Review ArticleReview

Cardiovascular Disease and Risk Factors in Patients with Psoriasis and Psoriatic Arthritis

ANNE-MARIE TOBIN, DOUGLAS J. VEALE, OLIVER FITZGERALD, SARAH ROGERS, PAUL COLLINS, DONAL O’SHEA and BRIAN KIRBY
The Journal of Rheumatology July 2010, 37 (7) 1386-1394; DOI: https://doi.org/10.3899/jrheum.090822

Abstract

Objective. Patients with psoriasis and psoriatic arthritis (PsA) have an increased incidence of cardiovascular disease (CVD) and cardiovascular risk factors such as smoking, hypertension, and metabolic syndrome compared to the normal population. Patients with psoriasis and PsA may also have increased risk from nonconventional risk factors such as raised levels of homocysteine and excessive alcohol consumption. We conducted a comprehensive review of the literature on CVD and all cardiovascular risk factors in patients with psoriasis and PsA.

Methods. Data sources: All studies identified from a Medline (www.ncbi.nlm.nih.gov) search pertaining to CVD, individual risk factors in psoriasis, and PsA were included. Study selection: Studies included a healthy reference population, were published between 1975 and 2009, and were written in English.

Results. Our search yielded 14 studies that documented rates of CVD in patients with psoriasis and PsA compared to controls. Substantial evidence points to elevated risk of CVD in patients with psoriasis and PsA.

Conclusion. It remains difficult to conclude if risk factors are caused by psoriasis or share a common pathogenesis. Physicians treating patients with psoriasis and PsA must be aware of all potential cardiovascular risk factors in their patients.

Psoriasis is now recognized as one of the commonest immune-mediated inflammatory disorders1. Its incidence has been assessed at 1%–3% of the population2,3. Ten percent of patients with psoriasis develop psoriatic arthritis (PsA), a seronegative spondyloarthropathy4. It is now apparent that patients with psoriasis and PsA suffer other morbidities in addition to their skin and joint disease. In particular, both populations have an increased risk of cardiovascular disease (CVD).

The objective of our review was to provide a current overview of the literature supporting the increased risk of CVD and all relevant risk factors. It is important that dermatologists and rheumatologists assess patients for CVD. Knowledge of a patient’s risk profile may enable early intervention and modification of risk factors.

MATERIALS AND METHODS

We conducted a literature search using the scientific literature database Medline up to June 30, 2009. We used different combinations of the following search terms: “psoriasis,” “psoriatic arthritis,” “cardiovascular disease,” “smoking,” “hypertension,” “cholesterol,” “diabetes,” “homocysteine,” “alcohol,” “thrombosis,” and “inflammation” with limits set to include humans. Our initial search yielded more than 2000 abstracts, which were reviewed to include only studies with a reference population, published between 1975 and 2009, and written in English. This yielded 47 studies, of which the full articles were then reviewed by the first and last authors.

RESULTS

Increased risk of CVD in patients with psoriasis and PsA

Our search yielded 14 studies that documented rates of CVD in patients with psoriasis and PsA compared to controls. The increased incidence of cardiovascular events in patients with psoriasis was recognized by McDonald and Calabresi in 19785. They reported patients with psoriasis had a 2.2 times higher incidence of arterial and venous vascular disease compared to controls in a clinic-based case-control study5.

Since then most studies have been large retrospective or prospective database studies (Table 1)5–14. The largest prospective study was that published by Gelfand, et al in 2006 using the UK General Practice Database6. Psoriasis appeared to confer an independent risk of myocardial infarction. The investigators controlled for diabetes, hyperlipidemia, hypertension, body mass index (BMI), age, sex, and smoking. Patients with psoriasis still had excess cardiovascular mortality compared to controls. This risk was greater for younger patients with severe psoriasis6. A second group utilizing the same data found an increased incidence of risk factors for CVD, as well as increased rates of myocardial infarction, angina, stroke, and peripheral vascular disease7. A more recent study using this database restricted diagnosis to patients with early psoriasis and did not find an increased risk of myocardial infarction8. Patients less than 60 years of age with more severe disease, however, had an increased risk [1.66, confidence interval (CI) 1.03–2.66]8.

View this table:
Table 1.

Studies identifying cardiovascular disease and risk factors in patients with psoriasis.

Retrospective studies from Sweden, Germany, and Finland previously documented increased rates of risk factors such as hypertension, diabetes, and obesity in patients with psoriasis9–14. Poikolainen, et al11 and Mallbris, et al12 reported increased cardiovascular mortality in patients who were hospitalized. Patients managed as outpatients, however, did not have excess risk, suggesting that more severe disease was associated with a higher risk of CVD. This association is replicated in studies by Brauchli, et al8 and Kimball, et al14, where more severe disease was associated with increased rates of CVD.

In a mortality study the leading cause of death in 428 Canadian patients with PsA was circulatory diseases (36.2%)15,16 (Table 2)15–19. An increase in the death rate of 1.3 (CI 7.72–1.53) (standard mortality rate, SMR) due to CVD was found compared to the general population15. In a subsequent study of 648 patients, patients with PsA had a significantly higher prevalence of myocardial infarction and hypertension17. Data generated from an administrative database identifying 3066 patients with PsA confirmed these findings18,19.

View this table:
Table 2.

Studies identifying cardiovascular disease and risk factors in patients with psoriatic arthritis.

Increased risk of subclinical CVD in psoriasis and PsA

Evidence also exists that demonstrates subclinical CVD in psoriasis and PsA. In 39 patients with moderate to severe psoriasis, arterial stiffness as measured by carotid and radial arterial wave velocity was significantly higher in patients than controls20. In another study of 43 patients, flow-mediated dilatation of the brachial artery and intimal medial thickness of the carotid were significantly lower and higher, respectively, in psoriasis patients without CVD risk factors, versus controls21. In 25 patients, 9 of whom had PsA, carotid wave pulse velocity, a measure of arterial stiffness, was significantly higher in patients with both psoriasis and PsA22. Patients with psoriasis were found to have increased coronary artery calcification in a recent direct imaging study compared to controls23.

Two case-control studies also demonstrated that patients with PsA had a higher prevalence of subclinical atherosclerosis as measured by arterial intima-media wall thickness24,25. Gonzalez-Juanatey, et al also found evidence of endothelial dysfunction in PsA patients without overt CVD24. A larger study of 82 patients with PsA in patients without clinical CVD found that 35% of patients had increased intimal medial thickness despite having low cardiovascular risk26.

Conventional risk factors in psoriasis

Cardiovascular risk factors found with increased frequency in patients with psoriasis include the conventional risk factors obesity, diabetes mellitus, hypertension, dyslipidemia, and smoking. Oxidative stress, endothelial cell dysfunction, abnormal platelet adhesion, and hyperhomocysteinemia, which may also increase cardiovascular risk, may all be regarded as risk factors specific to psoriasis and PsA and arise with greater prevalence in psoriasis.

Smoking in psoriasis

The increased rates of smoking in psoriasis are well documented27–32. Poikolainen, et al found excess mortality related to smoking in both male and female patients [SMR for men: 1.44 (CI 1.33–1.56), SMR for women: 1.61 (CI 1.45–1.77)]30. Other retrospective database studies also document increased rates of smoking in patients with psoriasis compared to controls10–14.

Smoking also appears to adversely affect the natural history of psoriasis33. In a hospital-based cross-sectional study of Italian patients admitted to hospital for treatment of psoriasis, smoking more than 20 cigarettes a day confers a 2-fold higher risk of clinically more severe psoriasis33. Behnam, et al in their review found both sexes who were smokers had reduced improvement rates31.

