Using Age- and Sex-Specific Risk Thresholds to Guide Statin Therapy
Key result
Age- and sex-specific statin risk thresholds improve diagnostic accuracy over a fixed 7.5% threshold.
- n=3,685
Why the study?
Whether 10-year CVD risk thresholds for statin therapy should be individualized by age and sex has not been explored.
Does using age- and sex-specific 10-year cardiovascular disease risk thresholds improve the sensitivity and specificity of statin therapy recommendations compared to a fixed 7.5% threshold in adults aged 40-75?
Study Design
Type
Cohort (n=3,685)
Multicenter
No
Structured PICO
Does using age- and sex-specific 10-year cardiovascular disease risk thresholds improve the sensitivity and specificity of statin therapy recommendations compared to a fixed 7.5% threshold in adults aged 40-75?
P
Population
3,685 adults aged 40 to 75 years free of cardiovascular disease at baseline were followed prospectively for 10 years to evaluate statin therapy risk thresholds.
E
Exposure
Statin therapy recommendation based on individualized age- and sex-specific 10-year cardiovascular disease (CVD) risk thresholds (optimized at 5% for ages 40-55, 7.5% for ages 56-65, 10% for women aged 66-75, and 15% for men aged 66-75).
C
Comparator
Statin therapy recommendation based on the 2014 ACC/AHA cholesterol guideline fixed 10-year CVD risk threshold of 7.5% or higher.
O
Outcome
Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the guideline statin treatment recommendations for incident 10-year new onset CVD events (defined as a nonfatal myocardial infarction, coronary heart disease death, fatal or nonfatal stroke, peripheral arterial disease, or heart failure).composite
Limitations
- The Framingham Offspring Study population is not nationally or racially representative.
- Participants contributed to the derivation cohort for the Pooled Cohort Equations, which may overestimate accuracy in this specific population.
- Enrollment primarily in the 1990s may not reflect contemporary risk factor distributions and lower overall CVD rates.
- The Framingham Offspring Study population is not nationally representative and lacks racial diversity.
- Adults in this study contributed to the derivation cohort for the Pooled Cohort Equations, potentially overestimating accuracy in this population.
- Enrollment predominantly occurred in the 1990s, so contemporary changes in risk factor distribution and lower overall rates of CVD could lead to an overestimation of PPV and underestimation of NPV.
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“We found that by raising that threshold to 15 percent, the guidelines could identify the same proportion of men who will go on to have heart disease, but would reduce treatment for those who will not. This would help eliminate unnecessary drug treatment for many patients.”
“The recommendations appear to be one-size-fits-all for patients in a variety of groups. We were interested in how tailoring the guidelines could get beneficial treatment to those who really need it, and avoid over-treating patients whose risk may only be their sex and age.”
Implication
Establishing age- and sex-specific 10-year risk thresholds for statin initiation significantly improves the balance of accurately identifying patients who will experience CVD events while reducing unnecessary therapy, especially in older men.
Abstract
Background New American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines emphasize 10-year risk of cardiovascular disease (CVD) to identify adults eligible for statin therapy for primary prevention. Whether these CVD risk thresholds should be individualized by age and sex has not been explored. Objectives To determine the potential impact of incorporating age- and sex-specific CVD risk thresholds into current cholesterol guidelines. Methods Using data from the Framingham Offspring Study, we evaluated current treatment recommendations among age- and sex-specific groups in 3685 participants free of CVD. Then, we evaluated how varying age- and sex-specific 10-year CVD risk thresholds for statin treatment affect the sensitivity and specificity for incident 10-year CVD events. Results Basing statin therapy recommendations on a 10-year fixed risk threshold of 7.5% results in lower statin consideration among women than men (63% vs. 33% <0.0001), yet the vast majority of those aged 66–75 years were recommended for treatment (90.3%). The fixed 7.5% threshold also had relatively low sensitivity for capturing 10-year events in younger women and men (aged 40-55 years). Sensitivity of the recommendations were substantially improved when the treatment threshold was reduced to 5% in those aged 40-55 years (changing sensitivity from 36% to 61% in women, and 49% to 71% in men). Among older adults (aged 66– 75) specificity was poor (18% in women, 3% in men), but when the treatment threshold was raised to 10% in women and 15% in men, specificity significantly improved (to 34% in women, 14% in men), with only small to no loss in sensitivity (95% to 87% in women, and 96% at both thresholds in men). Conclusions Cholesterol treatment recommendations could be improved by utilizing individualized age- and sex-specific CVD risk thresholds.
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Cite This Study
Navar‐Boggan et al. (2015) conducted a cohort in Cardiovascular disease risk assessment (n=3,685). 10-year fixed cardiovascular risk threshold of 7.5% for statin therapy vs. Age- and sex-specific 10-year cardiovascular risk thresholds was evaluated on Sensitivity and specificity for incident 10-year cardiovascular disease events. Applying age- and sex-specific 10-year cardiovascular risk thresholds for statin therapy improved sensitivity in younger adults and specificity in older adults compared to a fixed 7.5% threshold.