Aim: 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. Methods: 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. Results: 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). Conclusion: Sclerostin concentrations were associated with an accelerated natural course of arterial stiffening, but only in interaction with renin-angiotension system.
- MeSH
- adaptorové proteiny signální transdukční genetika MeSH
- analýza pulzové vlny MeSH
- dospělí MeSH
- genetická predispozice k nemoci genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- progrese nemoci MeSH
- receptor angiotensinu typ 1 genetika MeSH
- senioři MeSH
- tuhost cévní stěny genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Secondary prevention of atherosclerotic vascular diseases represents a cascade of procedures to reduce the risk of future fatal and non-fatal cardiovascular events. We sought to determine whether the expression of selected microRNAs influenced mortality of stable chronic cardiovascular patients. METHODS: The plasma concentrations of five selected microRNAs (miR-1, miR-19, miR-126, miR-133 and miR-223) were quantified in 826 patients (mean age 65.2 years) with stable vascular disease (6-36 months after acute coronary syndrome, coronary revascularization or first-ever ischemic stroke). All-cause and cardiovascular mortality rates were followed during our prospective study. RESULTS: Low expression (bottom quartile) of all five miRNAs was associated with a significant increase in five-year all-cause death, even when adjusted for conventional risk factors, treatment, raised troponin I and brain natriuretic protein levels [hazard risk ratios (HRRs) were as follows: miR-1, 1.65 (95% CI: 1.16-2.35); miR-19a, 2.27 (95% CI: 1.59-3.23); miR-126, 1.64 (95% CI: 1.15-2.33); miR-133a, 1.46 (95% CI: 1.01-2.12) and miR-223, 2.05 (95% CI: 1.45-2.91)]. Nearly similar results were found if using five-year cardiovascular mortality as the outcome. However, if entering all five miRNAs (along with other covariates) into a single regression model, only low miR-19a remained a significant mortality predictor; and only in patients with coronary artery disease [3.00 (95% CI: 1.77-5.08)], but not in post-stroke patients [1.63 (95% CI: 0.94-2.86)]. CONCLUSIONS: In stable chronic coronary artery disease patients, low miR-19a expression was associated with a substantial increase in mortality risk independently of other conventional cardiovascular risk factors.
- MeSH
- ateroskleróza krev genetika mortalita MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- hodnocení rizik metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA biosyntéza krev MeSH
- míra přežití trendy MeSH
- následné studie MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
Both vitamins K and D are nutrients with pleiotropic functions in human tissues. The metabolic role of these vitamins overlaps considerably in calcium homeostasis. We analyzed their potential synergetic effect on arterial stiffness. In a cross-sectional study, we analyzed aortic pulse wave velocity (aPWV) in 1023 subjects from the Czech post-MONICA study. Desphospho-uncarboxylated matrix γ-carboxyglutamate protein (dp-ucMGP), a biomarker of vitamin K status, was measured by sandwich ELISA and 25-hydroxyvitamin D3 (25-OH-D3) by a commercial immunochemical assay. In a subsample of 431 subjects without chronic disease or pharmacotherapy, we detected rs2228570 polymorphism for the vitamin D receptor. After adjustment for confounders, aPWV was independently associated with both factors: dp-ucMGP [β-coefficient(S.E.M.)=13.91(4.87); P=.004] and 25-OH-D3 [0.624(0.28); P=.027]. In a further analysis, we divided subjects according to dp-ucMGP and 25-OH-D3 quartiles, resulting in 16 subgroups. The highest aPWV had subjects in the top quartile of dp-ucMGP plus bottom quartile of 25-OH-D3 (i.e., in those with insufficient status of both vitamin K and vitamin D), while the lowest aPVW had subjects in the bottom quartile of dp-ucMGP plus top quartile of 25-OH-D3 [9.8 (SD2.6) versus 6.6 (SD1.6) m/s; P<.0001]. When we compared these extreme groups of vitamin K and D status, the adjusted odds ratio for aPWV≥9.3 m/s was 6.83 (95% CI:1.95-20.9). The aPWV was also significantly higher among subjects bearing the GG genotype of rs2228570, but only in those with a concomitantly poor vitamin K status. In conclusion, we confirmed substantial interaction of insufficient K and D vitamin status in terms of increased aortic stiffness.
- MeSH
- analýza pulzové vlny MeSH
- dospělí MeSH
- extracelulární matrix - proteiny metabolismus MeSH
- jednonukleotidový polymorfismus MeSH
- kalcifediol krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nedostatek vitaminu K patofyziologie MeSH
- proteiny vázající vápník metabolismus MeSH
- průřezové studie MeSH
- receptory kalcitriolu genetika MeSH
- regresní analýza MeSH
- senioři MeSH
- tuhost cévní stěny fyziologie MeSH
- vitamin D krev MeSH
- vitamin K krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
