Hypertensive Disorders of Pregnancy Lead to Earlier, More Severe CAD

Women who experience hypertensive disorders of pregnancy (HDP) go on to develop CAD earlier in life compared with women who are normotensive during pregnancy, according to an observational analysis. A history of HDP is linked to increased risks of myocardial infarction, whether that’s with obstructive coronary arteries or nonobstructive coronary arteries (MINOCA).

In fact, MINOCA was the diagnosis for nearly one in five women who developed ACS in the years following HDP, an overarching group of conditions that include not only preeclampsia but also gestational and chronic hypertension.

“This study underscores the need for timely detection and treatment of nonobstructive disease, in addition to traditional risk factors,” researchers say.

Senior author Vesna D. Garovic, MD, PhD (Mayo Clinic, Rochester, MN), told TCTMD that their work clarifies the mechanisms driving the relationship between the hypertensive disorders that occur during pregnancy and the risk of cardiovascular disease thereafter.

While imaging studies have already drawn a link between preeclampsia and greater atherosclerotic burden, that research did not—as this one does—make a connection between those changes and actual events. And it turns out, said Garovic, “that indeed women who had preeclampsia and have MI actually have more atherosclerosis in their coronary arteries than those who did not have preeclampsia.”

Their findings also serve as a reminder that “in general, women with hypertension in pregnancy need to be followed up closely,” she added. When women later in life report that they had previously experienced preeclampsia or having delivered their baby early due to complications, this further emphasizes the need “to be very watchful and treat risk factors in a timely fashion and aggressively,” said Garovic.

For Garovic, one thing that’s fascinating is that HDP’s impact over the long term isn’t universal. Some women don’t develop coronary artery disease and others go on to have an MI, whether that’s in the context of atherosclerotic lesions or nonobstructive disease. That heterogeneity with respect to CV outcomes supports the idea that HDP is itself heterogeneous, she explained.

Even preeclampsia, whose clinical presentation consistently involves hypertension, proteinuria, and systemic disease, can be caused by different underlying mechanisms. Whether the root cause is impaired immunomodulation, oxidative stress, or something else entirely, “these different mechanisms may have different implications when it comes to long-term outcomes” for the women who develop the condition during pregnancy, said Garovic.

Led by Lisa E. Vaughan, MS, and Yoshihisa Kanaji, MD, PhD (both Mayo Clinic), the study was published online recently in the Journal of the American College of Cardiology.

A Mixed Bag of Disorders, Outcomes

Vaughan, Kanaji, and colleagues focused on residents of Olmsted County, MN, using the Rochester Epidemiology Project to identify 506 parous female residents who’d given birth to at least one live baby and subsequently had their first diagnosis of incident CAD over a 14-year period ending in December 2016. Types of incident CAD events included 56% with MI, 29% with PCI, and 15% with CABG; all subjects had angiographic data available for analysis. Nineteen percent of the 506 women had a history of HDP, including gestational hypertension (9.1%), preeclampsia (8.9%), and chronic hypertension (1.2%).

Women with HDP tended to be younger than normotensive women at the time of their CAD event (median 64.8 vs 71.8 years; P = 0.030) and to have higher body mass index (BMI; 30.9 vs 28.0 kg/m²; P = 0.004) and higher prevalence of diabetes (52.6% vs 37.7%; P = 0.007) and hypertension (86.6% vs 76.5%; P = 0.030). They were less likely to have a history of smoking (42.3% vs 55.3%; P = 0.021).

Within the group of 506 parous women, 373 experienced ACS; these individuals were matched 1:2 by year of maternal birth to controls: parous women without CAD who lived in the same county at the same time. An unadjusted comparison of cases and controls showed that HDP were strongly associated with subsequent ACS (OR 1.48; 95% CI 1.07-2.05), and the relationship remained significant after accounting for comorbidities, BMI, and smoking status.

The researchers also explored patterns in MINOCA diagnosis and atherosclerotic burden by HDP status among the ACS cases. Adjusted for age, women with an HDP history were more likely to be diagnosed with MINOCA (OR 2.08; 95% CI 1.02-4.25) than women without HDP. They were twice as likely to have a higher SYNTAX score (OR 2.28; 95% CI 1.02-5.12).

In all, 11% of the ACS cases involved MINOCA. For women with prior HDP, however, the prevalence of MINOCA was 18%. Among the 13 women diagnosed with type 2 MI, 38.5% had a history of HDP, and among the 10 women with spontaneous coronary artery dissection, 20% had a history of HDP.

The evidence of a link between HDP and MINOCA is interesting, Garovic highlighted.

“I sort of intuitively was expecting to see that because at the end of the day, preeclampsia is all about endothelial dysfunction and . . . how blood vessels react to different stimuli,” she said. “But still it was an amazing finding, [one that’s] very helpful because we know that MINOCA happens more often in women, but we really did not know [the] sex-specific factors or reproductive-specific factors that may be contributing to that. And indeed, we are showing that hypertension in pregnancy may identify those at risk for MINOCA later in life.”

The next step for research, she suggested, should be a combination of preclinical and human studies to further delineate what influences the type of MINOCA women develop after HDP.

Michael C. Honigberg, MD (Massachusetts General Hospital, Boston, and the Broad Institute of MIT and Harvard, Cambridge), writing in an editorial, agrees that “granular details of presentation and endophenotypes of clinical CAD in women with HDP have not been well described to date.”

The new study reaffirms the idea that atherosclerosis development can be accelerated in women with HDP, he notes. However, “how best to translate this knowledge into practice to prevent cardiovascular disease in affected women remains incompletely defined, and novel preventive strategies in this population should be rigorously studied.”

That said, one thing that makes sense is taking steps to promote cardiometabolic health “upstream,” at times when women haven’t yet become pregnant or when they are between pregnancies, advises Honigberg. This approach, he adds, could have both short- and long-term benefits.