Is a high Framingham (Framingham Risk Score) score a contraindication for Hormone Replacement Therapy (HRT)?

High Framingham Risk Score and Hormone Replacement Therapy

A high Framingham Risk Score (FRS) is a relative contraindication for hormone replacement therapy (HRT) due to the increased risk of cardiovascular events in women with pre-existing cardiovascular risk factors.

Understanding Framingham Risk Score and Cardiovascular Risk

The Framingham Risk Score is a validated risk assessment tool that estimates an individual's 10-year risk of developing coronary heart disease (CHD) based on multiple factors including:

• Age
• Sex
• Total cholesterol
• HDL cholesterol
• Systolic blood pressure
• Smoking status
• Diabetes status 1

According to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III guidelines, patients are categorized into risk categories:

• High risk: CHD or CHD risk equivalents (10-year risk >20%)
• Intermediate risk: 2+ risk factors (10-year risk 10-20%)
• Low risk: 0-1 risk factor (10-year risk <10%) 2

HRT and Cardiovascular Risk

The relationship between HRT and cardiovascular risk is complex and depends on several factors:

Evidence Against HRT in High-Risk Women

• High-quality evidence from randomized controlled trials shows that HRT in women with established cardiovascular disease or high cardiovascular risk provides no protective effects for all-cause mortality, cardiovascular death, or non-fatal myocardial infarction 3

• HRT increases the risk of stroke (RR 1.24,95% CI 1.10 to 1.41), venous thromboembolic events (RR 1.92,95% CI 1.36 to 2.69), and pulmonary emboli (RR 1.81,95% CI 1.32 to 2.48) relative to placebo 3

• Historical data from the Framingham Study showed that postmenopausal women on hormones had a doubled risk of coronary heart disease 4

Timing of HRT Initiation

The cardiovascular impact of HRT appears to be influenced by when treatment is started relative to menopause:

• Women who started HRT less than 10 years after menopause showed lower mortality (RR 0.70,95% CI 0.52 to 0.95) and coronary heart disease (RR 0.52,95% CI 0.29 to 0.96) compared to placebo, though they were still at increased risk of venous thromboembolism 3

• Women who started HRT more than 10 years after menopause showed increased risk of stroke (RR 1.21,95% CI 1.06 to 1.38) and venous thromboembolism (RR 1.96,95% CI 1.37 to 2.80) with no benefit for mortality or coronary heart disease 3

Clinical Decision Algorithm for HRT in Women with High FRS

1. Assess baseline cardiovascular risk using FRS

   • Calculate 10-year CHD risk
   • Identify women with FRS >20% (high risk)

2. For women with high FRS (>20%):

   • Avoid HRT due to increased risk of cardiovascular events, particularly stroke and venous thromboembolism
   • Consider alternative treatments for menopausal symptoms

3. For women with intermediate FRS (10-20%):

   • Carefully weigh benefits against risks
   • Consider time since menopause (more favorable risk-benefit ratio if <10 years post-menopause)
   • Use lowest effective dose for shortest duration if HRT is prescribed

4. For women with low FRS (<10%):

   • HRT may be considered for symptom management if no other contraindications exist
   • Still use lowest effective dose for shortest duration

Important Caveats and Considerations

• Absolute risk matters: The absolute risk increase for stroke with HRT is approximately 6 per 1000 women, for venous thromboembolism 8 per 1000 women, and for pulmonary embolism 4 per 1000 women 3

• Lipid effects: While HRT (particularly estrogen) may have favorable effects on lipid profiles, including increased HDL cholesterol and decreased LDL cholesterol 5, these benefits do not translate to reduced cardiovascular events in high-risk women

• Exercise capacity: Although long-term estrogen replacement therapy has been associated with improved exercise capacity in postmenopausal women without known coronary artery disease 6, this benefit does not outweigh the cardiovascular risks in women with high FRS

• Risk calculation accuracy: The FRS may overestimate risk in certain populations, including Hispanic-American and Asian-American women 1, which should be considered in clinical decision-making

In conclusion, while HRT may have benefits for menopausal symptom management, the increased cardiovascular risks associated with HRT in women with high Framingham Risk Scores make it a relative contraindication in this population.