerotic events: analyses from five contemporary randomized trials.

Eur Heart J 2021 03;42(9):896-903

Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA.

Aims: The neutrophil-lymphocyte ratio (NLR) is a readily available inflammatory biomarker that may associate with atherosclerosis and predict cardiovascular (CV) events. The aims of this study are to determine whether the NLR predicts incident major adverse cardiovascular events (MACE) and is modified by anti-inflammatory therapy.

Methods And Results: Baseline and on-treatment NLRs were calculated from complete blood counts among 60 087 participants randomized in the CANTOS, JUPITER, SPIRE-1, SPIRE-2, and CIRT trials to receive placebo or canakinumab, rosuvastatin, bococizumab, or methotrexate, respectively, and followed up for MACE. All analyses were performed first in CANTOS, and then externally validated in the other four trials. For the five trials, hazard ratios for major CV events and mortality comparing NLR quartiles were computed using Cox proportional hazards models, and the effect of each randomized intervention on the NLR was evaluated in comparison to placebo. The NLR modestly correlated with interleukin-6, C-reactive protein, and fibrinogen levels but minimally with lipids. In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14-25%, P < 0.0001], 31% in SPIRE-1 (95% CI 14-49%, P = 0.00007), 27% in SPIRE-2 (95% CI 12-43%, P = 0.0002), 9% in CIRT (95% CI 0.2-20%, P = 0.045), and 11% in JUPITER (95% CI 1-22%, P = 0.03). While lipid-lowering agents had no significant impact on the NLR, anti-inflammatory therapy with canakinumab lowered the NLR (P < 0.0001).

Conclusion: The NLR, an easily obtained inflammatory biomarker, independently predicts CV risk and all-cause mortality, and is reduced by interleukin-1β blockade with canakinumab.
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http://dx.doi.org/10.1093/eurheartj/ehaa1034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936519PMC
March 2021

Association of neutrophil-to-lymphocyte ratio with non-calcified coronary artery burden in psoriasis: Findings from an observational cohort study.

J Cardiovasc Comput Tomogr 2021 Jul-Aug;15(4):372-379. Epub 2020 Dec 28.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Background: Inflammation in the form of elevated high-sensitivity c-reactive protein (hs-CRP) has been shown to be critical in the development of atherothrombosis. Psoriasis, a chronic inflammatory skin disease, is associated with high systemic-inflammation, elevated neutrophil-to-lymphocyte ratio (NLR) and accelerated non-calcified coronary artery burden (NCB) by coronary computed tomography angiography (CCTA). We hypothesized that NLR would associate with early, rupture-prone atherosclerosis assessed as NCB independent of hs-CRP.

Methods: 316 consecutive psoriasis participants were recruited with 233 having one-year follow-up as part of a prospective, observational cohort study design. CCTA scans were performed to assess NCB in all three major epicardial coronary arteries.

Results: Patients with above average NLR (>mean: 2.29 ​± ​1.21) were older (mean ​± ​SD; 52.0 ​± ​12.8 vs. 47.9 ​± ​12.6, p ​= ​0.002), had higher hs-CRP (med. IQR: 2.3 (0.9-7.3) vs. 1.4 (0.7-3.2), p ​= ​0.001) and had higher NCB (mean ​± ​SD; 1.21 ​± ​0.58 vs. 1.13 ​± ​0.49, p ​= ​0.018) when compared to patients with below average NLR. NLR associated with psoriasis area severity index score (β ​= ​0.14, p ​= ​0.017), hs-CRP (β ​= ​0.16, p ​= ​0.005), as well as NCB independent of traditional risk factors, body mass index, statin use and hs-CRP (β ​= ​0.08, p ​= ​0.009). One year of biologic therapy for psoriasis was associated with a reduction in NLR (-14.5%, p ​< ​0.001), and this change in NLR associated with change in NCB in fully adjusted models and beyond hs-CRP (β ​= ​0.17, p ​= ​0.002).

Conclusion: NLR associated with psoriasis severity, hs-CRP and NCB at baseline. Biologic therapy reduced NLR over time and this change in NLR associated with the change in NCB at one-year. Taken together, these findings suggest that NLR may capture psoriasis patients at higher risk of NCB due to residual inflammation not fully captured by hs-CRP.
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http://dx.doi.org/10.1016/j.jcct.2020.12.006DOI Listing
December 2020

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

J Am Acad Dermatol 2021 May 3;84(5):1329-1338. Epub 2021 Feb 3.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

Background: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome.

