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|Objective||To investigate the association between levels of blood triglycerides and CV and all-cause mortality.|
|Study design||Meta-analysis of prospective cohort studies in a general population reporting an association between triglycerides and CVD or all-cause mortality (to July 2013). All studies reported the relative risks (RRs) or hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) according to at least three categories of triglycerides levels, by unit of triglycerides or by logarithmic transformed triglycerides.|
A total of 61 studies were included in the meta-analysis; 33 studies reported data on CVD mortality (17,018 CVD deaths in 726,030 subjects) and 38 studies reported data on all-cause mortality (58,419 all-cause deaths in 330,566 subjects). The median age of subjects at recruitment was 48.0 years and the median duration of study follow-up was 12.0 years. Studies in subjects with diabetes, CVD, dyslipidaemia or cancer were excluded.
|Primary variable||RR for the association of blood triglycerides with CVD and all-cause mortality|
The Newcastle-Ottawa Quality Assessment Scale1 was applied to assess the quality of studies, based on selection of subjects, degree of comparability between study groups, and assessment of outcomes. Three separate meta-analyses were conducted to assess risk estimates on the basis of categories of triglycerides levels, unit triglycerides and logarithm of triglycerides. For categorical data, the level of blood triglycerides was categorised according to the Adult Treatment Panel III cholesterol guidelines; lowest group <90 mg/dL (1.02 mmol/L); intermediate group 90-<150 mg/dL (1.02 to <1.70 mmol/L); borderline hypertriglyceridaemia 150-<200 mg/dL (1.70 to <2.26 mmol/L); and hypertriglyceridaemia ≥200 mg/dL (2.26 mmol/L). The intermediate group was the referent. For studies reporting risk estimates by unit triglycerides, the RRs were standardised to a 1 mmol/L increase in blood triglycerides. For studies reporting risk estimates by logarithmically transformed data, the risk estimates per unit of log triglycerides were pooled.
Data are summarised in Table 1. Overall, each 1 mmol/L increase in triglycerides was associated with 13% increase in CVD mortality and 12%, increase in all-cause mortality. Sensitivity analyses confirmed the robustness of the data.
Table 1. Summary of main findings of meta-analysis
ln logarithmically transformed; TG triglycerides
|Author's conclusion||Elevated blood triglycerides were dose-dependently associated with a greater risk of both CVD and all-cause mortality. These findings suggest that controlling triglycerides can help to prevent CVD and other causes of death.|
The results of this meta-analysis show that elevated blood triglycerides, a marker for triglyceride-rich lipoproteins (TRLs), are associated with an increased risk for CVD and all-cause mortality in general populations free of CVD or diabetes at baseline. The generalisability of these findings is strengthened by the fact that subjects included in these studies were from America, Europe, Asia and Australia. These data are consistent with previous meta-analyses showing a link between triglycerides and CVD risk, and add to accumulating evidence from experimental models and Mendelian randomisation studies implicating a causal role for TRLs, and their remnants, in the atherosclerotic process.(2-6) Most recently, a genetic study showed that variants associated with pathways involved in TRL metabolism were associated with increased risk for coronary artery disease.(7)
Taken together, these findings reinforce the relevance of elevated TRL (and their remnants), a key component of atherogenic dyslipidaemia, as an important contributor to lipid-related residual CV risk. This is a view consistent with the mission of the Residual Risk Reduction Initiative (R3i), as well as expert bodies, including the European Atherosclerosis Society and International Atherosclerosis Society,8(-10) which propose therapeutic targeting of triglycerides to manage lipid-related residual cardiovascular risk. Thus, it is surprising that the recently published US guidelines for management of cholesterol(11) run counter to current thinking, providing instead a statin-centric focus and omitting discussion of the need to manage lipid abnormalities beyond low-density lipoprotein cholesterol (see From the Editor’s Desk).
1. Wells GSB, O'Connell D: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.