Psoriasis and atrial fibrillation: Exploring the intersection

Abstract

This review explores the emerging connection between psoriasis and atrial fibrillation (AF), focusing on shared inflammatory mechanisms, clinical implications, and research gaps. Psoriasis, characterized by chronic systemic inflammation, has been associated with increased AF risk, driven by elevated pro-inflammatory cytokines such as interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha. These inflammatory mediators contribute to atrial remodeling, fibrosis, and conduction abnormalities, evidenced by prolonged P-wave dispersion and atrial electromechanical delay in psoriasis patients. Severe psoriasis further exacerbates atrial dysfunction, increasing susceptibility to AF. This review synthesizes existing epidemiological and biological data, highlighting the need for interdisciplinary management of psoriasis patients to mitigate cardiovascular risks. However, the reliance on observational studies limits definitive conclusions about causality. We emphasize the necessity for large-scale, multicenter research to validate these findings, investigate genetic predispositions, and evaluate lifestyle factors and AF burden. Future research should aim to delineate the pathophysiological link between psoriasis and AF. By examining the interplay of systemic inflammation, electrophysiological changes, and clinical outcomes, this review aims to advance understanding of the psoriasis-AF link and guide strategies for early detection, prevention, and management of AF in psoriasis patients. Comprehensive care integrating dermatology and cardiology is essential for improving patient outcomes.

Key Words: Psoriasis; Atrial fibrillation; Inflammation; Cytokines; Cardiovascular disease; Biologic therapies

Core Tip: Emerging evidence indicates an intricate link between psoriasis and atrial fibrillation (AF) with a heightened risk of AF amongst psoriatic patients compared to general population. Although the exact mechanisms remain elusive, the role of chronic systemic inflammation is central to the pathogenesis of AF in psoriasis. By examining the interplay of systemic inflammation, electrophysiological changes, and clinical outcomes, this review aims to advance understanding of the psoriasis-AF link and guide strategies for early detection, prevention, and management of AF in psoriasis patients.

INTRODUCTION

Psoriasis is a chronic immune-mediated inflammatory disorder that primarily affects the skin but has widespread systemic implications. Traditionally regarded as a dermatological condition, psoriasis is now recognized as a multisystem disease associated with a range of comorbidities, particularly cardiovascular disorders[1]. Among these, atrial fibrillation (AF) has gained attention as an emerging yet underexplored comorbidity of psoriasis[2,3]. AF, the most common sustained cardiac arrhythmia, is associated with increased morbidity, stroke risk, and cardiovascular mortality. Identifying novel risk factors for AF is crucial for early intervention and prevention strategies.

Growing evidence suggests that chronic systemic inflammation in psoriasis may contribute to atrial remodeling, electrical instability, and increased AF risk[4]. Key inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-17 play a central role in both psoriasis pathogenesis and cardiovascular inflammation, creating a potential mechanistic link between the two conditions. Moreover, psoriasis patients often exhibit markers of atrial conduction abnormalities, including prolonged P-wave dispersion (PWD) and atrial electromechanical delay (AEMD), both of which are associated with AF development[5,6]. However, the precise biological mechanisms linking psoriasis and AF remain incompletely understood, and most available data come from observational studies.

This review aims to comprehensively examine the relationship between psoriasis and AF, focusing on shared inflammatory mechanisms, epidemiological evidence, electrophysiological and structural cardiac changes, and potential clinical implications. Additionally, we highlight the need for large-scale, multicenter studies to establish causality and explore genetic predispositions, lifestyle factors, and AF burden. By providing a better understanding of this association, we aim to encourage early cardiovascular risk assessment in psoriasis patients and promote an interdisciplinary approach to patient care.

EPIDEMIOLOGICAL EVIDENCE LINKING PSORIASIS AND AF

Liu and Li first proposed a hypothesis linking psoriasis to AF in response to evidence that systemic inflammation, especially elevated C-reactive protein (CRP), connects psoriasis to cardiovascular disease[7]. Drawing on their prior research showing that high baseline CRP levels predict both cardioversion failure and AF recurrence, they suggested that the inflammatory milieu of psoriasis—especially in patients with metabolic comorbidities—could contribute to atrial remodeling and arrhythmogenesis. Although direct evidence was limited at the time, their hypothesis highlighted a biologically plausible link that has since spurred further investigation. Additionally, they referenced early findings showing increased supraventricular premature beats in psoriasis patients, a potential precursor to AF[8].

