Insulin resistance biomarker tied to increase in risk of premature coronary heart disease

Jan. 22, 2021

To understand what factors put younger people at higher risk of premature coronary heart disease (CHD), researchers from Brigham and Women’s Hospital and the Mayo Clinic analyzed more than 50 risk factors in 28,024 women who participated in the decades-long Women’s Health Study, according to a news release from Brigham and Women’s Hospital.

Notably, women under 55 with type-2 diabetes had a tenfold greater risk of having CHD over the next two decades, with lipoprotein insulin resistance (LPIR) proving to be a strong, predictive biomarker as well. Findings were published in JAMA Cardiology.

The researchers analyzed approximately 50 biomarkers associated with cardiovascular health. Commonly used metrics like low-density lipoprotein (LDL) cholesterol and HbA1c had much weaker associations with CHD onset in women younger than 55 years than LPIR, a newer metric for insulin resistance. LPIR uses a weighted combination of six lipoprotein measures and is analyzed through specialized laboratory testing. Whereas LDL cholesterol was only associated with a 40 percent increase in risk of CHD onset in women under 55, LPIR demonstrated a sixfold (600 percent) increase.

“In otherwise healthy women, insulin resistance, type-2 diabetes, and its sister diagnosis, metabolic syndrome, were major contributors to premature coronary events,” said corresponding author Samia Mora, MD, MHS, of the Brigham’s Center for Lipid Metabolomics in the Division of Preventive Medicine and an Associate Professor at Harvard Medical School. Mora. “Women under 55 who have obesity had about a fourfold-increased risk for coronary events, as did women in that age group who smoked or had hypertension. Physical inactivity and family history are all part of the picture as well.”

The researchers acknowledged the study is limited in its generalizability — beyond its focus on women, who have been shown to have worse outcomes after premature cardiac events than men, its participants were over 95 percent white. According to Mora, findings could be even more dramatic in ethnic and racial groups that have a greater prevalence of metabolic syndrome, insulin resistance and diabetes, among other risk factors.

“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. “These could be innovative lifestyle-based strategies, like community efforts, greater public health efforts, ways to medically target metabolic pathways, or new surgical approaches.”

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