Objective: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis.

Methods: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria.

Results: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (β = .31; P < .001) and its individual factors of waist circumference (β = .33; P < .001), triglyceride levels (β = .17; P = .005), blood pressure (β = .18; P = .005), and fasting glucose (β = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden.

Limitations: Observational nature with limited ability to control for confounders.

Conclusions: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.
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http://dx.doi.org/10.1016/j.jaad.2020.12.044DOI Listing
May 2021

Inflammatory Bowel Disease and Atherosclerotic Cardiovascular Disease: JACC Review Topic of the Week.

J Am Coll Cardiol 2020 12;76(24):2895-2905

Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas, USA; Center for Outcomes Research, Houston Methodist, Houston, Texas, USA. Electronic address:

Chronic inflammatory diseases including human immunodeficiency virus infection, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus predispose to atherosclerotic cardiovascular disease (ASCVD). Inflammatory bowel disease (IBD) is a common chronic inflammatory condition, and the United States has the highest prevalence worldwide. IBD has so far been overlooked as a contributor to the burden of ASCVD among young and middle-age adults, but meta-analyses of cohort studies suggest that IBD is an independent risk factor for ASCVD. This review discusses the epidemiological links between IBD and ASCVD and potential mechanisms underlying these associations. ASCVD risk management of patients with IBD is challenging because of their young age and the inability of current risk scores to fully capture their increased risk. The role of IBD in current primary prevention guidelines is evaluated, and strategies for enhanced ASCVD risk reduction in patients with IBD are outlined. Finally, the authors discuss knowledge gaps and future research directions in this innovative field.
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http://dx.doi.org/10.1016/j.jacc.2020.10.027DOI Listing
December 2020

Association Among Noncalcified Coronary Burden, Fractional Flow Reserve, and Myocardial Injury in Psoriasis.

J Am Heart Assoc 2020 11 10;9(22):e017417. Epub 2020 Nov 10.

National Heart, Lung, and Blood Institute National Institutes of Health Bethesda MD.

Background Myocardial infarction and premature death have been observed in patients with psoriasis. Although inflammation-driven accelerated atherosclerosis has been proposed as a mechanism, the relationship between subclinical noncalcified coronary burden (NCB), functional coronary flow impairment, and myocardial injury is unclear. Methods and Results In an ongoing longitudinal cohort study, 202 consecutive patients with psoriasis (168 at 1 year) underwent coronary computed tomography angiography to identify coronary plaque, quantify NCB, and calculate coronary fractional flow reserve by computed tomography. Serum high-sensitivity troponin-T (hs-cTn-T) was measured using a fifth-generation assay. Overall, patients were middle-aged, predominantly male, and low cardiovascular risk. A higher than median NCB associated with a positive hs-cTn-T (fully adjusted model [odds ratio (OR), 1.72; 95% CI, 1.10-2.69, =0.018]) at baseline. Additionally, patients with a higher than median baseline NCB had higher odds of positive hs-cTn-T at 1 year in fully adjusted analyses (adjusted OR, 2.36; 95% CI, 1.47-3.79, <0.001). Higher NCB was associated with a higher frequency of fractional flow reserve by computed tomography ≤0.80 (36.11% versus 25.11%, Pearson χ=6.84, =0.009, unadjusted OR, 2.09; 95% CI, 1.36-3.22, <0.001) and higher frequency of a positive hs-cTn-T (54.36% versus 27.54%, Pearson χ=32.23, <0.001) in adjusted models (OR, 2.63; 95% CI, 1.56-4.42, <0.001). Conclusions NCB was associated with hs-cTn-T at baseline as well as at 1 year. Furthermore, patients with high NCB had higher prevalence of fractional flow reserve by computed tomography ≤0.80 and a >2- fold higher odds of positive hs-cTn-T. These findings underscore the importance of early vascular disease in driving myocardial injury, and support conduct of myocardial perfusion studies to better understand these findings.
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http://dx.doi.org/10.1161/JAHA.119.017417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763703PMC
November 2020

Cardiovascular risk assessment and management of patients undergoing hematopoietic cell transplantation.

Bone Marrow Transplant 2021 03 31;56(3):544-551. Epub 2020 Oct 31.

Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.

