Urinary biomarkers and cardiovascular outcomes in the UK Biobank: observational and Mendelian randomization analyses

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

doi:10.1101/499483

Cited by 7 publications

(10 citation statements)

References 36 publications

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“…This cardiac electrical instability associated with sodium excretion is at least in part in line with our results. In another study in the UK Biobank, Zanetti et al [25] found an inverse relationship between the ratio of urinary sodium and urinary potassium (uNA/uK) and AF, which stands somewhat in contrast to our results. However, disturbance in the potassium balance is far more arrhythmogenic than fluctuances in the sodium homeostasis [26], which could explain some of the discrepant results.…”

Section: Discussioncontrasting

confidence: 99%

“…Even though associated with some biases, we believe that relating urinary spot sample concentrations of sodium to the concentration of urinary creatinine gives a more reliable, concentration‐adjusted estimate than isolated spot measurements of two urinary electrolytes. Interestingly, Zanetti et al [25] found positive effects between raised uNa/uK and increased blood pressure in both, observational analysis and Mendelian randomization studies. Another UK Biobank study [27] reported suggestive causal effects between raised urinary sodium excretion and increased diastolic blood pressure, as well as between raised urinary potassium and lower systolic blood pressure in Mendelian randomization analysis.…”

Section: Discussionmentioning

confidence: 99%

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Estimated salt intake and risk of atrial fibrillation in a prospective community‐based cohort

et al. 2020

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Introduction. Hypertension predisposes to atrial fibrillation (AF)a major risk factor for ischaemic stroke. Since a high dietary salt consumption is associated with hypertension, we investigated the association between urinary sodium excretion as a marker for dietary sodium intake and risk of newonset AF in community-dwelling adults.Method. The UK Biobank includes 40-to 69-year-old British residents recruited 2006-2010. Participants were divided into sex-specific quintiles according to 24-hour sodium excretion estimated based on spot samples with the Kawasaki equation. We excluded participants with AF at baseline. Cox regression adjusted for cardiovascular risk factors was used to assess associations with risk of AF, using the third quintile as reference.Results. A total of 257 545 women and 215 535 men were included. During up to 10 years' follow-up, 2221 women and 3751 men were diagnosed with AF. There was a tendency for an increased risk of AF in the lowest and highest quintiles of estimated daily salt intake in both women and men. In the fully adjusted model, significant associations were seen amongst men in the lowest and highest quintiles of sodium excretion (hazard ratio, HR Qv1 , 1.20; 95% CI, 1.08-1.32, P < 0.001, and HR Qv5 1.15, 95% CI, 1.03-1.27, P = 0.011). Conclusion.We found evidence for a U-shaped association between estimated daily salt intake and AF risk amongst men. A suggestive Jshaped association in women was not statistically confirmed, but analyses were likely underpowered. Our results suggest that above a certain physiological minimum level progressively higher salt intake is associated with increasing risk of AF.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Estimated salt intake and risk of atrial fibrillation in a prospective community‐based cohort

et al. 2020

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“…Diagnosis of T2DM patients was based on the recommendations of American Diabetes Association (16). DN was diagnosed based on GFR level ( < 60 mL / min / 1.73m 2 ) or persistent microalbuminuria ( > 19 μg / mL) in the morning urine of patients (17,18). Demographical data were collected via a structural interview that was conducted during the visit.…”

Section: Subjectsmentioning

confidence: 99%

Clinical markers and some trace elements in patients with type-2 diabetic nephropathy : Impact of insulin resistance

2021

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INTRODUCTION : Diabetic Nephropathy (DN) is the leading reason of all excess death-rate over type-2 diabetes mellitus (T2DM) patients with microalbuminuria, macroalbuminuria or end-stage renal disease. This work was aimed to estimate insulin resistance (IR) effect on some markers and trace elements (Selenium, Zinc, Magnesium) levels for early predicting of DN in T2DM patients. METHODS : We conducted a cross-sectional clinical study. Blood and urine samples were collected from 63 subjects with T2DM and 33 healthy controls to assess glucose, insulin, IR, urea, creatinine, glomerular filtration rate (GFR), creatinine clearance (CrCl), homocysteine (Hcy), fructosamine (FA), cystatin C (CysC), albumin (Alb), neutrophil gelatinase-associated lipocalin (NGAL), 8-hydroxy-2`-deoxyguanosine (8-OHdG) and trace elements levels. Data were collected using a questionnaire that was filled out by specialized doctors. RESULTS : Compared with controls, the results revealed that T2DM patients with or without DN had significant increases in glucose, insulin, IR, urea, creatinine, Hcy, FA, CysC, Alb, NGAL and 8-OHdG and significant decreases in GFR, CrCl and trace elements levels. Body mass index (BMI) had no changes. CONCLUSION : Uncontrolled T2DM was associated with BMI, IR and physical activity in which elevated Hcy, FA, CysC, Alb, NGAL and 8-OHdG levels and decreased trace elements levels may be used as early clinical markers of DN.

