Reduced Dietary Sodium Intake Increases Heart Rate. A Meta-Analysis of 63 Randomized Controlled Trials Including 72 Study Populations

Reduced dietary sodium intake (sodium reduction) increases heart rate in some studies of animals and humans. As heart rate is independently associated with the development of heart failure and increased risk of premature death a potential increase in heart rate could be a harmful side-effect of sodium reduction. The purpose of the present meta-analysis was to investigate the effect of sodium reduction on heart rate. Relevant studies were retrieved from an updated pool of 176 randomized controlled trials (RCTs) published in the period 1973–2014. 63 of the RCTs including 72 study populations reported data on heart rate. In a meta-analysis of these data sodium reduction increased heart rate with 1.65 beats per minute [95% CI: 1.19, 2.11], p < 0.00001, corresponding to 2.4% of the baseline heart rate. This effect was independent of baseline blood pressure. In conclusion sodium reduction increases heart rate by as much (2.4%) as it decreases blood pressure (2.5%). This side-effect, which may cause harmful health effects, contributes to the need for a revision of the present dietary guidelines

Dose-response relation between dietary sodium and blood pressure:a meta-regression analysis of 133 randomized controlled trials

BACKGROUND:The projected reduced mortality effect of reduced sodium intake in model-based studies conflicts with the observed increased mortality associated with low sodium intake in population studies. This may reflect an overestimation of the dose-response relation between sodium reduction (SR) and blood pressure (BP) used in mortality modeling studies. OBJECTIVES:The present meta-regression analysis sought to estimate the dose-response relations between SR and BP in study groups with mean BP above or below the 75th percentile of the general population. METHODS:Based on a literature search from 1 January 1946 to 11 April 2018, we identified 133 randomized controlled trials allocating healthy or hypertensive individuals to SR or usual sodium intake. Multivariable regression analyses of the mean SR versus the mean blood pressure effect adjusted for effect modifiers were performed. RESULTS:In study groups with mean BP above the 75th percentile [131/78 mm Hg systolic BP (SBP)/diastolic BP (DBP)], there was strong evidence of a linear dose-response relation between SR and BP. For SBP, the dose-response relation was -7.7 mm Hg/100 mmol SR (95% CI: -10.4, -5.0), and for DBP it was -3.0 mm Hg/100 mmol SR (95% CI: -4.6, -1.4). In study groups with mean BP ≤ 131/78 mm Hg, the relation between SR and BP was weak. For SBP it was -1.46 mm Hg/100 mmol SR (95% CI: -2.7, -0.20) and for DBP it was: -0.07 mm Hg/100 mmol SR (95% CI: -1.5, 1.4). CONCLUSIONS:Only study groups with a BP in the highest 25th percentile of the population showed a clinically significant drop in BP with SR. The policy of lowering dietary sodium intake in the general population may need to be reframed to target patients with hypertension. This study was registered at PROSPERO 2015 as CRD42015017773

CD20 inhibitor treatment combined with single DMARD versus single DMARD: The effect of CD20 inhibitor treatment was highly significant (Z = 7.87).

<p>The 5 CD20 inhibitor studies showed no heterogeneity (I² = 0).</p

Analyses of bias factors and confounders, which differed significantly across treatment groups.

<p>Only 1 bias factor (TNFi studies: Complete outcome versus incomplete outcome, line 9) had a significant influence on the outcome. Abbreviations: SMD: Standardized mean difference. WMD: Weighted mean difference (SMD1-SMD2); DM: DMARD; GC: Glucocorticoid; DN: DMARD naive; DIA: DMARD inadequate responder; D: double; T: Triple; Sp: Sponsoring; DB: double-blind; CO: Complete outcome; IO: Incomplete outcome; Dur: Disease duration at baseline; PARPR: Percentage of annual radiographic progression rate; L: low; H: High.</p

Study Characteristics and Risk of Bias Factors.

<p>*Percentage of Annual Radiographic Progression Rate</p><p>Study Characteristics and Risk of Bias Factors.</p

Star shaped network showing the 6 different combination treatments anchored on single treatment as the common comparator.

<p>The loops (grey lines) with corresponding numbers (1, 2, 3) show the subgroups, which were directly compared in addition to being indirectly compared. N indicates the number of patients in the groups.</p

TNF inhibitor combined with methotrexate versus single DMARD (methotrexate): The effect of TNF inhibitor was highly significant (Z = 10.84).

<p>The 13 TNF inhibitor studies showed no significant heterogeneity (I² = 42%, p = 0.06). The borderline heterogeneity was due to two golimumab studies (GoBefore, GoForward) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106408#pone.0106408-Emery2" target="_blank">[46]</a>. The exclusion of these, did, however, not change the overall result (−0.33 SMD (CI: −0.39, −0.27)).</p