The purpose of this review is to provide a framework for the cardiovascular evaluation and management of patients undergoing hematopoietic cell transplantation (HCT). To accomplish this, we have performed an extensive literature review, critically analyzed the available evidence, and developed a set of recommendations to guide best practice. Herein, we discuss the cardiovascular risk profile of patients undergoing HCT along with putative mechanisms of HCT-induced cardiovascular injury. We then present an algorithm for cardiovascular testing and risk mitigation of potential recipients. Last, we address the management of the most prevalent cardiovascular conditions associated with HCT recipients.
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http://dx.doi.org/10.1038/s41409-020-01080-1DOI Listing
March 2021

Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time.

JCI Insight 2020 11 19;5(22). Epub 2020 Nov 19.

National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.

BACKGROUNDPsoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis.METHODSConsecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50).RESULTSPatients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc3 vs. 13370.7 ± 806.8 cc3, P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0-5.3 mg/L] vs. 1.2 mg/L [0.6-2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm2 vs. 0.91 ± 0.2 mm2, P < 0.001). VAT associated with NCB in fully adjusted models (β = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc3 to 15,158.7 ± 881.5 cc3; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc3 to 16310.4 ± 889.6 cc3; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (β = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (β = 0.39, P = 0.003).CONCLUSIONSInflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778569.FUNDINGThis study was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (HL006193-05), the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (no. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and Elsevier as well as private donors.
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http://dx.doi.org/10.1172/jci.insight.142534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710282PMC
November 2020

Time Course of LDL Cholesterol Exposure and Cardiovascular Disease Event Risk.

J Am Coll Cardiol 2020 09;76(13):1507-1516

Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: Incident cardiovascular disease (CVD) increases with increasing low-density lipoprotein cholesterol (LDL-C) concentration and exposure duration. Area under the LDL-C versus age curve is a possible risk parameter. Data-based demonstration of this metric is unavailable and whether the time course of area accumulation modulates risk is unknown.

Objectives: Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we assessed the relationship of area under LDL-C versus age curve to incident CVD event risk and modulation of risk by time course of area accumulation-whether risk increase for the same area increment is different at different ages.

Methods: This prospective study included 4,958 asymptomatic adults age 18 to 30 years enrolled from 1985 to 1986. The outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death.

Results: During a median 16-year follow-up after age 40 years, 275 participants had an incident CVD event. After adjustment for sex, race, and traditional risk factors, both area under LDL-C versus age curve and time course of area accumulation (slope of LDL-C curve) were significantly associated with CVD event risk (hazard ratio: 1.053; p < 0.0001 per 100 mg/dl × years; hazard ratio: 0.797 per mg/dl/year; p = 0.045, respectively).

Conclusions: Incident CVD event risk depends on cumulative prior exposure to LDL-C and, independently, time course of area accumulation. The same area accumulated at a younger age, compared with older age, resulted in a greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life.
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http://dx.doi.org/10.1016/j.jacc.2020.07.059DOI Listing
September 2020

Treatment of Psoriasis With Biologic Therapy Is Associated With Improvement of Coronary Artery Plaque Lipid-Rich Necrotic Core: Results From a Prospective, Observational Study.

Circ Cardiovasc Imaging 2020 09 15;13(9):e011199. Epub 2020 Sep 15.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (H.C., D.E.U., A.K.D., K.M.A., M.A., J.A.R., Y.A.E., A.R., A.K., J.E.-A., H.T., M.P.P., W.Z., M.Y.C., N.N.M.).

Background: Lipid-rich necrotic core (LRNC), a high-risk coronary plaque feature assessed by coronary computed tomography angiography, is associated with increased risk of future cardiovascular events in patients with subclinical, nonobstructive coronary artery disease. Psoriasis is a chronic inflammatory condition that is associated with increased prevalence of high-risk coronary plaque and risk of cardiovascular events. This study characterized LRNC in psoriasis and how LRNC modulates in response to biologic therapy.

Methods: Consecutive biologic naïve psoriasis patients (n=209) underwent coronary computed tomography angiography at baseline and 1-year to assess changes in LRNC using a novel histopathologically validated software (vascuCAP Elucid Bioimaging, Boston, MA) before and after biologic therapy over 1 year.

