Cardiovascular disease

RA is associated with greater CVD mortality, morbidity and preclinical atherosclerosis.5 The magnitude of the increased risk is similar to that of contemporarily managed diabetes. Recent studies have shown that the prevalence of CVD in PsA resembles that of RA,6 and that it is also comparable to diabetes.7 Furthermore, Ahlehoff et al found a similar risk of CVD in patients with PsA and severe psoriasis.7 In their study of the entire Danish population they found an increased rate of CVD mortality and morbidity in patients with mild and severe psoriasis. The relative risk was higher in young patients with severe psoriasis and PsA. Unfortunately, this study did not control for conventional CVD risk factors. Two studies which partly considered these risk factors analysed data from the UK-based General Practice Research Database (GPRD).1 8 They both found an increased CVD risk in young patients with severe psoriasis. However, a Dutch hospital-based study failed to show any increase.9 This latter study used a selection process which may have excluded some patients with psoriasis and did not examine severe patients separately, which may explain the discrepancies with GPRD-based studies. Nevertheless, it leaves doubt as to a clear increase in the risk of CVD in all patients with psoriasis.

Are there other sources of evidence to help resolve these uncertainties? Several surrogate marker studies using techniques such as coronary artery calcification and carotid intima-media thickness and plaque presence have been reported.10 11 The results of these generally support the hypothesis that psoriasis and PsA are associated with a heightened vascular risk. However, such studies are generally small to modest in size and, given other limitations, their results should be considered as hypothesis-generating rather than definitive proof of excess risk. Overall, therefore, it appears that the risk of CVD is most likely increased in patients with severe psoriasis and PsA. However, whether or not this is due to the disease itself or co-existing cardiovascular risk factors has not yet been established.

Obesity

There is plentiful evidence that obesity is more common in patients with psoriasis, and it is notably more common in PsA than in RA (28% vs 15% with BMI >27)).12 Some studies suggest that being overweight is a risk factor for developing psoriasis and PsA4 13 and others that it is a consequence.14 For example, a clear link between weight gain and incident psoriasis was found in the Nurses' Health Study.13 The severity of psoriasis (high psoriasis area and severity index score) has been linked to body mass index (BMI),15 and the prevalence of obesity is greater in those with severe compared with mild psoriasis with an OR of 1.47 (95% CI 1.32 to 1.63) in one recent study.16 Interestingly, the response to systemic therapy appears to be impaired in patients with a higher BMI17 whereas the effect of ciclosporin and biological therapies appears more marked in patients who lose weight.15 18 There are also several case reports of patients whose psoriasis has gone into remission following gastric bypass surgery.19 These findings suggest that obesity is at least causally relevant to the emergence and severity of psoriasis in some individuals. Of course, in some (but not all) individuals there may be a vicious cycle whereby excess weight contributes to psoriasis, and, as the disease progresses in severity, obesity may be further exacerbated by limited physical activity or enhanced caloric intake due to psychological effects. Other molecular interactions operating via as yet poorly characterised pathways are also possible for example, via adipocytokine expression.

Diabetes

Several studies have shown that patients with psoriasis and PsA are at increased risk of diabetes.20 21 The risk of diabetes increases with BMI, psoriasis duration and severity,20 22 and thus there appears to be an effect of psoriasis on diabetes risk independent of total adiposity. Patients with PsA are also more likely to have high fasting glucose than patients with RA (30% vs 16%, p<0.001).12 However, it has recently been suggested that treatment with tumour necrosis factor (TNF) inhibitor or hydroxychloroquine may reduce the risk of diabetes in both psoriasis and RA, although formal trial evidence is lacking.23 Consistent with the greater risk of diabetes, patients with psoriasis appear to have increased amounts of visceral fat.24 Furthermore, non-alcoholic fatty liver disease (NAFLD) is almost twice as prevalent in patients with psoriasis compared with BMI-matched controls without psoriasis.25 This is noteworthy as excess liver fat promotes hepatic insulin resistance and NAFLD is a recognised risk factor for diabetes.26

CVD risk

Large epidemiological studies are needed to evaluate the risk of CVD in patients with psoriasis of different disease severities and in those with PsA. Prospective studies taking into account established and emerging CVD risk factors would be of particular value. The effect of psoriasis treatment on CVD risk using proven surrogate markers would also be useful.

