Additive prognostic value of longitudinal myocardial deformation to SCORE2 in psoriasis.

Aims: Psoriasis has been associated with increased cardiovascular (CV) risk. We investigated whether markers of CV function and their change after treatment have a prognostic value for adverse outcomes. Methods and results: In a prospective study, at baseline and after 6 months of treatment with biological agents, we assessed in 298 psoriasis patients (i) left ventricular global longitudinal strain (GLS) and (ii) carotid-femoral pulse wave velocity (PWV), to evaluate their prognostic value for major adverse cardiovascular events (MACEs), including coronary artery disease, stroke, hospitalization for heart failure, and all-cause death over a 4-year follow-up period. During follow-up, 26 (8.7%) MACEs were recorded. By univariate analysis, decreasing absolute GLS values [hazard ratio (HR): 0.73, P < 0.001], decreasing GLS change after treatment (HR: 0.53, P = 0.008), and increasing PWV values (HR: 1.16, P = 0.049) were associated with adverse outcomes. Baseline GLS and its change post-treatment remained independent predictors of adverse events after adjusting for several confounders (P < 0.05). The addition of baseline GLS and its absolute change post-treatment to SCORE2 increased Harrell's C from 0.882 to 0.941. By multivariable analysis, for each 1% increase in absolute baseline GLS values, the risk of MACE decreased by 33% and for each 1% absolute increase of GLS post-treatment compared with the baseline value, the risk of MACE decreased by 58%. Conclusion: Global longitudinal strain has an independent and additive prognostic value to SCORE2 for adverse CV events in psoriasis, providing timely decision-making for intensive anti-inflammatory treatment and aggressive modification of risk factors to reduce CV risk.

Effects of Interleukin 17A Inhibition on Myocardial Deformation and Vascular Function in Psoriasis.

BACKGROUND: Interleukin (IL)-17A activity is implicated in psoriasis. We investigated the effects of IL-17A inhibition on vascular and left ventricular (LV) function in patients with psoriasis. METHODS: A total of 150 patients with psoriasis received either an anti-IL-17A agent (secukinumab, n = 50), cyclosporine (n = 50), or methotrexate treatment (n = 50). At baseline and after 4 and 12 months of treatment, we measured (1) LV global longitudinal strain (GLS), GLS rate (GLSR), GLSR at early diastole, LV twisting, and untwisting; (2) coronary flow reserve (CFR); (3) pulse wave velocity (PWV); and (4) malondialdehyde and protein carbonyl as markers of oxidative stress. RESULTS: Compared with cyclosporine and methotrexate, anti-IL-17A treatment resulted in a greater increase in GLS at 4 and 12 months after treatment (10% and 14% with anti-IL-17A vs 2% and 2% with cyclosporine vs 4% and 4% with methotrexate, respectively), GLSR, GLSR at early diastole (45% and 41% vs 5% and 4% vs 7% and 9%, respectively), and LV twisting (32% and 28% vs 6% and 8% vs 7% and 6%, respectively) (P < 0.05). Anti-IL-17A treatment resulted in greater improvement of CFR and PWV than cyclosporine or methotrexate (P < 0.05). PWV increased after cyclosporine treatment (+11% at 4 and +14% and 12 months) (P < 0.05). Markers of oxidative stress were reduced only after anti-IL-17A treatment (P < 0.05). Changes of myocardial deformation markers and CFR after anti-IL-17A treatment correlated with a concomitant reduction of oxidative stress. CONCLUSIONS: In psoriasis, inhibition of IL-17A results in a greater improvement of vascular and myocardial function compared with cyclosporine or methotrexate treatment, indicating a beneficial effect on overall cardiovascular function.

Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis.

BACKGROUND: Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis. METHODS AND RESULTS: One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: -17.7% versus -19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-α, and IL-6 post-treatment (P<0.05). Compared with anti-TNF-α and cyclosporine, anti-IL-12/23 treatment resulted in a greater improvement of global longitudinal strain (25% versus 17% versus 6%,), LV twist (27% versus 17% versus 1%), %untwMVO (31% versus 27% versus 17%), and coronary flow reserve (14% versus 11% versus 4%), as well as a greater reduction of IL-12 (-25% versus -4% versus -2%), malondialdehyde (-27% versus +5% versus +26%), and NT-proBNP(-26% versus -13.6% versus 9.1%) and increase of fetuin-a (P<0.01). Pulse wave velocity and augmentation index were improved only after anti-IL-12/23 treatment and correlated with changes in global longitudinal strain, LV twisting-untwisting (P<0.05). CONCLUSIONS: In psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-α inhibition or cyclosporine treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857.

