Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study.

AIMS: In a continuously ageing population of patients with congenital heart disease (CHD), understanding the long-term risk of morbidity is crucial. The aim of this study was to compare the lifetime risks of developing comorbidities in patients with simple CHD and matched controls. METHODS AND RESULTS: Using the Danish nationwide registers spanning from 1977 to 2018, simple CHD cases were defined as isolated atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis, or patent ductus arteriosus in patients surviving until at least 5 years of age. There were 10 controls identified per case. Reported were absolute lifetime risks and lifetime risk differences (between patients with simple CHD and controls) of incident comorbidities stratified by groups and specific cardiovascular comorbidities. Of the included 17 157 individuals with simple CHD, the largest subgroups were ASD (37.7%) and VSD (33.9%), and 52% were females. The median follow-up time for patients with CHD was 21.2 years (interquartile range: 9.4-39.0) and for controls, 19.8 years (9.0-37.0). The lifetime risks for the investigated comorbidities were higher and appeared overall at younger ages for simple CHD compared with controls, except for neoplasms and chronic kidney disease. The lifetime risk difference among the comorbidity groups was highest for neurological disease (male: 15.2%, female: 11.3%), pulmonary disease (male: 9.1%, female: 11.7%), and among the specific comorbidities for stroke (male: 18.9%, female: 11.4%). The overall risk of stroke in patients with simple CHD was mainly driven by ASD (male: 28.9%, female: 17.5%), while the risks of myocardial infarction and heart failure were driven by VSD. The associated lifetime risks of stroke, myocardial infarction, and heart failure in both sexes were smaller in invasively treated patients compared with untreated patients with simple CHD. CONCLUSION: Patients with simple CHD had increased lifetime risks of all comorbidities compared with matched controls, except for neoplasms and chronic kidney disease. These findings highlight the need for increased attention towards early management of comorbidity risk factors.

Randomized Clinical Comparison of the Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Combo Stent With the Sirolimus-Eluting Orsiro Stent in Patients Treated With Percutaneous Coronary Intervention: The SORT OUT X Trial.

BACKGROUND: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody-coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population. METHODS: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021. RESULTS: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26-2.41]; P=0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37-3.61]; P=0.0012). CONCLUSIONS: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03216733.

Randomized Comparison of the Polymer-Free Biolimus-Coated BioFreedom Stent With the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an All-Comers Population Treated With Percutaneous Coronary Intervention: The SORT OUT IX Trial.

BACKGROUND: In patients with increased bleeding risk, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent free from polymer, has shown superiority compared with a bare-metal stent. The aim of this study was to investigate whether the BioFreedom stent is noninferior to a modern ultrathin strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. METHODS: The SORT OUT IX trial (Scandinavian Organization for Randomized Trials With Clinical Outcome IX), was a large-scale, registry-based, randomized, multicenter, single-blind, 2-arm, noninferiority trial. The primary end point, major adverse cardiovascular events, was defined as the composite of cardiac death, myocardial infarction not related to any segment other than the target lesion, or target lesion revascularization within 1 year, analyzed by intention-to-treat. The trial was powered to assess noninferiority for major adverse cardiovascular events of the BioFreedom stent compared with the Orsiro stent with a predetermined noninferiority margin of 0.021. RESULTS: Between December 14, 2015 and April 21, 2017, 3151 patients were assigned to treatment with the BioFreedom stent (1572 patients, 1966 lesions) or to the Orsiro stent (1579 patients, 1985 lesions). Five patients were lost to follow-up because of emigration (99.9% follow-up rate). Mean age was 66.3±10.9, diabetes mellitus was seen in 19.3% of patients, and 53% of the patients had acute coronary syndromes. At 1 year, intention-to-treat analysis showed that 79 (5.0%) patients, who were assigned the BioFreedom stent, and 59 (3.7%), who were assigned the Orsiro stent, met the primary end point (absolute risk difference 1.29% [upper limit of one-sided 95% CI 2.50%]; Pnoninferiority=0.14). Significantly more patients in the BioFreedom stent group had target lesion revascularization than those in the Orsiro stent group (55 [3.5%] vs 20 [1.3%], rate ratio 2.77 [95% CI, 1.66-4.62]; P<0.0001). CONCLUSIONS: The biolimus A9-coated BioFreedom polymer-free stent did not meet criteria for noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02623140.

SuPAR is associated with death and adverse cardiovascular outcomes in patients with suspected coronary artery disease.

