Beta 2 Microglobulin and the Risk for Cardiovascular Events in Patients With Asymptomatic Carotid Atherosclerosis

Amighi, Jasmin; Hoke, M.; Mlekusch, Wolfgang; Schlager, Oliver; Exner, Markus; Haumer, Markus; Pernicka, Elisabeth; Koppensteiner, Renate; Minar, Erich; Rumpold, Helmut; Schillinger, Martin; Wagner, Oswald

doi:10.1161/strokeaha.110.600312

Cited by 74 publications

(70 citation statements)

References 31 publications

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“…However, changes in early kidney biomarkers, such as Cys-C in non-kidney diseases, have been associated with an increased rate of mortality from both CVD and non-CVD (pulmonary diseases, cancer, infections), as indicated by the quartiles of kidney function [47]. On the other hand, β2M, also used as an early kidney biomarker, has been reported to be independently associated with the mortality from heart attacks and strokes in patients with asymptomatic coronary atherosclerosis [48]. …”

Section: Discussionmentioning

confidence: 99%

Early kidney damage induced by subchronic exposure to PM2.5 in rats

et al. 2016

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BackgroundParticulate matter exposure is associated with respiratory and cardiovascular system dysfunction. Recently, we demonstrated that fine particles, also named PM2.5, modify the expression of some components of the angiotensin and bradykinin systems, which are involved in lung, cardiac and renal regulation. The endocrine kidney function is associated with the regulation of angiotensin and bradykinin, and it can suffer damage even as a consequence of minor alterations of these systems. We hypothesized that exposure to PM2.5 can contribute to early kidney damage as a consequence of an angiotensin/bradykinin system imbalance, oxidative stress and/or inflammation.ResultsAfter acute and subchronic exposure to PM2.5, lung damage was confirmed by increased bronchoalveolar lavage fluid (BALF) differential cell counts and a decrease of surfactant protein-A levels. We observed a statistically significant increment in median blood pressure, urine volume and water consumption after PM2.5 exposure. Moreover, increases in the levels of early kidney damage markers were observed after subchronic PM2.5 exposure: the most sensitive markers, β-2-microglobulin and cystatin-C, increased during the first, second, sixth and eighth weeks of exposure. In addition, a reduction in the levels of specific cytokines (IL-1β, IL-6, TNF-α, IL-4, IL-10, INF-γ, IL-17a, MIP-2 and RANTES), and up-regulated angiotensin and bradykinin system markers and indicators of a depleted antioxidant response, were also observed. All of these effects are in concurrence with the presence of renal histological lesions and an early pro-fibrotic state.ConclusionSubchronic exposure to PM2.5 induced an early kidney damage response that involved the angiotensin/bradykinin systems as well as antioxidant and immune imbalance. Our study demonstrates that PM2.5 can induce a systemic imbalance that not only affects the cardiovascular system, but also affects the kidney, which may also overall contribute to PM-related diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0179-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Early kidney damage induced by subchronic exposure to PM2.5 in rats

et al. 2016

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“…B2M is a polypeptide forming a small subunit of the major histocompatibility class I molecule on the surface of nucleated human cells and thrombocytes and is eliminated by the kidney. 9, 29 A few studies have reported a significant prospective association between B2M and CVD, 29, 30 but the mechanisms by which B2M confers CVD risk is not well understood. B2M may merely be a good marker for kidney dysfunction, 31 but, some investigators have suggested non-kidney pathways.…”

Section: Discussionmentioning

confidence: 99%

Cardiac and Kidney Markers for Cardiovascular Prediction in Individuals With Chronic Kidney Disease

