Background
Soluble receptors for advanced glycation end-products (sRAGEs) have been suggested to have a protective role neutralizing the advanced glycation end-products (AGEs) and their pathological ...effect on vessel walls. We aimed to investigate the association between circulating concentrations of sRAGEs and dynamic of arterial wall stiffening as a manifestation of vascular ageing in general population.
Methods
In a prospective cohort study, we longitudinally followed 530 general-population-based subjects (subsample of Czech post-Monica study). Aortic pulse wave velocity (PWV) was measured twice (at baseline and after ≈8 years of follow-up) using a Sphygmocor device (AtCor Medical Ltd.) and intra-individual change of PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE were assessed at baseline by ELISA methods (R&D Systems).
Results
Average ∆PWV/year significantly increased across the sRAGE quintiles (
p
= 0.0008) and drop by one sRAGE quintile was associated with ≈21% increase in the relative risk of accelerated age-dependent stiffening (∆PWV/year ≥0.2 m/sec). In a categorized manner, subjects in the bottom quintile of sRAGE (<889.74 pg/mL) had fully adjusted odds ratio of accelerated stiffening 1.72 (95% CI: 1.06–2.79),
p
= 0.028, while those with high sRAGE concentrations (≥1695.2 pg/mL) showed opposite effect with odds ratio 0.55 (95% CI: 0.33–0.90),
p
= 0.017.
Conclusion
Circulating status of sRAGE independently influenced individual progression of arterial stiffness overt time. This finding strongly supports hypothesis, that high sRAGE have protective role against vascular ageing.
Advanced glycation end products (AGEs) are involved in several pathophysiologic processes in vascular diseases, including progressive loss of elasticity of the vessel wall (arterial stiffness). ...Circulating soluble receptors for AGEs (sRAGE) act as a decoy and counterbalanced the harmful properties of AGEs as the natural protective factor. We compared the role of circulating or skin-deposed AGEs and sRAGE regarding the natural course of arterial stiffening. In a prospective cohort study, we longitudinally followed 536 general population-based subjects (subsample of Czech post-MONICA study). Aortic pulse-wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE and carboxymethyl lysine (circulating AGEs) were assessed at the follow-up visit by ELISA, while skin AGEs were measured using the autofluorescence-based device AGE Reader. Using multiple regressions, we found significant association between ∆PWV/year as a dependent variable, and both, sRAGE and skin AGEs as independent ones (each on its own model). However, the closest associations to ∆PWV/year were found for the ratio of these two factors (skin AGEs/sRAGE) β coeff = 0.0747 (SE 0.0189), p < 0.0001. In a categorized manner, subjects with skin AGEs/sRAGE ratio ≥ 3.3 showed about twofold higher risk having ΔPWV/year ≥ 0.2 m/s adjusted odds ratio was 2.09 (95% CI: 1.35-3.22), p = 0.001. In contrast, neither circulating AGEs nor circulating AGEs/sRAGE showed any significant relation to ΔPWV/year. In conclusion, skin AGEs/sRAGE ratio seems to be a more sensitive biomarker of vascular aging than these single factors themselves or circulation status of AGEs.
Stiffening of large arteries, clinically manifesting as increased aortic pulse wave velocity (PWV), is an inevitable outcome of aging. Among other mechanisms, impaired glucose metabolism plays an ...important role, leading to the deposition of advanced glycation end products (AGEs). This process is counterbalanced by the circulating soluble receptor for AGEs (sRAGE). We investigated the association between arterial stiffness on one side and multiple circulating biomarkers and the degree of skin deposition of AGEs on the other. In a cross-sectional design, 867 participants based on a general population sample (Czech post-MONICA studies) were examined. PWV was measured by SphygmoCor device (AtCor Medical Ltd.), while skin AGEs were measured using a dedicated autofluorescence method (AGE Reader mu
). To quantify the circulating status of AGEs, carboxymethyl lysine (CML) and sRAGE concentrations were assessed by ELISA, along with conventional glucose metabolism indicators. When analyzing the whole sample using multiple linear or logistic regression models and after adjustment for potential covariates, a significant association with PWV was found for fasting glycemia, HbA1c, sRAGE, skin AGEs, and the skin AGE-to-sRAGE ratio. Among these parameters, stepwise models identified the strongest association for the skin AGEs and AGE-to-sRAGE ratio, and this was also true when diabetic subjects were excluded. In contrast, neither CML nor its ratio relative to sRAGE showed any association with arterial stiffness. In conclusion, skin AGEs along with their ratio relative to sRAGE were closely associated with arterial stiffness and is a better indicator of the current status of deposited AGEs than other relevant factors.
