PSORIASIS and COMORBIDITIES – CARDIOVASCULAR DISEASE

WHAT IS COMORBIDITY?

Comorbidity is a concurrence of multiple diseases or disorders in association with a given disease, in this case, psoriasis.

 INCREASED RISK

 The patient with psoriasis has an increased risk of developing one or more of a number of other diseases/conditions that share many immunological features with psoriasis.

 CHART 1: Comorbidities Associated with Psoriasis 1,2,3

Metabolic Syndrome – Cardiovascular Disease

  • Arterial hypertension/ Atherosclerosis
  • Myocardial infarction (MI)
  • Dyslipidemia (Raised cholesterol)

The immunological abnormalities that lead to the development of psoriasis suggest that these patients may be at increased risk for other diseases associated with an inflammatory state. Research is yet to establish whether other diseases occur as a direct result of the systemic inflammation associated with psoriasis, as a consequence of genetically determined selection, or whether it is possible that the link between psoriasis and Cardiovascular disease and myocardial infarction (MI)  may be mediated by other factors beyond inflammation, such as psychological stress, sedentary lifestyle, or possibly poor compliance with management of cardiovascular risk factors.. 4.5

There is increasing evidence to suggest that the immune response, including activated T cells, antigen presenting cells, cytokines, and markers of systemic inflammation such as C-reactive protein, are important to the development of atherosclerosis (hardening and narrowing of the arteries) and ultimately, MI. 2 Research has shown that patients with psoriasis have a higher incidence of MI compared with control patients, with patients who have severe psoriasis as having the highest rate. The risk of MI associated with psoriasis is greatest in younger patients (under the age of 40) with severe psoriasis. This reduces with age but still remains an increased risk even after treatment for traditional cardiovascular risk factors that are associated with aging. 5

Psoriasis is also associated with hypertension (increased blood pressure). In one study researchers examined the association among hypertension, antihypertensive medication use, and risk of incident psoriasis using prospective data from a large cohort of US women. A total of 121,701 participants, of which 2477 participants were diagnosed with psoriasis, were followed for 11 years with 2 yearly questionnaires. Researchers found that a prior history of hypertension was associated with an increased risk of psoriasis among women with hypertension for 6 years or more. Specifically, hypertensive women without medication use and with current medication use were more likely to develop psoriasis compared with women who did not have hypertension. Among the individual antihypertensive drugs, only ?-blockers were associated with an increased risk of psoriasis after regular use for 6 years or more. 6

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In a United Kingdom study using a large (7.5 million patients from 415 practices) electronic medical records database (The Health Improvement Network (THIN), a random sample of patients with psoriasis between the ages of 25 and 64 years were identified. The identification parameters were a diagnosis of hypertension; confirmed psoriasis diagnosis and classified psoriasis severity. The severity classification was identified according to the National Psoriasis Foundation classification system 1) mild (limited disease with ?2% BSA affected), moderate (scattered disease with 3%-10% BSA affected), or 2) severe (extensive disease with >10% BSA affected). Blood pressure was compared to the UK National Institute of Health and Care Excellence clinical guidelines, with uncontrolled hypertension being defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. 

All patients with psoriasis who met the inclusion criteria were included in the study, yielding 680, 469, and 173 patients with mild, moderate, and severe psoriasis, respectively. The researchers found a significant positive relationship between psoriasis severity and uncontrolled hypertension independent of potential risk factors for poor blood pressure control. The likelihood of uncontrolled hypertension in patients with vs without psoriasis was greatest among those with moderate and severe skin disease, representing nearly half of the psoriasis patients seen by GPs in the United Kingdom. The findings have important clinical implications, highlighting a need for more effective management of blood pressure in patients with psoriasis, especially those with more extensive skin involvement (i.e. ?3% BSA affected).7 

The precise mechanisms that underlie psoriasis and hypertension are unknown. One theory proposed is that adipose (fat) tissue in psoriasis patients serves as a major source of angiotensinogen, which is subsequently converted to angiotensin II. Angiotensin II not only promotes salt retention by kidneys; it also stimulates T-cell proliferation. Angiotensin II also appears to promote inflammation and the development of atherosclerosis. Other theories suggest that increased visceral adipose tissue in psoriasis patients may contribute to hypertension development. Increased visceral adipose tissue may be associated with accumulation of perivascular fat, which can serve as a reservoir for activated effector T cells that promote dysfunction in both hypertension and psoriasis. Or that endothelin-1 may play an important role in the development of hypertension among psoriasis patients. Endothelin-1 is a protein that constricts blood vessels and increase blood pressure, and it is produced by several different cell types including keratinocytes. While the level of endothelin-1 is usually regulated through various mechanisms, their expression appears to be altered in psoriasis patients. 8 The connection between obesity and psoriasis, when taken in light of the above theories, is further strengthened. It is always advisable for those with moderate to severe psoriasis who are overweight to try to lose weight through sensible eating – reducing fast and fatty foods and increasing the intake of vegetables, especially green vegetables.