A Danish nationwide cohort study by Ahlehoff et al[9] was one of the first large-scale investigations to establish a quantifiable association between psoriasis and AF risk. The study followed 36765 patients with mild psoriasis and 2793 with severe psoriasis, comparing them to over 4.4 million individuals in the general population. The findings revealed a severity-dependent increase in AF risk, with rate ratios (RRs) of 1.50 and 2.98 in psoriasis patients under 50 years with mild and severe disease, respectively, and smaller but still significant increases in older age groups. These results provided early epidemiological support for the hypothesis that chronic systemic inflammation in psoriasis contributes to atrial remodeling and arrhythmogenesis. The study also highlighted a similar severity-dependent risk of ischemic stroke, reinforcing the broader cardiovascular implications of psoriasis. These findings have since paved the way for further investigations into the mechanistic pathways linking psoriasis and AF and underscore the need for early cardiovascular screening in psoriasis patients.

However, Armstrong et al[10] found no significant association between psoriasis and incident AF. In a large cohort study comparing 2078 psoriasis patients with 6234 matched controls, the 5-year incidence of AF was similar between the two groups (2.5% vs 3.3%, P = 0.4). Electrocardiographic analysis in a separate group of 169 psoriasis patients with coronary heart disease also showed no significant differences in conduction parameters compared to controls. These findings suggest that while systemic inflammation is a known contributor to AF risk, psoriasis alone may not be an independent predictor of AF. However, the study had limitations in power to detect small subgroup differences.

Egeberg et al[11] conducted a Danish nationwide cohort study that revealed an increased risk of AF and stroke in psoriasis patients with concomitant depression. The study found that while psoriasis alone was associated with a modestly increased AF risk [hazard ratio (HR) = 1.17, 95%CI: 1.11-1.24], this risk was significantly higher in psoriasis patients with depression (HR = 1.24, 95%CI: 1.12-1.38). A similar trend was observed for stroke, with patients with severe psoriasis and depression having the highest stroke risk (HR = 2.47, 95%CI: 2.07-2.95). These findings suggest that mental health may be a critical modifier of cardiovascular risk in psoriasis patients. Given the shared inflammatory pathways in psoriasis, depression, and AF, these results highlight the need for integrated management strategies addressing both dermatologic and psychiatric comorbidities to mitigate cardiovascular complications.

Parisi et al[12] conducted a large cohort study using the Clinical Practice Research Datalink to assess the relationship between psoriasis and major cardiovascular events (MACEs), including AF. Among 48523 psoriasis patients and 208187 controls followed for a median of 5.2 years, the study found that psoriasis patients had a higher prevalence of traditional cardiovascular risk factors such as hypertension, diabetes, and chronic kidney disease. However, after adjusting for these comorbidities, psoriasis was not independently associated with an increased risk of MACEs, including AF (HR = 1.02, 95%CI: 0.95-1.08).

The losartan intervention for endpoint (LIFE) study provided one of the strongest epidemiological links between psoriasis and new-onset AF, particularly in hypertensive patients with left ventricular hypertrophy[13]. In a cohort of 7099 hypertensive patients, Bang et al[13] found that patients with psoriasis had nearly double the risk of developing AF compared to those without psoriasis (HR = 1.97, 95%CI: 1.18-3.30, P = 0.01), even after adjusting for age, diabetes, and other cardiovascular risk factors. A propensity-matched analysis confirmed this association [odds ratio (OR) = 3.49, 95%CI: 1.24-9.81, P = 0.018]. These findings suggest that psoriasis contributes to atrial arrhythmogenesis beyond traditional cardiovascular risk factors, reinforcing the role of systemic inflammation as a key driver of AF development in psoriasis patients.

Rhee et al[14] conducted a nationwide cohort study using data from the Korean National Insurance Service to assess the relationship between psoriasis severity and AF risk over a 9.6-year follow-up[14]. Among 13385 psoriasis patients, those with severe psoriasis had a significantly higher risk of developing AF (adjusted HR = 1.44, 95%CI: 1.14-1.82, P = 0.002), while mild psoriasis showed no significant effect. Similarly, the risk of thromboembolic events was elevated in severe psoriasis patients (adjusted HR = 1.26, 95%CI: 1.07-1.47, P = 0.005). These findings suggest that the pro-inflammatory and pro-thrombotic state of severe psoriasis independently contributes to AF and TE risk, reinforcing the need for closer cardiovascular monitoring and stroke prevention strategies in high-risk patients.

