Faculty Bibliography

BACKGROUND:Psoriasis increases the risk of cardiovascular disease (CVD). Biomarkers for cardiovascular (CV) risk stratification in psoriasis are lacking, and the effects of psoriasis biologics on CV risk reduction remain unclear. OBJECTIVES/OBJECTIVE:To identify biomarkers of CV risk in psoriasis blood that are reduced by ustekinumab. METHODS:We quantified inflammatory and CV-related serum proteins with Olink's multiplex assay in 10 psoriasis patients (vs. 18 healthy controls) and after 12 weeks of ustekinumab treatment. For each protein down-regulated after treatment, the literature was reviewed for studies assessing the protein's association with CVD. Data was collected from each study to calculate CV risk thresholds for each protein, which were compared to protein levels in psoriasis patients before and after treatment. RESULTS:Out of 276 proteins, 43 were down-regulated after treatment, 25 of which were initially up-regulated at baseline (vs. controls, all p-values ≤ 0.1). 8 down-regulated proteins were initially elevated above thresholds associated with enhanced CV risk in the literature (myeloperoxidase, C-X-C motif chemokine 10, E-selectin, interleukin-6, cystatin B, von Willebrand factor, tumor necrosis factor receptor 1, and N-terminal prohormone brain natriuretic peptide). Treatment lowered these proteins to below their risk thresholds, except for IL-6, which was lowered but remained at its risk threshold despite successful psoriasis skin treatment. CONCLUSIONS:12 weeks of ustekinumab treatment reduced serum proteins present at levels associated with CV risk in psoriasis patients. Further studies can evaluate these proteins as potential ustekinumab-modulated biomarkers of CV risk in psoriasis and the impact of ustekinumab on CV risk reduction.

Circulating fatty acids (FA) may be important in the psoriatic pro-inflammatory phenotype. FADS1 converts linoleic acid (LA) to arachidonic acid (AA), a precursor to potent signaling molecules. HMG-CoA reductase inhibitors (statins) increase FADS1/2 expression in vitro. Psoriasis patients (42 ± 14 years/age, 47% male) were randomized to 40 mg of atorvastatin (n = 20) or nothing (n = 10) for two weeks and plasma FA measured pre and post treatment. After treatment, LDL-C was 44% lower in the statin compared to the no-treatment group. Statins increased FADS1/2 expression, and lowered LA 12% (33% - > 29%, p<0.001) and raised AA 14% (7.7% - > 9.0%, p<0.01) with no change in the no-treatment group. In psoriasis, statins enhance AA and decrease LA, consistent with the action of enhanced FADS expression in vivo. Therapies intended to blunt the effects of AA on platelet aggregation, such as aspirin or omega-3 fatty acids, may require dose adjustment when co-administered with atorvastatin. NCT: NCT03228017.

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 (K_p 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 K_p 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 K_p 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.

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

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.

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.