The Surprising Link Between Psoriasis and Heart Disease: What Patients Need to Know

The Surprising Link Between Psoriasis and Heart Disease: What Patients Need to Know

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Introduction

Psoriasis and cardiovascular disease are closely connected in ways that extend well beyond coincidental comorbidity. Psoriasis affects approximately 2 to 3 percent of the U.S. population, and individuals with this chronic inflammatory skin disease face up to a 50 percent higher risk of developing cardiovascular disease compared with those without psoriasis. The degree of cardiovascular risk correlates directly with psoriasis severity. Patients with severe disease exhibit up to a three-fold higher risk of myocardial infarction, a 60 percent higher likelihood of stroke, and a 40 percent greater risk of cardiovascular death. On average, life expectancy is reduced by about five years in patients with psoriasis, primarily due to cardiovascular complications.

The biological link between psoriasis and cardiovascular disease lies in systemic inflammation, which extends far beyond the skin and exerts effects on multiple organ systems. Psoriasis is now recognized as a systemic inflammatory disorder with significant cardiovascular implications rather than a condition confined to cutaneous manifestations. Pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-17, and interleukin-23 play central roles in driving chronic inflammation, which contributes to endothelial dysfunction, atherosclerosis, and thromboembolic risk.

Epidemiological data consistently demonstrate that psoriasis patients face higher risks across a wide spectrum of adverse cardiovascular outcomes. Pooled relative risk estimates confirm these associations, with values of 1.17 for myocardial infarction, 1.19 for stroke, 1.46 for cardiovascular death, 1.17 for ischemic heart disease, 1.36 for thromboembolism, and 1.35 for arrhythmia. These findings emphasize that cardiovascular complications in psoriasis are not isolated events but part of a broader systemic disease burden.

Given these risks, proactive cardiovascular risk assessment and management are critical in the care of patients with psoriasis. Screening should include evaluation of traditional risk factors such as hypertension, dyslipidemia, obesity, diabetes, and smoking status, alongside careful monitoring of systemic inflammation. Evidence suggests that lifestyle modifications, including improved diet, regular physical activity, weight control, and smoking cessation, substantially reduce cardiovascular risk in this population. Pharmacologic interventions, such as lipid-lowering and antihypertensive therapies, should be optimized where indicated. Furthermore, emerging data suggest that effective systemic treatment of psoriasis, particularly with biologic therapies targeting inflammatory pathways, may confer additional cardiovascular benefits by reducing systemic inflammation.

This review highlights the need for a multidisciplinary approach that integrates dermatology, cardiology, and primary care to address the systemic consequences of psoriasis. A comprehensive strategy that combines optimal skin disease control with aggressive management of cardiovascular risk factors has the potential to notably improve quality of life, health outcomes, and life expectancy for individuals living with psoriasis.

 

Systemic Inflammation in Psoriasis and Its Cardiovascular Impact

The connection between psoriasis and cardiovascular disease stems from a complex cascade of inflammatory events that begins in the skin and exerts systemic effects. Recent research has revealed specific molecular pathways through which psoriatic inflammation contributes to vascular dysfunction and ultimately increases cardiovascular risk.

IL-17A and TNF-α in Endothelial Dysfunction

The inflammatory milieu in psoriasis is characterized by elevated levels of IL-17A and TNF-α, which act in concert to compromise vascular health. These cytokines initiate endothelial damage through multiple mechanisms. IL-17A binds to IL-17RA receptors on endothelial cell membranes, promoting endothelial cell senescence—one of the principal causes of blood vessel dysfunction and a foundational element in atherosclerosis development. Moreover, when co-cultured with atheromatous plaques, IL-17A induces upregulation of proinflammatory mediators, particularly monocyte chemoattractant protein-1 (MCP-1) and matrix metalloprotease 9, both of which contribute to plaque instability.

