OP0248 GENETIC EVIDENCE REVEALS THE CAUSAL RELATIONSHIP BETWEEN OSTEOPOROSIS AND CARDIOVASCULAR DISEASE

Background

Osteoporosis(OP) is a systemic bone disease that leads to a decrease in bone mineral density(BMD), thus increasing the susceptibility to brittle fractures[1]. Epidemiological studies indicate a confirmed correlation between osteoporosis and cardiovascular disease (CVD)[2]. BMD as a risk factor for CVD events and death can better predict the development of lesions than traditional risk factors such as hyperlipidemia and smoking. However, observational studies may be influenced by potential confounders. At the same time, the Mendel randomization (MR) study can overcome these confounding factors to evaluate causality.

Objectives

This study aimed to evaluate the genetic correlation between OP and CVD through bi-directional MR and provide a new strategy for clinical prevention, treatment, and nursing of OP and CVD.

Methods

We selected three different sites[femoral neck bone mineral density (FN BMD), forearm BMD(FA BMD) and lumbar spine BMD (LS BMD)] from the GEnetic Factors for OSteoporosis (GEFOS) and heel BMD(eBMD) from UK biobank datasets as the phenotype of OP. The instrumental variables(IVs) of the whole genome significance level related to the 12 CVDs were from the published summary statistics. IVW was selected as the primary analytical method to evaluate the causal relationship between exposure and results because it provides the most convincing estimate when the directional multidirectional nature of IV is missing. Outlier variants identified by MR-PRESSO were removed to reduce heterogeneity and the effect of horizontal pleiotropy. To confirm the stability, we performed a "leave-one-out" approach for the sensitivity analysis.

Results

LS-BMD had a direct causal relationship with myocardial infarction(MI) and coronary heart disease(CHD)[MI-related analysis: odds ratio (OR) = 1.101, 95% confidence interval (CI) = (1.033,1.174), p = 0.003; CHD-related analysis: OR (95% CI) = 1.105 (1.043,1.170), p = 0.001]. FN BMD will increase the risk of large-artery atherosclerotic stroke(LAS), small-vessel stroke(SVS), coronary artery disease(CAD) and CHD[LAS-related analysis: OR (95% CI) = 1.152 (1.014,1.308), p = 0.029; SVS-related analysis: OR (95% CI) = 1.139 (1.015,1.128), p = 0.026; CAD-related analysis: OR (95% CI) = 1.088 (1.023,1.056), p = 0.007; CHD-related analysis: OR (95% CI) = 1.086 (1.023,1.154), p = 0.007]. At the same time, SVS, cardioembolic stroke(CES) and any stroke(AS) will increase the possibility of FN BMD[SVS-related analysis: OR (95% CI) = 1.051 (1.006,1.095), p = 0.024; CES-related analysis: OR (95% CI) = 1.034 (1.006,1.063), p = 0.018; AS-related analysis: OR (95% CI) = 1.074 (1.020,1.131), p = 0.006].

Conclusion

OP and CVD might mutually have a significant causal effect on each other. Our results supported the view that increased BMD is more likely to lead to cardiovascular events, and stroke may lead to increased FN BND.

References

[1]Ivanova, S., Vasileva, L., Ivanova, S., Peikova, L. & Obreshkova, D. Osteoporosis: Therapeutic Options. Folia Med (Plovdiv) 57, 181-190, doi:10.1515/folmed-2015-0037 (2015). [2]Tremollieres, F. & Ribot, C. Bone mineral density and prediction of non-osteoporotic disease. Maturitas 65, 348-351, doi:10.1016/j.maturitas.2009.12.023 (2010).

Acknowledgements:

NIL.

Disclosure of Interests

None Declared.