Circulating levels of soluble receptor for advanced glycation end-products (sRAGE) have been suggested to have a protective role in neutralizing advanced glycation end-products (AGEs) and their ...pathological effects on vessel walls. We aimed to investigate the association between the circulating concentration of sRAGE and the dynamics of arterial wall stiffening as a manifestation of vascular aging in the general population. In a prospective cohort study, we longitudinally followed 530 general-population-based subjects (subsample of Czech post-MONICA study). Aortic pulse wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE were assessed at baseline by ELISA (R&D Systems). The average ∆PWV/year significantly decreased across the sRAGE quintiles (p = 0.048), and a drop by one sRAGE quintile was associated with an ~21% increase in the relative risk of accelerated age-dependent stiffening (∆PWV/year ≥ 0.2 m/s). Subjects in the bottom quintile of sRAGE (<889.74 pg/mL) had a fully adjusted odds ratio of accelerated stiffening of 1.72 (95% CI: 1.06-2.79), p = 0.028, while those with high sRAGE concentrations (≥1695.2 pg/mL) showed the opposite effect odds ratio 0.55 (95% CI: 0.33-0.90), p = 0.017. In conclusion, the circulating status of sRAGE independently influenced the individual progression of arterial stiffness over time. This finding strongly supports the hypothesis that high sRAGE has a protective role against vascular aging.
Background
Advanced glycation end products (AGEs) are involved into several pathophysiologic processes in vascular diseases, including progressive loss of elasticity of vessel wall (arterial ...stiffness). Circulating soluble receptor for AGEs (sRAGE) act as a decoy and counterbalanced the harmful properties of AGEs as the natural protective factor
1
,
2
. We compared the role of circulating or skin-deposed AGEs and sRAGE regarding natural course of arterial stiffening.
Methods
In a prospective cohort study, we longitudinally followed 536 general-population-based subjects (subsample of Czech post-MONICA study). Aortic pulse wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd.), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE and carboxylmethyl lysine (circulating AGEs) were assessed at follow-up visit by ELISA, while skin AGEs were measured using autofluorescence-based device AGE Reader.
Results
Using multiple regressions, we found significant association between ∆PWV/year as dependent variable and both, sRAGE and skin AGEs as independent ones (each on its own model). However, the closest association to ∆PWV/year were found for ratio of these two factors (skin AGEs/sRAGE) coeff = 0.0747 (SE 0.0189),
p
< 0.0001. In categorized manner, subjects with skin AGEs/sRAGE ratio ≥3.3 showed about two-fold higher risk having PWV/year ≥0.2 m/sec adjusted odds ratio was 2.09 (95% CI: 1.35–3.22),
p
= 0.001. In contrast neither circulating AGEs nor circulating AGEs/sRAGE showed any significant relation to PWV/ year.
Conclusions
Skin AGEs/sRAGE ratio seems to be more sensitive biomarker of vascular ageing than these single factors themselves or circulation status of AGEs
3
.
We aimed to establish the association between sclerostin (a glycoprotein involved in bone metabolism) and development of pulse wave velocity (PWV) in the general population.
A prospective cohort ...study with a total of 522 subjects. Aortic PWV was measured twice (at baseline and after approximately 8 years of follow-up) and intraindividual change in PWV per year (ΔPWV/year) was calculated.
ΔPWV/year increased across the sclerostin quintiles, but generally in a strong age-dependent manner. However, a significant independent positive association between sclerostin and ΔPWV/year was observed exclusively in C allele carriers of rs5186 polymorphism for the angiotensin II receptor 1 (n = 246).
Sclerostin concentrations were associated with an accelerated natural course of arterial stiffening, but only in interaction with renin-angiotension system.
Arterial system is a system of vessels distributing blood. Ageing of arterial system leads to two distinct pathologies: atherosclerosis and arteriosclerosis - stiffening of arterial wall. These ...pathologies can coexist and interfere; however, they differ in their pathogenesis, location, scope and consequences. Progressive loss of elastic properties of large arteries is natural part of vascular ageing. It is directly responsible for several age dependent consequences, such as increase of central systolic pressure or prevalence of isolated systolic hypertension in the elderly. Clinically, central arteries stiffness manifests as aortic pulse wave velocity, which can be quantified, among other methods, using applanation tonometry. There is abundant evidence that aortic pulse wave velocity represents an independent predictor of cardiovascular mortality and morbidity. The most important mechanism in arterial stiffening is repeated mechanical damage which leads to fractures, fragmentation and thinning of elastin. Stiffening of large arteries can be accelerated by several other mechanisms, e.g. deposition of several substances (calcium, advanced glycation end-products, etc.), metabolic turnover of key elements of vascular extracellular matrix (collagen and elastin) or individual genetic susceptibility. In...
