Factors Associated With Premature Coronary Heart Disease in Women Identified

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Premature coronary heart disease risk was increased among women with diabetes, insulin resistance, hypertension, obesity, and those who smoked.

Premature coronary heart disease (CHD) risk was increased among women with diabetes, insulin resistance, hypertension, obesity, and those who smoked, according to the results of a cohort study published in JAMA Cardiology.

Data of 39,876 women ≥45 years without cancer or cardiovascular disease who participated in the Women’s Health Study between 1993 and 2004 were examined. In this study, participants were randomly assigned to receive vitamin E, b-carotene, aspirin, or placebo. For this analysis, 28,024 of those participants were assessed in 2016 for CHD, blood biomarkers, and mortality.

In this cohort, 94.5% had not developed CHD at follow-up. Rate of CHD incidence during follow-up (median, 21.4 years) was lowest among women aged <55 years (incidence rate, 0.07 per 100 person-years [py]) and highest among women aged ³75 years (incidence rate, 0.62 per 100 py). A greater percentage of participants in all age groups who developed vs did not develop CHD had at baseline: diabetes (range, 8.7%-19.8% vs 2.2%), metabolic syndrome (range, 40.2%-61.9% vs 23.3%), and hypertension (range, 40.9%-44.5% vs 25.2%).

Risk for CHD varied with age, comorbidities, lipid levels, and biomarkers of inflammation and metabolism.

Diabetes increased risk for incident CHD across all age groups, but this risk tended to lower with increasing age (<55 years: adjusted hazard ratio [aHR], 10.71; 55-<65 years: aHR, 10.92; 65-<75 years: aHR, 4.49; ³75 years: aHR, 3.47; P <.001).

Association between risk for incident CHD and the following comorbidities also decreased with age: metabolic syndrome, hypertension, obesity, current smoking (P <.001 for all), and myocardial infarction before age 60 years (P =.02).

The lipoprotein insulin resistance score had the strongest association of all biomarkers and risk factors examined with incident CHD. In women ages <55 years, incident CHD was associated with increasing levels of (per standard deviation increase): total cholesterol (aHR, 1.39; P <.001), low-density lipoprotein cholesterol (aHR, 1.38; P <.001), non-high-density lipoprotein cholesterol (aHR, 1.67; P <.001), triglycerides (aHR, 2.14; P <.001), apolipoprotein B (aHR, 1.89; P <.001), and hemoglobin A1C (aHR, 1.38; P <.001).

Study limitations include possible recall bias due to self-reported medical history.

“Future work should examine the role of these biomarkers in improving determination of the estimated probability and classification of premature CHD beyond traditional biomarkers to guide preventive efforts,” concluded the study authors. “This intervention is particularly relevant given that most countries are encumbered by a substantial burden of premature cardiovascular mortality and would benefit from strategies to improve identification of risk, screening, stratification, and early treatment.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Dugani S B, Moorthy M V, Li C, et al. Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women. JAMA Cardiol. 2021;e207073. doi:10.1001/jamacardio.2020.7073