METHODS: We enrolled 75 hypertensive patients with CKD into one-month salt restricting diet. 24-hour urinary sodium and potassium was measured to verify their salt intake followed by 1½ year follow-up.
RESULTS: Their creatinine clearance was 43 ± standard deviation 33ml/min/1.73m2. Urinary Na excretion (24HUNa) was 173±129mmol/day, reducing to 148±81 by 31±6 day. Mean, systolic and diastolic BP (MBP, SBP, DBP) were reduced from 102±9 to 97±11 (p<0.001), 148±10 to 139±16 (p<0.001), 78±12 to 75±12 mmHg (p=0.012) respectively. Moderate correlations were shown between reductions in 24-hour urinary Na and MBP, SBP, DBP: r=0.366, 0.260, 0.365; p=0.001, 0.025, 0.001; whereas 24-hour urinary Na-K ratio showed mild correlation. Subjects have some tendency to drift back to previous Na intake profile in follow-up and thus repetitive education is necessary. In subanalysis, 34 subjects with baseline 24HUNa >150 mmol/day, benefited significantly with MBP, SBP, DBP reduction from 102±9 to 95±9 (p=0.001), 146±10 to 135±14 mmHg (p=0.001), 80±11 to 75±11 mmHg (p=0.002) in line with 24HUNa reduction from 253±154 to 163±87mmol/day (p=0.004) and urinary protein-creation ratio reduction from geometric mean of 95 to 65 g/mol. Thirty five subjects with 24HUNa reduction of >20mmol/day have significant reduction in MBP, SBP, DBP: -8 vs -2, -15 vs -4, -5 vs -2 mmHg (p=0.027, 0.006, 0.218) and urinary protein-creatinine ratio: -82 vs 2g/mol (p=0.030) compared to the other forty subjects.
CONCLUSION: Quantification of 24-hour urinary Na helps in predicting potential antihypertensive effect with dietary salt reduction of CKD subjects. Salt restriction reduces BP especially in patients with estimated daily sodium intake of >150mmol/day. Reduction in sodium intake beyond 20mmol/day reduced both BP and proteinuria.
METHODS: The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all >50 participants) and cardiovascular disease and mortality in 255 communities (all >100 participants), and used individual-level data to adjust for known confounders.
FINDINGS: 95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p<0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile <4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile >5·08 g/day, mean intake 5·75 g/day, >5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p<0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries.
INTERPRETATION: Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate.
FUNDING: Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.
METHODS: In this pooled analysis, we studied 133,118 individuals (63,559 with hypertension and 69,559 without hypertension), median age of 55 years (IQR 45-63), from 49 countries in four large prospective studies and estimated 24-h urinary sodium excretion (as group-level measure of intake). We related this to the composite outcome of death and major cardiovascular disease events over a median of 4.2 years (IQR 3.0-5.0) and blood pressure.
FINDINGS: Increased sodium intake was associated with greater increases in systolic blood pressure in individuals with hypertension (2.08 mm Hg change per g sodium increase) compared with individuals without hypertension (1.22 mm Hg change per g; pinteraction<0.0001). In those individuals with hypertension (6835 events), sodium excretion of 7 g/day or more (7060 [11%] of population with hypertension: hazard ratio [HR] 1.23 [95% CI 1.11-1.37]; p<0.0001) and less than 3 g/day (7006 [11%] of population with hypertension: 1.34 [1.23-1.47]; p<0.0001) were both associated with increased risk compared with sodium excretion of 4-5 g/day (reference 25% of the population with hypertension). In those individuals without hypertension (3021 events), compared with 4-5 g/day (18,508 [27%] of the population without hypertension), higher sodium excretion was not associated with risk of the primary composite outcome (≥ 7 g/day in 6271 [9%] of the population without hypertension; HR 0.90 [95% CI 0.76-1.08]; p=0.2547), whereas an excretion of less than 3 g/day was associated with a significantly increased risk (7547 [11%] of the population without hypertension; HR 1.26 [95% CI 1.10-1.45]; p=0.0009).
INTERPRETATION: Compared with moderate sodium intake, high sodium intake is associated with an increased risk of cardiovascular events and death in hypertensive populations (no association in normotensive population), while the association of low sodium intake with increased risk of cardiovascular events and death is observed in those with or without hypertension. These data suggest that lowering sodium intake is best targeted at populations with hypertension who consume high sodium diets.
FUNDING: Full funding sources listed at end of paper (see Acknowledgments).