• PMOS, also known as PCOS, was independently associated with ASCVD risk.
• The association was only partially mediated by comorbidities including hypertension, diabetes, hyperlipidemia and obesity.

Polyendocrine metabolic ovarian syndrome was associated with increased risk for atherosclerotic cardiovascular disease events and the association was only partially mediated by the presence of baseline comorbidities, researchers reported.

Polyendocrine metabolic ovarian syndrome (PMOS), the new proposed name for polycystic ovary syndrome (PCOS), may be an independent predictor of ASCVD events, including coronary artery disease, cerebrovascular disease and peripheral artery disease, according to data published in The Lancet Obstetrics, Gynaecology, & Women’s Health.

“Women with PMOS are known to have an increased risk of multiple CVD risk factors, including metabolic syndrome and type 2 diabetes,” Snigdha Alur-Gupta, MD, MSCE, reproductive endocrinologist at University of Rochester Medicine, told Healio. “However, while the literature on this association is fairly robust, prior evidence is mixed as to whether these risk factors then translate into an increased risk for ASCVD events — for example, MI and ischemic stroke — in this population as well.

“We found that women with PMOS have significantly higher risk for composite ASCVD events compared with women without PMOS — over a 4.4 times higher probability of an ASCVD event in the time studied,” Alur-Gupta said. “This higher risk persisted even after adjusting for multiple relevant confounders including CVD risk factors such as hypertension and high cholesterol, as well as oral contraceptive and metformin use.”

For the present study, Alur-Gupta and colleagues conducted a nationwide, longitudinal, retrospective study using data from a deidentified healthcare claims database (Optum Clinformatics). Researchers identified 413,450 patients with PMOS/PCOS and matched them 1:5 to more than 2 million women without PMOS/PCOS, all with no history of ASCVD (mean age, 31 years).

The main outcome was a composite of ASCVD events including CAD, cerebrovascular disease or PAD.

Participants with PMOS/PCOS had a greater prevalence of comorbidities including obesity, diabetes, hypertension, hyperlipidemia, obstructive sleep apnea, metabolic dysfunction-associated steatotic liver disease, infertility and depression, according to the study.

Over a mean follow-up of nearly 4 years, researchers observed significantly higher risk for ASCVD events among people with PMOS/PCOS vs. no PMOS/PCOS (adjusted HR = 4.4; 95% CI, 4.23-4.58).

Risk was elevated for each individual component of the main outcome among people with PMOS/PCOS compared with people without it, according to the study:

• CAD (aHR = 4.41; 95% CI, 4.16-4.67);
• cerebrovascular disease (aHR = 4.33; 95% CI, 4.09-4.59); and
• PAD (aHR = 4.98; 95% CI, 4.53-5.47).

Results were similar when researchers conducted analyses stratified by age and when users of combined hormonal contraception and metformin were excluded from the analysis.

“I do not think these findings are a complete surprise per se, given that we knew about the predisposition to increased risk factors,” Alur-Gupta told Healio. “However, both our adjusted and mediation analyses highlight that there is a higher hazard of actual atherosclerotic events in this population, even outside of the typical risk factors. What this means is this association should be discussed, even in patients without traditional risk factors such as hypertension, type 2 diabetes and obesity.”

In other findings, researchers reported that baseline comorbidities including hypertension, diabetes, hyperlipidemia and obesity each mediated 10% to 15.6% of the ASCVD risk associated with PMOS/PCOS, and when combined mediated 36.3% of overall risk.

“Our findings highlight the need for healthcare professional and patient education and awareness as to this association. With this we hope there will be improved early screening, counseling and long-term surveillance in this population,” Alur-Gupta told Healio.

Snigdha Alur-Gupta, MD, MSCE, is reproductive endocrinologist and associate professor in the department of obstetrics and gynecology at University of Rochester Medicine. Alur-Gupta can be reached at cardiology@healio.com.