Comparison of Recommended Eligibility for Primary Prevention Statin Therapy Based on the US Preventive Services Task Force Recommendations vs the ACC/AHA Guidelines

Key Points

Question

How do the 2016 USPSTF primary prevention statin recommendations compare with the ACC/AHA 2013 guidelines in terms of the proportion of US adults potentially treated?

Findings

Using estimates based on data from 3416 participants in the 2009-2014 NHANES, the USPSTF recommendations would be associated with statin initiation in 16% of US adults aged 40 to 75 years without prior cardiovascular disease (CVD), compared with 24% according to the ACC/AHA guidelines. Of the 8.9% of adults who would no longer be recommended to receive therapy under the USPSTF recommendations, 55% are aged 40 to 59 years with a mean 30-year cardiovascular risk exceeding 30%, and 28% have diabetes.

Meaning

Compared with the 2013 ACC/AHA guidelines, adherence to the 2016 USPSTF recommendations could lead to a lower number of individuals recommended for primary prevention statin therapy, including many younger adults with high mean long-term CVD risk.

Abstract

Importance

There are important differences among guideline recommendations for using statin therapy in primary prevention. New recommendations from the US Preventive Services Task Force (USPSTF) emphasize therapy based on the presence of 1 or more cardiovascular disease (CVD) risk factors and a 10-year global CVD risk of 10% or greater.

Objective

To determine the difference in eligibility for primary prevention statin treatment among US adults, assuming full application of USPSTF recommendations compared with the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.

Design, Setting, and Participants

National Health and Nutrition Examination Survey (NHANES) data (2009-2014) were used to assess statin eligibility under the 2016 USPSTF recommendations vs the 2013 ACC/AHA cholesterol guidelines among a nationally representative sample of 3416 US adults aged 40 to 75 years with fasting lipid data and triglyceride levels of 400 mg/dL or less, without prior CVD.

Exposures

The 2016 USPSTF recommendations vs 2013 ACC/AHA guidelines.

Main Outcomes and Measures

Eligibility for primary prevention statin therapy.

Results

Among the US primary prevention population represented by 3416 individuals in NHANES, the median weighted age was 53 years (interquartile range, 46-61), and 53% (95% CI, 52%-55%) were women. Along with the 21.5% (95% CI, 19.3%-23.7%) of patients who reported currently taking lipid-lowering medication, full implementation of the USPSTF recommendations would be associated with initiation of statin therapy in an additional 15.8% (95% CI, 14.0%-17.5%) of patients, compared with an additional 24.3% (95% CI, 22.3%-26.3%) of patients who would be recommended for statin initiation under full implementation of the 2013 ACC/AHA guidelines. Among the 8.9% of individuals in the primary prevention population who would be recommended for statins by ACC/AHA guidelines but not by USPSTF recommendations, 55% would be adults aged 40 to 59 years with a mean 30-year cardiovascular risk greater than 30%, and 28% would have diabetes.

Conclusions And Relevance

In this sample of US adults from 2009-2014, adherence to the 2016 USPSTF recommendations for statin therapy, compared with the 2013 ACC/AHA guidelines, could lead to a lower number of individuals recommended for primary prevention statin therapy, including many younger adults with high mean long-term CVD risk.

This study uses NHANES data to compare the numbers of US adults eligible for primary prevention statin treatment under USPSTF vs ACC/AHA guideline criteria.

Introduction

In 2013, the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines substantially expanded the population eligible for statin therapy by basing recommendations on an elevated 10-year risk of atherosclerotic cardiovascular disease (ASCVD). In 2016, the US Preventive Services Task Force (USPSTF) released new recommendations for primary prevention statin therapy that increased the estimated ASCVD risk threshold for patients (including those with diabetes) and required the presence of at least 1 cardiovascular risk factor (ie, hypertension, diabetes, dyslipidemia, or smoking) in addition to elevated risk. This study used data from the National Health and Nutrition Examination Survey (NHANES) to compare the proportion of individuals in the United States who would be eligible for primary prevention statin treatment with the 2016 USPSTF recommendations compared with the 2013 ACC/AHA guideline recommendations.

Methods

For this analysis, we used data from the 2009-2014 fasting subsample of the continuous NHANES, which contains a representative sample of the US civilian noninstitutionalized population. We excluded persons younger than 40 years or older than 75 years, those with a history of cardiovascular disease (CVD) (defined as symptomatic coronary artery disease or ischemic stroke), those with a triglyceride level greater than 400 mg/dL (4.52 mmol/L), and those with missing values for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, total cholesterol, or systolic blood pressure.

