Search

Objective: The enzyme xanthine oxidoreductase (XOR) generates uric acid in the terminal steps of the purine metabolism; meanwhile reactive oxygen species are formed. We hypothesized that uric acid production, as assessed indirectly from XOR variants, is associated with hypertension., Methods: Among 2769 participants (48.3% men; mean age 40.7 years) randomly recruited from European populations, we genotyped 25 tagging XOR SNPs and measured blood pressure (BP) at baseline and follow-up (median 8.8 years). The relation between variants of the XOR gene with changes in pulse pressure and mean arterial pressure over time; and incidence of hypertension, were analyzed., Results: Compared with nonminor allele carriers, pulse pressure increased approximately 2 mmHg more in minor allele carriers of rs11904439 (P = 0.01), whereas mean arterial pressure and DBP increased approximately 1 mmHg less in minor allele carriers of rs2043013 (P = 0.01). In 2050, participants normotensive at baseline, hazard ratios contrasting risk of hypertension in minor allele carriers vs. nonminor allele carriers were 1.31 (95% confidence interval 1.03-1.68; P = 0.02) and 1.69 (95% confidence interval 1.11-2.57; P = 0.01) for rs11904439 and rs148756340, respectively. With the false discovery rate set at 0.25, the aforementioned associations retained significance. The changes in SBP from baseline to follow-up and the serum levels of uric acid at baseline (n = 1949) were not associated with XOR., Conclusion: Pending confirmation, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in BP and in the risk of hypertension.

Context: Extrapolations from observational studies and short-term intervention trials suggest that population-wide moderation of salt intake might reduce cardiovascular events., Objective: To assess whether 24-hour urinary sodium excretion predicts blood pressure (BP) and health outcomes., Design, Setting, and Participants: Prospective population study, involving 3681 participants without cardiovascular disease (CVD) who are members of families that were randomly enrolled in the Flemish Study on Genes, Environment, and Health Outcomes (1985-2004) or in the European Project on Genes in Hypertension (1999-2001). Of 3681 participants without CVD, 2096 were normotensive at baseline and 1499 had BP and sodium excretion measured at baseline and last follow-up (2005-2008)., Main Outcome Measures: Incidence of mortality and morbidity and association between changes in BP and sodium excretion. Multivariable-adjusted hazard ratios (HRs) express the risk in tertiles of sodium excretion relative to average risk in the whole study population., Results: Among 3681 participants followed up for a median 7.9 years, CVD deaths decreased across increasing tertiles of 24-hour sodium excretion, from 50 deaths in the low (mean, 107 mmol), 24 in the medium (mean, 168 mmol), and 10 in the high excretion group (mean, 260 mmol; P < .001), resulting in respective death rates of 4.1% (95% confidence interval [CI], 3.5%-4.7%), 1.9% (95% CI, 1.5%-2.3%), and 0.8% (95% CI, 0.5%-1.1%). In multivariable-adjusted analyses, this inverse association retained significance (P = .02): the HR in the low tertile was 1.56 (95% CI, 1.02-2.36; P = .04). Baseline sodium excretion predicted neither total mortality (P = .10) nor fatal combined with nonfatal CVD events (P = .55). Among 2096 participants followed up for 6.5 years, the risk of hypertension did not increase across increasing tertiles (P = .93). Incident hypertension was 187 (27.0%; HR, 1.00; 95% CI, 0.87-1.16) in the low, 190 (26.6%; HR, 1.02; 95% CI, 0.89-1.16) in the medium, and 175 (25.4%; HR, 0.98; 95% CI, 0.86-1.12) in the high sodium excretion group. In 1499 participants followed up for 6.1 years, systolic blood pressure increased by 0.37 mm Hg per year (P < .001), whereas sodium excretion did not change (-0.45 mmol per year, P = .15). However, in multivariable-adjusted analyses, a 100-mmol increase in sodium excretion was associated with 1.71 mm Hg increase in systolic blood pressure (P.<001) but no change in diastolic BP., Conclusions: In this population-based cohort, systolic blood pressure, but not diastolic pressure, changes over time aligned with change in sodium excretion, but this association did not translate into a higher risk of hypertension or CVD complications. Lower sodium excretion was associated with higher CVD mortality.

Objectives: The International Database on Ambulatory Blood Pressure Monitoring (1993-1994) lacked a prospective dimension. We are constructing a new resource of longitudinal population studies to investigate with great precision to what extent the ambulatory blood pressure improves risk stratification., Methods: The acronym IDACO refers to the new International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome. Eligible studies are population based, have fatal as well as nonfatal outcomes available for analysis, comply with ethical standards, and have been previously published in peer-reviewed journals. In a meta-analysis based on individual patient data, composite and cause-specific cardiovascular events will be related to various indexes derived by ambulatory blood pressure monitoring. The analyses will be stratified by cohort and adjusted for the conventional blood pressure and other cardiovascular risk factors., Results: To date, the international database includes 7609 patients from four cohorts recruited in Copenhagen, Denmark (n=2311), Noorderkempen, Belgium (n=2542), Ohasama, Japan (n=1535), and Uppsala, Sweden (n=1221). In these four cohorts, during a total of 69,295 person-years of follow-up (median 9.3 years), 1026 patients died and 929 participants experienced a fatal or nonfatal cardiovascular event. Follow-up in five other eligible cohorts, involving a total of 4027 participants, is still in progress. We expect that this follow-up will be completed by the end of 2007., Conclusion: The international database of ambulatory blood pressure in relation to cardiovascular outcome will provide a shared resource to investigate risk stratification by ambulatory blood pressure monitoring to an extent not possible in any earlier individual study.