Coronary artery events in Thai patients with psoriasis using Framingham and Ramathibodi–Electricity Generating Authority of Thailand risk scores

Ethics approval of this retrospective cohort study was obtained on 27^th February 2014 from the Siriraj Institutional Review Board, Siriraj Hospital, Mahidol University (Si 118/2014). Psoriasis patients aged ≥18 years who attended the Dermatology Clinic, Siriraj Hospital, between 2013 and 2014, were included. Patients were excluded if they had a history of peripheral vascular diseases or past cardiovascular events, including myocardial infarction or stroke. Patients with secondary hyperlipidemia because of medical conditions, such as nephrotic syndrome, hypothyroidism, obstructive liver diseases, and connective tissue diseases, were also excluded.

A history of psoriasis, smoking status, alcohol use, psoriasis treatment, and other medical conditions, such as diabetes mellitus (DM), dyslipidemia, and hypertension were recorded within 3-month follow-up visits using a questionnaire that was administered by a physician. Data regarding body mass index (BMI), waist circumference, blood pressure, severity of psoriasis, and blood chemistry were collected at the time point closest to or within a 6-month period before administration of the questionnaire. Waist circumference was measured at the midpoint between the lower costal margin and iliac crest. Obesity was defined as a BMI ≥25 kg/m² [6]. Severity of psoriasis was determined using the Psoriasis Area and Severity Index (PASI) score.

Two risk equations were used to predict the 10-year risk of CAD. The FRS was applied in patients aged 20–79 years. The FRS parameters include sex, age, total cholesterol, current smoking status, high density lipoprotein (HDL), and systolic blood pressure (including treated or untreated status). Those scoring less than 10% are at low risk, those scoring between 10% and 20% have a moderate risk, and those scoring 20% or more are at high risk [7, 8]. As the attributable risk of severe psoriasis (PASI ≥10) would increase yearly coronary artery events by an adjusted hazard ratio, an estimated value of 6.2% was added to the FRS in patients who had severe psoriasis, following recommendations by Mehta et al. [9].

The RAMA-EGAT score includes age, blood pressure, waist circumference, total cholesterol, HDL, DM, and current smoking, and alcohol consumption status. The RAMA-EGAT score stratifies patients into three risk categories: low (<10%), intermediate (10%-20%), and high (>20%). This cut-off was chosen based on the recommendations of the Adult Treatment Panel III (ATPIII) to determine goals for lipid-lowering therapy [3, 8].

The Statistical Package for the Social Sciences, version 18 (SPSS, Chicago, IL, USA) was used for analysis. Descriptive statistics, such as number, percentage, and mean ± standard deviation (SD), were used to describe demographic data and different risk categories according to different risk equations. A chi-square test, unpaired t test, and logistic regression were used to analyze the predictive factors that contributed to intermediate to high risk (≥10%) of CAD events. The variables that had P < 0.20 by univariate analysis or interested variables were selected to analyze for multivariate analysis. Statistical significance was set as a P < 0.05 for univariate and multivariate analysis.

A total of 145 patients with psoriasis (72 men and 73 women; mean age, 48.1 ± 14.1 years) were included. Demographic data of the patients are shown in Table 1. At the time of the study, 64% of the patients commenced systemic treatment and 65% had mild disease (PASI <10). The most common underlying disease was obesity, followed by hypertension, dyslipidemia, and DM, respectively.

The FRS and RAMA-EGAT equation score were calculated for 145 patients. On the basis of FRS, 21% and 4% had an intermediate (10%-20%) and high risk (>20%) of developing CAD events within 10 years, compared with 12% and 1% of patients according to the RAMA-EGAT score, respectively. Using the FRS with and without an attributable risk of psoriasis, 7% and 4% of the patients, respectively, had a high risk of developing CAD events within 10 years (Table 2).

In univariate analysis, duration of disease and type of treatment had significant association with intermediate-to-high CAD risk using FRS, whereas only duration of disease influenced CAD risk of ≥10% by RAMA-EGAT. However, the multivariate analysis for both scores showed that duration of disease and treatment were significantly associated with an increased risk of CAD (Tables 3and 4).

