Periodic Reporting for period 4 - COSIP (Clarifying Optimal Sodium Intake Project)
Reporting period: 2019-11-01 to 2020-10-31
Problem Being Addressed?
What is the optimal sodium (Salt) intake in populations?
Why is it important for Society?
All individuals consume sodium, most of which comes from salt intake, and some sodium intake is essential to health. However, high sodium (salt) intake is associated with hypertension and increased risk of cardiovascular disease (e.g. heart attack, stroke). Based on research on the association of sodium intake and blood pressure, current WHO guidelines recommend low sodium intake (<2.0 g/day). Recent observational research, however, has reported an increased risk of cardiovascular disease associated with low sodium intake (compared to moderate intake), which has created uncertainty about the optimal intake of sodium in populations. The COSIP research programme seeks to provide clarifying information on identifying the optimal range of sodium intake, through a series of related research studies.
What are the overall Objectives: of COSIP?
1. To determine whether sustained long-term low-sodium intake (compared to moderate intake) is associated with beneficial or adverse effects on biomarkers of cardiovascular risk.
2. To determine whether an ‘evening-bolus’ pattern of sodium consumption is associated with adverse effect on 24-hour blood pressure, compared to evenly distributed basal intake.
3. To determine whether the pattern and magnitude of association of sodium intake with cardiovascular and mortality varies by sex, ethnicity, dietary pattern and dietary factors.
4. To determine whether the pattern and magnitude of association of sodium intake with atrial fibrillation, syncope and falls.
5. To identify factors that may underlie the association between low sodium intake and increased risk of cardiovascular events and mortality.
6. To quantify the population-attributable fraction associated with sodium intake for cardiovascular events and mortality in 2 large epidemiologic studies in low, middle and high-income countries.
7. To explore the association of genetic variants (related to hypertension and proposed mechanism of ‘salt sensitivity’) with blood pressure and stroke, and further explore whether these polymorphisms modify the association of sodium intake with blood pressure and stroke risk.
What is the optimal sodium (Salt) intake in populations?
Why is it important for Society?
All individuals consume sodium, most of which comes from salt intake, and some sodium intake is essential to health. However, high sodium (salt) intake is associated with hypertension and increased risk of cardiovascular disease (e.g. heart attack, stroke). Based on research on the association of sodium intake and blood pressure, current WHO guidelines recommend low sodium intake (<2.0 g/day). Recent observational research, however, has reported an increased risk of cardiovascular disease associated with low sodium intake (compared to moderate intake), which has created uncertainty about the optimal intake of sodium in populations. The COSIP research programme seeks to provide clarifying information on identifying the optimal range of sodium intake, through a series of related research studies.
What are the overall Objectives: of COSIP?
1. To determine whether sustained long-term low-sodium intake (compared to moderate intake) is associated with beneficial or adverse effects on biomarkers of cardiovascular risk.
2. To determine whether an ‘evening-bolus’ pattern of sodium consumption is associated with adverse effect on 24-hour blood pressure, compared to evenly distributed basal intake.
3. To determine whether the pattern and magnitude of association of sodium intake with cardiovascular and mortality varies by sex, ethnicity, dietary pattern and dietary factors.
4. To determine whether the pattern and magnitude of association of sodium intake with atrial fibrillation, syncope and falls.
5. To identify factors that may underlie the association between low sodium intake and increased risk of cardiovascular events and mortality.
6. To quantify the population-attributable fraction associated with sodium intake for cardiovascular events and mortality in 2 large epidemiologic studies in low, middle and high-income countries.
7. To explore the association of genetic variants (related to hypertension and proposed mechanism of ‘salt sensitivity’) with blood pressure and stroke, and further explore whether these polymorphisms modify the association of sodium intake with blood pressure and stroke risk.
1. COSIP-1 trial is a Phase II clinical trial completed in April 2020 and will be reported shortly. COSIP-1 will determine whether sustained long-term low-sodium intake (compared to moderate intake) is associated with beneficial or adverse effects on biomarkers of CV risk.
2. COSIP-2 study, to determine whether within-day pattern of sodium consumption is associated with adverse effect on 24-hour blood pressure, compared to evenly distributed basal intake, has been initiated, and will be completed within 12 months. Results of the trial are expected before end of COSIP grant.
