Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey

doi:10.1016/j.jacl.2018.11.008

Journal of Clinical Lipidology

Volume 13, Issue 1, January–February 2019, Pages 100-108

https://doi.org/10.1016/j.jacl.2018.11.008 Get rights and content

Highlights

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We examined the prevalence of hypertriglyceridemia in US adults by statin use.
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We also examined the 10-year estimated ASCVD risk and number of events.
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In non-statin users 24.7% had TG ≥150 mg/dL versus 31.6% in statin users.
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Mean 10-year ASCVD risk ranged from 7.1% to 16.1% with TG<150–≥500 mg/dL.
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We estimate >3 million ASCVD events in 10 years in those with TG ≥ 150 mg/dL.

Background

Statin therapy remains the primary treatment for mixed dyslipidemia, even with moderate triglyceride (TG) elevations.

Objective

We examined the prevalence of elevated TG levels in adults with and without statin use and the associated 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk.

Methods

We studied 9593 US adults aged ≥20 years (219.9 million projected) in the US National Health and Nutrition Examination Surveys, 2007 to 2014. We determined the proportions of TG categories (<150, 150–199, 200–499, and ≥500 mg/dL) according to statin use, as well as the 10-year estimated ASCVD risk and number of events.

Results

Among those not taking statin therapy, the prevalence of TG < 150, 150 to 199, and ≥200 mg/dL was 75.3%, 12.8%, and 11.9%; among statin users, these proportions were 68.4%, 16.2%, and 15.4%, respectively. Among persons with low-density lipoprotein cholesterol <100 mg/dL (or <70 mg/dL in those with ASCVD), despite statin use, 27.7% had TG ≥ 150 mg/dL. The odds of TG ≥ 150 mg/dL in statin users was associated with greater age, higher body mass index, lower high-density lipoprotein cholesterol, higher low-density lipoprotein cholesterol, and diabetes. Estimated mean 10-year ASCVD risk from TG < 150 to ≥500 mg/dL, ranged from 11.3% to 19.1% in statin users and 6.0% to 15.6% in nonusers, with an overall 3.4 million ASCVD events expected in the next 10 years.

Conclusions

One-fourth of US adults overall, including nearly one-third of those on statin therapy, have suboptimal TG levels. More than 3 million ASCVD events are expected to occur over the next decade in those with TG ≥ 150 mg/dL, with approximately 1 million events expected in statin users.

Section snippets

Study sample

We used laboratory, medical history, and prescription medication information from 40,617 subjects who participated in 8-year NHANES data collection across four 2-year NHANES surveys spanning 2007 to 2014, of which 23,482 were aged ≥20 years. The general methodology of the NHANES data collection has been previously published.⁸ Our sample included people aged ≥20 years randomly assigned to a morning session, with available TG data and fasting for at least 8.5 hours, providing a final sample size

Results

Among our sample of 9593 subjects (projected to 219.9 M) analyzed in the current report from NHANES 2007 to 2014, overall 13.4% (29.5 M) had TG 150 to 199 mg/dL, 11.5% (25.3 M) had TG 200 to 499 mg/dL, and 1.0% (2.1 M) had TG ≥500 mg/dL (Table 1). Approximately 1847 (38.9 M, 17.6%) subjects were using statins. Statin users were less likely than nonusers to have TG < 150 mg/dL (68.4% vs 75.3%). Among statin users, 16.2% or 6.3 M had TG between 150 and 199 mg/dL, and 15.4% or 6.0 M had TG

Discussion

Our investigation among US adults documents nearly one-third of persons on statin therapy have suboptimal levels of TG (≥150 mg/dL), which is greater than the proportion with suboptimal TG among those not on statins. Moreover, even among those on statins who have achieved LDL-C levels <100 mg/dL (<70 mg/dL if with ASCVD), 28% have TG levels of ≥150 mg/dL and 12% have TG levels ≥200 mg/dL. Finally, we demonstrate overall at least 3.4 million ASCVD events can be expected among those with TGs of

Acknowledgments

This project was supported by a contract from Amarin Pharma, Inc, to the University of California, Irvine and was presented in part at the National Lipid Association Scientific Sessions, Las Vegas, April 2018.

Authors’ contributions: W.F. and N.D.W. wrote the article and conducted the analysis. S.P., C.G., and P.P.T. provided critical review, comment, and editorial suggestions. All authors have approved and determined the final article to be accurate.