Background
Accumulation of advanced glycation end-products (AGEs) is one of pathophysiological processes, responsible for progressive stiffening of vessel wall. In contrast, soluble isoform of ...receptor for AGEs (sRAGE) act as “decoy” and physiological defense against circulating AGEs. We hypothesized that low levels of sRAGE might be associated with accelerated age-dependent arterial stiffening.
Methods
We followed 429 population-based subjects (mean age 50.8 (±11.7) years, 41.5% males) in prospective study. Aortic pulse wave velocity (aPWV) was measured using a Sphygmocor device. sRAGE concentrations were assessed in frozen samples by ELISA methods (R&D Systems). Baseline examination was done in 2008/9, while follow-up visit in 2016/17 (median time of follow-up was 7.6 years)
Results
Mean intra-individual increase of aPWV during follow-up was 1.37 (±1.88) m/sec and was inversely associated with baseline sRAGE concentration — the aPWVV difference follow-up
minus
baseline across its quintiles was 2.08((±1.89), 1.51(±2.16), 1.20(±2.10), 0.99(±1.70), 1.13(±1.21) in 1st–5th quintiles of sRAGE, resp.; p = 0.003 (adjusted for age, gender and baseline mean arterial pressure) Baseline concentration of sRAGE <917 pg/mL (1st quintile) was associated with about two-fold higher risk, that aPWV increased by more than 0.8 m/sec (expectable “secular” age-dependent increase) even if adjusted for baseline risk profile and pharmacotherapy fully adjusted odds ratio was 1.95 (95%CI: 1.12–3.39, p = 0.018.
Conclusions
Low concentration of circulating sRAGE was in our sample of generally healthy subjects associated with markedly accelerated age-dependent arterial stiffening, probably as a consequence of higher deposition of AGEs in vessel wall (
supported by SVV 02684, PROGRES Q39 and AZV 15-27109 grants
).
Abstract only
Introduction:
Leptin is an adipocyte-derived peptide, involved in energy homeostasis and regulation of body weight. The position of leptin in cardiovascular pathophysiology remained ...controversial, some studies suggest a detrimental effect of hyperleptinemia on the cardiovascular (CV) system, while others assume the role of leptin as protective.
Hypothesis:
We explore whether high leptin status affects the mortality/ morbidity risk in stable patients with coronary heart disease.
Methods:
975 patients, ≥6 months after myocardial infarction (EUROASPIRE cohort) were followed in a prospective study. All-cause or CV death, non-fatal events (myocardial infarction, stroke or any revascularization) and hospitalizations for heart failure (HF) were registered as outcomes
Results:
High serum leptin concentrations (≥18.9 ng/mL, i.e. 4
th
quartile) indicate inferior survival, as well as a higher incidence of fatal vascular event or hospitalizations for HF (
see
Figure). Even after full adjustment for potential covariates, high leptin was associated with significantly increased 5-years risk of all-cause death HRR 2.10 (95%CIs:1.29-3.42), p<0.003, CV death HRR 2.65 (95%CIs:1.48-4.74), p<0.001 and HF hospitalization HRR 1.95 (95%CIs:1.11-3.44), p<0.020. In contrast, the incidence risk of non-fatal CV events was only marginally and non-significantly influenced HRR 1.27 (95%CIs:0.76-2.13), p=0.359
Conclusions:
High leptin concentration entails an increased risk of mortality (apparently driven by fatal CV events) and future worsening of HF, on top of conventional CV risk factors and the baseline status of left ventricular function.
Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Wall-to-lumen ratio (WLR) may ...represent the earliest step in hypertension-mediated organ damage.Our objective was to compare functional and structural parameters of retinal microcirculation in a randomly selected urban population sample, in hypertensive and normotensive individuals.
A total of 398 randomly selected individuals from an urban population aged 25-65 years, residing in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry, with data evaluable in 343 patients. Complete data were available for 342 individuals divided into four groups based on blood pressure and control status of hypertension: normotensive individuals ( n = 213), treated controlled hypertensive individuals ( n = 30), treated uncontrolled hypertensive individuals ( n = 26), and newly detected/untreated hypertensive individuals ( n = 73).
There was a tendency to higher wall thickness in treated but uncontrolled hypertensive patients (compared to normotensive and treated controlled hypertensive individuals). WLR was significantly increased in treated but uncontrolled hypertensive patients as well as in individuals with newly detected thus untreated hypertension or in patients with known but untreated hypertension. There was no difference in WLR in treated, controlled hypertensive patients compared with normotensive individuals.
Our results show that an increased WLR, reflecting early vascular damage, was found in newly detected individuals with hypertension and in untreated hypertensive patients, reflecting early hypertension-mediated vascular damage. Early initiation of hypertension treatment may be warranted.
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