Repeated administration of nitrate-rich interventions on blood pressure and arterial stiffness: A systematic review and meta-analysis of randomized controlled trials in individuals with and without cardiovascular disease risk

Objective: We aim to synthesize effects of repeated administration (≥3 days) of inorganic nitrate on blood pressure and arterial stiffness measures.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials with at least 3 days treatment of inorganic nitrate on blood pressure and arterial stiffness in individuals with or without elevated cardiovascular disease risk. MEDLINE, EMBASE and the Cochrane Library were searched through 2 July 2019. Two independent reviewers extracted relevant study data. Data were pooled using the generic inverse variance method with random-effects model, and expressed as mean differences with 95% confidence intervals. Certainty in the evidence was assessed using GRADE.

Results: Forty-seven trials were included (n = 1101). Administration of inorganic nitrate significantly lowered SBP [mean difference: -2.91 mmHg, 95% confidence interval (95% CI): -3.92 to -1.89, I = 76%], DBP (mean difference: -1.45 mmHg, 95% CI: -2.22 to -0.68, I = 78%], central SBP (mean difference: -1.56 mmHg, 95% CI: -2.62 to -0.50, I = 30%) and central DBP (mean difference: -1.99 mmHg, 95% CI: -2.37 to -1.60, I = 0%). There was no effect on 24-h blood pressure, augmentation index or pulse wave velocity. Certainty in the evidence was graded moderate for central blood pressure, pulse wave velocity and low for peripheral blood pressure, 24-h blood pressure and augmentation index.

Conclusion: Repeated administration (≥3 days) of inorganic nitrate lower peripheral and central blood pressure. Results appear to be driven by beneficial effects in healthy and hypertensive individuals. More studies are required to increase certainty in the evidence.