BACKGROUND: The inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with presence and severity of coronary artery disease (CAD) and incident death and myocardial infarction (MI). We sought to validate this finding in a further cohort of patients with suspected CAD. METHODS: Plasma suPAR was available in 1635 patients (73% with CAD) undergoing coronary angiography at a single regional Danish hospital between 2003 and 2005. Patients were followed for adverse cardiovascular outcomes of death, cardiac death and MI over a median follow-up of 4.2 years. RESULTS: In multivariate Cox models, adjusted for established cardiovascular risk factors, the biomarkers C-reactive protein, troponin-T and N-terminal-pro brain natriuretic peptide and the number of stenotic vessels, suPAR was independently associated with the combined endpoint of death/MI, hazard ratio (HR) 1.88; cardiovascular death, HR 2.01; and non-fatal MI, HR 1.53; (all p ≤ .037) per doubling of suPAR concentration. A plasma cutoff for suPAR ≥ 3.5 ng/mL was also significantly associated with death/MI, HR 1.51; p = .005. The C-statistic for the multivariate model predicting death/MI improved from 0.712 to 0.730 (p for difference .008) after inclusion of suPAR. However, suPAR was not associated with presence or extent of CAD (p > .05). CONCLUSION: These results validate previous findings that demonstrate suPAR to be an independent predictor of death/MI in patients with suspected or known CAD, however suPAR was not associated with presence or extent of CAD in our cohort. Probably because suPAR reflects end organ damage rather than the degree of atherosclerosis. BRIEF SUMMARY: We demonstrate that the inflammatory biomarker soluble urokinase plasminogen activator receptor is an independent predictor of death/myocardial infarction in patients with suspected or known coronary artery disease, but is not associated with the presence or severity of coronary artery disease.

Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk: A Danish Nationwide Cohort Study.

Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years was conducted, 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 disease endpoint. A total of 697 patients with localized scleroderma and 1,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion, systemic sclerosis is a significant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease.

Nationwide Study on the Risk of Abdominal Aortic Aneurysms in Patients With Psoriasis.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a complex multifactorial disease associated with a high morbidity and mortality. Increased inflammation including T-helper 17 cell-mediated effects has been implicated in AAA pathogenesis. Psoriasis is considered to be a T-helper 17-driven chronic inflammatory disease and in view of potentially overlapping inflammatory mechanisms, we investigated the risk of AAA in patients with psoriasis in a nationwide cohort. APPROACH AND RESULTS: The study comprised all Danish residents aged ≥18 years followed up from January 1, 1997, until diagnosis of AAA, December 31, 2011, migration or death. Information on comorbidity, concomitant medication, and socioeconomic status was identified by individual-level linkage of administrative registers. Incidence rates for AAA were calculated and incidence rate ratios adjusted for age, sex, comorbidity, medications, socioeconomic status, and smoking were estimated in Poisson regression models. A total of 5 495 203 subjects were eligible for analysis. During the study period, we identified 59 423 patients with mild psoriasis and 11 566 patients with severe psoriasis. The overall incidence rates of AAA were 3.72, 7.30, and 9.87 per 10 000 person-years for the reference population (23 696 cases), mild psoriasis (240 cases), and severe psoriasis (50 cases), respectively. The corresponding adjusted incidence rate ratios for AAA were increased in patients with psoriasis with incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (confidence interval, 1.21-2.32) for subjects with mild and severe disease, respectively. CONCLUSIONS: In a nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of AAA. The mechanisms and consequences of this novel finding require further investigation.

Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes based on phase III and long-term extension data in patients with plaque psoriasis.

BACKGROUND: Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis. OBJECTIVE: We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV events (MACEs) in patients with plaque psoriasis. METHODS: Changes in select CV risk factors and the incidence rate (IR) of MACEs were evaluated in patients who were treated with tofacitinib. RESULTS: Tofacitinib treatment was associated with small, dose-dependent increases in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, while the total/HDL cholesterol ratio was unchanged. There were no changes in blood pressure and glycated hemoglobin levels; C-reactive protein levels decreased. The IRs of a MACE were low and similar for both tofacitinib doses. Among 3623 subjects treated with tofacitinib, the total patient-years of exposure was 5204, with a median follow-up of 527 days, and the IR of MACEs was 0.37 (95% confidence interval, 0.22-0.57) patients with events per 100 patient-years. LIMITATIONS: There was relatively short follow-up time for patients who had MACEs. CONCLUSIONS: While treatment with tofacitinib is associated with a small increase in cholesterol levels, the total/HDL cholesterol ratio does not change, there are no unfavorable changes in several CV risk factors, and the incidence of MACEs is low.

