The inflammatory milieu of PsA extends beyond the joints and skin, contributing to systemic metabolic disturbances and an increased risk of cardiovascular disease (CVD).^[3,4] Immune dysregulation, driven primarily by pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-17 (IL-17), sustains a state of chronic inflammation. This chronic inflammatory process plays a key role in promoting endothelial dysfunction and metabolic derangements.^[3,5] Conversely, both endothelial dysfunction and metabolic disturbances can further exacerbate inflammation, creating a self-perpetuating cycle that underlies many chronic inflammatory diseases. Identifying a single initiating factor is often challenging due to this bidirectional interplay. Several studies have reported a link between systemic inflammation in PsA and dyslipidemia, insulin resistance, and obesity, all of which are well-established risk factors for cardiovascular disea- se.^[1,6,7] Notably, the presence of subclinical atherosclerosis and increased carotid intima-media thickness (IMT) in PsA patients further underscores the cardiovascular burden associated with the disease.^[2,8]

Dyslipidemia is a well-documented metabolic abnormality in PsA, with alterations in lipid profiles contributing to a pro-atherogenic state.^[5,6] Several studies have reported elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in PsA patients, accompanied by a paradoxical reduction or functional impairment in high-density lipoprotein cholesterol (HDL-C).^[2,6-10] The atherogenic index, which represents the balance between pro- and anti-atherogenic lipid fractions, is consistently elevated in PsA, further increasing the risk of cardiovascular events. Mechanistically, chronic inflammation is believed to modify lipoprotein metabolism, impairing reverse cholesterol transport and promoting oxidative modification of LDL-C, which accelerates endothelial dysfunction and plaque formation.^[4,8]

Obesity is highly prevalent in PsA, with epidemiological studies suggesting that excess adiposity not only predisposes individuals to the disease but also exacerbates its severity.^[11] Adipose tissue, once considered an inert energy reservoir, is now recognized as an active endocrine organ that secretes various adipokines, including leptin, adiponectin, and resistin, which influence inflammatory and metabolic pathways.^[8,12] Leptin, in particular, has been implicated in PsA pathogenesis due to its dual role as an energy regulator and pro-inflammatory mediator. Elevated leptin levels have been observed in PsA patients and correlate strongly with disease activity, hs-CRP levels, and measures of obesity such as body mass index (BMI) and waist circumferen- ce.^[13,14] The interplay between adipose tissue inflammation and systemic immune activation may further perpetuate metabolic dysfunction, thereby increasing the likelihood of developing metabolic syndrome and CVD in PsA patients.^[5,12]

High-sensitivity C-reactive protein (hs-CRP) is a widely recognized biomarker of systemic inflammation and an independent predictor of cardiovascular risk.^[3,9,15] Elevated hs-CRP levels in PsA have been associated with increased disease activity, joint damage progression, and subclinical atherosclerosis.^[9,13,14] Several studies have demonstrated that hs-CRP correlates with carotid IMT, arterial stiffness, and the presence of atherosclerotic plaques, underscoring its utility in cardiovascular risk stratification.^[3,6,9,11] The inclusion of hs-CRP in risk assessment models may enhance the early detection of vascular abnormalities and facilitate targeted interventions to mitigate cardiovascular morbidity and mortality in PsA patients.^[5,8,12]

Emerging evidence suggests that subclinical atherosclerosis develops earlier and progresses more rapidly in PsA compared to the general population. Carotid artery ultrasonography studies have revealed increased IMT and a higher prevalence of atherosclerotic plaques in PsA patients, independent of traditional cardiovascular risk factors.^[15] These findings suggest that systemic inflammation exerts direct effects on vascular health, promoting endothelial dysfunction, arterial stiffness, and plaque formation.^[3,9,15] The interplay between chronic immune activation, dyslipidemia, and metabolic disturbances contributes to accelerated vascular aging and an increased burden of cardiovascular complications.

