Hypertension Starts Years Earlier in Women Than Men, Serial BP Shows

Evidence from serial blood pressure measurements taken over decades shows that compared with men, women consistently have earlier and more-rapid onset of hypertension, beginning in their 20s, contrary to the accepted notion that crucial vascular changes and onset of disease tend to lag in women.

“We've known for decades that women and men present differently with different forms of cardiovascular disease, and they also present differently with the same type of cardiovascular disease, whether that be a heart attack, heart failure, etc,” senior study author Susan Cheng, MD (Cedars-Sinai Medical Center, Los Angeles, CA), told TCTMD. “But we've never completely understood why.”

The object of her group’s latest study, she explained, was to “go back to basics” and look at the factor that most commonly precedes cardiovascular symptoms in both sexes: hypertension. Rather than comparing hypertension between men and women, however, they sought to better understand subtle patterns that might be specific to each. 

In their study, published online January 15, 2020 in JAMA Cardiology, Cheng and colleagues led by Hongwei Ji, MD (Harvard Medical School, Boston, MA), examined serial BP measurements from four community cohorts: the Framingham Heart Study offspring cohort, the Atherosclerosis Risk in Communities study, the Coronary Artery Risk Development in Young Adults study, and the Multi-Ethnic Study of Atherosclerosis. In all, measurements were taken in 32,833 adults over 43 years, from 1971 to 2014.

Compared with men, women had faster and earlier systolic and diastolic increases (P < 0.001 for all  comparisons), even after adjustment for body mass index, total cholesterol, diabetes, and current smoking. The findings were consistent across all races and ethnicities.

Women also had greater increases in mean arterial pressure (MAP) over their life span than did men. Since MAP is a reflection of small-artery function, the finding may be a step toward understanding why women tend to have a higher rate of microvascular disease, the researchers suggest. As a whole, the BP findings also may give clues about other CVD anomalies in women versus men, such as the greater incidences of both nonobstructive coronary atherosclerosis and heart failure with preserved ejection fraction.

Challenge to Hormonal Theory of Protection

In an accompanying editorial, Nanette K. Wenger, MD (Emory University School of Medicine, Atlanta, GA), observes that by showing that BP trajectories in women begin early in life and “antedate the anticipated changes in hormonal milieu,” the new findings challenge the long-held hypothesis that estrogen levels protect women from heart disease early on, and that hormone replacement therapy can continue that protection after menopause.

Sex differences in blood pressure, Wenger adds, may “offer a clue” with regard to selecting therapeutic interventions that are best for the variations of cardiovascular disease that affect women most commonly.

We really shouldn't be putting women and men on the same axis. We should allow women to have their own y axis, their own starting point. Susan Cheng

Noting widespread evidence of undertreatment and the underresponse of women’s BP to treatment, Cheng said sex-based, tailored treatment might be a future goal, with more emphasis on monitoring and treating to goal at earlier ages and to different thresholds, as well as awareness about the impact of pregnancy on a woman’s life cycle of blood pressure. Getting to that point in this research will require sex-specific investigation to ensure that guideline-recommended therapies work as well in women as in men.

To TCTMD, Cheng said she was actually hesitant to even believe that women should be studied differently than men. But after seeing the BP results, she’s now a believer and is eager to examine other CVD risk factors that, if shown to be different between the sexes, could be a gateway toward enhancing detection and prevention efforts. 

“We really shouldn't be putting women and men on the same axis,” she continued. “We should allow women to have their own y axis, their own starting point, and allow men to have their own y axis, their own starting point.”

In the Genes

According to Cheng, her study is in line with recent work on genetic expression showing that fundamental sexual dimorphism is apparent even at the cellular level. This unique and emerging understanding of just how distinct the differences between males and females really are has important implications for understanding gender-based health and disease differences, she noted.

“Even though we have the same genetic blueprint, the way our genes are expressed are different in males and females. So that means that it is in some ways ‘in our genes.’ It starts in our genes and how those genes are expressed. It gets translated into different anatomy and physiology,” Cheng explained. “Women and men have different sized coronary arteries even after you adjust for body size. It's not just that women are smaller versions of men, we're different.”

Those physiologic differences coupled with lifestyle, responses to stress, and individual risk factors, she added, makes it even more important to work toward individualizing men and women’s cardiovascular health management.

“We really need better treatments or better tailored treatments . . . and we definitely need to do more work to understand exactly what's going on,” she concluded.