A total of 744 participants were randomised to a sodium intervention or control in TOHP I and 2382 in TOHP II (fig 1). Baseline characteristics were evenly distributed, except for age, which was higher in the sodium reduction intervention group in each trial (table 1).26 27
Change in weight was similar, and change in sodium excretion was greater among those randomised to sodium reduction interventions.
Fig 1 Flow of participants through two trials and status at follow-up
Table 1 Characteristics of participants in TOHP I and II according to allocation to sodium reduction intervention or control group. Numbers are means (SDs) unless stated otherwise
We obtained follow-up information on cardiovascular outcomes or death for 2415 participants (77%). Follow-up rates were similar in the sodium intervention and control groups, with higher response among those in TOHP II (table 2). We had information on mortality for all participants, including non-responders. Two hundred participants (8% of the responders) experienced study outcomes.
Table 2 Response to follow-up and cardiovascular disease and total mortality according to allocation to sodium intervention or control group
The crude rate of cardiovascular disease was somewhat lower among those assigned to the sodium reduction intervention (P=0.21 in stratified analysis) than corresponding controls (table 2). After adjustment for baseline characteristics, particularly the imbalance in age, there were significant differences between groups. Figure 2 shows adjusted cumulative incidence rates of cardiovascular disease by trial and intervention. After we controlled for clinic site, demographic information, and randomisation to a weight loss intervention (in TOHP II), the estimated reduction in relative risk of cardiovascular disease among those in the sodium reduction versus control interventions was 25% (relative risk 0.75, 95% confidence interval 0.57 to 0.99, P=0.04). Additional adjustment for baseline weight and sodium excretion strengthened the association (0.70, 0.53 to 0.94, P=0.02). Effect estimates were similar, although less significant, after further adjustment for change in weight during the trials (0.74, 0.55 to 1.01, P=0.06). Results were similar when we analysed them separately by trial. Analyses for interactions indicated that effects of the sodium reduction intervention were similar across categories defined by sex (P=0.98), race (white v black P=0.79, white v other P=0.63), age (30-44 v 45-54 years, P=0.43), body mass index (<25 v ≥25, P=0.34), and active weight loss intervention overall (P=0.55) or within TOHP II only (P=0.17) (table 3).When we excluded revascularisation procedures from the composite outcome, 124 participants experienced cardiovascular disease (76 myocardial infarctions, 19 strokes, six both, and 23 cardiovascular deaths with no previous reported myocardial infarction or stroke). The fully adjusted point estimates were similar to those for the primary outcome, but were not significant (0.72, 0.50 to 1.03, P=0.07).
Fig 2 Cumulative incidence of cardiovascular disease (CVD) by sodium intervention group in TOHP I and II, adjusted for age, sex, and clinic
Table 3 Effect of sodium reduction intervention on cardiovascular disease among subgroups in TOHP I and TOHP II, with hazard ratios for intervention versus control
Sixty seven of the 3126 participants died; 35 in the intervention groups and 42 in the comparison groups. The magnitude of risk reduction in this full intention to treat analysis was consistent with results for the primary outcome (table 2 and fig 3).After adjustment for baseline characteristics, including weight and sodium excretion, there was a 20% lower mortality among those in the sodium reduction intervention (0.80, 0.51 to 1.26, P=0.34). Results were similar for each trial. Twenty five deaths were due to cardiovascular disease; 10 in the intervention groups and 15 in the comparison groups (0.62, 0.28 to 1.40, P=0.25).
Fig 3 Total mortality by sodium intervention group in TOHP I and II, adjusted for age, sex, and clinic
The final follow-up questionnaire in 2004-5 about sodium use after the trial was received from 1400 (65%) of the 2164 event-free participants, with a higher response among those in the sodium reduction intervention in TOHP I (77% v 66% in intervention v control, respectively, P=0.01). In the two groups, 48% versus 32% (P<0.001) reported that they disliked salty foods, and 71% versus 64% (P=0.003) reported that they liked low sodium or unsalted foods. Additionally, 47% versus 29% reported that they usually or always used low sodium products (P<0.001); 66% versus 44% read food labels for sodium (P<0.001); and 28% versus 20% at least sometimes kept track of their daily intake of sodium (P<0.001) in the two groups, respectively.