Hypertension in psoriasis

Preece first described an association between psoriasis and raised blood pressure in 197734. An increased prevalence of hypertension in patients with psoriasis compared to controls has also been documented in those studies of cardiovascular risk factors using databases6,7,9,10,14.

In a hospital-based case-control study, Ena, et al reported a significantly higher prevalence of essential hypertension in 100 patients with psoriasis compared to controls35. Enhanced activity of the renin-angiotensin system was found in patients with psoriasis. Endothelin-1, a potent vasoconstrictor released from vascular endothelium, is increased in the serum of patients with psoriasis and may contribute to the increased incidence of hypertension in patients with psoriasis36.

Dyslipidemia in psoriasis

There are more than 9 published case-control studies measuring serum lipids in psoriasis, as summarized in Table 337–45. The largest study has been by Mallbris, et al — lipids at the onset of psoriasis in 200 patients demonstrated significantly higher very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) fractions45. This study controlled for sex, blood pressure, BMI, physical activity, smoking, alcohol consumption, and C-reactive protein (CRP). Two early studies by Ferretti, et al of 30 children with psoriasis found that they had increased total plasma cholesterol, increased HDL cholesterol, and a decrease in ratio of HDL to LDL cholesterol46,47. This suggests that psoriasis per se may be associated with dyslipidemia. Although there are inconsistencies between studies, it appears safe to conclude that patients with psoriasis have raised levels of triglycerides, raised VLDL and LDL cholesterol, and raised lipoprotein A1 and apolipoprotein A1.

View this table:
Table 3.

Summary of studies of dyslipidemia in patients with psoriasis.

Hyperlipidemia was also found to be more common in patients with psoriasis than controls from studies utilizing databases6,7. In Gelfand’s study, patients with psoriasis had a hazard ratio of 3.08–3.18 (CI 2.93–3.23 and 3.02–3.36) of having hyperlipidemia compared to controls6.

Dyslipidemia observed in psoriasis is compounded by increased oxidative stress and decreased antioxidant capacity42,48,49. Autoantibodies recognizing oxidized LDL have been found in psoriasis, their level correlating with disease activity as measured by the Psoriasis Area and Severity Index48.

Diabetes mellitus in psoriasis

An association between psoriasis and hyperglycemia was documented as early as 1967 by Lynch50. Numerous studies have since confirmed the association of psoriasis, hyperglycemia, and relative insulin resistance7,9.10,13,51–60. Genetic analysis of 2 non-major histocompatibility complexes in patients with psoriasis found the strongest phenotypic marker for a loci mapping to chromosome 6p22 (rs6908425; p = 0.00015)61. This marker maps to CDKAL1, a gene associated with type II diabetes, suggesting a possible role for pleiotropic susceptibility loci for both conditions61.

Patients with psoriasis also demonstrate hyperinsulinemia and insulin resistance, with an apparent correlation between disease severity and insulin secretion62,63. It is possible that increased levels of insulin result in excessive levels of insulin-like growth factors (IGF), which appear to have a role in epidermal hyperproliferation in psoriasis64–66. Induction of interleukin 6 and vascular endothelial growth factor has been postulated as underpinning IGF’s role in the development of psoriatic plaques67,68.

Obesity and metabolic syndrome in psoriasis

In a case-control study we found patients with psoriasis had higher BMI compared to controls (p < 0.004)69. In 2 case-control studies obesity was associated with increased frequency of psoriasis (OR 1.9), and psoriasis was associated with increased prevalence of obesity compared to the control population, respectively (8.4% vs 3.6; p < 0.001)52,53.

The prospective Nurses’ Health Study of 78,626 nurses found that increased adiposity and weight gain were strong risk factors for development of psoriasis70. When age, smoking status, and alcohol intake were all controlled for, a significant association was found, clearly indicating a graded association between BMI and risk of incident psoriasis71. Obesity is one of the major components of the metabolic syndrome. Metabolic syndrome may be considered to consist of central obesity, hypertension, dyslipidemia, and insulin resistance.

Sommer, et al found increased prevalence of metabolic syndrome in psoriasis patients admitted to hospital compared to other hospital-based controls (odds ratio 5.29, CI 2.78–12.8)51. Another hospital-based case-control study found that metabolic syndrome was significantly more common in psoriatic patients than in controls (30.1% vs 20.6%; odds ratio 1.65, CI 1.16–2.35, p = 0.005)52. In their cross-sectional study of patients with psoriasis identified from an Israeli database, Cohen, et al demonstrated that psoriasis was associated with metabolic syndrome (OR 1.3, CI 1.1–1.4)53.

Conventional risk factors in PsA

There has been less research on CVD and risk factors in PsA. It is apparent, however, that patients with PsA have an increased prevalence of cardiovascular risk factors18,19,72,73. In 2004, Peters, et al reviewed the literature regarding cardiovascular risk factors in the spondyloarthropathies, including PsA72. There had been no studies of the prevalence of smoking or hypertension in PsA. Patients did, however, have an atherogenic lipid profile, with a suggestion that as disease activity receded, lipid profile improved72.

In a cross-sectional comparative study of PsA patients identified from a US database, Han, et al found patients with PsA had a higher prevalence ratio for type II diabetes, hyperlipidemia, and hypertension compared to controls (1.5, 1.3, and 1.2, respectively)18. Kimhi, et al compared 47 patients with PsA to 100 healthy controls and found significantly higher levels of hypertension and hyperlipidemia compared to controls19.

One hundred two patients with PsA were screened for cardiovascular risk factors and compared to 82 control patients73. Patients had a higher prevalence of diabetes mellitus (OR 9.27, 95% CI 2.09, 41.09) and hypertension (OR 3.37, 95% CI 1.68, 6.72), and an increased prevalence of lower HDL cholesterol (OR 0.16, 95% CI 0.07, 0.41) following adjustment for BMI73. This atherogenic lipid profile was confirmed by Jones, et al in 50 patients with PsA74. Tam, et al found a slightly different pattern of dyslipidemia in their case-control study of 102 patients: patients with PsA had higher HDL cholesterol and apolipoprotein A1 levels, lower total cholesterol and LDL cholesterol levels, and a lower total cholesterol to HDL cholesterol ratio73. Two older studies had demonstrated that PsA patients with active synovitis had lower total cholesterol, LDL cholesterol, and HDL cholesterol75,76.

Raised BMI in patients with PsA has been documented in the 2 case-control studies by Kimhi, et al and Tam, et al19,26. The full spectrum of metabolic syndrome has not been formally studied in patients with PsA. Individual components of the metabolic syndrome such as obesity18,26, hypertension18,19,72, insulin resistance18,72, and dyslipidemia18,19,72,73 have been reported.

Nonconventional risk factors in psoriasis and PsA. Inflammation

Chronic inflammation has been shown to play a role in the development of atherosclerosis77,78. A picture of atherosclerosis as an inflammatory, autoimmune-like disease is emerging79. Both the innate immune system and T helper-1 lymphocytes appear to be involved in atherogenesis80,81. This is similar to the pattern of immune-mediated inflammation in psoriasis and PsA82–84. It is possible that psoriasis and PsA produce chronic, systemic inflammation, with higher levels of inflammatory cells and cytokines invoking endothelial inflammation and plaque formation85,86.

