Abstract
Background: The α-linolenic acid is a plant origin n-3 fatty acid that may reduce the risk of cardiovascular disease. However, the effect of α-linolenic acid (ALA) on the risk of heart failure (HF) remains unclear. In this meta-analysis, we aimed to determine the role of ALA in the risk of incident HF. Methods: Electronic databases were searched for studies up to August 10, 2021. Studies were included for meta-analysis if the adjusted risk of HF in different dietary intake or circulating levels of ALA was reported. We used the random-effects model to calculate the estimated hazard ratios (HRs) and 95% CI for higher ALA. Results: A total of 6 studies (7 cohorts) comprising 135,270 participants were included for meta-analysis. After a median follow-up duration of 10 years, 5,905 cases of HF were recorded. No significant heterogeneity was observed among all the included studies. Random-effects model analyses showed that there was no significant association between ALA and the risk of incident HF, either assessed as quintiles (highest quintile vs. lowest quintile: HR = 0.95, 95% CI = 0.86-1.06) or per 1 SD increment (HR = 0.99, 95% CI = 0.95-1.01). Furthermore, we did not observe any association between ALA and the risk of HF in subgroup analyses performed according to age, sex, follow-up duration, and measuring method of ALA. Conclusions: We found no association between ALA and the risk of incident HF, suggesting that ALA might not be effective in the prevention of HF.
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Key Points
This was a pooled analysis of observational studies to generate data on the associations between ALA and the risk of incident HF. The study did not find any association between ALA (measured either from dietary questionnaires or with a circulating biomarker) and the risk of incident HF. These results suggest that plant origin ALA cannot be regarded as a substitute for LC n-3 fatty acids in the viewpoint for the prevention of HF. Further studies with other populations (e.g., Asians, Africans) are needed to determine whether a high intake of ALA can prevent HF. First, most of the included studies were from the United States, and only one study was from Sweden. The association between ALA and incident HF was still unclear in other populations, especially those with different dietary patterns. Second, we performed this meta-analysis based on the study level. No individual participant data were available, so residual bias cannot be totally avoided. Third, the cardio-protective effects of ALA may be modified by different intakes of LC n-3 PUFAs. However, only two studies adjusted the level of DHA and EPA in the analysis. Finally, only one measurement of ALA at baseline was detected in most of the included studies, and the change of ALA overtime was not accounted for. However, the Physicians’ Health Study showed that the use of single baseline level ALA, or mean level of between baseline and long-term follow-up measures (up to 15 years), yielded similar associations (both null) on their relationship with HF.