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. Author manuscript; available in PMC: 2025 Feb 1.
Published in final edited form as: Mayo Clin Proc. 2024 Jan 6;99(2):271–282. doi: 10.1016/j.mayocp.2023.09.016

Trends of Lipid Concentrations, Awareness, Evaluation, and Treatment in Severe Dyslipidemia in US Adults

Naman S Shetty 1, Mokshad Gaonkar 1,2, Nirav Patel 1, Joshua W Knowles 3,4, Pradeep Natarajan 5,6,7, Garima Arora 1, Pankaj Arora 1,8
PMCID: PMC10873035  NIHMSID: NIHMS1935416  PMID: 38189687

Abstract

Objective:

To evaluate the contemporary trends of lipid concentrations, cholesterol evaluation, hypercholesterolemia awareness, and statin use among individuals with severe dyslipidemia [low-density lipoprotein cholesterol (LDL-C) level ≥190 mg/dL] between 2011 and 2020.

Patients and Methods:

This serial cross-sectional analysis included nonpregnant adults ≥20 years from the National Health and Nutrition Examination Survey between 2011 and 2020. Age-adjusted weighted trends of LDL-C, triglycerides, cholesterol evaluation in the past 5 years, hypercholesterolemia awareness, and documented statin use among individuals with severe dyslipidemia were estimated.

Results:

Among 24,722 participants included, the prevalence of severe dyslipidemia was 5.4% (SE:0.2%) which was stable across the study period (Ptrend=.78). Among individuals with severe dyslipidemia [mean age:55.3 (SE: 0.7) years; 52.2% females; 68.8% non-Hispanic White] LDL-C [224.3 (SE: 4.2) mg/dL in 2011–2012 to 224.2 (SE: 4.6) mg/dL in 2017–2020; Ptrend=.83] and triglyceride [123.3 (SE: 1.1) mg/dL in 2011–2012 to 101.8 (SE: 1.1) mg/dL in 2017–2020; Ptrend=.13] levels remained stable from 2011 to 2020. The rates of cholesterol evaluation in the past 5 years [72.0% (SE: 5.7%) in 2011–2012 to 78.0% (SE: 4.8%) in 2017–2020; Ptrend=.84], hypercholesterolemia awareness [48.1% (SE: 5.5%)] in 2011–2012 to 51.9% (SE: 5.8%) in 2017–2020; Ptrend=.77], and documented statin use [34.7% (SE: 4.5%) in 2011–2012 to 33.4% (SE: 4.0%) in 2017–2020; Ptrend=.55] remained stagnant in individuals with severe dyslipidemia between 2011–2020.

Conclusions:

Among individuals with severe dyslipidemia, cholesterol evaluation and hypercholesterolemia awareness rates were stable at ~75% and ~50% in the last decade. Only ~34% of individuals with severe dyslipidemia took statins between 2011–2020 which likely contributed to the stable LDL-C levels noted across the study period. Further investigations into the determinants of statin use and adherence to statins are needed.

Keywords: Severe Dyslipidemia, Cholesterol Evaluation, Awareness, Statins

Introduction

Severe dyslipidemia, defined as a low-density lipoprotein cholesterol (LDL-C) level >190 mg/dL, affects nearly 1 in 15 US adults and may be a manifestation of an underlying genetic etiology such as familial hypercholesterolemia.1–3 Severe dyslipidemia is an established risk factor for premature cardiovascular disease (CVD) and increases the risk of CVD by several folds compared to those with normal LDL-C levels (<130 mg/dL).4–6 Intensive lowering of LDL-C through lipid-lowering medications has been shown to have a dose-dependent reduction in the risk of CVD.7, 8 Therefore, early initiation of statin therapy effectively reduces the risk of CVD in individuals with severe dyslipidemia to that of the general population.9, 10

Even though treatment of severe dyslipidemia with statin has proven efficacy in CVD risk reduction, the reports of statin use in this high-risk population are discouraging. Current guidelines recommend the initiation of high-dose statins in individuals with severe dyslipidemia aged 20–75 years.11 While the rate of statin prescription has increased in the general population leading to lowering of cholesterol levels,12, 13 several studies have shown that the rates of statin use were low among individuals with severe dyslipidemia.14, 15 A prior nationwide analysis using data up to 2014 showed that only 4 in 10 individuals with severe dyslipidemia were on statin therapy.1 However, data on the contemporary trends of lipid concentrations, awareness of hypercholesterolemia, evaluation of cholesterol, and statin use in individuals with severe dyslipidemia are lacking.