A transcriptomic comparison between psoriatic skin lesions and atherosclerotic plaques revealed a dominant overlap of IFNγ and TNF-α–driven processes that synergistically inflame the endothelium, with a remarkable >5,000-fold increase in transcripts such as VCAM-1 and CXCL10 relative to control endothelial cells. Additionally, endothelial cells directly obtained from psoriasis patients exhibit a 2- to 8-fold upregulation of proinflammatory and chemotactic transcripts compared to control subjects.

Th1 and Th17 Cell Activation in Atherosclerosis

Historically, psoriasis was considered primarily a Th1-mediated disease, however, current understanding identifies it as an inflammatory condition mediated jointly by Th1 and Th17 cells. This shared immunopathogenic spectrum creates a mechanistic link between psoriasis and atherosclerosis.

In psoriasis, Th1 cells produce IFN-γ and IL-2, which act on keratinocytes to induce antimicrobial peptide production, perpetuating the inflammatory cascade. Similarly, Th1 cells play a critical role in atherosclerosis development, primarily through IFN-γ production. Elevated Th1 cells have been documented in patients with unstable angina and acute coronary syndrome, highlighting their contribution to cardiovascular pathology.

Concurrently, Th17 cells release cytokines including IL-17, IL-22, and TNF-α, which activate macrophages and dendritic cells, further propagating inflammation. Patients with acute coronary syndrome demonstrate increased Th17 cells and IL-17 levels compared to those with stable angina or non-cardiac chest pain. Animal studies underscore the pro-atherogenic role of IL-17A, as its inhibition markedly reduced atherosclerotic lesion area (P < 0.001) and maximum stenosis (P < 0.001) in mice fed a high-fat diet.

NETosis and Platelet-Neutrophil Aggregates

A novel mechanism connecting psoriasis to cardiovascular disease involves neutrophil extracellular traps (NETs) and platelet-neutrophil interactions. Neutrophils contribute to psoriasis pathogenesis by driving keratinocyte hyperproliferation through IL-17-dependent mechanisms. Furthermore, psoriasis increases neutrophil activation and the release of calcium-binding proteins (S100A8/A9), which may provide a direct link to cardiometabolic disease.

Platelet-neutrophil aggregates are approximately 40% higher in psoriasis patients compared to non-psoriatic individuals. These aggregates form when activated platelets express CD62P, which binds to P-selectin glycoprotein ligand-1 on neutrophils. Subsequently, platelets induce NET formation through various mechanisms, including CD62P signaling and release of high-mobility box group 1 protein.

Low-density granulocytes (LDGs), a neutrophil subtype, are 30% higher in psoriasis patients and correlate with coronary atherosclerosis. These LDGs colocalize with platelets and induce 50% higher in vitro endothelial damage and apoptosis through NETosis compared to other neutrophil subtypes. Additionally, platelets isolated from psoriasis patients induce up to a 20-fold increase in endothelial-derived proinflammatory cytokines such as IL-1β and IL-8.

 

Traditional Cardiovascular Risk Factors in Psoriasis Patients

Beyond systemic inflammation, psoriasis patients face an alarming prevalence of traditional cardiovascular risk factors that collectively affect more than 50% of these individuals. These modifiable risk factors remain under-recognized and undertreated, thus compounding cardiovascular risk in this population.

Hypertension and IL-17A Correlation

The relationship between psoriasis and hypertension extends beyond mere association. Hypertension severity directly correlates with IL-17A levels and psoriasis skin severity in both human patients and experimental models. In animal studies, IL-17A plays a critical role in hypertension development—mice with genetic deletion of IL-17A showed reduced hypertension and vascular dysfunction. Notably, administration of monoclonal antibodies against IL-17A and IL-17RA resulted in a 30 mm Hg decrease in blood pressure in hypertensive models. While the exact mechanism remains under investigation, IL-17A appears to affect renal sodium transporters, altering pressure natriuresis. Consequently, psoriasis patients with hypertension require more aggressive management—they are 9.5 times more likely to need dual antihypertensive therapy and 16.5 times more likely to require triple therapy compared to hypertensive patients without psoriasis.

