Brewing Beneath the Surface: The Link Between Psoriasis and Cardiovascular Disease

By Ipsita Subudhi

Peer Reviewed

When a patient comes in with skin plaques, bumps, and what might be a rash, the natural reaction might be to assume that these issues only lie skin deep. However, inflammatory skin diseases reflect a deeper underlying pathology, with the skin serving as a visual manifestation of a systemic disease process. For instance, psoriasis is linked to an increased risk of myocardial infarction and is more pronounced in those who develop psoriasis at an earlier age and with increased disease severity. Patients with severe psoriasis who are 30 years old have a 3.10 times higher risk of MI, while patients aged 60 have a 1.36 times higher risk.¹ Psoriasis is also associated with a 44% increased risk for stroke.² Therefore, it is crucial to assess the risk of cardiovascular disease in our patients presenting with psoriasis.

Psoriasis is an inflammatory skin disease affecting 125 million people globally and is characterized by demarcated scaly patches or plaques driven by unchecked immune responses.³ It confers a higher risk of comorbidities, including cardiovascular disease, depression, anxiety, and inflammatory bowel disease.³ The severity of psoriasis can be quantified by the Psoriasis Area and Severity Index (PASI) score, which takes into account induration, erythema, and percent of affected body surface. In a population-based cross-sectional study in the UK, computerized records of patients with psoriasis were matched with controls from the same medical practice; the study found that patients with a high PASI score, reflecting severe psoriasis, had a higher prevalence of cardiovascular risk factors such as obesity, hypertriglyceridemia, and hyperglycemia, which all contribute to metabolic syndrome.⁴ Therefore, metabolic and cardiovascular dysfunction underscore psoriasis as a systemic inflammatory disease.

Atherosclerosis is an inflammatory process triggered by endothelial injury and dysfunction, leading to lipid oxidation and activation of lipid-laden macrophages and leukocytes that further drive progression of disease. In the added context of skin inflammation, Baumer and colleagues (2018) demonstrated in a murine model of psoriasis that atherogenesis was accelerated compared to healthy controls without skin inflammation. Additionally, macrophages from mice with chronic skin inflammation showed an increase in cholesterol uptake.⁵ An observational, longitudinal cohort study following humans with psoriasis over four years found that those with elevated C-reactive protein (CRP), a marker of systemic inflammation, were more likely to have increased visceral adiposity and a greater coronary artery disease burden.⁶ While the exact mechanism through which skin inflammation increases cardiovascular risk is not fully understood, current evidence suggests that systemic inflammation in psoriasis promotes the inflammatory milieu that accelerates the progression of atherosclerotic disease.

While skin inflammation in psoriasis contributes to increased metabolic and cardiovascular risk, these dysfunctional metabolic factors in turn influence psoriasis progression. Preclinical work has shown that obesity can directly impact immune responses in the skin, further promoting dysregulated psoriasiform inflammation.⁷ In another study, a high-fat diet in healthy, nonobese mouse models exacerbated psoriasiform inflammation.⁷ These findings are further supported by the Nurses’ Health Study II, a prospective cohort study that found that women with increased adiposity and weight gain over the course of 14 years were more likely to develop psoriasis.⁸ Therefore, it is likely that altering the metabolic systemic state predisposes to or promotes psoriatic disease.

If cardiovascular disease and obesity contribute to the severity of skin inflammation, then does improving cardiovascular risk factors help alleviate skin disease? A clinical trial in Italy sought to answer this question by assessing whether a 20-week program of dietary intervention and physical exercise could impact psoriasis severity. While the study only included patients who were overweight or obese and had failed systemic therapy, this regimen led to a median reduction of 48% in PASI score.⁹ How these nonpharmacological interventions impact systemic inflammation is unclear.

To explore how modulating lipids affects systemic inflammation, the JUPITER trial assessed the impact of rosuvastatin on cardiovascular events and systemic inflammation as measured by CRP in otherwise healthy adults with elevated CRP but without hyperlipidemia.¹⁰ The trial was terminated after a median follow-up of 1.9 years because rosuvastatin significantly reduced cardiovascular events, cut LDL cholesterol levels by 50%, and, perhaps surprisingly, decreased CRP by 37%, indicating that statins may decrease systemic inflammation. In the context of psoriasis, there have been a handful of studies that have looked at the impact of statins on PASI scores. When combined in a meta-analysis, these studies demonstrated a statistically significant reduction in PASI scores following statin treatment, suggesting a potential benefit of statins in managing psoriasis.¹¹ While more research is needed to fully understand the link between metabolism and skin disease, modifying a patient’s metabolism with diet, exercise, or statin therapy may help attenuate systemic and skin inflammation in psoriasis.

It is difficult to untangle which comes first–the skin manifestations of psoriasis or the dysfunctional underlying metabolic and cardiovascular risk factors. The real answer, as suggested by previous and ongoing research studies and trials, is most likely a complex combination of both. So, the next time we encounter a patient with psoriasis, we should pause to check on their cardiovascular health. Patients with moderate-to-severe psoriasis are often underdiagnosed and undertreated, which makes it crucial to have a lower threshold to screen and treat cardiovascular disease risk factors such as hyperlipidemia, diabetes, and hypertension.¹² The American Heart Association’s (AHA) Predicting Risk of CVD EVENTs (PREVENT) equation, which has been validated for determining cardiovascular risk for primary prevention in the general population aged 30 to 79 years of age, does not account for inflammatory or autoimmune conditions;¹³ however, the AHA and American College of Cardiology’s 2018 guidelines on cholesterol management recognized psoriasis as one of the risk-enhancing factors that warrant initiation of statin therapy in patients between 40 and 75 years of age with an intermediate risk of cardiovascular disease.¹⁴ For rheumatoid arthritis, a “1.5 multiplier” to such equations has been suggested, which may also be a quick way to account for inflammatory risk.¹⁵ Such a multiplier has not been established or validated for inflammatory skin diseases.

While more research is underway to understand the interplay between psoriasis and cardiovascular disease, we clinicians must lower our threshold for addressing metabolic risk factors that could affect patients’ health, beyond just the symptoms brewing on their skin. After all, preventing cardiovascular disease is far more efficient than dealing with the long-term consequences, and even more so for our patients with psoriasis.

Ipsita Subudhi is a Class of 2027 medical student at NYU Grossman School of Medicine

Reviewed by Michael Tanner, MD, Executive Editor, Clinical Correlations

Image courtesy of Haley Otman, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

References

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