The increased prevalence of obesity seen in patients with psoriasis and PsA may also increase the burden of inflammation87. White adipose tissue accumulates in deposits close to blood vessels, where (as noted above) it secretes cytokines, chemokines, and hormone-like proteins88.

CRP has emerged as one of the predictors of CVD89–91. As its levels correlate well with joint inflammation, CRP is measured routinely in PsA92–95. A recent large cohort study from Italy, however, suggests that CRP is possibly more valuable in patients with more severe joint disease96. In a study of cardiovascular risk factors, Tam, et al reported that low-grade inflammation as measured by high sensitivity CRP (hs-CRP) was associated with obesity, hypertension, insulin resistance, and dyslipidemia73.

Fibrinogen is the other major acute-phase protein known to be associated with vascular events97,98. Fibrinogen levels are known to be increased in psoriasis and PsA14,49,72,98–101. Both these elevated markers indicate chronic inflammation in psoriasis and PsA and a possible role in elevating a patient’s cardiovascular risk.

Endothelial cell dysfunction

Atherosclerotic plaques may be considered the result of chronic inflammation of vessel endothelium, leading to endothelial dysfunction and plaque formation in the milieu of raised plasma lipids.

Oxidative stress and the generation of free radicals is believed to play a critical role in causing damage to the endothelial cells101. Increased levels of oxidized low-density lipoproteins in psoriatic plaques of 84 patients have been reported compared to healthy controls99,100. This finding was confirmed in a study that also reported decreased antioxidant capacity and a lipid and lipoprotein profile susceptible to oxidation102. Rocha-Pereira, et al reported that patients with psoriasis may be at increased risk of oxidative and proteolytic stress from neutrophils42.

Endothelial activation in patients with psoriasis is known to be important in the formation of plaques. Treatment of patients with anti-tumor necrosis factor-α(TNF-α) led to the downregulation of the vascular growth factors angiopoietin 1 and 2 and their receptor Tie-2, underpinning the role of angiogenesis in plaque formation103. There does not appear to be a reliable marker of either endothelial dysfunction or endothelial activation, however.

Atherothrombotic markers: fibronection and platelets

Atherothrombosis is the result of atherosclerotic progression that can result in vessel occlusion104. Atherosclerotic plaques rupture, and plaque contents interact with blood components, triggering the coagulation cascade involving platelets, thrombin, fibrin, and inflammatory cells105. Increased coagulation factors, decreased fibrinolysis, and increased or more reactive platelets all promote thrombus formation105.

Low levels of fibronectin have been suggested as a marker of atherothrombosis. Studies of fibronectin in psoriasis have been conflicting; Vanizor and colleagues found that levels of fibronectin were raised in patients with psoriasis99. Fibronectin levels were lower in patients with psoriasis in a second study; however, this was true of patients with active disease and not those in remission106. Fibronectin levels have been shown to be raised in patients with PsA compared to healthy controls107.

Increased platelet aggregation in patients with psoriasis compared to controls has been documented108. Thrombocytosis has also been documented in PsA: platelets may be acting as an acute-phase reactant in this instance109.

Homocysteine

Raised levels of homocysteine have been shown to be an independent risk factor for the development of CVD110. Homocysteine is believed to cause endothelial dysfunction by causing accumulation of asymmetrical dimethyl arginine, a natural inhibitor of nitric oxide synthase. It thus reduces the production of the vasodilator nitric oxide, which also protects the vessel wall against the pathogenesis of atherosclerosis and thrombosis.

In our case-control study, patients with psoriasis had a relative risk 7.1 times greater than controls of having significantly raised levels of homocysteine69. A recent controlled study has shown that patients with psoriasis have raised levels of homocysteine and lower levels of plasma folate compared to normal controls111; this is supported by 2 other uncontrolled studies, one of them in patients taking methotrexate100,112. It is proposed that keratinocyte turnover is accelerated in patients with psoriasis, and folate, which is used to methylate DNA in actively dividing cells, may be consumed, leading to higher levels of homocysteine113–115. High levels of homocysteine have been documented in a small number of patients with PsA116.

Increased alcohol consumption

Although moderate alcohol consumption has been shown in several epidemiological studies to be cardioprotective, excessive alcohol consumption increases cardiovascular risk and mortality117. Poikolainen, et al found alcohol in a retrospective study to be the leading cause of excess mortality in patients hospitalized for treatment of psoriasis11. Excessive alcohol consumption is widely documented in patients with psoriasis118,119. We have shown a higher prevalence and incidence of psoriasis in a population of patients with alcoholic liver disease120,121. There is also a suggestion that alcohol consumption may adversely affect treatment outcomes in patients who continue to consume excess alcohol122.

There have been few studies of alcohol consumption in patients with PsA apart from those being treated with methotrexate.

Conclusion

The evidence that patients with psoriasis and PsA have an elevated risk of developing CVD is substantial. This may be due to the increased prevalence of conventional risk factors but also other risk factors that are disease-specific. From published studies it would appear that risk is greatest in those with more severe disease and longer disease. This implies that aggressive treatment of both diseases should lower cardiovascular risk. Data from the British Biologics Registry do support the reduction in myocardial infarction in patients with rheumatoid arthritis treated with TNF inhibitors123. It may be too early, however, for registries to fully conclude the benefits of TNF inhibitors. Two studies have looked at the effects of TNF inhibitors on cardiovascular risk factors in PsA124,125. In a double-blind study the TNF inhibitor onercept significantly lowered lipoprotein(a) and homocysteine but also increased triglyceride levels124. In a review of published studies, Channual, et al found that etanercept and infliximab appeared to have no effect on dyslipidemia, and treatment with each resulted in significant weight gain in both psoriasis and PsA125. Hence the benefit of lowering inflammation would appear to be counteracted by unique effects of individual drugs. Methotrexate decreased cardiovascular mortality in a large cohort of patients with psoriasis125. This may be due to the concomitant use of folic acid and to beneficial effects on homocysteine. A placebo-controlled clinical trial on methotrexate use in patients with stable CVD may further elucidate the role of methotrexate126. To date there is insufficient evidence to conclude that aggressive disease control improves cardiovascular risk. Biologics registries may be helpful in providing an answer to this question.

The European League Against Rheumatism has issued guidelines based on a systematic literature search of cardiovascular risk management in PsA127. It recommends annual screening of PsA patients for cardiovascular risk and management according to the SCORE or Framingham model, or national guidelines. They note commonly used thresholds are a systolic blood pressure of 140 mm Hg and LDL cholesterol of 2.5 mmol/l. The initiation of antihypertensives and statins should be similar to the general population. They also recommend being mindful of the associated increased cardiovascular risk associated with nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors, and corticosteroids. Smoking cessation is to be recommended.

In a consensus document published in the American Journal of Cardiology the following was recommended for patients with psoriasis128: Patients with psoriasis and ≥ 1 abnormal serum lipid level, and/or elevated plasma hs-CRP, should adopt a multifaceted lifestyle approach to reduce risk. This involves weight loss, increased physical activity, and alcohol reduction. If this is unsuccessful in achieving target LDL cholesterol levels then a statin should be introduced. Cigarette smoking cessation should be promoted. Patients with hypertension should first undertake lifestyle changes, including reduction of weight and dietary sodium and, if unsuccessful, antihypertensive medication should be commenced. Beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II blockers can worsen psoriasis. The National Psoriasis Foundation recommends implementing the American Heart Association guidelines129, which recommend smoking cessation by age 40 years, alcohol reduction, and exercising for 30 minutes 3 times a week in patients without risk factors. More intensive intervention is warranted for people with risk factors, as outlined on the website of the American Heart Association: www.american-heart.org.

