ABC | Volume 113, Nº2, August 2019

Original Article Oliveira et al Cardiovascular risk in psoriasis patients Arq Bras Cardiol. 2019; 113(2):242-249 The echocardiographist could not be blinded to psoriasis, since skin manifestations of the disease are clinically evident. Statistical analysis Categorical variables were expressed as counts and percentages. Numerical variables were tested for normality by the Shapiro-Wilk test and expressed as mean ± standard deviation (SD) (normally distributed variables) or median and interquartile range (variables without normal distribution). Association between categorical variables was assessed by Fisher’s exact test or the chi-square test of independence. Between-group comparisons of numerical variables were performed by the Student’s t-test or the Wilcoxon Mann- Whitney test, according to the normality of data distribution. The analysis was performed using the R software, version 3.3.2 and a 5% significance level was used. Mean differences of AS between PG and CG were estimated, and the sample size was calculated to test the difference between two means. For calculation of the sample size, we assumed that the variance of the AS measurements in PG and CG would be the same. In addition, we used a ratio of three controls to one psoriatic patient, due to the difficulty in identifying patients with moderate or severe psoriasis (PASI ≥ 7), not using corticosteroids, considering a significance level of α = 5% and power (1 –  β ) of 80%. Results The study sample was composed of 44 subjects, 11 of the PG and 33 of the CG. Mean age was 60.5 ± 11.3 years and 59.1% was white. Mean values of BSA, BMI and WHR were 1.93 ± 0.20 m 2 , 28.1 ± 5.2 kg/m 2 and 0.96 ± 0.06, respectively. Age was not different between the groups (Table 1). Regarding lifestyle and comorbidities, 29.5% of participants consumed alcohol, 29.5% were smokers, 40.9% had systemic arterial hypertension, 20.5% had diabetes and 29.5% dyslipidemia, with no difference between the groups. With respect to laboratory tests, PG showed higher levels of TC, LDL cholesterol, and C-reactive protein (p < 0.01) (Table 1). The most common medication in the study group was angiotensin II receptor blockers (29.5%), statins (22.7%) and diuretics (18.2%), with no difference between the groups (data not shown). For the psoriasis treatment, two patients (18%) of the PG used methotrexate. Only one patient of the PG (9%) used topical corticosteroids regularly for the skin lesions during the study period. PG patients showed increased PWV (9.1 ± 1.8 and 8 ± 2 m/s, p = 0.033), increased IMT of the left common carotid artery (p = 0.018) and higher percentage of patients above the 75 th percentile according to the ELSA table (54.5 and 18.2%, p = 0,045) when compared with the CG. Compared with the CG, the PG also showed increased peripheral SBP (137.1 ± 13.2 vs . 122.3 ± 11.6 mmHg, p = 0.004), central SBP (127 ± 13 vs . 112.5 ± 10.4 mmHg, p = 0.005), peripheral DBP (89.9 ± 8.9 vs . 82.2 ± 8 mmHg, p = 0.022), central DBP (91 ± 9.3 vs . 82.2 ± 8.3 mmHg, p=0.014), total cholesterol (252±43.5 vs . 198±39.8mg/dL , p < 0.001), LDL cholesterol (167 ± 24 vs . 118 ± 40.8 mg/dL , p < 0.001) and C-reactive protein (7.6 ± 35.4 vs . 1 ± 1.2 mg/L , p < 0,001). There was no difference in AIx@75 between the groups (Table 2). Discussion Psoriasis has been considered an autoimmune, inflammatory disease with important consequences in other systems. 5,6,8 There are evidences of higher incidence of obesity, diabetes mellitus, arterial hypertension and CVDs – such as acute myocardial infarction and stroke among psoriatic patients. 30,31 Thus, skin manifestations seem to be just one of the factors associated with this complex condition. It has been speculated that the high amounts of blood inflammatory mediators in psoriatics, in addition to C-reactive protein, such as TNFa and IL-6 may be associated with the inflammatory response to vascular remodeling and cardiovascular changes. 31,32 In the present study, we included psoriasis patients with PASI>7, i.e ., with moderate and severe psoriasis. High C-reactive protein levels found in PG compared with the CG suggests increased inflammatory response, which was associated with higher blood pressure and LDL-cholesterol levels, may contribute to arterial remodeling, as well as to structural and hemodynamic changes observed in these patients. 7,10 Coban et al. 33 showed that systemic inflammation in psoriasis leads to insulin resistance, which, in turn, causes changes in the synthesis of adipokines, including visfatin, vaspin, omentin and adiponectin, which can increase blood pressure, and LDL-cholesterol and TC levels. 33 In the pathogenesis of atherosclerosis, factors like an altered lipid metabolism, and inappropriate immune response are involved, resulting in arterial wall inflammation. The increased levels of circulating inflammatory mediators contribute to vascular inflammatory response associated with migration of monocytes and oxidation of LDL-cholesterol, which are key elements in the formation of atherosclerotic plaque. 31,32 However, there are also reports describing the so-called “lipid paradox” in inflammatory diseases, mainly rheumatoid arthritis, marked by a significant decrease in LDL-cholesterol and TC levels 3-5 years before the onset of signs of the disease. 34,35 There also evidences of possible influence of pharmacological interventions on lipid profile of these patients. 36 In our study, despite considerable impairment observed in psoriatic patients, this group showed significant increase in atherogenic lipoprotein levels compared with the CG. Only two (18%) patients used systemic medication, particularly methotrexate. None of the patients used biological drugs. The use of systemic corticosteroids was an exclusion criterion to avoid a bias in the findings. A systematic review evaluated the metabolic effects of methotrexate in patients with rheumatoid arthritis; 37 while one study reported differences in lipid profile after one year of treatment, another study reported improvement in lipid concentrations, and their correlation with changes in C-reactive protein levels and blood sedimentation rate, and another study did not find any change in the levels of 244