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      Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study

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          To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP).


          This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001–2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively.


          Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31–1.82)), PsA (1.76 (1.59–1.95)) and uSpA (1.36 (1.05–1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37–0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06–1.48)) and PsA (1.34 (1.22–1.48)), and nonsignificantly increased in uSpA (1.16 (0.91–1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP.


          Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13075-017-1315-z) contains supplementary material, which is available to authorized users.

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          Most cited references 42

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          Prevalence of cardiovascular risk factors in patients with psoriasis.

          Previous studies suggest that patients hospitalized for psoriasis have an increased frequency of a variety of cardiovascular comorbidities. Limited population-based data exist on this association, and few studies have determined which factors are independently associated with psoriasis. We sought to determine whether the prevalence of the major cardiovascular risk factors was higher in mild and severe psoriasis than in patients without psoriasis. We conducted a population-based study in the United Kingdom using the General Practice Research Database. Patients were classified as having severe psoriasis if they received a code for psoriasis as well as systemic therapy. Patients were defined as having mild psoriasis if they ever received a psoriasis code but no systemic therapy. Control subjects were selected from the same practices and start dates as psoriasis patients. Patients were classified as having risk factors if they received codes for diabetes, hypertension, hyperlipidemia, obesity, or smoking. Analyses were performed by using conditional logistic regression, and adjustments were made considering age, gender, person-years, and all cardiovascular risk factors. We identified 127,706 patients with mild psoriasis and 3854 with severe psoriasis. Respective prevalence rates of risk factors in those with severe psoriasis, mild psoriasis, and in controls were as follows: diabetes (7.1%, 4.4%, 3.3%), hypertension (20%, 14.7%, 11.9%), hyperlipidemia (6%, 4.7%, 3.3%), obesity (20.7%, 15.8%, 13.2%), and smoking (30.1%, 28%, 21.3%). Patients with mild psoriasis had a higher adjusted odds of diabetes (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08-1.18]), hypertension (OR, 1.03; 95% CI, 1.01-1.06), hyperlipidemia (OR, 1.16; 95% CI, 1.12-1.21), obesity (OR, 1.27; 95% CI, 1.24-1.31), and smoking (OR, 1.31; 95% CI, 1.29-1.34) than controls. Patients with severe psoriasis had a higher adjusted odds of diabetes (OR, 1.62; 95% CI, 1.3-2.01), obesity (OR, 1.79; 95% CI, 1.55-2.05), and smoking (OR, 1.31; 95% CI, 1.17-1.47) than controls. Additionally, diabetes (OR, 1.39; 95% CI, 1.22-1.58) and obesity (OR, 1.47; 95% CI, 1.32-1.63) were more prevalent in those with severe psoriasis than with mild psoriasis. The study was cross-sectional and therefore the directionality of the associations could not be determined. Multiple cardiovascular risk factors are associated with psoriasis. Cardiovascular risk factors that are key components of the metabolic syndrome are more strongly associated with severe psoriasis than with mild psoriasis.
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            Cardiovascular risk factors and venous thromboembolism: a meta-analysis.

            The concept that venous thromboembolism (VTE) and atherosclerosis are 2 completely distinct entities has recently been challenged because patients with VTE have more asymptomatic atherosclerosis and more cardiovascular events than control subjects. We performed a meta-analysis to assess the association between cardiovascular risk factors and VTE. Medline and EMBASE databases were searched to identify studies that evaluated the prevalence of major cardiovascular risk factors in VTE patients and control subjects. Studies were selected using a priori defined criteria, and each study was reviewed by 2 authors who abstracted data on study characteristics, study quality, and outcomes. Odds ratios or weighted means and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of chi2 and I2 statistics. Twenty-one case-control and cohort studies with a total of 63 552 patients met the inclusion criteria. Compared with control subjects, the risk of VTE was 2.33 for obesity (95% CI, 1.68 to 3.24), 1.51 for hypertension (95% CI, 1.23 to 1.85), 1.42 for diabetes mellitus (95% CI, 1.12 to 1.77), 1.18 for smoking (95% CI, 0.95 to 1.46), and 1.16 for hypercholesterolemia (95% CI, 0.67 to 2.02). Weighted mean high-density lipoprotein cholesterol levels were significantly lower in VTE patients, whereas no difference was observed for total and low-density lipoprotein cholesterol levels. Significant heterogeneity among studies was present in all subgroups except for the diabetes mellitus subgroup. Higher-quality studies were more homogeneous, and significant associations remained unchanged. Cardiovascular risk factors are associated with VTE. This association is clinically relevant with respect to individual screening, risk factor modification, and primary and secondary prevention of VTE. Prospective studies should further investigate the underlying mechanisms of this relationship.
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              Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study.