This nationwide population-level analysis leverages the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2020 to assess the contemporary trends of cholesterol evaluation, awareness, and statin use in individuals with severe dyslipidemia and compare the trends with the general population.

Methods

Data Source

The NHANES is a biennial survey conducted by the National Center for Health Statistics (NCHS) and Center for Disease Control and Prevention that aims to assess the health and nutritional status of the civilian, non-institutionalized population of the US using a sample population.16–22 A multistage probability sampling design is utilized to select this nationally representative sample population.16–22 The survey consists of a home interview and a physical examination. During the home interview, data on demographics, past medical history, and medication use were collected.16–22 Consenting participants were invited to a mobile examination center for physical examination. A detailed physical examination, measurement of vital signs, and venous blood collection for laboratory testing were performed during the visit.16–22 Ethical oversight for the current study was provided by the University of Alabama at Birmingham Institutional Review Board.

Data from 4 NHANES cycles between 2011 and March 2020 were utilized in the current study. Due to the COVID-19 pandemic, data collection in the 2019–2020 cycle was suspended in March 2020. Therefore, the NHANES recommends combining the 2017–2018 cycle with the 2019-March 2020 cycle to generate reliable population-level estimates.23

The current study included nonpregnant adult participants ≥20 years of age. Participants who lacked physical examination data were excluded. Sex and race and ethnicity were self-reported. Self-reported race and ethnicity included non-Hispanic White, non-Hispanic Black, Mexican American, non-Hispanic Asian, and others.

Laboratory Measurements

Venous blood collected during the physical examination at the physical examination visit was used to measure lipid levels. Blood samples were stored in appropriate frozen conditions until they were shipped to the University of Minnesota for analysis. LDL-C and triglyceride levels were measured in the subset of fasted individuals who presented in the morning session of the examination. LDL-C levels were estimated from total cholesterol, triglyceride, and high-density lipoprotein levels using the Friedwald equation. Triglyceride levels were measured enzymatically. To account for the cholesterol lowering effect of lipid-lowering medications, measured LDL-C levels were multiplied by 1.43 to estimate the untreated levels of LDL-C in individuals who confirmed the use of lipid-lowering medication at the home interview or presented statins at the physical examination.1, 24, 25 For reference, the correction factor for high-intensity statin to estimate LDL-C levels would be 1.5.

Evaluation of Cholesterol

Self-reported evaluation for cholesterol in the past 5 years was assessed using the “When was blood cholesterol last checked” question.

Awareness of Hypercholesterolemia

Self-reported awareness of hypercholesterolemia was ascertained through an affirmative response to the question, “Have you ever been told by a doctor or other health professional that your blood cholesterol was high?”.

Statin Use

Data on statin use was gathered using self-report and by verification of the medications that the participants brought to the physical examination visit. Self-reported statin use was determined by an affirmative response to the following questions: “To lower your blood cholesterol, have you ever been told by a doctor or other health professional to take prescribed medicine?” and “Are you now following this advice to take prescribed medicine?”. Documented statin use was assessed at the physical examination visit based on the medications that the participant presented at the visit.

Missing data

Among the 24,722 participants included in the study, LDL-C levels and triglyceride levels were missing in 13,765 (55.7%) and 13,624 (55.1%) participants, respectively. To overcome the bias due to missing data, multiple imputation under the missing at random assumption was performed. The model for multiple imputation utilized the variables of interest (LDL-C and triglyceride levels), total cholesterol levels, and 5 additional variables with no missing data (age, sex, survey weights, and a unique identifier that combined the stratum and primary survey unit).12 Due to the skewed distribution of triglyceride levels, the variable was log-transformed before imputation. Ten imputed datasets were created using a multivariable normal distribution.