There is a paucity of information on the effects of lipid-lowering agents and antihypertensives on cardiovascular risk and no data on the optimal use of aspirin. Large prospective cohort studies are required to produce adequate evidence-based guidelines. Further, a comprehensive study of nonconventional risk factors in patients with psoriasis and PsA has not been done. It is important that such studies be conducted to define patients who are at risk and identify potential biomedical markers of cardiovascular risk.

Footnotes

  • Accepted for publication February 8, 2010.

REFERENCES

  1. 1.↵
    1. Griffiths CE,
    2. Barker JN
    . Pathogenesis and clinical features of psoriasis. Lancet 2007;370:263–71.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Christophers E
    . Psoriasis — epidemiology and clinical spectrum. Clin Exp Dermatol 2001;15:20–3.
    OpenUrl
  3. 3.↵
    1. Stern R,
    2. Nijsten T,
    3. Feldman S,
    4. Margolis J,
    5. Rolstad T
    . Psoriasis is common, carries a substantial burden even when not extensive, and is associated with wide-spread treatment dissatisfaction. J Invest Dermatol 2004;9:136–9.
    OpenUrlCrossRef
  4. 4.↵
    1. Veale DJ,
    2. Fitzgerald O
    . Psoriatic arthritis — pathogenesis and epidemiology. Clin Exp Rheumatol 2002;20:S27–33.
    OpenUrlPubMed
  5. 5.↵
    1. McDonald CJ,
    2. Calabresi P
    . Psoriasis and occlusive vascular disease. Br J Dermatol 1978;99:469–75.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Gelfand JM,
    2. Neimann AL,
    3. Shin DB,
    4. Wang X,
    5. Margolis DJ,
    6. Troxel AB
    . Risk of myocardial infarction in patients with psoriasis. JAMA 2006;296:1735–41.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Kaye JA,
    2. Li L,
    3. Jick SS
    . Incidence of risk factors for myocardial infarction and other vascular diseases in patients with psoriasis. Br J Dermatol 2008;159:895–902.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Brauchli YB,
    2. Jick SS,
    3. Miret M,
    4. Meier CR
    . Psoriasis and risk of incident myocardial infarction, stroke or transient ischaemic attack: an inception cohort study with a nested case-control analysis. Br J Dermatol 2009;160:1048–56.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Lindegard B
    . Diseases associated with psoriasis in a general population of 159,200 middle-aged, urban, native Swedes. Dermatologica 1986;172:298–304.
    OpenUrlPubMed
  10. 10.↵
    1. Henseler T,
    2. Christophers E
    . Disease concomitance in psoriasis. J Am Acad Dermatol 1995;32:982–6.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Poikolainen K,
    2. Karvonen J,
    3. Pukkala E
    . Excess mortality related to alcohol and smoking among hospital treated patients with psoriasis. Arch Dermatol 1999;135:1490–3.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Mallbris L,
    2. Akre O,
    3. Granath F,
    4. Yin L,
    5. Lindelof B,
    6. Ekbom A,
    7. et al.
    Increased risk for cardiovascular mortality in psoriasis inpatients but not in outpatients. Eur J Epidemiol 2004;19:225–30.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Shapiro J,
    2. Cohen AD,
    3. David M,
    4. Hodak E,
    5. Chodik G,
    6. Viner A,
    7. et al.
    The association between psoriasis, diabetes mellitus, and atherosclerosis in Israel: a case-control study. J Am Acad Dermatol 2007;56:629–34.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Kimball AB,
    2. Robinson D Jr,
    3. Wu Y,
    4. Guzzo C,
    5. Yeilding N,
    6. Paramore C,
    7. et al.
    Cardiovascular disease and risk factors among psoriasis patients in two US healthcare databases, 2001–2002. Dermatology 2008;217:27–37.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Wong K,
    2. Gladman DD,
    3. Husted J,
    4. Long JA,
    5. Farewell VT
    . Mortality studies in psoriatic arthritis: results from a single outpatient clinic. I. Causes and risk of death. Arthritis Rheum 1997;40:1868–72.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Gladman DD,
    2. Farewell VT,
    3. Wong K,
    4. Husted J
    . Mortality studies in psoriatic arthritis: results from a single outpatient center. II. Prognostic indications for death. Arthritis Rheum 1998;41:1103–10.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Gladman DD,
    2. Ang M,
    3. Su L,
    4. Tom BDM,
    5. Schentag CT,
    6. Farewell VT
    . Cardiovascular morbidity in psoriatic arthritis. Ann Rheum Dis 2009;68:1131–5.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Han C,
    2. Robinson DW Jr,
    3. Hackett MV,
    4. Paramore LC,
    5. Fraeman KH,
    6. Bala MV
    . Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol 2006;33:2167–72.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Kimhi O,
    2. Caspi D,
    3. Bornstein NM,
    4. Maharshak N
    . Prevalence and risk factors of atherosclerosis in patients with psoriatic arthritis. Semin Arthritis Rheum 2007;36:203–9.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Gisondi P,
    2. Fantin F,
    3. Del Giglio M,
    4. Valbusa F,
    5. Marino F,
    6. Zamboni M,
    7. et al.
    Chronic plaque psoriasis is associated with increased arterial stiffness. Dermatology 2009;218:110–3.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Balci DD,
    2. Balci A,
    3. Karazincir S,
    4. Ucar E,
    5. Iyigun U,
    6. Yalcin F,
    7. et al.
    Increased carotid-artery intima media thickness and impaired endothelial function in psoriasis. J Eur Acad Dermatol Venereol 2009;23:1–6.
    OpenUrlPubMed
  22. 22.↵
    1. Soy M,
    2. Yildiz M,
    3. Sevki Uyanik M,
    4. Karaca N,
    5. Güfer G,
    6. Piskin S
    . Susceptibility to atherosclerosis in patients with psoriasis and psoriatic arthritis as determined by carotid-femoral (Aortic) pulse-wave velocity measurement. Rev Esp Cardiol 2009;62:96–9.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Ludwig RJ,
    2. Herzog C,
    3. Rostock A,
    4. Ochsendorf FR,
    5. Zollner TM,
    6. Thaci D,
    7. et al.
    Psoriasis: a possible risk factor for development of coronary artery calcification. Br J Dermatol 2007;156:271–6.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Gonzalez-Juanatey C,
    2. Llorca J,