We assessed eligibility for statin therapy according to the criteria outlined in the USPSTF recommendations and the 2013 ACC/AHA guidelines (see eAppendix in the Supplement for criteria details). LDL-C values were calculated using the Friedewald equation; dyslipidemia was defined as LDL-C level greater than 130 mg/dL (3.37 mmol/L) or high-density lipoprotein cholesterol level less than 40 mg/dL (1.04 mmol/L) per the USPSTF recommendations; hypertension was defined as systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or self-reported use of antihypertensive medication; and diabetes was defined as hemoglobin A_1c concentration 6.5% or greater or a self-reported diagnosis of diabetes.

We determined the proportion of adults eligible for statin therapy under each recommendation following NHANES analytic guidelines, using sample weights to account for the complex multistage probability-sampling design, nonresponse rates, and oversampling of certain segments of the population. Adults with LDL-C levels of 190 mg/dL (4.92 mmol/L) or greater and those who reported use of lipid-lowering medications were considered “recommended,” because pretreatment lipid levels were unavailable. We examined clinical characteristics and average ASCVD risk of individuals with concordant and discordant recommendations by the 2 guidelines in the overall sample and by age group (40-59 years and 60-75 years). We also investigated the reasons some individuals would no longer meet eligibility for treatment recommendation when transitioning from ACC/AHA guidelines to USPSTF recommendations. Analyses were performed using SAS version 9.4 (SAS Institute Inc).

All individuals provided informed consent to participate in the NHANES study. The NHANES survey data are available publically, and the survey has been approved by the National Center for Health Statistics ethics review board. The analyses reported in this article were considered exempt by the Duke University institutional review board (PRO00078278).

Results

After exclusion of 577 individuals (13.6%) with CVD, 66 (1.6%) with triglyceride levels greater than 400 mg/dL (4.52 mmol/L), and 175 (4.1%) with missing laboratory or blood pressure data, the study sample consisted of 3416 adults aged 40 to 75 years, free of CVD with triglyceride levels of 400 mg/dL or less. Of these, 747 (21.5% of the primary prevention population [95% CI, 19.3%-23.7%]) reported that they were currently taking lipid-lowering medication.

Full implementation of the USPSTF recommendations would be associated with an incremental increase of 15.8% (95% CI, 14.0%-17.5%) of US adults receiving statin treatment. In contrast, full implementation of the ACC/AHA guidelines would be associated with an incremental increase of 24.3% (95% CI, 22.3%-26.3%) in statin users. The ACC/AHA and USPSTF recommendations for treatment were concordant for 36.9% (95% CI, 34.4%-39.3%) of individuals (21.5% [95% CI, 19.3%-23.7%] currently taking lipid-lowering therapy; 15.4% [95% CI, 13.7%-17.1%] not taking lipid-lowering therapy) and were concordant for no treatment in 53.8% (95% CI, 51.2%-56.4%). Few individuals (0.4% [95% CI, 0.2%-0.6%]) would be recommended for treatment by USPSTF but not by ACC/AHA; these individuals have LDL-C levels less than 70 mg/dL (1.81 mmol/L), at least 1 cardiovascular risk factor, and a 10-year ASCVD risk 10% or greater.

In contrast, 8.9% (95% CI, 7.7%-10.2%) of individuals in the primary prevention population would be recommended for statin therapy under the ACC/AHA guidelines but not under the USPSTF recommendations. Further exploration by age group (Table 1) revealed that among these adults, 55% (representing 4.9% [95% CI, 4.0%-5.9%] of the primary prevention population) were aged 40 to 59 years. This group had a relatively low mean 10-year risk of CVD (7.0% [95% CI, 6.5%-7.5%]), but their mean 30-year risk was 34.6% (95% CI, 32.7%-36.5%).

Table 1. Characteristics of Groups According to Concordant and Discordant Recommendations From ACC/AHA and USPSTF for Statin Use by Age Group, Excluding Those Already Taking Lipid-Lowering Therapy^a.