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“…We identified 108 risk factors from the IEU OpenGWAS database for inclusion in our analysis. ( 19 (38); urinary sodium-potassium ratio (39); and waist-to-hip ratio (40).…”

Section: Risk Factor Selectionmentioning

confidence: 99%

Separating the direct effects of risk factors for atherosclerotic cardiovascular disease from those mediated by type 2 diabetes

Walker

Vujkovic

Carter

et al. 2021

Preprint

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BackgroundType 2 diabetes and atherosclerotic cardiovascular disease share several risk factors. However, it is unclear whether the effect of these risk factors on liability to atherosclerotic cardiovascular disease is independent of their effect on liability to type 2 diabetes.MethodsWe performed univariate Mendelian randomization to quantify the effects of continuous risk factors from the IEU OpenGWAS database on liability to three outcomes: type 2 diabetes, coronary artery disease, and peripheral artery disease, as well as the effects of liability to type 2 diabetes on the risk factors. We also performed two-step Mendelian randomization for mediation to estimate the mediating pathways between the risk factors, liability to type 2 diabetes, and liability to the atherosclerotic cardiovascular disease outcomes where possible.ResultsWe found evidence for 53 risk factors as causes of liability to coronary artery disease, including eight which were causes of liability to type 2 diabetes only and four which were consequences only. Except for fasting insulin and hip circumference, the direct and total effects from the two-step Mendelian randomization were similar. This suggests that the combination of these risk factors with liability to type 2 diabetes was unlikely to alter liability to coronary artery disease beyond their individual effects. We also found 13 risk factors that were causes of liability peripheral artery disease, including six which were causes of liability to type 2 diabetes only and four which were consequences only. Again, the direct and total effects were similar for these ten risk factors apart from fasting insulin.ConclusionsMost risk factors were likely to affect liability to atherosclerotic cardiovascular disease independently of their relationship with liability to type 2 diabetes. Control of modifiable risk factors therefore remains important for reducing atherosclerotic cardiovascular disease risk regardless of patient liability to type 2 diabetes.RESEARCH IN CONTEXTWhat is already known about this subject?Type 2 diabetes, coronary artery disease and peripheral artery disease, share several risk factorsType 2 diabetes is also one of the strongest independent risk factors for both coronary and peripheral artery diseaseWhat is the key question?Which risk factors for atherosclerotic cardiovascular disease are mediated by liability to type 2 diabetes and which are independent?What are the new findings?Among 108 risk factors in this study, there was evidence to support: 10 risk factors as causes, 23 risk factors as consequences, and 34 risk factors as both causes and consequences of liability to type 2 diabetesIn addition, we found evidence for 53 risk factors as causes of liability to coronary artery disease and 42 risk factors as causes of liability to peripheral artery diseaseUsing two-step Mendelian randomization for mediation, we found most risk factors for atherosclerotic cardiovascular disease were likely to act independently of liability to type 2 diabetesHow might this impact on clinical practice in the foreseeable future?Our findings support continued control of modifiable risk factors as this is likely to reduce atherosclerotic cardiovascular disease, regardless of patient liability to type 2 diabetes

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Urinary biomarkers and cardiovascular outcomes in the UK Biobank: observational and Mendelian randomization analyses

Cited by 7 publications

References 36 publications

Estimated salt intake and risk of atrial fibrillation in a prospective community‐based cohort

Estimated salt intake and risk of atrial fibrillation in a prospective community‐based cohort

Clinical markers and some trace elements in patients with type-2 diabetic nephropathy : Impact of insulin resistance

Separating the direct effects of risk factors for atherosclerotic cardiovascular disease from those mediated by type 2 diabetes

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