    3. Amogo Diaz E
    . High prevalence of subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. Arthritis Rheum 2007;57:1074–80.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Gonzalez-Juanatey C,
    2. Llorca J,
    3. Miranda-Filloy JA
    . Endothelial dysfunction in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. Arthritis Rheum 2007;57:287–93.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Tam LS,
    2. Shang Q,
    3. Li EK,
    4. Tomlinson B,
    5. Chu TT,
    6. Li M,
    7. et al.
    Subclinical carotid atherosclerosis in patients with psoriatic arthritis. Arthritis Rheum 2008;59:1322–31.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Herron MD,
    2. Hinckley M,
    3. Hoffman MS
    . Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol 2005;141:1527–34.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Williams HC
    . Smoking and psoriasis. BMJ 1994;308:428–9.
    OpenUrlFREE Full Text
  29. 29.↵
    1. Mills CM,
    2. Srivastava ED,
    3. Harvey IM,
    4. Swift GL,
    5. Newcombe RG,
    6. Holt PJ,
    7. et al.
    Smoking habits in psoriasis: a case control study. Br J Dermatol 1992;127:18–21.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Poikolainen K,
    2. Renula T,
    3. Karvonen J
    . Smoking, alcohol and life events related to psoriasis among women. Br J Dermatol 1994;130:473–7.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Behnam SM,
    2. Behnam SE,
    3. Koo JY
    . Smoking and psoriasis. Skinmed 2005;4:174–6.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Setty AR,
    2. Curhan G,
    3. Choi HK
    . Smoking and the risk of psoriasis in women: Nurses’ Health Study II. Am J Med 2007;120:953–9.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Fortes C,
    2. Mastroeni S,
    3. Leffondre K,
    4. Sampogna F,
    5. Melchi F,
    6. Mazzotti E,
    7. et al.
    Relationship between smoking and the clinical severity of psoriasis. Arch Dermatol 2005;141:1580–4.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Preece JF
    . Raised blood pressure and psoriasis. J R Coll Gen Pract 1977;27:713–5.
    OpenUrlPubMed
  35. 35.↵
    1. Ena P,
    2. Madeddu P,
    3. Glorioso N,
    4. Cerimele D,
    5. Rappelli A
    . High prevalence of cardiovascular diseases and enhanced activity of the renin-angiotensin system in psoriatic patients. Acta Cardiol 1985;40:199–205.
    OpenUrlPubMed
  36. 36.↵
    1. Bonifati C,
    2. Mussi A,
    3. Carducci M,
    4. Pittarello A,
    5. D’Auria L,
    6. Venuti A,
    7. et al.
    Endothelin-1 levels are increased in sera and lesional skin extracts of psoriatic patients and correlate with disease severity. Acta Derm Venereol 1998;78:22–6.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Vahlquist C,
    2. Michaelsson G,
    3. Vessby B
    . Serum lipoproteins in middle-aged men with psoriasis. Acta Derm Venerol 1987;67:12–5.
    OpenUrlPubMed
  38. 38.↵
    1. Seckin D,
    2. Tokgozoglu L,
    3. Akkaya S
    . Are lipoprotein profile and lipoprotein(a) levels altered in men with psoriasis? J Am Acad Dermatol 1994;31:445–9.
    OpenUrlCrossRefPubMed
  39. 39.↵
    1. Seishima M,
    2. Mori S,
    3. Noma A
    . Serum lipid and apolipoprotein levels in patients with psoriasis. Br J Dermatol 1994;130:738–42.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Uyanik BS,
    2. Ari Z,
    3. Onur E,
    4. Gunduz K,
    5. Tanulki S,
    6. Durkan C
    . Serum lipids and apolipoproteins in patients with psoriasis. Clin Chem Lab Med 2002;40:65–8.
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Piskin S,
    2. Gurkok F,
    3. Ekuklu G,
    4. Senol M
    . Serum lipid levels in psoriasis. Yonsei Med J 2003;44:24–6.
    OpenUrlPubMed
  42. 42.↵
    1. Rocha-Pereira P,
    2. Santos-Silva A,
    3. Rebelo I,
    4. Quintanilha A,
    5. Teixeira F
    . Dislipidemia and oxidative stress in mild and in severe psoriasis as a risk for cardiovascular disease. Clin Chim Acta 2001;303:33–9.
    OpenUrlCrossRefPubMed
  43. 43.↵
    1. Akhyani M,
    2. Ehsani AH,
    3. Robati RM,
    4. Robati AM
    . The lipid profile in psoriasis: a controlled study. J Eur Acad Dermatol Venereol 2007;21:1330–2.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Cimsit G,
    2. Orem A,
    3. Deger O,
    4. Alpay K,
    5. Kiran E,
    6. Orem C
    . The variation of serum lipoprotein (a) level with disease activity in psoriasis. Br J Dermatol 1998;138:917–9.
    OpenUrlPubMed
  45. 45.↵
    1. Mallbris L,
    2. Granath F,
    3. Hamsten A,
    4. Stahle M
    . Psoriasis is associated with lipid abnormalities at the onset of skin disease. J Am Acad Dermatol 2006;54:614–21.
    OpenUrlCrossRefPubMed
  46. 46.↵
    1. Ferretti G,
    2. Simonetti O,
    3. Offidani AM,
    4. Messini L,
    5. Cinti B,
    6. Marshiseppe I,
    7. et al.
    Changes of plasma lipids and erythrocyte membrane fluidity in psoriatic children. Pediatr Res 1993;33:506–9.
    OpenUrlPubMed
  47. 47.↵
    1. Ferretti G,
    2. Alleva R,
    3. Taus M,
    4. Simonetti O,
    5. Cinti B,
    6. Offidani AM
    . Abnormalities of plasma lipoprotein composition and fluidity in psoriasis. Acta Derm Venerol 1994;74:171–5.
    OpenUrlPubMed
  48. 48.↵
    1. Offidani AM,
    2. Ferretti G,
    3. Taus M,
    4. Simonetti O,
    5. Dousset N,
    6. Valdiguie P
    . Lipoprotein peroxidation in adult psoriatic patients. Acta Derm Venerol Suppl Stockh 1994;186:38–40.
    OpenUrl
  49. 49.↵
    1. Vanizor Kural B,
    2. Orem A,
    3. Cimsit G,
    4. Yandi YE,
    5. Calapoglu M
    . Evaluation of the atherogenic tendency of lipids and lipoprotein content and their relationships with oxidant-antioxidant system in patients with psoriasis. Clin Chim Acta 2003;328:71–82.
    OpenUrlCrossRefPubMed
  50. 50.↵
    1. Lynch PJ
    . Psoriasis and blood sugar levels. Arch Dermatol 1967;95:255–8.
    OpenUrlCrossRefPubMed
  51. 51.↵
    1. Sommer DM,
    2. Jenisch S,
    3. Suchan M,
    4. Christophers E,
    5. Weichenthal M
    . Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis. Arch Dermatol Res 2006;298:321–8.
    OpenUrlCrossRefPubMed
  52. 52.↵
    1. Gisondi P,
    2. Tessari G,
    3. Conti A,
    4. Piaserico S,
    5. Schianchi S,
    6. Peserico A,
