Cause of Mortality in Two Psoriasis Studies Conflict

MONTREAL — Mortality rates are significantly increased in patients with severe psoriasis compared with the general population, according to two new studies.

But studies have conflicting results regarding the cause of death, researchers reported at the annual meeting of the Society for Investigative Dermatology. A study by Dr. Rahat Azfar showed an age-dependent, significantly increased risk of cardiovascular death with severe psoriasis, compared with patients without psoriasis.

“Severe psoriasis may be an independent risk factor for cardiovascular mortality,” noted Dr. Azfar of the University of Pennsylvania, Philadelphia, whose study showed a 50% increase in cardiovascular death.

Her findings are in direct contrast to another study presented in the same session and conflict with a growing body of evidence. Dr. Robert Stern presented results from the 30-year PUVA Follow-Up Study, which showed no increase in cardiovascular death risk in severe psoriasis patients, all of whom had undergone PUVA.

“In patients with extremely severe psoriasis, there is an increased risk of death from noncardiovascular, but not cardiovascular causes,” said Dr. Stern, professor of dermatology at Harvard Medical School and vice chair of dermatology at Beth Israel Deaconess Medical Center in Boston.

“Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done,” commented Dr. Azfar, who declared no conflicts of interest.

Her study, which she presented at the meeting, was funded by the National Institutes of Health and a grant from Centocor. It examined more than 3,000 patients with severe psoriasis, matched to more than 14,000 controls from the United Kingdom's General Practice Research Database.

Compared with controls, patients with severe psoriasis had a significantly increased risk of all-cause mortality (odds ratio 1.78), she said. After the researchers controlled for traditional cardiovascular risk factors, psoriasis patients had a clinically significant increased risk of cardiovascular death (hazard ratio [HR] 1.55). This risk was modified by age, with patients aged 40 and younger being at greater risk (HR 2.65) than patients aged between 41 and 60 (HR 1.90). This translated to an excess risk of 5.78 cardiovascular deaths per 10,000 person-years at age 40, and 58.9 per 10,000 person-years at age 60, she said.

Dr. Stern, who declared no conflicts of interest, agreed that cardiovascular risk factors are important, but his data suggest they are no more important than other risk factors.

The data show “that liver disease and nonmelanoma skin cancer accounted for more than half the approximately 70 excess deaths we observed,” he said. His prospective study followed 1,376 patients from the PUVA Follow-Up for 28 years, from 1976 to 2004. The patients had participated in a therapeutic PUVA study in 1975–1976 in 16 tertiary care academic centers across the United States.

Comparing the observed and expected mortality rates among patients and controls, the researchers found an increased all-cause mortality rate (HR 1.51) among only those patients with the most severe psoriasis. When cause of death was examined in this group, noncardiovascular reasons explained the increased risk (HR 1.74), and there was a nonsignificant increase in the rate of cardiovascular deaths, compared with controls (HR 1.29), Dr. Stern said.

“Dr. Stern's study results need to be interpreted with extreme caution due to the inherent bias in his study design,” warned Dr. Joel Gelfand, also of the University of Pennsylvania, and principal investigator on Dr. Azfar's study.

Dr. Stern's study design compares apples to oranges, commented Dr. Gelfand. “Patients who participate in psoriasis clinical trials at tertiary care medical centers may be healthier, better educated, and have better access to medical care than the general U.S. population,” he noted. “Our study … was population based.”

'Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done.' DR. AZFAR

MONTREAL — Mortality rates are significantly increased in patients with severe psoriasis compared with the general population, according to two new studies.

But studies have conflicting results regarding the cause of death, researchers reported at the annual meeting of the Society for Investigative Dermatology. A study by Dr. Rahat Azfar showed an age-dependent, significantly increased risk of cardiovascular death with severe psoriasis, compared with patients without psoriasis.

“Severe psoriasis may be an independent risk factor for cardiovascular mortality,” noted Dr. Azfar of the University of Pennsylvania, Philadelphia, whose study showed a 50% increase in cardiovascular death.

Her findings are in direct contrast to another study presented in the same session and conflict with a growing body of evidence. Dr. Robert Stern presented results from the 30-year PUVA Follow-Up Study, which showed no increase in cardiovascular death risk in severe psoriasis patients, all of whom had undergone PUVA.

“In patients with extremely severe psoriasis, there is an increased risk of death from noncardiovascular, but not cardiovascular causes,” said Dr. Stern, professor of dermatology at Harvard Medical School and vice chair of dermatology at Beth Israel Deaconess Medical Center in Boston.

“Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done,” commented Dr. Azfar, who declared no conflicts of interest.

Her study, which she presented at the meeting, was funded by the National Institutes of Health and a grant from Centocor. It examined more than 3,000 patients with severe psoriasis, matched to more than 14,000 controls from the United Kingdom's General Practice Research Database.