Psoriasis and New-onset Depression: A Danish Nationwide Cohort Study.

Psoriasis is associated with an increased risk of depression, but results are inconsistent. This study examined the risk of new-onset depression in patients with psoriasis in a nationwide Danish cohort including some 5 million people in the period 2001-2011. A total of 35,001 patients with mild psoriasis and 7,510 with severe psoriasis were identified. Incidence rates per 1,000 person-years and incidence rate ratios (IRRs) were calculated. Incidence rates for depression were 20.0 (95% confidence interval 19.9-20.0), 23.9 (23.1-24.7) and 31.6 (29.5-33.8) for the reference population, mild, and severe psoriasis, respectively. Adjusted for age, sex, and inclusion year, IRRs were 1.08 (1.04-1.12) in mild and 1.36 (1.27-1.46) in severe psoriasis. After adjustment for comorbidity, the IRR was significant in only patients < 50 years with severe psoriasis (IRR 1.23 (1.03-1.46)). In conclusion, the risk of new-onset depression in psoriasis is mediated primarily by comorbidities, except in younger individuals with severe psoriasis, in whom psoriasis itself may be a risk factor.

Increased risk of aortic valve stenosis in patients with psoriasis: a nationwide cohort study.

AIM: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular disease including atherosclerosis. The pathogenesis of aortic valve stenosis (AS) also includes an inflammatory component. We therefore investigated the risk of AS in patients with psoriasis compared with the general population in a nationwide cohort. METHODS: The study comprised the entire Danish population aged ≥18 years followed from 1 January 1997 until diagnosis of AS, 31 December 2011, or death. Information on comorbidity, concomitant medication, and socioeconomic status was identified by individual-level linkage of administrative registers. Incidence rates for AS were calculated and incidence rate ratios (IRRs) adjusted for age, gender, calendar year, comorbidity, medications, and socioeconomic status, were estimated in Poisson regression models. RESULTS: A total of 5 107 624 subjects were eligible for analysis. During the study period, we identified 58 747 patients with mild psoriasis and 11 918 patients with severe psoriasis. The overall incidence rates for AS were 8.09, 16.07, and 20.08 per 10 000 person-years for the reference population (48 539 cases [mean follow-up 12.3 years]), mild psoriasis (509 cases [mean follow-up 6.2 years]), and severe psoriasis (99 cases [mean follow-up 5.4 years]), respectively. Correspondingly, the fully adjusted IRRs for AS were markedly increased in patients with psoriasis with IRR 1.22 (95% confidence interval [CI] 1.12-1.33) and IRR 1.61 (CI 1.32-1.96) for subjects with mild and severe disease, respectively. CONCLUSION: In a nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of AS. The mechanisms underlying this novel finding require further study.

Non-steroidal anti-inflammatory drugs and risk of cardiovascular disease in patients with rheumatoid arthritis: a nationwide cohort study.

OBJECTIVE: To examine the risk of major cardiovascular disease associated with non-steroidal anti-inflammatory drugs (NSAIDs) in a large 'real-world' contemporary rheumatoid arthritis (RA) cohort. METHODS: A longitudinal cohort study was conducted with use of Danish nationwide individual-level registry data on inpatient and outpatient health care provision, pharmacotherapy and income during 1997-2009. 17 320 RA patients were identified and matched with 69 280 controls (4 : 1) by age and sex. NSAID-associated risk of major cardiovascular disease defined as the combined endpoint of myocardial infarction, stroke or cardiovascular mortality was assessed in multivariable survival models. RESULTS: During follow-up (median 4.9 years) 6283 events occurred. The cardiovascular risk associated with overall NSAID use was significantly lower in RA patients than in controls (HR 1.22 (95% CI 1.09 to 1.37) vs 1.51 (1.36 to 1.66), p<0.01). The pattern of lower NSAID-associated risk in RA patients was generally found with the individual NSAIDs investigated. While use of rofecoxib (HR 1.57 (1.16 to 2.12)) and diclofenac (HR 1.35 (1.11 to 1.64)) was associated with increased cardiovascular risk in RA patients, there was no significant risk increase associated with use of other NSAIDs in these patients. CONCLUSIONS: The cardiovascular risk associated with NSAID use in RA patients was modest and significantly lower than in non-RA individuals. Moreover, only a few of the individual NSAIDs were associated with increased cardiovascular risk. NSAID use should be assessed in the individual patient based on the indication for pain relief and risk factors for adverse effects, and not automatically be avoided due to concerns of severe cardiovascular outcomes alone.