Statistical Analysis

All analyses were performed as per the recommendations of the NCHS. To account for combining NHANES cycles from 2011–2012 and 2017-March 2020, sample weights were adjusted according to the recommendations of the NCHS.16 The fasting subsample weights were used to estimate LDL-C and triglyceride levels. The remaining analysis, including the estimation of total cholesterol, evaluation for cholesterol, awareness for hypercholesterolemia, and statin use was done using examination weights.12 Age adjustment was performed using the direct method of age standardization using the 2010 US Census population.20 In the imputed datasets, the PROC SURVEYFREQ procedure was used to estimate the weighted percentages for categorical variables and the PROC SURVEYMEANS procedure was used to estimate the mean (standard error) for continuous variables. The PROC MIANALYZE was used to combine the results obtained from the 10 imputed datasets. To account for the skewed distribution of triglyceride levels, geometric means were calculated instead of arithmetic means. Multivariable adjusted weighted logistic and linear regression models were used to assess the trends of the outcomes of interest, as appropriate. The regression models were adjusted for age, insurance status, level of education, income, and number of yearly healthcare visits.17, 18, 21, 26 All analyses were performed in individuals with severe dyslipidemia and in the general population. SAS 9.4 (Cary, NC) was used for statistical analysis. The type 1 error was set at 0.05.

Results

There were 24,722 participants, representing 231.2 million individuals of the US population, in the NHANES cycles between 2011 and March 2020. The mean age of the study population was 48.0 (SE: 0.3) years and 51.5% (SE: 0.4%) were female. On stratifying by race and ethnicity, 64.4% (SE: 1.6%) were non-Hispanic White, 11.4% (SE: 0.9%) were non-Hispanic Black, 8.5% (SE: 0.8%) were Mexican American, and 5.6% (SE: 0.5%) were non-Hispanic Asian individuals. The prevalence of severe dyslipidemia was 5.4% (SE: 0.2%) in the NHAHES cycles between 2011 and March 2020. The prevalence of severe dyslipidemia did not change across the study period [5.7% (SE: 0.7%) in 2011–2012 to 5.0% (SE: 0.6%) in 2017-March 2020]. (Figure 1) Among individuals with severe dyslipidemia, the mean age was 55.3 (SE: 0.7) years, 52.2% (SE: 2.6%) were females, 68.8% (SE: 2.5%) were non-Hispanic White, 11.3% (SE: 1.2%) were non-Hispanic Black, 6.6% (SE: 0.9%) were Mexican American, and 4.9% (SE: 0.7%) were non-Hispanic Asian. Individuals with severe dyslipidemia were older and more likely to have other cardiovascular risk factors such as a past history of smoking [34.5% (SE: 2.4%) compared with 29.8% (SE: 0.6%)], obesity [41.8% (SE: 2.7%) compared with 38.7% (SE: 0.6%)], hypertension [62.2% (SE: 2.7%) compared with 48.5% (SE: 0.6%)], and diabetes [18.2% (SE: 2.3%) compared with 13.9% (SE: 0.3%)]. (Table 1)

Figure 1: Age-Adjusted Trend in the Prevalence of Severe Dyslipidemia, National Health and Nutrition Examination Survey 2011–2020.

Figure 1:

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Error bars depict the 95% confidence intervals.

Table 1:

Baseline Characteristics in the General Population and Stratified by the Presence of Severe Dyslipidemia