Compared with controls, patients with severe psoriasis had a significantly increased risk of all-cause mortality (odds ratio 1.78), she said. After the researchers controlled for traditional cardiovascular risk factors, psoriasis patients had a clinically significant increased risk of cardiovascular death (hazard ratio [HR] 1.55). This risk was modified by age, with patients aged 40 and younger being at greater risk (HR 2.65) than patients aged between 41 and 60 (HR 1.90). This translated to an excess risk of 5.78 cardiovascular deaths per 10,000 person-years at age 40, and 58.9 per 10,000 person-years at age 60, she said.

Dr. Stern, who declared no conflicts of interest, agreed that cardiovascular risk factors are important, but his data suggest they are no more important than other risk factors.

The data show “that liver disease and nonmelanoma skin cancer accounted for more than half the approximately 70 excess deaths we observed,” he said. His prospective study followed 1,376 patients from the PUVA Follow-Up for 28 years, from 1976 to 2004. The patients had participated in a therapeutic PUVA study in 1975–1976 in 16 tertiary care academic centers across the United States.

Comparing the observed and expected mortality rates among patients and controls, the researchers found an increased all-cause mortality rate (HR 1.51) among only those patients with the most severe psoriasis. When cause of death was examined in this group, noncardiovascular reasons explained the increased risk (HR 1.74), and there was a nonsignificant increase in the rate of cardiovascular deaths, compared with controls (HR 1.29), Dr. Stern said.

“Dr. Stern's study results need to be interpreted with extreme caution due to the inherent bias in his study design,” warned Dr. Joel Gelfand, also of the University of Pennsylvania, and principal investigator on Dr. Azfar's study.

Dr. Stern's study design compares apples to oranges, commented Dr. Gelfand. “Patients who participate in psoriasis clinical trials at tertiary care medical centers may be healthier, better educated, and have better access to medical care than the general U.S. population,” he noted. “Our study … was population based.”

'Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done.' DR. AZFAR

MONTREAL — Mortality rates are significantly increased in patients with severe psoriasis compared with the general population, according to two new studies.

But studies have conflicting results regarding the cause of death, researchers reported at the annual meeting of the Society for Investigative Dermatology. A study by Dr. Rahat Azfar showed an age-dependent, significantly increased risk of cardiovascular death with severe psoriasis, compared with patients without psoriasis.

“Severe psoriasis may be an independent risk factor for cardiovascular mortality,” noted Dr. Azfar of the University of Pennsylvania, Philadelphia, whose study showed a 50% increase in cardiovascular death.

Her findings are in direct contrast to another study presented in the same session and conflict with a growing body of evidence. Dr. Robert Stern presented results from the 30-year PUVA Follow-Up Study, which showed no increase in cardiovascular death risk in severe psoriasis patients, all of whom had undergone PUVA.

“In patients with extremely severe psoriasis, there is an increased risk of death from noncardiovascular, but not cardiovascular causes,” said Dr. Stern, professor of dermatology at Harvard Medical School and vice chair of dermatology at Beth Israel Deaconess Medical Center in Boston.

“Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done,” commented Dr. Azfar, who declared no conflicts of interest.

Her study, which she presented at the meeting, was funded by the National Institutes of Health and a grant from Centocor. It examined more than 3,000 patients with severe psoriasis, matched to more than 14,000 controls from the United Kingdom's General Practice Research Database.

Compared with controls, patients with severe psoriasis had a significantly increased risk of all-cause mortality (odds ratio 1.78), she said. After the researchers controlled for traditional cardiovascular risk factors, psoriasis patients had a clinically significant increased risk of cardiovascular death (hazard ratio [HR] 1.55). This risk was modified by age, with patients aged 40 and younger being at greater risk (HR 2.65) than patients aged between 41 and 60 (HR 1.90). This translated to an excess risk of 5.78 cardiovascular deaths per 10,000 person-years at age 40, and 58.9 per 10,000 person-years at age 60, she said.

Dr. Stern, who declared no conflicts of interest, agreed that cardiovascular risk factors are important, but his data suggest they are no more important than other risk factors.

The data show “that liver disease and nonmelanoma skin cancer accounted for more than half the approximately 70 excess deaths we observed,” he said. His prospective study followed 1,376 patients from the PUVA Follow-Up for 28 years, from 1976 to 2004. The patients had participated in a therapeutic PUVA study in 1975–1976 in 16 tertiary care academic centers across the United States.

Comparing the observed and expected mortality rates among patients and controls, the researchers found an increased all-cause mortality rate (HR 1.51) among only those patients with the most severe psoriasis. When cause of death was examined in this group, noncardiovascular reasons explained the increased risk (HR 1.74), and there was a nonsignificant increase in the rate of cardiovascular deaths, compared with controls (HR 1.29), Dr. Stern said.

“Dr. Stern's study results need to be interpreted with extreme caution due to the inherent bias in his study design,” warned Dr. Joel Gelfand, also of the University of Pennsylvania, and principal investigator on Dr. Azfar's study.

Dr. Stern's study design compares apples to oranges, commented Dr. Gelfand. “Patients who participate in psoriasis clinical trials at tertiary care medical centers may be healthier, better educated, and have better access to medical care than the general U.S. population,” he noted. “Our study … was population based.”

'Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done.' DR. AZFAR