Meeting News

PAD different in women vs. men

Judith G. Regensteiner

ANAHEIM, Calif. — Peripheral artery disease is prevalent in men and women, yet significant differences in presentation and treatment exist and type 2 diabetes makes an impact, a speaker said at the American Heart Association Scientific Sessions.

“Premenopausal women without diabetes have fewer CV events than men without diabetes at the same age, but the advantage is lost in the context of type 2 diabetes,” said Judith G. Regensteiner, PhD, professor of medicine, director of the Center for Women’s Health Research and Judith and Joseph Wagner Endowed Chair in Women’s Health Research at the University of Colorado School of Medicine.

“The reasons for the difference in heightened CV risk in women vs. men with diabetes remain unclear, but they may include the impact of sex hormones, sex differences in CV risk factors and gender disparities in diagnosis and treatment of diabetes and CVD,” she said during her presentation.

Clues but no conclusions

In terms of CVD, Regensteiner said CAD, cerebrovascular disease and PAD all begin with atherosclerosis, noting that it is essentially “one disease with three manifestations” and that patients can often have more than one manifestation at the same time. However, these diseases, particularly PAD, usually present differently in women than men.

The prevalence of PAD is similar between men and women, but women more often have asymptomatic disease as well as severe ischemia, according to Regensteiner.

As for data showing sex differences in PAD with type 2 diabetes, until recently, many studies have excluded patients with type 2 diabetes because the presence of the disease complicates the study. Therefore, the most of the data to date are primarily old and observational, she said.

However, results from previous studies provide some information on the sex differences in PAD in patients with diabetes.

The Framingham Heart Study, for instance, showed a three- to fourfold increased risk for CAD, stroke and HF in women with diabetes and intermittent claudication vs. diabetes or intermittent claudication alone, whereas men with both conditions had only a twofold increased risk for stroke and a threefold increased risk for HF vs. either condition alone, Regensteiner said.

Additionally, one Japanese observational study comparing men and women with PAD showed that women were older and more likely to have diabetes, hyperlipidemia and more severe PAD. Another 2012 study also reported that women with PAD younger than 60 years had an increased risk for CV events compared with men of the same age, whereas no difference was seen in patients older than 60 years.

“These are clues, but we don’t have conclusive information about the difference between men and women with regards to PAD and diabetes or to diabetes and heart disease,” Regensteiner said.

Examining risks, symptoms

Risk factors for PAD and CHD, including smoking, diabetes, age, hypertension and dyslipidemia are comparable, with cigarette smoking and diabetes having the strongest association with PAD. The prevalence of type 2 diabetes in patients with PAD is also higher than in those with CAD, according to Regensteiner.

Although little is known about PAD with type 2 diabetes, researchers know that diabetes alone confers decreased mobility and decreased maximal oxygen function, even without CVD.

They also have some data on the differences between men and women in the symptoms of PAD without diabetes. In a study examining responses to the Walking Impairment Questionnaire, women with PAD seemed to have greater functional decline and greater mobility loss than men. Women with claudication walked more slowly in the community setting, particularly for short, continuous durations for up to 5 minutes and during intermittent walking at peak cadences, Regensteiner said.

“Both PAD and diabetes clearly have adverse effects on function, but we don’t know as much about why, what and where as we’d like to,” she said.

Differences in revascularization outcomes

Treatment of PAD and its outcomes between men and women also often differs, according to Regensteiner.

For instance, the associations between sex and survival after lower-extremity revascularization are altered by the presence of diabetes. According to a study from 1993, results demonstrated similar perioperative mortality rates among women and men undergoing infrainguinal bypass for ischemia but decreased long-term survival in women vs. men (3-year survival, 54% vs. 72%). The same study also showed that women with diabetes had increased postsurgical mortality compared with men with diabetes, Regensteiner said.

“Women seem not to do as well after this very common procedure for PAD,” she said. “One reason for this may be that women might be offered treatment later in the course of the disease.”

