Stark Differences Between Males and Females in Hypertension Trials

Tara Chang, MD

More women may need to be included in future hypertension trials.

In a retrospective look presented during the American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia, Tara Chang, MD, associate professor of medicine at the Stanford University Medical Center, said there are key differences in patient outcomes between the 2 genders that should change how clinical trials are conducted.

“You could argue from this that we need to do better in terms of controlling blood pressure for both men and women, but there may be a need to particularly focus on women particularly older women,” Chang said.

While the prevalence of hypertension is significantly higher in the older age groups, there is also are differences between the 2 sexes.

“And for adults who are under the age of 60, the prevalence of hypertension is higher in men than women,” Chang said. “But for adults who are over the age of 60, the prevalence is now

higher in women as compared with men.”

Chang explained that hypertension control will also differ by both age and gender.

“[For men] the blood pressure control remained about the same at about 60% regardless of the age category and regardless of the era in which the study was conducted,” Chang said. “The same is not true for women…and what you're seeing is that younger age groups, women have better control of blood pressure than men, but that this proportion of women with control hypertension drops as women get older.”

According to Chang, 1 of the main focal points in the discrepancy between the 2 sexes in hypertension control is blood pressure targets, as seen from the SPRINT study.

SPRINT was a systolic blood pressure intervention trial involving 9361 patients, who were randomly assigned to 1 of 2 different blood pressure target—a standard blood pressure target of less than 144 and an intensive blood pressure treatment target of less than 120.

Each participant was followed and evaluated for a composite primary outcome of non-fatal and fatal cardiovascular events.

Chang explained that age was fairly similar between men and women in Sprint, but women had a lower estimated glomerular filtration rate than men, resulting in a higher proportion of women having baseline chronic kidney disease.

“Their baseline their blood pressure was also slightly higher in the women as compared with the men,” she said. “But despite these risk factors for cardiovascular disease you could see that their Framingham Risk Score was actually markedly lower among women, as compared with men.”

However, women did have a similar achieved blood pressure compared with men. At 3 years in the standard arm, the systolic blood pressure was on average 137 for women and 136 for men. In the intensive group, it was 120 for women and 121 for men.

Also, looking at the proportion of participants who suffered adverse events during the study, the event rates were lower for women, possibly related to their lower baseline cardiovascular risk.

Chang added that for women older than 65, the blood pressure is actually worse than men in the same age category.

Chang explained some of the factors in the differences related to sex include lifestyle, environmental factors, sex hormones and a variety of other things.

Another discussion point was the potential sex differences in pharmacogenetics, which impacts the pharmacodynamics and clinical response of blood pressure medications.

Some of these differences are due to woman having a smaller body surface area with a different body composition and higher fat content, which could affect volume and distribution. Women also have differences in metabolism and excretion of medications, which could affect the clearance levels.

Studies have shown that these factors can make a difference in a number of drugs, including beta blockers and calcium channel blockers. Women also generally report more edema with calcium channel blockers and tend to have more problems with hypoglycemia.

However, on a positive note, Chang said women are very well represented in hypertension studies that could close the gap on patient outcomes, but more work is needed.

“So, I think it's important to plan for the equitable inclusion of women in trials from the very beginning,” Chang said.