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. 2022 Aug 10;2022(8):CD015207. doi: 10.1002/14651858.CD015207

Suppa 1988.

Study characteristics
Methods Study design: Randomised controlled trial
Study grouping: Parallel group
Country: Italy
Setting: Intervention conducted in households; outcomes measured at 31 clinical centres
Aim of study: To evaluate the effects of a low‐sodium/high potassium salt as an additional treatment in patients with mild and moderate hypertension on beta‐blockers
Unit of allocation: adults (aged 18 years or older)
Start date: NR
End date: NR
Relevant study limitations as reported by study authors: NR
Sample size calculation: NR
Participants Baseline Characteristics
LSSS intervention

  • Age: in years, mean (SD): 47.1 (9.8)

  • Gender: Female, % (n/N): 35.6 (58/163)

  • Ethnicity/race: European

  • Smoking: NR

  • Body Mass Index (BMI): NR

  • Blood pressure status: WHO stage I hypertension, % (n/N): 65 (106/163); stage II hypertension, % (n/N): 35 (57/163)

  • Antihypertensive medication used: β‐blocker monotherapy (metoprolol), % (n/N): 100 (163/163)

  • Cardiovascular disease or stroke: NR

  • Diabetes mellitus: NR

  • Renal impairment: Serum creatinine >= 1.5 mg/dL (133 µmol/L), % (n/N): 0 (0/163)

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: in mmol/24‐h, mean (SD): 65.5 (20.6)

  • Urinary sodium excretion: in mmol/24‐h, mean (SD): 205.5 (76.9)


Control

  • Age: in years, mean (SD): 47.8 (10.1)

  • Gender: Female, % (n/N): 39 (62/159)

  • Ethnicity/race: European

  • Smoking: NR

  • Body Mass Index (BMI): NR

  • Blood pressure status: WHO stage I hypertension, % (n/N): 65.4 (104/159); stage II hypertension, % (n/N): 34.6 (55/159)

  • Antihypertensive medication used: β‐blocker monotherapy (metoprolol), % (n/N): 100 (159/159)

  • Cardiovascular disease or stroke: NR

  • Diabetes mellitus: NR

  • Renal impairment: Serum creatinine >= 1.5 mg/dL (133 µmol/L), % (n/N): 0 (0/159)

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: in mmol/24‐h, mean (SD): 67.4 (21.8)

  • Urinary sodium excretion: in mmol/24‐h, mean (SD): 211.1 (90.6


Inclusion criteria: Participants with supine diastolic BP greater or equal to 95 mmHg only taking metoprolol 200 mg daily
Exclusion criteria: Patients with contraindications for β‐blockers; secondary hypertension; renal failure (serum creatinine >= 1.5 mg/dL or 133 µmol/L; eGFR females, mean age 47 years: 41mL/min; males, mean age 47 years: 54 mL/min) or other major diseases, and women of childbearing potential
Pretreatment: None
Method of recruitment of participants: NR
Informed consent obtained: NR
Clusters: n/a
Subgroups planned/measured: NR
Subgroups reported: NR
 
Participant flow
Assessed for eligibility: n = 358
Excluded (number with reasons): n = 36 (n = 6 due to undesirable side effects such as asthenia, insomnia, hypotension and headaches, n = 4 due to severe hypertension, n = 26 for poor compliance mainly to collecting urine samples)
Randomised: n = 322
Allocated to LSSS intervention(s): n = 163
Allocated to control: n = 159
Received allocated LSSS intervention(s): NR
Did not receive allocated LSSS intervention(s): NR
Lost to follow‐up (LSSS intervention group): n = 0
Discontinued intervention (LSSS intervention group): n = 0
Analysed (LSSS intervention group): n = 163
Excluded from analysis (LSSS intervention group): n = 0 (DBP; SBP) n = 50; (urinary sodium and potassium): Study authors only analysed data from participants if 3 urine samples were correctly collected.
Received allocated control: NR
Did not receive allocated control: NR
Lost to follow‐up (control group): n = 0
Discontinued intervention (control group): n = 0
Analysed (control group): n = 159
Excluded from analysis (control group): n = 0 (DBP, SBP) n = 51 (urinary sodium and potassium): Study authors only analysed data from participants who collected 3 urine samples correctly.
Interventions Intervention Characteristics
LSSS intervention

  • Theoretical basis: Increased potassium salt intake may exert antihypertensive effects by means of vasodilation, natriuresis, decreased sympathetic tone and stimulation of Na/K pump activation.

