Project Summary
High dietary sodium intake increases risk of cardiovascular disease (CVD) independent of established risk
factors, including blood pressure (BP). Non-BP mediated mechanisms underlying the increased risk of CVD
associated with dietary sodium intake are not well understood, but observational studies suggest direct target
organ damage in the heart and vasculature might play an important role. Little evidence exists from
randomized controlled trials (RCTs) on target organ effects of dietary sodium reduction, and the National
Academy of Medicine has recommended future research to “test the effects of different sodium intake levels on
endothelial and vascular function” in order to “to better characterize the relationship between sodium intake
and chronic disease”. Further, no RCTs have been powered to test the effect of dietary sodium reduction on
subclinical cardiovascular structure and function in African Americans, who are more sensitive to dietary
sodium intake and at higher risk for CVD. The overall objective of the proposed mechanistic trial is to test the
effect of dietary sodium reduction on cardiac and vascular structure and function. Specifically, the proposed
trial will test whether dietary sodium reduction (targeting a dietary sodium intake of <2,300 mg/day) will
improve left ventricular mass index (LVMI), left ventricular global longitudinal strain (LVGLS), carotid-femoral
pulse wave velocity (cfPWV), and flow-mediated dilation (FMD) compared to usual intake. Additionally, we will
test whether this effect is independent from BP reduction. We will recruit 240 African Americans with elevated
BP or hypertension from the greater New Orleans area and randomly assign them to a dietitian-led behavioral
intervention aimed at decreasing dietary sodium intake to <2,300 mg/day for 12 months or to a usual diet.
Study outcomes, including cardiac magnetic resonance imaging (CMR)-determined LVMI and LVGLS, cfPWV,
and FMD, will be measured at baseline, 6-month, and 12-month clinic visits using standardized protocols with
stringent quality control. These outcomes are validated biomarkers for target organ damage and predict the
risk of clinical CVD events. In primary analyses, the effect of sodium reduction on each subclinical CVD
endpoint will be compared between the sodium reduction and usual diet groups according to the intention-to-
treat principle without adjusting for covariates. In secondary analyses, changes in ambulatory and clinical BP
will be adjusted to assess the BP-independent effect of dietary sodium reduction on each subclinical CVD
endpoint. The proposed trial has 85% statistical power to detect a clinically significant difference in changes of
the four co-primary outcomes (10 g/m2 in LVMI, 1.3% in LVGLS, 0.9 m/s in cfPWV, and 1.1% in FMD) over 12
months between the two groups at a 2-sided significance level of 0.0125 (0.05/4). This study is the first RCT to
test the effect of dietary sodium reduction on subclinical CVD endpoints in African Americans. Findings from
this trial will fill the knowledge gap of the underlying mechanisms of dietary sodium intake on CVD risk and
provide further evidence on sodium reduction for CVD prevention.