Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based case–control study

Authors

  • P. Gisondi,

    1. Section of Dermatology, Department of Biomedical and Surgical Science, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, I-37126 Verona, Italy Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
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  • G. Tessari,

    1. Section of Dermatology, Department of Biomedical and Surgical Science, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, I-37126 Verona, Italy Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
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  • A. Conti,

    1. Section of Dermatology, Department of Biomedical and Surgical Science, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, I-37126 Verona, Italy Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
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  • S. Piaserico,

    1. Department of Dermatology, University of Padua, Padua, Italy
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  • S. Schianchi,

    1. Section of Dermatology, Department of Biomedical and Surgical Science, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, I-37126 Verona, Italy Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
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  • A. Peserico,

    1. Department of Dermatology, University of Padua, Padua, Italy
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  • A. Giannetti,

    1. Section of Dermatology, Department of Biomedical and Surgical Science, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, I-37126 Verona, Italy Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
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  • G. Girolomoni

    1. Section of Dermatology, Department of Biomedical and Surgical Science, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, I-37126 Verona, Italy Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
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  • Conflicts of interest
    None declared.

Paolo Gisondi.
E-mail: paolo.gisondi@univr.it

Summary

Background  Psoriasis is a chronic inflammatory disease associated with an increased cardiovascular risk. Metabolic syndrome is a significant predictor of cardiovascular events.

Objective  To investigate the prevalence of metabolic syndrome in patients with psoriasis.

Methods  We performed a hospital-based case–control study on 338 adult patients with chronic plaque psoriasis and 334 patients with skin diseases other than psoriasis.

Results  Metabolic syndrome was significantly more common in psoriatic patients than in controls (30·1% vs. 20·6%, odds ratio 1·65, 95% confidence interval 1·16–2·35; P = 0·005) after the age of 40 years. Psoriatic patients also had a higher prevalence of hypertriglyceridaemia and abdominal obesity, whereas hyperglycaemia, arterial hypertension and high-density lipoprotein cholesterol plasma levels were similar. Although psoriasis patients were more frequently smokers, the association of psoriasis with metabolic syndrome was independent from smoking. There was no correlation between severity of psoriasis and prevalence of metabolic syndrome. Psoriatic patients with metabolic syndrome were older and had a longer disease duration compared with psoriatic patients without metabolic syndrome.

Conclusion  Psoriatic patients have a higher prevalence of metabolic syndrome, which can favour cardiovascular events. We suggest psoriatic patients should be encouraged to correct aggressively their modifiable cardiovascular risk factors.

Psoriasis is a chronic inflammatory skin disease that affects about 3% of the population.1,2 Psoriasis can be associated with other diseases, which may have a major impact on patients. The more common comorbidities include psoriatic arthritis and anxiety/depression disorder.3–5 More recently, psoriasis has also been reported to be associated with metabolic disorders including obesity, dyslipidaemia and diabetes.6–8 Moreover, an increased mortality from cardiovascular disease in patients with severe psoriasis has been documented, and psoriasis may confer an independent risk of myocardial infarction especially in young patients.9–11 Major factors that may contribute to this unfavourable cardiovascular risk profile include cigarette smoking, obesity, physical inactivity, hyperhomocysteinaemia and psychological stress, which have a higher prevalence among patients with psoriasis.12 In addition, many traditional systemic therapies for psoriasis may also worsen cardiovascular risk factors such as hyperlipidaemia, hypertension and hyperhomocysteinaemia.13

Metabolic syndrome is a cluster of risk factors including central obesity, atherogenic dyslipidaemia, hypertension and glucose intolerance, and is a strong predictor of cardiovascular diseases, diabetes and stroke.14–16 The importance of metabolic syndrome is that it may confer a cardiovascular risk higher than the individual components. Men with metabolic syndrome are almost three times more likely to die of coronary artery disease after adjustment for conventional cardiovascular risk factors.17 The aim of this study was to investigate the prevalence of metabolic syndrome in patients with psoriasis. The results indicate that psoriatic patients have a higher prevalence of metabolic syndrome. The association between psoriasis and metabolic syndrome is also true for mild severity psoriasis and it is independent from the tendency of psoriatic patients to be obese.