Results: Study participants were middle-aged, predominantly male with similar cardiometabolic and psoriasis status between treatment groups. In all participants at baseline, LRNC was associated with Framingham risk score (β [standardized β]=0.12 [95% CI, 0.00-0.15]; =0.045), and psoriasis severity (β=0.13 [95% CI, 0.01-0.26]; =0.029). At 1-year, participants receiving biologic therapy had a reduction in LRNC (mm; 3.12 [1.99-4.66] versus 2.97 [1.84-4.35]; =0.028), while those who did not receive biologic therapy over 1 year demonstrated no significant change with nominally higher LRNC (3.12 [1.82-4.60] versus 3.34 [2.04-4.74]; =0.06). The change in LRNC was significant compared with that of the nonbiologic treated group (ΔLRNC, -0.22 mm versus 0.14 mm, =0.004) and remained significant after adjusting for cardiovascular risk factors and psoriasis severity (β=-0.09 [95% CI, -0.01 to -0.18]; =0.033).

Conclusions: LRNC was associated with psoriasis severity and cardiovascular risk factors in psoriasis. Additionally, there was favorable modification of LRNC in those on biologic therapy. This study provides evidence of potential reduction in LRNC with treatment of systemic inflammation. Larger, longer follow-up prospective studies should be conducted to understand how changes in LRNC may translate into a reduction in future cardiovascular events in psoriasis.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.011199DOI Listing
September 2020

Coronary Computed Tomography Angiography From Clinical Uses to Emerging Technologies: JACC State-of-the-Art Review.

J Am Coll Cardiol 2020 09;76(10):1226-1243

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

Evaluation of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) has seen a paradigm shift in the last decade. Evidence increasingly supports the clinical utility of CCTA across various stages of CAD, from the detection of early subclinical disease to the assessment of acute chest pain. Additionally, CCTA can be used to noninvasively quantify plaque burden and identify high-risk plaque, aiding in diagnosis, prognosis, and treatment. This is especially important in the evaluation of CAD in immune-driven conditions with increased cardiovascular disease prevalence. Emerging applications of CCTA based on hemodynamic indices and plaque characterization may provide personalized risk assessment, affect disease detection, and further guide therapy. This review provides an update on the evidence, clinical applications, and emerging technologies surrounding CCTA as highlighted at the 2019 National Heart, Lung and Blood Institute CCTA Summit.
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http://dx.doi.org/10.1016/j.jacc.2020.06.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480405PMC
September 2020

Relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease in psoriasis: Findings from a longitudinal observational cohort study.

Atherosclerosis 2020 10 29;310:37-44. Epub 2020 Jul 29.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Background And Aims: Amygdalar 18F-fluorodeoxyglucose (FDG) uptake represents chronic stress-related neural activity and associates with coronary artery disease by coronary computed tomography angiography (CCTA). Allostatic load score is a multidimensional measure related to chronic physiological stress which incorporates cardiovascular, metabolic and inflammatory indices. To better understand the relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease, we studied the association between amygdalar FDG uptake, allostatic load score and subclinical non-calcified coronary artery burden (NCB) in psoriasis.

Methods: Consecutive psoriasis patients (n = 275 at baseline and n = 205 at one-year follow-up) underwent CCTA for assessment of NCB (QAngio, Medis). Amygdalar FDG uptake and allostatic load score were determined using established methods.

Results: Psoriasis patients were middle-aged, predominantly male and white, with low cardiovascular risk by Framingham risk score and moderate-severe psoriasis severity. Allostatic load score associated with psoriasis severity (β = 0.17, p = 0.01), GlycA (a systemic marker of inflammation, β = 0.49, p < 0.001), amygdalar activity (β = 0.30, p < 0.001), and NCB (β = 0.39; p < 0.001). Moreover, NCB associated with amygdalar activity in participants with high allostatic load score (β = 0.27; p < 0.001) but not in those with low allostatic load score (β = 0.07; p = 0.34). Finally, in patients with an improvement in allostatic load score at one year, there was an 8% reduction in amygdalar FDG uptake (p < 0.001) and a 6% reduction in NCB (p = 0.02).

Conclusions: In psoriasis, allostatic load score represents physiological dysregulation and may capture pathways by which chronic stress-related neural activity associates with coronary artery disease, emphasizing the need to further study stress-induced physiological dysregulation in inflammatory disease states.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587126PMC
October 2020

Coronary Artery Bypass Grafting in Cancer Patients: Prevalence and Outcomes in the United States.

Mayo Clin Proc 2020 09;95(9):1865-1876

Cardio-Oncology Program, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH. Electronic address:

Objective: To characterize the contemporary efficacy and utilization patterns of coronary artery bypass grafting (CABG) in specific cancer types.