Characteristic	ACC/AHA and USPSTF Concordant		ACC/AHA and USPSTF Discordant
	Neither Recommend Statin Therapy	Both Recommend Statin Therapyb	Statin Eligible by USPSTF but Not ACC/AHA	Statin Eligible by ACC/AHA but Not USPSTF
Overall
No. in sample	1651	663	25	330
Percentage of primary prevention population, % (95% CI)c	53.8 (51.2-56.4)	15.4 (13.7-17.1)	0.4 (0.2-0.6)	8.9 (7.7-10.2)
Age, median (IQR), y	48 (43-54)	63 (56-68)	65 (60-69)	57 (49-64)
Women, No. (weighted %) [95% CI]d	1015 (32.6) [30.6-34.6]	248 (6.1) [5.1-7.1]	8 (0.2) [0.06-0.3]	130 (3.4) [2.6-4.3]
LDL-C, median (IQR), mg/dL	119.2 (99.4-140.9)	136.9 (110.5-173.1)	58.6 (47.6-65.1)	122.4 (104.6-148.1)
Hypertension, No. (weighted %) [95% CI]d	337 (11.1) [9.7-12.6]	432 (10.2) [8.8-11.7]	20 (0.3) [0.1-0.5]	114 (3.2) [2.3-4.0]
Diabetes, No. (weighted %) [95% CI]d	15 (0.3) [0.1-0.5]	184 (3.8) [3.0-4.6]	11 (0.1) [0.04-0.2]	98 (2.5) [1.9-3.1]
Currently smoking, No. (weighted %) [95% CI]d	269 (8.2) [6.5-10.0]	199 (4.2) [3.5-4.9]	8 (0.1) [0.03-0.2]	63 (1.9) [1.2-2.6]
10-y ASCVD risk, mean (95% CI), %e	2.6 (2.5-2.8)	16.3 (15.2-17.4)	16.3 (12.8-19.9)	8.4 (8.0-8.7)
Aged 60-75 y
No. in sample	205	449	20	147
Percentage of primary prevention population, % (95% CI)f	6.3 (5.5-7.2)	9.4 (8.2-10.6)	0.3 (0.1-0.5)	4.0 (3.1-4.9)
Age, median (IQR), y	62 (60-64)	67 (63-71)	68 (65-70)	65 (62-69)
Women, No. (weighted %) [95% CI]d	176 (5.2) [4.3-6.1]	185 (4.2) [3.4-5.0]	8 (0.2) [0.06-0.3]	67 (1.9) [1.3-2.6]
LDL-C, median (IQR), mg/dL	119.9 (102.7-142.9)	127.1 (106.0-148.2)	59.4 (47.6-65.7)	116.0 (104.1-129.2)
Hypertension, No. (weighted %) [95% CI]d	54 (1.6) [1.0-2.2]	316 (6.8) [5.8-7.9]	17 (0.3) [0.1-0.5]	40 (1.1) [0.5-1.6]
Diabetes, No. (weighted %) [95% CI]d	3 (0.1) [0-0.2]	112 (2.2) [1.6-2.8]	9 (0.1) [0.02-0.2]	9 (0.3) [0.03-0.5]
Currently smoking, No. (weighted %) [95% CI]d	15 (0.4) [0.03-0.8]	94 (1.4) [1.0-1.8]	5 (0.07) [0-0.1]	7 (0.3) [0.01-0.6]
10-y ASCVD risk, mean (95% CI), %e	5.0 (4.6-5.4)	18.9 (18.1-19.7)	17.5 (13.1-22.0)	10.1 (9.6-10.6)
Aged 40-59 y
No. in sample	1446	214	5	183
Percentage of primary prevention population, % (95% CI)g	47.5 (44.9-50.1)	6.0 (4.9-7.0)	0.1 (0-0.1)	4.9 (4.0-5.9)
Age, median (IQR), y	47 (43-52)	54 (50-57)	53 (52-54)	50 (46-55)
Women, No. (weighted %) [95% CI]d	839 (27.4) [25.6-29.2]	63 (1.9) [1.4-2.4]	0	63 (1.5) [0.9-2.0]
LDL-C, median (IQR), mg/dL	119.0 (99.1-140.9)	161.9 (123.0-206.1)	52.5 (15.0-60.2)	130.2 (105.1-154.2)
Hypertension, No. (weighted %) [95% CI]d	283 (9.5) [8.3-10.7]	116 (3.4) [2.6-4.2]	3 (0.04) [0-0.09]	74 (2.1) [1.5-2.6]
Diabetes,No. (weighted %) [95% CI]d	12 (0.2) [0.07-0.4]	72 (1.5) [1.1-2.0]	2 (0.02) [0-0.05]	89 (2.2) [1.7-2.8]
Currently smoking, No. (weighted %) [95% CI]d	254 (7.8) [6.3-9.4]	105 (2.8) [2.1-3.5]	3 (0.05) [0-0.1]	56 (1.6) [1.0-2.3]
10-y ASCVD risk, mean (95% CI), %e	2.3 (2.2-2.4)	12.1 (9.6-14.7)	11.4 (10.1-12.8)	7.0 (6.5-7.5)
30-y CVD risk, mean (95% CI), %h	14.2 (13.8-14.7)	42.4 (39.0-45.7)	26.6 (19.0-34.1)	34.6 (32.7-36.5)

Abbreviations: ACC, American College of Cardiology; AHA, American Heart Association; ASCVD, atherosclerotic cardiovascular disease; CVD, cardiovascular disease; IQR, interquartile range; LDL-C, low-density lipoprotein cholesterol; USPSTF, US Preventive Services Task Force.

