YiDing Yu

Attributable Risk Estimate of Severe Psoriasis on Major Cardiovascular Events

BACKGROUND Recent studies suggest that psoriasis, particularly if severe, may be a risk factor for major adverse cardiac events, such as myocardial infarction, stroke, and mortality from cardiovascular disease. We compared the risk of major adverse cardiac events between patients with psoriasis and the general population and estimated the attributable risk of severe psoriasis. METHODS We performed a cohort study in the General Practice Research Database. Severe psoriasis was defined as receiving a psoriasis diagnosis and systemic therapy (N=3603). Up to 4 patients without psoriasis were selected from the same practices and start dates for each patient with psoriasis (N=14,330). RESULTS Severe psoriasis was a risk factor for major adverse cardiac events (hazard ratio 1.53; 95% confidence interval, 1.26-1.85) after adjusting for age, gender, diabetes, hypertension, tobacco use, and hyperlipidemia. After fully adjusted analysis, severe psoriasis conferred an additional 6.2% absolute risk of 10-year major adverse cardiac events. CONCLUSION Severe psoriasis confers an additional 6.2% absolute risk of a 10-year rate of major adverse cardiac events compared with the general population. This potentially has important therapeutic implications for cardiovascular risk stratification and prevention in patients with severe psoriasis. Future prospective studies are needed to validate these findings.

Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study

Objectives We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general population after adjusting for traditional cardiovascular risk factors. Methods A population-based longitudinal cohort study from 1994 to 2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the UK. Patients aged 18–89 years of age with PsA, RA or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents and the composite outcome (MACE). Cox proportional hazards models were used to calculate the HRs for each outcome adjusted for traditional risk factors. A priori, we hypothesised an interaction between disease status and disease-modifying antirheumatic drug (DMARD) use. Results Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=81 573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in patients with PsA not prescribed a DMARD (HR 1.24, 95% CI 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95% CI 1.28 to 1.50, DMARD: HR 1.58, 95% CI 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95% CI 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95% CI 1.17 to 1.73). Conclusions Cardiovascular risk should be addressed with all patients affected by psoriasis, PsA or RA.

Systemic and Vascular Inflammation in Patients With Moderate to Severe Psoriasis as Measured by [18F]-Fluorodeoxyglucose Positron Emission Tomography –Computed Tomography (FDG-PET/CT): A Pilot Study

OBJECTIVE To evaluate the feasibility of using [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) to detect and quantify systemic inflammation in patients with psoriasis. DESIGN Case series with a nested case-control study. SETTING Referral dermatology and preventive cardiology practices. PARTICIPANTS Six patients with psoriasis affecting more than 10% of their body surface area and 4 controls age and sex matched to 4 of the patients with psoriasis for a nested case-control study. MAIN OUTCOME MEASURES The FDG uptake in the liver, musculoskeletal structures, and aorta measured by mean standardized uptake value, a measure of FDG tracer uptake by macrophages and other inflammatory cells. RESULTS FDG-PET/CT identified numerous foci of inflammation in 6 patients with psoriasis within the skin, liver, joints, tendons, and aorta. Inflammation in the joints was observed in a patient with psoriatic arthritis as well as in 1 patient with no history of joint disease or joint symptoms. In a nested case-control study, FDG-PET/CT imaging demonstrated increased vascular inflammation in multiple segments of the aorta compared with controls. These findings persisted after adjustment for traditional cardiovascular risk factors in multivariate analysis (mean β = 0.33; P < .001). Patients with psoriasis further demonstrated increased hepatic inflammation after adjusting for cardiovascular risk factors (β = 0.18; P < .001), but the association was no longer significant when adjusted for alcohol intake (β = -0.25; P = .07). CONCLUSION FDG-PET/CT is a sensitive tool for identifying inflammation and can be used to identify clinically observed inflammation in the skin and subclinical inflammation in the blood vessels, joints, and liver of patients with psoriasis.

Abnormal lipoprotein particles and cholesterol efflux capacity in patients with psoriasis

