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Hidradenitis suppurativa is associated with iron deficiency anemia, anemia of chronic disease, and sickle cell anemia-A single-center retrospective cohort study

Parameswaran, Anupama; Garshick, Michael S; Revankar, Rishab; Lu, Catherine Pei-Ju; Chiu, Ernest S; Sicco, Kristen I Lo
PMID: 35028363
ISSN: 2352-6475
CID: 5116322

A Randomized Open Label Clinical Trial of Lipid-Lowering Therapy in Psoriasis to Reduce Vascular Endothelial Inflammation

Garshick, Michael S; Drenkova, Kamelia; Barrett, Tessa J; Schlamp, Florencia; Fisher, Edward A; Katz, Stuart; Jelic, Sanja; Neimann, Andrea L; Scher, Jose U; Krueger, James; Berger, Jeffrey S
PMID: 34808233
ISSN: 1523-1747
CID: 5063372

Ticagrelor added to methotrexate improves rheumatoid arthritis disease severity

Garshick, Michael S; Rosenthal, Pamela B; Luttrell-Williams, Elliot; Cronstein, Bruce N; Berger, Jeffrey S
PMID: 34142122
ISSN: 1462-0332
CID: 4950932

Solar Activity Is Associated With Diastolic and Systolic Blood Pressure in Elderly Adults

Wang, Veronica A; Zilli Vieira, Carolina L; Garshick, Eric; Schwartz, Joel D; Garshick, Michael S; Vokonas, Pantel; Koutrakis, Petros
Background Since solar activity and related geomagnetic disturbances modulate autonomic nervous system activity, we hypothesized that these events would be associated with blood pressure (BP). Methods and Results We studied 675 elderly men from the Normative Aging Study (Boston, MA) with 1949 BP measurements between 2000 and 2017. Mixed-effects regression models were used to investigate the association of average 1-day (ie, day of BP measurement) to 28-day interplanetary magnetic field intensity, sunspot number, and a dichotomized measure of global geomagnetic activity (Kp index) in 4-day increments with diastolic and systolic BP. We adjusted for meteorological conditions and other covariates associated with BP, and in additional models adjusted for ambient air pollutants (particulate matter with an aerodynamic diameter ≤2.5 µm, black carbon, and particle number) and ambient particle radioactivity. There were positive associations between interplanetary magnetic field, sunspot number, and Kp index and BP that were greatest with these exposures averaged over 16 through 28 days before BP measurement. An interquartile range increase of 16-day interplanetary magnetic field and sunspot number and higher Kp index were associated with a 2.5 (95% CI, 1.7‒3.2), 2.8 (95% CI, 2.1‒3.4), and 1.7 (95% CI, 0.8‒2.5) mm Hg increase, respectively, for diastolic BP as well as a 2.1 (95% CI, 0.7‒3.6), 2.7 (95% CI, 1.5‒4.0), and 0.4 (95% CI, -1.2 to 2.1) mm Hg increase, respectively, for systolic BP. Associations remained after adjustment for ambient air pollutants and ambient particle radioactivity. Conclusions Solar activity and solar-driven geomagnetic disturbances were positively associated with BP, suggesting that these natural phenomena influence BP in elderly men.
PMID: 34713707
ISSN: 2047-9980
CID: 5042822

Platelet activity and platelet-induced endothelial inflammatory pathways in treated hiv is lowered by clopidogrel: A randomized control trial [Meeting Abstract]

Schwartz, T; Maracantoni, E; Allen, N; Cambria, M; Dann, R; Garshick, M; Berger, J S
Background : Patients with Human Immunodeficiency Virus (HIV) exhibit an activated platelet phenotype and an increased risk of Cardiovascular Disease (CVD). Aims : We conducted a randomized controlled trial to investigate the efficacy of aspirin and clopidogrel (two anti-platelet medications commonly used to prevent CVD) to reduce platelet activation and platelet effector cell properties in HIV patients. Methods : Fifty five HIV positive patients (mean age 53.5 +/- 7.8 years, 42.6% female, mean CD4+ T-cell count 665.6 cells/m 3 ), were enrolled to receive clopidogrel ( n = 22, 75 mg/d), aspirin ( n = 22, 81 mg/d), or no-treatment ( n = 11) for 14-days. Platelet aggregation and platelet receptor expression of p-selectin and pac-1 was assessed at baseline and day 14. To assess the impact of platelet inhibition on the endothelium ( in vitro ), platelets isolated from 6 patients (2/ group) at baseline and follow-up were incubated in HUVECs and proinflammatory HUVEC gene expression was assessed (Nanostring, 594 transcripts). Results : Aspirin treatment significantly reduced platelet aggregation to arachidonic acid (AA) (84% to 31%, P < 0.01) while clopidogrel reduced platelet aggregation to adenosine diphosphate (ADP) (85% to 41%, P < 0.001), confirming study drug compliance. Clopidogrel treatment decreased platelet p-selectin (-5.9%, P = 0.04), p-selectin plus thrombin (-40.8%, P = 0.03), pac-1 expression (-8%, P = 0.02), and pac-1 plus ADP (-24.0%, P = 0.03) and AA (-24.0%, P < 0.01). In contrast, aspirin did not affect p-selectin or pac-1 expression. When compared to no-treatment, HIV patients on clopidogrel exhibited a reduction in the composite pro-inflammatory transcript expression of platelet treated HUVECS (Log2 Fold DELTA -0.07 +/- 0.58 vs. -0.12 +/- 0.53, P < 0.001) while aspirin treated platelets upregulated HUVEC transcript expression (Log2 Fold DELTA-0.07 +/- 0.58 vs. 0.19 +/- 0.59, P < 0.001). Conclusions : Clopidogrel, but not aspirin, reduced platelet activation and HUVEC pro-inflammatory gene expression. Our results suggest that clopidogrel as opposed to aspirin may be preferential to reduce CV risk in HIV; however, larger clinical trials are needed to expand upon these findings
ISSN: 2475-0379
CID: 5044642