Increased risk of atrial fibrillation and stroke during active stages of inflammatory bowel disease: a nationwide study.

AIMS: Inflammation is considered to play a role in the development of atrial fibrillation (AF). Hence inflammatory bowel disease (IBD) may be associated with AF. We therefore examined the incidence of AF and stroke in patients with IBD. METHODS AND RESULTS: From Danish nationwide registries 1996-2011, we identified 24 499 patients with new-onset IBD and 236 275 age- and sex-matched controls. Poisson regression analyses with continuously updated covariates were used to estimate incidence rate ratios (IRRs) of AF and stroke. Disease activity stages of flare (new disease activity), persistent activity, and remission were defined by corticosteroid prescriptions, IBD hospital admissions, and biological treatment. Inflammatory bowel disease patients had a mean age of 43.9 years, 53.9% were women, and mean follow-up was 6.8 years. Among IBD patients, 685 had AF and 549 had a stroke, corresponding to incidence rates per 1000 person-years of 4.16 vs. 2.70 for AF and 3.33 vs. 2.44 for stroke, compared with matched controls. Overall IBD-associated risk of AF corresponded to IRR 1.26 (1.16-1.36), but was driven by increased AF incidence during IBD flares [IRR 2.63 (2.26-3.06)] and persistent activity [IRR 2.06 (1.67-2.55)], whereas no increased AF risk was observed in remission periods [IRR 0.97 (0.88-1.08)]. Likewise increased stroke risk was exclusively found during active IBD [IRRs: 1.57 (1.27-1.93), 1.71 (1.32-2.21), and 1.04 (0.93-1.15) for flares, persistent activity, and remission, respectively]. CONCLUSION: Active IBD is associated with increased risk of AF and stroke. These findings may be relevant to clinical practice.

Use of secondary prevention pharmacotherapy after first myocardial infarction in patients with diabetes mellitus.

BACKGROUND: Despite recommended pharmacotherapies the use of secondary prevention therapy after myocardial infarction (MI) remains suboptimal. Patients with diabetes mellitus (DM) have worse prognosis after MI compared to patients without DM and aggressive secondary prevention pharmacotherapy in this population is therefore warranted. We examined the changes in use of evidence-based secondary prevention pharmacotherapy in patients with and without DM discharged after first MI. METHODS: All patients aged 30 years or older admitted with first MI in Denmark during 1997-2006 were identified by individual-level linkage of nationwide registries of hospitalizations. Univariate and multivariate logistic regression models were used to identify patient characteristics associated with initiation of acetylsalicylic acid, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, ß-blockers, and clopidogrel within 90 days, and statins within 180 days of discharge, respectively. RESULTS: A total of 78,230 patients were included, the mean age was 68.3 years (SD 13.0), 63.5% were men and 9,797 (12.5%) had diabetes. Comparison of claimed prescriptions in the period 1997-2002 and 2003-2006 showed significant (p < 0.001) increases in claims for acetylsalicylic acid (38.9% vs. 69.7%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (38.7% vs. 50.4%), ß-blockers (69.2% vs. 77.9%), clopidogrel (16.7% vs. 66.3%), and statins (41.3% vs. 77.3%). During 2003-2006, patients with DM claimed significantly less acetylsalicylic acid (odds ratio [OR] 0.81 [95% confidence interval [CI] 0.74-0.88) and clopidogrel (OR 0.91 [95% CI 0.83-1.00]) than patients without DM. CONCLUSIONS: Despite sizeable increase in use of evidence-based secondary prevention pharmacotherapy after MI from 1997 to 2006, these drugs are not used in a substantial proportion of subjects and patients with DM received significantly less antiplatelet therapy than patients without DM. Increased focus on initiation of secondary prevention pharmacotherapy after MI is warranted, especially in patients with DM.

Temporal trends in stroke admissions in Denmark 1997-2009.