Despite growing recognition of the cardiovascular implications of PsA, metabolic and lipid abnormalities remain underdiagnosed and undertreated in routine clinical practice.^[16] Current management strategies primarily focus on controlling joint inflammation and skin manifestations, often overlooking the broader systemic consequences of the disease.^[17] Given the high prevalence of dyslipidemia, obesity, and subclinical atherosclerosis in PsA, there is an urgent need for comprehensive risk assessment tools and targeted therapeutic approaches that address both inflammatory and metabolic components.^[16–18]

Disease activity was evaluated using standard clinical indices: tender joint count (TJC), swollen joint count (SJC), and the ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP). Pain intensity was measured using a 100-mm Visual Analog Scale (VAS). The extent and severity of psoriatic skin involvement were quantified using the Psoriasis Area and Severity Index (PASI).

Metabolic parameters were assessed through both anthropometric and biochemical methods. Anthropometric measurements included waist and hip circumference, height, body weight, and calculation of body mass index (BMI, kg/m²), obtained using a standardized medical scale and stadiometer (Seca 700, Hamburg, Germany).

Venous blood samples were collected after an overnight fast and processed within 2 hours. Serum concentrations of TC, HDL-C, and TG were measured using enzymatic colorimetric methods with a Cobas c502 analyzer (Roche Diagnostics, Mannheim, Germany). LDL-C was calculated using the Friedewald formula: LDL-C = TC−(TG/2.2)−HDL-C, applicable only when TG<4.5 mmol/L.

The atherogenic coefficient (AC) was calculated as: AC = (TC−HDL-C) / HDL-C, with values >4.0 considered indicative of high cardiovascular risk.

The marker of systemic inflammation and cardiovascular risk, hs-CRP, was quantified using immunoturbidimetry on the same analyzer. hs-CRP levels were categorized as low (<1 mg/L), moderate (1–3 mg/L), or high (>3 mg/L), in accordance with the American Heart Association guidelines.

Serum leptin concentrations were determined using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (Human Leptin Quantikine ELISA, R&D Systems, Minneapolis, MN, USA), with a detection range of 7.8–1000 pg/mL. All samples were measured in duplicate, and intra-assay coefficients of variation were maintained below 5%.

Carotid artery ultrasonography was performed to evaluate subclinical atherosclerosis, including IMT and the presence of atherosclerotic plaques (AP). Mean and maximum IMT values were recorded, with an IMT measurement between 0.9 mm and 1.2 mm considered indicative of increased thickness, while localized thickening >1.2 mm was classified as atherosclerotic plaque formation.

Statistical analyses were conducted using STATISTICA 9.0 (StatSoft). Descriptive statistics were applied to summarize continuous variables, reported as means with standard deviations (M±SD) for normally distributed data and as medians with interquartile ranges for non-normally distributed data. A p-value <0.05 was considered statistically significant.

This study was conducted in accordance with the Declaration of Helsinki, and written informed consent was obtained from all participants prior to inclusion in the study.

We observed significantly elevated levels of TC, LDL-C, and TG in PsA patients compared to controls, while HDL-C levels were relatively preserved. Notably, 41.2% of PsA patients had an atherogenic coefficient (AC) >4.0, reinforcing the elevated CV risk in this population. These findings corroborate prior studies reporting altered lipid profiles in PsA, such as those by Ernste et al.^[18], who linked dyslipidemia with increased incidence of CV events, and others who described elevated LDL-C and TG in PsA despite modest changes in HDL-C^[2,8,12].

Importantly, our study enhances these previous observations by quantifying the atherogenic burden through AC and stratifying risk using widely accessible clinical biomarkers. Unlike most previous reports, we analyzed lipid profiles in conjunction with systemic inflammation and early atherosclerotic changes, thus offering a more integrated clinical model.

Our findings also revealed a fivefold increase in obesity prevalence among PsA patients, as well as significantly elevated leptin levels. More than half of PsA patients were overweight or obese, and 58% exhibited elevated leptin levels versus only 8% in controls. These findings are consistent with earlier research highlighting the central role of adiposity in systemic inflammation.^[3,9,13] However, what distinguishes our work is the strong correlation between leptin and hs-CRP (R=0.59), BMI (R=0.75), and body weight (R=0.69), which underscores leptin’s dual role as both an adipokine and an inflammatory mediator.