              The role of C-reactive protein (CRP) as a novel plasma marker of atherothrombotic disease is currently under investigation. Previous studies have mostly related CRP to coronary heart disease, were often restricted to a case-control design, and failed to include pertinent risk factors to evaluate the joint and net effect of CRP on the outcome. We related plasma CRP levels to incidence of first ischemic stroke or transient ischemic attack (TIA) in the Framingham Study original cohort. There were 591 men and 871 women free of stroke/TIA during their 1980 to 1982 clinic examinations, when their mean age was 69.7 years. CRP levels were measured by using an enzyme immunoassay on previously frozen serum samples. Analyses were based on sex-specific CRP quartiles. Risk ratios (RRs) were derived, and series of trend analyses were performed. During 12 to 14 years of follow-up, 196 ischemic strokes and TIAs occurred. Independent of age, men in the highest CRP quartile had 2 times the risk of ischemic stroke/TIA (RR=2.0, P=0.027), and women had almost 3 times the risk (RR=2.7, P=0.0003) compared with those in the lowest quartile. Assessment of the trend in risk across quartiles showed unadjusted risk increase for men (RR=1.347, P=0.0025) and women (RR=1.441, P=0.0001). After adjustment for smoking, total/HDL cholesterol, systolic blood pressure, and diabetes, the increase in risk across CRP quartiles remained statistically significant for both men (P=0.0365) and women (P=0.0084). Independent of other cardiovascular risk factors, elevated plasma CRP levels significantly predict the risk of future ischemic stroke and TIA in the elderly.

                Author and article information

                +46(0)31-3429790 , karin.si.bengtsson@vgregion.se
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                18 May 2017
                18 May 2017
                : 19
                [1 ]ISNI 0000 0000 9919 9582, GRID grid.8761.8, Department of Rheumatology and Inflammation Research, , Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, ; Box 480, 405 30 Gothenburg, Sweden
                [2 ]ISNI 0000 0001 1034 3451, GRID grid.12650.30, Departments of Public Health and Clinical Medicine, Rheumatology, , Umeå University, ; 901 87 Umeå, Sweden
                [3 ]ISNI 0000 0001 0930 2361, GRID grid.4514.4, Section of Rheumatology, Department of Clinical Sciences, , Malmö, Lund University, ; 202 13 Malmö, Sweden
                [4 ]GRID grid.465198.7, Clinical Epidemiology Unit and Rheumatology Unit, Department of Medicine Solna, , Karolinska Institutet, ; 171 77 Solna, Sweden
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funded by: FundRef http://dx.doi.org/10.13039/501100005760, Göteborgs Universitet;
                Funded by: FundRef http://dx.doi.org/10.13039/501100005689, Göteborgs Läkaresällskap;
                Funded by: FundRef http://dx.doi.org/10.13039/100007212, Västra Götalandsregionen;
                Funded by: FundRef http://dx.doi.org/10.13039/501100005754, Sahlgrenska Universitetssjukhuset;
                Funded by: FundRef http://dx.doi.org/10.13039/501100008106, Reumatikerdistriktet i Göteborg;
                Funded by: Swedish Rheumatism Association
                Research Article
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                © The Author(s) 2017


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