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SRAGE and risk of diabetes, cardiovascular disease, and death.

ABSTRACT: Advanced glycation end products (AGEs) and their receptors are strongly implicated in the development of diabetes complications. When stimulated by AGEs, the receptors for AGEs (RAGEs) induce inflammation and are thought to fuel disease progression. Soluble circulating RAGE (sRAGE) may counteract the detrimental effects of RAGE. We measured sRAGE in stored plasma from a random sample of 1,201 participants in the Atherosclerosis Risk in Communities (ARIC) Study who were aged 47-68 years, had normal kidney function, and had no history of cardiovascular disease. In cross-sectional analyses, black race, male sex, higher BMI, and higher C-reactive protein were independently associated with low sRAGE. The racial difference was striking, with blacks approximately three times more likely to have low sRAGE compared with whites even after adjustment. During ~18 years of follow-up, there were 192 incident coronary heart disease events, 53 ischemic strokes, 213 deaths, and 253 cases of diabetes (among the 1,057 persons without diabetes at baseline). In multivariable Cox models comparing risk in the first quartile with that in the fourth quartile of baseline sRAGE, low levels of sRAGE were significantly associated with risk of diabetes (hazard ratio 1.64 [95% CI 1.10-2.44]), coronary heart disease (1.82 [1.17-2.84]), and mortality (1.72 [1.11-2.64]) but not ischemic stroke (0.78 [0.34-1.79]). In conclusion, we found that low levels of sRAGE were a marker of future chronic disease risk and mortality in the community and may represent an inflammatory state. Racial differences in sRAGE deserve further examination.

SUBMITTER: Selvin E

PROVIDER: S-EPMC3661610 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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sRAGE and risk of diabetes, cardiovascular disease, and death.

Selvin Elizabeth E Halushka Marc K MK Rawlings Andreea M AM Hoogeveen Ron C RC Ballantyne Christie M CM Coresh Josef J Astor Brad C BC

Diabetes 20130208 6

Advanced glycation end products (AGEs) and their receptors are strongly implicated in the development of diabetes complications. When stimulated by AGEs, the receptors for AGEs (RAGEs) induce inflammation and are thought to fuel disease progression. Soluble circulating RAGE (sRAGE) may counteract the detrimental effects of RAGE. We measured sRAGE in stored plasma from a random sample of 1,201 participants in the Atherosclerosis Risk in Communities (ARIC) Study who were aged 47-68 years, had norm ...[more]

PMID: 23396398

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Project description:BackgroundObservational studies suggest that early menopause is associated with increased risk of death and cardiovascular disease (CVD); however, the results of these studies have been inconsistently. We aimed to assess the association of menopause with death and CVD and whether this association was modified by cardiovascular risk factors.MethodsThe study population was women age 35-64 years living in two communities of Beijing who were enrolled in the Chinese Multi-provincial Cohort Study in 1992. Participants were followed until first cardiovascular event, death, or the end of follow-up (2018). Self-reported age at menopause was recorded. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of death and CVD after adjusting for baseline covariates of age, family history of CVD, and white blood cell count, as well as time-varying covariates of menopause, use of oral estrogen, and conventional risk factors. Additionally, we assessed the combined effect of age at menopause and risk factors on the primary endpoint.ResultsOf 2104 eligible women, 124 died and 196 had a first CVD event (33 fatal CVD and 163 non-fatal CVD). Compared with women who experienced menopause at age 50-51 years, the risk of death was higher in women with menopause at age 45-49 years (HR 1.99, 95% CI 1.24-3.21; P = 0.005), and the risk of ischemic stroke was higher in women with menopause at age < 45 years (HR 2.16, 95% CI 1.04-4.51; P = 0.04) and at age 45-49 years (HR 2.05, 95% CI 1.15-3.63; P = 0.01). Women who had menopause before age 50 years and at least one elevated risk factor at baseline had a higher risk of death (HR 11.10, 95% CI 1.51-81.41; P = 0.02), CVD (HR 3.98, 95% CI 1.58-10.01; P = 0.003), ischemic CVD (HR 4.53, 95% CI 1.63-12.62; P = 0.004), coronary heart disease (HR 8.63, 95% CI 1.15-64.50; P = 0.04), and stroke (HR 2.92, 95% CI 1.03-8.29; P = 0.04) than those with menopause at age 50-51 years and optimal levels of all risk factors.ConclusionsEarlier menopause may predict death and ischemic stroke. Furthermore, there is a combined effect of earlier menopause and elevated risk factors on death and CVD.

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SRAGE and risk of diabetes, cardiovascular disease, and death.

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sRAGE and risk of diabetes, cardiovascular disease, and death.

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