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. 2020 Apr 22;369:m824.
doi: 10.1136/bmj.m824.

Estimated Population Wide Benefits and Risks in China of Lowering Sodium Through Potassium Enriched Salt Substitution: Modelling Study

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Free PMC article

Estimated Population Wide Benefits and Risks in China of Lowering Sodium Through Potassium Enriched Salt Substitution: Modelling Study

Matti Marklund et al. BMJ. .
Free PMC article

Abstract

Objectives: To estimate the effects of nationwide replacement of discretionary salt (used at table or during cooking) with potassium enriched salt substitute on morbidity and death from cardiovascular disease in China.

Design: Modelling study.

Setting: China.

Population: Adult population in China, and specifically individuals with chronic kidney disease (about 17 million people).

Interventions: Comparative risk assessment models were used to estimate the effects of a nationwide intervention to replace discretionary dietary salt with potassium enriched salt substitutes (20-30% potassium chloride). The models incorporated existing data and corresponding uncertainties from randomised trials, the China National Survey of Chronic Kidney Disease, the Global Burden of Disease Study, and the Chronic Kidney Disease Prognosis Consortium.

Main outcome measures: Averted deaths from cardiovascular disease, non-fatal events, and disability adjusted life years from a reduction in blood pressure were estimated after implementation of potassium enriched salt substitution. In individuals with chronic kidney disease, additional deaths from cardiovascular disease related to hyperkalaemia from increased intake of potassium were calculated. The net effects on deaths from cardiovascular disease were estimated as the difference and ratio of averted and additional deaths from cardiovascular disease.

Results: Nationwide implementation of potassium enriched salt substitution could prevent about 461 000 (95% uncertainty interval 196 339 to 704 438) deaths annually from cardiovascular disease, corresponding to 11.0% (4.7% to 16.8%) of annual deaths from cardiovascular disease in China; 743 000 (305 803 to 1 273 098) non-fatal cardiovascular events annually; and 7.9 (3.3 to 12.9) million disability adjusted life years related to cardiovascular disease annually. The intervention could potentially produce an estimated 11 000 (6422 to 16 562) additional deaths related to hyperkalaemia in individuals with chronic kidney disease. The net effect would be about 450 000 (183 699 to 697 084) fewer deaths annually from cardiovascular disease in the overall population and 21 000 (1928 to 42 926) fewer deaths in individuals with chronic kidney disease. In deterministic sensitivity analyses, with changes to key model inputs and assumptions, net benefits were consistent in the total population and in individuals with chronic kidney disease, with averted deaths outweighing additional deaths.

Conclusions: Nationwide potassium enriched salt substitution in China was estimated to result in a substantial net benefit, preventing around one in nine deaths from cardiovascular disease overall. Taking account of the risks of hyperkalaemia, a substantial net benefit was also estimated for individuals with chronic kidney disease.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from Bloomberg Philanthropies, the Bill and Melinda Gates Foundation, Gates Philanthropy Partners, and the Chan Zuckerberg Foundation for the submitted work; LH, MM, BN, and JHYW report research funding from the National Health and Medical Research Council, and JHYW reports research funding from UNSW. MT, BN, JHYW, and LH report provision of salt substitute for research trials by Beijing Salt Manufacturing, Jiangsu Sinokone Technology, and NuTek. RG reports research grants from the National Institutes of Health, outside the present work. KM reports grants and personal fees from Kyowa Kirin and personal fees from Akebia, outside the submitted work. RM reports research grants from the National Institutes of Health (NIH) and Bill and Melinda Gates Foundation, Nestle, and Danone; and personal fees from Bunge and Development Initiatives; all outside the present work. LJA reports research grants from NIH and honorariums from UpToDate, outside the present work. DM reports research funding from NIH and the Bill and Melinda Gates Foundation; personal fees from GOED, Danone, Motif FoodWorks, Nutrition Impact, Pollock Communications, Bunge, Indigo Agriculture, Amarin, Acasti Pharma, Cleveland Clinic Foundation, and America’s Test Kitchen; scientific advisory board, Elysium Health (with stock options), Omada Health, and DayTwo; and chapter royalties from UpToDate; all outside the submitted work.

Figures

Fig 1
Fig 1
Conceptual models used to estimate benefits, harms, and net effects of replacing dietary salt (sodium chloride) with potassium enriched salt substitutes. Distribution of potassium enriched salt substitutes to replace dietary salt was expected to reduce blood pressure in the adult population, with greater effects at older ages. In 24 age-sex groups, blood pressure distribution before the intervention and the lower blood pressure distribution after the intervention (that is, after replacement) were used to calculate a potential impact fraction (PIF), with risk estimates for blood pressure on outcomes of cardiovascular disease, for each of 11 subtypes of cardiovascular disease. The age, sex, and subtype specific PIF was multiplied by the pre-intervention estimates of the same groups for deaths from cardiovascular disease, non-fatal events, or disability adjusted life years to estimate the number of averted deaths, non-fatal events, or disability adjusted life years. In each age-sex group, the total number of averted deaths from cardiovascular disease, prevalence of chronic kidney disease, and the death risk from cardiovascular disease in patients with chronic kidney disease (compared with others) were used to estimate the number of averted deaths from cardiovascular disease attributed to individuals with chronic kidney disease. For each chronic kidney disease stage (G3a, G3b, G4, and G5), estimates of the expected increase in potassium intake from replacement of dietary salt with potassium enriched salt substitutes, the dose-response relation of dietary and serum potassium, and pre-intervention serum potassium distribution were used to estimate the post-intervention serum potassium distribution. The serum potassium distributions (before and after the intervention) and known risk estimates of serum potassium with deaths from cardiovascular disease were used to calculate a PIF for each chronic kidney disease stage. The PIF and stage specific estimate of pre-intervention deaths from cardiovascular disease were used to calculate the additional deaths from cardiovascular disease. The additional deaths were subtracted from averted deaths to estimate net benefits (averted deaths) in individuals with chronic kidney disease exclusively and in the total adult population, including those with chronic kidney disease. Table 1 presents the model inputs and the appendix provides detailed information and rationales on model calculations and assumptions
Fig 2
Fig 2
Ratio of averted-to-additional deaths from cardiovascular disease in individuals with chronic kidney disease and in the total adult population in China, including individuals with chronic kidney disease, estimated by the primary model and by one way deterministic sensitivity analyses. Diamonds represent point estimates and error bars 95% uncertainty intervals. Values above one indicate net benefit (that is, greater number of deaths averted from reduction in systolic blood pressure than additional deaths from increased serum potassium). Hernandez et al conducted meta-analyses to evaluate the effect of salt substitutes on blood pressure and excretion of potassium in 24 hours. The estimates for excretion of potassium (11.5 mmol/day, 95% confidence interval 8.4 to 14.6) were multiplied by a factor of 1.3 to estimate the corresponding increase in potassium intake and changed the assumptions of the effects of blood pressure and potassium intake in the sensitivity analysis

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