Materials and methods

Study population

This was a hospital-based case–control study involving a series of 338 psoriatic patients (cases) and 334 controls consecutively admitted to the outpatient clinics of three university hospitals in north Italy. Inclusion criteria for cases were age more than 18 years and clinical diagnosis of chronic plaque psoriasis (diagnosis of psoriasis lasting at least 6 months). Patients receiving any systemic treatment for psoriasis including acitretin, ciclosporin, methotrexate, phototherapy or biologics for at least 1 month before enrolment were not included in the study. Psoriatic arthritis (PsA) was diagnosed according to standard criteria.18 Controls were enrolled among patients referred for dermatological conditions other than psoriasis. The source population for cases and controls was the same. After signed informed consent, all subjects were visited by a dermatologist who registered demographic, biometric and the other relevant data on a case report form. Relevant data collected included age, gender, weight, height, body mass index (BMI), waist circumference, blood pressure, smoking habit, age of psoriasis onset, type and severity of psoriasis, presence and distribution of psoriatic arthropathy and concomitant medications. BMI was calculated as weight (kg)/height (cm2). To determine waist circumference, we located the upper hip bone and placed a measuring tape at the level of the uppermost part of the hipbone around the abdomen (ensuring that the tape measure was horizontal). The tape measure was snug but did not cause compressions on the skin. Blood pressure was recorded as the average of two measurements after subjects had been sitting for 5 min. Severity of psoriasis was assessed according to Psoriasis Area and Severity Index (PASI),19 body surface area (BSA) measurement and static Physician’s Global Assessment (PGA).20 Chronic plaque psoriasis was considered localized or disseminated when it covered less or more than 10% of the BSA. Metabolic syndrome was diagnosed in the presence of three or more criteria of the National Cholesterol Education Program’s Adult Panel III (ATP III): waist circumference > 102 cm in men or > 88 cm in women; hypertriglyceridaemia > 1·7 mmol L−1; high-density lipoprotein (HDL) cholesterol < 1·0 mmol L−1 in men or < 1·3 mmol L−1 in women; blood pressure > 135/85 mmHg; fasting plasma glucose > 6·1 mmol L−1.21 Venous samples were taken at the enrolment visit after the subjects had fasted overnight (at least 8 h). Serum cholesterol and triglycerides were measured with enzymatic procedures. Plasma glucose was measured using a glucose oxidase method.

Statistical analysis

Analysis was carried out using the STATA (version 6.0 Stata-Corp LP, College Station, TX, U.S.A.) and Graphpad (version 4.0 GraphPad Software, El Camino Real, San Diego, CA, U.S.A.) software packages. Standard descriptive statistics such as mean, standard deviation and prevalence proportion were computed. Associations between the presence of psoriasis and various covariates were tested by using the Fisher’s exact test for categorical variables and t-test for continuous variables. The proportion of patients with metabolic syndrome in cases was compared with that in controls stratifying data by sex and age according to the Mantel–Haenszel χ2 test. Linear correlation between covariates was analysed according to the Spearman test. To account simultaneously for the effect of age, sex and smoking habit unconditional multiple logistic regression was performed. All P-values are two-sided and < 0·05 was considered statistically significant. Sample size of the study population was determined as follows: prevalence of metabolic syndrome in the control group was expected to be about 20%,22 and we posited a prevalence difference of about 5% in patients with psoriasis. For α = 0·05 and 1 − β = 0·90, it was necessary to enrol at least 302 patients per group in order to guarantee the above-significance level and power.

