Acta Cardiol 2010; 65(3): 337-340
doi: 10.2143/AC.65.3.2050351
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REVIEW ARTICLE
Psoriasis and cardiovascular diseases
Enrico VIZZARDI, MD; Riccardo RADDEVO, MD; Melissa TELI, MD; Elio GORGA, MD; Giulio BRAMBILLA, MD; Livio DEI CAS, PhD Dept. of Cardiology, University of Brescia, Italy. Psoriasis is a chronic Immune-mediated disorder that affects about 2% to 3% of the adult population. Several reports have demonstrated an association between psoriasis and cardiovascular diseases such as myocardial infarction, hypertension, valvular disease and arrhythmia. In this reviev\^ we analysed the link between psoriasis and cardiovascular disease and the possible physiopathologic mechanism of this correlation. Keywords: Psoriasis - cardiovascular disease.
Psoriasis is a chronic immune-mediated disorder that affects about 2% to 3% of the adult population'"2. Approximately 6% to 11% of patients with psoriasis also have an associated inflammatory arthropathy (psoriatic arthritis)^"''. Psoriasis is a chronic inflammatory disease characterized by a combination of genetic and environmental factors. The immune system has a main role in the development of psoriasis. Several subsets of T lymphocytes are involved in the pathogenesis and different cytokines and chemokines have been identified in tissue lesions. The pathophysiology is characterized by an increase in antigen presentation, T-cell activation, and T-helper cell type 1 ( T H O cytokines^"^. Psoriasis is also associated with markers of systemic inflammation, such as increased C-reactive protein levels^"^. Several reports have demonstrated an association between psoriasis and cardiovascular diseases such as myocardial infarction, hypertension, valvular diseases and arrhythmia. Previous studies suggest that patients hospitalized for psoriasis have an increased frequency of cardiovascular events. Limited populationbased data exist on this association, and few studies have determined which factors are independently associated with psoriasis. The role of conventional cardiovascular risk factors in psoriasis is particularly relevant because patients affected by psoriasis have a higher prevalence of hyper-
Address for correspondence: Dr. Enrico Vizzardi, Chair of Cardiology, University of Brescia, Pzzle Spedali civili 1, 25128 Brescia, Italy. E-mail:
[email protected] Received 5 November 2009; revision accepted for publication 5 April 2010.
tension, insulin resistance, diabetes mellitus, smoking, lipid abnormalities and obesity. Patients with psoriasis are often affected by hypertension, a possible adverse effect of therapy (for example cyclosporine) or related to obesity. Obesity is also associated with a state of chronic infiatnmation and infiammatory markers, such as C-reactive protein and fibrinogen, have been associated with elevated cardiovascular risk"'"'^. Psoriasis is also associated with abnormalities in the lipid profile and loss of balance in the relation oxidants/antioxidants. It is unclear whether the adverse lipid changes are connected to an infiammatory systemic state or related to medical therapy. Patients with psoriasis have a high prevalence of insuline resistance or diabetes mellitus, but the involved mechanism is yet unclear. Neiman et al. realized a study'^ about the prevalence of cardiovascular risk factors in patients with psoriasis. It is shown that patients with mild and severe psoriasis were more likely to be current smokers and have diabetes, hypertension, hyperlipidaemia, and increased BMI compared with control subjects. Patients with mild psoriasis had increased probability of having each of the cardiovascular risk factors that persisted when adjusting for age, gender and person-years. The results of this study suggest that diabetes, hypertension, hyperlipidaemia, smoking, and increased BMI are associated with both mild and severe psoriasis. Another recent study published by Mehta et al.''* confirmed that patients with severe psoriasis have an increased risk of cardiovascular mortality independent of traditional cardiovascular risk factors. A recent study realized by Kaye and Jick'^ demonstrated increased incidence of diabetes, hypertension, obesity and hyperlipidaemia.
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Patients with psoriasis also had a higher risk of myocardial infarction (HR 1.21; 95% CI 1.10-1.32), angina (HR 1.20; 95% CI 1.12-1.29), atherosclerosis (HR 1.28; 95% CI 1.10-1.48), peripheral vascular disease (HR 1.29; 95% CI 1.13-1.47) and stroke (HR 1.12; 95% CI 1.00-1.25). Gelfand et al.'^ have observed that patients with psoriasis had an increased adjusted relative risk (RR) for myocardial infarction (MI) that varied by age. For example, for a 30-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.29 (95% CI, 1.14-1.46) and 3.10 (95% CI, 1.984.86), respectively. For a 60-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.08 (95% CI, 1.03-1.13) and 1.36 (95% CI, 1.131.64), respectively. Psoriasis therefore may act as an independent risk of MI. The risk of MI associated with psoriasis is greatest in young patients with severe psoriasis, is attenuated with age, and remains increased even after controlling for traditional cardiovascular risk factors. The findings demonstrate a dose-response effect, because patients classified as severe had a higher risk of MI than patients with mild psoriasis, consistent with the hypothesis that greater immune activity in psoriasis is related to a higher risk of MI. The reason for the higher risk ratio of MI in younger patients with psoriasis is unclear. Probably persons with an earlier onset of the disease (before age 40) have a more severe grade of disease and a stronger association with htiman leukocyte antigen (HLA)-Cw6 than patients with onset of psoriasis occurring after the age of 40years'^"'^. A recent Chinese study, conduced by Xiao et al., confirmed the positive correlation between psoriasis and severity of Ml'^. Psoriasis is also correlated to increased incidence of arrhythmia, in particular of atrialfibrillation(AF). Several studies have demonstrated the possible implication of inflammation and oxidative stress in the pathogenesis of AF^"'^^. These studies have also shown that increased baseline levels of inflammatory markers such as CRP are associated with a greater risk for immediate failure of electrical cardioversion and AF recurrence after successful electrical cardioversion. CRP tends to be more elevated in patients with severe psoriasis complicated with obesity and diabetes mellitus. Markuszeski and colleagues^^ have shown that heart rate was significantly higher both during the day and at night in patients with psoriasis than in the control group. There was a positive correlation between the increased heart rate and severity of the disease. Single supraventricular beats were significantly more frequently observed in psoriatic patients than in the control group. There is no direct evidence for an association between psoriasis and AF and the underlying physiopathologic mechanism is not clear. Probably the inflammatory state related with psoriasis might contribute to the development of AF.