OBJECTIVES Psoriasis is a Th-1/17 mediated inflammatory disease associated with increased risk of cardiovascular disease (CVD). Inflammation may modulate lipoprotein particle number and directly impair HDL functions, in particular reverse cholesterol transport (RCT). We sought to study how chronic in vivo inflammation modulates lipoprotein particle composition using nuclear magnetic resonance spectroscopy (NMR) and HDL efflux in psoriasis. METHODS AND RESULTS We prospectively enrolled a consecutive sample of patients with psoriasis (n = 122) and compared lipoprotein and metabolic risk factors to patients without psoriasis (n = 134). Fasting lipids, insulin, glucose were measured by standard assays, and lipoprotein concentration and size were measured by NMR. In a random subset (n = 100 each group), HDL efflux capacity was quantified using a validated ex vivo system involving the incubation of macrophages with apolipoprotein B-depleted serum from patients. Traditional lipid concentrations were similar in both groups except for HDL concentration which was lower in psoriasis (43 mg/dl (36-58) vs 50 (42-62), p < 0.01). However, NMR showed an atherogenic profile in psoriasis similar to that observed in diabetes, with significant increase in LDL particle concentration [1210.5 (1002-1498) vs 1115 (935-1291), p = 0.02] with decrease in LDL size [20.6 (20.3-21.1) vs 21.3 (20.6-21.1), p < 0.001] beyond CV risk factors and HOMA-IR (p = 0.001). Finally, HDL efflux capacity was lower in psoriasis compared to controls in fully adjusted models (beta -0.14, p = 0.001). CONCLUSIONS These data support a more atherogenic lipoprotein profile by NMR and decreased HDL efflux capacity in psoriasis patients compared to controls beyond CVD risk factors. The abnormal lipoprotein particle composition and HDL efflux capacity in psoriasis may provide a link between psoriasis and CVD.

The impact of psoriasis on 10-year Framingham risk

Psoriasis is a chronic inflammatory skin disease, and when severe, may be a risk factor for major adverse cardiac events (MACE) including myocardial infarction1, stroke and cardiovascular (CV) death. Indeed, recent studies evaluating the risk of MACE with IL-12/23 inhibitors in randomized trials emphasize the need for efforts at decreasing the risk of cardiovascular disease in psoriasis patients. 2. Risk stratification and treatment goals for cholesterol and blood pressure in psoriasis remains understudied, and the Framingham Risk score (FRS) for CV risk may underestimate long term risk of MACE in psoriasis patients. The Adult Treatment Panel for lipid management recommends that providers consider emerging risk factors when deciding on lipid treatment but does not provide specific guidelines. We described an initial estimate of this excess attributable risk of severe psoriasis on MACE3 and herein describe how this AR may affect FRS in psoriasis. We consecutively enrolled patients (n=138), and calculated FRS before and after adding the AR of psoriasis (6.2%)3, and estimated the reclassification rate by examining patients moved from a lower risk category to a higher risk category. Patients with psoriasis were relatively young with higher than expected tobacco use, alcohol use, body mass index and lipids (Table 1). Nonetheless, their risk for MACE by FRS was low (<10%) (male mean FRS 7.4 ± 7.75, female 5.9 ± 5.86), attributable to their young age. After considering the estimated AR, (mean FRS 13.36 ± 7.10, male 13.92 ± 7.77, female 12.48 ± 5.86), the majority of patients were re-classified to a higher-risk category: 73% (95% CI 61.5%–82.3%) of low risk patients were reclassified as intermediate, and 53% (95% CI 36.4%–64.1%) of intermediate risk patients were reclassified as high risk (Table 2). These findings suggest that adding the estimated AR of psoriasis on MACE to the FRS results in clinically important changes in prevention strategies3. Table 1 Demographic characteristics of study sample Table 2 Category of risk before and after adding psoriasis attributable risk with treatment goals Due to the young age of our population, the majority of patients were in the low risk category, which would not warrant aggressive risk reduction strategies. However, when considering an AR estimate of MACE, the majority of our patients were reclassified into the intermediate risk category which would warrant change in treatment plans and goals for over 60% of our patients (Table 2), an important finding in this population potentially at higher risk for CV disease with increased subclinical vascular inflammation4. We recognize this proof of concept study is limited by the generalizability of UK data to a US population. However, guidelines for identifying CVD risk factors are similar. Secondly, our AR was derived in severe psoriasis defined by treatment with systemic therapy or phototherapy; similarly, over 80% of our patients had been exposed to these therapies permitting this estimate to be applicable in this proof of concept study. The major implication of these findings is that patients with psoriasis may warrant more aggressive control of established CV risk factors. Measures to decrease CV risk include lifestyle and dietary education through targeted counseling. The percentage of these patients requiring drug interventions such as statins and anti-hypertensive is unknown but likely to be small. Finally, this illustration provides a quantitative approach for CV risk estimation in psoriasis, an approach gaining acceptance in the care of patients with rheumatoid arthritis5.

The Role of PET with [18-F] Fluorodeoxyglucose in the Diagnosis and Management of Thoracic Vascular Disease.

Investigating the functional activity of cellular inflammatory mediators is fundamental to understanding the pathophysiology and improving the treatment of numerous vascular conditions. PET with FDG allows noninvasive in vivo assessment of inflammatory vascular processes and may be coupled to CT or MRI to provide simultaneous anatomic information. These unique properties have provided additional insight into the pathophysiology, diagnosis, and management of thoracic vascular diseases. In this article, the role of FDG-PET in the assessment of thoracic vascular disease and the influence of this technique on the diagnostic and management approaches are discussed.