Results

The study included 338 cases and 334 controls. Descriptive characteristics of the study population are reported in Table 1. There was no significant interhospital variability within the dataset collected. Moreover, the three hospitals contributed to the study with similar numbers of cases and controls. Patients had mild to severe psoriasis with a PASI score ranging from 1·3 to 60·2 with a median 7·9 [95% confidence interval (CI) 7·4–9·6]; 186 (57·3%) patients had a PASI score < 10, whereas 152 (42·7%) had a PASI score ≥ 10. BSA affected ranged from 1% to 95%, with a median of 10·6 (95% CI 14·9–19·1); 152 (45·3%) patients had a BSA < 10%, whereas 183 (54·7%) had a BSA ≥ 10%. Static PGA mean value was 3 (95% CI 2·8–3·0). Chronic plaque psoriasis was the more common clinical type accounting for 96·3% of cases. PsA was present in 71 patients (21%). Prevalence of dermatological diagnoses in the control group were as follows: 38·2% had melanoma and nonmelanoma skin cancers (mainly actinic keratosis and basal cell carcinoma), 24·9% eczema, 14·3% vitiligo, 12·9% infective skin diseases (mainly viral warts), 9·7% autoimmune bullous diseases (mainly bullous pemphigoid). Psoriatic patients had a higher mean BMI and were more frequently smokers compared with controls. We found a higher prevalence of metabolic syndrome in cases than in controls [30·1% vs. 20·6%, odds ratio (OR) 1·65, 95% CI 1·16–2·35; = 0·005] after controlling for sex and age. Multiple logistic regression analysis revealed that metabolic syndrome was associated with psoriasis independently of age and smoking habit. The higher prevalence of metabolic syndrome in psoriatic patients was confirmed in all age classes of 40 years and older (Fig. 1). Metabolic syndrome was present in 35·2% of patients with PsA (= 0·003). Prevalence of metabolic syndrome was not correlated to severity of psoriasis. In particular, there was no difference in the prevalence of metabolic syndrome in patients with a PASI score lower or higher than 10 (30·1% vs. 29·4%, respectively; = 0·9), or in patients with BSA involvement lower or greater than 10% (32·2% vs. 28·4%, respectively; = 0·4). There were no differences in the prevalence of metabolic syndrome between men and women, but it was more frequent after the age of 40 in both cases and controls. Waist circumference > 102 cm in men or > 88 cm in women, and triglyceridaemia > 1·7 mmol L−1 were significantly more prevalent in cases than in controls. In contrast, there were no significant differences regarding the prevalence of low HDL cholesterol, hypertension and fasting plasma glucose between cases and controls. We found a mild but significant correlation between severity of psoriasis and triglyceridaemia in patients with psoriasis (= 0·16; = 0·04) and between plasma fasting glucose and triglyceridaemia in subjects with metabolic syndrome (= 0·23; = 0·0006). In contrast, we found no significant correlation between psoriasis severity with waist circumference, blood pressure, fasting plasma glucose and body weight. There was a direct correlation between PASI score and disease duration (= 0·21; = 0·02).

Table 1.   Study population. Descriptive characteristic of cases and controls
 Cases (n = 338)Controls (= 334)P-value
  1. HDL, high-density lipoprotein.

Sex M/F160/178150/1840·8
Age at enrolment (years), mean ± SD 62·1 ± 15·1 63·8 ± 20·40·7
Body mass index, mean ± SD 27·7 ± 4·8 25·4 ± 4·90·0001
Smoker, n (%)121 (36·2) 72 (21·0)0·0001
Metabolic syndrome, n (%) 102 (30·1) 69 (20·6)0·005
Waist circumference > 102 cm (M) or > 88 cm (F), n (%) 193 (57·1)159 (47·6)0·01
Triglyceridaemia > 1·7 mmol L−1, n (%)128 (37·8) 78 (23·3)0·001
HDL cholesterol < 1·0 mmol L−1 (M) or < 1·3 mmol L−1 (F), n (%) 61 (18·0) 72 (21·5)0·2
Blood pressure > 135/85 mmHg, n (%)138 (40·8)132 (39·5)0·7
Fasting plasma glucose > 6·1 mmol L−1, n (%) 65 (19·2) 70 (20·9)0·6
Figure 1.