BACKGROUND: The Stroke burden is increasing in many populations where health institutions may experience more patients. We wanted to examine whether incidence rates and absolute number of hospitalized stroke patients remained stable in Denmark during a 13 years period where exposure to major stroke risk factors decreased, changes in stroke treatment was implemented, and the age of the population increased. METHODS: The Danish National Patient Register was used to identify all subjects 25 years of age or above admitted with a first time stroke in Denmark from 1997-2009. Incidence rates (IRs) and age-adjusted Poisson regression analyses were used to examine trends in age-, gender- and stroke subtype (ischaemic or unspecified). RESULTS: During the 13-year observation period there were 53.5 million person-years at risk (PY) and a total of 84,626 male and 84,705 female stroke patients were admitted to Danish hospitals. The IRs of hospitalized strokes per 1000 PY was 3.21 (95% confidence interval [CI] 3.16-3.27) in 1997, 3.85 (95% CI 3.79-3.91) in 2003 and 3.22 (95% CI 3.16-3.28) in 2009, respectively.Incidence rate ratios of hospitalized stroke events adjusted for age in the period 2007-2009 compared to 1997-2000 were 0.89 (95% CI 0.87- 0.91) for men and 0.92 (95% CI 0.90-0.94) for women.The incidence of hospitalized unspecified strokes decreased from 1997 to 2009 whereas there was a steep rise in incidence for hospitalization with specified ischemic stroke during this period. CONCLUSION: This study found a constant rate of stroke hospitalization in Denmark from 1997-2009. The overall rate of hospitalized strokes adjusted for age decreased during this period.

Psoriasis and risk of atrial fibrillation and ischaemic stroke: a Danish Nationwide Cohort Study.

AIMS: Psoriasis is a chronic inflammatory disease and inflammation contributes to the pathogenesis of atrial fibrillation (AF) and ischaemic stroke. We therefore investigated the risk of these endpoints in patients with psoriasis. METHODS AND RESULTS: Cohort study of the entire Danish population followed from 1997 to 2006 by individual-level-linkage of nationwide prospectively recorded registers. Multivariable Poisson's regression and sensitivity analyses were used to assess the psoriasis-related risk of AF and ischaemic stroke. A total of 36 765 patients with mild psoriasis and 2793 with severe psoriasis were compared with 4 478 926 individuals, i.e., the reference population. In patients with mild psoriasis, the adjusted rate ratios (RRs) for AF were 1.50 (1.21-1.86) and 1.16 (1.08-1.24) in patients aged <50 and ≥50 years, respectively. Patients with severe psoriasis had a higher risk of AF with RRs 2.98 (1.80-4.92) in patients aged <50 years and 1.29 (1.01-1.65) in patients aged ≥50 years. Patients with psoriasis also demonstrated a disease severity-dependent increased risk of ischaemic stroke, i.e. RRs 1.97 (1.66-2.34) and 2.80 (1.81-4.34) in patients aged <50 years with mild and severe psoriasis, and RRs 1.13 (1.04-1.21) and 1.34 (1.04-1.71) in patients aged ≥50 years with mild and severe psoriasis, respectively. A range of sensitivity analyses yielded comparable results. CONCLUSION: Psoriasis is associated with increased risk of AF and ischaemic stroke. These novel results add to a growing body of evidence, suggesting that patients with psoriasis could be considered at increased cardiovascular risk.

Clopidogrel discontinuation after myocardial infarction and risk of thrombosis: a nationwide cohort study.

AIMS: The benefit of extending clopidogrel treatment beyond the 12-month period recommended in current guidelines after myocardial infarction (MI) is debated. We analysed the risk of adverse cardiovascular outcomes after discontinuation of 12 months of clopidogrel treatment. METHODS AND RESULTS: This Danish retrospective nationwide study included all patients treated with clopidogrel after discharge from a first-time MI during 2004-09. The risk of death or recurrent MI after the discontinuation of clopidogrel was studied by multivariable Poisson regression models. Patients treated with and without percutaneous coronary intervention (PCI) were analysed separately. The follow-up was 18 months. Of the 29,268 patients included, 3214 (11.0%) experienced death or recurrent MI. There were 9819 (33.6%) patients treated only medically and 19,449 (66.4%) patients treated with PCI. Twelve months after the index MI, for patients treated only medically, the risk of death or recurrent MI in the first 90-day period of clopidogrel discontinuation was 1.07 (0.65-1.76; P= 0.79) [adjusted incidence rate ratio (IRR) and 95% confidence interval] compared with the next 90-day period of discontinuation. For patients treated with PCI, the corresponding IRR was 1.59 (1.11-2.30; P= 0.013). The risk of recurrent MI yielded an IRR of 0.77 (0.36-1.67; P= 0.51) for patients treated only medically and 1.87 (1.11-3.15; P= 0.019) for PCI-treated patients. CONCLUSION: Discontinuation of clopidogrel 12 months after MI is associated with an increased risk of death or recurrent MI in the first 90 days of discontinuation compared with the next 90-day period of discontinuation for patients treated with PCI, but not for patients not treated with PCI.