Individuals with Severe Dyslipidemia (LDL-C ≥190 mg/dL) [n=1,531 (13,824,536)*] Individuals without Severe Dyslipidemia (LDL-C < 190 mg/dL) [n=23,191 (217,368,507)*] General Population [ n=24,722 (231,193,043)*]
Age, years 55.3 (0.7) 47.5 (0.3) 48.0 (0.3)
Female sex 52.2 (2.6) 51.5 (0.4) 51.5 (0.4)
Race and Ethnicity
Mexican American 6.6 (0.9) 8.6 (0.8) 8.5 (0.8)
Other Hispanic 5.6 (1.0) 6.7 (0.5) 6.7 (0.5)
Non-Hispanic White 68.8 (2.5) 64.2 (1.6) 64.4 (1.6)
Non-Hispanic Black 11.3 (1.2) 11.4 (0.9) 11.4 (0.9)
Non-Hispanic Asian 4.9 (0.7) 5.7 (0.5) 5.6 (0.5)
Other Races 2.9 (0.7) 3.4 (0.2) 3.4 (0.2)
Education
Less than high school 39.3 (2.5) 36.9 (1.0) 37.1 (1.0)
Some college 30.6 (2.4) 31.8 (0.6) 31.7 (0.6)
College Graduate 30.1 (2.6) 31.3 (1.2) 31.3 (1.2)
Insured 89.5 (1.1) 83.9(0.7) 84.3 (0.7)
Poverty Income Ratio
≤3.5 43.4 (2.8) 42.9 (1.2) 42.9 (1.2)
1.30 −3.5 35.8 (2.4) 35.1 (0.8) 35.1 (0.8)
< 1.30 20.9 (1.8) 22.0 (0.8) 21.9 (0.8)
Body Mass Index
Normal weight (≤24.9 kg/m2) 22.7 (2.0) 29.7 (0.6) 29.3 (0.6)
Overweight (25–29.9 kg/ m2) 35.6 (2.2) 31.7 (0.5) 32.0 (0.5)
Obese (≥30 kg/m2) 41.8 (2.7) 38.6 (0.7) 38.7 (0.6)
Diabetes 18.2 (2.3) 11.4 (0.7) 13.9 (0.3)
Smoking Status
Never 44.4 (2.5) 48.4 (0.8) 48.2 (0.8)
Current 21.2 (2.1) 22.1 (0.7) 22.1 (0.6)
Past 34.5 (2.4) 29.5 (0.7) 29.8 (0.6)
Hypertension 62.2 (2.7) 47.5 (0.7) 48.5 (0.6)
Personal History of Early ASCVD 11.1 (1.5) 6.3 (0.3) 6.6 (0.3)
Family History of Early ASCVD 15.3 (1.7) 13.0 (0.4) 13.2 (0.4)
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Values are present as mean (standard error) for continuous variables and percentage (standard error) for categorical variables.

*

Number represents the weighted sample size.

Trends of Lipid Concentrations

Among individuals with severe dyslipidemia, the LDL-C [224.3 (SE: 4.2) mg/dL in 2011–2012 to 224.2 (SE: 4.6) mg/dL; Ptrend=.83] and triglyceride [123.3 (SE: 1.1) mg/dL in 2011–2012 to 101.8 (SE: 1.1) mg/dL; Ptrend=.13] remained stagnant from 2011 to March 2020. (Table 2) Similarly, a stable trend in LDL-C and triglyceride levels was observed on stratification by sex (Table 2) and race and ethnicity (Table 2) across the study period.

Table 2:

Trends of Low-Density Lipoprotein Cholesterol and Triglycerides in Individuals with Severe Dyslipidemia and the General Population