While observational studies have reported an association between psoriasis and increased cardiovascular risk, residual confounding has made it difficult to establish a direct causal relationship. A recent mendelian randomization (MR) study aimed to address this limitation by leveraging genetic data to assess whether psoriasis itself, independent of traditional risk factors, contributes to an elevated risk of AF[15]. The analysis found that genetic susceptibility to psoriasis was associated with a modest but statistically significant increase in AF risk (OR = 1.04, 95%CI: 1.02-1.07, P = 0.000327), suggesting a potential causal link. Additionally, psoriasis was also linked to other cardiovascular conditions, including heart failure and large artery stroke, reinforcing the notion that chronic systemic inflammation plays a key role in cardiovascular pathology.

Understanding how psoriasis progresses to cardiovascular disease over time is crucial for identifying high-risk patients early. A large-scale registry-based study explored 5-year comorbidity trajectories in psoriasis patients and found a statistically significant sequence from psoriasis to hypertension to AF and flutter, suggesting a progressive cardiovascular risk pattern in these individuals[16]. These results emphasize the importance of routine cardiovascular screening and proactive management of hypertension in psoriasis patients to mitigate long-term arrhythmic complications.

A meta-analysis by Yang et al[3] pooled data from six observational studies including 11187 AF patients and found that psoriasis was associated with a 39% increased risk of developing AF [pooled relative risk (RR) = 1.39, 95%CI: 1.257-1.523, P < 0.0001]. The risk appeared to be higher in patients with severe psoriasis, and regional differences were noted, with North American studies reporting a slightly greater risk (RR = 1.48) compared to European studies (RR = 1.43). Despite heterogeneity among studies, these findings reinforce the need for heightened cardiovascular surveillance in psoriasis patients, particularly those with severe disease.

A systematic review and meta-analysis by Jain et al[2] further confirmed the association between psoriasis and AF by analyzing seven cohort studies involving 10974668 participants. The study found that psoriasis patients had a significantly increased AF risk (HR = 1.28, 95%CI: 1.20-1.36, P < 0.00001), with a slightly higher risk in severe psoriasis (HR = 1.32) compared to mild psoriasis (HR = 1.21), although this difference was not statistically significant (P = 0.17).

The variation in findings across these studies may, in part, reflect important methodological differences. Differences in AF definitions [e.g., electrocardiogram (ECG) -confirmed vs coded diagnoses], the inclusion of predominantly mild psoriasis cases in some cohorts, limited power for subgroup analyses, and variable adjustment for confounding factors such as biologic use, depression, and cardiovascular comorbidities likely contribute to the heterogeneity. For instance, the null association reported by Armstrong et al[10] may be attributed to their reliance on a largely mild psoriasis cohort and the potential underdetection of paroxysmal AF, while studies like the LIFE[13] and Rhee et al[14] cohorts focused on higher-risk populations, such as those with hypertension or more severe skin disease. Similarly, the findings of Parisi et al[12], in which the association between psoriasis and AF lost significance after adjustment for comorbid conditions, underscore the influence of confounding in attenuating observed risk estimates. These methodological nuances are critical to consider when interpreting the strength and generalizability of the association between psoriasis and AF.

PATHOPHYSIOLOGY OF PSORIASIS AND SYSTEMIC INFLAMMATION

Psoriasis is characterized by epidermal hyperplasia, parakeratosis, and a dense inflammatory infiltrate consisting primarily of T cells, dendritic cells, and neutrophils, which collectively contribute to the release of pro-inflammatory mediators with systemic effects[17]. Psoriasis is increasingly recognized as a systemic inflammatory disorder that extends beyond the skin, potentially contributing to AF through chronic immune activation. Elevated levels of pro-inflammatory cytokines, including IL-2, IL-6, IL-12, and TNF-α, are common in psoriasis and are known to promote vascular inflammation, arterial stiffness, and endothelial dysfunction—all of which are associated with AF development[18,19]. These inflammatory mediators have been implicated in atrial remodeling, facilitating both structural and electrical changes that create a substrate for arrhythmia[20].