Psoriasis and Cardiovascular Disease: Novel Mechanisms and Evolving Therapeutics

Weber, Brittany; Merola, Joseph F; Husni, M Elaine; Di Carli, Marcelo; Berger, Jeffrey S; Garshick, Michael S
PURPOSE OF REVIEW/OBJECTIVE:Psoriasis is a chronic inflammatory skin condition that is associated with increased cardiovascular risk compared to those without psoriasis. This review will cover emerging mechanisms of cardiovascular risk, key pathways targeted with biologic therapies, and the current evidence on therapies to modulate this risk in patients with psoriasis. RECENT FINDINGS/RESULTS:Recent scientific work has highlighted mechanisms that contribute to this enhanced risk, including the role of vascular endothelial dysfunction, platelet activation, dyslipidemia, and increased cardiometabolic comorbidities. Newer biologic and targeted synthetic therapies have transformed psoriasis treatment with high rates of clinical remission and durable skin disease control now possible. Epidemiological evidence suggests that many of these therapies may lower cardiovascular risk in psoriasis, although prospective interventional data is lacking (or mixed). Recently, caution has also been raised that some treatments may negatively affect cardiovascular risk. Overall, the current data suggests a positive or neutral ability to reduce cardiovascular risk for TNF, IL-17A, and IL-12/23p40 inhibitors, but current evidence remains conflicting for anti-IL-23/p19 and JAK inhibitors. More studies that include prospective cohorts, larger number of patients, treatment duration, and validated surrogate outcomes are needed to better evaluate the role of biologic therapies on cardiovascular risk in psoriasis.
PMID: 34468875
ISSN: 1534-6242
CID: 4998452

Aortic closure signal length on doppler echocardiography differentiates aortic patient-prosthesis mismatch from prosthetic stenosis

Ali, Thara; Garshick, Michael S; Saric, Muhamed; Skolnick, Adam H
PURPOSE/OBJECTIVE:The purpose of this study was to investigate the diagnostic potential of the aortic closure (A2) signal length on Doppler echocardiography in distinguishing aortic patient-prosthesis mismatch (PPM) from prosthetic stenosis among patients with elevated gradients over bioprosthetic valves. METHODS:The A2 signal length was retrospectively measured for 150 patients with bioprosthetic aortic valves (50 with PPM, 50 with prosthetic stenosis, and 50 with normally functioning valves) from transthoracic echocardiograms performed at NYU Langone Health between 01/01/2012 and 08/01/2018. RESULTS:Mean A2 signal length was shorter among patients with PPM (11.1 ms ± 5.2 ms), than among those with prosthetic stenosis (21.1 ms ± 6.0 ms), P < .001 and controls (21.7 ms ± 7.4 ms), P < .001. There was no difference in A2 signal length between prosthetic stenosis and controls. The A2 signal length yielded an AUC of 0.89 (95% CI 0.82-0.95) for predicting PPM over prosthetic stenosis. CONCLUSION/CONCLUSIONS:Among patients with bioprosthetic aortic valves, the length of the A2 signal on Doppler echocardiography is shorter in PPM than in prosthetic stenosis and normally functioning valves. The A2 signal length may represent a novel metric to distinguish PPM from prosthetic stenosis.
PMID: 33665868
ISSN: 1097-0096
CID: 4800372