CAD is worldwide health problem, including in developing countries. Major cardiovascular risk factors include obesity, hypertension, hyperlipidemia, and DM. A national health survey in 21,960 Thais in 2009 (aged ≥15 years) showed that 30% of men and 40% of women were obese (BMI ≥25 kg/m²). The mean BMI values of 23.1 kg/m² in men and 24.4 kg/ m² in women in the 2009 survey are comparable to those in a previous survey in 2000 (5305 adults, aged ≥35 years, mean BMI of 23 kg/m² in men and 24.8 kg/m² in women) [10, 11]. A recent study suggested that psoriasis increases the risk of obesity and cardiovascular events [5]. Our study showed that there was a higher percentage of obesity in patients with psoriasis (59%) than in average Thais, and that the mean BMI value of these patients was 26.4 kg/m². The common comorbid diseases in our patients were obesity, hypertension, dyslipidemia, and DM. These may emphasize the greater risk of Thai patients with psoriasis developing CAD events compared with the general population.

The application of FRS and RAMA-EGAT score to other populations with different background risk of CAD remains questionable. Both scores have been validated in 785 HIV-infected Thai patients [12]. The study showed that the prevalence of 10-year risk of CAD ≥10% in HIV-infected Thai patients was 9.9% and 2.1% by FRS and RAMA-EGAT score respectively. However, it seemed that FRS probably overestimated risk of CAD in HIV-infected Thai patients because RAMA-EGAT score demonstrated better agreement with the D:A:D risk equation (Data Collection on Adverse Effects of Anti-HIV Drugs) than FRS and D:A:D risk equations. The D:A:D risk equation was developed from a data set of 22,625 HIV-infected individuals in 20 countries across Europe and Australia [13]. Similarly, the FRS equation predicted a higher risk of CAD than the RAMA-EGAT equation especially when the risk of severe psoriasis was taken into account in our study. Observed events from long-term follow-up data are required to determine whether the FRS overestimated or the RAMA-EGAT score underestimated the 10-year risk of CAD in Thai patients with psoriasis. It should be noted that the prevalence of 10-year risk of CAD ≥10% of Thai patients with psoriasis in our study was higher than that of HIV-infected Thai patients by FRS and RAMA-EGAT score [12]. There are a limited number of studies regarding FRS in Asian patients with psoriasis. A previous study on the FRS in 159 Koreans with psoriasis showed that most of them were at low-to-intermediate risk of developing CAD, similar to the FRS of Thai patients in our study [14]. Previous studies using the FRS in patients with psoriasis from Brazil, Spain, Portugal, and the USA showed that 7%–18.6% of the patients were at high risk (>20%), while 4% of our patients, and 5.1% of Korean patients were at high risk (>20%) [15-19]. These studies suggest that Asian patients with psoriasis have a lower 10-year risk of CAD than white patients of European ancestry with psoriasis. Asian lifestyle, dietary habits, and genetic susceptibility may be other reasons for these different outcomes.

Previous studies from Spain (395 patients), Brazil (98 patients), and the USA (1591 patients) showed that the severity, duration, and treatment of psoriasis did not affect high cardiovascular risk scores using the FRS equation [15-17]. By contrast, our study showed that duration of disease and treatment had significant association with an increased CAD risk using multivariate analysis for both scores. The wide range of inflammatory cytokines in the long disease duration of psoriasis, such as tumor necrosis factor, interleukin-1 and interleukin-2 are probably risk factors for CAD in psoriasis patients [5]. Our study only included a relatively small number of patients compared with other studies, and estimation of CAD risk was investigated on the basis of risk equations instead of observed risk. More studies with a large number of psoriasis patients are warranted to determine predictive factors that contribute to high CAD risk in Asian populations.

In conclusion, Thai patients with psoriasis had several comorbid diseases that contributed to CAD events. A substantial portion of patients had intermediate-to-high risk of developing CAD events within 10-years using the FRS and RAMA-EGAT score. Early screening for CAD and appropriate treatments for psoriasis may be helpful to prevent CAD in psoriasis patients.