Histopathological studies of atrial tissue in AF patients have shown inflammatory cell infiltration, cardiomyocyte necrosis, and increased fibrosis, reinforcing the role of inflammation in AF pathogenesis[21]. Elevated CRP levels, frequently observed in psoriasis, have been correlated with greater AF burden and lower success rates of cardioversion, suggesting that chronic inflammation may not only initiate but also perpetuate arrhythmia[22]. TNF-α, in particular, has been shown to activate the transforming growth factor-beta (TGF-β) signaling pathway, promoting fibrosis through the upregulation of matrix metalloproteinases-2 and -9[23]. Additionally, platelet-derived growth factor-A (PDGF-A) secreted by mast cells stimulates fibroblast proliferation and collagen deposition, further contributing to atrial fibrosis and structural remodeling[24].

Beyond structural changes, inflammatory cytokines also influence atrial electrical properties, promoting arrhythmogenesis. TNF-α has been shown to alter calcium handling in pulmonary vein cardiomyocytes, which can trigger abnormal automaticity and conduction disturbances[25]. Similarly, PDGF-A has been associated with shortened action potential duration and reduced calcium transients, creating a pro-arrhythmic environment[1]. The combination of structural and electrical remodeling driven by chronic inflammation appears to be a key mechanism linking psoriasis to AF (Figure 1).

Figure 1 Conceptual diagram illustrating the mechanisms linking psoriasis-related chronic systemic inflammation to increased risk of atrial fibrillation. Chronic inflammatory mediators (interleukin-6, interleukin-17, tumor necrosis factor-alpha, C-reactive protein, interleukin-12) promote vascular dysfunction, atrial structural remodeling, and electrical disturbances. These interconnected pathways lead to increased atrial fibrillation vulnerability and thromboembolic risk. Additional risk modifiers and comorbidities (e.g., depression, metabolic syndrome) may exacerbate cardiovascular risk in psoriasis patients. IL: Interleukin; TNF-α: Tumor necrosis factor-alpha; TGF-β: Transforming growth factor-beta; CRP: C-reactive protein.

Beyond systemic inflammation, adipose tissue dysfunction has been proposed as a key contributor to cardiovascular complications in psoriasis. Inflammatory activation of epicardial adipose tissue (EAT), which surrounds the heart, may play a role in atrial remodeling and the development of AF[26]. EAT secretes pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, which can directly affect atrial structure and function, contributing to conduction abnormalities and increased thromboembolic risk[27,28]. Increased EAT volume and inflammation have been observed in psoriasis patients, correlating with systemic inflammatory markers and cardiovascular risk[29]. These insights suggest that strategies targeting systemic and adipose tissue inflammation could play a role in reducing AF risk in this population.

ELECTROPHYSIOLOGICAL AND STRUCTURAL CARDIAC CHANGES IN PSORIASIS

One of the earliest studies investigating the cardiac electrophysiology of psoriasis patients revealed a significant increase in heart rate and supraventricular beats, even in the absence of preexisting cardiovascular disease[8]. Using 24-hour Holter monitoring, Markuszeski et al[8] found that psoriasis patients had a higher mean heart rate both during the day (88 ± 8 bpm vs 73 ± 6 bpm, P < 0.0001) and at night (71 ± 7 bpm vs 63 ± 4 bpm, P < 0.0001) compared to healthy controls. Notably, the frequency of single supraventricular beats was significantly elevated (34 ± 25 beats per 24 hours vs 10 ± 15 beats per 24 hours, P < 0.0001), suggesting subclinical conduction abnormalities. Furthermore, there was a positive correlation between increased heart rate and disease severity [Psoriasis Area Severity Index (PASI) score], reinforcing the hypothesis that systemic inflammation in psoriasis contributes to autonomic dysfunction and pro-arrhythmic conditions. While ventricular arrhythmias and conduction disturbances were not significantly different between the two groups, the findings indicate that psoriasis may predispose patients to atrial electrophysiological changes, potentially serving as an early marker for AF risk.

