This prospective study demonstrated an increased risk of diabetes and hypertension in women with psoriasis, even after adjusting for age, BMI, alcohol intake and smoking. Hence, our study advances previous findings from cross-sectional studies and emphasizes the need to better understand the mechanisms that underlie these associations.
The risk of diabetes among individuals with psoriasis has been shown in cross-sectional studies to be elevated with RR between 1.27 and 2.48 [4
], consistent with our prospective study. Although obesity and the metabolic syndrome had been proposed as an explanation for this increased risk [5
], we found that the risk of diabetes was independent of BMI. Inflammation could be a biologically plausible mechanism underlying this association; insulin resistance has been attributed to inflammation previously [26
] and elevated C-reactive protein levels are predictive of diabetes [17
]. Alternatively, therapy for psoriasis may promote development of diabetes, especially if patients were treated with systemic steroids. In our study, information on psoriasis-related therapy is not available. Nonetheless, systemic steroids are not the standard of care for psoriasis in the United States and are typically avoided in psoriasis patients due to the potential for disease worsening [28
]. Topical steroids often used in psoriasis may be systemically absorbed if used on large body surface areas for extended periods of time [29
]. This could explain the observed increase in risk for diabetes, although adherence with long-term topical steroids use is generally low [30
An increased risk of hypertension of 1.2 to 2-fold has been reported in cross-sectional studies. In our study, individuals with psoriasis were at slightly increased risk for hypertension. Although psoriasis and hypertension share common risk factors such as smoking and obesity, we observed an independent association between psoriasis and hypertension after adjusting for smoking and BMI. Potential explanations for this association include systemic inflammation and psoriasis treatment. As mentioned above, psoriasis is a chronic inflammatory disease [32
], and inflammation is a risk factor for hypertension [5
]. In one study, although the risk for other cardiovascular risk factors was higher in severe psoriasis, a similar association between psoriasis severity and risk of hypertension was not found [12
]. Previous work has shown that elevated levels of C-reactive protein were associated with a 52% increase in the risk of developing hypertension in women [33
]. Systemic therapy for psoriasis with medications such as cyclosporine may increase risk of hypertension directly, albeit this risk is low [34
]; we did not have data on therapy in our study but long-term cyclosporine use in psoriasis is not common [35
]. Individuals with psoriasis may also be less likely to exercise due to physical or social discomfort [36
], hence increasing their risk for hypertension. In our study, we controlled for physical activity and found no material change in risk for hypertension.
Our study was restricted to predominantly Caucasian women. Hence we cannot generalize these results to men or other racial groups. Our study was observational; thus, we cannot rule out the possibility that unmeasured factors might contribute to the observed associations. While we observed no material change in the results that excluded those with at least one physical examination during the follow-up, we cannot eliminate potentially increased ascertainment of our outcomes among women with psoriasis. A major strength of the study was detailed collection of information on body mass index, smoking and alcohol. Similar to other epidemiologic studies of psoriasis [37
], we did not confirm the nurses' self-reported physician-diagnosis of psoriasis clinically with an examination by a dermatologist. Previous validation studies in the Nurses Health Study I for another skin condition, i.e. basal cell carcinoma, found self-reports to be >90% accurate [21
]. While we expect the overall accuracy of self-reported physician-diagnosis of psoriasis to be high among registered nurses, the corresponding accuracy against a dermatologist's examination is not available. Confirming our results using more specific case definitions of psoriasis and evaluating for various psoriasis subtypes, severity, and treatment effects would be valuable.
In conclusion, our prospective study indicates that women with psoriasis have an increased risk of diabetes and hypertension, confirming the findings from previous cross-sectional studies. These data illustrate the importance of considering psoriasis a systemic disorder rather than simply a skin disease. Further research is needed to better understand the mechanisms underlying these associations and whether psoriasis therapy can reduce risk for diabetes and hypertension.