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8 June 2015
MULTI-GAP: Non-high-density lipoprotein cholesterol goal attainment and elevated triglycerides

Results from the Hungarian Multi-Goal Attainment Problem (MULTI-GAP) programme highlight the association between low attainment of non-high-density lipoprotein cholesterol (non-HDL-C) goal and elevated triglycerides (TG) in individuals with type 2 diabetes and cardiovascular disease (CVD).

Mark L, Vallejo-Vaz AJ, Reiber I, Paragh G, Kondapally Seshasai SR, Ray KK. Non-HDL cholesterol goal attainment and its relationship with triglyceride concentrations among diabetic subjects with cardiovascular disease: A nationwide survey of 2674 individuals in Hungary. Atherosclerosis 2015;241:62-68.
Summary
Comments & References
STUDY SUMMARY
Objective: To estimate the proportion of individuals with diabetes at very high cardiovascular (CV) risk who achieve the optional non-HDL-C goal of 2.6 mmol/L, using data from a subgroup of the Hungarian Multi-Goal Attainment Problem (MULTI-GAP) programme
Study design: Prospective survey (conducted annually since 2007) using structured questionnaires focused on the reporting of lipid levels and attainment of recommended treatment targets
Study population: 2,674 patients with diabetes and CVD at baseline (mean age 64.8 years, 58% male, 95.5% on statins, mean HbA1C 7.2%) in the Hungarian MULTI-GAP programme
Primary variable: Proportion of patients attaining the guideline-recommended non-HDL-C goal of 2.6 mmol/L (100 mg/dL). Non-HDL-C was calculated by subtracting HDL-C from total cholesterol.
Secondary variable: Proportion of patients attaining the guideline-recommended low-density lipoprotein cholesterol (LDL-C) goal of 1.8 mmol/L (70 mg/dL).
Methods: Univariate logistic regression analyses were used to investigate the association between patient baseline characteristics and attainment of LDL-C and non-HDL-C goals. Variables that showed an association (p <0.1) with goal attainment were used in multivariable-adjusted regression models. To ensure uniformity, associations with continuous variables were based on a 1-standard deviation (SD) change in the specific variable. Data showing a skewed distribution were log-transformed before regression analyses. Only patients with complete data on all the covariates included in the models were considered.
Main results:

• Although there was improvement over time, lipid goal attainment was still suboptimal at the last study endpoint (2011). At this time, 17.2% of patients attained the LDL-C goal of <1.8 mmol/L (70 mg/dL) and 22.9% attained the non-HDL-C goal of <2.6 mmol/L (100 mg/dL).
• Both LDL-C and non-HDL-C goal attainment was lower in patients with higher triglycerides (TG). With increasing TG concentrations, non-HDL-C increased continuously whereas LDL-C levels plateaued at TG concentrations of approximately 2.0-2.5 mmol/L. Levels of TG-rich lipoprotein-cholesterol (i.e. non-HDL-C minus LDL-C) rose continuously with TG levels.



Figure. Percent of patients meeting LDL-C and non-HDL-C goals according to TG concentrations

• TG levels were more strongly associated with non-HDL-C than with LDL-C goal attainment (odds ratio per 1-SD increase in log-TG was 0.74, 95% CI 0.61-0.89, for LDL-C goal attainment, and 0.49, 95% CI 0.38-0.61, for non-HDL-C goal attainment).

Authors’ conclusion: Non-HDL-C goal attainment was suboptimal in people with diabetes and co-existing CVD. This was most marked at higher TG levels, possibly due to higher levels of TG-rich lipoproteins.

COMMENT

While LDL-C is indisputably regarded as the principal lipid treatment target, non-HDL-C is a secondary – and preferable - lipid target in high CV risk individuals with insulin resistant conditions and elevated TG.1 Non-HDL-C target corresponds to [LDL-C target + 30 mg/dL].  This approach is also supported by findings from the current study, in which TG levels were more strongly associated with non-HDL-C than LDL-C goal attainment.

There is biological justification to consider non-HDL-C as the more appropriate lipid target in this patient group. By definition, non-HDL-C represents the sum of cholesterol in pro-atherogenic, apolipoprotein-B-containing lipoproteins, including TG-rich lipoproteins (very low-density lipoprotein [VLDL]-cholesterol, intermediate-density lipoprotein-cholesterol, chylomicrons, and their remnants) and LDL-C. Accumulating evidence from epidemiologic and genetic studies supports the atherogenicity of these TG-rich lipoproteins as a contributor to the development of atherosclerosis and an additional cause of cardiovascular disease and all-cause mortality.2-4 Mechanistically, elevated plasma levels of TG-rich lipoproteins, especially during the postprandial phase, accentuate inflammatory responses, thereby increasing endothelial dysfunction, and may also contribute directly to plaque formation and progression.5

In diabetes, elevated TG, often in association with low HDL-C plasma concentration (atherogenic dyslipidaemia) is a key driver of CV risk, even when LDL-C level is at target. TG-rich lipoproteins therefore represent an important contributor to residual CV risk (beyond LDL-C) in this patient group. However, the current study highlights that non-HDL-C goal attainment is far from optimal, with less than 25% of patients attaining this goal. Importantly, among patients with elevated TG, goal attainment was even lower, with <10% of patients with TG ³2.0 mmol/L (180 mg/dL) achieving the recommended non-HDL-C goal of <2.6 mmol/L (100 mg/dL). The findings from the study are strengthened by the large sample size and the completeness of lipid data in patients included in this analysis.

In conclusion, the results from this study reinforce the need to target elevated TG, to improve attainment of non-HDL-C goal and reduce residual vascular risk in high CV risk patients with type 2 diabetes.

References

1. 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.

 2. Varbo A, Nordestgaard BG, Tybjaerg-Hansen A et al. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population. Ann Neurol 2011;69:628-34.

3. Varbo A, Benn M, Tybjærg-Hansen A et al. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013;61:427-36.

4. Thomsen M, Varbo A, Tybjærg-Hansen A, Nordestgaard BG. Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study. Clin Chem 2014;60:737-46.

5. Fruchart JC, Davignon J, Hermans MP et al. Residual macrovascular risk in 2013: what have we learned? Cardiovasc Diabetol 2014;13:26.

6. Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet 2014;384:626-35.

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