Mortality in heart failure with and without autoimmune disease.

AIMS: Autoimmune diseases (AIDs) are associated with a higher risk of heart failure (HF). However, data on the prognosis of HF patients with a history of AID are limited. The aim was to investigate the rates of all-cause mortality and HF hospitalization in a large, nationwide cohort of patient with HF according to a history of 29 AIDs. METHODS AND RESULTS: Using Danish nationwide registries, each HF patient (diagnosed 2000-18) with a history of AID was matched with four HF patients without AID by age, sex, and year of HF diagnosis. Rates of outcomes were compared by Cox regression models. The prevalence of AID in patients with HF was 10.7%. In total, 21 256 HF patients with a history of AID were matched with 85 024 HF patients without AID (median age 77 years; 58.9% female). During a median follow-up of 3.2 years, the incidence rates per 100 person-years for all-cause mortality were 17.1 (95% confidence interval, 16.9-17.4) and 14.4 (14.3-14.6) in patients with and without AID, respectively. The corresponding rates for HF hospitalization were 5.0 (4.9-5.1) and 5.2 (5.1-5.4), respectively. A history of AID was associated with higher rate of all-cause mortality [hazard ratio (HR) 1.14 (1.12-1.17)], but not HF hospitalization [HR 1.00 (0.96-1.04)] compared with no AID. CONCLUSIONS: In a nationwide cohort study, patients with HF and a history of AID had a higher associated rate of mortality than those without a history of AID.

This study examined the rates of all-cause mortality and hazard ratio (HF) hospitalization in a large, nationwide cohort of patient with HF with and without a history of 29 autoimmune diseases (AIDs). Among HF patients, a history of AID was associated with higher mortality. Further research elucidating the explanations for the observed excess mortality is needed. Among HF patients, a history of AID was not associated with higher HF hospitalization.

Initiation and adherence to secondary prevention pharmacotherapy after myocardial infarction in patients with rheumatoid arthritis: a nationwide cohort study.

OBJECTIVES: To examine whether rheumatoid arthritis (RA) is associated with less optimal secondary prevention pharmacotherapy after first-time myocardial infarction (MI). METHODS: The authors identified all patients with first-time MI in the Danish National Patient Register from 2002 to 2009 and gathered individual level information including pharmacy records from nationwide registers. Initiation of standard care post-MI secondary prevention drugs, that is, aspirin, ß-blockers, clopidogrel, renin angiotensin system (RAS) blockers and statins, was determined after discharge. In addition, adherence to each drug was evaluated as the proportion of patients on treatment during follow-up and time to first treatment gap. RESULTS: A total of 66 107 MI patients (37% women) were discharged alive; 877 were identified as RA patients (59% women). Thirty days after discharge, RA was associated with significantly lower initiation of aspirin (OR 0.80 (0.67-0.96)), ß-blockers (0.77 (0.65-0.92)) and statins (0.69 (0.58-0.82)), while initiation of RAS blockers (0.80 (0.57-1.11)) and clopidogrel (0.88 (0.75-1.02)) was non-significantly reduced. These estimates were virtually unchanged at day 180 and the results were corroborated by Cox regression analyses. Adherence to statins was lower in RA patients relative to non-RA patients (HR for treatment gap of 90 days: 1.26 (1.07-1.48)), while no significant differences were found in adherence to the other drugs. CONCLUSIONS: In this nationwide study of unselected patients with first-time MI, a reduced initiation of secondary prevention pharmacotherapy was observed in RA patients. This undertreatment may contribute to the increased cardiovascular disease burden in RA and the underlying mechanisms warrant further study.

Prognosis after percutaneous coronary intervention in patients with psoriasis: a cohort study using Danish nationwide registries.

