Guideline recommended statin eligibility and use among U.S. adults ages 20 to 39 years

Abstract

Objective

Guidelines for statin therapy emphasize treatment of adults ages 40–75 years, with less guidance for the treatment of younger adults, ages 20–39 years. Only two class 1 recommendations for statin apply to younger adults: 1) secondary prevention and 2) severe hypercholesterolemia (LDL-C ≥ 190 mg/dL). The implementation of guidelines within this age group has not been well studied.

Methods & Results

Here, we use data from the National Health and Nutrition Examination Survey (2013–2020) to estimate statin eligibility and use among US younger adults. Based on this nationally representative sample, we extrapolate that approximately 923,000 younger adults had a history of atherosclerotic cardiovascular disease, but only ∼24 % were on statin. Among younger adults in the primary prevention group, we extrapolate that at least 1.09 million had severe hypercholesterolemia. To expand on this analysis, we calculated untreated LDL-C values for individuals on statin using two methods, and we estimate that only ∼11–20 % of younger adults with severe hypercholesterolemia were on statin. Lastly, among untreated younger adults with a class 1 indication for statin, fewer than 25 % reported that a doctor or healthcare provider had recommended cholesterol medication.

Conclusion

The implementation of class 1 recommendations for statin treatment in younger adults is poor. While efforts to improve risk prediction in the young have recently received significant attention, our results indicate that identifying high risk younger adults is insufficient. We must also improve guideline-recommended treatment in this age group.

1. Introduction

Since 2013, cholesterol guidelines have provided age-specific recommendations for statin use, with a predominant focus on cardiovascular risk reduction in middle-age and older adults ages 40 to 75 years old [1,2]. There are only two class 1 recommendations for statin that apply to younger adults (age 20–39 years): 1) prior history of atherosclerotic cardiovascular disease (ASCVD) and 2) severe hypercholesterolemia, defined as low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL. It is unknown how many younger US adults have these indications, and the uptake of guidelines in this age group has not been previously studied. We aimed to estimate statin eligibility, use, and recommendation awareness in US adults ages 20–39 years old using nationally representative data.

2. Methods

We performed a cross-sectional analysis of pooled data from the US National Health and Nutrition Examination Survey (NHANES) from January 2013 to March 2020. We included all participants 20–39 years old with fasting lipid values. We excluded pregnant individuals and those with triglycerides >400 mg/dL. LDL-C was calculated using the Friedewald equation. The secondary prevention sample was identified by self-reported history of ASCVD (coronary heart disease, myocardial infarction, angina, or stroke). The severe hypercholesterolemia sample was identified as participants without prior ASCVD who had LDL-C ≥ 190 mg/dL. We used the observed (‘uncorrected’) LDL-C to estimate a lower bound for the number of individuals with severe hypercholesterolemia. To account for individuals on lipid-lowering therapy at the time of survey, we used two methods for estimating untreated LDL-C. The ‘simple correction’ multiplies the observed LDL-C by 1.43 if measured on statin [3]. The ‘tiered correction’ uses medication-specific multiplication factors: atorvastatin, 1.87; rosuvastatin, 1.99; simvastatin, 1.58; pravastatin, 1.33; other statin, 1.43; ezetimibe, 1.24 [4]. No participants were on cholestyramine, niacin, or PCSK9 inhibitors. National estimates were calculated using the fasting subsample weights, accounting for the complex multistage probability-sampling survey design. The study was based on deidentified publicly available data, which is considered nonhuman participants research under the US Department of Health and Human Services’ Office for Human Research Protection (the Common Rule) and does not require institutional review board review or informed consent.

3. Results

The unweighted sample included 2512 participants, representing an estimated 80.8 million US adults ages 20–39 years. The Table 1 shows weighted national estimates for the total population and by statin eligibility. We extrapolate that approximately 923,000 (1.1 %) younger adults had a prior history of ASCVD, and among this group, 24.3 % were on statin. Based on uncorrected LDL-C values, we extrapolate that at least 1.09 million (1.3 %) younger adults without prior ASCVD had severe hypercholesterolemia. After adjusting for medication, this estimate increased to 1.13 million (1.4 %) using the simple correction and 1.25 million (1.5 %) using the tiered correction. The proportion on statin ranged from 7.5 % when using uncorrected LDL-C values to 19.5 % when using the tiered correction.

Table 1.

Characteristic of US adults ages 20–39 based on the NHANES sample (January 2013-March 2020) by guideline-recommended statin eligibility.

