Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Raised blood pressure (BP), cholesterol and smoking, are the major risk factors. Among these, raised BP is the most important cause, accounting for 62% of strokes and 49% of coronary heart disease. Importantly, the risk is throughout the range of BP, starting at systolic 115 mm Hg. There is strong evidence that our current consumption of salt is the major factor increasing BP and thereby CVD. Furthermore, a high salt diet may have direct harmful effects independent of its effect on BP, for example, increasing the risk of stroke, left ventricular hypertrophy and renal disease. Increasing evidence also suggests that salt intake is related to obesity through soft drink consumption, associated with renal stones and osteoporosis and is probably a major cause of stomach cancer. In most developed countries, a reduction in salt intake can be achieved by a gradual and sustained reduction in the amount of salt added to food by the food industry. In other countries where most of the salt consumed comes from salt added during cooking or from sauces, a public health campaign is needed to encourage consumers to use less salt. Several countries have already reduced salt intake, for example, Japan (1960–1970), Finland (1975 onwards) and now the United Kingdom. The challenge is to spread this out to all other countries. A modest reduction in population salt intake worldwide will result in a major improvement in public health.

A comprehensive review on salt and health and current experience of worldwide salt reduction programmes.

KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease

Background
A reduction in salt intake lowers blood pressure (BP) and, thereby, reduces cardiovascular risk. A recent meta-analysis by Graudal implied that salt reduction had adverse effects on hormones and lipids which might mitigate any benefit that occurs with BP reduction. However, Graudal's meta-analysis included a large number of very short-term trials with a large change in salt intake, and such studies are irrelevant to the public health recommendations for a longer-term modest reduction in salt intake. We have updated our Cochrane meta-analysis.  

Objectives
To assess (1) the effect of a longer-term modest reduction in salt intake (i.e. of public health relevance) on BP and whether there was a dose-response relationship; (2) the effect on BP by sex and ethnic group; (3) the effect on plasma renin activity, aldosterone, noradrenaline, adrenaline, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides.

Search methods
We searched MEDLINE, EMBASE, Cochrane Hypertension Group Specialised Register, Cochrane Central Register of Controlled Trials, and reference list of relevant articles.

Selection criteria
We included randomised trials with a modest reduction in salt intake and duration of at least 4 weeks.

Data collection and analysis
Data were extracted independently by two reviewers. Random effects meta-analyses, subgroup analyses and meta-regression were performed.

Main results
Thirty-four trials (3230 participants) were included. Meta-analysis showed that the mean change in urinary sodium (reduced salt vs usual salt) was -75 mmol/24-h (equivalent to a reduction of 4.4 g/d salt), the mean change in BP was -4.18 mmHg (95% CI: -5.18 to -3.18, I 2=75%) for systolic and -2.06 mmHg (95% CI: -2.67 to -1.45, I 2=68%) for diastolic BP. Meta-regression showed that age, ethnic group, BP status (hypertensive or normotensive) and the change in 24-h urinary sodium were all significantly associated with the fall in systolic BP, explaining 68% of the variance between studies. A 100 mmol reduction in 24 hour urinary sodium (6 g/day salt) was associated with a fall in systolic BP of 5.8 mmHg (95%CI: 2.5 to 9.2, P=0.001) after adjusting for age, ethnic group and BP status. For diastolic BP, age, ethnic group, BP status and the change in 24-h urinary sodium explained 41% of the variance between studies. Meta-analysis by subgroup showed that, in hypertensives, the mean effect was -5.39 mmHg (95% CI: -6.62 to -4.15, I 2=61%) for systolic and -2.82 mmHg (95% CI: -3.54 to -2.11, I 2=52%) for diastolic BP. In normotensives, the mean effect was -2.42 mmHg (95% CI: -3.56 to -1.29, I 2=66%) for systolic and -1.00 mmHg (95% CI: -1.85 to -0.15, I 2=66%) for diastolic BP. Further subgroup analysis showed that the decrease in systolic BP was significant in both whites and blacks, men and women. Meta-analysis of hormone and lipid data showed that the mean effect was 0.26 ng/ml/hr (95% CI: 0.17 to 0.36, I 2=70%) for plasma renin activity, 73.20 pmol/l (95% CI: 44.92 to 101.48, I 2=62%) for aldosterone, 31.67 pg/ml (95% CI: 6.57 to 56.77, I 2=5%) for noradrenaline, 6.70 pg/ml (95% CI: -0.25 to 13.64, I 2=12%) for adrenaline, 0.05 mmol/l (95% CI: -0.02 to 0.11, I 2=0%) for cholesterol, 0.05 mmol/l (95% CI: -0.01 to 0.12, I 2=0%) for LDL, -0.02 mmol/l (95% CI: -0.06 to 0.01, I 2=16%) for HDL, and 0.04 mmol/l (95% CI: -0.02 to 0.09, I 2=0%) for triglycerides.