Bacaksiz et al[30] provided further electrocardiographic evidence linking psoriasis vulgaris to atrial conduction abnormalities, reinforcing the hypothesis that chronic inflammation may predispose psoriasis patients to AF. The study found that PWD, a known predictor of AF risk, was significantly prolonged in psoriasis patients compared to healthy controls (69.1 ± 22.6 ms vs 45.6 ± 19.4 ms, P < 0.001). Additionally, maximum P-wave duration (Pmax) was longer (112.6 ± 22.7 ms vs 93.0 ± 12.8 ms, P < 0.001), while minimum P-wave duration (Pmin) was lower in psoriasis patients (42.2 ± 12.5 ms vs 47.4 ± 14.3 ms, P = 0.04). Notably, PWD correlated with both psoriasis severity (PASI score) and high-sensitivity CRP (hsCRP) levels (P < 0.01), suggesting that inflammation-driven atrial conduction abnormalities may serve as an early marker of AF susceptibility in psoriasis.

Aksan et al[6] provided echocardiographic evidence of atrial conduction abnormalities in psoriasis patients, supporting the role of systemic inflammation in AF susceptibility. The study found prolonged AEMD in psoriasis patients compared to controls (21.7 ± 5.6 ms vs 15.2 ± 4.1 ms, P < 0.001) and an increase in PWD (40.2 ± 9.1 ms vs 36.1 ± 7.9 ms, P = 0.043). Both parameters correlated with psoriasis severity (PASI score) and hsCRP levels. Yildiz et al[5] also reported prolonged intra-atrial (15 ± 7 ms vs 12 ± 5 ms, P = 0.009) and inter-atrial (28 ± 7 ms vs 23 ± 7 ms, P = 0.002) AEMD in psoriasis patients, along with significantly higher PWD (35 ± 9 ms vs 20 ± 6 ms, P < 0.001).

Tasal et al[31] further reinforced the link between psoriasis and atrial conduction abnormalities by demonstrating that intra- and interatrial electromechanical delay (IA-EMD) were significantly prolonged in psoriasis patients compared to controls. A positive correlation was observed between psoriasis severity (PASI score) and IA-EMD (r = 0.261, P < 0.001), as well as between hsCRP levels and IA-EMD (P = 0.022). These findings further highlight the potential role of electromechanical delay as a predictor of AF risk in psoriasis patients.

Emerging evidence suggests that psoriasis may induce subclinical atrial dysfunction, contributing to AF risk even before overt arrhythmic manifestations occur. Duman et al[32] assessed total atrial conduction time (TACT) and left atrial global longitudinal strain (LAGLS) in psoriasis patients, identifying prolonged TACT (103.5 ± 3.7 ms vs 99.1 ± 4.4 ms, P < 0.05) and reduced LAGLS (28.2% ± 7.4% vs 42.0% ± 3.7%, P < 0.05) compared to healthy controls. These changes correlated with disease duration and severity (PASI score), suggesting that chronic inflammation and oxidative stress contribute to atrial remodeling. The study also found a moderate positive correlation between TACT and PWD, reinforcing the role of conduction heterogeneity in AF predisposition. These findings highlight the potential of LAGLS and TACT as early echocardiographic markers of atrial vulnerability in psoriasis patients, underscoring the need for routine cardiovascular assessment, particularly in those with long-standing disease.

Evidence continues to build supporting the role of subclinical cardiac abnormalities in psoriasis, particularly in relation to atrial conduction and pulmonary vascular changes. Aryanian et al[33] conducted a case-control study evaluating PWD and pulmonary artery pressure (PAP) in psoriasis patients without known cardiovascular disease. The study found that PWD was significantly higher in psoriasis patients compared to controls (P = 0.022). Additionally, abnormal PAP (> 30 mmHg) was observed in a significantly greater proportion of psoriasis patients (P < 0.001). While left ventricular diastolic function was not significantly different between groups, these findings highlight the need for early cardiovascular assessment in psoriasis patients to identify potential arrhythmic and hemodynamic risks before clinical manifestations develop.