Methods: We leveraged the data from the National Inpatient Sample and plotted trends of utilization and outcomes of isolated CABG (with no other additional surgeries during the same hospitalization) procedures from January 1, 2003, through September 1, 2015. Propensity score matching was used to assess for potential differences in outcomes by type of cancer status among contemporary (2012-2015) patients.

Results: Overall, the utilization of CABG decreased over time (250,677 in 2003 vs 134,534 in 2015, P<.001). However, the proportion of those with comorbid cancer increased (7.0% vs 12.6%, P<.001). Over time, in-hospital mortality associated with CABG use in cancer remained unchanged (.9% vs 1.0%, P=.72); yet, cancer patients saw an increase in associated major bleeding (4.5% vs 15.3%, P<.001) and rate of stroke (.9% vs 1.5%, P<.001) over time. In-hospital cost-of-care associated with CABG-use in cancer also increased over time ($29,963 vs $33,636, P<.001). When stratified by cancer types, in-hospital mortality was not higher in breast, lung, prostate, colon cancer, or lymphoma versus non-cancer CABG patients (all P>.05). However, there was a significantly higher prevalence of major bleeding but not stroke in patients with breast and prostate cancer only compared with non-cancer CABG patients (P<.01). Discharge dispositions were not found to be different between cancer sub-groups and non-cancer patients (P>.05), except for breast cancer patients who had lower home care, but higher skilled care disposition (P<.001).

Conclusion: Among those undergoing CABG, the prevalence of comorbid cancer has steadily increased. Outside of major bleeding, these patients appear to share similar outcomes to those without cancer indicating that CABG utilization should be not be declined in cancer patients when otherwise indicated. Further research into the factors underlying the decision to pursue CABG in specific cancer sub-groups is needed.
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http://dx.doi.org/10.1016/j.mayocp.2020.05.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860624PMC
September 2020

Readmission after inferior vena cava filter placement for acute venous thromboembolism in the United States: Impact of a cancer diagnosis.

J Card Surg 2020 Sep 22;35(9):2275-2278. Epub 2020 Jul 22.

Cardio-Oncology Program, Division of Cardiology, The Ohio State University, Columbus, Ohio.

Background: Inferior vena cava filter (IVCF) use is common after a venous thromboembolic event (VTE). Cancer is associated with higher rates of VTEs and is also seen in a significant proportion of patients requiring IVCF. As hospital readmissions remain a frequently scrutinized metric, we sought to evaluate the impact of cancer on hospital-readmission rates and in-hospital outcomes among patients with VTEs who received an IVCF.

Methods: Leveraging the 2013 to 2014 Nationwide Readmission Database, we identified adult patients presenting with a VTE in the United States and evaluated 30-day readmission rates and readmission in-hospital outcomes postindex-admission. Multivariable logistic regression was used to identify factors associated with readmission after an index-procedure, including traditional and nontraditional cardiovascular risk factors, as well as hospital-level characteristics.

Results: Among the 619 241 patients presenting with a VTE at index-admission, 11.2% of patients received IVCF on index-admission, of which 30.9% had cancer. The 30-day readmission rate amongst IVCF recipients was 15.8% (N = 10 927), and 19.9% amongst those with cancer compared to 13.9% in patients without cancer (P < .001). Moreover, cancer patients had longer lengths of stay in the hospital (4.5 ± 0.2 vs 4.0 ± 0.1 days; P = .02), higher cost of care ($10 900 ± 308 vs $9242 ± 206; P = .007), but no difference in mortality (8.3% vs 6.3%; P = .70) during readmission compared to noncancer patients.

Conclusion: Readmission after IVCF placement is common. In patients readmitted after an IVCF implantation, those with cancer have longer hospital stays and higher costs of care. However, in-hospital mortality is similar to those without cancer.
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http://dx.doi.org/10.1111/jocs.14820DOI Listing
September 2020

Neighborhood environment perceptions associate with depression levels and cardiovascular risk among middle-aged and older adults: Data from the Washington, DC cardiovascular health and needs assessment.

Aging Ment Health 2020 Jul 21:1-12. Epub 2020 Jul 21.

