Abstract
Background:
The 2023 Predicting Risk of CVD EVENTs (PREVENT) equations estimate 30-year atherosclerotic cardiovascular disease (ASCVD) risk for adults age 30 to 59 in order to inform preventative treatment decisions. We aimed to characterize 30-year ASCVD risk in the eligible US population.
Methods:
We examined adults ages 30 to 59 without known ASCVD who participated in the National Health and Nutrition Examination Survey, 2017 to March 2020 cycle. Using survey weighting to generate nationally representative estimates with 95% confidence intervals, we described 10-year and 30-year ASCVD risk and risk factor control. We then estimated the absolute risk reduction of statin use in populations at high 30-year risk (≥20%.
Results:
The cohort included 3,229 participants without known ASCVD (mean [SD] age, 44.6 [8.8] years; 49.8% women), representative of 101.9 million (95% CI, 92.2 – 111.6) US adults. The mean estimated 10-year ASCVD risk was 2.0% (95% CI, 1.9% to 2.1%) and the mean 30-year risk was 9.7% (95% CI, 9.4%–10.1%). Of the 9% of the population with high estimated 30-year ASCVD risk, 32.4% (95% CI, 24.0% - 40.7%) reported statin use. Most adults with high 30-year ASCVD risk had multiple uncontrolled risk factors, including elevated blood pressure (70.8%; 95% CI, 62.4% - 79.2%), obesity (59.9%; 95% CI, 52.6% - 67.2%) and, and elevated total cholesterol (56.2%; 95% CI, 45.5% - 66.9%). Expanding primary prevention statins to adults with high 30-year ASCVD risk would change recommendations for 2.5 million (95% CI, 1.9–3.2) adults not currently receiving statins, with an average number needed to treat (NNT) over 10 years to prevent one ASCVD event of 78.3 (95% CI, 74.6–82.0).
Conclusion:
Use of the PREVENT 30-year ASCVD risk equations would identify a population of US adults with low 10-year but high 30-year who may warrant enhanced primary prevention strategies.
Keywords: Atherosclerotic cardiovascular disease, risk estimation, primary prevention, statins
INTRODUCTION
Estimation of atherosclerotic cardiovascular disease (ASCVD) risk is now central to primary prevention efforts. Traditional 10-year atherosclerotic cardiovascular disease (ASCVD) risk calculators have been criticized, however, for leading to undertreatment of younger at-risk people (1,2). Use of risk equations with longer time horizons, such as 30 years or life-time, have been proposed to help guide preventative treatment decisions, including the use of lipid lowering therapies, for middle-aged and younger adults. For example, the 2019 American College of Cardiology (ACC) and American Heart Association (AHA) guideline on the primary prevention of cardiovascular disease recommends calculation of 30-year or life-time risk as a “communication strategy for reinforcing adherence to lifestyle recommendations” (3) while the 2018 AHA/ACC guideline on the management of blood cholesterol recommends 30-year or life-time risk “can be used to inform intensity of primary prevention efforts” (4).
To facilitate this, in 2023 the AHA Cardiovascular-Kidney-Metabolic Scientific Advisory Group developed the Predicting Risk of Cardiovascular Disease Events (PREVENT) equations which included a new measure for predicting 30-year ASCVD risk using the same clinical inputs as for 10-year ASCVD risk (5). Compared to the currently recommended pooled cohort equations (PCEs) (6), the PREVENT equations were developed from a combination of more diverse and contemporary prospective cohorts and routinely collected electronic health record data, removed race, and added measures of renal function and statin use to risk prediction. This novel 30-year risk measure builds on prior calculators to estimate long-term risk based on more limited cohort studies (7).
The population health implications of routinely estimating 30-year ASCVD risk and incorporating 30-year risk thresholds into primary prevention decisions are not known. One prior study described discordance between 10-year and 30-year PREVENT estimates of overall cardiovascular disease risk (inclusive of heart failure) (8), but there has not been an examination of 30-year ASCVD risk or of the potential population health implications of using these data. Thus, we used data from the National Health and Nutrition Examination Survey (NHANES) (9) to describe 30-year ASCVD risk in adults ages 30 to 59 at the population level and compare 30-year risk estimates to 10-year ASCVD risk estimates generated by the PREVENT equations. We then assessed differences in cardiovascular risk factor control across categories of 30-year ASCVD risk and estimated the potential impact of expanding primary prevention statin recommendations to individuals with elevated 30-year risk.
METHODS
Data Source
All data are been made publicly available at the NHANES website and all study materials will be made available upon reasonable request. Our study analyzed the combined 2017 to March 2020 cycle of the NHANES. NHANES is conducted by the National Center of Health Statistics using a stratified, multistage probability-cluster sampling design (9,10). Questionnaire, laboratory, and physical examination information is collected via in-home interviews and visits to a mobile examination center. This cross-sectional study was exempt from review and informed consent by the Common Rule given its use of publicly available aggregated data. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline (Supplemental Methods).
Study Population
NHANES participants aged 30 to 59 years who completed the mobile examination center visit were included in the study population as this is the target population of the PREVENT 30-year risk equations (5). Adults with known ASCVD, defined as self-reported history of acute myocardial infarction, angina, coronary artery disease, or stroke, were excluded. Additional exclusions were pregnancy and missing variables used by the PREVENT risk calculators (Figure S1).
