Non-fasting triglycerides: a predictor of ischaemic cardiovascular risk in Japanese subjects

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8 February 2015

Non-fasting triglycerides are predictive of risk of ischemic cardiovascular disease in Japanese men and women, according to this report from the Circulatory Risk in Communities Study (CIRCS).

Iso H, Imano H, Yamagishi K, Ohira T, Cui R, Noda H, Sato S, Kiyama M, Okada T, Hitsumoto S, Tanigawa T, Kitamura A; CIRCS Investigators.
Fasting and non-fasting triglycerides and risk of ischemic cardiovascular disease in Japanese men and women: the Circulatory Risk in Communities Study (CIRCS). Atherosclerosis 2014;237:361-8.

STUDY SUMMARY

Objective:

To investigate whether non-fasting triglycerides are a better predictor for ischaemic cardiovascular disease than fasting triglycerides in Asian populations, which typically have a lower prevalence of dyslipidaemia than Western populations

Study design:

Community-based prospective study

Study population:

10,659 (4,264 men and 6,395 women) Japanese subjects aged 40 to 69 years recruited from four areas, who were free from ischaemic heart disease and stroke at baseline. Serum triglycerides concentrations at baseline were obtained for 2,424 fasting (³8 h after meal) and 8,235 non-fasting (<8 h after meal) subjects. The baseline surveys were conducted over the period 1975 to 1986.

Primary variable:

Ischaemic cardiovascular disease (ischaemic heart disease and ischaemic stroke). Ischaemic heart disease was defined as definite and probable myocardial infarction, angina pectoris and sudden cardiac death within 1 hour of onset. Incident stroke was defined as a focal neurological disorder with rapid onset and persisting for at least 24 hours or until death. Stroke subtypes were differentiated primarily by using computed tomography/magnetic resonance imaging findings (81%), or clinically. The final diagnosis for ischaemic heart disease and ischaemic stroke was made by a panel of 3-4 physicians who were blinded to study risk factor data.

Methods:

Cox proportional hazards regression models were used to calculate the sex-specific and sex-adjusted hazard ratios and 95% confidence intervals (CIs) for incident ischaemic cardiovascular disease using the risk for persons with the lowest category of serum triglycerides as reference (for both non-fasting and fasting triglycerides). Adjustment was made for age, sex, community, systolic blood pressure, antihypertensive medication use, serum total cholesterol, sex-specific quartiles of body mass index, smoking status, alcohol intake, serum glucose category (normal, impaired glucose tolerance and diabetes), time since last meal (<2, 2, 3-7 and 8 h or more), and menopausal status in women.

Main results:

Over the median 22-year follow-up, there were 284 cases of ischaemic heart disease (165 men and 119 women) and 666 cases of ischaemic stroke (349 men and 317 women).
Multivariate adjusted hazard ratios (95%CI) for ischaemic cardiovascular disease (ischaemic heart disease and ischaemic stroke) for the highest versus lowest quartiles of triglycerides were 1.71 (1.14 to 2.59), p for trend<0.05, for fasting subjects, and 1.60 (1.25 to 2.05), p for trend <0.001, for nonfasting subjects.
The associations were similar for fasting and non-fasting triglycerides in men. However, in women, the association was stronger for non-fasting triglycerides (see Table).
While adjustment for HDL-C slightly attenuated these associations, they were still statistically significant.

Table. Hazard ratios of ischaemic cardiovascular disease (ischaemic heart disease and ischaemic stroke)

	Fasting TG		Non-fasting TG
	Hazard ratio* (95% CI)	p-value	Hazard ratio (95% CI)	p-value
All subjects	1.71 (1.14 to 2.59)	<0.05	1.60 (1.25 to 2.05)	<0.001
Men	1.75 (1.03 to 3.07)	0.056	1.34 (0.95 to 1.88)	0.016
Women	1.36 (0.70 to 2.64),	0.342	1.87 (1.28 to 2.73)	0.0001

*Hazard ratios for highest versus lowest triglycerides quartiles (i.e. 0.26 to 0.95 mmol/L [Quartile 1] and 1.87 to 23.71 mmol/L [Quartile 4]), adjusted as defined above. TG: triglycerides

Authors’ conclusion:

Non-fasting as well as fasting triglycerides are predictive of risk of ischaemic cardiovascular disease for Japanese men, as are non-fasting triglycerides for women.

COMMENT

While lipid levels are usually measured in the fasting state, there is accumulating evidence to support the use of non-fasting triglycerides for assessing cardiovascular risk. Mechanistically, elevated levels of non-fasting triglycerides, measured 2-4 hours postprandially, may be of even greater relevance to cardiovascular risk since, in the postprandial state, atherogenic cholesterol-containing lipoprotein remnants (generated from very low density lipoproteins and chylomicrons secreted by the liver and intestine) circulate in higher concentrations than in the fasting state. These lipoprotein remnants are capable of penetrating the arterial intima and becoming trapped within the arterial wall, leading to cholesterol deposition and development of atherosclerosis.¹ There is also support from clinical studies showing that elevated levels of non-fasting triglycerides, a measure of remnant lipoproteins load, are associated with risk of ischaemic heart disease and stroke;^2-4 in contrast, prolonged exposure to low levels of non-fasting plasma triglycerides, due to carriage of certain genetic variants, are associated with reduced risk for myocardial infarction, as well as all-cause mortality.^5,6

The question remains as to whether populations with lower levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides, such as in Japan, have similar potential risk from elevated postprandial triglycerides. Until recently, this question has not been answerable, given the lack of studies investigating associations between non-fasting and fasting triglycerides and risk of cardiovascular disease in Asian countries. This analysis from the CIRCS group aimed to redress this imbalance of evidence.

CIRCS clearly showed that non-fasting triglycerides are a predictor of ischaemic cardiovascular disease in both Japanese men and women; in women, non-fasting triglycerides was the preferred predictive index. The study findings are strengthened by the use of a community-based study design, which would favour wider extrapolation to the overall Japanese population. Additionally, and more generally, the results from CIRC extend the evidence-base in support of use of non-fasting triglycerides in cardiovascular risk assessment, in both Western and Asian populations. Such an approach would undoubtedly simplify clinical care for patients worldwide.

The Residual Risk Reduction Initiative and other expert consensus groups have drawn attention to the need to treat elevated fasting and non-fasting triglycerides as a risk factor for residual cardiovascular risk.^7,8 Results from CIRCS adds to the case for considering the use of non-fasting triglycerides in addressing this residual risk.

References

1. Zilversmit DB. Atherogenesis: a postprandial phenomenon. Circulation 1979;60:473e85.

2. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007; 298: 309–316.

3. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007; 298: 299–308

4. Varbo A, Nordestgaard BG, Tybjaerg-Hansen A, Schnohr P, Jensen GB, Benn M. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population. Ann Neurol 2011;69:628-34.

5. 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.

6. Jørgensen AB1, Frikke-Schmidt R, West AS, Grande P, Nordestgaard BG, Tybjærg-Hansen A. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J 2013;34:1826-33.

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

8. 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

Key words

nonfasting triglycerides; ischaemic cardiovascular risk; stroke; residual cardiovascular risk