Study: Increased Risk for Premature Coronary Heart Disease in Women With Diabetes


Insulin resistance and type 2 diabetes were major contributors to premature coronary heart disease, according to the study results.

Coronary Heart Disease

Diabetes and insulin resistance are strongly associated with the highest relative risk for coronary heart disease (CHD) in women younger than 55 years, according to the results of a study recently published in JAMA Cardiology.1

Investigators analyzed more than 50 biomarkers and additionally found hypertension, obesity, and smoking to be strong risk factors for premature CHD in women.1

Outcomes among younger adults with CHD have been suboptimal despite progress in prevention and management, according to investigators. Data collected from 2010 to 2015 showed that CHD mortality has declined in all age groups except for ages 55 to 64 years—mortality rates within this population has either stagnated or slightly increased.1,2

“We’re going to see, unfortunately, younger and younger people having heart attacks,” said corresponding author Samia Mora, MD, MHS, Brigham’s Center for Lipid Metabolomics in the Division of Preventive Medicine and an associate professor at Harvard Medical School.2 “When a younger individual has a cardiovascular event, it will affect their quality of life going forward, their productivity, and their contribution to society.”

To explore the impact that lifestyle has on heart health in women, researchers randomized 28,024 women without cardiovascular disease or cancer, between April 1993 and January 1996, to receive aspirin, vitamin E, beta-carotene, or matching placebo to assess cardiovascular outcomes.1 The randomized intervention ended in 2004, and participants received follow-up for a median of 21.4 years, through 2016, for incident CHD. Incident CHD was defined as a composite of first myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, or CHD death.

The study took blood samples to measure levels of about 50 biomarkers, such as apolipoproteins, lipids, triglycerides, lipoprotein, inflammatory markers, intercellular adhesion molecule 1, and metabolic markers (creatinine, hemoglobin A1c, homocysteine, and branched-chain amino acids, including leucine, isoleucine, and valine).

Incident CHD occurred in 1548 participants (5.5%) during the study period. Women with diabetes had the highest adjusted hazard ratio (aHR) for CHD onset at any age, with individuals younger than 55 years showing an aHR of 10.71 (95% CI, 5.57-20.60). Women younger than 55 years also showed increased risks for metabolic syndrome, hypertension, obesity, and smoking.

In regard to biomarkers, data associated LPIR score, which reflects insulin resistance, with the highest standardized relative risk of incident CHD in most age groups.

“The study findings underscore the importance of diabetes and insulin resistance as major determinants of premature CHD, as well as other modifiable major risk factors that can be addressed with lifestyle or preventative interventions,” the study authors wrote.

“Diabetes is mostly preventable, but it’s a systems-wide problem, and we urgently need further research into new strategies to address it,” Mora said.­2 “These could be innovative lifestyle-based strategies, like community efforts, greater public health efforts, ways to medically target metabolic pathways, or new surgical approaches.”


1. Dugani SB, Moorthy MV, Li C, et al. Association of lipid, inflammatory, and metabolic biomarkers with age at onset for incident coronary heart disease in women. JAMA Cardiology. January 20, 2021. doi:10.1001/jamacardio.2020.7073.

2. Diabetes Powerfully Associated with Premature Coronary Heart Disease in Women. News Release. Brigham Health; January 20, 2021. Accessed February 1, 2021.

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