Increased levels of circulating platelet-derived microparticles in psoriasis: Possible implications for the associated cardiovascular risk.

AIM: To evaluate platelet activation markers in psoriasis patients, compared to controls, and investigate their association with the inflammatory burden of psoriasis. METHODS: Forty psoriatic patients without cardiovascular disease, and 12 healthy controls were subjected to measurement of baseline platelet CD62P, CD63 and CD42b expression, platelet-leukocyte complexes, i.e., platelet-monocyte complexes (PMC), platelet-neutrophil complexes (PNC) and platelet-lymphocyte complexes, and concentrations of platelet-derived microparticles (PMPs) using flow cytometry. Both larger-size (0.5-0.9 µm) and smaller-size (< 0.5 µm) PMPs were determined. Serum interleukin (IL)-12 and IL-17 levels were also measured by enzyme-linked immunosorbent assay. The severity of psoriasis was evaluated by the Psoriasis Area Severity Index (PASI). RESULTS: PMP concentrations were significantly higher in psoriasis patients than controls [mean ± standard error of mean (SEM): 22 ± 5/µL vs 11 ± 6/µL; P = 0.018), for both smaller-size (10 ± 2/µL vs 4 ± 2/µL; P = 0.033) and larger-size (12 ± 3/µL vs 6 ± 4/µL; P = 0.014) PMPs. Platelet CD62P, CD63 and CD42b expression and circulating PMC and PNC were similar between the two groups. Lower circulating PLC were observed in psoriasis patients compared to controls (mean ± SEM: 16% ± 3% vs 23% ± 6%; P = 0.047). Larger-size PMPs were related with IL-12 levels (P < 0.001) and smaller-size PMPs with both IL-12 and IL-17 levels (P < 0.001). Total PMPs also correlated with IL-12 (P < 0.001). CD63 expression was positively correlated with both IL-12 and IL-17 (P < 0.05). Increased PASI score was associated with increased levels of larger-size PMPs (r = 0.45; P = 0.011) and increased CD63 expression (r = 0.47; P < 0.01). CONCLUSION: PMPs, known to be predictive of cardiovascular outcomes, are increased in psoriasis patients, and associated with high inflammatory disease burden. Enhanced platelet activation may be the missing link leading to cardiovascular events in psoriatic patients.

Similarities in coronary function and myocardial deformation between psoriasis and coronary artery disease: the role of oxidative stress and inflammation.

BACKGROUND: Psoriasis has been associated with increased risk for coronary artery disease (CAD). We investigated the presence of vascular and subclinical left ventricular (LV) dysfunction in patients with psoriasis compared with patients with CAD. METHODS: We compared 59 patients with psoriasis without evidence of CAD (psoriasis area and severity index [PASI], 11.5 ± 8) with 59 patients with angiographically documented CAD and 40 controls. We measured (1) the carotid-femoral pulse wave velocity (PWVc) and central augmentation index (CAI), (2) coronary flow reserve (CFR) by Doppler echocardiography, (3) flow-mediated dilation (FMD) of the brachial artery and carotid intima media thickness (IMT), (4) LV global longitudinal strain (GLS) and GLS rate (GLSR) using speckle tracking echocardiography, and (5) malondialdehyde (MDA) and interleukin-6 (IL-6) levels. RESULTS: Patients with psoriasis had higher PWVc, CAI, IMT, MDA, and IL-6 levels and lower FMD, CFR, GLS, and GLSR than did controls (P < 0.05), but they had values of these markers that were similar to those of patients with CAD (P > 0.05) after adjustment for atherosclerotic risk factors: (PWVc [m/s], 10.4 ± 1.8 vs 8.6 ± 1.5 vs 10.3 ± 2, respectively; CFR, 2.4 ± 0.1 vs 3.4 ± 0.6 vs 2.6 ± 0.6, respectively; GLS [%], -16.2 ± 4 vs -21.9 ± 1.6 vs -16.6 ± 4.5, respectively; GLSR [L/sec], -0.85 ± 0.2 vs -1.2 ± 0.12 vs -0.9 ± 0.4, respectively; MDA [nM/L], 1.68 vs 1.76 vs 1.01, respectively; IL-6 [pg/mL], 2.26 vs 2.2 vs 1.7, respectively; P < 0.05 for all comparisons). PASI was related to IMT (r = 0.67; P < 0.01). Decreased GLS was associated with increased MDA, IL-6, PWVc, CAI, and reduced CFR (P < 0.05). CONCLUSIONS: Psoriasis and CAD present similar vascular and LV myocardial dysfunction, possibly because of similar underlying inflammatory and oxidative stress processes. Vascular dysfunction in psoriasis is linked to abnormal LV myocardial deformation.