Abstract
Sirtuin-1 (Sirt1) is a NAD+-dependent deacetylase involved in multiple cardioprotective effects. The dysregulation of Sirt1 is associated with different pathophysiological mechanisms that are common in patients with heart failure with preserved ejection fraction (HFpEF). However, its role in HFpEF is largely unknown. Resveratrol, a natural polyphenol, is a well-known activator of Sirt1. Novel data suggests that unsaturated fatty acids (UFA) and other dietary products can also modulate Sirt1. Thus, the objective of this study is to investigate whether 1) Sirt1 is reduced in HFpEF, 2) is associated with clinical markers of disease severity and 3) if dietary interventions can modify it.
Circulating Sirt1 was analyzed before and after: 1) 4 weeks of DASH diet in 14 recently decompensated HFpEF patients (GOURMET-HF study); 2) 12 weeks of high-UFA diet in 10 chronic stable HFpEF (UFA-Preserved study); and 3) a single dose of 500 mg of resveratrol in 13 healthy individuals. Clinical markers of disease severity including days alive and out of hospital (DAOH) and cardiorespiratory fitness (CRF) were evaluated. We compare between-group differences (Mann-Whitney U test or unpaired T-test), and repeated measures to assess within-group changes (Wilcoxon signed-rank test or paired T-test). Correlations were assessed using Spearman rank.
Sirt1 plasma concentrations were significantly reduced in HFpEF compared to healthy controls (Fig. 1, left). Notably, Sirt1 was further reduced in patients with HFpEF that were recently decompensated when compared to those who were stable (Fig. 1, left). Both DASH diet and high-UFA diet increased Sirt1 concentrations in recently decompensated and stable HFpEF patients, respectively (Fig. 1, right). As expected, a single dose of resveratrol also increased Sirt1 in the control group (Fig. 1, right). Interestingly, changes in Sirt1 after high-UFA diet were positively associated with changes in CRF (exercise time, r=+0.75, p=0.052) and changes in Sirt1after DASH diet were positively associated with DAOH (r=+0.79, p=0.034).
Patients with HFpEF present with reduced circulating Sirt1, which is further decreased in those who were recently admitted for acute decompensated HF. Moreover, Sirt1 can be modified through different dietary interventions, as well as resveratrol. Notably, changes in Sirt1 were positively associated with markers of disease severity. Future studies targeting Sirt1 in patients with HFpEF are warranted, with one or a combination of the proposed interventions to investigate their effects on cardiovascular health.