Authors' conclusions
A modest reduction in salt intake for 4 or more weeks causes significant and, from a population viewpoint, important falls in BP in both hypertensive and normotensive individuals, irrespective of sex and ethnic group. With salt reduction, there is a small physiological increase in plasma renin activity, aldosterone and noradrenaline. There is no significant change in lipid levels. These results provide further strong support for a reduction in population salt intake. This will likely lower population BP and, thereby, reduce cardiovascular disease. Additionally, our analysis demonstrates a significant association between the reduction in 24-h urinary sodium and the fall in systolic BP, indicating the greater the reduction in salt intake, the greater the fall in systolic BP. The current recommendations to reduce salt intake from 9-12 to 5-6 g/d will have a major effect on BP, but are not ideal. A further reduction to 3 g/d will have a greater effect and should become the long term target for population salt intake.

Effect of longer-term modest salt reduction on blood pressure.

Reducing population salt intake worldwide: from evidence to implementation.

Diabetic nephropathy is a significant cause of chronic kidney disease and end-stage renal failure globally Much research has been conducted in both basic science and clinical therapeutics, which has enhanced understanding of the pathophysiology of diabetic nephropathy and expanded the potential therapies available This review will examine the current concepts of diabetic nephropathy management in the context of some of the basic science and pathophysiology aspects relevant to the approaches taken in novel, investigative treatment strategies

/pdf/diabetic-nephropathy-complications-and-treatment-arovwpix56.pdf

Diabetic nephropathy - complications and treatment.

OBJECTIVE —Diabetic subjects have a high prevalence of hypertension, increased total body exchangeable sodium levels, and an impaired ability to excrete a sodium load. This study assessed the effect of dietary sodium restriction on the efficacy of losartan in hypertensive subjects with type 2 diabetes and albumin excretion rates of 10–200 μg/min. RESEARCH DESIGN AND METHODS —In this study, 20 subjects were randomized to losartan 50 mg/day ( n = 10) or placebo ( n = 10). Drug therapy was given in two 4-week phases separated by a washout period. In the last 2 weeks of each phase, patients were assigned to low- or regular-sodium diets, in random order. In each phase, 24-h ambulatory blood pressure, urinary albumin-to-creatinine ratio (ACR), and renal hemodynamics were measured. RESULTS —Achieved urinary sodium on a low-sodium diet was 85 ± 14 and 80 ± 22 mmol/day in the losartan and placebo groups, respectively. In the losartan group, the additional blood pressure-lowering effects of a low-sodium diet compared with a regular-sodium diet for 24-h systolic, diastolic, and mean arterial blood pressures were 9.7 mmHg (95% confidence interval [CI], 2.2−17.2; P = 0.002), 5.5 mmHg (2.6−8.4; P = 0.002), and 7.3 mmHg (3.3− 11.3; P = 0.003), respectively. In the losartan group, the ACR decreased significantly on a low-sodium diet versus on a regular-sodium diet (−29% [CI −50.0 to −8.5%] vs. + 14% [−19.4 to 47.9%], respectively; P = 0.02). There was a strong correlation between fall in blood pressure and percent reduction in the ACR ( r = 0.7, P = 0.02). In the placebo group, there were no significant changes in blood pressure or ACR between regular- and low-sodium diets. There were no significant changes in renal hemodynamics in either group. CONCLUSIONS —These data demonstrated that a low-sodium diet potentiates the antihypertensive and antiproteinuric effects of losartan in type 2 diabetes. The blood pressure reduction resulting from the addition of a low-sodium diet to losartan was of similar magnitude to that predicted from the addition of a second antihypertensive agent.

https://care.diabetesjournals.org/content/diacare/25/4/663.full.pdf

Amynta L. Baxter

Papers

A Low-Sodium Diet Potentiates the Effects of Losartan in Type 2 Diabetes