Atherosclerotic Cardiovascular Disease Risk Estimation
We examined the 2023 PREVENT equations for estimating 10-year and 30-year risk of ASCVD. The PREVENT 10-year equations have previously been externally validated in NHANES with moderate-to-strong discrimination and calibration (11). Both calculators include values for age, sex, total and high-density lipoprotein (HDL) cholesterol, systolic blood pressure (BP), diabetes status, smoking status, estimated glomerular filtration rate (GFR), antihypertensive medication use, and statin use. Sex, race, smoking status, and medication use were ascertained by NHANES participant self-report. Diabetes was identified by self-reported history or a hemoglobin A1c ≥ 6.5%. Total and HDL cholesterol were reported in mg/dL and converted to mmol/L using the conversion factor 0.02586 mg/dL per 1 mmol/L to match calculator units. BP was recorded as the average of up to three readings taken after resting for five minutes in a seated position, using a validated oscillometric device. Serum creatinine was used to calculate GFR using the 2021 Chronic Kidney Disease Epidemiology Collaboration equations (12), consistent with PREVENT methodology. We did not examine the expanded PREVENT model with optional variables for hemoglobin A1c, urine albumin-creatinine ratio, and social deprivation index as prior studies suggest little difference between enhanced and baseline PREVENT models (5,13). Though PREVENT excluded individuals with outlier values of continuous measurements, we included these individuals and adjusted outlier measurements to calculator cut-offs in order to be consistent with clinical practice (e.g., systolic BP of 205 mm Hg was recategorized to the maximum allowed value of 200 mm Hg).
Eligibility for Primary Prevention Statin
Adults were defined as eligible for primary prevention statin use based on the 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease (3), which recommends statins for three groups of adults aged 40 to 75 years: those with diabetes, those with a fasting low-density lipoprotein (LDL) cholesterol greater than 190 mg/dL, and those with an estimated 10-year ASCVD risk of 7.5% or greater. The guideline further subdivides 10-year ASCVD risk as intermediate (7.5%−19.9%) or high (20% or greater). Individuals with estimated risk <5% are classified as low risk and those with an estimated risk of 5% to 7.4% as borderline risk, both groups are not routinely recommended pharmacotherapy in the absence of other risk enhancing factors, and thus are referred to as low risk for this study. As fasting LDL cholesterol data is available for only a subset of NHANES participants and most individuals with an LDL >190 mg/dL also meet criteria for primary prevention by elevated 10-year ASCVD risk (13), we did not examine LDL cholesterol separately.
Statistical Analysis
All analyses used NHANES mobile examination center weights for the 2017- March 2020 cycle to result in nationally representative estimate results with 95% confidence intervals (9). Our analysis consisted of three steps. First, we calculated probability density distributions of estimated 10-year and 30-year ASCVD risk overall and across demographic characteristics of sex, age, race and ethnicity, and diabetes status. Then we graphically plotted a cross-tabulation of estimated 10-year and 30-year ASCVD risk using the PREVENT equations.
Second, we calculated the prevalence and control of ASCVD risk factors among adults stratified by the 30-year ASCVD risk categories. We examined the prevalence of hypertension (systolic BP > 130 mm Hg or diastolic BP > 80 mm Hg), high total cholesterol (above 200 mg/dL), low HDL cholesterol (<40 mg/dL for mean and <50 mg/dL for women), diabetes (any and with hemoglobin A1c >7.0%), current smoking, obesity (body mass index of ≥30 kg/m2 or greater), and chronic kidney disease (glomerular filtration rate [GFR] <60 mL/min/1.83 m2). We also examined the current use of antihypertensives, statins, and diabetes medications.
Third, we calculated the total numbers of 1) adults ages 40 to 59 meeting current guideline recommendations for primary prevention statin use based on the 2019 AHA/ACC primary prevention guidelines (3), 2) adults ages 30 to 39 with diabetes or 10-year ASCVD risk >7.5% not currently recommended primary prevention statin use because the PCEs did not estimate 10-year risk in this age group, but for whom 10-year risk is now able to be estimated using PREVENT equations, and 3) individuals not currently recommended primary prevention statin use but with elevated estimated 30-year ASCVD risk, using risk thresholds of 20%, 15%, and 10%. For each group, we calculated the number not currently taking statins and then estimated the number of estimated ASCVD events in 10 years among individuals not currently taking statins and the estimated number of ASCVD events in 10 years if these individuals were taking statins. To conduct these estimations, we multiplied each individual’s 10-year estimated ASCVD risk by the expected relative risk reductions of 25% for statin therapy based on prior meta-analyses (14,15). We then calculated the average absolute risk reduction (ARR) and average number needed to treat (NNT) across each group (16). This process was repeated to estimate ASCVD events, ARR and NNT for at the 30-year horizon. The underlying PREVENT equations were adjusted for competing risks of death from non-cardiovascular causes, estimated risk reductions accounted similarly accounted for competing risks (5).
RESULTS
The study sample included 3,229 NHANES participants, which was representative of 101.9 million (95% CI, 92.2 – 111.6) non-pregnant US adults without known ASCVD between the ages of 30 and 59 years after survey weighting. The weighted mean [SD] age of the cohort was 44.6 [8.8] years, 49.8% were female, 6.1% identified as Asian, 10.8% as Black, 9.3% as Mexican American, 8.0% as other Hispanic, and 61.1% as White (Table 1).
Table 1.