Dyslipidemia and Oxidized HDL in Psoriasis

Psoriasis patients exhibit a distinctly atherogenic lipid profile characterized by approximately 15% lower HDL cholesterol and almost 80% reduced HDL efflux capacity. This dysfunctional HDL profile resembles that seen in diabetic patients, featuring increased LDL particle concentration and decreased LDL size.

The qualitative changes in lipoproteins are particularly concerning. Compared to healthy controls, psoriasis patients have higher lipoprotein(a) levels and 15% higher oxidized HDL, with the degree of oxidation correlating with non-calcified coronary plaque burden. Furthermore, HDL function, rather than merely its quantity, appears compromised—the paraoxonase 1 (PON1) activity, a major antioxidant enzyme that protects against HDL and LDL oxidation, shows altered levels in psoriasis. Essentially, chronic inflammation drives these lipid abnormalities, creating a vicious cycle that accelerates atherosclerosis.

Obesity and Visceral Fat Inflammation

Obesity frequently accompanies psoriasis and plays a dual role—both contributing to disease onset and exacerbating its severity through enhanced inflammatory processes. Unlike subcutaneous fat, visceral adipose tissue (VAT) demonstrates heightened metabolic activity, producing harmful mediators including leptin, resistin, and proinflammatory cytokines.

The VAT/SAT (visceral adipose tissue/subcutaneous adipose tissue) ratio has been identified as an independent predictor of death and coronary events, regardless of other cardiovascular risk factors or existing coronary artery disease. Recent data indicate correlations between unfavorable body composition profiles in psoriasis patients, disease activity, and cardiometabolic measures—specifically cholesterol:HDL ratio and triglycerides. Hence, visceral adiposity represents a critical link between psoriasis and cardiovascular disease, with adipose tissue functioning not merely as an energy storage depot but as an active immune organ producing inflammatory mediators.

Smoking and Psoriasis Severity Link

Smoking exhibits a troubling relationship with psoriasis—both as a risk factor for disease onset and as a modifier of disease severity. A meta-analysis revealed the pooled odds ratio for psoriasis risk in current smokers versus never-smokers was 1.63 (95% CI: 1.48-1.80). Additionally, a dose-response relationship exists between smoking intensity and psoriasis severity.

The pathophysiologic mechanisms connecting smoking and psoriasis are multifaceted. Nicotine activates nicotinic acetylcholine receptors found on keratinocytes and inflammatory cells, while also inducing increased secretion of inflammatory cytokines including TNF-α and IL-2. Although former smokers show reduced risk (pooled OR: 0.80, 95% CI: 0.67-0.95), the impact on treatment response remains concerning—current smokers change biologic therapies due to poor efficacy more frequently than non-smokers.

 

Screening Guidelines and Risk Assessment Tools

Effective management of cardiovascular risk in psoriasis patients requires specialized screening guidelines that account for their heightened risk profile. Current recommendations from major medical organizations offer structured approaches to identify at-risk individuals and guide appropriate interventions.

AAD/NPF 1.5x Risk Multiplier for Severe Psoriasis

The American Academy of Dermatology and National Psoriasis Foundation (AAD/NPF) guidelines recommend performing cardiovascular risk assessment in all patients with psoriasis at the time of diagnosis. According to these guidelines, patients with moderate to severe psoriasis (PASI >10% or body surface area >10%) or psoriatic arthritis have worse cardiovascular outcomes, including a significantly higher likelihood of cardiovascular events than those with mild disease.

For risk calculation, the AAD/NPF advises applying a 1.5 multiplication factor to standard cardiovascular risk scores when the patient has a body surface area involvement >10% or is a candidate for systemic therapy or phototherapy. In practice, this means a patient initially classified as “borderline risk” (5% to <7.5%) would be reclassified as “intermediate risk” (≥7.5% to <20%) after applying the multiplier.

