Acta Dermato-Venereologica 99-7CompleteContent | Page 28

SHORT COMMUNICATION 705 Increased Risk of Cardiovascular Diseases in Female Rosacea Patients: A Nested Case-control Study Suvi-Päivikki SINIKUMPU 1,2 , Jari JOKELAINEN 3 , Juha AUVINEN 3,4 , Katri PUUKKA 5,6 , Kari KAIKKONEN 7 , Kaisa TASANEN 1,2 * and Laura HUILAJA 1,2 1 PEDEGO Research Unit, University of Oulu, 2 Department of Dermatology and Medical Research Center Oulu, Oulu University Hospital P.O. Box 20, FIN-90029 Oulu, 3 Center for Life Course Health Research, Faculty of Medicine, University of Oulu and Oulu University Hospital, Oulu, 4 Oulunkaari Health Center, Ii, 5 NordLab Oulu, Medical Research Center Oulu, Oulu University Hospital, 6 Department of Clinical Chemistry, University of Oulu, and 7 Deparment of Cardiology, Medical Research Center Oulu, University and University Hospital of Oulu, Oulu, Finland. *E-mail: [email protected] Accepted Mar 8, 2019; E-published Mar 8, 2019 Rosacea is a chronic inflammatory disease with a preva- lence varying between 1 and 20% and is the highest in fair-skinned Europeans (1). The appearance of rosacea differs between the sexes; there is a female predominance and the onset of the disease is earlier in females than in males (1). Of the 4 subtypes of rosacea (erythematote- leangiectatic, papulopustular, ocular and phymatotic) the erythematoteleangiectatic type is more common in females and the phymatous type in males (2). There is a rising consensus that rosacea is not only limited to the skin but is a chronic systemic inflammatory disease. Several systemic diseases have recently been shown to be associated with rosacea (3). However, it is disputed whether rosacea is associated with cardiovascu- lar (CV) diseases. The risk for comorbidities in rosacea has also been suggested to differ between sexes. Egeberg et al. found that rosacea is associated with type 1 diabetes, celiac disease, multiple sclerosis and rheumatoid arthritis particularly in females (4). The aim of this study was to clarify the CV risk factors in rosacea patients by comprehensively studying the CV risk profile of middle-aged patients with rosacea. PATIENTS AND METHODS This was a nested case-control study of the Northern Finland Birth Cohort 1966 (NFBC1966). NFBC1966 is a longitudinal research program, which initially included 12,058 children, in the two northernmost provinces in Finland, whose expected dates of birth were between 1 st of January and 31 st of December 1966. The whole cohort population has been regularly evaluated, since birth, by the means of health questionnaires and clinical examinations. At the age of 46 years the cohort subjects were invited to parti- cipate in a multidisciplinary health study, which included a full dermatological examination. A dermatologist or an experienced resident performed the examination. All skin diseases, including rosacea, were documented (5). Evaluable data were available for 1,932 cohort members in the Oulu area; 292 of which had been diagnosed with rosacea. The majority of them presented with erythematoteleangiectatic rosa- cea (n = 242, 82.9%), while 45 cases (15.4%) had papulopustular rosacea. Three cases (1.0%) had symptoms of phymatous rosacea and one case (0.3%) had ocular rosacea. Each case was matched to two control subjects by body mass index (BMI) and tobacco use. Controls were free from both rosacea and other skin diseases and presented only with benign melanocytic naevi. (Table SI 1 ) Cardio- https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3167 1 vascular risk factors were comprehensively studied in all subjects and the carotid intima-media thickness (CIMT) was assessed by a cardiologist. All methods are described in detail in Appendix S1 1 . The characteristics of the study population are presented as proportions, means and medians. The Mann-Whitney U-test and Person’s Chi-square test were used to compare the distribution of cardiovascular risk factors in rosacea cases and controls. Statis- tical analyses were performed using the SAS software package (version 9.4, SAS Institute, Inc, Cary, NC) and a p-value < 0.05 was considered statistically significant. Confounders Socioeconomic status (SES) was based on the education level, which has been defined as the most specific indicator of the socioeconomic status. The cohort members were classified into 3 subgroups based on education. Data concerning education were obtained from the National Education Register and were supplemented by self-reported questionnaires, regarding perso- nal educational history. Study participants were classified into 4 groups according to the body mass index (BMI) (Table SI 1 ). The information on smoking, physical activity, alcohol consumption and skin type was self-reported (5). RESULTS We found that the mean CIMT was significantly greater in the rosacea group than in controls, as were levels of insulin and serum free testosterone. The free androgen index was significantly higher in female rosacea patients. Other cardiovascular risk factors did not differ between the female groups (Table SII 1 ). None of the studied risk factors were associated with rosacea in male patients (data not shown). DISCUSSION We found that females with rosacea had increased CIMT when compared with the controls. CIMT has been con- sidered as a surrogate marker of atherosclerosis and an early stage of hidden systemic inflammation (6). An in- creased CIMT is associated with several CV risk factors and with prevalent CV diseases, such as stroke (6). Our finding supports the previous finding of Belli et al. who first reported the relationship between rosacea and CIMT (7). However, the association has not been previously studied by sexes. Our female study cases with rosacea had increased testosterone and insulin levels. High testos- terone levels correlate with the degree of atherosclerosis This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3167 Acta Derm Venereol 2019; 99: 705–706