Regensteiner also cited another study of nearly 3,000 patients with claudication or critical limb ischemia undergoing infrainguinal endovascular revascularization that highlighted differences in characteristics between men and women with PAD. The data indicated that smoking, previous CHD and diabetes were more common in men than women. Men also more often presented with claudication and underwent treatment for lesions below the knee, whereas women more often underwent treatment for lesions above the knee.

“As we know, above-knee procedures are more serious in terms of sequelae and damage done to quality of life than below-knee procedures, so this is a concerning finding,” Regensteiner said.

Also, in the study, women were generally older, more likely to present with rest pain and were more often discharged to rehabilitation and had longer hospital stays than men. Regensteiner said this finding could be partly due to social factors, as women are more often widowed and may not have someone at home.

Other treatments

Aside from revascularization, the only drug currently approved by the FDA for claudication is cilostazol. Although this drug was tested in far fewer women than men before initial approval, it appears to be moderately efficacious in both women and men, according to Regensteiner.

Moreover, in studies of claudication, women with PAD and diabetes do not respond as well to exercise training, despite excellent adherence, as women without diabetes, men without diabetes and men with diabetes. Women without diabetes, men without diabetes and men with diabetes, however, demonstrated significant improvement in measures of walking ability, including claudication onset time and peak walking time. Exercise training is a powerful treatment for symptomatic and asymptomatic PAD in terms of improving walking, so more studies should evaluate this treatment in women as well as men, she said.

“The differences between men and women in risk factors, symptoms and treatment of PAD are not well understood. Much more research is called for to understand these sex differences and how they compare to sex differences with CAD,” Regensteiner said during her presentation. “The question is confused because PAD is coronary risk equivalent, so separating out those influences will prove more complicated, but this is the ultimate goal.” – by Melissa Foster

Reference:

Pradan A, et al. VA.CVS.742. Vascular Disease as a Women's Health Concern. Presented at: American Heart Association Scientific Sessions; Nov. 11-15, 2017; Anaheim, Calif.

Disclosure: Regensteiner reports no relevant financial disclosures.

Judith G. Regensteiner

ANAHEIM, Calif. — Peripheral artery disease is prevalent in men and women, yet significant differences in presentation and treatment exist and type 2 diabetes makes an impact, a speaker said at the American Heart Association Scientific Sessions.

“Premenopausal women without diabetes have fewer CV events than men without diabetes at the same age, but the advantage is lost in the context of type 2 diabetes,” said Judith G. Regensteiner, PhD, professor of medicine, director of the Center for Women’s Health Research and Judith and Joseph Wagner Endowed Chair in Women’s Health Research at the University of Colorado School of Medicine.

“The reasons for the difference in heightened CV risk in women vs. men with diabetes remain unclear, but they may include the impact of sex hormones, sex differences in CV risk factors and gender disparities in diagnosis and treatment of diabetes and CVD,” she said during her presentation.

Clues but no conclusions

In terms of CVD, Regensteiner said CAD, cerebrovascular disease and PAD all begin with atherosclerosis, noting that it is essentially “one disease with three manifestations” and that patients can often have more than one manifestation at the same time. However, these diseases, particularly PAD, usually present differently in women than men.

The prevalence of PAD is similar between men and women, but women more often have asymptomatic disease as well as severe ischemia, according to Regensteiner.

As for data showing sex differences in PAD with type 2 diabetes, until recently, many studies have excluded patients with type 2 diabetes because the presence of the disease complicates the study. Therefore, the most of the data to date are primarily old and observational, she said.

However, results from previous studies provide some information on the sex differences in PAD in patients with diabetes.

PAGE BREAK

The Framingham Heart Study, for instance, showed a three- to fourfold increased risk for CAD, stroke and HF in women with diabetes and intermittent claudication vs. diabetes or intermittent claudication alone, whereas men with both conditions had only a twofold increased risk for stroke and a threefold increased risk for HF vs. either condition alone, Regensteiner said.

