Psoriasis is a chronic genetic-based inflammatory disease characterized by lesions that primarily affect the skin, although it may have systemic effects. The disease affects up to 3% of the population worldwide and tends to appear similarly in both sexes.¹ The onset of symptoms can occur at any age, but the disease is less common in children than adults.²

The inflammation in psoriasis may promote effects on the cardiac conduction system. Additionally, studies demonstrate that patients with this disease have a significantly higher prevalence of cardiovascular risk factors, including hypertension, diabetes mellitus, and hyperlipidemia.³ Cardiovascular disease is the most common cause of morbidity and mortality in patients with psoriasis.⁴ Studies have also reported that psoriasis is related to abnormal autonomic function, ventricular repolarization impairment, and arrhythmias (both atrial and ventricular).^5-8

Previous research demonstrated that transmural dispersion of repolarization plays a significant role in arrhythmogenesis. The QT dispersion (QTdis), the corrected QT dispersion (Qtdisc), the peak-to-end interval of the T wave (Tp -e), the Tp-e/QT ratio, and the corrected Tp-e/QT ratio (Tp-e/QTc) have been accepted as new electrocardiographic markers for the assessment of ventricular repolarization and arrhythmogenesis. The increase in these markers reflects a predisposition to ventricular arrhythmias and a risk of sudden cardiac death.⁹ These intervals can be prolonged in psoriasis due to increased inflammation, which suggests the tendency of the myocardium to rhythm disturbances, as previously demonstrated in smaller sample studies.^10-12

The present study aimed to investigate new electrocardiographic markers to assess ventricular repolarization in outpatients with psoriasis from a tertiary care center in Brazil.

This was an observational cross-sectional study. The study population consisted of 65 adult patients (≥18 years old) with long-term psoriasis (at least two years of diagnosis), severe disease, characterized by a Psoriasis Area and Severity Index (PASI) score of at least 10 points at the moment of outpatient admission, and requiring systemic treatment. Patients underwent follow-up at the dermatology outpatient clinic at the Hospital Universitário de Santa Maria, between May and December 2018. This is a university hospital in the city of Santa Maria, RS, Brazil, which is a reference for psoriasis care for a population of approximately 500,000 inhabitants. The control group (CG) consisted of a sample of 65 adult (≥ 18 years old), without psoriasis or any other inflammatory systemic diseases, who had periodically undergone follow-up (at least annually) in a primary outpatient clinic for periodic cardiovascular health control. The CG was selected from a primary cardiovascular outpatient clinic in the private health system. The selection strategy was based on simple random sampling of a list of 2,000 patients who had been evaluated at the cardiovascular outpatient clinic since 2013. The diagnosis of psoriasis was made by two dermatologists certified by the Brazilian Society of Dermatology (LPV and RMLC ), based on a clinical or histopathological examination of all patients. To determine the level of systemic inflammation at the moment of the evaluation, levels of the C-reactive protein (CRP) testing were determined, using the immunoturbidimetric method. The exclusion criteria for both cases and controls included individuals with coronary artery disease, heart failure, moderate or severe valvular disease, any documented arrhythmogenic disease (including atrial fibrillation and ventricular arrhythmias), the presence of conduction disturbances (including those who had pacemakers), and bundle branch block. Those individuals with inflammatory diseases (other than psoriasis), active infections, neoplasm (diagnosis or suspected), and electrocardiograms (ECGs) with artifacts or no clearly analyzable QT segment were also excluded from the present study. All individuals had at least one provocative test that was negative for ischemic heart disease and one echocardiographic test showing normal left ventricular function without signs of segmental dysfunction.

The present study was approved by the local Research Ethics Committee.

The main results are presented in the Central Illustration. A total of 130 individuals were evaluated, with a mean age of 53.1±15.1 years (range 18 to 90 years), most males (50.8%). There were 65 cases of psoriasis and 65 controls. The mean age of individuals with psoriasis was lower than that of those without psoriasis (P= 0.003). Despite the absence of cardiovascular disease in all patients, the cardiovascular risk (determined by Atherosclerotic Cardiovascular Disease Atherosclerotic Cardiovascular Disease [ASCVD] risk assessment of the American College of Cardiology).²⁰ showed an elevated risk of cardiovascular diseases in both samples of patients with psoriasis and the CG. There was also a high proportion of diagnosis of hypertension in the CG when compared to the psoriasis group (PG). Additionally, the proportion of active smokers among those with psoriasis was significantly higher than the individuals in the CG. The detailed characteristics of the groups are described in Table 1.

