Utility of triglycerides/HDL-C ratio in acute coronary syndrome patients

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18 May 2015

An elevated ratio of triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) is an important prognostic indicator of all-cause mortality and cardiovascular disease outcomes in acute coronary syndrome (ACS) after coronary revascularisation, according to this report from China.

Wan K, Zhao J, Huang H, et al. The association between triglyceride/high-density lipoprotein cholesterol ratio and all-cause mortality in acute coronary syndrome after coronary revascularization. PLoS ONE 10(4): e0123521. doi:10.1371/journal. pone.0123521

STUDY SUMMARY

Objective:

To determine whether the ratio of TG/HDL-C predicts cardiovascular events and total mortality among ACS patients after coronary revascularisation

Study design:

Prospective cohort study

Study population:

416 patients with ACS (mean age 64 years; 75% male) defined by the following criteria:

· ³50% stenosis in at least one proximal epicardial coronary artery

· ischaemic chest discomfort that worsened or occurred at rest and

· elevated cardiac troponin T levels (³0.03 mg/L); or new or presumably new electrocardiographic deviation in at least two contiguous leads (pathological Q-waves, ST segment depression or persistent ST segment elevation).

Patient data were summarised by log TG/HDL-C tertiles (lower 0.27–1.129; middle 1.129–2.067; and upper 2.067 -14.33). Use of medications known to affect cardiovascular outcomes (aspirin, lipid-lowering drugs, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and hormone replacement therapy) was similar across these tertiles.

Primary variable:

All-cause mortality according to logarithmic (log) TG-HDL-C ratio

Secondary variables:

Major adverse cardiovascular events (MACE), defined as nonfatal myocardial infarction (MI), including acute and old MI, cardiac death, and revascularisation.

Methods:

Cox proportional hazard models were used to investigate the association between TG/HDL-C and mortality, using a basic model (adjusting for age and gender), as well as models incorporating cardiovascular risk factors (history of smoking, history of hypertension, and history of diabetes). Multiple logistic regression analysis models were used to evaluate the association between log TG/HDL-C ratio and MACE. The median follow-up duration was 3 years.

Main results:

Over the follow-up period, there were 43 deaths (11 in the lower tertile, 10 in the middle tertile and 22 in the upper tertile of log TG/HDL-C), and 75 MACEs.

Kaplan-Meier analysis showed that survival decreased with increasing log TG/HDL-C ratio.

Key results are summarised in Table 1.

The log TG/HDL-C was a powerful predictor of mortality independent of age, gender, smoking, and diabetes. With the fully adjusted model, the risk of mortality was more than 5-fold higher for patients with the log TG/HDL-C ratio in the higher versus lower tertile (hazard ratio 5.32, 95% CI 2.06–13.73).
Adjusted analysis also showed that patients in the upper tertile for log TG/HDL-C had nearly 3-fold higher risk of a MACE compared with those in the lower tertile (odds ratio 2.94, 95% CI 1.22–7.09).

Table 1. Risk of all-cause mortality and MACE according to log TG/HDL-C ratio*

	All-cause mortality	MACE
Upper versus lower tertile	Hazard ratio 5.32(2.06–13.73),p<0.001	Odds ratio 2.94(1.22–7.09), p=0.016

* Fully adjusted model including age, gender, smoking, history of hypertension, history of diabetes, and CAD severity score

Authors’ conclusion:

The TG/HDL-C ratio is a powerful independent predictor of all-cause mortality and is a risk factor of cardiovascular events.

COMMENT

Patients with ACS are at high risk of mortality and recurrent events, especially during the first 6 months after the event.1,2 This high residual risk is exemplified by the current study, in which there were 43 deaths over a median 3-year follow-up. Lipid factors that are not the principal targets of statins, notably elevated TG and low HDL-C (atherogenic dyslipidaemia), are important contributors to this residual cardiovascular risk.3-6

An elevated TG/HDL-C ratio has already been shown to be an independent predictor of coronary events and CVD mortality among patients with cardiometabolic abnormalities,7,8 and this study extends the evidence to ACS patients after coronary revascularisation. Importantly, even after adjustment for traditional risk factors and the severity score of ACS, the log TG/HDL-C ratio remained a strong predictor of all-cause mortality in this high-risk population. This risk appeared to be confined to patients in the highest tertile (log TG/HDL-C ³2.067); the risk of death was more than 5-fold higher and of MACE nearly 3-fold higher in this group, when compared with individuals in the lower log TG/HDL-C tertile. These findings provide support for consideration of lipid-modifying therapy beyond statins that specifically target atherogenic dyslipidaemia components in these individuals.

The TG/HDL-C ratio is a simple, inexpensive, and reproducible marker of CVD risk. The findings of this study suggest that measurement of this ratio has utility in targeting pharmacotherapy for atherogenic dyslipidaemia to these high risk individuals so as to improve both all-cause and CVD outcomes.

References

1. Cannon CP, Braunwald E, McCabe CH et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350: 1495-504.

2. Ray KK, Cannon CP, McCabe CH et al. Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 2005;46: 1405-10.

3. Miller M, Cannon CP, Murphy SA, t 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;51:724-30.

4. Barter P, Gotto AM, LaRosa JC et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007;357): 1301-10.

5. Olsson AG, Schwartz GG, Szarek M et al., High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial. Eur Heart J 2005;26: 890-6.

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

7. Vega GL, Barlow CE, Grundy SM et al. Triglyceride-to-high-density-lipoprotein-cholesterol ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men. J Investig Med 2014;62:345-9.

8. Hermans MP, Ahn SA, Rousseau MF. The atherogenic dyslipidemia ratio [log(TG)/HDL-C] is associated with residual vascular risk, beta-cell function loss and microangiopathy in type 2 diabetes females. Lipids Health Dis 2012;11:132.

Key words

triglycerides/HDL-C ratio; acute coronary syndrome; coronary revascularisation; mortality; cardiovascular outcomes