C-reactive protein and clinical outcomes in patients with COVID-19

Smilowitz, Nathaniel R; Kunichoff, Dennis; Garshick, Michael; Shah, Binita; Pillinger, Michael; Hochman, Judith S; Berger, Jeffrey S
BACKGROUND:A systemic inflammatory response is observed in coronavirus disease 2019 (COVID-19). Elevated serum levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with severe disease in bacterial or viral infections. We aimed to explore associations between CRP concentration at initial hospital presentation and clinical outcomes in patients with COVID-19. METHODS AND RESULTS/RESULTS:Consecutive adults aged ≥18 years with COVID-19 admitted to a large New York healthcare system between 1 March and 8 April 2020 were identified. Patients with measurement of CRP were included. Venous thrombo-embolism (VTE), acute kidney injury (AKI), critical illness, and in-hospital mortality were determined for all patients. Among 2782 patients hospitalized with COVID-19, 2601 (93.5%) had a CRP measurement [median 108 mg/L, interquartile range (IQR) 53-169]. CRP concentrations above the median value were associated with VTE [8.3% vs. 3.4%; adjusted odds ratio (aOR) 2.33, 95% confidence interval (CI) 1.61-3.36], AKI (43.0% vs. 28.4%; aOR 2.11, 95% CI 1.76-2.52), critical illness (47.6% vs. 25.9%; aOR 2.83, 95% CI 2.37-3.37), and mortality (32.2% vs. 17.8%; aOR 2.59, 95% CI 2.11-3.18), compared with CRP below the median. A dose response was observed between CRP concentration and adverse outcomes. While the associations between CRP and adverse outcomes were consistent among patients with low and high D-dimer levels, patients with high D-dimer and high CRP have the greatest risk of adverse outcomes. CONCLUSIONS:Systemic inflammation, as measured by CRP, is strongly associated with VTE, AKI, critical illness, and mortality in COVID-19. CRP-based approaches to risk stratification and treatment should be tested.
PMID: 33448289
ISSN: 1522-9645
CID: 4785432

Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice

Garshick, Michael S; Nikain, Cyrus; Tawil, Michael; Pena, Stephanie; Barrett, Tessa J; Wu, Benjamin G; Gao, Zhan; Blaser, Martin J; Fisher, Edward A
Since alterations in the intestinal microbiota may induce systemic inflammation and polarization of macrophages to the M1 state, the microbiome role in atherosclerosis, an M1-driven disease, requires evaluation. We aimed to determine if antibiotic (Abx) induced alterations to the intestinal microbiota interferes with atherosclerotic plaque inflammation resolution after lipid-lowering in mice. Hyperlipidemic Apoe-/- mice were fed a western diet to develop aortic atherosclerosis with aortas then transplanted into normolipidemic wild-type (WT) mice to model clinically aggressive lipid management and promote atherosclerosis inflammation resolution. Gut microbial composition pre and post-transplant was altered via an enteral antibiotic or not. Post aortic transplant, after Abx treatment, while plaque size did not differ, compared to Apoe-/- mice, Abx- WT recipient mice had a 32% reduction in CD68-expressing cells (p = 0.02) vs. a non-significant 12% reduction in Abx+ WT mice. A trend toward an M1 plaque CD68-expresing cell phenotype was noted in Abx+ mice. By 16S rRNA sequence analysis, the Abx+ mice had reduced alpha diversity and increased Firmicutes/Bacteroidetes relative abundance ratio with a correlation between gut Firmicutes abundance and plaque CD68-expressing cell content (p < 0.05). These results indicate that in a murine atherosclerotic plaque inflammation resolution model, antibiotic-induced microbiome perturbation may blunt the effectiveness of lipid-lowering to reduce the content of plaque inflammatory CD68-expressing cells.
PMID: 33903700
ISSN: 2045-2322
CID: 4889262

Cardiovascular Risk in Patients With Psoriasis: JACC Review Topic of the Week

Garshick, Michael S; Ward, Nicole L; Krueger, James G; Berger, Jeffrey S
Psoriasis is a chronic inflammatory skin disease that affects 2% to 3% of the U.S. population. The immune response in psoriasis includes enhanced activation of T cells and myeloid cells, platelet activation, and up-regulation of interferons, tumor necrosis factor-α, and interleukins (ILs) IL-23, IL-17, and IL-6, which are linked to vascular inflammation and atherosclerosis development. Patients with psoriasis are up to 50% more likely to develop cardiovascular disease (CV) disease, and this CV risk increases with skin severity. Major society guidelines now advocate incorporating a psoriasis diagnosis into CV risk prediction and prevention strategies. Although registry data suggest treatment targeting psoriasis skin disease reduces vascular inflammation and coronary plaque burden, and may reduce CV risk, randomized placebo-controlled trials are inconclusive to date. Further studies are required to define traditional CV risk factor goals, the optimal role of lipid-lowering and antiplatelet therapy, and targeted psoriasis therapies on CV risk.
PMID: 33795041
ISSN: 1558-3597
CID: 4875532