Circulating levels of sclerostin are associated with cardiovascular mortality

Abstract

Cardiovascular diseases are a health problem throughout the world, especially in people with diabetes. The identification of cardiovascular disease biomarkers can improve risk stratification. Sclerostin is a modulator of the Wnt/β-catenin signalling pathway in different tissues, and it has recently been linked to vascular biology. The current study aimed to evaluate the relationship between circulating sclerostin levels and cardiovascular and non-cardiovascular mortality in individuals with and without type 2 diabetes. We followed up a cohort of 130 participants (mean age 56.8 years; 48.5% females; 75 with type 2 diabetes; 46 with prevalent cardiovascular disease) in which serum sclerostin levels were measured at the baseline. Time to death (both of cardiovascular and non-cardiovascular causes) was assessed to establish the relationship between sclerostin and mortality. We found that serum sclerostin concentrations were significantly higher in patients with prevalent cardiovascular disease (p<0.001), and independently associated with cardiovascular mortality (p = 0.008), showing sclerostin to be a stronger predictor of mortality than other classical risk factors (area under the curve = 0.849 vs 0.823). The survival analysis showed that an increase of 10 pmol/L in the serum sclerostin level resulted in a 31% increase in cardiovascular mortality. However, no significant association was observed between sclerostin levels and non-cardiovascular mortality (p = 0.346).From these results, we conclude that high sclerostin levels are related to mortality due to cardiovascular causes. The clinical implication of these findings is based on the possible use of serum sclerostin as a new biomarker of cardiovascular mortality risk in order to establish preventive strategies.

Serum sclerostin and irisin as predictive markers for atherosclerosis in Egyptian type II diabetic female patients: A case control study

“…This study showed that the mean of serum SOST level in T2DM+ATHR cohort was significantly higher than T2DM-ATHR and control cohorts. Consistently, it has been lately suggested that SOST might act as an independent predictor of cardiovascular mortality in a population comprising subjects with and without T2DM[ 30 ]. Also, the mean of SOST of T2DM-ATHR cohort showed relative increase when compared to the control cohort.…”

Impact of long‐lasting spontaneous physical activity on bone morphogenetic protein 4 in the heart and tibia in murine model of heart failure

“…As a negative regulator of TGF‐β/BMP and Wnt/β catenin pathways (Asadipooya & Weinstock, 2019), sclerostin is involved not only in bone remodeling, but also (through TGF‐β and Wnt signaling) might play a role in the adverse cardiac remodeling, particularly in the progression of heart failure (Guo & Dong, 2014; Hermans & Blankesteijn, 2015). Higher serum sclerostin concentrations have been found in patients with prevalent cardiovascular disease and were independently associated with cardiovascular mortality (Novo‐Rodríguez et al, 2018). When considering the impact of exercise on the sclerostin level, it has been demonstrated that a single bout of exercise leads to acute increase in blood sclerostin levels (Kouvelioti et al, 2019; Pickering et al, 2017) but several weeks of interval training (Janik, Stuss, Michalska‐Kasiczak, Jegier, & Sewerynek, 2018) decrease blood sclerostin level, which suggests positive, antiosteoporotic effects of a long‐term exercise.…”

Sost Haploinsufficiency Provokes Peracute Lethal Cardiac Tamponade without Rescuing the Osteopenia in a Mouse Model of Excess Glucocorticoids

“… 52 , 64 No evidence suggests that sclerostin plays a causal role in cardiovascular disease, rather recent studies have reported an association between sclerostin levels and cardiovascular disorders. 65 , 66 , 67 , 68 The precise function of sclerostin in the regulation of the cardiovascular system remains to be defined.…”