Anti-inflammatory therapy with tumour necrosis factor inhibitors is associated with reduced risk of major adverse cardiovascular events in psoriasis.

BACKGROUND: Psoriasis is a systemic chronic inflammatory condition associated with increased risk of cardiovascular disease. Data demonstrating that decreased skin inflammation reduces cardiovascular events in patients with psoriasis may be generalizable to other chronic inflammatory states with heightened cardiovascular risk. OBJECTIVE: To determine whether tumour necrosis factor inhibitor (TNFi) therapy is associated with decreased major adverse cardiovascular events (MACE) in patients with psoriasis. METHODS: In this retrospective cohort study using the KPSC health plan, patients had at least three ICD-9 codes for psoriasis and no antecedent MACE codes. Propensity score-adjusted multivariable Cox regression assessed hazard ratios (HR) of MACE associated with TNFi use. RESULTS: After adjusting for cardiovascular risk factors, the TNFi cohort had significantly lower MACE HR compared with the topical cohort (HR, 0.80; 95% CI, 0.66-0.98). The oral/phototherapy cohort had similar MACE HR compared with the topical cohort (HR, 1.19 (95% CI, 0.99-1.42)). CONCLUSIONS: We observed significantly lower MACE risk in patients with psoriasis receiving TNFi compared to topical or oral/phototherapy agents. TNFi therapy may have benefits beyond skin disease in mitigating cardiovascular event risk.

Cutaneous lupus erythematosus and the risk of deep venous thrombosis and pulmonary embolism: A Danish nationwide cohort study.

Background Venous thromboembolism (VTE) is a major public health concern. Lupus erythematosus (LE) is a chronic autoimmune disease ranging from localized cutaneous disease (CLE) to systemic involvement (SLE). Patients with SLE have an increased risk of venous thromboembolism (VTE), but little is known about the CLE-related risk of VTE. Methods To evaluate the risk of VTE in patients with SLE and CLE as compared to the general population, a retrospective cohort study was conducted. Incidence rates and hazard ratios (HRs) with 95% confidence intervals (CIs) from multivariable Cox regression models were used to evaluate and compare the risk of VTE. Registries of hospitalizations, outpatient visits, and prescription drug use were studied to determine the risk of VTE in patients with CLE and SLE and the general population between 1997 and 2011. Results A total of 3234 patients with CLE and 3627 patients with SLE were identified and compared to 5,590,070 individuals in the reference population. The incidence rates per 1000 year of VTE were higher in patients with LE, i.e. 1.20, 3.06, and 5.24 for the reference population, CLE, and SLE, respectively. In adjusted models, both CLE (HR 1.39; 95% CI 1.10-1.78) and SLE (HR 3.32; 95% CI 2.73-4.03) were associated with a statistically significant increased risk of VTE, compared to the reference population. Conclusion In this nationwide study, both CLE and SLE were significant risk factors for VTE. The results add to our understanding of comorbidities in patients with LE, and call for further studies and increased awareness of thromboembolic complications in patients with CLE.

Cutaneous lupus erythematosus and systemic lupus erythematosus are associated with clinically significant cardiovascular risk: a Danish nationwide cohort study.

Systemic lupus erythematosus (SLE) is a well-known cardiovascular risk factor. Less is known about cutaneous lupus erythematosus (CLE) and the risk of developing cardiovascular disease (CVD). Therefore, we investigated the risk of mortality and adverse cardiovascular events in patients diagnosed with SLE and CLE. We conducted a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular endpoint and all-cause mortality, for patients with SLE and CLE. A total of 3282 patients with CLE and 3747 patients with SLE were identified and compared with 5,513,739 controls. The overall HR for the composite CVD endpoint was 1.31 (95% CI 1.16-1.49) for CLE and 2.05 (95% CI 1.15-3.44) for SLE. The corresponding HRs for all-cause mortality were 1.32 (95% CI 1.20-1.45) for CLE and 2.21 (95% CI 2.03-2.41) for SLE. CLE and SLE were associated with a significantly increased risk of CVD and all-cause mortality. Local and chronic inflammation may be the driver of low-grade systemic inflammation.

Myocardial function and effects of biologic therapy in patients with severe psoriasis: a prospective echocardiographic study.