    7. et al.
    Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based case-control study. Br J Dermatol 2007;157:68–73.
    OpenUrlCrossRefPubMed
  53. 53.↵
    1. Cohen AD,
    2. Sherf M,
    3. Vidavsky L,
    4. Vardy DA,
    5. Shapiro J,
    6. Meyerovitch J
    . Association between psoriasis and the metabolic syndrome. A cross-sectional study. Dermatology 2008;216:152–2.
    OpenUrlCrossRefPubMed
  54. 54.↵
    1. Binazzi M,
    2. Calandra P,
    3. Lisi P
    . Statistical association between psoriasis and diabetes: further results. Arch Dermatol Res 1975;254:43–8.
    OpenUrlCrossRefPubMed
  55. 55.↵
    1. Fratino P,
    2. Pelfine C,
    3. Jucci A,
    4. Bellazi R
    . Glucose and insulin in psoriasis: the role of obesity and diabetic genetic history. Panminerva Med 1979;21:167–72.
    OpenUrlPubMed
  56. 56.↵
    1. Pelfini C,
    2. Jucci A,
    3. Fratino P,
    4. De Marco R,
    5. Serri F
    . Insulinogenic indexes in psoriasis. Acta Derm Venereol Suppl Stockh 1979; 87:48–50.
    OpenUrlPubMed
  57. 57.↵
    1. Reynoso-von Drateln C,
    2. Martinez-Abundis E,
    3. Balcazar-Munoz BR,
    4. Bustos-Saldana R,
    5. Gonzalez-Ortiz M
    . Lipid profile, insulin secretion, and insulin sensitivity in psoriasis. J Am Acad Dermatol 2003;48:882–5.
    OpenUrlCrossRefPubMed
  58. 58.↵
    1. Neimann AL,
    2. Shin DB,
    3. Wang X,
    4. Margolis DJ,
    5. Troxel AB,
    6. Gelfand JM
    . Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol 2006;55:829–35.
    OpenUrlCrossRefPubMed
  59. 59.↵
    1. Huerta C,
    2. Rivero E,
    3. Rodriguez LA
    . Incidence and risk factors for psoriasis in the general population. Arch Dermatol 2007; 143:1559–65.
    OpenUrlCrossRefPubMed
  60. 60.↵
    1. Naldi L,
    2. Chatenoud L,
    3. Belloni A,
    4. Peserico A,
    5. Balato N,
    6. Virgili AR,
    7. et al.
    Medical history, drug exposure and the risk of psoriasis. Evidence from an Italian case-control study. Dermatology 2008;216:125–30.
    OpenUrlCrossRefPubMed
  61. 61.↵
    1. Wolf N,
    2. Quaranta M,
    3. Prescott NJ,
    4. Allen M,
    5. Smith R,
    6. Burden AD,
    7. et al.
    Psoriasis is associated with pleiotropic susceptibility loci identified in type II diabetes and Crohn’s disease. J Med Genet 2008;45:114–6.
    OpenUrlAbstract/FREE Full Text
  62. 62.↵
    1. Ucak S,
    2. Ekmekci TR,
    3. Basat O,
    4. Koslu A,
    5. Altuntas Y
    . Comparison of various insulin sensitivity indices in psoriatic patients and their relationship with type of psoriasis. J Eur Acad Dermatol Venereol 2006;20:517–22.
    OpenUrlCrossRefPubMed
  63. 63.↵
    1. Boehncke S,
    2. Thaci D,
    3. Beschmann H,
    4. Ludwig RJ,
    5. Ackermann H,
    6. Badenhoop K,
    7. et al.
    Psoriasis patients show signs of insulin resistance. Br J Dermatol 2007;157:1249–51.
    OpenUrlCrossRefPubMed
  64. 64.↵
    1. Xu S,
    2. Cwyfan-Hughes SC,
    3. van der Stappen JW,
    4. Sansom J,
    5. Burton JL,
    6. Donnelly M,
    7. et al.
    Altered insulin-like growth factor-II (IGF-II) level and IGF-binding protein-3 (IGFBP-3) protease activity in interstitial fluid taken from the skin lesion of psoriasis. J Invest Dermatol 1996;106:109–12.
    OpenUrlCrossRefPubMed
  65. 65.↵
    1. Hodak E,
    2. Gottlieb AB,
    3. Anzilotti M,
    4. Krueger JG
    . The insulin-like growth factor 1 receptors is expressed by epithelial cells with proliferative potential in human epidermis and skin appendages: correlation of increased expression with epidermal hyperplasia. J Invest Dermatol 1996;106:564–70.
    OpenUrlCrossRefPubMed
  66. 66.↵
    1. Wraight CJ,
    2. White PJ,
    3. McKean SC,
    4. Fogarty RD,
    5. Venables DJ,
    6. Liepe IJ,
    7. et al.
    Reversal of epidermal hyperproliferation in psoriasis by insulin-like growth factor 1 receptor antisense oligonucleotides. Nat Biotechnol 2000;18:521–6.
    OpenUrlCrossRefPubMed
  67. 67.↵
    1. Kwon YW,
    2. Jang ER,
    3. Lee YM,
    4. Kim YS,
    5. Kwon KS,
    6. Jang HS,
    7. et al.
    Insulin-like growth factor II induces interleukin-6 expression via NF kappa B activation in psoriasis. Biochem Biophys Res Commun 2000;278:312–7.
    OpenUrlCrossRefPubMed
  68. 68.↵
    1. Kwon YW,
    2. Kwon KS,
    3. Moon HE,
    4. Park JA,
    5. Choi KS,
    6. Kim YS,
    7. et al.
    Insulin-like growth factor–II regulates the expression of vascular endothelial growth factor by the human keratinocye cell line HaCaT. J Invest Dermatol 2004;123:152–8.
    OpenUrlCrossRefPubMed
  69. 69.↵
    1. Tobin AM,
    2. Hughes R,
    3. Hand E,
    4. Leong T,
    5. Graham IM,
    6. Kirby B
    . Homocysteine status and cardiovascular risk factors in patients with psoriasis: a case control study. Clin Exp Dermatol 2010 (in press).
  70. 70.↵
    1. Arathi RS,
    2. Curhan G,
    3. Hyon CK
    . Obesity, waist circumference, weight change, and the risk of psoriasis in women. Nurses’ Health Study II. Arch Intern Med 2007;176:13–27.
    OpenUrl
  71. 71.↵
    1. Bastard JP,
    2. Maachi M,
    3. Lagathu C,
    4. Kim MJ,
    5. Caron M,
    6. Vidal H,
    7. et al.
    Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006;17:4–12.
    OpenUrlPubMed
  72. 72.↵
    1. Peters MJ,
    2. van der Horst-Bruinsma IE,
    3. Dijkmans BA,
    4. Nurmohamed MT
    . Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheum 2004;34:585–92.
    OpenUrlCrossRefPubMed
  73. 73.↵
    1. Tam LS,
    2. Tomlinson B,
    3. Chu TT,
    4. Li M,
    5. Leung YY,
    6. Kwok LW,
    7. et al.
    Cardiovascular risk profile of patients with psoriatic arthritis compared to controls — the role of inflammation. Rheumatology 2008;47:718–23.
    OpenUrlAbstract/FREE Full Text
  74. 74.↵
    1. Jones SM,
    2. Harris CP,
    3. Lloyd J,
    4. Stirling CA,
    5. Reckless JP,
    6. McHugh NJ
    . Lipoproteins and their subfractions in psoriatic arthritis: identification of an atherogenic profile with active joint disease. Ann Rheum Dis 2000;59:904–9.
    OpenUrlAbstract/FREE Full Text
  75. 75.↵
    1. Lazarevic MB,
    2. Vitic J,
    3. Mladenovic V,
    4. Moynes BL,
    5. Skosey JL,
    6. Swedler WI
    . Dyslipoproteinemia in the course of active rheumatoid arthritis. Semin Arthritis Rheum 1992;22:172–8.