 Prevalence of metabolic syndrome in different age classes.

Comparing psoriatic patients with and without metabolic syndrome (Table 2), we observed that patients with metabolic syndrome had a higher mean age, an earlier age of onset of psoriasis and a longer disease duration. There were no differences regarding gender, clinical type of psoriasis, psoriasis severity and prevalence of smokers.

Table 2.   Descriptive characteristics of psoriatic patients with and without metabolic syndrome
 Psoriatic patients with metabolic syndrome (= 102)Psoriatic patients without metabolic syndrome (= 236)P-value
  1. BSA, body surface area; PASI, Psoriasis Area and Severity Index.

Sex M/F65/37161/750·4
Age at enrolment (years), mean ± SD63·1 ± 10·9 51·7 ± 15·30·0001
Age at onset of psoriasis (years), mean ± SD49·4 ± 18·8 36·6 ± 15·50·0001
Duration of psoriasis (years), mean ± SD18·1 ± 16·1 13·3 ± 12·00·03
Smoker, n (%)32 (31) 89 (37)0·2
Type of psoriasis, n (%)
 Chronic plaque localized  (BSA < 10%)46 (45)104 (44)0·2
 Chronic plaque disseminated  (BSA > 10%)53 (51)123 (52) 
 Pustular 3 (4)  3 (1) 
 Other (inverse, erythrodermic) 0  6 (2) 
PASI, mean ± SD11·1 ± 10·4 11·2 ± 9·40·9
PASI > 10, n (%)41 (42·6) 98 (42·8)0·9
BSA, mean ± SD17·3 ± 18·0 18·5 ± 20·80·6

Discussion

Psoriasis is a chronic inflammatory skin disease, which confers an unfavourable cardiovascular risk profile. A higher mortality risk for arterial and venous thrombosis,9 and a higher risk of myocardial infarction especially in young patients with severe psoriasis10 have been reported. Major factors that may contribute to this increased cardiovascular risk include cigarette smoking, dyslipidaemia, obesity, physical inactivity, hyperhomocysteinaemia and psychological stress, all of which have a higher occurrence among patients with psoriasis.11 A direct correlation between severity of psoriasis and the prevalence of obesity, dyslipidaemia and hyperhomocysteinaemia has been reported in psoriatic patients,12,23,24 suggesting that skin changes (inflammation) caused by psoriasis have a direct role in determining these risk factors. Also PsA has been found to be associated with relevant cardiovascular risk factors.25 Other T-helper 1-mediated autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus are characterized by accelerated atherosclerosis and consequently higher cardiovascular morbidity and mortality rates.26,27 The concomitant occurrence of dyslipidaemia, glucose intolerance, insulin resistance, obesity and hypertension constitutes the metabolic syndrome, which has been similarly defined by the World Health Organization, the National Cholesterol Education Program’s ATP III and the European Group on Insulin Resistance.21,28,29 Each panel group agrees on the essential components, but they differ in the details and criteria. Metabolic syndrome is a strong predictor of cardiovascular diseases, diabetes and stroke and significantly increases the risk of cardiovascular mortality compared with the individual factors.16,30 Metabolic syndrome also increases the risk of all-cause and colon cancer mortality.31,32 Comparison of published prevalence for different populations is difficult because of the different diagnostic criteria used. Just as the prevalence of the individual components of the syndrome varies among populations, so does the prevalence of the metabolic syndrome itself. Differences in genetic background, diet, levels of physical activity, population age and sex, levels of over- and undernutrition, and body habits all influence its prevalence. According to the ATP III definition, almost 25% of U.S. adults have metabolic syndrome.33 In Western Europe the prevalence of metabolic syndrome is similar to the U.S.A. ranging from 15% to 35%;34 in developing countries the prevalence of metabolic syndrome is lower, but recent epidemiological studies are registering a rapid increase.35 A very consistent finding among different studies is that prevalence of metabolic syndrome is strictly age dependent, increasing sharply after the age of 60.36