BACKGROUND: Psoriasis is an inflammatory disease associated with increased risk of coronary artery disease. However, the potential impact of psoriasis on the prognosis following percutaneous coronary revascularization (PCI) is unknown. METHODS: The study comprised the entire Danish population undergoing first-time PCI in the period 2002-09. Cox regression models, controlling for age, gender, socioeconomic status, pharmacological treatment, and comorbidity were used to assess the risk of 1) all-cause mortality and 2) a composite endpoint of death, myocardial infarction, and stroke. RESULTS: A total of 53,141 patients with first-time PCI in the study period were identified. Of these, 1074 had mild psoriasis and 315 had severe psoriasis. Patients with severe psoriasis, but not those with mild disease had increased risk of both endpoints compared to patients without psoriasis. The incidence rates for all-cause mortality were 30.5 (CI 29.7-31.3), 29.9 (CI 24.7-36.1), and 47.2 (CI 35.0-63.6) per 1000 patient years for patients without psoriasis, with mild psoriasis, and with severe psoriasis, respectively. Hazard ratios were 1.10 (CI 0.91-1.33) and 1.67 (CI 1.24-2.26) for mild and severe psoriasis, respectively. Patients with severe psoriasis were less likely to receive secondary prevention pharmacotherapy with betablockers, statins and platelet inhibitors. CONCLUSION: This first study of the prognosis following PCI in patients with psoriasis demonstrated an increased risk of all-cause mortality and of a composite of death, myocardial infarction and stroke, respectively, in patients with severe psoriasis compared to patients without psoriasis. Further studies of this novel association are needed.

Decreased Arterial Vascular Tone in Small Arteries in Severe Hidradenitis Suppurativa - A Study Using Finger Photopulseplethysmography.

A previous study has found an association between chronic inflammatory disorders e.g. psoriasis, rheumatoid arthritis, and inflammatory bowel disease and increased vascular stiffness(1). Psoriasis and hidradenitis suppurativa (HS) are believed to have shared comorbidities and pathophysiology despite their morphologically different manifestations in the skin. In order to evaluate a putative association between the chronic inflammatory skin disease HS and arterial stiffness, an observational cross-sectional retrospective study was carried out as part of the Danish General Suburban Population Study (GESUS) (1), in which 430 patients with HS from the general population (representing mild HS; Table 1), 32 patients with HS from a hospital-based out-patient clinic (representing severe HS, Table 1), and 20,780 controls underwent measurements of arterial vascular tone and stiffness using photoplethysmography (Pulse Trace PCA2®; Micro Medical Ltd, Kent, UK). The method of Pulse Trace has been validated by correlation with intra-arterial sensing techniques, and is a simple cost-effective screening method[2]. All analyses were performed using SAS 9.3. This study was accepted by the ethics committee of Region Zealand (project number SJ-191, SJ-113, SJ-114) in Denmark (2,3). RESULTS Reflection index (RI) is an expression of arterial vascular tone and stiffness of small arteries. The raw data showed a significantly lower RI for both HS groups groups, compared to controls. The results remained significant when adjusting for confounders (age, sex, smoking and metabolic syndrome) in the out-patient clinic HS group (-11.26 (-17.75- -4.76), P=0.0002*), but not in the population HS group (Table 2). Stiffness index (SI) expresses arterial stiffness in large arteries. Both HS groups showed no significant difference in either SI or vascular age in multivariate analysis, when compared with controls (Table 2). DISCUSSION This study suggests that decreased vascular tone and stiffness of small arteries may be associated with severe HS, and at the same time found no difference in arterial stiffness in large arteries. The significance for the out-patient clinic HS group, but not the population HS group may reflect a dose-response relationship. Vascular tone in vascular smooth muscle cells of small arteries depends on competing vasodilators and vasoconstrictors. We speculate that the inflammation of HS may induce a dysfunctional balance e.g. through increased TNF-alpha with subsequent increase of the vasodilator nitric oxide resulting in the lower arterial vascular tone observed. Additionally, mast cells are increased in HS [4], possibly increasing levels of the vasodilator histamine. HS patients often suffer from stress which could increase sympathetic activity, thereby adrenalin/cortisol and subsequent vasodilation in e.g. muscles. The more peripheral an artery is, the more collagen it contains and the stiffer it is. The finding of lower vascular tone may also be suggestive of a different elastin:collagen ratio in small arteries in HS. The healing process of HS lesions is known to involve scarring formation of sinus tracts [5], which may suggest a hypothesis of altered connective tissue. This study found no difference in SI expressing arterial stiffness of large arteries between HS and controls. Our previous study found an association between HS and myocardial infarction, but no association with stroke, nor peripheral arterial stiffness of lower extremities in medium/large arteries [6], suggesting regional differences in vascular beds in HS. The major limitation of the study is the missing values of pulse trace measurement (Table 1) creating possible selection bias. Although unable to draw any clinical conclusions, we believe these results may contribute to the future research of the complexity of HS and cardiovascular risk profiling. This study suggests that decreased vascular tone and stiffness of small arteries may be associated with severe HS, and at the same time found no difference in arterial stiffness in large arteries. The significance for the out-patient clinic HS group, but not the population HS group may reflect a dose-response relationship. Vascular tone in vascular smooth muscle cells of small arteries depends on competing vasodilators and vasoconstrictors. We speculate that the inflammation of HS may induce a dysfunctional balance e.g. through increased TNF-alpha with subsequent increase of the vasodilator nitric oxide resulting in the lower arterial vascular tone observed. Additionally, mast cells are increased in HS [4], possibly increasing levels of the vasodilator histamine. HS patients often suffer from stress which could increase sympathetic activity, thereby adrenalin/cortisol and subsequent vasodilation in e.g. muscles. The more peripheral an artery is, the more collagen it contains and the stiffer it is. The finding of lower vascular tone may also be suggestive of a different elastin:collagen ratio in small arteries in HS. The healing process of HS lesions is known to involve scarring formation of sinus tracts [5], which may suggest a hypothesis of altered connective tissue. This study found no difference in SI expressing arterial stiffness of large arteries between HS and controls. Our previous study found an association between HS and myocardial infarction, but no association with stroke, nor peripheral arterial stiffness of lower extremities in medium/large arteries [6], suggesting regional differences in vascular beds in HS. The major limitation of the study is the missing values of pulse trace measurement (Table 1) creating possible selection bias. Although unable to draw any clinical conclusions, we believe these results may contribute to the future research of the complexity of HS and cardiovascular risk profiling.