    OpenUrlCrossRefPubMed
  76. 76.↵
    1. Skoczynska AH,
    2. Turczyn B,
    3. Brancewicz-Losek M,
    4. Martynowicz H
    . High-density lipoprotein cholesterol in patients with psoriatic arthritis. J Eur Acad Dermatol Venereol 2003;17:362–3.
    OpenUrlCrossRefPubMed
  77. 77.↵
    1. Hansson GK,
    2. Robertson AK,
    3. Soderberg-Naicler C
    . Inflammation and atherosclerosis. Annu Rev Pathol 2006;1:297–329.
    OpenUrlCrossRefPubMed
  78. 78.↵
    1. Chung CP,
    2. Norton GR,
    3. Raggi P,
    4. Stein CM
    . Atherosclerosis and inflammation: insights from rheumatoid arthritis. Clin Rheumatol 2007;26:1228–33.
    OpenUrlCrossRefPubMed
  79. 79.↵
    1. Kuiper J,
    2. van Puijvelde GH,
    3. van Wanrooij EJ,
    4. van Es T,
    5. Habets K,
    6. Hauer AD,
    7. et al.
    Immunomodulation of the inflammatory response in atherosclerosis. Curr Opin Lipidol 2007;18:521–6.
    OpenUrlPubMed
  80. 80.↵
    1. Hansson GK,
    2. Libby P,
    3. Schonbeck U,
    4. Yan ZQ
    . Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 2002;91:281–9.
    OpenUrlAbstract/FREE Full Text
  81. 81.↵
    1. Hansson GK,
    2. Libby P
    . The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 2006;6:508–19.
    OpenUrlCrossRefPubMed
  82. 82.↵
    1. Nickoloff BJ,
    2. Gin JZ,
    3. Nestle FO
    . Immunopathogenesis of psoriasis. Clin Rev Allergy Immunol 2007;33:45–56.
    OpenUrlCrossRefPubMed
  83. 83.↵
    1. Veale DJ,
    2. Rogers S,
    3. Fitzgerald O
    . Immunolocalization of adhesion molecules in psoriatic arthritis, psoriatic and normal skin. Br J Dermatol 1995;132:32–8.
    OpenUrlCrossRefPubMed
  84. 84.↵
    1. Veale DJ,
    2. Ritchlin C,
    3. Fitzgerald O
    . Immunopathology of psoriasis and psoriatic arthritis. Ann Rheum Dis 2005;64:26–9.
    OpenUrl
  85. 85.↵
    1. Wakkee M,
    2. Thio HB,
    3. Prens EP,
    4. Sijbrands EJ,
    5. Neumann HA
    . Unfavourable cardiovascular risk profiles in untreated and treated psoriasis patients. Atherosclerosis 2007;190:1–9.
    OpenUrlCrossRefPubMed
  86. 86.↵
    1. Hahn BH,
    2. Grossman J,
    3. Chen W,
    4. McMahon M
    . The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of inflammation and dyslipidaemia. J Autoimmun 2007;28:69–75.
    OpenUrlCrossRefPubMed
  87. 87.↵
    1. Hammings EA,
    2. van der Lely AJ,
    3. Neumann HA,
    4. Thio HB
    . Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypotheses 2006;67:768–73.
    OpenUrlCrossRefPubMed
  88. 88.↵
    1. Thalmann S,
    2. Meier CA
    . Local adipose tissue depots as cardiovascular risk factors. Cardiovasc Res 2007;75:690–701.
    OpenUrlAbstract/FREE Full Text
  89. 89.↵
    1. Danesh J,
    2. Wheleler JG,
    3. Hirschfield GM,
    4. Eda S,
    5. Eiriksdottir G,
    6. Rumley A,
    7. et al.
    C-reactive protein and other circulating markers of inflammation in the prediction of coronary artery disease. N Engl J Med 2004;350:1387–97.
    OpenUrlCrossRefPubMed
  90. 90.↵
    1. Bisoendial RJ,
    2. Kastelein JJ,
    3. Stroes ES
    . C-reactive protein and atherogenesis: from fatty streak to clinical event. Atherosclerosos 2007;195:10–8.
    OpenUrlCrossRef
  91. 91.↵
    1. Chodorowska G,
    2. Wojnowska D,
    3. Juszkiewicz-Borowiec M
    . C-reactive protein and alpha 2-macroglobulin plasma activity in medium-severe and severe psoriasis. J Eur Acad Dermatol Venereol 2004;18:180–3.
    OpenUrlCrossRefPubMed
  92. 92.↵
    1. Chodorowska G,
    2. Juszkiewicz-Borowiec M,
    3. Czelej D,
    4. Wojnowska D,
    5. Kowal M
    . Activity of tumour necrosis factor-alfa (TNF-alpha) and selected acute phase proteins in plasma of psoriatic patients receiving local treatment. Ann Univ Mariae Curie Sklodowska (Med) 2001;56:165–9.
    OpenUrlPubMed
  93. 93.↵
    1. Rowe IF,
    2. Sheldon J,
    3. Riches PG,
    4. Keat AC
    . Comparative studies of serum and synovial fluid C reactive protein concentrations. Ann Rhem Dis 1987;46:721–6.
    OpenUrlAbstract/FREE Full Text
  94. 94.↵
    1. Sitton NG,
    2. Dixon JS,
    3. Bird HA,
    4. Wright V
    . Serum biochemistry in rheumatoid arthritis, seronegative arthropathies, osteoarthritis, SLE and normal subjects. Br J Dermatol 1987;26:131–5.
    OpenUrl
  95. 95.↵
    1. Cervini C,
    2. Leardini G,
    3. Mathieu A,
    4. Punzi L,
    5. Scarpa R
    . Psoriatic arthritis: epidemiological and clinical aspects in a cohort of 1,306 Italian patients. Reumatismo 2005;57:283–90.
    OpenUrlPubMed
  96. 96.↵
    1. Kakafika AI,
    2. Liberopoulos EN,
    3. Mikhailidis DP
    . Fibrinogen: a predictor of vascular disease. Curr Pharm Des 2007;13:1647–59.
    OpenUrlCrossRefPubMed
  97. 97.↵
    1. Dziedzic T
    . Clinical significance of acute phase reaction in stroke patients. Front Bisoci 2008;13:2922–7.
    OpenUrlCrossRef
  98. 98.↵
    1. Rocha-Pereira P,
    2. Santos-Silva A,
    3. Rebelo I,
    4. Figuiredo A,
    5. Quintanilha A,
    6. Teixera F
    . The inflammatory response in mild and in severe psoriasis. Br J Dermatol 2004;150:917–28.
    OpenUrlCrossRefPubMed
  99. 99.↵
    1. Vanizor Kural B,
    2. Orem A,
    3. Cimsit G,
    4. Yandi YE,
    5. Calapoglu M
    . Plasma homocysteine and its relationship with atherothrombotic markers in psoriatic patients. Clin Chim Acta 2003;332:23–30.
    OpenUrlCrossRefPubMed
  100. 100.↵
    1. Marongiu F,
    2. Sorano GG,
    3. Bibbo C,
    4. Pistis MP,
    5. Conti M,
    6. Mulas P,
    7. et al.
    Abnormalities of blood coagulation and fibrinolysis in psoriasis. Dermatology 1994;189:32–7.
    OpenUrlPubMed
  101. 101.↵
    1. Matsuura E,
    2. Kobayashi K,
    3. Tabuchi M,
    4. Lopez LR
    . Oxidative modification of low-density lipoprotein and immune regulation of atherosclerosis. Prog Lipid Res 2006;45:466–86.
    OpenUrlCrossRefPubMed
  102. 102.↵
    1. Tekin NS,
    2. Tekin IO,
    3. Barut F,
    4. Sipahi EY
    . Accumulation of oxidized low-density lipoprotein in psoriatic skin and changes of plasma lipid levels in psoriatic patients. Mediators Inflamm 2007;2007:78454. Epub 2006 Dec 27.
  103. 103.↵
    1. Markham T,
    2. Mullan R,
    3. Golden-Mason L,
    4. Rogers S,
    5. Bresnihan B,
    6. Fitzgerald O,
