Heart failure (HF) is the terminal manifestation of cardiovascular disease (1). In recent years, the prevalence of HF has gradually increased, and its mortality and disability rate have also increased. The number of people with HF worldwide is predicted to be close to 64.3 million (2). Despite continuous progress in the treatment of HF, due to frequent hospital stays and ongoing treatment, patients with HF have severe everyday limits and bear a heavy financial burden (3). Moreover, 50% of people with HF with a decreased ejection fraction pass away within 5 years after being diagnosed (4). Thus, it is essential to inhibit the occurrence and development of HF.

With a focus on diet, people have realized that traditional western diet, such as red meat, high sugar food and fried food, are harmful to heart health (5), while omega-3 fatty acids (6), polyphenolic and flavonoids (7), as well as other micronutrients that are abundant in Indo-Mediterranean diets (8), may all play a protective role in maintaining the heart health. Anthocyanidins are one of the six major categories of flavonoids, and the anthocyanidins consumed in diet are mainly provided by fruits such as berries (9). Anthocyanidins have powerful anti-inflammatory and antioxidant properties, making them useful in the prevention of a variety of chronic diseases, such as eye and kidney complications and many cancer types (10–13). An increasing number of evidences show that anthocyanidins is related to circulatory disease, and have shown significant lipid-lowering effects in many studies (14, 15). Anthocyanidins also have positive effects on endothelial function and have antiatherogenic and anti-arterial stiffness properties (16). According to the meta-analysis, dietary anthocyanidins intake was linked to a lower risk of coronary heart disease and a lower mortality of cardiovascular diseases (17). Moreover, the link between anthocyanidins and cardiovascular diseases has been verified by numerous experimental research. Such as, anthocyanidins played a chemo-preventive role in atherosclerosis via activation of Nrf2-ARE pathway (18); through suppression of the ROS-JNK-Bcl-2 pathway, anthocyanidins reduces myocardial ischemia-induced damage (19).

However, the protective effect of anthocyanidins on HF has not been reported. Therefore, the purpose of this study was to assess the impact of dietary anthocyanidins on HF in the general American population.

As far as we know, this study was the first time to demonstrate the association between dietary anthocyanidins intake and HF, dietary anthocyanidins consumption (categorical) and HF were found to be negatively correlated in the NHANES 2007–2010 and 2017–2018. When dietary anthocyanidins intake was in the Q4 group, the incidence of HF was lowered by 50% after adjusting probable confounding factors. This negative correlation is still stable in subgroups of female, ≥45 years, former smoker, non-Hispanic White or without diabetes, stroke, renal failure. Moreover, compared with anthocyanidins intake between HF and non-HF for each quartile, it was found that only anthocyanins intake of Q4 was different between HF and non-HF, the intake of anthocyanins in non-HF was higher than that in HF (Supplementary Figure S1; Supplementary Table S2).

At present, cardiovascular disease has caused great social burden, so many scholars are emphasizing the importance of dietary habits in the prevention and treatment of cardiovascular diseases (23). With the increasing demand for flavonoids (24), anthocyanidins have been discovered many benefits for cardiovascular system, which is a subgroup of flavonoids (25). As some studies have shown, a high dietary intake of anthocyanidins was linked to decreased total cardiovascular disease incidence and mortality. For example, Adriouch S et al. found that participants in the highest tertiles of anthocyanidins had a 34% lower risk of major cardiovascular events than those in the lowest tertiles following multivariable adjustment (26). Besides, Lin Xu et al. confirmed that dietary intake of anthocyanidins significantly decreased the risk of death from all cardiovascular diseases in meta-analysis including 2,36,648 subjects and 9,765 cases (RR: 0.91, 95% CI [0.87, 0.96]; p < 0.001), it was also found that dietary anthocyanidins may have a more significant protective effect on total CVD mortality in women (27). Additionally, dietary anthocyanidins intake is also beneficial in vascular diseases. Such as, Margarethe E Goetz et al. reported that anthocyanidins intake was negatively correlated with incident of coronary heart disease after matching age, sex, race and residence (28). Moreover, anthocyanidins consumption in the diet is crucial for preventing subclinical injury of cardiovascular disease, such as hyperlipidemia, obesity, vascular endothelial function, arterial stiffness, decreased cardiac systolic function (29–32) Although some studies believed that purified anthocyanidins had more cardioprotective effects than dietary anthocyanidins (27), this conclusion is still controversial due to incompleteness of dietary data and differences in interventions (33–36). The evidence for the benefits of dietary anthocyanidins on cardiovascular system is very strong, but our research revealed for the first time a connection between dietary anthocyanidins intake and the presence of HF in the general population.

Although our clinical studies revealed an association between dietary intake of anthocyanidins and HF, the underlying mechanism had not been clarified. Thus, we summarized the following four possible mechanisms through literature summary. First, oxidative stress disorder plays a crucial role in the in the occurrence and development of HF. When the production of reactive oxygen species (ROS) exceeds the internal defense capacity of cells, excess ROS will attack cells, leading to protein and lipid peroxidation, DNA damage, and ultimately cell death (37). Anthocyanidins, a naturally occurring plant pigment, not only serves as a colorant but also has strong antioxidant properties, ROS such superoxide anion, singlet oxygen, and peroxide free radical can be neutralized by anthocyanidins (38). Second, in the pathophysiological process of chronic HF, a long-lasting inflammatory response causes adverse ventricular remodeling (39). The anti-inflammatory capabilities of anthocyanidins have also been proven in numerous research (40–44), anthocyanidins can inhibit NF-κB activity to reduce inflammation level. Third, some clinical studies have found that anthocyanidins can improve cardiovascular metabolic disorder and obesity, which are high risk factors for HF (29, 30). Fourth, rich-anthocyanidins foods also contain dietary fiber, vitamins and various polyphenols, which also have certain protective effects on heart health (45–48). To investigate established and speculative mechanisms, further basic and clinical research is required.

Nevertheless, there were some limitations in this study. First, as a cross-sectional study, this study was unable to confirm the causal relationship between dietary intake of anthocyanidins and HF. Second, this study only evaluated the effect of anthocyanidins in food, but whether the purified anthocyanidins had the same effect still needs further randomized controlled experiments. Third, the NHANES database does not provide brain natriuretic peptide and echocardiography data, so this study cannot further evaluate the relationship between dietary intake of anthocyanidins and the severity of HF. Moreover, uncontrollable confounding variables may also need further analysis, such as physical activity and nutritional supplements. Finally, the subjects of this study were adult Americans, excluding adolescents and children, which would affect the promotion of the research results.

In conclusion, dietary intake of anthocyanidins was associated with HF negatively, people can decrease the presence of HF by increasing anthocyanidins in their daily diets. To determine their clear relationship, more cellular, animal, and human investigations are necessary.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.

The studies involving human participants were reviewed and approved by National Health and Nutrition Examination Survey (NHANES). The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

ZT conceived and designed the study. RZ, WZ, and ZJ were responsible for the management and retrieval of data, contributed to initial data analysis, and interpretation. ZT drafted the initial manuscript. XC, RH, and XL revised the manuscript and were the guarantors of this work and had full access to all the data in the study. GM take responsibility for its integrity and the accuracy of the data analysis. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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