Severe Dyslipidemia General Population
2011–2012 2013–2014 2015–2016 2017–2020 P trend 2011–2012 2013–2014 2015–2016 2017–2020 P trend
Low-Density Lipoprotein Levels
Overall 224.3 (4.2) 220.3 (3.5) 221.6 (4.1) 224.2 (4.6) .83 121.7 (1.4) 118.2 (0.9) 119.3 (1.2) 116.0 (1.0) .003
Sex
 Male 220.6 (4.8) 218.2 (4.5) 219.6 (5.3) 225.6 (6.4) .71 120.0 (1.9) 119.3 (1.4) 121.4 (2.0) 117.2 (1.4) .25
 Female 227.2 (5.4) 223.6 (4.5) 224.1 (6.4) 221.0 (4.7) .46 123.2 (1.6) 117.0 (1.3) 117.2 (1.6) 114.7 (1.7) <.001
Race and Ethnicity
 Non-Hispanic White 223.9 (6.3) 219.4 (5.0) 222.4 (5.5) 225.6 (7.5) .95 122.2 (1.9) 119.1 (1.2) 119.9 (1.7) 116.1 (1.6) .01
 Non-Hispanic Black 227.6 (5.9) 224.6 (6.9) 222.2 (6.7) 223.4 (6.9) .55 120.7 (1.5) 117.1 (1.5) 117.2 (1.7) 114.3 (1.4) .001
 Mexican American 218.5 (7.9) 221.7 (6.4) 220.2 (6.5) 220.7 (10.3) .82 119.1 (2.0) 116.5 (1.8) 118.4 (2.0) 114.9 (1.8) .25
 Non-Hispanic Asian 224.2 (7.9) 219.9 (7.4) 219.8 (9.4) 219.9 (6.1) .76 119.4 (2.2) 115.5 (2.2) 116.7 (2.0) 116.5 (1.8) .35
Triglyceride Levels
Overall 123.3 (1.1) 107.3 (1.1) 103.9 (1.1) 101.8 (1.1) .13 109.7 (1.0) 97.5 (1.0) 93.2 (1.0) 89.7 (1.0) <.001
Sex
 Male 139.9 (1.1) 117.9 (1.1) 111.4 (1.1) 107.6 (1.1) .12 119.7 (1.0) 105.4 (1.0) 100.7 (1.0) 96 (1.0) <.001
 Female 112.0 (1.1) 96.5 (1.1) 95.7 (1.1) 97.2 (1.1) .43 100.8 (1.0) 90.4 (1.0) 86.4 (1.0) 83.9 (1.0) <.001
Race and Ethnicity
 Non-Hispanic White 129.4 (1.1) 105.5 (1.1) 105 (1.1) 105.1 (1.1) .38 112.8 (1.0) 98.1 (1.0) 94.7 (1.0) 90.5 (1.0) <.001
 Non-Hispanic Black 106.2 (1.1) 100.5 (1.2) 88.1 (1.1) 90.8 (1.1) .11 95.8 (1.0) 86.9 (1.0) 82.6 (1.0) 78.5 (1.0) <.001
 Mexican American 139.6 (1.2) 117.6 (1.2) 110.4 (1.2) 105.0 (1.2) .26 112.8 (1.0) 105.9 (1.0) 96.8 (1.0) 95.8 (1.0) <.001
 Non-Hispanic Asian 116.1 (1.2) 103 (1.2) 102.7 (1.2) 101.6 (1.1) .62 105.1 (1.0) 95.5 (1.0) 91.0 (1.0) 89.8 (1.0) <.001
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Age-standardized mean values have been presented. Triglyceride values are presented as geometric mean.

In the general population, the LDL-C levels decreased from 121.7 (SE: 1.4) mg/dL in 2011–2012 to 116.0 (SE: 1.0) mg/dL (Ptrend=.003) and triglyceride levels decreased from 109.7 (SE: 1.0) mg/dL in 2011–2012 to 89.7 (SE: 1.0) mg/dL in 2017-March 2020; Ptrend <.001). (Table 2) On sex stratification, the triglyceride levels decreased in males (Ptrend <.001) and females (Ptrend <.001) across the study period but LDL-C decreased only in females (Ptrend =<.001). (Table 2) Race and ethnicity stratified analysis showed that the triglyceride levels decreased in all 4 racial groups (Ptrend <.001) and LDL-C levels decreased in non-Hispanic White (Ptrend=.01) and non-Hispanic Black individuals (Ptrend=.001). (Table 2)

Evaluation of Cholesterol Levels

The rate of cholesterol evaluation in the past 5 years among individuals with severe dyslipidemia was stable across the study period [72.0% (SE: 5.7%) in 2011–2012 to 78.0% (SE: 4.8%) in 2017-March 2020; Ptrend=.84]. (Supplementary Table 1, Figure 2)

Figure 2: Age-Adjusted Trends of Cholesterol Evaluation, Awareness of Hyperlipidemia, Self-Reported Lipid-Lowering Medication Use, and Documented Statin Use in Individuals with Severe Dyslipidemia and the General Population, National Health and Nutrition Examination Survey 2011–2020.

Figure 2:

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Error bars depict the 95% confidence intervals. Individuals with severe dyslipidemia and the general population are presented in red circles and blue squares, respectively.