Obesity and psoriasis: causes and consequences

Is obesity a cause or a consequence of psoriasis and PsA? Several mechanisms are possible. For example, the skin adipose inflammatory milieu may be potentiated by obesity and contribute to skin plaque formation. Insulin resistance may also impair the normal inflammatory suppressive effects of insulin on immune cells. However, these are just hypotheses and need further investigation.

With regard to future research, accelerometers (being more measures of activity) could be used to evaluate whether the association between obesity and psoriasis and PsA is partly due to reduced activity levels. It would be interesting to conduct both longitudinal studies to assess if activity levels fall with progressively worsening disease and to cross-sectionally compare physical activity levels in patients with different disease severities.

The effect of increased physical activity and dietary interventions on disease activity would also be of interest but, of course, the key here is to identify better ways to help patients make sustainable changes to their lifestyle.

Link between diabetes/NAFLD and psoriasis

As discussed above, the increased rates of diabetes and NAFLD in psoriasis and PsA are probably due to a greater propensity for central fat storage. Although there is some evidence to support this, further imaging studies are needed. Furthermore, a reduced ability to store subcutaneous fat due to skin manifestations of the disease is a possible contributing factor and warrants investigation. Finally, the recent observation that TNF inhibitor or hydroxychloroquine is associated with a lower risk of diabetes in patients with RA and psoriasis is intriguing and hypothesis-generating, and perhaps demands direct mechanistic insulin resistance studies in randomised trials.23

Who should screen?

Dermatologists, rheumatologists and primary care physicians may all be involved in the care of patients with psoriasis and PsA. Primary care physicians are probably those best positioned to conduct such CVD risk screening. Nevertheless, rheumatologists and dermatologists should be aware of CVD risk factors, given potential causal links of some of these factors to the progression of psoriasis in their patients. They could helpfully liaise with their primary care colleagues as part of the totality of care offered to patients.

CVD risk screening and management

General population CVD screening is confined to those aged >40 years in most countries. It is only pursued in younger individuals with a family history of premature vascular disease or those with familial hypercholesterolaemia where multiple-fold relative risks for vascular disease exist. On this basis, it is debatable whether the small proportion of younger patients (<40 years of age) with severe psoriasis should be prioritised for CVD risk screening. It also seems premature to adopt a multiplication factor to account for their potentially greater vascular risk. The European League Against Rheumatism recommends that CVD risk screening should be considered annually in patients with PsA.27 The frequency of testing is debatable, and less frequent testing would be appropriate in those at low absolute vascular risk. A reasonable approach would be to use established CVD risk charts. Of note, blood pressure measurement and the addition of non-fasting lipids to regular blood samples are the only additional tests required to complete such screening.27 Based on the results, patients should be managed in accordance with national guidelines.

Smoking status also has a significant influence on the risk of CVD, and this is particularly pertinent for patients with psoriasis who are more likely to smoke.16 Thus, smoking cessation is an important part of CVD risk management in this patient group.

Obesity screening and management

BMI is used to define overweight and obesity and patients with a BMI >25 kg/m2 benefit from weight reduction.28 Many patients with psoriasis and PsA could obtain multiple benefits from lifestyle advice aimed to prevent further weight gain or, if possible, to lose and sustain weight loss over the longer term.

Patients with psoriasis and PsA should be made aware that favourable lifestyle changes will not only lower their risk for metabolic diseases—particularly diabetes—but that their psoriasis or arthritis may also improve or be prevented from worsening. In other words, patients with psoriasis should be reminded that they may have ‘more to gain’ from lifestyle changes than do individuals without psoriasis or PsA. There is now clear evidence that lifestyle changes focusing more on dietary changes than activity have better success with regard to weight loss.28 This approach may also be more acceptable for many patients, especially those with PsA where mobility is compromised.

Diabetes screening and management

Given that the relative risk for diabetes in patients with psoriasis is generally modest (typically less than twofold),20 we suggest that only overweight and obese patients with psoriasis and PsA should be screened for diabetes. HBA1c has recently gained international acceptance as a diagnostic measure for diabetes.29 It simplifies screening as it does not require fasting and is also better associated with cardiovascular events than glucose-based measures.30

With regard to the risk of NAFLD, it is premature to suggest liver radiology for all patients with psoriasis and PsA. Rather, only those with significantly raised liver function tests (eg, transaminases >3 times upper limit of normal or when aspartate aminotransferase levels rise above alanine transaminase levels, indicative of fibrosis risk) may require such tests. In terms of interventions, it is clear that the lifestyle changes described above will, in addition to tackling weight change, also help to lessen the risks of diabetes and NAFLD.