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361 CLINICAL REPORT Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk: A Danish Nationwide Cohort Study Jeanette Halskou HESSELVIG 1 , Kristian KOFOED 1 , Jashin J. WU 2 , Lene DREYER 3 , Gunnar GISLASON 4 and Ole AHLEHOFF 5 Departments of 1 Dermato-Allergology, 3 Rheumatology and 4 Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark, 2 Department of Dermatology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA, and 5 Department of Cardiology, Odense University Hospital, Odense, Denmark Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular di- sease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the enti- re 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 cardiovascu- lar disease endpoint. A total of 697 patients with lo- calized scleroderma and 1,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclero- sis, the adjusted HR was 2.22 (95% confidence inter- val 1.99–2.48). No association was seen between pa- tients with localized scleroderma and cardiovascular disease. In conclusion, systemic sclerosis is a signifi- cant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease. Key words: localized scleroderma; systemic sclerosis; cardio- vascular risk; cardiovascular disease; inflammation; epidemio- logy. Accepted Nov 13, 2017; Epub ahead of print Nov 14, 2017 Acta Derm Venereol 2018; 98: 361–365. Corr: Kristian Kofoed, Department of Dermato-Allergology, Herlev and Gentofte University Hospital, Kildegaardsvej 28, DK-2900 Hellerup, Den- mark. E-mail: [email protected] R ecent findings indicate that patients with systemic sclerosis (SSc) have an increased risk of cardiovas- cular disease (CVD) (1, 2), but population-based cohort studies are lacking (3, 4). In addition, little is known about the risk of CVD in patients with localized sclero- derma (LS). SSc is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. LS, also known as morphea, is characterized by excessive deposition of collagen leading to thickening of the dermis, sub- cutaneous tissues, or both. Depending on the subtype and site affected, adjacent structures, such as adipose tissue, muscles, joints and bones, may be involved, but the internal organs are not affected and no progression to SSc occurs (5). Other autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are associated with increased risk of developing CVD (6–8). One of the reasons for this association is related to chronic inflammation that predisposes to atheroscle- rosis (9–12). The aim of this Danish nationwide cohort study was to determine whether patients with LS and SSc have increased risk of CVD and all-cause mortality, compared with the general population, based on the unique Danish Health registers. MATERIALS AND METHODS Data sources and study population The study was approved by the Danish Data Protection Agency. In Denmark, ethics committee approval is not required for register studies. The following registries were used: the Civil Registration System, which holds information on patient date of birth, sex and vital status (13); the National Patient Registry, which holds information on all inpatient and outpatient visits to Danish hospitals since 1978, with diagnoses according to the International Classification of Diseases (ICD) (prior to 1994, according to the 8 th revision (ICD-8) and thereafter the 10 th re- vision (ICD-10)) (14), which was used to identify patients with scleroderma and to obtain information on comorbidity; and the Registry of Medicinal Product Statistics, which holds informa- tion on all prescription claims since 1995 (15). All drugs are classified according to the Anatomical Therapeutical Chemical (ATC) classification. Pharmacies in Denmark are required to register all dispensed prescriptions. Data on death (16), comorbidity, concomitant medication and socioeconomic status (17) were linked at the individual level. The study population comprised all Danish citizens ≥ 18 and ≤ 100 years of age from 1 January 1997 to 31 December 2011. All residents in Denmark have a 10-digit personal identification number, which is th e same throughout all national registries, and hence register linkage is possible. Patients with a diagnosis of LS were identified by ICD-10: DL940 localized scleroderma, DL940B sclerodermia circum­ scripta or DL941 scleroderma lineare, and patients with SSc by ICD-10: DM340 progressive systemic scleroderma, DM348 other forms of systemic scleroderma, DM348B systemic scleroderma with acrosclerosis or DM349 systemic sclerosis unspecified. It was decided not to include patients with DM342 systemic scleroderma caused by drugs or chemicals, DL903 Pasini-Pierinis atropho- derma, and DM341 CREST syndrome because of discrepancies in how these codes were used. Patients with a history of CVD prior to the beginning of the study were excluded. Medical treatment and co-morbidity The baseline (up to 6 months prior to inclusion) pharmacological treatment was identified by patient prescriptions (from the Danish This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340/00015555-2842 Acta Derm Venereol 2018; 98: 361–365