Psoriasis Severity, Systemic Inflammation Associated with Cardiovascular Disease

Axel Svedbom, PhD

Credit: International Psoriasis Council

Psoriasis severity levels as well as systemic inflammation—measured through glycan biomarker of N-acetyl side chains of acute-phase proteins (GlycA) levels—are shown in a recent analysis to be linked with cardiovascular disease.¹

This analysis was led in part by Axel Svedbom, PhD, from the division of dermatology and venereology at the Karolinska Institutet’s department of medicine in Stockholm. Prior data have pointed to the development of cardiovascular disease in psoriasis, as there are a set of shared risk factors.

Svedbom et al. highlighted the prevalent hypothesis which concludes that the displacement of inflammatory signals from skin impacted by psoriasis to the circulation promotes systemic inflammation.² This, the hypothesis suggests, may drive buildup of coronary plaque as well as ruptures. Nevertheless, the team noted that the evidence for such a hypothesis had been limited.

“Therefore, we explored whether systemic inflammation may be a mediator of the association between psoriasis skin disease severity and CVD using data on (1) subclinical atherosclerosis in US patients with prevalent psoriasis and (2) future cardiovascular events in Swedish patients with incident psoriasis,” Svedbom and colleagues wrote.¹

Trial Design

The investigative team’s cohort study implemented data drawn from 2 distinct investigations: a cross-sectional analysis known as the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative (PACI), carried out between January 2013 - February 2022, and an inception cohort analysis known as the Stockholm Psoriasis Cohort (SPC), carried out between January 2000 - December 2005.

In PACI, consecutive patients who had been given referrals by dermatologists in Maryland were included. In SPC, consecutive patients had been referred from a wide range of different practices located in Sweden.

Overall, the research team’s analysis involved subjects with existing psoriasis drawn from the PACI cohort and newly-diagnosed psoriasis patients drawn from the SPC cohort. Their data on the 2 studies was assessed between October 2023 - January 2024.

Systemic inflammation was evaluated through the use of a glycan biomarker (GlycA) that measures N-acetyl side chains of acute-phase proteins. Severity of the skin disease, on the other hand, was determined by the team through the Psoriasis Area and Severity Index (PASI).

A mediation analysis was applied to look into a potential connection between exposure, mediator, and outcomes. The research team’s focus was on subjects with PASI scores in the first and third tertiles, with GlycA levels corresponding to those observed in individuals with PASI scores in the first tertile.

The PACI arm provided data on noncalcified coronary burden (NCB). Those included in the SPC arm contributed information on cardiovascular events such as death or hospitalization. The team’s statistical tests were 2-sided, with significance determined at a P-value of less than .05, and no adjustments were done for multiple comparisons.

Notable Findings

The researchers looked at a total of 260 eligible subjects from the PACI, with 62.3% having been reported to be male and the median age being 51 years. There were a total of 509 eligible subjects from the SPC, with 46.6% having been male and the median age being 43 years.

The investigators found that PASI scores in both cohorts were linked with GlycA level and cardiovascular disease. They also concluded that GlycA levels had an association with cardiovascular disease.

The effects, both direct and indirect, of PASI on noncalcified coronary burden were estimated by the investigators at 0.94 (95% CI, 0.26-1.74) and at 0.19 (95% CI, 0.02-0.47), respectively. The research team further reported that the odds ratios for the direct and indirect effects of PASI score on cardiovascular events were estimated at 1.23 and 1.16 (95% CI, 0.70-1.92 and 1.04-1.42, respectively).

“In conclusion, we found evidence suggesting that systemic inflammation, measured using GlycA level, may mediate the association between psoriasis disease severity, measured using PASI score, and CVD in individuals with psoriasis,” they wrote. “Future research could explore whether controlling skin disease severity can modulate subclinical atherosclerosis and the risk of future cardiovascular events.”¹

References

1. ^{Svedbom A, Mallbris L, González-Cantero Á, et al. Skin Inflammation, Systemic Inflammation, and Cardiovascular Disease in Psoriasis. JAMA Dermatol. Published online November 20, 2024. doi:10.1001/jamadermatol.2024.4433.}
2. ^{Boehncke WH. Systemic inflammation and cardiovascular comorbidity in psoriasis patients: causes and consequences. Front Immunol. 2018;9:579. doi:10.3389/fimmu.2018.00579.}