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Potassium and Hypertension:

Basis for a NRV-NCD

Mary R. L’Abbé, PhDEarle W. McHenry Professor and

Chair, Department of Nutritional Sciences

CRN-I Annual Symposium

Codex CCNFSDU - Kronberg, GermanyNovember 20, 2015

10%

0

5,000,000

10,000,000

15,000,000

20,000,000

25,000,000

0-29 30-69 70-80+

Communicable,maternal, perinatal andnutritional conditions

Noncommunicablediseases

Injuries

De

ath

s in

20

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In 2011, 13.8 million people, between age of 30-70, died from NCDs: More than 85% of these deaths occurred in developing countries

Source: WHO, Sept 2014

GENERAL PRINCIPLES FOR

ESTABLISHING NRVs

For individuals older than 36 months

Daily intake values refer to nutrient intakes provided by FAO/WHO (or other recognized scientific bodies) … that are based on a recent review of the science should be taken into consideration as the primary source in establishing NRVs

INL98 is the daily intake reference value to meet the nutrient requirement of 98% of the population

Source: Codex Alimentarius GUIDELINES ON NUTRITION LABELLING

CAC/GL 2-1985 (rev 2015)

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SELECTION OF NUTRIENTS AND

APPROPRIATE BASIS FOR NRVS-NCD

Convincing/ generally accepted scientific evidence or the

comparable level of evidence under the GRADE

classification

relationship between a nutrient and NCD risk, including

validated biomarkers for the disease risk, for at least one

major segment of the population (e.g. adults).

Public health importance of the nutrient-NCD

relationship(s)

Relevant and peer-reviewed scientific evidence for

quantitative reference values for daily intake

Source: Codex Alimentarius GUIDELINES ON NUTRITION LABELLING

CAC/GL 2-1985 (rev 2015)

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WHO REPORTS

Source: http://www.who.int/nutrition/publications/guidelines/potassium_intake/en/

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Nutrition Guidelines Led by the WHO Dept. of Nutrition for Health and

Development

WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health (15 members)

• Multidisciplinary, regional representation

• Subject and technical experts/methodologists without competing conflicts of interest

• No commercial or industry representatives

• Plus 7 External Resource persons who did not participate in decision making

External groups provided comments on: • Priority questions; and

• Draft guidelines

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PROCESS ISSUESTaken from my experiences with WHO

Nutrition Guidance Expert Advisory Committee – Subcommittee on Diet and

Chronic Disease (NUGAG)*

*With information provided by Dr. Joerg Meerpohl, Co-Director, Cochrane

Germany; University of Freiburg, GRADE Methodology External Resource

Person

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SYSTEMATIC REVIEW OF

ALL THE EVIDENCE …

THE GRADE PROCESS

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Guideline Development ProcessPrioritize Problems, establish panel

Systematic Review

Evidence Profile

Relative importance of outcomes

(Overall) quality of evidence

Benefit – downside evaluation

Strength of recommendation

Implementation and evaluation of guidelines

GRADE

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Quality of Evidence

Likelihood of,

and

confidence in

an outcome

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Simple hierarchies are (too) simplistic

STUDY DESIGN

• Randomized Controlled Trials

• Prospective Cohort Studies and

Case Control Studies

• Case Reports and Case Series,

Non-systematic observations

• Ecologic studies

BIAS

Exp

ert Op

inio

n

Adapted from Schünemann & Bone, 2003

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GRADE – Assessment of quality

Quality of evidence

Study design Rating down if… Rating up if…

High randomized study (RCT)

study limitations-1 serious-2 very seriousinconsistency- 1 serious- 2 very seriousindirectness-1 serious-2 very seriousimprecision-1 serious-2 very seriouspublication bias-1 likely-2 very likely

magnitude of effect+ 1 large+ 2 very large

dose-response gradient+ 1 evidence of an

application outcome relationship

all plausible confounding+ 1 would reduce a

demonstrated effect + 1 would suggest a spurious

effect when results show no effect

Middle

Low observational study

Very low

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Study Design and Execution

From Cates , CDSR 2008

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Is the evidence sound? Observational

Studies

Overall judgment required

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Inconsistency of results - heterogeneity

Look for explanations

• patients, intervention(s), outcome, methods

Judgment of consistency

• variation in size of effect

• poor overlap in confidence intervals

• statistical significance of heterogeneity

• high I2

Unexplained inconsistency downgrade quality

Guyatt et al. JCE 2011

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Rating up quality of evidenceparticularly relevant for observational studies

3 categories:

• Magnitude of effect

– large: RR > 2 (< 0,5): rate up +1

– very large: RR > 5 (< 0,2): rate up +2

– Particulary if there are more than two observational

studies without plausible confounders and consistent

results

• existence of a dose-response gradient for the outcome of

interest: rate up +1

• all remaining, plausible confounding would reduce the

estimated effect or suggest a spurious effect when results

show no effect: rate up +1

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Systematic review

F

PICO

Outcome

Outcome

Outcome

Outcome

Critical

Important

Critical

NotSummary of findings & estimate of effect for each outcome

Grade overall quality of evidence

across a variety of outcomes

1. Risk of bias2. Inconsistency3. Indirectness4. Imprecision5. Publication

bias

Gra

de

d

ow

nG

rad

e u

p 1. Large effect2. Dose

response3. Opposing bias/

Confounders

Very low

Low

Moderate

High

Governments and OthersScientific Review

Quality of evidence

Balance benefits/harms

Risk Management

Values and preferences

Intended use/application

Resource use (cost)

WHO Guidelines

OOO

O

OO

National Policy RecommendationsCodex Guidelines

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Outcome – Resting Systolic BP

Summary

21 Studies

-3.06

(-4.70 to -1.42)

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Greatest impact, when achieved a potassium intake of 90–120 mmol/ day (3510

– 4680 mg) 5.82 mmHg (95%CI: -0.79, 12.43) (quality of evidence moderate).

SBP - Effect higher in Hypertensives

Summary

16 Studies in

hypertensives

-4.68

(-6.96 to -2.40)

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Outcome – Resting Diastolic BP

Summary

21 Studies

-2.84

(-4.66 to -1.01)

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Greatest impact, when achieved a potassium intake of 90–120 mmol/ day (3510

– 4680 mg) of 3.52 mmHg (95%CI: -1.24, 8.28) (quality of evidence moderate).

DBP- Effect higher in Hypertensives

Summary

16 Studies in

hypertensives

-3.66

(-6.40 to -0.91)

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SUB-GROUP EFFECT ESTIMATES

BP Status (normotensive, hypertensive, mixed)

Achieved K intake in intervention (<70, 70-90, 90-120, >120

mmol)

Difference in achieved K intakes - intervention vs control

(<30, 30-60, >60 mmol)

K intake at baseline (40 vs 40-60 vs >60)

Na intake at baseline (<2, 2-4, >4 g/day)

Duration (<2, 2-4, >4 months)

Type of BP device (automatic, manual)

Type of BP measure (supine, seated, standing, ND)

Hypertension medication status (No, Yes, mixed/ND)

Study design (parallel vs cross-over)

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GRADE - Summary of Findings

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Resting BP reduced by 3.06 mm Hg with increased K intake

CONTEXT

Blood pressure as a valid biomarker for hard outcomes.

Hypertension is considered a major risk factor for CVD 1,

especially CHD and stroke; estimated to contribute to 49%

of all CHD and 62% of all stroke 2

Blood pressure during childhood has a significant

association with blood pressure during adulthood, and are

at high risk as adults 3 and during childhood itself 4

IOM Evaluation of Biomarkers and Surrogate Outcomes

(2010) and others

1 Lewington S, et al. Lancet, 2002 2 Mackay et al., Atlas of Heart Disease and Stroke, WHO

2004; 3 Chen X, Wang Y. Circulation, 2008; 4 Daniels et al. Circulation, 1998,

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WHO recommends an increase in potassium intake

from food to reduce blood pressure and risk of

cardiovascular disease, stroke and coronary heart

disease in adults (strong recommendation 1). WHO

suggests a potassium intake of at least 90 mmol/day

(3510 mg/day) for adults (conditional recommendation

2).

WHO suggests an increase in potassium intake from

food to control blood pressure in children (conditional

recommendation). The recommended potassium intake

of at least 90 mmol/day should be adjusted downward

for children, based on the energy requirements of

children relative to those of adults.

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WHO RECOMMENDATIONS FROM

EVIDENCE REVIEW

Examples of Typical Potassium Levels

in Foods

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Codex Guidelines on Nutrition

Labelling CAC/GL 2-1985 (rev 2015)

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10 The selection of these nutrients for the establishment of an NRV was based on “high quality” evidence for a

relationship with a biomarker for NCD risk in adults as reported in the respective 2012 WHO Guidelines on

sodium and potassium intake for adults and children.

Funding

Thank You - QuestionsMary R. L’Abbe, PhD

Earle W. McHenry Professor, and

Chair, Department of Nutritional Sciences

Faculty of Medicine, University of Toronto

FitzGerald Building, 150 College Street

Toronto, ON, Canada M5S 3E2

mary.labbe@utoronto.ca

E.W. McHenry

Endowed Chair

(M. L’Abbe)

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