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Sixty-six cases were identified, and 45 had multiple measurements for time-course evaluation. Those with initial Tg values of <4000 mg/dL achieved Tg levels of <1000 mg/dL in <3 days, whereas 18.8% with higher values took 5–9 days. Insulin therapy was associated with a longer duration of HTg, whereas ethanol was associated with a shorter duration. Tg clearance in ethanol-associated HTg appeared independent of insulin treatment. Time to Tg levels of <500 mg/dL versus <1000 mg/dL was significantly longer when the initial Tg levels were >2000 mg/dL.
A threshold of 4000 mg/dL for the initial Tg levels in HTg pancreatitis appears to separate patients who are likely to achieve Tg levels of <1000 mg/dL in <3 versus >3 days, independent of cause or treatment. Insulin therapy is appropriate for patients with hyperglycemia but appears unnecessary for those with isolated ethanol-associated HTg. A threshold Tg level of <1000 mg/dL appears more practical than that of <500 mg/dL for resuming nutritional intake.
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To explore the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs.
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We estimate 3.6 million US adults to be REDUCE-IT eligible, and the observed five-year first event rate without IPE of 19.0% (95% confidence interval [CI] 16.6%-19.5%) could be lowered to 13.1% (95% CI 12.8%-13.5%) with five years of IPE treatment, preventing 212,000 (uncertainty range 163,000-262,000) events. We projected the annual IPE treatment cost for all eligible persons to be $6.0 billion (95% CI $4.7-$7.5 billion), but saving $1.8 billion annually due to first events prevented (net annual cost $4.3 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% (95% CI 39.6%-45.4%) to 28.9% (95% CI 26.9-30.9%) with five years of IPE therapy, preventing 490,000 (uncertainty range 370,000-609,000) events (net annual cost $2.6 billion).
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Citation Excerpt :
In an analysis of the NHANES from 2001-2006, only 0.05% of individuals had TG levels of >2,000 mg/dL.18 A subsequent study evaluating data from the NHANES from 2007-2014 demonstrated that just 1% of individuals had TG levels ≥500 mg/dL; in contrast, more modest levels of hypertriglyceridemia were far more common, with 13.4% and 11.5% of individuals having TG levels of 150-199 mg/dL and 200-499 mg/dL, respectively.19 Based on prevalence alone, greater effort should be focused on improved accuracy of LDL-C assessment among those with more modest TG elevations.
Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is important for guiding cholesterol-lowering therapy. Different methods currently exist to estimate LDL-C.
This study sought to assess discordance of estimated LDL-C using the Friedewald, Sampson, and Martin/Hopkins equations.
Electronic health record data from patients with atherosclerotic cardiovascular disease and triglyceride (TG) levels of <400 mg/dL between October 1, 2015, and June 30, 2019, were retrospectively analyzed. LDL-C was estimated using the Friedewald, Sampson, and Martin/Hopkins equations. Patients were categorized as concordant if LDL-C was <70 mg/dL with each pairwise comparison of equations and as discordant if LDL-C was <70 mg/dL for the index equation and ≥70 mg/dL for the comparator.
The study included 146,106 patients with atherosclerotic cardiovascular disease (mean age: 68 years; 56% male; 91% White). The Martin/Hopkins equation consistently estimated higher LDL-C values than the Friedewald and Sampson equations. Discordance rates were 15% for the Friedewald vs Martin/Hopkins comparison, 9% for the Friedewald vs Sampson comparison, and 7% for the Sampson vs Martin/Hopkins comparison. Discordance increased at lower LDL-C cutpoints and in those with elevated TG levels. Among patients with TG levels of ≥150 mg/dL, a >10 mg/dL difference in LDL-C was present in 67%, 27%, and 23% of patients when comparing the Friedewald vs Martin/Hopkins, Friedewald vs Sampson, and Sampson vs Martin/Hopkins equations, respectively.
Clinically meaningful differences in estimated LDL-C exist among equations, particularly at TG levels of ≥150 mg/dL and/or lower LDL-C levels. Reliance on the Friedewald and Sampson equations may result in the underestimation and undertreatment of LDL-C in those at increased risk.

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Original ArticleHypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey

Highlights

Background

Objective

Methods

Results

Conclusions

Section snippets

Study sample

Results

Discussion

Acknowledgments

Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies

Circulation

Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies

J Cardiovasc Risk

High triglycerides are associated with increased cardiovascular events, medical costs, and resource use: a real-world administrative claims analysis of statin-treated patients with high residual cardiovascular risk

J Am Heart Assoc

Increased cardiovascular risk in hypertriglyceridemic patients with statin-controlled LDL cholesterol

J Clin Endocrinol Metab

Hypertriglycerdemia and its pharmacologic treatment among US adults

Arch Intern Med

Residual dyslipidemia among United States adults treated with lipid modifying therapy (Data from National Health and Nutrition Examination Survey 2009-2010)

Am J Cardiol

J Am Coll Cardiol

The new American heart association 2020 goal: achieving ideal cardiovascular health

J Cardiovasc Med

2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American college of cardiology/American heart association task force on practice guidelines

J Am Coll Cardiol

Remnant cholesterol as a causal risk factor for ischemic heart disease

J Am Coll Cardiol

Original Article
Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey