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. 2023 Dec 22:10:1250509.
doi: 10.3389/fnut.2023.1250509. eCollection 2023.

Sodium intake and the risk of various types of cardiovascular diseases: a Mendelian randomization study

Qingming Fu #  1 , Rumeng Chen #  2 , Yining Ding #  3 , Shuling Xu  4 , Chunxia Huang  1 , Binsheng He  5 , Ting Jiang  1 , Bin Zeng  1 , Meihua Bao  5   6 , Sen Li  3
Affiliations

Sodium intake and the risk of various types of cardiovascular diseases: a Mendelian randomization study

Qingming Fu et al. Front Nutr. .

Abstract

Background: The existing literature on the link between sodium intake and cardiovascular disease (CVD) largely consists of observational studies that have yielded inconsistent conclusions. In this study, our objective is to assess the causal relationship between sodium intake and 50 CVDs using two-sample Mendelian randomization (MR) analysis.

Methods: MR analyses were performed to investigate the associations between urinary sodium/creatinine ratio (UNa/UCr), an indicator of sodium intake, and 50 CVDs. The genome-wide association study (GWAS) for UNa/UCr was from the UK Biobank (UKBB), and the GWASs for CVDs were from FinnGen. A false discovery rate (FDR) threshold of 5% was applied for multiple comparison correction.

Results: The inverse-variance weighted method indicated that the genetically predicted UNa/UCr was significantly associated with 7 of 50 CVDs, including "Coronary atherosclerosis" (OR = 2.01; 95% CI: 1.37, 2.95), "Diseases of arteries, arterioles and capillaries" (OR = 1.88; 95% CI: 1.20, 2.94), "Hard cardiovascular diseases" (OR = 1.71; 95% CI: 1.24, 2.35), "Ischemic heart diseases" (OR = 2.06; 95% CI: 1.46, 2.93), "Major coronary heart disease event" (OR = 1.99; 95% CI: 1.36, 2.91), "Myocardial infarction" (OR = 2.03; 95% CI: 1.29, 3.19), and "Peripheral artery disease" (OR = 2.50; 95% CI: 1.35, 4.63). Similar results were obtained with the MR-Egger and weighted median methods. No significant heterogeneity or horizontal pleiotropy was found in this analysis.

Conclusion: Our study has uncovered a significant positive causal relationship between UNa/UCr and various CVDs. These results offer a new theoretical foundation for advocating the restriction of sodium intake as a preventive measure against CVD.

Keywords: FinnGen; Mendelian randomization; UK Biobank; cardiovascular disease; sodium intake.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
P-value distribution of associations between urinary sodium/creatinine ratio (UNa/UCr) and 50 CVDs in the Mendelian randomization analysis. The dashed line represents the significance threshold adjusted by the false discovery rate.
Figure 2
Figure 2
Associations between genetically predicted UNa/UCr and seven CVDs examined by three MR methods. MR, Mendelian randomization; UNa/UCr, urinary sodium/creatinine ratio; IVW, inverse-variance weighted; WM, weighted median; OR, odds ratio; CI, confidence interval.
Figure 3
Figure 3
Scatter plot showing the causal effects of UNa/UCr on seven CVDs. SNP, single-nucleotide polymorphism; UNa/UCr, urinary sodium/creatinine ratio.
Figure 4
Figure 4
Funnel plot indicating the causal associations of UNa/UCr on seven CVDs. SNP, single-nucleotide polymorphism; UNa/UCr, urinary sodium/creatinine ratio; IV, instrumental variable; SE, standard error.
Figure 5
Figure 5
Leave-one-out sensitivity analysis examining the causal estimates of UNa/UCr on seven CVDs by the IVW method after excluding a specific SNP from the analysis. MR, Mendelian randomization; SNP, single-nucleotide polymorphism; UNa/UCr, urinary sodium/creatinine ratio; IVW, inverse-variance weighted.
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