Whereas prior studies typically examined leptin in isolation or as a marker of adiposity, our approach places leptin within a network of interacting variables contributing to inflammation and vascular risk.^[7,9,15] This supports the growing recognition that metabolic inflammation – driven by adipokines such as leptin – plays a key role in PsA pathophysiology and CV complications.

Another novel aspect of our study is the identification of a quantitative relationship between systemic inflammation (hs-CRP) and carotid IMT. Patients with hs-CRP >10 mg/L exhibited the highest IMT values (mean 0.88 mm; max 1.07 mm) and double the rate of carotid plaque formation. This highlights chronic inflammation as a direct contributor to early vascular pathology in PsA, even in the absence of clinical CV disease.

These findings are in line with the literature on early vascular aging in PsA, such as the work by Gonzalez-Juanatey et al.^[17], and with meta-analyses demonstrating that inflammatory activity accelerates atherosclerosis^[11,18,19]. However, our study adds value by integrating these vascular findings with serum biomarkers (hs-CRP, leptin, lipid fractions), thus offering a clinically applicable model for stratifying CV risk.

Although the link between inflammation and dyslipidemia in PsA has been acknowledged in literature^[6,9], this study presents a practical framework combining easily measurable biomarkers with ultrasonographic findings to improve CV risk prediction in PsA. The use of AC, hs-CRP, and leptin – parameters that are either inexpensive or already included in clinical care – can be easily implemented in rheumatology practice.

Our findings support current guideline recommendations for aggressive CV risk management in PsA^[16,18] but also point to existing gaps in care. Lipid abnormalities, obesity, and inflammatory markers often go undetected or untreated, despite their cumulative impact on vascular health.

Future research should explore how targeted biologic therapies influence both lipid metabolism and vascular outcomes in PsA patients. Longitudinal studies incorporating multiplex cytokine profiling, advanced imaging, and intervention trials could help identify the most effective strategies to mitigate long-term CV risk.^[14,16]

This study reinforces the concept of PsA as a multisystemic disease with profound metabolic and cardiovascular consequences. By highlighting the interrelationship between lipid disturbances, leptin dysregulation, systemic inflammation, and subclinical atherosclerosis, our findings argue for a multidisciplinary approach to PsA care – one that prioritizes both rheumatologic control and cardiovascular prevention.

This study has several limitations that should be considered when interpreting the findings. First, the cross-sectional design limits the ability to establish causality between systemic inflammation, lipid metabolism alterations, and cardiovascular risk in PsA patients. Longitudinal studies are needed to determine the temporal relationship and causative mechanisms underlying these associations.

Second, while the study included a well-defined cohort of PsA patients and matched controls, potential confounding factors such as lifestyle habits, dietary intake, physical activity, and medication use (e.g., statins, biologic disease-modifying antirheumatic drugs) were not comprehensively analyzed. These factors could have influenced lipid profiles, inflammatory markers, and cardiovascular outcomes.

Third, although hs-CRP was used as a key marker of systemic inflammation and cardiovascular risk, additional biomarkers such as IL-6, TNF-α, and oxidized LDL-C were not assessed. Future studies should incorporate a broader panel of inflammatory and metabolic markers to better characterize the interplay between inflammation, lipid metabolism, and atherosclerosis in PsA.

Finally, the study population was derived from a single-center rheumatology and nephrology department, which may limit the generalizability of the findings to broader PsA populations with diverse genetic, ethnic, and environmental backgrounds. Multicenter studies with larger sample sizes and diverse cohorts are warranted to validate these results and enhance their applicability to clinical practice.

Despite these limitations, the study provides valuable insights into the metabolic and cardiovascular implications of PsA, emphasizing the need for early cardiovascular risk assessment and multidisciplinary management approaches in this patient population.