BACKGROUND: Psoriasis is a chronic inflammatory disease and is associated with cardiovascular events. Little is known about subclinical myocardial dysfunction and potential changes in myocardial function during anti-inflammatory treatment in these patients. We prospectively studied left ventricular function in patients with severe psoriasis who initiated biologic therapy. METHODS: Between November 1 2013 and May 31 2014 the study subjects underwent physical, laboratory and comprehensive echocardiographic examination at baseline and after 3 months of treatment. Pearson correlation coefficients and Student's t-test were applied to assess changes in diastolic function (defined as the E/e' ratio) and global longitudinal strain (GLS). RESULTS: Eighteen patients with severe psoriasis treated with biologic therapy with a mean follow-up of 85.6 ± 18.2 days were included. The patients had a baseline psoriasis area and severity index (PASI) of 12.0 ± 4.1 and normal left ventricular ejection fraction [(LVEF) 56.3 ± 3.8%], diastolic dysfunction (E/e' 8.1 ± 2.1) and GLS (-16.8 ± 2.1%). At follow-up, an improvement (baseline vs. follow-up) of PASI (12.0 ± 4.1 vs. 2.7 ± 3.1, P < 0.001), E/e' (8.1 ± 2.1 vs. 6.7 ± 1.9, P ≤ 0.001) and GLS (-16.8 ± 2.1 vs. -18.3 ± 2.3%, P < 0.001) were recorded. No changes were demonstrated in LVEF (56.3 ± 3.8 vs. 56.8 ± 3.3%, P = 0.31), body mass index (30.9 ± 5.7 vs. 31.0 ± 5.8 kg/m(2) , P = 0.90), mean arterial blood pressure (103.1 ± 8.5 vs. 103.7 ± 10.8 mmHg, P = 0.74). Likewise, no changes were seen in total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, estimated glomerular filtration rate and glycosylated haemoglobin. CONCLUSION: In patients with severe psoriasis treatment with biologic therapy was associated with improved PASI and amelioration of myocardial dysfunction.

Risk of thromboembolism and fatal stroke in patients with psoriasis and nonvalvular atrial fibrillation: a Danish nationwide cohort study.

OBJECTIVES: Psoriasis is a chronic inflammatory disease that is associated with a prothrombotic state and cardiovascular disease, including atrial fibrillation and thromboembolism. We therefore evaluated the impact of psoriasis in patients with atrial fibrillation and the performance of the CHA2 DS2 VASc score in these patients. DESIGN, SETTING AND PARTICIPANTS: The study comprised all Danish patients hospitalized with nonvalvular atrial fibrillation in the period 1997-2011 (n = 99,357). Follow-up started 7 days from discharge and excluded subjects treated with anticoagulation. Poisson regression adjusted for CHA2 DS2 VASc score was used to estimate the incidence rate ratios and 95% confidence intervals. MAIN OUTCOME MEASURE: Hospitalization or death from thromboembolism. RESULTS: Mean follow-up was 3.5, 3.1, and 2.8 years for patients with no psoriasis, mild psoriasis and severe psoriasis, respectively. Patients with psoriasis were younger compared to patients without psoriasis, but CHA2DS2VASc score did not differ between the three groups. Thromboembolism rates per 100 patient-years (95% confidence intervals) were 4.8 (4.7-4.9), 4.8 (4.2-5.4) and 6.1 (5.0-7.5) for patients with no psoriasis, mild psoriasis and severe psoriasis, respectively. Importantly, the observed thromboembolism rates in patients with severe psoriasis were markedly higher (2.6- to3.4-fold) than predicted by the CHA2 DS2 VASc score. Relative to no psoriasis, incidence rate ratios were 0.99 (0.87-1.11) and 1.27 (1.02-1.57) for mild and severe psoriasis, respectively. Correspondingly, incidence rate ratios for fatal stroke were 0.97 (0.80-1.12) and 1.51 (1.12-2.05). CONCLUSIONS: In patients with nonvalvular atrial fibrillation not treated with oral anticoagulation, severe psoriasis was associated with increased risk of thromboembolism. In these patients, CHA2 DS2 VASc underestimated the risk of thromboembolism.

Nationwide population-based study of cause-specific death rates in patients with psoriasis.

BACKGROUND: Psoriasis is a common chronic disease, mediated by type 1 and 17 helper T cell-driven inflammation. Epidemiological studies have demonstrated a wide range of comorbidities and increased mortality rates. However, the current evidence on psoriasis-related mortality is limited and nationwide data have not been presented previously. METHODS: In a nationwide population-based cohort we evaluated all-cause and cause-specific death rates in patients with psoriasis as compared to the general population. RESULTS: The entire Danish population aged 18 and above, corresponding to a total of 5,458,627 individuals (50.7% female, 40.9 years ± 19.7), including 94,069 with mild psoriasis (53% female, 42.0 ± 17.0 years) and 28,253 with severe psoriasis (53.4% female, 43.0 ± 16.5 years), was included. A total of 884,661 deaths were recorded, including 10 916 in patients with mild psoriasis and 3699 in patients with severe psoriasis. The age at time of death varied by psoriasis status, i.e. 76.5 ± 14.0, 74.4 ± 12.8 and 72.0 ± 13.4 years, for the general population, mild psoriasis and severe psoriasis respectively. In general, the highest death rates were observed in patients with severe psoriasis. Overall death rates per 1000 patient years were 13.8 [confidence interval (CI) 13.8-13.8], 17.0 (CI 16.7-17.3) and 25.4 (CI 24.6-26.3) for the general population, patients with mild psoriasis and patients with severe psoriasis respectively. CONCLUSION: This nationwide population-based study of cause-specific death rates in patients with psoriasis demonstrated reduced lifespan and increased rates of all examined specific causes of death in patients with psoriasis compared to the general population.

Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis: 5-year follow-up of a Danish nationwide cohort.

BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients with severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy. RESULTS: A total of 6902 patients (9662 treatment exposures) with a maximum follow-up of 5 years were included. Incidence rates per 1000 patients-years for cardiovascular events were 4.16, 6.28, 6.08, 18.95 and 14.63 for biological drugs, methotrexate, cyclosporine, retinoid and other therapies respectively. Relative to other therapies, methotrexate (HR 0.53; CI 0.34-0.83) was associated with reduced risk of the composite endpoint and a comparable but non-significant protective effect was observed with biological drugs (HR 0.58; CI 0.30-1.10), whereas no protective effect was apparent with cyclosporine (HR 1.06; CI 0.26-4.27) and retinoids (HR 1.80; CI 1.03-2.96). Tumour necrosis factor inhibitors (HR 0.46; CI 0.22-0.98) were linked to reduced event rates, whereas the interleukin-12/23 inhibitor ustekinumab (HR 1.52; CI 0.47-4.94) was not. CONCLUSION: Systemic anti-inflammatory treatment with methotrexate was associated with significantly lower rates of cardiovascular events during long-term follow-up compared to patients treated with other antipsoriatic therapies. The treatment strategy in patients with severe psoriasis may have an impact on cardiovascular outcomes and randomized trials to evaluate the cardiovascular safety and efficacy of systemic antipsoriatic therapies are called for.

Cardiovascular disease event rates in patients with severe psoriasis treated with systemic anti-inflammatory drugs: a Danish real-world cohort study.

OBJECTIVES: Psoriasis is a chronic inflammatory disorder associated with cardiovascular morbidity and mortality. Systemic anti-inflammatory drugs, including biological agents, are widely used in the treatment of patients with moderate to severe psoriasis and may attenuate the risk of cardiovascular disease events. We therefore examined the rate of cardiovascular disease events in patients with severe psoriasis treated with systemic anti-inflammatory drugs. DESIGN, SETTING AND PARTICIPANTS: Individual-level linkage of nationwide administrative databases was used to assess the event rates associated with use of biological agents, methotrexate or other therapies, including retinoids, cyclosporine and phototherapy, in Denmark from 2007 to 2009. MAIN OUTCOME MEASURE: Death, myocardial infarction and stroke. RESULTS: A total of 2400 patients with severe psoriasis, including 693 patients treated with biological agents and 799 treated with methotrexate, were identified. Incidence rates per 1000 patient-years and 95% confidence intervals (CIs) for the composite endpoint were 6.0 (95% CI 2.7-13.4), 17.3 (95% CI 12.3-24.3) and 44.5 (95% CI 34.6-57.0) for patients treated with biological agents, methotrexate and other therapies, respectively. Age- and sex-adjusted hazard ratios (HRs) were 0.28 (95% CI 0.12-0.64) and 0.65 (95% CI 0.42-1.00) for patients treated with biological agents and methotrexate, respectively, using other therapies as the reference cohort. Corresponding HRs for a secondary composite endpoint of cardiovascular death, myocardial infarction and stroke were 0.48 (95% CI 0.17-1.38) and 0.50 (95% CI 0.26-0.97). CONCLUSION: In this nationwide study of patients with severe psoriasis, systemic anti-inflammatory treatment with biological agents or methotrexate was associated with lower cardiovascular disease event rates compared to patients treated with other anti-psoriatic therapies.

Bleeding risk in 'real world' patients with atrial fibrillation: comparison of two established bleeding prediction schemes in a nationwide cohort.

