Abstract
BackgroundIncreased urinary excretion of IgM and low-grade albuminuria are associated with increased risk of cardiovascular morbidity and mortality. The objective of this study was to investigate the association between urinary IgM, albuminuria, and vascular parameters reflecting arterial structure and function.MethodsSubjects of the present study were from the Malmö Offspring study (MOS) cohort, and included 1531 offspring (children and grand-children) to first-generation subjects that participated in the Malmö Diet Cancer-Cardiovascular Arm study cohort. At baseline, technical measurements of arterial stiffness (carotid-femoral pulse wave velocity; c-f PWV), carotid arterial morphology, 24-h ambulatory blood pressure recordings, ankle-brachial-index (ABI), and evaluation of endothelial function (reactive hyperemia index, RHI) were performed. Urinary (U) IgM, U-albumin, and U-creatinine were measured. Multivariate adjusted logistic regression was used to test whether U-IgM excretion and increasing urinary albumin excretion were related to vascular parameters.ResultsDetectable U-IgM was independently associated with higher systolic blood pressure, odds ratio (OR) 1.021, 95% confidence interval (CI, 1.003–1.039), p = 0.025 and lower ABI; ABI dx: OR 0.026, 95% CI (0.002–0.381), p = 0.008, ABI sin: OR 0.040, 95% CI (0.003–0.496), p = 0.012. Low-grade albuminuria was independently associated with systolic and diastolic blood pressure, aortic blood pressure, the c-f PWV and the number of carotid intima plaques (p < 0.05).ConclusionsIn young to middle-aged, mostly healthy individuals, increased U-IgM excretion and low-grade albuminuria are associated with adverse vascular parameters. Increased U-IgM excretion may reflect subclinical peripheral atherosclerosis, whereas increased U-albumin excretion is associated with a wide range of cardiovascular abnormalities. This may reflect different pathophysiological mechanisms.
Highlights
Increased urinary excretion of IgM and low-grade albuminuria are associated with increased risk of cardiovascular morbidity and mortality
We used multivariable adjusted logistic regression to test whether urinary IgM (U-IgM) excretion and increasing urinary albumin excretion (U-albumin/creatinine ratio (ACR) > 2.9, U-albumin/creatinine ratio (U-ACR) 1.5–2.9 and U-ACR 0.1–1.4 mg/mmol compared with non-detectable urine albumin) were related to vascular parameters
In 76 of 1339 (5.7%) subjects, IgM was detected in urine and the median urinary IgM/creatinine ratio was 1.56 μg/mol, with the 25th– 75th percentile ranging from 0.90–2.57 μg/mol)
Summary
Increased urinary excretion of IgM and low-grade albuminuria are associated with increased risk of cardiovascular morbidity and mortality. Low grade albuminuria/microalbuminuria (3–30 mg albumin/mmol creatinine or 30–300 mg albumin/g creatinine), or 20 to 200 μg albumin excreted in the urine per minute (daytime)) is well-known to predict cardiovascular events and mortality in various clinical cohorts, and in subjects with hypertension and diabetes from the general population [12]. These findings are independent of renal function (estimated glomerular filtration rate; eGFR), and are believed to represent a link between albuminuria, atherosclerosis and systemic endothelial dysfunction [11, 13, 14]. The association between normoalbuminuria/ microalbuminuria and abnormal cardiovascular conditions such as arterial stiffness, manifest atherosclerosis and markers of endothelial dysfunction in younger populations is not well documented
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