In the overall population, the rate of cholesterol evaluation in the past 5 years was lower than in those with severe dyslipidemia and increased to a lesser extent from 66.2% (SE: 1.1%) in 2011–2012 to 70.9% (SE: 1.1%) in 2017-March 2020 (Ptrend=.02). (Supplementary Table 1, Figure 2)

Awareness of Hypercholesterolemia

Among individuals with severe dyslipidemia, the awareness of hypercholesterolemia was stable from 2011–2012 [48.1% (SE: 5.5%)] to 2017-March 2020 [51.9% (SE: 5.8%)] (Ptrend=.77). (Supplementary Table 1, Figure 2)

In the general population, the awareness of hypercholesterolemia remained stable across the study period [29.9% (SE: 0.9%) in 2011–2012 and 30.1% (SE: 0.7%) in 2017-March 2020; Ptrend=.38]. (Supplementary Table 1, Figure 2)

Self-Reported Use of Lipid-Lowering Medications

In individuals with severe dyslipidemia, the self-reported use of lipid-lowering medications was stagnant between 2011–2012 [36.7% (SE: 4.3%)] and 2017-March 2020 [42.1% (SE: 4.3%)] (Ptrend=.73). (Supplementary Table 1, Figure 2)

In the overall population, the self-reported lipid-lowering medication use was stable across the study [18.6 (SE: 0.7) in 2011–2012 to 20.7% (SE: 0.7%) in 2017-March 2020; Ptrend=.09].

Documented Statin Use

Documented statin use rates remained stable between 2011–2012 [34.7% (SE: 4.5%)] and 2017-March 2020 [33.4% (SE: 4.0%)] in individuals with severe dyslipidemia (Ptrend=.55). (Supplementary Table 1, Figure 2)

In the overall population, documented statin use did not change across the study period [13.8% (SE: 0.7%) in 2011–2012 to 13.7% (SE: 0.7%) in 2017-March 2020; Ptrend=.43]. (Supplementary Table 1, Figure 2)

Documented use of any Lipid-Lowering Medication

To account for the use of alternative lipid-lowering medications such as ezetimibe, fibrates, bile acid sequestrants, and PCSK9 inhibitors, the trends of the documented use of statin or any one of the previously mentioned medications were assessed in individuals with severe dyslipidemia and the general population between 2011 and 2020. Among individuals with severe dyslipidemia, the documented use of any lipid-lowering medication was stable between 2011 [34.9% (SE: 4.4%)] and 2020 [33.9% (SE: 3.8%)] (Ptrend=.38). A similar trend was noted in the general population, where the rate of use of any lipid-lowering medication was 14.5% (SE: 0.8%) in 2011 and 14.5% (SE: 0.6%) in 2020 (Ptrend=.44). (Figure 3)

Figure 3: Age-Adjusted Trends of Any Lipid Lowering Medication Use in Individuals with Severe Dyslipidemia and the General Population, National Health and Nutrition Examination Survey 2011–2020.

Figure 3:

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Error bars depict the 95% confidence intervals. Individuals with severe dyslipidemia and the general population are presented in red circles and blue squares, respectively. Lipid lowering medications include statins, ezetimibe, fibrates, bile acid sequestrants, and PCSK9 inhibitors.

Trends of cholesterol evaluation, hypercholesterolemia awareness, and statin use stratified by sex and race and ethnicity have been described in the Supplementary Results. The trends of cholesterol evaluation, awareness, and lipid-lowering medication use were stable across sex and race and ethnicity subgroups. Compared with the imputed data, complete case analysis led to a higher rate of awareness of hypercholesterolemia and self-reported lipid lowering medication use among individuals with severe dyslipidemia. (Supplementary Table 2)

Discussion

This population-level analysis of >25,000 individuals provides a comprehensive assessment of the trends of lipid concentrations, evaluation, awareness, and statin use among individuals with severe dyslipidemia and compares them with the general population. The population-level prevalence of severe dyslipidemia was 5.4% (~1 in 19 individuals) with a stable prevalence across the study period. Contrary to the decreasing trend of LDL-C levels in the general population, the LDL-C levels in individuals with severe dyslipidemia were stable in the past decade. Nearly 3 out of 4 individuals with severe dyslipidemia underwent cholesterol evaluation over the past decade. However, only one in two individuals with severe dyslipidemia were aware that they had hypercholesterolemia across the study period. Furthermore, the rates of documented statin use were much lower than the rates of cholesterol evaluation and awareness of hypercholesterolemia. Only 1 in 3 individuals with severe dyslipidemia were reported to be on statins. Even accounting for other lipid-lowering medications such as ezetimibe, PCSK9 inhibitors, bile acid sequestrants, and fibrates, the proportion of individuals with severe dyslipidemia on therapy remained low at ~35%. Taken together, the cholesterol evaluation rates were not accompanied by similar rates of hypercholesterolemia awareness and the treatment of hyperlipidemia remains low, as evidenced by the stable LDL-C levels among individuals with severe dyslipidemia across the study period.