Characteristics of US Adults Aged 30–59 Years Without Known Atherosclerotic Cardiovascular Disease, Overall and by 30-Year Atherosclerotic Cardiovascular Disease Risk Category
| Estimated 30-Year Atherosclerotic Cardiovascular Disease Risk Category | ||||
|---|---|---|---|---|
| Total | Low Risk (<7.5%) |
Intermediate Risk (7.5% - 19.9%) |
High Risk (≥20.0%) |
|
| Unweighted No. | 3229 | 1453 | 1398 | 378 |
| Weighted No., millions (95% CI) | 101.9 (92.2 – 111.6) | 47.9 (42.9 – 52.9) | 45.0 (40.3 – 49.6) | 9.1 (7.4 – 10.8) |
| Characteristic, Column % (95% CI) | ||||
| Age, years | ||||
| 30–39 | 33.7 (31.1 – 36.4) | 62.5 (59.0 – 65.9) | 9.6 (6.4 – 12.9) | 1.5 (0.2 – 2.8) |
| 40–49 | 32.5 (30.1 – 34.9) | 32.1 (28.8 – 35.3) | 35.3 (31.7 – 38.8) | 21.5 (13.3 – 29.7) |
| 50–59 | 33.7 (31.2 – 36.3) | 5.5 (4.0 – 6.9) | 55.1 (51.2 – 59.0) | 77.0 (68.9 – 85.1) |
| Gender | ||||
| Female | 49.8 (47.5 – 52.2) | 62.0 (59.6 – 64.4) | 40.0 (36.0 – 44.1) | 34.1 (27.6 – 40.7) |
| Male | 50.2 (47.8 – 52.5) | 38.0 (35.6 – 40.4) | 60.0 (55.9 – 64.0) | 65.9 (59.3 – 72.4) |
| Race and ethnicity | ||||
| Asian | 6.1 (4.0 – 8.2) | 6.9 (4.4 – 9.3) | 5.5 (3.3 – 7.6) | 5.4 (3.1 – 7.6) |
| Black | 10.8 (8.0 – 13.5) | 10.3 (7.1 – 13.5) | 9.8 (7.6 – 12.1) | 17.9 (11.8 – 23.9) |
| Mexican American | 9.3 (6.9 – 11.7) | 10.1 (7.2 – 13.0) | 8.5 (6.4 – 10.6) | 9.3 (4.9 – 13.8) |
| Other Hispanic | 8.0 (6.0 – 10.0) | 8.5 (6.2 – 10.8) | 7.4 (5.2 – 9.7) | 8.5 (4.1 – 13.0) |
| White | 61.1 (55.4 – 66.7) | 60.1 (53.1 – 67.0) | 63.9 (59.1 – 68.7) | 52.3 (39.4 – 65.2) |
| Other * | 4.7 (3.7 – 5.8) | 4.3 (2.7 – 5.8) | 4.8 (2.8 – 6.9) | 6.6 (1.7 – 11.4) |
| Education | ||||
| < 12th grade | 10.1 (8.5 – 11.7) | 8.4 (6.5 – 10.3) | 10.9 (8.7 – 13.0) | 15.4 (10.0 – 20.8) |
| High school graduate | 22.5 (19.3 – 25.8) | 18.6 (14.2 – 23) | 24.3 (19.8 – 28.8) | 34.2 (24.9 – 43.5) |
| Some college | 31.7 (28.7 – 34.7) | 31.8 (27.3 – 36.3) | 32.1 (28.4 – 35.9) | 29.2 (23.3 – 35.1) |
| College graduate | 35.6 (30.9 – 40.4) | 41.1 (34.2 – 48.0) | 32.7 (27.8 – 37.6) | 21.2 (13.6 – 28.7) |
| Health Insurance | ||||
| Commercial | 63.4 (60.1 – 66.7) | 63.5 (58.1 – 68.8) | 65.4 (61.2 – 69.7) | 52.8 (42.5 – 63.1) |
| Medicare | 1.7 (1.2 – 2.2) | 0.7 (0.2 – 1.2) | 2.0 (1.1 – 3.0) | 5.1 (1.5 – 8.7) |
| Medicaid | 9.6 (7.9 – 11.4) | 10.2 (8.2 – 12.3) | 9.1 (6.4 – 11.8) | 9.4 (5.7 – 13.2) |
| Other insurance | 10.5 (7.9 – 13.2) | 9.8 (6.4 – 13.2) | 10.4 (7.5 – 13.2) | 15.1 (7.1 – 23.1) |
| Uninsured | 14.3 (11.8 – 16.8) | 15.2 (12.0 – 18.4) | 12.8 (10.0 – 15.7) | 17.1 (10.3 – 23.9) |
| Missing | 0.4 (0.2 – 0.7) | 0.6 (0.2 – 1.0) | 0.3 (0.0 – 0.5) | 0.5 (0.0 – 1.1) |
| Access to care | ||||
| Routine place for care | 82.0 (79.7 – 84.3) | 79.4 (76.1 – 82.7) | 84.1 (80.7 – 87.5) | 85.3 (78.4 – 92.1) |
| Care in the last year | 81.6 (79.4 – 83.8) | 79.6 (76.8 – 82.3) | 83.0 (79.5 – 86.4) | 85.5 (79.5 – 91.5) |
Other Race per survey includes Multi-Racial
The mean estimated 10-year ASCVD risk for the cohort was 2.0% (95% CI, 1.9% to 2.1%) and nearly all of the cohort had low (<7.5%) estimated risk (97.4%; 95% CI, 96.6% – 98.1%) (Figure S2). Of the 10.5% (95% CI 8.9% - 12.1%) of the cohort that had diabetes, the majority also had low estimated 10-year risk (79.6%; 95% CI, 72.4% - 86.9%).
30-Year Estimated ASCVD Risk
The mean estimated 30-year ASCVD risk across the cohort was 9.7% (95% CI, 9.4% – 10.1%) and Figure 1 depicts the distributions of 30-year risk across demographic groups. Mean 30-year risk was higher in men (11.5%; 95% CI, 11.0% - 12.0%) than women (7.9%; 95% CI, 7.5% - 8.4%) and higher with each decade of age. Among adults ages 30 to 39, only 0.4% (95% CI 0.1% - 0.7%) had a high (≥20%) 30-year risk, compared with 20.3% (95% CI, 17.1% - 23.5%) of adults ages 50 to 59. Estimated 30-year risk was similar between racial and ethnic groups. Estimated 30-year risk was substantially higher among adults with diabetes (21.2%; 95% CI, 20.1% - 22.3%) than adults without diabetes (8.4%; 95% CI, 8.1% - 8.7%).
