Cardiovascular risk in psoriasis, the association between psoriatic inflammation and atherosclerosis, and the cardiovascular-risk-reducing effects of biologics

In a recent study published in the Journal of Clinical Medicine, researchers explored the impact of biological interventions in reducing cardiovascular risk among psoriasis patients.

Background

Psoriasis manifests as a chronic inflammatory skin condition associated with a significant proportion of cardiovascular disease (CVD), hypertension, dyslipidemia, diabetes, obesity, and metabolic syndrome.

Cardiovascular disease is the leading cause of mortality and morbidity among psoriasis patients. Because CVD is related to considerable morbidity and death, primary care practitioners focus more on reducing the CVD risk in psoriasis patients. Systemic medications that target tumor necrosis factor α (TNFα), interleukin (IL)-17, and IL-12/23 can significantly improve the psoriasis manifestation. Recent research indicates that these inflammatory cytokines may increase atherosclerosis, indicating that biologics may be useful for treating psoriasis and lowering CVD risk.

Cardiovascular events in psoriasis patients

Psoriasis is a systemic and chronic inflammatory disorder associated with several events, including CVD, hypertension, obesity, metabolic syndrome, diabetes mellitus, and dyslipidemia. Studies have also shown that psoriatic arthritis increases CVD risk. Previous research has indicated that psoriasis patients display a significant prevalence of obesity. Obesity was also found to be associated with psoriasis severity. The pooled odds ratio (OR) was 1.46 for obese individuals with mild psoriasis and 2.23 for severe psoriasis. In addition, obesity may impact the therapeutic strategy and clinical response to medications.

In the intention-to-treat analysis, the median psoriasis area and severity index (PASI) reduction observed in the dietary intervention arm was 48%, and in the information-only arm was 25.5%. Encouraging diet restriction and physical activity among psoriasis patients who are overweight or obese can facilitate the reduction of psoriasis severity, resulting in an increase in adiponectin levels, thus preventing CVD development.

Most studies indicated that psoriasis increased CVD risk; however, some studies revealed no association of psoriasis with CVD risk. In mild and severe psoriasis requiring systemic medication, the risk of myocardial infarction (MI) and stroke was elevated in severe psoriasis. A systematic analysis demonstrated that psoriasis elevated the risk of CVDs such as stroke and MI, and statin medication is suggested for those at risk for CVD to minimize their CVD risk. In practice, however, only a minority of physicians prescribe statins to patients who require statin therapy.

Atherosclerosis in patients with psoriasis

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Psoriasis patients have displayed a higher prevalence of coronary artery plaques than healthy individuals. Inflammatory cytokines like TNF-α, IL-17, and IL-23 contribute to the underlying etiology and systemic inflammation presented in psoriasis. It has been observed that IL-1β-targeting therapies diminish atherosclerosis. Hence, researchers have proposed that TNF-α, IL-17, and IL-23-targeting therapies, which play an important role in determining psoriasis pathogenesis, may also help to decrease atherosclerosis.

Interferon (IFN)-Ɣ also plays a role in proinflammatory cytokine production, the upregulation of adhesion molecules'  gene expression, psoriasis-related cytokine production, and vascular endothelial cells and macrophage activation. Evidence shows that these activities contribute to the generation of atherosclerotic lesions.

Psoriasis treatments and CVD risk

It has been discovered that statin therapy decreases the levels of inflammatory markers in vascular endothelium. Thus, it is evident that cholesterol management is essential for minimizing the risk of CVD. Additionally, the results of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) study provided evidence that the inhibition of inflammatory cytokines lowered CVD risk. Results also confirmed that anti-inflammatory therapy using canakinumab decreased the recurrence of CVD cases. In addition, a recent study demonstrated that biologics could lower the perivascular fat attenuation index, which measures coronary inflammation.

By lowering inflammation, biologics can reduce intima-media thickness (IMT), indicating the development of subclinical atherosclerotic plaque. In a Danish cohort study, people with psoriasis who received biological treatment reported reduced CVD events. Therefore, anti-inflammatory medication that targets TNF-α, IL-17, and IL-23, the primary pathogenic agents in psoriasis, can potentially reduce the risk of CVD and psoriatic skin rash.

The IL-23/IL-17 axis is crucial to the etiology of psoriasis, and inhibiting IL-23 is extremely beneficial for treating psoriasis lesions. Several investigations demonstrated the proatherogenic function of IL-23. While high IL-23 expression is noted in atherosclerotic lesions, high IL-23 serum levels are also observed in carotid atherosclerosis patients compared to healthy controls.

Furthermore, IL-23 and IL-23R messenger ribonucleic acid (mRNA) levels are markedly increased in carotid plaques. Additionally, patients having high serum IL-23 levels reported a higher mortality rate. Also, granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances IL-23-mediated plaque progression and improves the susceptibility of macrophages to apoptosis.

Conclusion

The study findings highlighted the importance of treating psoriasis not only as a skin condition but as a systemic disease to prevent fatal cardiovascular complications. Focusing on obesity, diabetes, dyslipidemia, metabolic syndrome, and hypertension frequently related to psoriasis and offering integrated treatment is necessary. Inflammatory cytokines, primarily TNF-α, IL-17, and IL-23, are hypothesized to enhance CVD, causing both psoriasis and vascular dysfunction. Consequently, it is hypothesized that biologics targeting these molecules can positively impact psoriasis pathogenesis and the risk of CVD.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.