Several explanations exist for the study findings of the large disconnect between cholesterol evaluation and statin use rates in individuals with severe dyslipidemia. The increase in cholesterol evaluation may indicate that healthcare providers are adequately facilitated by the recommendations of the guidelines.27 Similar efforts should focus on increasing the awareness of hypercholesterolemia in individuals with severe dyslipidemia. However, the low rates of statin use may be attributed to factors at the provider or patient level. Prescription rates for statins and other lipid-lowering medications have been reported to increase over the last two decades.28, 29 Among individuals with severe dyslipidemia, statin prescription rates have been reported to be 60–70%.15, 30–32 Therefore, the low prevalence of statin use may be attributed to patient-level factors. Even among patients with a high risk of ASCVD, the probability that a patient would remain on statins at the end of 1 year was ~50%, which reduced to ~20% at the end of 5 years.33 Among those non-adherent to statins, >50% of patients were worried about the side effects of statins or wanted to try an alternative method to decrease cholesterol levels such as diet and exercise.34, 35 Furthermore, negative media coverage of statins has also been associated with a decrease in adherence to statins.36, 37 These patient-level factors may act together to decrease statin use in the statin-eligible population.

The current study expands on the prior literature on severe dyslipidemia. Prior electronic health record-based and single-center studies have underestimated the prevalence of severe dyslipidemia at 2.9%−4.4%.14, 32 The prior NHANES study utilizing the cycles between 1999–2014 estimated that severe dyslipidemia affected 6.6% of US adults. However, this study did not account for the variation in the prevalence of severe dyslipidemia by age. The current study estimates that the age-adjusted prevalence of severe dyslipidemia was 5.4%. This study used a conservative correction factor for LDL-C levels to account for statin use which may underestimate the prevalence of severe dyslipidemia. Regarding evaluation for cholesterol levels, a study utilizing documented ICD codes for hypercholesterolemia to estimate awareness of severe dyslipidemia reported that ~46% of individuals with severe dyslipidemia were aware of the disease. Similar to the previous NHANES study, the current study reports that nearly 50% of individuals with severe dyslipidemia were aware of having hypercholesterolemia. The discordance between the relatively higher rates of cholesterol evaluation and hypercholesterolemia awareness compared to the rates of statin use has been noted in the prior nationwide analysis similar to the current study.1 However, the prior study noted an increase in documented statin use from ~30% in 1999 to ~40% in 2014 among individuals with severe dyslipidemia. The current study demonstrates that document statin use among individuals with severe dyslipidemia has stagnated at ~34%. This study adds to the previous literature by providing the contemporary trends of awareness of hypercholesterolemia, evaluation of cholesterol levels, and statin use among individuals with severe dyslipidemia using population-level data to provide robust estimates.

The current study has several public health implications. Severe dyslipidemia has been shown to increase the risk of ASCVD by about 5-fold.4 Additionally, severe dyslipidemia has been associated with a higher prevalence of other cardiovascular risk factors such as hypertension, obesity, and diabetes as noted in the current and prior studies1 which act together to increase the risk of developing ASCVD tremendously. Furthermore, severe dyslipidemia may be considered an indicator of underlying familial hypercholesterolemia.2 Familial hypercholesterolemia is 23 times more common in individuals with severe dyslipidemia than in the general population.38 With the widespread availability and decreasing costs of genetic testing, genetic screening of individuals with severe dyslipidemia may improve the detection of familial hypercholesterolemia. Identification of the proband may facilitate cascade screening in the relative of the proband.39 Such an effort may identify high-risk individuals and guide preventive measures to decrease the burden of ASCVD. Considering that statins are highly effective in preventing ASCVD40, 41, there is a need to understand the determinants of low statin use rates. The insurance status, presence of a usual source of care, and age have been shown to predict statin use among individuals with severe dyslipidemia.1 Health policies may be changed to improve access to healthcare through improving health literacy and helping patients select low-cost options for insurance.42 Policies should incorporate methods to enhance statin initiation and adherence which could include reducing the copays and providing extended supplies of medications and automatic medication refills. Additionally, public health campaigns may be initiated to halt the spread of misinformation on statins and provide information on the benefits and adverse events expected with statin use. At the level of the provider, the implementation of algorithms in electronic health record systems has been shown to optimize the physician’s adherence to treatment guidelines and patient-level adherence to statins.43 Healthcare providers may help combat the misinformation on statins by having a transparent discussion with patients during statin initiation. Educating patients about the known adverse events and frequency of these events and providing patients with educational materials on statins may help improve adherence to statins. In patients with additional comorbidities, a polypill strategy may be explored to facilitate adherence to the multiple medications prescribed. Furthermore, it is necessary for physicians to recognize statin intolerance in patients. Among statin-intolerant patients, several alternate drugs, including ezetimibe and PCSK9 inhibitors, are available. Both have been shown to decrease LDL-C levels and reduce the risk of CVD effectively.44–46 However, utilization of these alternatives remains low.12 Strategies to improve the utilization of these medications should be created and implemented to facilitate control of LDL-C among individuals with severe dyslipidemia.

