Petra Karnosová

Automated compared to manual office blood pressure and to home blood pressure in hypertensive patients

Abstract We studied the relationships of automated blood pressure (BP), measured in the healthcare centre, with manual office BP and home BP. Stable outpatients treated for hypertension were measured automatically, seated alone in a quiet room, six times after a 5 min rest with the BpTRU device, and immediately afterwards using the auscultatory method. Home BP was measured in a subgroup during 7 days preceding the visit. The automated, office and home BP values were 131.2 ± 21.8/77.8 ± 12.1 mmHg, 146.9 ± 20.8/85.8 ± 12.4 mmHg and 137.7 ± 17.7/79.4 ± 8.2 mmHg, respectively. Limits of agreement between office and automated BP (2 SDs in Bland–Altman plots) were +42.6 to –12.6/+22.6 to –6.6 mmHg for systolic/diastolic BP; for home and automated BP they were +45.8 to –25.8/+20.8 to –12.6 mmHg. For patients with two visits, intraclass correlation coefficients of BP values measured during the first and second visits were 0.66/0.72 for systolic/diastolic automated BP and 0.68/0.74 for systolic/diastolic office BP. Automated BP was lower than home BP and no more closely related to home BP than to office BP. It did not show better repeatability than office BP. Whether automated BP and the “white-coat effect”, calculated cas the office BP–automated BP difference, have clinical and prognostic importance deserves further studies.

The abnormal status of uncarboxylated matrix Gla protein species represents an additional mortality risk in heart failure patients with vascular disease.

BACKGROUND Matrix Gla protein (MGP) is a natural inhibitor of tissue calcification. In a previous study, we observed the positive association between abnormal concentrations of uncarboxylated MGP species and increased mortality risk in stable vascular patients. We explore whether co-incidence of abnormal status of uncarboxylated MPG and heart failure (HF) affects the mortality risk. METHODS We examined 799 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total uncarboxylated MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays. RESULTS Elevated (>100 ng/L) circulating brain natriuretic peptide (BNP) and abnormal status of plasma uncarboxylated MGP species (i.e.: dp-ucMGP ≥ 977 pmol/L or t-ucMGP ≤ 2825 nmol/L) were all identified as robust predictors of all-cause 5-year mortality. However, their co-incidence represented a substantial additional risk. We observed the highest mortality risk in patients with elevated BNP plus high dp-ucMGP compared to those with normal BNP plus low dp-ucMGP; fully adjusted HRRs were 4.86 (3.15-7.49). Likewise, the risk was increased when compared with patients with elevated BNP plus low dp-ucMGP; HRR 2.57 (1.60-4.10). Similar result we observed when co-incidence of elevated BNP and low t-ucMGP was analyzed [corresponding HRRs were 4.16 (2.62-6.61) and 1.96 (1.24-3.12)]. CONCLUSIONS The concomitant abnormality of uncarboxylated MGP and mild elevation of BNP leads in chronic patients with vascular disease to about two-fold increase of the relative mortality risk. We hypothesize that abnormal homeostasis of MGP is involved in the pathophysiology of HF.

Serum Vitamin D Status, Vitamin D Receptor Polymorphism, and Glucose Homeostasis in Healthy Subjects

Low vitamin D status has been frequently associated with impaired glucose metabolism. We examined associations between 25-hydroxyvitamin D (25-OH-D) and several parameters of glucose homeostasis in virtually healthy subjects, and explored possible interaction with vitamin D receptor (VDR) polymorphism. Nondiabetic subjects without chronic medication or any known significant manifest disease were selected from large general-population based population survey. Insulin sensitivity and β cell secretion were calculated by homeostasis model assessment (HOMA) and soluble isoform of receptor for advanced glycation end-products (sRAGE) using commercial ELISA. Subjects were also genotyped for rs2228570 polymorphism of VDR. After adjustment for potential confounders, we observed a significant relationship between 25-OH-D and fasting glycemia (β coefficient=-5.904; p=0.002) or insulin sensitivity (β=0.042; p=0.001), but not with β cell secretion or sRAGE. We found also an interaction with VDR polymorphism. Subjects with low 25-OH-D and AA genotype had significantly lower insulin sensitivity than those with GG genotype plus highest 25-OH-D concentrations (107.3% vs. 183.9%, p=0.021). In conclusion, low vitamin D status was in virtually healthy subjects associated with decreased insulin sensitivity, namely in those with GG genotype of rs2228570 VDR polymorphism.