Figure 1.
Marginal Distributions of Estimated 30-Year Atherosclerotic Cardiovascular Disease Risk (ASCVD): A)Overall and by Gender; b) By Age; C)By Race and Ethnicity; and D) By Diabetes Status. Lines and area under them represent probability density of 30-year ASCVD risk for each group. Data from National Health and Nutrition Examination Survey 2017–2020 were survey weighted to the eligible US population.
Overall, 10-year ASCVD risk scores were highly predictive of 30-year ASCVD risk scores (r2 = 0.85). A weighted estimate of 9.1 million (95% CI 7.4 – 10.8) adults ages 30 – 59 years had high estimated 30-year risk ≥ 20% of which 6.6 million (95% CI 5.0 – 8.1) had a 10-year risk <7.5% (Figure S3, Table S1). Among adults with low (<7.5%) estimated 10-year ASCVD risk, 48.2% (95% CI, 46.2% to 50.3%) also had a low (<7.5%) estimated 30-year ASCVD, 45.2% (95% CI, 43.2% to 47.1%) had intermediate (7.5% - 19.9%) 30-year risk, and only 6.6% (95% CI, 5.3% to 7.9%) had high (≥20%) 30-year risk. Nearly all of adults with intermediate 10-year ASCVD risk, had high 30-year ASCVD risk.
Cardiovascular Risk Factor Control
Among adults with high 30-year ASCVD risk, uncontrolled modifiable risk factors were common: 70.8% (95% CI, 62.4% - 79.2%) had elevated BP, 59.9% (95% CI, 52.6% - 67.2%) had obesity, 56.2% (95% CI, 45.5% - 66.9%) had elevated total cholesterol, 53.2% (95% CI, 44.6% - 61.8%) had low HDL cholesterol, 31.1% (95% CI, 24.2% - 38.5%) reported current smoking and 31.4% (95% CI, 24.2% - 38.5%) had an elevated hemoglobin A1c (Table 2). The prevalence of uncontrolled cardiovascular risk factors was lower among adults with low and intermediate 30-year ASCVD risk, but one-third of low-risk adults and two-thirds of intermediate risk adults had two or more uncontrolled risk factors. In all groups elevated BP, elevated total cholesterol, and obesity were the most common risk factors. Among individuals with high 30-year ASCVD risk, the presence of three or more uncontrolled risk factors was more common in adults ages 30 to 49 (82.5%; 95% CI, 76.9% to 88.1%)) than adults ages 50–59 (68.3%; 95% CI, 60.9%to 75.8%), almost no adults in either age category had zero uncontrolled risk factors (Table S2).
Table 2.
Prevalence and Control of Cardiovascular Risk Factors Among US Adults Aged 30–59 Years, by 30-year Atherosclerotic Cardiovascular Disease Risk
| 30-year ASCVD Risk | |||
|---|---|---|---|
| Low (<7.5%) |
Intermediate (7.5% - 19.9%) |
High (≥20.0%) |
|
| Unweighted No. | 1453 | 1398 | 378 |
| Weighted No., millions (95% CI) | 47.9 (42.9 – 52.9) | 45.0 (40.3 – 49.6) | 9.1 (7.4 – 10.8) |
| Cardiovascular risk factors, Column % (95% CI) | |||
| Elevated Blood Pressure | |||
| BP >130/80 mm Hg | 19.7 (16.9– 22.4) | 46.3 (41.5 – 51.1) | 70.8 (62.4 – 79.2) |
| Taking any antihypertensive | 6.5 (4.9 – 8.2) | 26.3 (23.1 – 29.5) | 57.6 (50.3 – 64.9) |
| Taking single antihypertensive | 5.0 (3.3 – 6.7) | 19.2 (16.1 – 22.3) | 39.4 (33.0 – 45.9) |
| Taking multiple antihypertensives | 1.5 0.8 – 2.3) | 7.0 (5.5 – 8.5) | 17.5 (11.6 – 23.3) |
| Cholesterol | |||
| Total cholesterol ≥200 mg/dL | 30.4 (26.6 – 34.1) | 46.8 (41.5 – 52.1) | 56.2 (45.5 – 66.9) |
| Low HDL cholesterol* | 23.5 (20.3 – 26.7) | 30.7 (26.9 – 34.5) | 53.2 (44.6 – 61.8) |
| Taking statin | 2.5 (1.1 – 3.8) | 11.6 (8.7 – 14.6) | 32.4 (24.0 – 40.7) |
| Diabetes | |||
| Diabetes | 0.5 (0.2 – 0.8) | 10.9 (8.2 – 13.5) | 61.4 (55.2 – 67.6) |
| Hemoglobin A1c >7.0% | 0.1 (0.0 – 0.3) | 5.2 (3.6 – 6.8) | 31.4 (24.2 – 38.5) |
| Taking diabetes medications | 1.0 (0.3 – 1.7) | 9.3 (6.2 – 12.3) | 40.4 (33.5 – 47.3) |
| Additional Risk Factors | |||
| Current smoking | 14.2 (10.5 – 17.9) | 21.9 (19.4 – 24.4) | 31.1 (23.2 – 39.0) |
| BMI >30 kg/m2 | 34.9 (30.6 – 39.2) | 48.6 (36.3 – 53.0) | 59.9 (52.6 – 67.2) |
| GFR <60 mL/min/1.73 m2 | 0.6 (0.1 – 1.0) | 1.5 (0.5 – 2.4) | 3.6 (1.8 – 5.4) |
| No. of uncontrolled risk factors, Column % (95% CI) † | |||
| 0 | 28.4 (24.5 – 32.2) | 6.6 (4.3 – 8.9) | 0.2 (0.0 – 0.6) |
| 1 | 33.8 (30.7 – 37.0) | 26.3 (23.1 – 29.4) | 5.0 (0.0 – 10.3) |
| 2 | 25.6 (23.4 – 27.9) | 36.1 (31.0 – 41.2) | 23.1 (18.5 – 27.8) |
| ≥3 | 12.2 (9.8 – 14.6) | 31.0 (26.3 – 35.7) | 71.6 (65.6 – 77.6) |
Note: Abbreviations: BMI, body mass index; BP, blood pressure; GFR, glomerular filtration rate; HDL, high-density lipoprotein
Defined as a high-density cholesterol level of <40 mg/dL for men and <50 mg/dL for women
Uncontrolled risk factors include BP > 130/80 mmHg, total cholesterol > 200 mg/dL, HDL cholesterol <40 mg/dL for men or <50 mg/dL for women, hemoglobin A1c greater than 7.0%, current smoking, BMI >30 kg/m2, and GFR <60 mL/min/1.73 m2.
