Using Age- and Sex-Specific Risk Thresholds to Guide Statin Therapy | Journal Scan

Study Questions:

How would incorporating age- and sex-specific cardiovascular disease (CVD) risk thresholds for statin treatment impact the current American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guidelines?


Using data from the Framingham Offspring Study, the authors evaluated current statin recommendations among age- and sex-specific groups in 3,685 participants free of CVD. They then evaluated how varying age- and sex-specific 10-year CVD risk thresholds for statin treatment affect the sensitivity and specificity and predictive value for incident 10-year CVD events (defined as nonfatal myocardial infarction, coronary heart disease death, fatal or nonfatal stroke, peripheral arterial disease, or heart failure). The threshold for statin therapy was varied between 3% to 20% 10-year risk to determine the effect of statins on guideline performance characteristics.


Mean age was 57 years, 46.5% were male, mean non–high-density lipoprotein cholesterol (HDL-C) was 159 mg/dl, and 16% were on lipid-lowering treatment. The 10-year CVD observed rate was 16% (23% in men and 11% in women). Overall, 46.8% met criteria for statins basing the recommendation on a 10-year fixed risk threshold of 7.5%, which resulted in lower statin consideration among women than men (33% vs. 63%, p < 0.0001), but 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 was 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 years), 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).


Cholesterol treatment recommendations could be improved by utilizing individualized age- and sex-specific CVD risk thresholds.


The accuracy of various CV risk assessment scores including the new ACC-AHA-ASCVD score has been the subject of much controversy including the recent report by DeFilippis AP, et al., (Ann Intern Med 2015;162:266-75), which found they generally overestimate the event rates, particularly when derived prior to the statin era, as with the Framingham Offspring study. The authors make a cogent argument that supports using age–gender specific cutpoints for statin thresholds, but the actual recommendations will require large and contemporary cohorts. Further, there was no discussion of the frequency with which subjects fell into the two other categories (besides a 7.5% 10-year event rate) for treating men and women without atherosclerotic CVD (ASCVD), e.g., adults with diabetes, aged 40-75 years with low-density lipoprotein cholesterol (LDL-C) levels of 70 and 189 mg/dl, and adults with LDL-C levels of 190 mg/dl or higher.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Acute Heart Failure

Keywords: Cholesterol, Cholesterol, HDL, Cholesterol, LDL, Coronary Disease, Dyslipidemias, Heart Failure, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipoproteins, HDL, Lipoproteins, LDL, Myocardial Infarction, Peripheral Arterial Disease, Primary Prevention, Risk, Risk Assessment, Stroke

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