Diabetes and insulin resistance associated with highest relative risk for premature CHD in women
Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women
Introduction and methods
Identifying individuals at increased risk of premature coronary heart disease (CHD) is important to reduce premature morbidity and mortality rates. Premature CHD is generally defined as CHD occurring in women before age 65 years and in men before age 55 years [1-3]. This study evaluated the associations of more than 50 clinical risk factors and biomarkers with incident CHD in women.
The study was conducted among 28024 US female health professionals participating in the Women’s Health Study [4-7]. All participants were women (aged ≥45 years) without known CVD at baseline. Baseline risk factors were determined and blood samples for biomarker measurements (including lipid, lipoprotein, inflammatory and metabolic biomarkers) were obtained at baseline (April 30, 1993, to January 24, 1996). Median follow-up was 21.4 years and analyses were conducted from October 1, 2017, to October 1, 2020. The primary outcome was incident CHD, defined as the composite of first MI, PCI, CABG, or CHD death. CHD incidence rates were determined in 4 age groups: <55, 55 to <65, 65 to <75, and ≥75 years. Adjusted hazard ratios (aHRs) were estimated for incident CHD per SD increment of each biomarker and for clinical risk factors.
- Of the clinical factors, diabetes had the highest relative risk for incident CHD in women (aHR in women >55 years: 10.71, 95%CI 5.57-20.60; aHR in women 55 to 65 years: 10.92, 95%CI 8.44-14.13; aHR in women 65 to <75 years: 4.49, 95%CI 3.46-5.83; aHR in women ≥75 years: 3.47, 95%CI 2.47-4.87).
- Clinical risk factors that were also associated with increased risk of incident CHD in women younger than 55 years include metabolic syndrome (aHR: 6.09, 95%CI 3.60-10.29), hypertension (aHR: 4.58, 95%CI 2.76-7.60), obesity (aHR: 4.33, 95%CI 2.31-8.11), and smoking (aHR: 3.92, 95%CI 2.32-6.63). Relative risks attenuated with age. MI in a parent before age 60 years was associated with 1.5- to 2-fold higher risk of CHD in participants up to age 75 years.
- The biomarker that was associated with the highest relative risk for incident CHD in women younger than 55 years was LPIR score reflecting lipoprotein insulin resistance (aHR: 6.40, 95%CI 3.14-13.06). Relative risks attenuated with age.
- Hemaglobin A1c level was associated with incident CHD (aHR in women >55 years: 1.38, 95%CI 1.26-1.50, aHR’s attenuated with age). Other metabolic biomarkers showed no association with incident CHD across age groups.
- All examined inflammatory biomarkers (CRP, Fibrinogen, ICAM-1, and GlycA) were significantly associated with incident CHD in all age groups (aHR ranged from 1.2 to 1.84). aHR’s attenuated with age.
- Lipids and lipoproteins that were significantly associated with increased risk of CHD onset in women younger than 55 years include total cholesterol (aHR:1.39, 95%CI 1.12-1.73), LDL-c (aHR: 1.38, 95%CI 1.10-1.74), non-HDL-c (aHR: 1.67, 95%CI 1.36-2.04), apoB (aHR: 1.89, 95%CI 1.52-2.35), and triglycerides (aHR: 2.14, 95%CI 1.72-2.67). Relative risks attenuated with age.
- Significant risk associations with CHD were also found for small LDL particles, total LDL particles, total TRL particles, TRL triglyceride, TRL cholesterol, TRL large particles, TRL medium particles and TRL very small particles. Most HDL particles had an inverse association with CHD, except small HDL particles.
This study identified diabetes and insulin resistance as major determinants of premature CHD in women. Other clinical factors associated with premature CHD in women include metabolic syndrome, hypertension, obesity, and smoking.