BACKGROUND: Oral anticoagulation (OAC) in patients with atrial fibrillation (AF) is a double-edged sword, because it decreases the risk of stroke at the cost of an increased risk of bleeding. We compared the performance of a new bleeding prediction scheme, HAS-BLED, with an older bleeding prediction scheme, HEMORR(2)HAGES, in a cohort of 'real-world' AF patients. METHODS: By individual-level-linkage of nationwide registers, we identified all patients (n = 118,584) discharged with non-valvular AF in Denmark during the period 1997-2006, with and without OAC. Major bleeding rates during 1 year of follow-up were determined, and the predictive capabilities of the two schemes were compared by c-statistics. The risk of bleeding associated with individual risk factors composing HAS-BLED was estimated using Cox proportional-hazard analyses. RESULTS: Of AF patients receiving OAC (n = 44,771), 34.8% and 47.3% were categorized as 'low bleeding risk' by HAS-BLED and HEMORR(2)HAGES, respectively, and the bleeding rates per 100 person-years were 2.66 (95% confidence interval [CI], 2.40-2.94) and 3.06 (2.83-3.32), respectively. C-statistics for the two schemes were 0.795 (0.759-0.829) and 0.771 (0.733-0.806), respectively. The risk factors composing HAS-BLED were associated with varying risks, with a history of bleeding (hazard ratio [HR] 2.98; 95% CI 2.68-3.31) and being elderly (HR 1.93; 95% CI 1.71-2.18) being associated with the highest risks. Comparable results were found in AF patients not receiving OAC (n = 77,813). CONCLUSIONS: In an unselected nationwide cohort of hospitalized patients with atrial fibrillation, the HAS-BLED score performs similarly to HEMORR(2)HAGES in predicting bleeding risk but HAS-BLED is much simpler and easier to use in everyday clinical practise.

Prognosis following first-time myocardial infarction in patients with psoriasis: a Danish nationwide cohort study.

OBJECTIVES: The magnitude of cardiovascular risk associated with psoriasis has been debated and the prognostic impact of psoriasis following myocardial infarction (MI) is unknown. Therefore, we investigated the risk of mortality and adverse cardiovascular events in patients with psoriasis following first-time MI. DESIGN, SETTING AND PARTICIPANTS: Cohort study of the entire Danish population including all individuals who experienced first-time MI during the period 2002-2006. Multivariable Cox regression models were used to assess the post-MI prognostic impact of psoriasis. Main outcome measures. All-cause mortality and a composite cardiovascular end-point of recurrent MI, stroke and cardiovascular death. RESULTS: A total of 462 patients with psoriasis and 48 935 controls (mean age 69.5 and 70.6 years, respectively) were identified with first-time MI during the study period. The mean follow-up was 19.5 months [standard deviation (SD) 16.5] for patients with psoriasis and 22 .0 months (SD 18.7) for those without psoriasis. Incidence rates (IRs) per 1000 patient-years for all-cause mortality were 119.4 [95% confidence interval (CI) 117.2-138.3] and 138.3 (95% CI 114.1-167.7) for patients without and with psoriasis, respectively, and the adjusted hazard ratio (HR) associated with psoriasis was 1.18 (95% CI 0.97-1.43). For the composite end-point, the IRs were 149.7 (95% CI 147.1-152.4) and 185.6 (95% CI 155.8-221.0) for patients without and with psoriasis, respectively, with an HR of 1.26 (95% CI 1.04-1.54) for patients with psoriasis. CONCLUSION: This first study of the impact of psoriasis on prognosis after first-time MI indicated a significantly impaired prognosis in patients with psoriasis. Further studies of this novel association are warranted.

Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study.

OBJECTIVE: The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis-related risk of adverse cardiovascular events and mortality. DESIGN, SETTING AND SUBJECTS: We conducted a cohort study of the entire Danish population aged ≥18 years followed from 1997 to 2006 by individual-level linkage of nationwide registers. Psoriasis was defined by prescription claims and classified as severe if patients received hospital-based treatment. Time-dependent Poisson regression models were applied to assess cardiovascular risk in patients with psoriasis and psoriatic arthritis. MAIN OUTCOME MEASURES: All-cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded. RESULTS: A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including 607 with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all-cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients with psoriasis. The rate ratio increased with disease severity and decreased with age of onset. The overall RRs for the composite endpoint were 1.20 (95% confidence interval [CI] 1.14-1.25) and 1.58 (95% CI 1.36-1.82) for mild and severe psoriasis, respectively. The corresponding RRs for cardiovascular death were 1.14 (95% CI 1.06-1.22) and 1.57 (95% CI1.27-1.94). The risk was similar in patients with severe skin affection alone and those with psoriatic arthritis. CONCLUSIONS: Psoriasis is associated with increased risk of adverse cardiovascular events and all-cause mortality. Young age, severe skin affection and/or psoriatic arthritis carry the most risk. Patients with psoriasis may be candidates for early cardiovascular risk factor modification.