ACC/AHA Risk Enhancer Classification

In contrast to the AAD/NPF approach, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines designate psoriasis as a “cardiovascular risk enhancer” without specifying any psoriasis severity threshold. These guidelines recommend that clinicians consider risk-enhancing factors, including psoriasis, when making decisions about initiating or intensifying statin therapy, especially for those with “borderline” or “intermediate” calculated risk.

The main impact of this classification is that it lowers the threshold for treatment with standard cardiovascular prevention medications. This acknowledges that traditional 10-year risk estimators often underestimate cardiovascular risk in psoriasis patients, who present with myocardial infarction approximately five years earlier than those without psoriasis.

Use of hs-CRP and Coronary Calcium Scoring

Beyond conventional risk calculation, additional tools can refine cardiovascular risk assessment in psoriasis patients. High-sensitivity C-reactive protein (hs-CRP) serves as a useful cardiovascular risk enhancer marker, often tracking with psoriasis skin severity, vascular inflammation, and coronary atherosclerosis. This inflammatory marker can help guide providers in performing a more personalized cardiovascular risk assessment.

Coronary artery calcium (CAC) scoring represents another valuable tool for risk stratification. Psoriasis patients, compared to matched non-psoriasis controls, have a two-fold greater odds of coronary artery calcium and a burden comparable to diabetic patients without psoriasis. CAC scoring can be particularly helpful in patients with borderline or intermediate ASCVD risk when decisions about lipid-lowering medication remain uncertain. Importantly, a CAC score of zero still indicates excess risk in autoimmune populations compared to controls. Dermatologists may refer patients to cardiologists for CAC scoring and interpretation within the context of overall patient risk.

 

 

Treatment Strategies to Reduce Cardiovascular Risk

Managing cardiovascular risk in psoriasis requires a multi-faceted approach targeting both inflammation and traditional risk factors. Evidence-based interventions can substantially mitigate heart disease risk while sometimes improving skin symptoms.

Statin Therapy in Psoriasis: Observational Evidence

Statins represent a cornerstone therapy for cardiovascular risk reduction in psoriasis patients. A retrospective study of approximately 9,000 individuals with psoriasis followed for 4.3 years revealed statin therapy reduced incident myocardial infarction with a hazard ratio of 0.31. Statins exert dual benefits—beyond lipid-lowering, they possess anti-inflammatory properties. Oral statins decreased PASI scores after eight weeks of treatment (standardized mean difference: -0.92). For borderline-risk patients (5–7.4% 10-year risk), moderate-intensity statins should be considered after shared decision-making, whereas intermediate-risk patients (7.5–19.9%) should initiate therapy to reduce LDL cholesterol by 30-49%.

Aspirin and COX-1 Inhibition in Endothelial Inflammation

Low-dose aspirin offers unique benefits through platelet COX-1 inhibition. In a randomized trial, 81 mg daily aspirin reduced brachial vein endothelial inflammatory transcript expression by over 70% compared to no treatment. This effect correlated with changes in serum thromboxane B2 levels (r=0.48). Aspirin therapy decreased endothelial IL1β and COX-2 expression, thereby improving vascular health in psoriasis patients. Presently, though, cardiovascular outcomes data for aspirin in psoriasis populations remains limited.

Lifestyle Interventions: Diet, Exercise, Smoking Cessation

Lifestyle modifications form an essential foundation for cardiovascular risk reduction. The National Psoriasis Foundation recommends:

• Hypocaloric diet for overweight/obese patients, which yields a threefold higher skin clearance rate when combined with psoriasis treatment
• Mediterranean diet, which correlates with improved skin condition, reduced fat mass, and lower hs-CRP
• Smoking cessation, which addresses both cardiovascular risk and psoriasis severity

A care coordination model implementing these interventions demonstrated high feasibility, with over 85% of participants completing cardiovascular risk assessment.