Limitations

This study has several limitations. Considering the cross-sectional nature of the NHANES, causality could not be inferred from this study. Secondly, individual-level changes in the study outcomes could not be assessed. Thirdly, self-reported data were utilized to estimate the awareness, evaluation, and treatment rates susceptible to recall bias. Fourth, due to a large amount of missing data in LDL-C levels, multiple imputation was used to impute missing data. Fifth, this study could not distinguish between a physician’s failure to prescribe statins and the participant’s non-adherence to statins. Sixth, among the participants who presented medications at the examination visit, this study could not assess adherence to the medication. Seventh, the NHANES lacked data on the doses of the statins used by the participants. Therefore, this study used a conservative correction factor of 1.43 for statin use which may undercorrect the LDL-C levels for high-dose statins. Lastly, self-reported sex and race and ethnicity were utilized for the current study. Self-identified race and ethnicity may not accurately represent the underlying genetic ancestry.

Conclusions

In a nationally representative population of US adults, the prevalence of severe dyslipidemia was stable at ~5.5%. Among individuals with severe dyslipidemia, the trends of evaluation for cholesterol (~75%) and awareness of hypercholesterolemia (~50%) were stable across the study period. However, only 1 in 3 individuals with severe dyslipidemia were on statins across the study period which may explain the stable LDL-C levels between 2011 and 2020. Future investigations should focus on determining the factors affecting statin use and strategies to promote the utilization of statin alternatives in individuals with severe dyslipidemia.

Supplementary Material

1

Source of Funding:

Dr. Pankaj Arora is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) awards R01HL160982, R01HL163852, R01HL163081, and K23HL146887. Dr. Joshua W. Knowles is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH awards R01DK116750, R01DK120565, R01DK106236, R01DK107437, and P30DK116074.

Abbreviations

CVD

cardiovascular disease

LDL-C

low-density lipoprotein cholesterol

NCHS

National Center for Health Statistics

NHANES

National Health and Nutrition Examination Survey

Footnotes

CRediT Author Statement

Naman S. Shetty: Conceptualization, Methodology, Validation, Writing, Data interpretation, Visualization

Mokshad Gaonkar: Software, Validation, Formal Analysis, Data Curation, Visualization

Nirav Patel: Methodology, Writing, Supervision, Data interpretation

Joshua W. Knowles: Writing, Data interpretation

Pradeep Natarajan: Writing, Data interpretation

Garima Arora: Writing, Data interpretation, Supervision

Pankaj Arora: Conceptualization, Methodology, Validation, Writing, Data interpretation, Supervision

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Disclosures: Dr. Pankaj Arora reports grant support from Merck Sharp & Dohme LLC and Bristol-Myers Squibb and consulting income from Bristol-Myers Squibb, which are all unrelated to this work. Pradeep Natarajan reports grant support from Amgen, Apple, AstraZeneca, and Boston Scientific; consulting income from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech, and Novartis; and spousal employment at Vertex, which is all unrelated to the current work. None of the other authors had any conflicts of interest or financial disclosures to declare.

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Supplementary Materials

1
NIHMS1935416-supplement-1.pdf (3MB, pdf)

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