Individuals with Low 10-year and High 30-year ASCVD Risk
Among individuals with low 10-year ASCVD risk (<7.5%), the majority also had low 30-year ASCVD risk, (<20%), but an estimated 6.6 million (95% CI 5.0 – 8.1 million) individuals had elevated 30-year risk of ≥20% (Table 3). In all key risk factors except gender, individuals with a high 30-year risk (≥20%) but low 10-year risk (<7.5%) had values that were between those whose risk were low for both 10-year and 30-year and those whose risk was high for both. For example, 29.5% (95% CI, 27.0 – 31.9%) of those whose risk was low for both were 50–59 years old, compared to 72.5% (95% CI, 61.2 – 83.9%) of those who were low 10-year but high 30-year and 88.6% (95% CI, 82.3 – 94.9%) of those who had high 10-year and 30-year risk. Among adults with low 10-year and high 30-year ASCVD risk, nearly all had at least 2 uncontrolled modifiable risk factors including 68.8% with elevated BP (95% CI, 59.4 – 78.3%), 51.8% with diabetes (95% CI 42.1% – 61.5%), and 48.7% with elevated cholesterol. In this group with low 10-year ASCVD risk, 35.8% (95% CI 24.1 – 47.4) were taking statins and 55.3% (95% CI 46.7% – 63.9%) were taking antihypertensives.
Table 3.
Cardiovascular Risk Factors and Control of US Adults Aged 30–59 Years by 10-Year and 30-Year Atherosclerotic Cardiovascular Disease Risk
| 10-Year Risk < 7.5% | 10-Year Risk ≥ 7.5% and 30-Year Risk ≥ 20%* |
||
|---|---|---|---|
| 30-Year Risk < 20% | 30-Year Risk ≥ 20% | ||
| Unweighted No. | 2847 | 259 | 119 |
| Weighted No., millions (95% CI) | 92.7 (83.8 – 101.6) | 6.6 (5.0 – 8.1) | 2.5 (1.8 – 3.2) |
| Non-modifiable cardiovascular risk factors, Column % (95% CI) | |||
| Age, years | |||
| 30–39 | 36.9 (34.0 – 39.8) | 1.6 (0.0 – 3.2) | 1.3 (0.0 – 3.6) |
| 40–49 | 33.7 (31.2 – 36.1) | 25.9 (14.3 – 37.5) | 10.1 (5.1 – 15.0) |
| 50–59 | 29.5 (27.0 – 31.9) | 72.5 (61.2 – 83.9) | 88.6 (82.3 – 94.9) |
| Gender | |||
| Female | 51.4 (48.9 – 54.0) | 32.7 (25.6 – 39.8) | 37.8 (20.5 – 55.2) |
| Male | 48.6 (46.0 – 51.1) | 67.3 (60.2 – 74.4) | 62.2 (44.8 – 79.5) |
| Modifiable cardiovascular risk factors, Column % (95% CI) | |||
| Elevated Blood Pressure | |||
| BP >130/80 mm Hg | 32.5 (29.2 – 35.8) | 68.8 (59.4 – 78.3) | 75.9 (60.4 – 91.4) |
| Taking antihypertensive | 16.0 (14.3 – 17.7) | 55.3 (46.7 – 63.9) | 63.7 (50.5 – 76.9) |
| Cholesterol | |||
| Total cholesterol ≥200 mg/dL | 38.3 (34.8 – 41.8) | 48.7 (35.8 – 61.6) | 75.6 (64.3 – 87.0) |
| Low HDL cholesterol† | 27.0 (23.9 – 30.2) | 53.7 (44.1 – 63.4) | 51.9 (37.5 – 66.2) |
| Taking statin | 6.9 (5.3 – 8.5) | 35.8 (24.1 – 47.4) | 23.6 (15.3 – 31.8) |
| Diabetes | |||
| Diabetes | 5.5 (4.2 – 6.8) | 51.8 (42.1 – 61.5) | 86.3 (78.4 – 94.1) |
| Hemoglobin A1c >7.0% | 2.6 (1.8 – 3.4) | 25.7 (17.0 – 34.4) | 46.1 (32.0 – 60.2) |
| Taking diabetes medications | 5.0 (3.5 – 6.5) | 37.2 (27.7 – 46.7) | 48.8 (35.4 – 62.1) |
| Additional Risk Factors | |||
| Current smoking | 18 (15.4 – 20.5) | 27.7 (16.4 – 39) | 40.0 (25.2 – 54.9) |
| BMI >30 kg/m2 | 41.5 (38.0 – 45.0) | 57.0 (47.3 – 66.7) | 67.3 (56.6 – 78.1) |
| GFR <60 mL/min/1.73 m2 | 0.8 (0.4 – 1.3) | 1.1 (0.0 – 2.2) | 10.2 (3.3 – 17.1) |
| No. of uncontrolled risk factors, Column % (95% CI) ‡ | |||
| 0 | 17.9 (15.4 – 20.3) | 0.2 (0.0 – 0.5) | 0.4 (0.3 – 0.6) |
| 1 | 30.2 (28.3 – 32.2) | 7.0 (0.0 – 14.1) | 0.0 (0.0 – 0.0) |
| 2 | 30.7 (27.9 – 33.6) | 28.7 (22.6 – 34.7) | 8.8 (1.9 – 15.7) |
| ≥3 | 21.2 (18.1 – 24.2) | 64.2 (56.3 – 72.1) | 90.7 (83.8 – 97.7) |
Note: Abbreviations: BMI, body mass index; BP, blood pressure; GFR, glomerular filtration rate; HDL, high-density lipoprotein