Effect of implantable cardioverter-defibrillators in patients with non-ischaemic systolic heart failure and concurrent coronary atherosclerosis.

AIMS: Prophylactic implantable cardioverter-defibrillators (ICD) reduce mortality in patients with ischaemic heart failure (HF), whereas the effect of ICD in patients with non-ischaemic HF is less clear. We aimed to investigate the association between concomitant coronary atherosclerosis and mortality in patients with non-ischaemic HF and the effect of ICD implantation in these patients. METHODS AND RESULTS: Patients were included from DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-Ischaemic Systolic Heart Failure on Mortality), randomizing patients to ICD or control. Study inclusion criteria for HF were left ventricular ejection fraction ≤ 35% and increased levels (>200 pg/mL) of N-terminal pro-brain natriuretic peptide. Of the 1116 patients from DANISH, 838 (75%) patients had available data from coronary angiogram and were included in this subgroup analysis. We used Cox regression to assess the relationship between coronary atherosclerosis and mortality and the effect of ICD implantation. Of the included patients, 266 (32%) had coronary atherosclerosis. Of these, 216 (81%) had atherosclerosis without significant stenoses, and 50 (19%) had significant stenosis. Patients with atherosclerosis were significantly older {67 [interquartile range (IQR) 61-73] vs. 61 [IQR 54-68] years; P < 0.0001}, and more were men (77% vs. 70%; P = 0.03). During a median follow-up of 64.3 months (IQR 47-82), 174 (21%) of the patients died. The effect of ICD on all-cause mortality was not modified by coronary atherosclerosis [hazard ratio (HR) 0.94; 0.58-1.52; P = 0.79 vs. HR 0.82; 0.56-1.20; P = 0.30], P for interaction = 0.67. In univariable analysis, coronary atherosclerosis was a significant predictor of all-cause mortality [HR, 1.41; 95% confidence interval (CI), 1.04-1.91; P = 0.03]. However, this association disappeared when adjusting for cardiovascular risk factors (age, gender, diabetes, hypertension, smoking, and estimated glomerular filtration rate) (HR 1.05, 0.76-1.45, P = 0.76). CONCLUSIONS: In patients with non-ischaemic systolic heart failure, ICD implantation did not reduce all-cause mortality in patients either with or without concomitant coronary atherosclerosis. The concomitant presence of coronary atherosclerosis was associated with increased mortality. However, this association was explained by other risk factors.