Biologic Therapies and Their Impact on Vascular Inflammation

Biologic therapies may offer cardiovascular protection alongside skin improvement. Observational data indicate TNF-α inhibitors reduce myocardial infarction risk by 50% compared to topical therapy alone. Alongside symptom control, biologics reduce inflammatory markers including hs-CRP, IL-6, and platelet-lymphocyte aggregates. Furthermore, a study using coronary CT angiography demonstrated biologic therapy decreased coronary inflammation measured via perivascular fat attenuation index. Nevertheless, despite significant skin clearance, some studies report biologics do not consistently improve metabolic parameters like lipid profiles after 12 months of therapy.

 

 

Residual Cardiovascular Risk and Research Gaps

Even with optimal treatment and apparent skin clearance, patients with psoriasis continue to face cardiovascular challenges that extend beyond visible symptoms. This residual risk presents a critical concern for clinicians managing these complex patients.

Persistent Inflammatory Markers Despite Skin Clearance

A multinational study revealed that 36.3% of psoriasis patients on biologic therapy maintained elevated high-sensitivity C-reactive protein (hs-CRP) levels ≥2 mg/L despite achieving substantial improvement in skin symptoms. This persistent systemic inflammation may account for approximately 20-30% of residual risk for cardiovascular events in psoriasis patients. On account of this continuing inflammatory state, patients require ongoing monitoring of their metabolic health, chiefly among those with obesity or fatty liver disease. Inflammation acts as a causal factor in atherosclerosis, yet studies examining anti-inflammatory therapies in psoriasis have produced conflicting cardiovascular outcomes.

Transcriptomic Evidence of Residual Disease

Molecular analyzes demonstrate that once psoriatic pathology occurs, not all changes revert to normal—even in visually healed skin. Research indicates that memory T-cells persist in resolved lesions while whole transcriptome data reveal a residual disease signature containing approximately 25% of affected genes. In reality, biopsies of apparently normal skin post-treatment show that inflammation (defined by expression of key cytokines and chemokines) remains incompletely resolved. This residual disease transcriptomic profile (DRTP) involves genes associated with WNT, TNF, and mTOR signaling pathways, potentially explaining site-specific recurrence of psoriatic lesions following treatment cessation.

Need for Randomized Trials with CV Endpoints

Currently, only canakinumab and colchicine have demonstrated ability to lower cardiovascular events, whereas most psoriasis treatments show inconclusive cardiovascular benefits. Simultaneously, randomized placebo-controlled trials targeting psoriasis skin disease to reduce vascular inflammation remain largely inconclusive. Among multiple studies examining TNF-α inhibitors, phototherapy, and IL-17A inhibitors, most patients displayed adequate skin response alongside reductions in circulating pro-inflammatory biomarkers—yet vascular arterial inflammation, the primary endpoint, typically remained unimproved after three months of treatment. Larger clinical trials with hard cardiovascular endpoints are urgently needed to better understand how anti-inflammatory medications impact long-term cardiovascular outcomes in psoriasis patients.

 

 

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Conclusion

The complex interplay between psoriasis and cardiovascular disease extends beyond mere association, representing a critical health concern for this patient population. Through multiple inflammatory pathways involving IL-17A, TNF-α, T-cell dysregulation, and neutrophil-platelet interactions, psoriasis creates a persistent pro-inflammatory state that accelerates atherosclerotic processes. Consequently, patients face substantially elevated risks for myocardial infarction, stroke, and cardiovascular mortality compared to the general population.

Traditional risk factors notably compound this inflammatory burden, with hypertension, dyslipidemia, obesity, and smoking occurring at higher rates among psoriasis patients. Therefore, comprehensive cardiovascular risk assessment must become a standard component of psoriasis management. Clinicians should apply either the AAD/NPF 1.5x risk multiplier or follow ACC/AHA guidelines categorizing psoriasis as a cardiovascular risk enhancer when calculating treatment thresholds.

