Suboptimal Triglyceride Levels Among Statin Users in the National Health and Nutrition Examination Survey

By Heather Nelson Cortes, PhD and Kevin C Maki, PhD

 

Statin therapy is the primary treatment for dyslipidemia, even in those with moderately elevated triglycerides (TG).1  Hypertriglyceridemia, an independent risk factor of coronary heart disease (CHD), is defined as fasting TG >150 mg/dL.2  Meta-analyses have shown a 1.7-fold greater risk for CHD in those in the highest TG tertile compared to those in the lowest tertile.2,3  In a more recent longitudinal, real-world administrative database analysis, increased cardiovascular disease risk and direct healthcare costs were associated with hypertriglyceridemia, despite statin therapy and controlled low-density lipoprotein cholesterol (LDL-C) when compared to those with TG <150 mg/dL.4,5  Another study has also reported that approximately one-third of patients treated for dyslipidemia still have suboptimal TG levels.6

In the US population, limited data have been available on the prevalence and impact of hypertriglyceridemia in patients treated for dyslipidemia or with normal LDL-C levels, especially given the increase in statin use.  To help address this gap, Fan et al. analyzed National Health and Nutrition Examination Surveys (NHANES) from 2007-2014 to determine the prevalence of elevated TG levels in adults with and without statin use, as well as the associated 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk.7  The study included 9,593 US adults aged 20 years (219.9 million projected) and determined the proportion of persons with TG levels according to the categories of <150, 150-199, 200-499, and 500 mg/dL for both non-statin and statin users.

Proportion of US adults According to TG Category7

 

<150 mg/dL

150-199 mg/dL

≥ 200 mg/dL

Non-statin users

75.3%

12.8%

11.9%

Statin Users

68.4%

16.2%

15.4%

 

Among those with LDL-C <100 mg/dL (or <70 mg/dL in those with ASCVD), 27.6% had TG 150 mg/dL, despite statin use.  Significantly greater odds of TG 150 mg/dL in statin users were associated with higher age, higher body mass index, lower high-density lipoprotein cholesterol, higher LDL-C, and diabetes.  The estimated mean 10-year ASCVD risk from TG <150 to 500 mg/dL, ranged from 6.0-15.6% in those not taking statins, and 11.3-19.1% in statin users. This translates to a predicted 3.4 million ASCVD events over the next 10 years in those with TG 150 mg/dL.

Comment.  Based on these results in US adults, suboptimal TG levels are found in ~25% of the overall population and nearly one-third of adults on statin therapy.  TG elevation is associated with increased ASCVD risk, even when the LDL-C level is low.8  Lifestyle therapies are key in the management of an elevated TG level, including increased physical activity, weight loss, reduced glycemic load and alcohol restriction.1,9  The recently published results from the Reduction of Cardiovascular Events with Icosapent Ethyl (REDUCE-IT) trial demonstrated that ASCVD event risk was lowered by an impressive 25% in statin-treated high-risk patients with elevated TG by the addition of 4 g/d of icosapent ethyl (eicosapentaenoic acid [EPA] ethyl esters).10  Two additional large-scale trials are underway with TG-lowering drug therapies (Outcomes Study to Assess Statin Residual Risk Reduction with Epanova in High CV Risk Patients [STRENGTH] and Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes [PROMINENT]), which are evaluating effects of EPA + docosahexaenoic acid (DHA) carboxylic acids and pemafibrate, respectively.11,12  The results from the present survey suggest that the population-attributable risk due to elevated TG in the US is substantial, which underscores the importance of recognizing hypertriglyceridemia as a marker for ASCVD risk that can be addressed through lifestyle and pharmacologic therapies.

References

 

  1. Stone NJ, Robinson JG, Lichtenstein AH, et al. American College of Cardiology/American Heart Association task force on practice guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889–2934
  2. Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115(4): 450–458.
  3. Hokanson JE, Austin MA. 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. 1996;3(2):213–219.
  4. Toth PP, Granowitz C, Hull M, et al. 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. 2018;7:e008740.
  5. Nichols GA, Philip S, Reynolds K, et al. Increased cardiovascular risk in hypertriglyceridemic patients with statin-controlled LDL cholesterol. J Clin Endocrinol Metab. 2018;103:3019–3027.
  6. Wong ND, Chuang J, Wong K, et al. Residual dyslipidemia among United States adults treated with lipid modifying therapy (Data from National Health and Nutrition Examination Survey 2009-2010). Am J Cardiol. 2013;112:373–379.
  7. Fan W, Philip S, Granowitz C, et al. Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey. J Clin Lipidol. 2019;13:100–108.
  8. Miller M, Cannon CP, Murphy SA, et al. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2008;51:724–730.
  9. Jacobson A, Savji N, Blumenthal RS, Martin SS. American College of Cardiology Expert Analysis. Hypertriglyceridemia management according to the 2018 AHA/ACC guideline. January 11, 2019. Available at https://www.acc.org/latest-in-cardiology/articles/2019/01/11/07/39/hypertriglyceridemia-management-according-to-the-2018-aha-acc-guideline.
  10. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11–22.
  11. Nicholls SJ, Lincoff AM, Bash D, et al. Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: rationale and design of the STRENGTH trial. Clin Cardiol. 2018;41:1281–1288.
  12. Pradhan AD, Paynter NP, Everett BM, et al. Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study. Am Heart J. 2018;206:80–93.

 

 

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