    7. et al.
    Resolution of endothelial activation and down-regulation of Tie 2 receptor in psoriatic skin after infliximab therapy. J Am Acad Dermatol 2006;54:1003–12.
    OpenUrlCrossRefPubMed
  104. 104.↵
    1. Viles-Gonzalez JF,
    2. Fuster V,
    3. Badimon JJ
    . Links between inflammation and thrombogenicity in atherosclerosis. Curr Mol Med 2006;6:489–99.
    OpenUrlCrossRefPubMed
  105. 105.↵
    1. Davi G,
    2. Patrano C
    . Platelet activation and atherothrombosis. N Engl J Med 2007;13:2482–94.
    OpenUrl
  106. 106.↵
    1. De Pita O,
    2. Ruffelli M,
    3. Cadoni S,
    4. Frezzolini A,
    5. Biava GF,
    6. Simom R,
    7. et al.
    Psoriasis: comparison of immunological markers in patients with acute and remission phase. J Dermatol Sci 1996;13:118–24.
    OpenUrlCrossRefPubMed
  107. 107.↵
    1. Cutolo M,
    2. Accardo S,
    3. Cimmino MA,
    4. Rovida S
    . Plasma fibronectin in psoriatic arthritis subgroups. Clin Rheumatol 1984;3:129–36.
    OpenUrlCrossRefPubMed
  108. 108.↵
    1. Hayashi S,
    2. Shimizu I,
    3. Miyauchi H,
    4. Watanabe S
    . Increased platelet aggregation in psoriasis. Acta Derm Venereol 1985;65:258–62.
    OpenUrlPubMed
  109. 109.↵
    1. Valentini G,
    2. Chianese U,
    3. Tirri G,
    4. Giordano M
    . Thrombocytosis in progressive generalized sclerosis (scleroderma) and in other rheumatic disease. Z Rheumatol 1978;37:233–41.
    OpenUrlPubMed
  110. 110.↵
    1. Graham IM,
    2. Daly LE,
    3. Refsum HM,
    4. Robinson K,
    5. Brattström LE,
    6. Ueland PM,
    7. et al.
    Plasma homocysteine as a risk factor for vascular disease: The European Concerted Action Project. JAMA 1997;277:1775–81.
    OpenUrlCrossRefPubMed
  111. 111.↵
    1. Malerba M,
    2. Gisondi P,
    3. Radaeli A,
    4. Sala R,
    5. Calzavara Pinton PG,
    6. Girolomoni G
    . Plasma homocysteine and folate levels in patients with chronic plaque psoriasis. Br J Dermatol 2006;155:1165–9.
    OpenUrlCrossRefPubMed
  112. 112.↵
    1. Refsum H,
    2. Helland S,
    3. Ueland PM
    . Fasting plasma homocysteine as a sensitive parameter of antifolate effect: a study of psoriasis patients receiving low-dose methotrexate treatment. Clin Pharmacol Ther 1989;46:510–20.
    OpenUrlCrossRefPubMed
  113. 113.↵
    1. Hild DH
    . Folate losses from the skin in exfoliative dermatitis. Arch Intern Med 1969;123:51–7.
    OpenUrlCrossRefPubMed
  114. 114.↵
    1. Fry L,
    2. Macdonald A,
    3. Almeyda J,
    4. Griffin CJ,
    5. Hoffbrand A
    . The mechanism of folate deficiency in psoriasis. Br J Dermatol 1971;84:539–44.
    OpenUrlPubMed
  115. 115.↵
    1. Touraine R,
    2. Revuz J,
    3. Zittoun J,
    4. Jarret J,
    5. Tulliez M
    . Study of folate in psoriasis: blood levels, intestinal absorption and cutaneous loss. Br J Dermatol 1973;89:335–41.
    OpenUrlPubMed
  116. 116.↵
    1. Segal R,
    2. Baumoehl Y,
    3. Elkayam O,
    4. Levartovsky D,
    5. Litinsky I,
    6. Paran D,
    7. et al.
    Anemia, serum vitamin B12, and folic acid in patients with rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus. Rheumatol Int 2004;24:14–9.
    OpenUrlCrossRefPubMed
  117. 117.↵
    1. Criqui MH
    . The role of alcohol in the epidemiology of cardiovascular diseases. Acta Med Scand Suppl 1987;717:73–85.
    OpenUrlPubMed
  118. 118.↵
    1. Higgins E
    . Alcohol, smoking and psoriasis. Clin Exp Dermatol 2000;25:10.
    OpenUrl
  119. 119.↵
    1. Poikolainen K,
    2. Reunala T,
    3. Karvonen J,
    4. Lauharanta J,
    5. Kärkkäinen P
    . Alcohol intake: a risk factor for psoriasis in young and middle-aged men. BMJ 1990;300:780–3.
    OpenUrlAbstract/FREE Full Text
  120. 120.↵
    1. Tobin AM,
    2. Higgins EM,
    3. Norris S,
    4. Kirby B
    . The prevalence of psoriasis in patients with alcoholic liver disease. Clin Exp Derm 2009;34:698–701.
    OpenUrlCrossRefPubMed
  121. 121.↵
    1. Kirby B,
    2. Dudley J,
    3. Tobin AM,
    4. Barry R,
    5. Rogers S,
    6. Collins P
    . Psychological distress but not alcohol intake affects the time to clearance of psoriasis patients treated with narrow-band UVB. Clin Exp Dermatol 2010 (in press).
  122. 122.↵
    1. Gupta MA,
    2. Schork NJ,
    3. Gupta AK,
    4. Ellis CN
    . Alcohol intake and treatment responsiveness of psoriasis: a prospective study. J Am Acad Dermatol 1993;28:730–2.
    OpenUrlCrossRefPubMed
  123. 123.↵
    1. Dixon WG,
    2. Watson KD,
    3. Lunt M,
    4. Hyrich KL,
    5. British Society for Rheumatology Biologics Register Control Centre Consortium,
    6. Silman AJ,
    7. et al.
    Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 2007;56:2905–12.
    OpenUrlCrossRefPubMed
  124. 124.↵
    1. Sattar N,
    2. Crompton P,
    3. Cherry L,
    4. Kane D,
    5. Lowe G,
    6. McInnes IB
    . Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. Arthritis Rheum 2007;56:831–9.
    OpenUrlCrossRefPubMed
  125. 125.↵
    1. Channual J,
    2. Wu J,
    3. Dann F
    . Effects of tumor necrosis factor-alpha blockade on metabolic syndrome components in psoriasis and psoriatic arthritis and additional lessons learned from rheumatoid arthritis. Dermatol Ther 2009;22:61–73.
    OpenUrlCrossRefPubMed
  126. 126.↵
    1. Prodanovich S,
    2. Ma F,
    3. Taylor JR,
    4. Pezon C,
    5. Fasihi T,
    6. Kirsner RS
    . Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis. J Am Acad Dermatol 2005;52:262–7.
    OpenUrlCrossRefPubMed
  127. 127.↵
    1. Ridker PM
    . Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT). J Thromb Haemost 2009; Suppl 1:332–9.
  128. 128.↵
    1. Friedewald VE,
    2. Cather JC,
    3. Gelfand JM,
    4. Gordon KB,
    5. Gibbons GH,
    6. Grundy SM,
    7. et al.
    AJC editor’s consensus: psoriasis and coronary artery disease. Am J Cardiol 2008;102:1631–43.
    OpenUrlCrossRefPubMed
  129. 129.↵
    1. Kimball AB,
    2. Gladman D,
    3. Gelfand JM,
    4. Gordon K,
    5. Horn EJ,
    6. Korman NJ,
    7. et al.
    National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening. J Am Acad Dermatol 2008;58:1031–42.
    OpenUrlCrossRefPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools

 Request Permissions

Bookmark this article

Jump to section