SSc in Men More Severe Than in Women, and More Quickly Leads to PAH, Study Says

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by Magdalena Kegel |

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SSc-PAH sex differences

Men with systemic sclerosis (SSc) who develop pulmonary arterial hypertension (PAH) tend to have poorer survival rates in  the first five years after diagnosis, a University of Toronto study reported. Men were also found to develop PAH at an earlier stage in comparison to women, and to suffer a more severe SSc disease.

While the ratio between women and men affected by SSc is often estimated at 3–4 women for every man, studies suggesting that men affected with the disease have reduced survival and increased mortality have been reported in the last 15 years.

PAH secondary to SSc is one of the main causes of death in systemic sclerosis, affecting about 7 percent of patients. Data on the outcomes of PAH in SSc patients by sex have, however, not been consistent. Some studies found that men with SSc-PAH have an increased risk of death and poorer survival rates, while others find no differences in death and survival between the two groups.

In this study, Sex disparities in systemic sclerosis-associated pulmonary arterial hypertension: a cohort study, researchers analyzed data from a published Canadian PAH database, and identified 378 SSc-PAH patients of whom 58 (15.3 percent) were male, representing a female/male ratio of 5.5:1 in the cohort evaluated. The team then analyzed the time from PAH diagnosis to death from all causes, the primary outcome of the study.

Although men seemed to have lower survival rates — measured as percent of men and women who survived at 1, 2, 3 and 5 years post PAH diagnosis — more in-depth analyses could not support any differences in mortality between men and women.

Secondary measurements were sex differences in age at PAH diagnosis, the time from SSc diagnosis to PAH diagnosis, the duration of PAH, subtype of SSc (limited, diffuse), and the clinical manifestations of SSc. Comorbidities, medications, lung function, and heart physiological parameters were also compared.

The results, published in the journal Arthritis Research & Therapy, showed that men had a shorter mean time from SSc diagnosis to PAH diagnosis, and a shorter PAH disease duration.

Men were also found to be more likely to experience serious SSc manifestations. Renal crisis appeared in 19 percent of men versus 8 percent of women. Interstitial lung disease was present in 67 percent of men and 48 percent of women, and diffuse cutaneous disease in 40 percent of men compared to 22 percent of women. Adjusting the analyses for the presence of interstitial lung disease did not affect the outcome of the results.

The research team noted no differences between men and women in the presence of Raynaud’s phenomenon, telangiectasia, digital ulcers, esophageal motility problems, the presence of autoantibodies, 6-minute walk distance, WHO functional class, brain natriuretic peptide levels, comorbidities, or medications.

According to the authors, this study is the largest one assessing sex impact on SSc-PAH, and it showed that men often experience more severe SSc disease, and develop PAH more often and at an earlier stage than women. Currently, scientists do not know why these differences exist, and more research is needed to understand sex differences in SSc-PAH.