The group of 10-year ASCVD risk >=7.5% and 30-year ASCVD risk <20% was only an unweighted sample size of 4 (weighted, millions [95% CI]; 0.1 [0.0–0.3]) so it was not included in this table
Defined as a high-density cholesterol level of <40 mg/dL for men and <50 mg/dL for women
Uncontrolled risk factors include BP > 130/80 mmHg, total cholesterol > 200 mg/dL, HDL cholesterol <40 mg/dL for men or <50 mg/dL for women, hemoglobin A1c greater than 7.0%, current smoking, BMI >30 kg/m2, and GFR <60 mL/min/1.73 m2.
Estimated Impact of Expanding Primary Prevention Statin Indications
Among adults ages 40 to 59, 9.7 million (95% CI 7.8 million – 11.6 million) meet current guideline criteria for statins for primary prevention, 2.6 million (95% CI, 1.9 million – 3.3 million) due to estimated 10-year ASCVD risk of 7.5% or greater and 7.1 million (95% CI, 5.2 million – 9.0 million) due to diabetes with low ASCVD risk (Table S3). Of statin-eligible adults, 5.7 million (95% CI, 4.5 million – 6.9 million) were not taking statins, the majority of whom were adults with diabetes and low ASCVD risk. By 10-year ASCVD risk category, the mean NNT of using statins for 10 years to prevent 1 ASCVD event was 18.5 (95% CI, 13.7 – 23.4) for the high-risk group (≥20%), 40.4 (95% CI, 36.7 – 44.1) for the intermediate-risk group (7.5–19.9%), and 111.4 (95% CI, 96.3 – 126.5) for the group with diabetes and low ASCVD risk (<7.5%) (Table 4).
Table 4.
Impact of Primary Prevention Statin Use Among US Adults Aged 30–59 Years Not Currently Taking Statins, by Risk Category
| No. Not Currently Receiving Statins, thousands (95% CI) | Mean Estimated 10-year ASCVD Risk, % (95% CI) | Mean 10-year Absolute Risk Reduction, % (95% CI) | NNT for 10 Years to Prevent 1 ASCVD Event, No. (95% CI) | |
|---|---|---|---|---|
| Currently Recommended Primary Prevention Statins | ||||
| Overall: Ages 40–59 currently recommended statins | 5,690.9 (4,478.0 – 6,903.8) | 6.5 (6.0 – 7.1) | 1.6 (1.5 – 1.8) | 86.5 (74.2 – 98.7) |
| Ages 40–59 with 10-year ASCVD risk ≥20% | 53.0 (0.0 – 208.2) | 22.3 (13.9 – 29.8) | 5.6 (3.7 – 7.5) | 18.5 (13.7 – 23.4) |
| Ages 40–59 with 10-year ASCVD risk 7.5% – 19.9% | 1,926.6 (1,317.9 – 2,535.3) | 10.5 (9.5 – 11.5) | 2.6 (2.4 – 2.9) | 40.4 (36.7 – 44.1) |
| Ages 40–59 with diabetes and 10-year risk <7.5% | 3,711.3 (2,614.7 – 4,807.9) | 4.3 (3.9 – 4.6) | 1.1 (1.0 – 1.1) | 111.4 (96.3 – 126.5) |
| Expanding Current Recommendations to Ages 30–39 | ||||
| Ages 30–39 with diabetes or 10-year risk ≥7.5% | 1,379.9 (1,120.1 – 1,639.7) | 2.5 (2.3 – 2.8) | 0.6 (0.6 – 0.7) | 211.1 (194.5 – 227.7) |
| Expanding Recommendations Based on Estimated 30-year ASCVD Risk * | ||||
| Ages 30–59 with 30-year ASCVD risk ≥20% | 2,492.9 (1,878.2 – 3,197.6) | 5.3 (5.0 – 5.5) | 1.3 (1.3 – 1.4) | 78.3 (74.6 – 82.0) |
| Ages 30–59 with 30-year ASCVD risk 15% – 19.9% | 8,519.6 (6,912.2 – 10,126.9) | 3.5 (3.4 – 3.7) | 0.9 (0.8 – 0.9) | 116.6 (112.2 – 121.1) |
| Ages 30–59 with 30-year ASCVD risk 10% – 14.9% | 17,319.5 (14,776.5 – 19,862.4) | 2.2 (2.1 – 2.3) | 0.5 (0.5 – 0.6) | 191.3 (184.7 – 197.8) |
| Ages 30–59 with 30-year ASCVD risk 7.5% – 9.9% | 10,642.9 (9,230.8 – 12,055.3) | 1.4 (1.4 – 1.4) | 0.4 (0.3 – 0.4) | 288.3 (282.1 – 294.4) |
Excludes adults with diabetes, or 10-year ASCVD risk ≥7.5% who are already recommended primary prevention statins
Expansion of current primary prevention statin recommendations to adults ages 30–39 would result in an estimated 1.4 million (95% CI, 1.1 million – 1.6 million) adults being newly eligible for statin pharmacotherapy. This group would have a much higher NNT (211.1; 95% CI, 194.5 – 227.7) compared to populations currently statin-eligible, as the majority of this group consists of individuals with diabetes and low (<7.5%) ASCVD risk.