BIOMARKERS AND INFLAMMATORY MEDIATORS IN PSORIASIS AND AF

CXC motif chemokine ligand 1 (CXCL1), a key player in neutrophil recruitment and inflammation, has been implicated in both psoriasis and AF. CXCL1 functions through its primary receptor, CXCR2, which is expressed on vascular endothelial cells and immune cells, contributing to inflammatory responses and vascular remodeling[34]. Studies have shown that increased CXCL1 expression, driven by pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-17, correlates with both psoriasis severity and cardiovascular dysfunction[35]. Elevated CXCL1 levels have been associated with increased neutrophil infiltration, endothelial dysfunction, and pro-thrombotic states, all of which may contribute to AF pathogenesis[36]. Additionally, the activation of the CXCL1-CXCR2 axis in cardiac tissue has been linked to atrial fibrosis, a key structural alteration predisposing to AF[24,37]. Given its role in both skin and cardiovascular inflammation, CXCL1 represents a potential biomarker for assessing AF risk in psoriasis patients and may serve as a therapeutic target for mitigating cardiovascular complications in this population.

Recent bioinformatics and immune infiltration analyses have identified potential molecular mechanisms linking psoriasis and AF. A study using data from the Gene Expression Omnibus database identified 1627 differentially expressed genes in psoriasis and AF, with 119 genes common to both conditions[4]. Key hub genes such as GZMB, FCGR3B, LILRB2, IL7R, CD2, MYD88, NCF2, TLR2, GZMA, and CXCR2 were implicated in shared inflammatory pathways, with receiver operating characteristic analysis confirming their diagnostic potential in both diseases. Additionally, immune cell infiltration analysis revealed significant changes in T follicular helper cells, gamma delta T cells, and monocytes, suggesting a role for immune dysregulation in AF pathogenesis among psoriasis patients. Moreover, HLA-DR+ natural killer cells and CD39-expressing granulocytes were identified as potential immunophenotypic traits influencing both conditions, reinforcing the hypothesis that systemic immune activation contributes to atrial remodeling and arrhythmogenesis.

CLINICAL IMPLICATIONS AND RISK ASSESSMENT

A recent multicenter study investigating catheter ablation outcomes in AF patients with psoriasis revealed that psoriasis patients had significantly higher preprocedural CRP levels (0.85 mg/dL vs 0.3 mg/dL, P < 0.001), indicating an underlying inflammatory burden that could contribute to atrial remodeling and arrhythmogenesis[38]. Electroanatomical mapping demonstrated a greater extent of left atrial low-voltage regions (20% vs 5%, P = 0.013), suggesting more severe atrial cardiomyopathy in psoriasis patients. Over a median follow-up of 20 months, 40% of psoriasis patients experienced AF recurrence post-ablation, compared to 24% of matched controls (P = 0.023). Multivariable analysis identified psoriasis history (HR = 2.2, P = 0.046) and pre-ablation CRP levels (HR = 1.2, P = 0.016) as independent predictors of AF recurrence. Notably, a CRP threshold of 1 mg/dL was associated with significantly increased AF recurrence risk, with survival free from arrhythmia dropping to 15% in psoriasis patients with CRP > 1 mg/dL compared to 76% in those with lower CRP levels.

The Danish nationwide cohort study by Ahlehoff et al[39] highlighted that psoriasis patients with nonvalvular AF have a significantly higher risk of thromboembolism and fatal stroke. Among 99,357 AF patients, those with severe psoriasis had a 27% higher risk of thromboembolism [Incidence RR (IRR) = 1.27, 95%CI: 1.02-1.57] and a 51% increased risk of fatal stroke (IRR = 1.51, 95%CI: 1.12-2.05) compared to AF patients without psoriasis. Further, the CHA₂DS₂-VASc score is known to underestimate stroke risk in severe psoriasis patients, suggesting that conventional thromboembolism risk stratification tools may not fully account for inflammation-driven cardiovascular risk in this population[40]. These findings underscore the need for more aggressive stroke prevention strategies, including reconsideration of anticoagulation thresholds, in psoriasis patients with AF.

Identifying simple, cost-effective biomarkers for cardiovascular risk in psoriasis is crucial for early intervention. Conic et al[41] investigated red cell distribution width (RDW) and mean platelet volume (MPV), two markers routinely measured in complete blood counts, as predictors of MACE, including AF. The study found that psoriasis patients with elevated RDW had a significantly higher risk of AF (OR = 2.5, 95%CI: 2.2-2.7), while those with high MPV also showed increased AF risk (OR = 1.71, 95%CI: 1.47-1.99). These findings suggest that RDW and MPV could serve as simple screening tools to identify psoriasis patients at greater cardiovascular risk. While further validation is needed, incorporating these markers into routine assessments may help dermatologists and cardiologists stratify risk and initiate preventive strategies earlier in high-risk patients.

