Higher nonfasting triglycerides increase the risk of heart failure

Nonfasting Triglycerides, Low-Density Lipoprotein Cholesterol, and Heart Failure Risk: Two Cohort Studies of 113 554 Individuals

Literature - Varbo A and Nordestgaard BG. - ATVB 2018; published online ahead of print

Background

There are strong associations between high concentrations of nonfasting TGs and risk of ischemic stroke, MI, ischemic heart disease (IHD), and all-cause mortality [1,2], as well as between TGs, diabetes and HF [3,4]. Hence, high concentrations of nonfasting TGs might also be associated with HF, although existing data have led to conflicting results [5-7].

In this study, it was evaluated whether high concentrations of nonfasting TGs and LDL-c are associated with a higher risk of HF in the general population. For this purpose 103 860 individuals with 2146 cases of HF from the Copenhagen General Population Study (2003–2014) were included, and the results were confirmed in the Copenhagen City Heart Study with 9694 individuals and 1447 cases of HF (1991–1994) and with minimal use of statins.

Individuals were divided into groups by their concentrations of nonfasting triglycerides and LDL-c, based on clinically meaningful cut points and without excluding extremely high concentrations, since they represent theoretically the highest risk of HF.

Main results

When compared with low nonfasting TGs (below 1 mmol/L or 88 mg/dL), stepwise higher nonfasting TGs were associated with a stepwise higher HF risk, with multivariable adjusted HRs ranging from 1.32 (95% CI: 1.06–1.65) for nonfasting TGs of 1-1.99 mmol/L (88-175 mg/dL) to 2.59 (95% CI: 1.48–4.54) for nonfasting TGs ≥5 mmol/L (440 mg/dL).
The HR for HF for a 1 mmol/L (88 mg/dL) higher concentration of nonfasting TGs was 1.19 (95% CI: 1.12–1.26), which was similar after stratification for conventional HF risk factors. There was no evidence for interactions between nonfasting TGs and HF risk factors.
The analysis of the Copenhagen City Heart Study confirmed the findings of the Copenhagen General Population Study: compared with low nonfasting TGs, multivariable adjusted HRs for nonfasting TGs of 1-1.99 mmol/L ranged from 1.28 (95% CI: 0.93–1.75) to 2.33 (95% CI: 1.22–4.45) for nonfasting TGs ≥5 mmol/L.
The cumulative incidence of HF was higher for stepwise higher nonfasting TGs: the subHRs ranged from 1.17 (95% CI: 1.04–1.32) for nonfasting TGs of 1-1.99 mmol/L to 1.95 (95% CI: 1.45–2.63) for nonfasting TGs ≥5 mmol/L, when compared with individuals with low nonfasting TGs.
The proportion of effect mediated through IHD was 34% (95% CI: 26%–49%), for MI 22% (95% CI: 16%–32%), and for IHD without MI 13% (95% CI: 9%–18%).
There was no association between stepwise higher LDL-c concentrations and HF risk. The HR for HF for a 1 mmol/L (38.6 mg/dL) higher LDL-c was 0.95 (95% CI; 0.88–1.04).

Conclusion

Stepwise higher concentrations of nonfasting TGs were associated with stepwise higher risk of HF, which was not the case for LDL-c. These findings support the need for further investigations examining whether TG and remnant cholesterol lowering in those with high concentrations would lower the HF risk.

References

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