Further expanding statin recommendations to adults ages 30–59 with ≥20% 30-year ASCVD risk would result in 2.5 million (95% CI, 1.9 million – 3.2 million) adults newly eligible for primary prevention statins not already taking them. This group had a NNT to prevent 1 ASCVD event in 10 years of 78.3 (95% CI, 74.6 – 82.0). Further expanding recommendations to adults with 30-year risk between 7.5% and 20% would result in large increases in the population recommended statins, between 8 and 36 million depending on cutoff used. However, groups with intermediate 30-year risk would have a mean absolute risk reduction less than 1% resulting in an estimated NNT between 117 and 288.
At a 30-year horizon, the NNT for individuals currently recommended statins to prevent 1 ASCVD event in 30 years of 19.7 (95% CI, 17.9 – 21.6) (Table S4). If statin recommendations were expanding to adults ages 30–59 with ≥20% 30-year ASCVD risk the NNT to prevent 1 ASCVD event in 30 years would be 17.8 (95% CI, 17.3 – 18.2).
DISCUSSION
In this cross-sectional study of applying the 2023 PREVENT equations to a nationally representative population of adults ages 30 to 59 without known ASCVD, we found that 9% had a high estimated 30-year risk (≥20.0%) and 44% had an intermediate estimated 30-year risk from (7.5% - 19.9%). Elevated 30-year risk was highly concentrated among the oldest ages in our cohort (ages 50 to 59), with less than 1% of adults ages 30 to 39 estimated to have elevated 30-year risk and over 20% of those ages 50–59. Treating by 30-year ASCVD risk always has a lower 10-year absolute risk reduction than treating by 10-year risk, but similar risk reductions to patients with diabetes with low 10-year ASCVD risk who are currently statin eligible. All scenarios of expanding current primary prevention statin eligibility would result in lower 10-year absolute risk reduction compared to increasing uptake of statin therapy among the approximately 2 million adults with high and intermediate 10-year risk who are currently eligible but not receiving primary prevention pharmacotherapy.
The PREVENT 30-year risk equations build on prior long-term risk estimates (7,17,18) using more contemporary prospective cohort and electronic health record data and including additional risk factors and modifiers including kidney function and statin use. Our study builds on a recent brief report describing 30-year cardiovascular disease risk estimated by PREVENT equations which found that 1 in 7 patients had 30-year risk greater than 20% (8). The PREVENT cardiovascular disease risk estimates are based on different equations than the PREVENT ASCVD equations and include the development of heart failure as an outcome. We focused on ASCVD risk, which has more direct implications for guiding preventative lipid lowering therapy decisions.
Despite state-of-the-art methods, the accuracy of the PREVENT 30-year risk estimation in today’s population is difficult to accurately assess. Average follow-up in the PREVENT equations was less than 5-years and maximal follow-up was 15 years, so 30-year risk estimates were developed by combining shorter risk assessments (5). The PREVENT equations were modeled using age as a time scale which may result in an overestimation of 30-year risk, since improving medical care will likely make ASCVD risk in the coming 30 years lower than what was observed in the cohorts informing PREVENT, though they did account for competing risks of non-cardiovascular death. Additionally, while the 10-year PREVENT equations have been externally validated in NHANES, the 30-year equations have not been examined (11). Furthermore, potential errors and missing data in the electronic health record data that provided the majority of data on which the PREVENT equations were based could alter the equations’ results, but the direction of possible bias is unknown.
Current guideline recommendations differ for adults ages 30 to 39 and the precise clinical use of 30-year risk in this population is undetermined. The 2018 AHA/ACC guideline on cholesterol management recommends estimating long-term ASCVD risk in younger adults to inform intensity of primary prevention efforts, and considering primary prevention statins in younger adults with a family history of premature ASCVD, in people whose LDL is above 160, and in patients with diabetes of >10 years duration or with evidence of nephropathy, retinopathy, neuropathy or peripheral vascular disease (4). The 2019 AHA/ACC primary prevention guideline emphasizes the role of 30-year risk as being to improve communication and encourage medication adherence (3), while the 2022 US Preventative Services Task Force makes no clinical recommendations for younger adults or on the use of long-term risk calculation (19). The US Preventative Services Task Force does identify the need for more studies on the efficacy and safety of statin use in younger populations, particularly those with elevated long-term risk.