Matsushita

Sang

Ballew

et al. 2014

ATVB

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Objective Traditional predictors suboptimally predict cardiovascular disease (CVD) in individuals with chronic kidney disease (CKD). This study compared five non-traditional cardiac and kidney markers regarding the improvement of cardiovascular prediction among those with CKD. Approach and Results Among 8,622 participants aged 52–75 years in the ARIC Study, cardiac troponin T [cTnT], N-terminal pro-B-type natriuretic peptide [NT-proBNP], cystatin C, β2-microglobulin, and β-trace protein were compared for improvement in predicting incident CVD after stratifying by CKD status (940 participants with CKD [kidney dysfunction or albuminuria]). During a median follow-up of 11.9 years, there were 1,672 CVD events including coronary disease, stroke, and heart failure (336 cases in CKD). Every marker was independently associated with incident CVD in participants with and without CKD. The adjusted HRs (per 1 SD) were larger for cardiac markers than kidney markers, particularly in CKD (1.61 [95% CI, 1.43–1.81] for cTnT, 1.50 [1.34–1.68] for NT-proBNP, and <1.26 for kidney markers). Particularly in CKD group, cardiac markers compared to kidney markers contributed to greater c-statistic increment (0.032–0.036 vs. 0.012–0.015 from 0.679 with only conventional predictors in CKD and 0.008–0.011 vs. 0.002–0.010 from 0.697 in non-CKD) and categorical net reclassification improvement (0.086–0.127 vs. 0.020–0.066 in CKD and 0.057–0.077 vs. 0.014–0.048 in non-CKD). The superiority of cardiac markers was largely consistent in individual CVD outcomes. Conclusions A greater improvement in cardiovascular prediction was observed for cardiac markers than kidney markers in persons with CKD. These results suggest that cTnT and NT-proBNP are useful for better CVD risk classification in this population.

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“…In a prospective cohort study of nondisabled people 65 years and older, Β2M concentrations better predicted death than high sensitivity C-reactive protein (CRP), an established inflammatory marker (1). In addition, several cohort studies, including the Atherosclerosis Risk in Communities Study (ARIC) (7), have reported positive associations between Β2M and aging, various cardiovascular conditions, and mortality from diabetes, CVD and all causes, suggesting that serum B2M may also serve as an inflammatory biomarker (7, 17, 18). …”

Section: Introductionmentioning

confidence: 99%

Circulating Beta-2 Microglobulin and Risk of Cancer: The Atherosclerosis Risk in Communities Study (ARIC)

Prizment

Linabery

Lutsey

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Serum β-2 microglobulin (Β2M), a major histocompatibility complex class I molecule that is a biomarker of kidney filtration and increased cell turnover, is elevated at the time of diagnosis in hematological and some solid cancers. However, serum Β2M was not examined prospectively as a marker for cancer risk. We hypothesized that in a population without a prior cancer diagnosis, serum Β2M is associated with risk of cancer (n=2,436), including colorectal (n=255), lung (n=298), breast (n=424), prostate (n=524) cancers, and hematological (n=176) malignancies. Methods The analytical cohort (n=12,300) was followed for incident cancers from 1990 through 2006. Β2M (range: 0.9–57.8 mg/L) was measured in stored serum collected in 1990–1992. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for cancer incidence and mortality in relation to quartiles of Β2M. Results Adjusting for age, sex, race, center, education, body mass index, smoking, aspirin and hormone therapy (in women) and comparing highest to lowest Β2M quartiles, HRs were 1.25 (1.06–1.47; P-trend=0.002) for total cancer risk and 2.21 (1.32–3.70; P-trend=0.001) for colorectal cancer risk, with similar HRs for colon and rectal cancers. These associations remained after adjustment for an inflammatory biomarker, C-reactive protein, and after excluding the first three years of follow-up. Significant associations were also observed for mortality from total, lung and hematological cancers. Conclusions These findings provide the first evidence that higher serum Β2M is associated with increased colorectal cancer risk. Impact This study supports B2M as a potential biomarker for colorectal cancer risk.

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Beta 2 Microglobulin and the Risk for Cardiovascular Events in Patients With Asymptomatic Carotid Atherosclerosis

Cited by 74 publications

References 31 publications

Early kidney damage induced by subchronic exposure to PM2.5 in rats

Early kidney damage induced by subchronic exposure to PM2.5 in rats

Cardiac and Kidney Markers for Cardiovascular Prediction in Individuals With Chronic Kidney Disease

Circulating Beta-2 Microglobulin and Risk of Cancer: The Atherosclerosis Risk in Communities Study (ARIC)

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