The Prognostic Importance of Impaired Fasting Glycemia in Chronic Coronary Heart Disease Patients

OBJECTIVES Impaired glucose metabolism represents one the most important cardiovascular risk factors, with steeply raising prevalence in overall population. We aimed to compare mortality risk of impaired fasting glycaemia (IFG) and overt diabetes mellitus (DM) in patients with coronary heart disease (CHD). STUDY DESIGN prospective cohort study METHODS: A total of 1685 patients, 6-24 months after myocardial infarction and/or coronary revascularization at baseline, were followed in a prospective cohort study. Overt DM was defined as fasting glucose ≥ 7 mmol/L and/or use of antidiabetic treatment, while IFG as fasting glucose 5.6-6.99 mmol/L, but no antidiabetic medication. The main outcomes were total and cardiovascular mortality during 5 years of follow-up. RESULTS During follow-up of 1826 days, 172 patients (10.2%) deceased, and of them 122 (7.2%) from a cardiovascular cause. Both exposures, overt DM (n=623, 37.0% of the whole sample) and IFG (n=436, 25.9%) were associated with an independent increase of 5-year total mortality, compared to normoglycemic subjects [fully adjusted hazard risk ratio (HRR) 1.63 (95%CI: 1.01-2.61)]; p=0.043 and 2.25 (95%CI: 1.45-3.50); p<0.0001, respectively]. In contrast, comparing both glucose disorders one with each other, no significant differences were found for total mortality [HRR 0.82 (0.53-1.28); p=0.33]. Taking 5-years cardiovascular mortality as outcome, similar pattern was observed [HRR 1.96 (95%CI: 1.06-3.63) and 3.84 (95%CI: 2.19-6.73) for overt DM and IFG, respectively, with HRR 0.63 (95%CI: 0.37-1.07) for comparison of both disorders]. CONCLUSIONS Impaired fasting glycaemia adversely increases mortality of CHD patients in the same extent as overt DM.

[PP.37.07] ASSOCIATION BETWEEN NITRIC OXIDE SYNTHASE POLYMORPHISMS AND ARTERIAL PROPERTIES IN GENERAL POPULATION

Objective: Nitric oxide plays an important role in vascular biology. Several single nucleotide polymorphisms (SNP) in the endothelial nitric oxide gene (NOS3) have been previously associated with arterial hypertension. We investigated whether these SNPs might be associated with arterial phenotypes in the Czech general population. Design and method: We genotyped three NOS3 SNPs in 426 subjects not treated for arterial hypertension (mean age, 49.1 years; 55.9% women). Arterial properties were measured using applanation tonometry. In multivariate-adjusted analyses, we assessed the gene effects of rs3918226 (665 C > T), rs1799983 (glu298asp G > T) and rs2070744 (786 T > C) on augmentation index (AIx), central augmentation pressure (AP) and aortic pulse wave velocity (PWV). Results: Carriers of rs3918226 mutated T allele (8% of the sample) had marginally higher AIx (145.3 ± 2.5 vs. 140.2 ± 1.1%; P = 0.064) and significantly higher AP (12.7 ± 0.7 vs. 11.1 ± 0.3 mmHg; P = 0.033). These associations were independent of potential confounding factors (sex, age, heart rate and smoking). Aortic PWV was not different in the two rs39182226 genotypes groups (P = 0.35). In single gene analyses, we did not observe any association between measured phenotypes and rs1799983 or rs2070744 (P > 0.11). In haplotype analysis, we observed trend for higher PWV in haplotypes containing rs3918226 mutated T allele compared with other allelic combination (P < 0.079). Conclusions: Mutated T allele of rs3918226 polymorphism in NOS3 gene was associated with parameters reflecting central arterial stiffness and wave reflection. We hypothesize that genetic modulation of intermediate arterial phenotypes might lead to higher blood pressure.

OS 13-04 SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END-PRODUCTS AND INCREASED AORTIC STIFFNESS IN THE GENERAL POPULATION.

Objective: Accumulation of advanced glycation end-products (AGE) has been suggested to be involved in several pathophysiological processes in the vessel wall. Soluble isoform of receptor for AGE (sRAGE) acts as a decoy for capturing circulating AGE, thus preventing them from binding to the cell-surface receptor (RAGE) and protecting against the RAGE-AGE axis-elicited processes. We hypothesized that low sRAGE levels might be associated with increased arterial stiffness. Design and Method: In a cross-sectional design, we analyzed 1077 subjects, aged 25 to 64 years, from the Czech population-based study (“Post-MONICA”). Aortic pulse wave velocity (aPWV) measured by the Sphygmocor device, was used to assess aortic stiffness. sRAGE concentrations were assessed in frozen samples by ELISA methods (R&D Systems). Results: Aortic PWV significantly (p < 0.0001) decreased across the sRAGE quartiles. After adjustment for all potential confounders, non-diabetic subjects in the bottom quartile of sRAGE (< 918 pg/mL) had odds ratio of raised aortic PWV (≥ 9.3 m/sec, top quartile) 1.8 (95% CI: 1.19–2.72, p = 0.006); the association was stronger when only hypertensive non-diabetic individuals were included: their odds ratio was 2.05 (95%CI: 1.26–3.32, p = 0.004). In contrast, using similar regression models, low sRAGE was rejected as an independent predictor of raised aortic aPWV in diabetic or in normotensive subjects. Conclusions: Low circulating sRAGE was independently associated with increased arterial stiffness in a general population-based sample, but mainly in hypertensive non-diabetic patients. The lack of association in diabetics was probably due to low dispersion of sRAGE values and relatively small number of subjects (9% of the sample).