Evidence increasingly suggests that therapeutic approaches targeting both skin disease and cardiovascular risk provide optimal outcomes. Statins offer particular promise through dual lipid-lowering and anti-inflammatory effects. Additionally, lifestyle modifications including Mediterranean diet adoption, weight management, and smoking cessation should accompany pharmacologic interventions. Though biologic therapies effectively target cutaneous inflammation, their impact on cardiovascular outcomes remains incompletely defined, underscoring the need for long-term studies with hard cardiovascular endpoints.

Perhaps most concerning, patients maintain elevated inflammatory markers and transcriptomic abnormalities despite apparent skin clearance. This residual disease activity likely explains persistent cardiovascular risk even after successful psoriasis treatment. Accordingly, dermatologists and cardiologists must collaborate to monitor cardiovascular health throughout the disease course, regardless of skin appearance.

Future research should focus on developing targeted interventions specifically addressing this residual inflammatory risk. Until then, clinicians must remain vigilant about comprehensive cardiovascular risk management for all psoriasis patients, particularly those with moderate-to-severe disease. The evidence clearly indicates that optimal psoriasis care extends well beyond skin clearance, ultimately requiring a holistic approach that addresses both dermatologic symptoms and cardiovascular health to improve overall patient outcomes and longevity.

Key Takeaways

Psoriasis patients face critical cardiovascular risks that extend far beyond skin symptoms, requiring comprehensive medical management and lifestyle changes.

• Psoriasis increases heart disease risk by 50% – Severe cases triple myocardial infarction odds and reduce life expectancy by 5 years due to systemic inflammation.
• Apply 1.5x risk multiplier for severe psoriasis – Use AAD/NPF guidelines to reclassify cardiovascular risk and lower treatment thresholds for prevention medications.
• Statin therapy reduces heart attacks by 69% – Beyond cholesterol benefits, statins provide anti-inflammatory effects that improve both cardiovascular and skin outcomes.
• Inflammation persists despite clear skin – 36% of patients maintain elevated inflammatory markers even after successful treatment, requiring ongoing cardiovascular monitoring.
• Lifestyle changes are essential – Mediterranean diet, weight loss, smoking cessation, and exercise significantly reduce both psoriasis severity and heart disease risk.

The key insight: Psoriasis is not just a skin condition but a systemic inflammatory disease requiring dermatologists and cardiologists to work together for optimal patient outcomes. Even when skin appears clear, cardiovascular vigilance must continue throughout the patient’s lifetime.

 

Frequently Asked Questions:

FAQs

Q1. How does psoriasis increase the risk of heart disease? Psoriasis increases heart disease risk through systemic inflammation that affects multiple organ systems. This inflammation can lead to endothelial dysfunction, atherosclerosis, and other cardiovascular complications. Patients with severe psoriasis have up to a 3-fold increased risk of myocardial infarction and a 60% higher risk of stroke.

Q2. What lifestyle changes can help manage both psoriasis and heart disease risk? Adopting a Mediterranean diet, maintaining a healthy weight, quitting smoking, and regular exercise can markedly reduce both psoriasis severity and heart disease risk. These lifestyle modifications form an essential foundation for overall health improvement in psoriasis patients.

Q3. Are psoriasis treatments effective in reducing cardiovascular risk? While psoriasis treatments, especially biologics, are effective in managing skin symptoms, their impact on cardiovascular outcomes is not fully established. Some studies show that biologics may reduce inflammation markers, but long-term cardiovascular benefits require further research.

Q4. Should all psoriasis patients undergo cardiovascular risk assessment? Yes, it’s recommended that all psoriasis patients undergo cardiovascular risk assessment at the time of diagnosis. For patients with moderate to severe psoriasis, guidelines suggest applying a 1.5 multiplication factor to standard cardiovascular risk scores to account for their increased risk.

Q5. Can psoriasis patients still have cardiovascular risk even if their skin appears clear? Yes, even when skin symptoms improve, many psoriasis patients maintain elevated inflammatory markers and transcriptomic abnormalities. This residual disease activity likely explains the persistent cardiovascular risk even after successful psoriasis treatment, emphasizing the need for ongoing cardiovascular monitoring.

 

 

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