The development of atherosclerosis and its increased prevalence may be partially explained by the presence of atherosclerotic risk factors, e.g., diabetes, hypertension, obesity, and hyperlipidemia (increased levels of lipids in the blood, including cholesterol and triglycerides) as well as by the chronic inflammatory processes that are commonly observed in psoriasis. 9 

Researchers have found that psoriasis patients have impaired endothelial function and greater thickness of the innermost two layers of the wall of the carotid artery which leads to increased arterial stiffness. 9

Atherosclerosis, the underlying process resulting in cardiovascular events, is caused by the build up of atheromatous plaques in the inner layer of the arteries. Atheromatous plaques are an accumulation of degenerative material in the inner layer of an artery wall. The material consists of mostly macrophage cells, or debris, containing lipids, calcium and a variable amount of fibrous connective tissue. The interaction between metabolic abnormalities such as diabetes, high cholesterol etc. and the systemic proinflammatory mechanisms operating involved in psoriasis and psoriatic arthritis may explain the accelerated atherosclerotic process in these patients. Patients with psoriatic disease display abnormalities in the innate and adaptive immune system that result in high serum levels of proinflammatory cytokines that may upregulate cell-mediated immunity, promote inflammatory cell migration through the vascular endothelium (tissue that lines the interior surface of blood vessels), resulting in endothelial dysfunction and thus causing plaque formation and build up. 10

Recent studies clearly demonstrated that inflammation impairs reverse cholesterol transfer (High-density lipoprotein (HDL) cholesterol efflux) in vivo, providing evidence that inflammation impairs HDL function. HDL is a complex lipoprotein particle with a broad variety of functions, exerting atheroprotective activity via effects on the endothelium and by potent anti-inflammatory capabilities. Functional impairment of HDL may contribute to the increased cardiovascular mortality experienced by psoriatic patients. HDL from psoriasis patients and healthy controls was assessed for changed HDL composition. Researchers found that there was a significant reduction in apoA-I levels of HDL from psoriatic patients, whereas levels of apoA-II and proteins involved in acute-phase response, immune response, and endopeptidase /protease inhibition were increased. Psoriatic HDL also contained reduced phospholipid and cholesterol. The researchers found that the compositional alterations impaired the ability of psoriatic HDL to promote cholesterol efflux from macrophages. Importantly, HDL cholesterol efflux capability was more impaired as the psoriasis area and severity increased. 11

Efflux is a mechanism responsible for moving compounds, like cholesterol out of the cells.  The efflux process is extremely important because cholesterol overloading, such as occurs in the cells of the arterial walls, leads to the development of atherosclerotic plaque.12

Chronic systemic inflammation associated with psoriasis and psoriatic arthritis induces endothelial dysfunction, altered glucose metabolism, and insulin resistance that plays a significant role in the development of obesity, diabetes mellitus, dyslipidemia (high cholesterol), and cardiovascular disease such as atherosclerosis and myocardial infarction.

Those with moderate to severe psoriasis should ensure that they visit their General Practitioner to have their blood pressure and cholesterol checked and to have an ECG regularly to ensure the health of their heart.

 

 

 

 

REFERENCES

 

  1. Arzu K?l?ç, Seray Cakmak; PSORIASIS AND COMORBIDITIES; EMJ Dermatol. 2013;1:78-85.
  2. Howa Yeung et al.;Psoriasis Severity and the Prevalence of Major Medical Comorbidity – A Population-Based Study; JAMA Dermatol. 2013;149(10):1173-1179. doi:10.1001/jamadermatol.2013.5015
  3. Aurangabadkar SJ. Comorbidities in psoriasis. Indian J Dermatol Venereol Leprol 2013;79, Suppl S1:10-7
  4. Elgendy A, Alshawadfy E, Altaweel A, Elsaidi A (2016) Cardiovascular and Metabolic Comorbidities of Psoriasis. Dermatol Case Rep 1: 106.
  5. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, et al. (2006) Risk of myocardial infarction in patients with psoriasis. JAMA 296: 1735-1741.
  6. Wu S, Han J, Li W, Qureshi AA. Hypertension, Antihypertensive Medication Use, and Risk of Psoriasis.JAMA Dermatol. 2014;150(9):957-963. doi:10.1001/jamadermatol.2013.9957
  7. Takeshita J, Wang S, Shin DB, et al. Effect of Psoriasis Severity on Hypertension Control: A Population-Based Study in the United Kingdom.JAMA dermatology. 2015;151(2):161-169. doi:10.1001/jamadermatol.2014.2094.
  8. Wang Armstrong A. et al; Psoriasis and Hypertension Severity: Results from a Case-Control Study; PLoS ONE 6(3):e18227 · March 2011
  9. Kalkan G , Karada? A.s.:The Association Between Psoriasis and Cardiovascular Diseases: Eur J Gen Med 2013; 10 (Suppl 1):10-16
  10. Eder L. and Gladman D.D.; Atherosclerosis in psoriatic disease: latest evidence and clinical implications; Ther Adv Musculoskel Dis 2015, Vol. 7(5) 187–195 DOI: 10.1177/ 1759720X15591801
  11. Holzer M. et al.; Psoriasis alters HDL composition and cholesterol efflux capacity; Journal of Lipid Research Volume 53, 2012
  12. Phillips M.C.; Molecular Mechanisms of Cellular Cholesterol Efflux; J Biol Chem. 2014 Aug 29; 289(35): 24020–24029.