SI conversion factor: To convert LDL-C values to mmol/L, multiply by 0.0259.

^aStudy population includes the primary prevention population of adults aged 40 to 75 years with triglyceride levels of 400 mg/dL (4.52 mmol/L) or lower.

^bData for individuals with a concordant recommendation for statin therapy exclude those currently taking lipid-lowering therapy.

^cPercentages do not include the 747 individuals (21.5% of the overall primary prevention population) currently taking lipid-lowering therapy.

^dPercentage of the total primary prevention population.

^eSee 2013 ACC/AHA guideline on assessment of cardiovascular risk.

^fPercentages do not include the 437 individuals (10.3% of the overall primary prevention population) aged 60 to 75 years and currently taking lipid-lowering therapy.

^gPercentages do not include the 310 individuals (11.2% of the overall primary prevention population) aged 40 to 59 years and currently taking lipid-lowering therapy.

^hDetermined using a Framingham risk function, which pertains only to those 60 years or younger.

Further examination of individuals with diabetes not already taking lipid-lowering therapy revealed that, among older adults (60-75 years), the proportions recommended for statins would be similar under both the USPSTF recommendations and the ACC/AHA guidelines: 2.3% (95% CI, 1.7%-2.9%) and 2.5% (95% CI, 1.9%-3.1%) of the primary prevention population, respectively (Table 1). However, among younger individuals (40-59 years), the USPSTF recommendations would recommend statins for 42% of those recommended for statins under the ACC/AHA guidelines (representing 1.6% [95% CI, 1.1%-2.1%] vs 3.8% [95% CI, 3.0%-4.6%] of the primary prevention population).

Table 2 shows reasons that the 8.9% of individuals with an ACC/AHA recommendation for lipid-lowering therapy would no longer be recommended for statins according to the USPSTF guidelines. These include (1) adults free of diabetes and with 10-year risk of 7.5% to 10.0% (5.3% of the primary prevention population [95% CI, 4.4%-6.2%]), primarily men with high rates of smoking, dyslipidemia, and high median LDL-C levels; (2) adults with diabetes and LDL-C levels of 70 mg/dL (1.81 mmol/L) or greater and with a 10-year risk less than 10% (2.5% of the primary prevention population [95% CI, 1.9%-3.1%]), primarily younger women with high rates of obesity; and (3) adults with 10-year risk 10% or greater but no cardiovascular risk factor defined by the USPSTF recommendations (ie, hypertension, diabetes, dyslipidemia, or smoking) (1.1% of the primary prevention population [95% CI, 0.7%-1.5%]), generally older men with lower median LDL-C levels.

Table 2. Characteristics of Adults Aged 40-75 Years Without Cardiovascular Disease Who Were Recommended for Statin Therapy Under the ACC/AHA Guidelines but Excluded From Statin Therapy Under USPSTF Recommendations^a.

Characteristic	No Diabetes, 10-y Risk 7.5%-10.0% (n = 190)	Diabetes, 10-y Risk <10% (n = 98)	10-y Risk ≥10% but No Cardiovascular Risk Factor (n = 42)b
Percentage of primary prevention population, % (95% CI)	5.3 (4.4-6.2)	2.5 (1.9-3.1)	1.1 (0.7-1.5)
Age, median (IQR), y	59 (53-64)	49 (46-54)	69 (65-73)
Women, No. (weighted %) [95% CI]c	62 (32.0) [21.3-42.6]	60 (58.5) [46.0-71.1]	8 (21.5) [8.0-34.9]
Cholesterol, median (IQR), mg/dL
Total	211.3 (188.1-234.2)	192.5 (166.8-215.5)	195.1 (178.5-203.7)
LDL-C	134.3 (108.5-154.6)	112.7 (95.8-133.8)	118.4 (102.0-123.6)
HDL-C	50.0 (42.2-67.3)	45.4 (39.9-53.9)	60.8 (46.8-66.7)
Dyslipidemia, No. (weighted %) [95% CI]c	104 (57.3) [48.1-66.4]	41 (36.0) [23.0-48.9]	0
Systolic blood pressure, median (IQR), mm Hg	126.3 (116.5-135.0)	122.8 (111.6-132.7)	129.2 (114.4-132.3)
Hypertension, No. (weighted %) [95% CI]c	79 (40.1) [29.4-50.9]	35 (40.5) [27.1-54.0]	0
Current antihypertensive therapy, No. (weighted %) [95% CI]c	46 (28.1) [17.1-39.1]	98 (28) [15.0-41.1]	0
Diabetes, No. (weighted %) [95% CI]c	0	98 (100) [100-100]	0
Currently smoking, No. (weighted %) [95% CI]c	54 (31.4) [22.0-40.8]	9 (10.4) [2.8-18.1]	0
Obese, No. (weighted %) [95% CI]c,d	61 (26.5) [18.2-34.7]	73 (74.9) [62.6-87.3]	7 (19.2) [6.0-32.3]