	All	Secondary prevention	Primary prevention
			LDL-C ≥ 190 mg/dL, Uncorrecteda	LDL-C ≥ 190 mg/dL, simple correctionb	LDL-C ≥ 190 mg/dL, tiered correctionc
No. in sample	2512	30	33	36	40
Weighted national estimate, in millions	80.82	0.92	1.09	1.13	1.25
Age, median (IQR), y	29 (24–34)	35 (28–38)	29 (26–36)	29 (27–36)	30 (27–38)
Female sex, No. (weighted %)	1315 (49.9)	20 (65.5)	13 (40.8)	15 (41.7)	17 (41.0)
Race and ethnicity, No. (weighted %)
Non-Hispanic Asian	354 (6.4)	0	5 (8.3)	5 (8.0)	6 (8.3)
Non-Hispanic Black	514 (12.6)	9 (15.4)	6 (12.1)	7 (12.8)	7 (11.6)
Non-Hispanic White	835 (55.9)	13 (60.6)	13 (57.1)	14 (56.2)	15 (56.1)
Mexican American	413 (12.7)	3 (9.3)	8 (20.1)	9 (20.7)	10 (20.0)
Other Hispanic	257 (8.0)	3 (8.9)	1 (2.4)	1 (2.3)	2 (4.1)
Other, including multi-racial	139 (4.4)	2 (5.8)	0 (0.0)	0	0
Body mass index, median (IQR), kg/m2	27.4 (23.2–33.1)	33.7 (26.1–42.1)	26.2 (23.2–32.5)	26.4 (23.4–33.4)	26.4 (24.1–33.7)
Hypertension, No. (weighted %)	366 (14.1)	13 (50.8)	7 (13.7)	9 (15.6)	10 (15.2)
Diabetes, No. (weighted %)	60 (2.0)	4 (17.4)	1 (2.3)	3 (4.7)	4 (5.6)
Total cholesterol, median (IQR), mg/dL	173 (152–197)	167 (154–200)	286 (277–303)	283 (275–300)	279 (271–298)
HDL-C, median (IQR), mg/dL	51 (42–61)	40 (34–57)	48 (40–55)	48 (40–55)	48 (40–56)
Triglycerides, median (IQR), mg/dL	77 (53–118)	90 (51–132)	115 (91–187)	123 (92–188)	115 (90–188)
LDL-C, median (IQR), mg/dL
Uncorrected	101 (83–123)	107 (84–121)	209 (194–226)	206 (194–224)	201 (193–222)
Simple correction	102 (83–124)	113 (87–145)	209 (194–228)	211 (195–229)	204 (194–226)
Tiered correction	102 (83–124)	113 (93–148)	209 (194–228)	211 (195–230)	206 (196–229)
Statin, No. (weighted %)	27 (1.4)	4 (24.3)	2 (7.5)	5 (10.9)	9 (19.5)
Ezetimibe, No. (weighted %)	1 (0.1)	0	1 (6.1)	1 (5.9)	1 (5.3)

Abbreviations: IQR, interquartile range; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

^aUncorrected: observed LDL-C values.

^bSimple correction: LDL-C values multiplied by 1.43 if on statin.

^cTiered correction: LDL-C values multiplied by 1.87 for atorvastatin, 1.99 for rosuvastatin, 1.58 for simvastatin, 1.33 for pravastatin, 1.43 for other statins, 1.24 for ezetimibe.

In total, we extrapolate that approximately 1.71 million (2.1 %) younger adults had a class 1 indication for statin but were untreated. Among this untreated group, more than half reported having previously had their cholesterol checked (Fig. 1). For those with severe hypercholesterolemia, more than half were aware that they had high cholesterol. However, within either statin indication, fewer than 25 % reported that a doctor or healthcare professional had recommend that they take cholesterol-lowering medication.

Fig. 1.

Cholesterol awareness among an extrapolated 1.71 million untreated US young adults with class 1 indications for statin therapy

Young adults were defined as ages 20–39 years. Mutually exclusive indications for statin were defined as secondary prevention (prior atherosclerotic cardiovascular disease) or primary prevention with severe hypercholesterolemia (low-density lipoprotein cholesterol ≥190 mg/dL). Weighted national estimates are shown.

4. Discussion

In summary, the implementation of class 1 recommendations for statin therapy in adults 20–39 years old is poor. Our findings suggest that an important driver of this shortcoming may be clinicians failing to recommend statin to younger adults when indicated. Importantly, it is precisely during this age when LDL-C reduction may have the greatest impact for preventing premature cardiovascular morbidity and mortality [5,6].

Current guidelines often fail to identify high-risk younger adults [7]. This observation has motivated efforts to improve clinical risk prediction for adults under the age of 40 [[8], [9], [10]], and it has catalyzed research into the unique value of polygenic risk scores for younger populations [11,12]. However, we show that even among the high-risk groups that current guidelines do recognize, implementation of recommended statin therapy is inadequate. Thus, as we work to improve risk estimation in the young, we must also improve physician and patient uptake of guideline directed medical therapies.

A limitation of this study is that we relied on participant self-report to assess for prior ASCVD and to assess awareness of statin eligibility. A second limitation is that we did not have untreated LDL-C values for those participants on statin at the time of survey. To address this limitation, we estimated untreated LDL-C values using two approaches for statin correction. By examining both uncorrected and corrected values, we hoped to provide a plausible range of estimates for severe hypercholesterolemia in younger adults. Notably, this limitation does not affect the analysis of untreated individuals. Lastly, the overall sample size in our study cohort was relatively small. Our estimates of statin use were in accordance with National Center for Health Statistics recommendations regarding minimal denominator sample sizes [13]. However, even within the recommendations, smaller samples lead to less precise extrapolations. Such imprecisions could impact our conclusions.

Author agreement

All authors have seen and approved the final version of the manuscript being submitted. The article is the authors' original work, hasn't received prior publication and isn't under consideration for publication elsewhere.

CRediT authorship contribution statement

Shoa L. Clarke: Writing – review & editing, Writing – original draft, Methodology, Investigation, Formal analysis, Conceptualization. Blake Thomson: Writing – review & editing, Methodology, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.