3. In the COSIP project, a number of observational studies have been completed, and some have been published in key journals. Additional manuscripts are being completed for publication in peer-review journals. Our findings from epidemiologic studies has reported that the association of high sodium intake and cardiovascular risk occurs mostly in people with hypertension, that the association of sodium intake and cardiovascular risk/mortality is J-shaped, and that the risk associated with high sodium intake appears to be mitigated by higher potassium intake and higher quality of overall diet. Our findings have been published in high-impact journals, including the BMJ, The Lancet and American Journal of hypertension, and presented at international conferences.
2. COSIP-2 study, to determine whether within-day pattern of sodium consumption is associated with adverse effect on 24-hour blood pressure, compared to evenly distributed basal intake, has been initiated, and will be completed within 12 months. Results of the trial are expected before end of COSIP grant.
3. In the COSIP project, a number of observational studies have been completed, and some have been published in key journals. Additional manuscripts are being completed for publication in peer-review journals. Our findings from epidemiologic studies has reported that the association of high sodium intake and cardiovascular risk occurs mostly in people with hypertension, that the association of sodium intake and cardiovascular risk/mortality is J-shaped, and that the risk associated with high sodium intake appears to be mitigated by higher potassium intake and higher quality of overall diet. Our findings have been published in high-impact journals, including the BMJ, The Lancet and American Journal of hypertension, and presented at international conferences.
Inform current recommendations on sodium (salt) intake:
Most of the world’s population consumes between 3 and 6 g/day of sodium (7.5-15 g of salt). International guidelines on CV disease prevention recommend that the entire population consume less than 2.0 g/day, but achieving this target will require a substantial change in diet for most people in Europe. Given the requirements to realistically achieve the target set by WHO (and other guidelines) of low sodium intake in the entire population, the evidence that underpins the recommendation for low sodium intake needs to be robust. Moreover, it is essential that population health resources are not invested in an intervention that is not effective (or feasible), or associated with adverse effects on sub-populations, especially where there are other areas in population health where these resources could be diverted (e.g. smoking cessation). COSIP employs novel outcomes in clinical trials of dietary interventions, and innovative approaches to determining the potential effect-modifying role of ethnicity, genetics and population characteristics. COSIP may also provide information about whether evening ‘bolus’ pattern of consumption has adverse effects on blood pressure pattern, which may have implications for both future research and recommendations. Finally, it may be that the controversy can only be resolved with a large definitive randomized controlled trial of CV events. The COSIP research projects will provide key information to guide the design and feasibility of studies trials, and I would plan to play a central role in future large clinical trials. Low sodium intake is a cornerstone paradigm of CV prevention guidelines, the COSIP research project will add further insights into current guideline recommendations, and may have a major impact on this area.
Most of the world’s population consumes between 3 and 6 g/day of sodium (7.5-15 g of salt). International guidelines on CV disease prevention recommend that the entire population consume less than 2.0 g/day, but achieving this target will require a substantial change in diet for most people in Europe. Given the requirements to realistically achieve the target set by WHO (and other guidelines) of low sodium intake in the entire population, the evidence that underpins the recommendation for low sodium intake needs to be robust. Moreover, it is essential that population health resources are not invested in an intervention that is not effective (or feasible), or associated with adverse effects on sub-populations, especially where there are other areas in population health where these resources could be diverted (e.g. smoking cessation). COSIP employs novel outcomes in clinical trials of dietary interventions, and innovative approaches to determining the potential effect-modifying role of ethnicity, genetics and population characteristics. COSIP may also provide information about whether evening ‘bolus’ pattern of consumption has adverse effects on blood pressure pattern, which may have implications for both future research and recommendations. Finally, it may be that the controversy can only be resolved with a large definitive randomized controlled trial of CV events. The COSIP research projects will provide key information to guide the design and feasibility of studies trials, and I would plan to play a central role in future large clinical trials. Low sodium intake is a cornerstone paradigm of CV prevention guidelines, the COSIP research project will add further insights into current guideline recommendations, and may have a major impact on this area.