Belgian Study

Fatal and Nonfatal Outcomes, Incidence of Hypertension, and Blood Pressure Changes in Relation to Urinary Sodium Excretion

Katarzyna Stolarz-Skrzypek, Tatiana Kuznetsova, Lutgarde Thijs, Valérie Tikhonoff, Jitka Seidlerová, Tom Richart, Yu Jin, Agnieszka Olszanecka, Sofia Malyutina, Edoardo Casiglia, Jan Filipovský, Kalina Kawecka-Jaszcz, Yuri Nikitin, Jan A. Staessen, for the European Project on Genes in Hypertension (EPOGH) Investigators
JAMA.

2011;305(17):1777-1785.doi:10.1001/jama.2011.574

Author Affiliations

Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (Drs Stolarz-Skrzypek, Kuznetsova, Thijs, Richart, Jin, and Staessen); First Department of Cardiology and Hypertension, Jagiellonian University Medical College, Kraków, Poland (Drs Stolarz-Skrzypek, Olszanecka, and Kawecka-Jaszcz); Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy (Drs Tikhonoff and Casiglia); Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic (Drs Seidlerová and Filipovský); Institute of Internal Medicine, Novosibirsk, Russian Federation (Drs Malyutina and Nikitin); and Department of Epidemiology, Maastricht University, Maastricht, the Netherlands (Drs Richart and Staessen).

Abstract 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.

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