  • Description: Dietary salt (Novasal) (NaCl 50%, KCl 25% and K3C6H5 O7 15%): 4 g (34 mmol Na; 19.3 mmol K)

  • LSSS category: < 30% KCl

  • Contains fortificant: NR

  • Delivery: Discretionary use

  • Duration of run‐in period: 6 weeks (2‐week washout period; 4‐week period of β‐blocker monotherapy)

  • Duration of active intervention: 4 weeks

  • Duration of follow‐up (as reported): none

  • Total duration of study (as reported): 4 weeks

  • Timing: 2 g twice daily at lunch and dinner, used at the table

  • Implementation: identical 2 g packets

  • Providers: NR

  • Co‐interventions: Metoprolol 200 mg daily

  • Resource requirements: NR

  • Integrity of delivery: 'Common' salt used in cooking; dietary habits remained unchanged. The number of residual salt packets and metoprolol tablets were counted at each visit. Number of salt packets consumed per day: NR; pill counts (metoprolol tablets): NR


Control

  • Theoretical basis: To enable comparison of LSSS intervention with standard practice

  • Description: 'Common' salt (100% NaCl): 4 g (174 mmol Na)

  • Contains fortificant: NR

  • Delivery: Discretionary use

  • Duration of run‐in period: 6 weeks (2‐week washout period; 4‐week period of β‐blocker monotherapy)

  • Duration of active intervention: 4 weeks

  • Duration of follow‐up (as reported): none

  • Total duration of study (as reported): 4 weeks

  • Timing: 2 g twice daily at lunch and dinner used at the table

  • Implementation: identical 2 g packets

  • Providers: NR

  • Co‐interventions: Metoprolol 200 mg daily

  • Resource requirements: NR

  • Integrity of delivery: 'Common' salt used in cooking; dietary habits remained unchanged. The number of residual salt packets and metoprolol tablets were counted at each visit. Number of salt packets consumed per day: NR; pill counts (metoprolol tablets): NR
Outcomes Outcomes
Primary outcomes: 

  • Diastolic Blood Pressure (DBP): Outcome measurement: measurement with conventional mercury sphygmomanometer according to WHO guidelines. Time point: supine DBP, standing DBP 2, 4 weeks

  • Systolic Blood Pressure (SBP): Outcome measurement: measurement with conventional mercury sphygmomanometer according to WHO guidelines. Time point: supine, standing SBP at 2, 4 weeks

  • Hypertension (as reported, or SBP > 140 mmHg or DBP > 85 mmHg): NR

  • Blood pressure control (achieving blood pressure threshold or 'control' as prespecified): NR

  • Cardiovascular events‐stroke: NR

  • Cardiovascular events‐myocardial infarction: NR

  • Cardiovascular events‐other: bradycardia; outcome measurement: NR; time points: 2, 4 weeks

  • Cardiovascular mortality: NR

  • Blood potassium: NR

  • Hyperkalaemia: NR

  • Hypokalaemia: NR


Secondary outcomes: 

  • All‐cause mortality: NR

  • Adverse events: mild drowsiness, insomnia, decreased libido, depression, asthenia; outcome measurement: NR; time points: duration of study

  • Antihypertensive medication use: NR

  • Body Mass index (BMI): NR

  • Serum creatinine: NR

  • Albuminuria: NR

  • Urinary albumin‐to‐creatinine ratio (uACR): NR

  • Fasting blood glucose: NR

  • Blood triglycerides: NR

  • Total blood cholesterol: NR

  • 24‐h urinary sodium excretion: 24‐hour urine sample. Time points: 4 weeks

  • 24‐h urinary potassium excretion: 24‐hour urine sample. Time points: 4 weeks
Notes Funding source: NR
Authors name: Giuseppe Suppa
Institution: The Italian Group for the Prevention and Care of Arterial Hypertension
Email: NR
Possible conflicts of interest (for study authors): NR
Sources used for data extraction: Journal article with results of the trial
Trial registration details: NR
 
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Insufficient information on how the randomisation sequence was generated
Allocation concealment (selection bias) Unclear risk Insufficient information on how the randomisation sequence was protected
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk The study was reported as 'double‐blinded' but it was unclear what this meant. The salt was packaged in identical packets; therefore it was likely that participants were blinded. However, it was unclear whether the personnel were blinded.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk The study was reported as 'double blinded', but it was unclear what this meant. BP measurements were conducted with a non‐automated conventional device and therefore detection bias was possible if outcome assessors were not blinded.
Incomplete outcome data (attrition bias)
All outcomes Low risk No incomplete data reported for SBP, DBP outcomes
Selective reporting (reporting bias) Unclear risk Study protocol or prospective trial registry entry not available
Other bias Low risk None identified
Overall risk of bias Unclear risk Unclear risk of bias for allocation concealment; low risk of bias for incomplete outcome data