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Metabolic risk factors for coronary heart disease in women: perspective from the Framingham Study
Insights
Metabolic risk factors like high cholesterol, impaired glucose tolerance, and central obesity significantly increase coronary heart disease (CHD) risk in women. Menopause also elevates CHD risk, highlighting the need for targeted prevention strategies.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Epidemiology
Background:
- Coronary heart disease (CHD) risk factors in women are not fully understood.
- Women often have a lower CHD risk than men, but this advantage diminishes with certain metabolic changes.
Purpose of the Study:
- To identify and quantify antecedent metabolic risk factors for coronary heart disease (CHD) in women.
- To compare CHD risk prediction in women versus men based on various biomarkers.
Main Methods:
- Longitudinal surveillance of 2873 women over 30 years.
- Analysis of metabolic risk factors including blood lipids (total cholesterol, LDL, HDL, triglycerides), glucose tolerance, uric acid, menopause status, obesity, and fibrinogen.
Main Results:
- Serum total cholesterol, LDL, and HDL fractions are strong CHD predictors in women. A total-to-HDL cholesterol ratio > 7.5 equalizes risk between sexes.
- Impaired glucose tolerance confers a three-fold increased risk in women, eliminating their CHD risk advantage. Central obesity is linked to increased CHD risk and metabolic dysfunction.
- Post-menopausal status increases age-adjusted CHD risk 2-3 fold. Fibrinogen levels are higher in women and independently add to CHD risk.
Conclusions:
- Metabolic factors like dyslipidemia, impaired glucose tolerance, central obesity, and menopause significantly contribute to CHD risk in women.
- Specific risk factors, such as impaired glucose tolerance and a high total-to-HDL cholesterol ratio, diminish or eliminate the sex-based difference in CHD risk.
- Fibrinogen represents an additional risk factor for CHD in women, particularly when combined with other metabolic abnormalities.
Abstract:
In over 30 years of surveillance of 2873 women, 574 developed initial clinical manifestations of CHD. A number of antecedent metabolic risk factors proved atherogenic, including blood lipids, glucose tolerance, uric acid, and menopause. Serum total cholesterol predicts as strongly in women as in men. The predictive power of cholesterol is strengthened when the total cholesterol is partitioned into its atherogenic LDL and protective HDL fractions. Contrary to the case in men, triglyceride may be a contributor to risk in older women. A total-to-HDL cholesterol ratio exceeding 7.5 equalizes the risk in men and women. Impaired glucose tolerance also eliminates the female CHD risk advantage over men, conferring a three-fold increased risk. Serum uric acid, although lower in women than in men, is equally predictive in the sexes. Central obesity confers an increased CHD risk in women and predisposes to diabetes, hyperuricemia, hypertension, and an unfavorable LDL/HDL cholesterol ratio. A combination of obesity, low HDL cholesterol, and impaired glucose tolerance predisposes especially. Age-adjusted risk of CHD is increased two- to threefold compared to pre menopausal women, even when induced surgically without removing the ovaries. It is not clear whether post menopausal estrogen replacement eliminates this excess risk. Fibrinogen is higher in women than in men, and is increased with hypertension, diabetes, hypercholesterolemia, high hematocrit, and cigarette smoking. At any level of multivariate risk, fibrinogen added to the CHD risk in women.