Gunes et al.^^ have realized a study about increased frequency of pulmonary hypertension in psoriasis patients. They demonstrated that mild pulmonary hypertension (30-40 mmHg) occurred significantly more frequently in psoriasis patients than in the control group. A recent issue performed by Nijsten and Wakkee^^ questions the association between psoriasis and comorbidities. Researchers consider several factors that may play important roles and confound this association. First, psoriasis has a significant impact on a patient's quality of life and is associated with depressive symptoms in a large proportion of patients. Impaired health-related quality of life may lead to unhealthy lifestyle behaviour such as smoking, alcohol consumption, decreased physical activity, which are themselves independent cardiovascular risk factors. In addition psoriasis therapies may increase the risk of several co-morbidities. Secondly, Nijsten and Wakkee suggest that psoriasis patients are more likely to visit physicians than the general population; therefore they are more likely to undergo screening for other diseases. This detection bias is especially important in the diagnosis of common diseases that are typically underdiagnosed, such as hypertension. At last, researchers assert that the detection of associations between psoriasis and co-morbidities is challenging because it has required the use of existing databases that were not designed for this purpose. The limitation of these large datasets is that they usually have incomplete information about important confounders. Another recent study by Schmitt and Ford^' on a population-based case-control study of 3147 pairs of patients with psoriasis and age- and gender-matched control subjects has investigated the complex association between psoriasis and cardiovascular risk factors and myocardial infarction. This study replicated the previously reported positive association between psoriasis and major cardiovascular risk factors such as hypertension, diabetes, obesity and dyslipidaemia. According to this study, there is no statistically significant correlation between psoriasis and myocardial infarction (OR 1.14; CI 95% 0.81-1.62). According to literature data we can conclude that the association between psoriasis and co-morbidities in particular cardiovascular disease is very complex and not clear. The trend in scientific literature has been to upgrade psoriasis from a cutaneous to a systemic disease. Therefore, a multidisciplinary management of the psoriasis patient is very important. Different specialists should learn to cooperate to ensure the best treatment for the patient. For this reason psoriasis patients could be evaluated in a multidisciplinary management. Not all the patients with psoriasis have to undergo screening tests, but every single patient should be evaluated, considering the specific risk factors and co-morbidities. It should
Psoriasis and the heart be kept in mind that patients with moderate to severe psoriasis seem to be at higher risk for cardiovascular disease than patients with mild disease'*. These patients or patients with concomitant psoriasis and multiple cardiovascular risk factors or symptoms/signs of cardiovascular disease should be sent to the cardiologist. The role of the inflammatory mechanisms on the pathogenesis are known and several studies indicate that these patients should know the possible link between psoriasis and coronary artery disease (CAD). The cardiologist and dermatologist should have more attention for these patients. They should assess patients with moderate to severe psoriasis for their risk factors for CAD and prescribe appropriate lifestyle and pharmacologie therapies for patients with psoriasis who are at increased risk for CAD. The physicians should treat more aggressively the cardiovascular risk factors (obesity, smoking, dyslipidaemia, hypertension, diabetes mellitus, hyperhomocysteinaemia) in patients with moderate to severe psoriasis. There are no studies that have determined whether patients with psoriasis with cardiovascular disease should be treated differently from the general population. In these patients the cardiologist can prescribe beta-blockers, angiotensinconverting enzyme inhibitors and angiotensin receptor blockers but the patients should be monitored for worsening of the psoriasis. Besides, dermatologists can prescribe ultraviolet treatment or medical therapy for psoriasis without regard to cardiovascular risk. Only anti-TNF a drugs should be used with caution in patients with congestive heart failure. New randomized studies are indispensable to determine which is the best management for the cardiovascular risk. A more aggressive treatment of psoriasis may reduce the infiammatory burden of these patients and then decrease long-term risk of developing comorbidities including cardiovascular disease. Conflict of interest: none declared.
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