Connection between skin disease, heart health ushers in ‘holistic’ era of dermatology

Key takeaways:

• Skin diseases, such as psoriasis and hidradenitis suppurativa, bring with them severe cardiovascular risks.
• Addressing these risks through holistic means, including anti-obesity drugs, may improve health.

In honor of American Heart Month, Healio Dermatology interviewed experts and explored the connection between skin disease and heart health.

The discovery of this relationship can be traced back to October 2006, when JAMA Dermatology published a landmark study confirming psoriasis as an independent risk factor of myocardial infarction, or heart attacks.

The study, led by Joel M. Gelfand, MD, MSCE, FAAD, James J. Leyden Professor of Clinical Investigation, professor of dermatology and epidemiology at University of Pennsylvania’s Perelman School of Medicine and Healio Dermatology’s Chief Medical Editor, opened the door to this growing idea that skin disease and heart health are connected.

“There is emerging evidence that many dermatological conditions have systemic inflammation on a chronic basis, and in some skin diseases, this is supported by well-established evidence,” Benjamin Ungar, MD, director of the Alopecia Center of Excellence and the Rosacea & Seborrheic Dermatitis Clinic at Mount Sinai and a member of the Healio Allergy/Asthma Peer Perspective Board, told Healio. “And that chronic inflammation contributes to increased risk for cardiovascular disease (CVD).”

Psoriasis

Currently, the disease with the strongest link to cardiovascular events is psoriasis, with the indication considered an independent risk factor for heart attacks.

In the aforementioned JAMA Dermatology study, the incidences of heart attacks per 1,000 person-years for controls, patients with mild psoriasis and patients with severe psoriasis were 3.58 (95% CI, 3.52-3.65), 4.04 (95% CI, 3.88-4.21) and 5.13 (95% CI, 4.22-6.17), respectively. This was found even after adjusting for all comorbidities.

The relative risk for experiencing a heart attack varied by age, with young patients being the most at risk. For example, the study found that a patient aged 30 years with severe psoriasis was 3.1 times (95% CI, 1.98-4.86) more likely to have a heart attack than someone without psoriasis, whereas a patient aged 60 years with severe psoriasis was only 1.36 times (95% CI, 1.13-1.64) more likely.

Joel M. Gelfand

“The relationship between psoriasis and CVD is multi-factorial and likely bi-directional,” Gelfand told Healio. “The genetics that drive CVD can cause psoriasis and vice versa.”

Researchers have found that inflammatory cytokines associated with psoriasis, including T-helper cell type 1 cytokines, are also associated with accelerated atherosclerosis, which is the rapid progression of plaque buildup within arteries that can lead to a heart attack.

Gelfand’s study supports this idea, showing that other T-helper cell type 1-mediated diseases such as rheumatoid arthritis are associated with an increased risk for myocardial infarctions as well. This indicates that T-helper cell type-1-mediated diseases predispose patients to heart attacks.

Mark G. Lebwohl

“As a single standing cardiovascular risk factor, psoriasis is as important a risk factor as hypertension or diabetes,” Mark G. Lebwohl, MD, dean of clinical therapeutics and chair emeritus of the Kimberly and Eric J. Waldman Department of Dermatology at Icahn School of Medicine at Mount Sinai, told Healio. “But it turns out there are many comorbidities of psoriasis that also predispose patients to heart attacks.”

Two of these comorbidities include smoking and obesity, with a 2005 study in JAMA Dermatology by Herron and colleagues finding that the prevalence of obesity in patients in Utah with psoriasis was 34% vs. 18% in the general population (P < .001). These obesity rates were deemed a consequence of psoriasis and not a risk factor for onset of disease. The prevalence of smoking was also higher in the psoriasis population vs. the general population (37% vs. 13%; P < .001).

“The stress of psoriasis and coping mechanisms such as smoking and drinking can further increase CVD risk,” Gelfand explained, pointing out that patients with psoriasis are systemically under-screened and undertreated for cardiovascular risk factors such as high blood pressure, diabetes and cholesterol. “The result is that patients with psoriasis experience premature mortality, much of it due to excess cardiovascular risk.”

Other dermatologic indications

The connection between heart health and psoriasis may be the strongest, but it is certainly not the only one. Research has also shown that patients with hidradenitis suppurativa experience heightened cardiovascular risks.

As Healio previously reported, genetic variants found in HS may also be correlated to genetic variants in coronary artery disease and diabetes, according to a 2024 study by Nielsen and colleagues.

The JAMA Dermatology study found that patients with a high genetic risk for developing HS were 1.09 times (95% CI, 1.06-1.12) and 1.13 times (95% CI, 1.1-1.17) more likely to develop coronary artery disease and diabetes, respectively, compared with individuals with a low genetic risk for HS.

Although not as established as HS, preliminary evidence has also shown an association between poor cardiovascular outcomes and atopic dermatitis.