Social Determinants of Obesity and Cardiovascular Risk Laboratory, Cardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Objectives: Little is understood about associations between neighborhood characteristics and depression, a cardiovascular disease (CVD) risk factor, in diverse populations. We examined relationships between perceived/objective neighborhood characteristics, depression, and CVD markers within the Washington, DC CV Health/Needs Assessment, an evaluation among predominantly African-American (AA) adults in resource-limited DC communities.

Method: Factor analysis of overall neighborhood environment perception (NEP) identified three NEP sub-scores:1) violence; 2) physical/social environment; 3) social cohesion (higher score = more favorable perception). Objective neighborhood characteristics were measured by geospatially-derived scores of walkability, transportation, and crime. Depression was defined by the revised Center for Epidemiologic Studies Depression Scale (CESD-R). We used linear-regression modeling to examine neighborhood measures and CESD-R associations. To investigate a subsequent connection with CVD risk, we examined relationships between CESD-R and CVD-associated cytokines in a population subset.

Results: Participants ( = 99; mean age = 59.06; 99% AA) had a mean CESD-R score = 5.8(SD = 8.88). In adjusted models, CESD-R scores decreased by 0.20 units ( = 0.01) for every overall NEP unit-increase. Perceived physical/social environment (β = -0.34,  = 0.04) and social cohesion (β = -0.82,  = 0.01) were related to CESD-R while perceived violence was not (β = -0.28,  = 0.1). Of objective neighborhood environment measures (i.e. walk, transit, bike, personal crime, and property crime scores), only property crime score was associated with depression (β = 4.99,  < 0.03). In population subset ( = 42), higher CESD-R associated with higher IL-1β (β = 21.25,  < 0.01) and IL-18 (β = 0.006,  = 0.01).

Conclusion: Favorable neighborhood perceptions are related to lower depressive symptoms in a predominantly AA cohort from Washington, DC resource-limited communities. Neighborhood perceptions appear to be strongly associated with depressive symptoms compared to objective characteristics. Increasing CESD-R scores were related to higher pro-inflammatory markers. Improving neighborhood perceptions may be beneficial to psychological well-being and CV health for urban minority residents.
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http://dx.doi.org/10.1080/13607863.2020.1793898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855489PMC
July 2020

Hyperlipidaemia and IFNgamma/TNFalpha Synergism are associated with cholesterol crystal formation in Endothelial cells partly through modulation of Lysosomal pH and Cholesterol homeostasis.

EBioMedicine 2020 Sep 6;59:102876. Epub 2020 Jul 6.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA. Electronic address:

Background: Inflammation plays an important role in the development of cardiovascular disease (CVD). Patients with chronic inflammation diseases have high levels of inflammation and early fatal myocardial infarction due to early, unstable coronary plaques. Cholesterol crystals (CC) play a key role in atherogenesis. However, the underlying mechanisms of endothelial cell (EC)-derived CC formation are not well understood in chronic inflammation.

Methods: We utilized a combination of a mouse psoriasis model (K14-Rac1V12 mouse model) and human psoriasis patients to study the effect of inflammatory cytokines on CC formation in ECs. Lysosomal pH, alterations in lipid load and inflammatory proteins were evaluated as potential mechanisms linking inflammatory cytokines to CC formation. Coronary CT angiography was performed (n = 224) to characterize potential IFNγ and TNFα synergism on vascular diseases in vivo.

Findings: We detected CC presence in the aorta of K14-Rac1V12 mice on chow diet. IFNγ and TNFα were found to synergistically increase LDL-induced CC formation by almost 2-fold. There was an increase in lysosomal pH accompanied by a 28% loss in pH-dependent lysosomal signal and altered vATPaseV1E1 expression patterns. In parallel, we found that LDL+IFNγ/TNFα treatments increased free cholesterol content within EC and led to a decrease in SOAT-1 expression, an enzyme critically involved cholesterol homeostasis. Finally, the product of IFNγ and TNFα positively associated with early non-calcified coronary burden in patients with psoriasis (n = 224; β = 0.28, p < 0.001).

Interpretation: Our results provide evidence that IFNγ and TNFα accelerate CC formation in endothelial cells in part by altering lysosomal pH and free cholesterol load. These changes promote early atherogenesis and contribute to understanding the burden of CVD in psoriasis.

Funding: Funding was provided by the Intramural Research Program at NIH (NNM) and the National Psoriasis Foundation (NNM and YB).
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http://dx.doi.org/10.1016/j.ebiom.2020.102876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502673PMC
September 2020
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