THERAPEUTIC CONSIDERATIONS AND FUTURE DIRECTIONS

Emerging evidence suggests that the cardiovascular effects of biologic therapies may be shaped by their specific immunologic targets. IL-17 and IL-23 inhibitors, widely used in psoriasis, may attenuate atrial inflammation by suppressing neutrophil recruitment via the CXCL1–CXCR2 axis, thereby reducing local cytokine release and oxidative stress that contribute to atrial remodeling[34]. In contrast, TNF-α inhibitors (TNFi), while broadly anti-inflammatory, may have complex effects on cardiac electrophysiology. TNF-α can modulate TGF-β and PDGF signaling pathways, both of which are implicated in atrial fibrosis and structural remodeling, but it also influences calcium handling in cardiomyocytes, potentially promoting arrhythmogenesis under certain conditions[42,43]. Thus, the net effect of biologics on AF risk may vary by pathway, with IL-17/23 blockade offering a potentially more targeted anti-fibrotic effect, whereas TNF-α blockade may exert broader, but less predictable, influence on atrial structure and conduction.

The role of biologic therapies in modifying cardiovascular risk in psoriasis patients remains an area of active investigation. While TNFi (e.g., adalimumab, etanercept) have been associated with potential cardioprotective effects, evidence on other biologic therapies, such as IL-12/23 inhibitors (e.g., ustekinumab), has been limited. A large cohort study by Lee et al[44] analyzed data from 60028 patients with psoriasis or psoriatic arthritis to compare the risk of new-onset AF and MACE in ustekinumab vs TNFi users. The study found no significant difference in AF risk between the two groups (adjusted HR = 1.08, 95%CI: 0.76-1.54), suggesting that ustekinumab does not confer an additional AF risk compared to TNFi. These findings provide reassurance regarding the cardiovascular safety of IL-12/23 pathway inhibition, though further long-term studies are needed to clarify its effects on inflammation-mediated arrhythmogenesis. Future research should also explore whether specific biologic agents may differentially impact AF risk in psoriasis patients based on underlying inflammatory profiles and cardiovascular comorbidities.

While biologic therapies appear to reduce cardiovascular risk across inflammatory diseases, their impact may vary by diagnosis. In a large Australian cohort, biologic use was associated with lower cardiovascular event rates in both rheumatoid arthritis and psoriatic arthritis, with comparable benefit after adjustment[45]. However, psoriasis may differ from RA in its dominant cytokine pathways (IL-17/IL-23), tissue-specific inflammation, and involvement of epicardial fat, potentially leading to a distinct cardiovascular profile. Further research is needed to determine whether these disease-specific mechanisms influence AF risk and modify the cardiovascular effects of biologics in psoriasis.

A recent pharmacovigilance study using the Food and Drug Administration Adverse Event Reporting System analyzed the association between newly approved psoriasis biologics and AF, reporting elevated reporting OR (RORs) for several agents[46]. Among the biologics reviewed, risankizumab (an IL-23 inhibitor) showed the strongest association with AF (ROR = 2.4, 95%CI: 1.9-2.9, P < 0.0001), followed by tildrakizumab (another IL-23 inhibitor) (ROR = 2.5, 95%CI: 1.1-5.5, P < 0.0001) and ixekizumab (an IL-17 inhibitor) (ROR = 1.6, 95%CI: 1.3-1.9, P < 0.0001). Additionally, secukinumab (also an IL-17 inhibitor) had the highest absolute number of reported AF cases (249 adverse events). Further research is needed to clarify whether these observed signals represent true pharmacologic effects or arise from underlying patient predispositions, and whether different biologic classes differentially affect AF risk.

A proactive approach to cardiovascular monitoring and management is essential in psoriasis patients. Regular ECG screening, inflammatory marker assessments, and early identification of high-risk patients can help prevent complications. Additionally, careful selection of biologic therapies is crucial. Multidisciplinary collaboration between dermatologists and cardiologists can further optimize patient outcomes. Table 1 summarizes key recommendations for monitoring and managing psoriasis patients at risk of AF. Implementing these strategies may help reduce AF burden and improve long-term cardiovascular outcomes in this population.

Table 1 Recommendations for monitoring and managing atrial fibrillation risk in psoriasis patients.