Table 1

Population = 130	CASES	CONTROLS	P
Number (N)	65	65
Malea	32 (49.2%)	34 (52.3%)	0.726
Age (years)	49.2±14.2	57.07±15.1	0.003
CRP (mg/dl)b	0.97±2.06	0.75±1.42*	0.752
ASCVD Riskb (10-years risk)	10.7±11.55	12.01±12.17	0.606
Lifetime ASCVDb	43.63±15.49	44.41±13.45	0.817
Smokera	19(29,2%)	3(4,6%)	0.05
Diabetes Mellitusa	12(18.5%)	6(9,2%)	0.203
Hypertensiona	20(30.8%)	39(60%)	0.01
Cholesterolb (mg/dL)	196.62±35.9	195.82±38.6	0.905
HDLb (mg/dL)	49.86±14.2	53.08±11.4	0.163
LDLb (mg/dL)	121.15±33.2	112.88±31.2	0.157
Systolic blood pressureb (mmHg)	129.18±18.2	135.25±18.4	0.062
Diastolic blood pressureb (mmHg)	81.43±12.2	83.77±10.9	0.253

a: Absolute value; b: Mean and standard deviation; * Control group: in 10 patients PCR was used in the other hsPCR. hsPCR: high-sensitive C-reactive Protein; ASCVD: 10-year Atherosclerotic Cardiovascular Disease Risk from the American College of Cardiology; Lifetime ASCVD: lifetime Atherosclerotic Cardiovascular Disease Risk from the American College of Cardiology; mg/dL: milligrams per deciliter; mmHg: millimiters of mercury; HDL: high-density lipoprotein; LDL: low-density lipoprotein; CRP: C-reactive protein.

Psoriasis is a chronic inflammatory disorder that affects both the skin and the cardiovascular system. This disease tends to show higher mortality rate, mainly because of cardiovascular diseases.²¹ Inflammation plays a significant role in the pathogenesis of psoriasis. Several studies have also suggested that there is a link between arrhythmias and chronic inflammation.^22,23 This can be corroborated by the fact that some systemic inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, are associated with a higher incidence of atrial and ventricular arrhythmias.^24-26

The present study showed that some ventricular repolarization features were shorter in psoriatic patients when compared to the controls (Qtdisc, Tp-e and Tp-e/QTc). Moreover, no relevant correlation was found between psoriatic activity (measured by PASI score or CRP) and repolarization parameters. These findings were surprising and somehow contrary to the current biological and clinical evidence so far available.^10,27 For example, Arisoy et al. observed impaired repolarization parameters in patients with psoriasis when compared to controls. This finding was reflected in higher values of QTc, Qtdis, Tp-e, and Tp-e/QT in patients with the disease.¹⁰ Despite a median PASI score of 8.7, most of the repolarization parameters in psoriasis were higher in the study of Arisoy et al. than those in our study.¹⁰ Additionally, Ozluk et al. demonstrated mean QTc values of 415.1±22 ms in patients with psoriasis, which is slightly higher than the mean values of 411.2±21.2 ms observed in the present study.²⁷ Such factors highlight a different profile of psoriatic patients in our study, which consisted of a population with a long-term diagnosis and severe systemic disease.

The present study also failed to observe any clinically relevant correlation between PASI scores or CRP levels and ventricular repolarization values. However, a statistically significant correlation was identified between CRP and Qtdisc. However, this correlation was weak and of negligible clinical relevance. Such findings also differ from the study conducted by Arisoy et al., who observed that CRP was an independent predictor of the Tp-e/QT ratio.¹⁰

Several factors may explain the differences between the present study and the observed publications. There was a significant difference of age between groups, with a significantly higher mean age in the CG. Despite the absence of clinical cardiovascular disease, it is possible that subclinical atherosclerotic disease may have influenced the repolarization parameters. It is also important to mention that, despite a negative screening for coronary artery disease in our population, a substantial risk for cardiovascular diseases must be addressed. This was observed by a high 10-year ASCVD risk calculated in both cases and controls, a factor that could impact the repolarization parameters.^28,29

Additional limitations should be stressed in the present study. First, due to the cross-sectional design, it is difficult to derive casual relationships. At the same time, because individuals were not followed prospectively, it was not possible to determine whether or not repolarization parameters actually predict ventricular arrhythmias in the population with psoriasis. Second, our CG was not age-matched with cases, and there were significant differences in comorbidities and risk factors between case and CGs (such as hypertension and smoking). These factors may have influenced repolarization parameters. Third, the sample size was small, and the repolarization differences may well be related to statistical error.

The evaluation of ventricular repolarization parameters in a sample of outpatients with psoriasis in southern Brazil showed that ventricular repolarization values were lower than the controls. In addition, it was not possible to relate disease activity with ventricular repolarization parameters. Further studies with larger sample sizes and prospective designs are needed to elucidate the above results.