This study demonstrates that estimated 30-year risk is closely correlated but does not precisely mirror 10-year risk, so there are adults with high 30-year-risk, but relatively low or moderate 10-year risk. However, the primary determinant of 30-year risk is age, not individual risk factors. Some clinicians encourage early treatment for individuals with high 30-year and lifetime risk with statins and aggressive blood pressure reduction. This is due to the possibility of “legacy effects,” where early treatment might have cumulative benefit when people are higher risk later in life (20). The legacy effect has not been clearly seen randomized trials, though those are usually brief (20–22). It is observed in Mendelian randomization studies, observational cohorts, and it is biologically plausible (23). An important concern about guiding statin treatment using 30-year risk is that statins increase diabetes risk (24). If the increase in diabetes risk accumulates with prolonged statin use, this could be an unexpected harm of early statin use and warrants further study. Furthermore, the burden of recommending life-long preventative medications in younger adults is not well-established and may impact acceptance and adherence to other preventative cardiovascular medications (e.g. antihypertensives).
Clinical Implications
The clinical implications of this study are broad. Individuals with elevated 30-year ASCVD risk will most importantly benefit from counseling on strategies to optimize lifestyle factors including physical activity, diet quality, smoking cessation and weight loss for the more than half of patients in this group who were obese. Statins and blood-pressure-lowering medications are already among the most used medications in the world and the introduction of 30-year risk into clinical practice could broaden that use to millions more Americans. These medications’ relatively low costs and good safety profile make them practical, though their appropriateness compared to non-pharmacologic lifestyle modifications is unclear. As statins have been observed to have a consistent relative risk reduction across baseline levels of ASCVD risk, broadening treatment recommendations to lower risk groups will be less efficient than increasing uptake in groups with elevated 10-year risk who are not currently receiving statins.
Study Limitations
Our study has limitations. The 2017 to 2020 NHANES cycle response rate was 47% but were adjusted by NHANES to account for nonresponse. The 10-year PREVENT equations were developed to estimate risk for adults aged 30 to 79 years, we focused on the subset of adults aged 30 to 59 years for whom the PREVENT equations also estimate 30-year ASCVD risk. Estimates of clinical outcomes resulting from scenarios of statin eligibility expansion were based on assumptions of consistent relative risk reductions from meta-analysis, however actual risk reductions may vary with medication adherence, dosage and other clinical characteristics of patients. We did not examine other risk enhancers (eg, family history, additional biomarkers, or coronary calcium), as this data is not fully available in NHANES, but these factors may guide decision-making for patients with borderline risk. We did not examine the population health impact of lowering currently accepted 10-year ASCVD risk thresholds for treatment, which has also been proposed (25), and acknowledge that guideline recommended thresholds are typically the result of expert opinion and may vary, as demonstrated by current differences between USPSTF and AHA/ACC guidelines. We did not examine the broader PREVENT equations for estimating 10-year and 30-year risk of cardiovascular disease, which is a composite of ASCVD and heart failure, as primary prevention strategies for heart failure are not clearly established and may different from prevention of ASCVD. Finally, given the cross-sectional nature of this study we are unable to test the “legacy effect,” of early treatment. If the legacy effect is large, this could alter the results meaningfully.
Conclusions
Use of the PREVENT 30-year ASCVD risk equations would identify a population of US adults with low 10-year but high 30-year who may warrant enhanced primary prevention strategies. However, guiding treatment by 30-year risk prevents fewer events per year of treatment than guiding treatment by 10-year risk, indicating a larger population benefit from increasing primary prevention uptake among individuals currently recommended primary prevention pharmacotherapy due to elevated 10-year risk.
Supplementary Material
What is Known:
Estimation of atherosclerotic cardiovascular disease (ASCVD) risk is central to primary prevention efforts but has largely relied on 10-year risk estimates which may lead to undertreatment of younger at-risk people.
The 2023 American Health Association Predicting Risk of Cardiovascular Disease Events (PREVENT) equations include a new 30-year ASCVD risk estimate using the same clinical inputs as for 10-year ASCVD risk estimate.
What this Study Adds:
Applying the PREVENT equations to a nationally representative population of adults ages 30 to 59, we found that 9% had an elevated estimated 30-year ASCVD risk of 20% or greater and 44% had an intermediate estimated 30-year risk of 7.5% to 19.9%, with elevated risk highly concentrated among individuals ages 50 to 59.
Among adults with elevated 30-year ASCVD risk, nearly all had at least 2 uncontrolled modifiable risk factors, most commonly elevated blood pressure, body mass index, and total cholesterol.
Expanding primary prevention statin recommendations to adults with 30-year ASCVD risk of 20% or greater would change recommendations for 2.5 million adults not currently receiving statins, with an average number needed to treat (NNT) over 10 years to prevent one ASCVD event of 78, comparable to estimated NNTs for adults currently recommended but not using primary prevention statins.
SOURCES OF FUNDING
Funded by the National Institute on Aging (K76AG074878, PI Dr. Anderson).
Role of the Funder/Sponsor:
The National Institute on Aging had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
DISCLOSURES
Dr. Anderson reports receiving grants from the National Institutes of Health, Department of Veterans Affairs, and American Heart Association as well as personal fees from the American Medical Association and consulting fees from American Medical Student Association outside the submitted work. Ms. Wilson reports receiving personal fees from the American Medical Student Association outside the submitted work. Dr. Sussman reports grants from the Department of Veterans Affairs and National Institutes of Health outside of the submitted work
Abbreviations
- ACC
American College of Cardiology
- AHA
American Heart Association
- ASCVD
Atherosclerotic cardiovascular disease
- GFR
Glomerular filtration rate
- HDL
High-density lipoprotein
- LDL
Low-density lipoprotein
- NHANES
National Health and Nutrition Examination Survey
- PREVENT
Predicting Risk of Cardiovascular Disease Events
- PCEs
Pooled cohort equations
- STROBE
Strengthening the Reporting of Observational Studies in Epidemiology
- BP
Systolic blood pressure
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