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1 June 2013
NHANES: atherogenic dyslipidemia is suboptimally treated

Recent data from the US National Health and Nutrition Examination Survey (NHANES) 2009-2010 show that lipid management remains suboptimal in many patients despite guideline recommendations. In particular, one in five patients had residual atherogenic dyslipidemia, the combination of elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C), despite lipid-lowering treatment.

Wong ND, Chuang J, Wong K, Pham A, Neff D, Marrett E. 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. doi:pii: S0002-9149(13)00902-8. 10.1016/j.amjcard.2013.03.041. [Epub ahead of print]
Summary
Comments & References
STUDY SUMMARY
Objective To investigate the extent of residual dyslipidemia in US adults
Study design Cross-sectional survey
Study population

This analysis included data from 2,509 adults aged ≥18 years in the US National Health and Nutrition Examination Survey (NHANES) 2009-2010. In total, 1,129 (41.8%) had hyperlipidemia on the basis of current treatment guidelines for low-density lipoprotein cholesterol (LDL-C), of whom 484 (mean age 60.1 ± 14.9 years, 52% men) were treated with lipid-modifying therapy.

Primary variable
  • Percentage of subjects achieving LDL-C goals (see Table 1).

Table 1. LDL-C and non-HDL-C goals (mg/dL)1


Risk category

LDL-C goal

Non-HDL-C goal

Pre-existing CHD

<70

<100

Other CVD, >20% 10-year absolute Framingham risk for total CVD, diabetes and/or CKD

<100

<130

³2 risk factors or 10-year Framingham risk 10-20%

<130

<160

<2 CVD risk factors or 10-year Framingham risk <10%

<160

<190

CHD coronary heart disease; CVD cardiovascular disease; CKD chronic kidney disease

 
Secondary variables
  • Percentage of subjects achieving desirable triglyceride levels (<150 mg/dL) or HDL-C levels (³40 mg/dL in men or ³50 mg/dL in women)
  • Percentage of subjects achieving non-HDL-C goals (see Table 1).
Methods

Hyperlipidemia was defined as an elevated LDL-C level or evidence of ongoing treatment for elevated cholesterol (any prescription for statins, bile acid sequestrants, fibrates, cholesterol absorption inhibitors, niacin or omega 3-fatty acids). Global CVD risk estimation was based on the Framingham risk score. Subjects were also categorised according to the presence of metabolic syndrome, diabetes, CKD and CVD.

Main results

The proportion of subjects achieving lipid goals is summarised in Table 2.  Overall, only 36.5% of treated subjects achieved all lipid goals.  Most treated subjects were receiving statin monotherapy (82%), with only a minority receiving combination therapy (8.1%) or other treatment as monotherapy (9.5%). One in five treated subjects had residual atherogenic dyslipidemia (Figure 1).

Table 2. Lipid characteristics of subjects with hyperlipidemia

 

% achieving lipid goal or desirable level

Category

LDL-C

Triglycerides

HDL-C

Non-HDL-C

 

 

 

 

 

All (treated and untreated), n=1,129

26.5

63.6

66.4

32.6

  CVD

22.7

65.6

59.1

31.9

  Diabetes

38.6

58.5

61.4

38.5

  Metabolic syndrome

25.6

37.9

39.6

24.3

  CKD

27.7

69.2

64.7

31.0

 

 

 

 

 

All treated, n=484

62.3

63.7

71.1

61.4

  CVD

34.7

61.6

60.9

42.5

  Diabetes

62.1

55.0

62.0

54.2

  Metabolic syndrome

57.9

36.3

43.6

47.4

  CKD

52.4

66.2

65.2

52.1

Figure 1. Proportion of lipid abnormalities in treated subjects
Elevated LDL-C: 18% as single lipid abnormality, 11.4% with elevated triglycerides (TG) or low HDL-C, and 8.2% with all 3 abnormalities
Elevated TG: 8.4% as single lipid abnormality, 19.8% with low HDL-C and 16.4% with elevated LDL-C
Low HDL-C: 6% as single abnormality and 11.4% with elevated LDL-C.
All 3 lipid abnormalities: 8.2%


Author's conclusion Despite widely available treatments for dyslipidemia, many patients remain at suboptimal lipid levels, indicating the need for greater adherence to lifestyle and medical therapies to address these gaps in the management of dyslipidemia. 
 

COMMENT

Despite modern pharmacotherapy, a substantial proportion of patients have residual dyslipidemia.  A particular concern is the high proportion of treated patients with elevated triglycerides and low HDL-C – i.e. atherogenic dyslipidemia. In this study, about one in three patients had elevated triglycerides and/or low HDL-C, and one in five had both lipid abnormalities. Given that this dyslipidemic profile is recognised as a key driver of atherogenic risk, especially in individuals with cardiometabolic disease,2,3 there is clearly much to be done to improve clinical management.

It is acknowledged that this study has limitations, due to its cross-sectional design and methodology. For example, treatment information was based on prescribed medication containers, and there is no information relating to doses, or over-the-counter treatments, including functional foods. Treatment adherence and clinical inertia are also recognised as a contributing factor in failure to achieve lipid targets,4 although this was not investigated in this study.

Even taking these limitations into account, this study highlights the extent of undertreatment of dyslipidemia in patients with and without cardiovascular disease. Based on these data, it is estimated that 5.8 million individuals in the US have elevated triglycerides and 4.6 million have low HDL-C, despite lipid-modifying therapy. The burden of undertreatment of atherogenic dyslipidemia may be even higher in certain regions, such as Asia and the Middle East, where rapidly developing economies are key drivers of escalating rates of sedentary lifestyle, obesity, metabolic syndrome and type 2 diabetes,5,6 all of which are characterised by a high prevalence of atherogenic dyslipidemia.2

Given that almost all treated individuals were on a statin (~90%), it is clear that statin therapy, although effective in lowering LDL-C concentration, is insufficient for managing atherogenic dyslipidemia, supported by evidence from major prospective studies.7 This is also a key message of the Residual Risk Reduction Initiative,8 as discussed in recent videos on this website. Thus, there are significant opportunities for improved lipid management of atherogenic dyslipidemia beyond lifestyle changes, by combination of a statin with existing therapies such as fibrates, or a number of novel treatments, such as selective peroxisome proliferator-activated receptor alpha modulators (SPPARMa) or proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody therapy, as highlighted in previous reports on this site. These treatments offer the possibility to reduce the high residual cardiovascular risk that persists in individuals with atherogenic dyslipidemia that is not addressed by statins.

References

1.  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
2. Chapman MJ, Ginsberg HN, Amarenco P et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345-61.
3. Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-818.
4. Bates TR, Connaughton VM, Watts GF. Non-adherence to statin therapy: a major challenge for preventive cardiology. Expert Opin Pharmacother 2009;10:2973–85.
5. Ramachandran A, Snehalatha C. Rising burden of obesity in Asia. J Obes. 2010;2010. pii: 868573. doi: 10.1155/2010/868573.
6. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. International J Obesity 2008;32:1431–37.
7. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005;366:1267–78.
8. Fruchart JC, Sacks FM, Hermans MP et al. The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients. Diabetes Vasc Dis Res 2008;5: 319-35.