Effects of metabolic syndrome on arterial function in different age groups: the Advanced Approach to Arterial Stiffness study.

OBJECTIVE: The aim of the Advanced Approach to Arterial Stiffness study was to compare arterial stiffness measured simultaneously with two different methods in different age groups of middle-aged and older adults with or without metabolic syndrome (MetS). The specific effects of the different MetS components on arterial stiffness were also studied. METHODS: This prospective, multicentre, international study included 2224 patients aged 40 years and older, 1664 with and 560 without MetS. Patients were enrolled in 32 centres from 18 European countries affiliated to the International Society of Vascular Health & Aging. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the carotid-femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40-49, 50-59, 60-74, 75-90 years. In this report, we present the baseline data of this study. RESULTS: Both CF-PWV and CAVI increased with age, with a higher correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age-adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated (r = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not CAVI were higher in presence of MetS (CF-PWV: 9.57 ±â€Š0.06 vs. 8.65 ±â€Š0.10, P < 0.001; CAVI: 8.34 ±â€Š0.03 vs. 8.29 ±â€Š0.04, P = 0.40; mean ±â€ŠSEM; MetS vs. no MetS). The absence of an overall effect of MetS on CAVI was related to the heterogeneous effects of the components of MetS on this parameter: CAVI was positively associated with the high glycaemia and high blood pressure components, whereas lacked significant associations with the HDL and triglycerides components while exhibiting a negative association with the overweight component. In contrast, all five MetS components showed positive associations with CF-PWV. CONCLUSION: This large European multicentre study reveals a differential impact of MetS and age on CAVI and CF-PWV and suggests that age may have a more pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This important finding may be due to heterogeneous effects of MetS components on CAVI. The clinical significance of these original results will be assessed during the longitudinal phase of the study.

Main results of the ouabain and adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin.

BACKGROUND: The Ouabain and Adducin for Specific Intervention on Sodium in Hypertension (OASIS-HT) Trial was a phase-2 dose-finding study of rostafuroxin, a digitoxygenin derivative, which selectively antagonizes the effects of endogenous ouabain (EO) on Na+,K+-ATPase and mutated adducin. Rostafuroxin lowered blood pressure (BP) in some animal models and in humans. METHODS: OASIS-HT consisted of 5 concurrently running double-blind cross-over studies. After 4 weeks without treatment, 435 patients with uncomplicated systolic hypertension (140-169 mm Hg) were randomized to rostafuroxin (0.05, 0.15, 0.5, 1.5 or 5.0 mg/d) or matching placebo, each treatment period lasting 5 weeks. The primary endpoint was the reduction in systolic office BP. Among the secondary endpoints were diastolic office BP, 24-h ambulatory BP, plasma EO concentration and renin activity, 24-h urinary sodium and aldosterone excretion, and safety. ANOVA considered treatment sequence (fixed effect), subjects nested within sequence (random), period (fixed), and treatment (fixed). RESULTS: Among 410 analyzable patients (40.5% women; mean age, 48.4 years), the differences in the primary endpoint (rostafuroxin minus placebo) ranged from -0.18 mm Hg (P = 0.90) on 0.15 mg/d rostafuroxin to 2.72 mm Hg (P = 0.04) on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (P = 0.03) for systolic office BP; 0.70 mm Hg (P = 0.08) for diastolic office BP; 0.36 mm Hg (P = 0.49) for 24-h systolic BP; and 0.05 mm Hg (P = 0.88) for 24-h diastolic BP. In the 2 treatment groups combined, systolic (-1.36 mm Hg) and diastolic (-0.97 mm Hg) office BPs decreased from week 5 to 10 (P for period effect ≤ 0.028), but carry-over effects were not significant (P ≥ 0.11). All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo. CONCLUSIONS: In 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT00415038.

Comparison of brachial-ankle pulse wave velocity in Japanese and Russians.

Pulse wave velocity (PWV) is a well-known indicator of arterial stiffness and a marker of the presence of vascular lesions. Cardiovascular mortality in Russia has become the highest in the world. The Japanese are enjoying long lives, and the mortality caused by cardiovascular diseases has thus far remained at lower levels than that in Russia. In this study, we focused on brachial-ankle pulse wave velocity (baPWV) obtained from normal human subjects in Russia as well as in Japan, and compared their respective cardiovascular risks. We evaluated baPWV in 337 Japanese and 138 Russian healthy subjects. The baPWV was recorded using a PWV diagnosis device. BaPWV was measured between 2 locations of the arterial tree. The baPWV in the Russian group was significantly higher than that obtained in the Japanese of two groups categorized by age (40-59 years and 60- years). Further, body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure in the Russian group were significantly higher than those obtained in Japanese in three age groups (under 39 years, 40-59 years, and 60- years). Moreover, the baPWV indicated a positive correlation with age, BMI and SBP in both Japanese and Russians, although the increasing trend of the baPWV against age of the Russian group had a larger value than that of the Japanese. Therefore, we suggest that arterial stiffness might be promoted earlier in the Russian group, which might be the main cause of the increased cardiovascular risk in Russia.

A Japanese-Russian collaborative study on aging and atherosclerosis.

In Russia, the average life span is decreasing. This phenomenon has not been previously observed in the western hemisphere during periods of relative peace. Although this trend can be attributed to various causes, the available statistics suggest that approximately 55% of the total mortality in Russia at the present time is due to cardiovascular events. Similarly, cardiovascular events are also increasing in Japan and are associated with changes in eating habits. A Japanese-Russian international collaborative study was therefore initiated to investigate this. Data on 102 normal Russian subjects were obtained from a total of 345 patients treated at the Smolensk State Medical Academy outpatients' clinic. The data on the Japanese patients were collected at Tohoku University, Tohoku Rosai Hospital, and Fukuda Denshi Company. Sixty-seven healthy male Japanese volunteers were compared with 44 healthy male Russian patients. In this study, Vasera VS1000 (Fukuda Denshi, Tokyo) was utilized to measure pulse wave velocity (PWV). Linear regression analysis was performed, and the results showed that brachial-ankle PWV (baPWV) was significantly higher in the Russian compared with the Japanese study group. With regard to aging, PWV was found to increase both in the Japanese and Russian subjects, with a significant increase in the latter group during their 40s compared with the Japanese, and with this tendency being carried forward into the 50s. This may be the principal cause for the higher incidence of cardiovascular events reported among Russians. Furthermore, when a straight line regression analysis was performed, the zero axis intercept in both cases showed almost the same value. These results indicated that the PWV may be almost the same in Japanese and Russian populations at the time of birth. In conclusion, at the time of birth, there is no difference in the atherosclerotic status of Japanese and Russian infants. However, over time atherosclerosis becomes more apparent and progresses significantly in the case of Russian subjects. This finding is observed through the analysis of PWV. The present authors intend to continue their study aimed at preventing the further development of atherosclerosis through medical intervention.