We have found that the prevalence of metabolic syndrome is significantly higher in psoriatic patients compared with controls after the age of 40 years, and it directly correlates to psoriasis duration. The prevalence of metabolic syndrome in our control population was similar to that recently estimated among Italian adults.22 As expected, we have found that psoriatic patients have a BMI and a waist circumference significantly higher compared with controls patients. Overwhelming evidence points towards the primary role of insulin resistance in pathogenesis of metabolic syndrome. More recently, chronic inflammation has been suggested as a part of the insulin resistance syndrome. Therapeutic intervention based on methotrexate and tumour necrosis factor (TNF)-α antagonists seems to diminish the insulin resistance state.37 However, it has been reported that patients with psoriasis have no deficit in insulin secretion or sensitivity compared with control patients.38 Total plasma triglycerides directly correlated to psoriasis severity and, as expected, to plasma glucose levels. An atherogenic lipid profile at the onset of psoriasis has been observed in a well-designed study, which excluded the possible role of confounding factors such as obesity, hypertension, cigarette smoking and physical activity.39 We did not find differences between cases and controls regarding prevalence of the other cardiovascular risk factors including diabetes, hypertension and reduction of HDL cholesterol. In contrast to our findings, a recent hospital-based case–control study from Northern Europe showed that diabetes mellitus type 2 and arterial hypertension as well as coronary artery disease occurred significantly more frequently in patients with psoriasis than in controls.40 The same authors observed a very low prevalence of metabolic syndrome in both patients (4·3%) and controls (1·1%), and there was a consistent trend for an enhanced risk of metabolic syndrome when comparing patients with severe psoriasis to those with moderate psoriasis.

In our study, we found that psoriasis is associated with metabolic syndrome independently of its severity, estimated with both PASI and BSA scoring and smoking habit. The study was cross-sectional and therefore the directionality of the association between psoriasis and metabolic syndrome could not be determined. We cannot determine at the moment what comes first, but the absence of correlation between psoriasis severity and metabolic syndrome may suggest that it is obesity that favours psoriasis. Some evidence indicates that psoriasis comes first. It is possible that depression, eating habits, physical inactivity, alcohol consumption, stress and inflammatory mediators associated with psoriasis favour obesity in predisposed individuals. On the other hand, obesity may in turn favour psoriasis. Indeed obesity is a proinflammatory state and the adipose tissue is a rich source of inflammatory mediators know as adipocytokines. These include adiponectin, leptin, resistin and visfatin, which are thought to provide an important link between obesity, insulin resistance and related inflammatory disorders. Other products of adipose tissue that have been characterized include TNF-α, interleukin 6 and monocyte chemoattractant protein 1. These products have well-known roles in the pathogenesis of psoriasis and at the interface between the immune and metabolic systems. In line with this hypothesis is the evidence that obesity is a risk factor for other inflammatory diseases such as atherosclerosis and asthma.41,42

Our study presents several limitations. Firstly, it was a cross-sectional study that does not allow the directionality of the association to be ascertained. Secondly, the study was conducted in tertiary care centres, and thus patients are biased toward having more severe psoriasis; and, thirdly, the study was conduced in northeast Italy and the population analysed may not be representative of the entire country.

In conclusion, we have found a higher prevalence of metabolic syndrome in patients with psoriasis, which could play a relevant role in accelerating atherosclerosis. The association is not limited to severe cases but also occurs with mild cases. The hypothesis that obesity can favour psoriasis needs to be urgently addressed in prospective studies. We suggest that all patients with psoriasis should be encouraged to correct aggressively their modifiable cardiovascular risk factors, in particular, metabolic syndrome.

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