“There are a number of epidemiologic studies that demonstrate that people with AD are at an increased risk of various cardiovascular outcomes,” Ungar told Healio. “Depending on the study, that can be anything from myocardial infarction or stoke to congestive heart failure.”

In a study conducted by Ungar and colleagues published in the Journal of Allergy and Clinical Immunology: In Practice, 27 patients with AD and 12 healthy controls were imaged using F-fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging. The study found that patients with AD had a 1.45 times elevated aortic max target-to-background ratio value compared with healthy controls, meaning patients with AD experienced increased cardiovascular inflammation, particularly of the large vessels of the heart.

“A number of these inflammatory diseases that historically were considered skin diseases are now being recognized as being systemic inflammatory diseases as well as inflammatory skin diseases,” Ungar explained. “This is still something that is being expanded on further as time goes on.”

The future of treating cardiovascular comorbidities

The emergence of evidence regarding heart health in dermatologic conditions has shifted the conversation among clinicians on how to approach treatment with some suggesting broader options.

“I think in general the field is moving, and should be moving, towards considering the impact of skin disease beyond just the skin,” Ungar said.

Lebwohl agrees, stating that one of the aspects beyond skin that clinicians should consider when treating their patients is obesity as he argues that the growing popularity of anti-obesity medications, also known as glucagon-like peptide-1 receptor agonists, may present an additional benefit in the dermatological landscape.

“I am now routinely using them in my practice,” Lebwohl told Healio. “They are great, and patients love them.”

According to Lebwohl, several studies have shown an improvement in psoriasis after addressing obesity. One such study by Paolo and colleagues published in The American Journal of Clinical Nutrition reported that 66.7% of patients who had overweight saw a 75% in their psoriasis severity after 24 weeks of a low-calorie diet.

Another study by Haran and colleagues concluded that GLP-1s may be a promising treatment for psoriasis patients with diabetes or obesity comorbidities as they have the potential to protect against cardiovascular events as well as improve psoriasis symptoms.

“Not only does psoriasis get better but the response to psoriasis drugs improves, hypertension gets better, obesity gets better, diabetes gets better and there’s a reduction in myocardial infarctions. I mean, literally everything gets better,” Lebwohl explained. “Using an obesity drug to treat obesity will make psoriasis get better while using a psoriasis drug to treat psoriasis does not make obesity better, so the combination of the two drugs may be the best thing you could do.”

Addressing obesity benefits other dermatological conditions as well, including HS. For example, according to a 2024 research letter by Lyons and colleagues, semaglutide treatment, a GLP-1 receptor agonist, reduced the mean frequency of patient-reported flares from once every 8.5 weeks to once every 12 weeks, and reduced the average DLQI score from 13 to 9 (95% CI, 1.696-10.68).

A study by Krajewski and colleagues in 2024 also concluded that adding GLP-1s into a biologic regimen for HS can help manage significant metabolic comorbidities and, as a result, cardiovascular risks.

“I think it’s a no-brainer to use anti-obesity medicines in patients who have HS,” Lebwohl said. “I think we will find that simply reducing body weight makes HS better. It will also improve the response to HS drugs just as it does in psoriasis patients.”

As the data connecting skin disease and heart health continue to mount and anti-obesity drugs take the spotlight, researchers are beginning to pay more attention to holistic care in dermatology.

“We need to treat psoriasis holistically,” Gelfand said, “treating not just the skin and joint disease but also screening for cardiovascular risk factors and encouraging patients to have a healthy diet and exercise regularly.”

According to Gelfand, research efforts in psoriasis regarding heart health, insulin resistance, atherosclerosis and more are currently intensifying and may change the future of dermatology in other indications as well.

“These types of studies also need to be extended to other chronic inflammatory diseases,” Gelfand said, “particularly atopic eczema and HS so that we can better counsel and care for our patients.”

For more information:

Benjamin Ungar, MD, can be reached at benjamin.ungar@mountsinai.org.

References:

• Gelfand JM, et al. JAMA. 2006;doi:10.1001/jama.296.14.1735.
• Haran K, et al. Psoriasis (Auckl). 2024;doi:10.2147/PTT.S485061.
• Herron MD, et al. Arch Dermatol. 2005;doi:10.1001/archderm.141.12.1527.
• Krajewski PK, et al. J Clin Med. 2024;doi:10.3390/jcm13216292.
• Lyons D, et al. Br J Dermatol. 2024;doi:10.1093/bjd/ljae216.
• Nielsen VW, et al. JAMA Dermatol. 2024;doi:10.1001/jamadermatol.2024.3779.
• Paolo G, et al. Am J Clin Nutr. 2008;doi:10.3945/ajcn.2008.26427.
• Ungar B, et al. J Allergy Clin Immunol Pract. 2020;doi:10.1016/j.jaip.2020.07.018.