Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank

Zanetti, Daniela; Bergman, Helena; Burgess, Stephen; Assimes, Themistocles L.; Bhalla, Vivek; Ingelsson, Erik

doi:10.1161/hypertensionaha.119.14028

Cited by 33 publications

(19 citation statements)

References 40 publications

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“…The possibility of confounding the association between AF and CKD is always present in observational studies [ 35 ]. Consistent with our MR results suggesting a lack of causal effect of the eGFR decrease on the risk of AF/F, an MR study revealed that the urine albumin adjusted for creatinine as a proxy for kidney function did not exert a significant causal effect on the outcome of AF (beta, 0.105; 95% CI, -0.064–0.274; P = 0.23) [ 36 ].…”

Section: Discussionsupporting

confidence: 84%

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Causal effect of atrial fibrillation/flutter on chronic kidney disease: A bidirectional two-sample Mendelian randomization study

2021

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Chronic kidney disease (CKD) and atrial fibrillation are both major burdens on the health care system worldwide. Several observational studies have reported clinical associations between CKD and atrial fibrillation; however, causal relationships between these conditions remain to be elucidated due to possible bias by confounders and reverse causations. Here, we conducted bidirectional two-sample Mendelian randomization analyses using publicly available summary statistics of genome-wide association studies (the CKDGen consortium and the UK Biobank) to investigate causal associations between CKD and atrial fibrillation/flutter in the European population. Our study suggested a causal effect of the risk of atrial fibrillation/flutter on the decrease in serum creatinine-based estimated glomerular filtration rate (eGFR) and revealed a causal effect of the risk of atrial fibrillation/flutter on the risk of CKD (odds ratio, 9.39 per doubling odds ratio of atrial fibrillation/flutter; 95% coefficient interval, 2.39–37.0; P = 0.001), while the causal effect of the decrease in eGFR on the risk of atrial fibrillation/flutter was unlikely. However, careful interpretation and further studies are warranted, as the underlying mechanisms remain unknown. Further, our sample size was relatively small and selection bias was possible.

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Section: Discussionsupporting

confidence: 84%

“…for kidney function did not exert a significant causal effect on the outcome of AF (beta, 0.105; 95% CI, -0.064-0.274; P = 0.23) [36].…”

Section: Plos Onementioning

confidence: 84%

Causal effect of atrial fibrillation/flutter on chronic kidney disease: A bidirectional two-sample Mendelian randomization study

2021

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“…For example, a mendelian randomisation design could be used to assess causal associations, as has been done to investigate the effects of alcohol consumption on cardiovascular disease 57. A mendelian randomisation study using the UK Biobank dataset has identified a causal association between the sodium/potassium (Na/K) ratio and blood pressure 58. Although this study identified inverse observational associations between Na/K ratio derived from spot urine samples and cardiovascular events, there was not enough power to conduct mendelian randomisation for these events.…”

Section: How To Resolve the Controversymentioning

confidence: 99%

Sodium and health—concordance and controversy

Cook

MacGregor

et al. 2020

BMJ

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“…Most of the trait GWASs were conducted in UK Biobank by the Neale lab [28]. Twelve of the selected GWASs were from other sources: adiponectin [29]; alcoholic drinks per week [30]; body fat [31]; BMI [32]; cigarettes per day [30]; fasting glucose [33]; fasting insulin [33]; heart rate [34]; neuroticism [35]; total cholesterol [36]; urinary sodiumpotassium ratio [37]; and waist/hip ratio [38].…”

Section: Resultsmentioning

confidence: 99%

Separating the direct effects of traits on atherosclerotic cardiovascular disease from those mediated by type 2 diabetes

et al. 2022

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Aims/hypothesis Type 2 diabetes and atherosclerotic CVD share many risk factors. This study aimed to systematically assess a broad range of continuous traits to separate their direct effects on coronary and peripheral artery disease from those mediated by type 2 diabetes. Methods Our main analysis was a two-step Mendelian randomisation for mediation to quantify the extent to which the associations observed between continuous traits and liability to atherosclerotic CVD were mediated by liability to type 2 diabetes. To support this analysis, we performed several univariate Mendelian randomisation analyses to examine the associations between our continuous traits, liability to type 2 diabetes and liability to atherosclerotic CVD. Results Eight traits were eligible for the two-step Mendelian randomisation with liability to coronary artery disease as the outcome and we found similar direct and total effects in most cases. Exceptions included fasting insulin and hip circumference where the proportion mediated by liability to type 2 diabetes was estimated as 56% and 52%, respectively. Six traits were eligible for the analysis with liability to peripheral artery disease as the outcome. Again, we found limited evidence to support mediation by liability to type 2 diabetes for all traits apart from fasting insulin (proportion mediated: 70%). Conclusions/interpretation Most traits were found to affect liability to atherosclerotic CVD independently of their relationship with liability to type 2 diabetes. These traits are therefore important for understanding atherosclerotic CVD risk regardless of an individual’s liability to type 2 diabetes. Graphical abstract

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Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank

Abstract: Supplemental Digital Content is available in the text.

Cited by 33 publications

References 40 publications

Causal effect of atrial fibrillation/flutter on chronic kidney disease: A bidirectional two-sample Mendelian randomization study

Causal effect of atrial fibrillation/flutter on chronic kidney disease: A bidirectional two-sample Mendelian randomization study

Sodium and health—concordance and controversy

Separating the direct effects of traits on atherosclerotic cardiovascular disease from those mediated by type 2 diabetes

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