Abbreviations: ACC, American College of Cardiology; AHA, American Heart Association; ASCVD, atherosclerotic cardiovascular disease; HDL-C, high-density lipoprotein cholesterol; IQR, interquartile range; LDL-C, low-density lipoprotein cholesterol; USPSTF, US Preventive Services Task Force.

SI conversion factors: To convert total cholesterol, LDL-C, and HDL-C values to mmol/L, multiply by 0.0259.

^aStudy population includes the primary prevention population of adults aged 40 to 75 years with triglyceride levels 400 mg/dL (4.52 mmol/L) or lower.

^bCardiovascular risk factors, as defined by USPSTF, include hypertension (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or self-reported use of antihypertensive medication), diabetes (hemoglobin A_1cconcentration ≥6.5% or a self-reported diagnosis of diabetes), dyslipidemia (LDL-C level >130 mg/dL or HDL-C level <40 mg/dL), or smoking (self-reported).

^cPercentage of the total population within each column.

^dDefined as body mass index 30 or greater (calculated as weight in kilograms divided by height in meters squared).

Discussion

In this study based on NHANES participants from 2009-2014, it was estimated that, if fully implemented, the USPSTF recommendations would be associated with statin initiation in 15.8% of US adults aged 40 to 75 years without prior CVD, in addition to the 21.5% of adults already taking lipid-lowering therapy; in comparison, the ACC/AHA guidelines would be associated with statin initiation in an additional 24.3%. If these estimates are accurate and assuming these proportions can be projected to the US population, there could be an estimated 17.1 million vs 26.4 million US adults with a new recommendation for statin therapy, based on the USPSTF recommendations vs the ACC/AHA guideline recommendations, respectively—an estimated difference of 9.3 million individuals. Further exploration of those who are recommended to receive statins by the ACC/AHA guidelines but not by the USPSTF recommendations revealed that younger adults (4.9% of the primary prevention population) and persons with diabetes (2.5% of the primary prevention population) would account for much of this difference. Even though younger individuals have modest short-term CVD risk (7.0% over 10 years), approximately one-third would be expected to experience a cardiovascular event in the next 30 years. Given that half of all CVD events in men and one-third in women occur before age 65 years, reliance on 10-year ASCVD risk alone may miss many younger individuals who could potentially benefit from long-term statin therapy. Alternative approaches to augmenting risk-based cholesterol guidelines, including those that explicitly incorporate potential benefit of therapy, should be considered.

This study should be interpreted in light of several caveats and limitations. First, the analysis depends on the representativeness and accuracy of NHANES data, which in part relies on self-report. Second, it is not possible to accurately determine the effects of new recommendations for individuals currently receiving lipid-lowering therapy. Third, the analysis did not take into account the controversy that exists over whether the ASCVD risk score overestimates risk in certain subgroups. Fourth, this analysis was based on a cross-sectional sample that does not account for changes in risk and treatment patterns over time. Fifth, the study assumed that treatment recommendation equated with treatment initiation, whereas USPSTF recommendations and ACC/AHA guidelines also recommend an informed risk-benefit discussion between patients and clinicians.

Conclusions

In this sample of US adults from 2009-2014, adherence to the 2016 USPSTF recommendations for statin therapy, compared with the 2013 ACC/AHA guidelines, could lead to a lower number of individuals recommended for primary prevention statin therapy, including many younger adults with high mean long-term CVD risk.

Supplement.

eAppendix. Eligibility for Primary Prevention Statin Therapy

eReferences