Risk tier	Category	Recommendation	Evidence level
All patients	Integrated care approach	Multidisciplinary collaboration between dermatologists, cardiologists, and primary care providers	Class C3
Low risk (e.g., mild psoriasis, no comorbidities)	Inflammation control and lifestyle	Lifestyle modification (weight loss, smoking cessation, physical activity)	Class B2
	Cardiovascular screening	Routine evaluation of BP, lipids, glucose	Class A1
	Cardiovascular screening	Baseline ECG and risk factor review	Class B2
Moderate risk (e.g., moderate psoriasis, single comorbidity)	Risk stratification	Assess and manage comorbid obesity, diabetes, depression, hypertension	Class A1
	Cardiovascular screening	Periodic ECG focusing on P-wave dispersion and conduction delays	Class B2
	Inflammation control and lifestyle	Systemic anti-inflammatory strategies targeting adipose tissue inflammation	Class C3
High risk (e.g., severe psoriasis, ≥ 2 comorbidities, prior stroke/AF)	Risk stratification	Consider severe psoriasis (high PASI score) as high AF risk	Class B2
	Risk stratification	Use biomarkers like RDW and MPV to flag elevated CV risk	Class C3
	Stroke prevention	Early echocardiography (LA strain, fibrosis, pulmonary pressure)	Class B2
	Stroke prevention	Lower threshold for initiating anticoagulation (e.g., modified CHA2DS2-VASc)	Class B2
	Biologic therapies	Weigh AF risk in selecting biologics (e.g., IL-17, IL-23 vs TNFi)	Class C3
	Biologic therapies	Closely monitor patients starting biologics with reported AF signals in pharmacovigilance data (e.g., risankizumab, ixekizumab)	Class C3

¹Class A: Strong evidence from randomized controlled trials or meta-analyses.

²Class B: Moderate evidence from observational or non-randomized studies.

³Class C: Expert opinion or clinical rationale.

AF: Atrial fibrillation; BP: Blood pressure; CRP: C-reactive protein; IL: Interleukin; MPV: Mean platelet volume; PASI: Psoriasis Area and Severity Index; RDW: Red cell distribution width; TNFi: Tumor necrosis factor inhibitor; CV: Cardiovascular; LA: Left atrial.

Despite substantial progress in understanding the link between psoriasis and AF, several critical gaps remain. While MR studies suggest a genetic connection, large prospective cohort studies are needed to confirm a causal relationship and determine whether psoriasis-related inflammation directly induces atrial remodeling or if shared genetic and environmental factors contribute to both conditions. Further research should also explore the role of cytokines like IL-17 and TNF-α in atrial fibrosis and electrical remodeling, as well as investigate EAT as a potential modifiable target for reducing AF risk. Additionally, comparative studies of different biologic therapies, including TNFi, IL-12/23, IL-17, and IL-23 inhibitors, are necessary to assess their long-term cardiovascular safety, while post-marketing surveillance and real-world data analyses should continue monitoring for arrhythmias in biologic-treated psoriasis patients. Advancements in precision medicine approaches, such as identifying biomarkers or imaging-based predictors, could help stratify psoriasis patients by AF risk and guide personalized cardiovascular management strategies. Further studies should also examine whether a combined approach, integrating systemic anti-inflammatory treatment with targeted AF management, could more effectively reduce the burden of cardiovascular complications in psoriasis patients.

CONCLUSION

Psoriasis is increasingly recognized as a systemic inflammatory disorder with widespread cardiovascular implications, including an elevated risk of AF. Chronic inflammation, atrial remodeling, and immune dysregulation appear to drive this association, with severe psoriasis patients exhibiting a higher prevalence of atrial conduction abnormalities and stroke risk. While observational studies and genetic analyses suggest a strong link, further research is needed to establish causality and optimize clinical management strategies. Given these findings, early cardiovascular screening, proactive stroke prevention, and careful selection of biologic therapies are essential for mitigating AF risk in psoriasis patients. The integration of dermatologic and cardiologic care, alongside targeted inflammation control strategies, will be critical in reducing cardiovascular morbidity and mortality in this population. Future studies should focus on mechanistic insights, precision medicine approaches, and long-term safety evaluations of systemic therapies, ensuring a comprehensive strategy to manage both psoriasis and its cardiovascular comorbidities effectively.