Additionally, one Japanese observational study comparing men and women with PAD showed that women were older and more likely to have diabetes, hyperlipidemia and more severe PAD. Another 2012 study also reported that women with PAD younger than 60 years had an increased risk for CV events compared with men of the same age, whereas no difference was seen in patients older than 60 years.

“These are clues, but we don’t have conclusive information about the difference between men and women with regards to PAD and diabetes or to diabetes and heart disease,” Regensteiner said.

Examining risks, symptoms

Risk factors for PAD and CHD, including smoking, diabetes, age, hypertension and dyslipidemia are comparable, with cigarette smoking and diabetes having the strongest association with PAD. The prevalence of type 2 diabetes in patients with PAD is also higher than in those with CAD, according to Regensteiner.

Although little is known about PAD with type 2 diabetes, researchers know that diabetes alone confers decreased mobility and decreased maximal oxygen function, even without CVD.

They also have some data on the differences between men and women in the symptoms of PAD without diabetes. In a study examining responses to the Walking Impairment Questionnaire, women with PAD seemed to have greater functional decline and greater mobility loss than men. Women with claudication walked more slowly in the community setting, particularly for short, continuous durations for up to 5 minutes and during intermittent walking at peak cadences, Regensteiner said.

“Both PAD and diabetes clearly have adverse effects on function, but we don’t know as much about why, what and where as we’d like to,” she said.

PAGE BREAK

Differences in revascularization outcomes

Treatment of PAD and its outcomes between men and women also often differs, according to Regensteiner.

For instance, the associations between sex and survival after lower-extremity revascularization are altered by the presence of diabetes. According to a study from 1993, results demonstrated similar perioperative mortality rates among women and men undergoing infrainguinal bypass for ischemia but decreased long-term survival in women vs. men (3-year survival, 54% vs. 72%). The same study also showed that women with diabetes had increased postsurgical mortality compared with men with diabetes, Regensteiner said.

“Women seem not to do as well after this very common procedure for PAD,” she said. “One reason for this may be that women might be offered treatment later in the course of the disease.”

Regensteiner also cited another study of nearly 3,000 patients with claudication or critical limb ischemia undergoing infrainguinal endovascular revascularization that highlighted differences in characteristics between men and women with PAD. The data indicated that smoking, previous CHD and diabetes were more common in men than women. Men also more often presented with claudication and underwent treatment for lesions below the knee, whereas women more often underwent treatment for lesions above the knee.

“As we know, above-knee procedures are more serious in terms of sequelae and damage done to quality of life than below-knee procedures, so this is a concerning finding,” Regensteiner said.

Also, in the study, women were generally older, more likely to present with rest pain and were more often discharged to rehabilitation and had longer hospital stays than men. Regensteiner said this finding could be partly due to social factors, as women are more often widowed and may not have someone at home.

Other treatments

PAGE BREAK

Aside from revascularization, the only drug currently approved by the FDA for claudication is cilostazol. Although this drug was tested in far fewer women than men before initial approval, it appears to be moderately efficacious in both women and men, according to Regensteiner.

Moreover, in studies of claudication, women with PAD and diabetes do not respond as well to exercise training, despite excellent adherence, as women without diabetes, men without diabetes and men with diabetes. Women without diabetes, men without diabetes and men with diabetes, however, demonstrated significant improvement in measures of walking ability, including claudication onset time and peak walking time. Exercise training is a powerful treatment for symptomatic and asymptomatic PAD in terms of improving walking, so more studies should evaluate this treatment in women as well as men, she said.

“The differences between men and women in risk factors, symptoms and treatment of PAD are not well understood. Much more research is called for to understand these sex differences and how they compare to sex differences with CAD,” Regensteiner said during her presentation. “The question is confused because PAD is coronary risk equivalent, so separating out those influences will prove more complicated, but this is the ultimate goal.” – by Melissa Foster

Reference:

Pradan A, et al. VA.CVS.742. Vascular Disease as a Women's Health Concern. Presented at: American Heart Association Scientific Sessions; Nov. 11-15, 2017; Anaheim, Calif.

Disclosure: Regensteiner reports no relevant financial disclosures.

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