Association of a Difference in Systolic Blood Pressure Between Arms with Vascular Disease and Mortality: A Systematic Review and Meta-analysis

Abstract

Conclusion:Antioxidant consumption can acutely restore endothelial dysfunction in elderly patients.Summary: Endothelial dysfunction likely contributes to atherosclerosis through a reduction in bioavailability of nitrite oxide (NO). There is also an age-related increase in plasma free radical concentration that contributes to a decrease in the bioavailability of NO. The authors investigated whether acute antioxidant treatment would result in a reversal of the decrease in endothelial function in elderly patients. As markers of endothelial function, the authors used flow-mediated vasodilatation and reactive hyperemia, which were evaluated after the individual consumed placebo or an oral antioxidant cocktail consisting of 1000 mg of vitamin C, 600 IU of vitamin E, and 600 mg of ␣-lipoic acid. This study was performed in 87 healthy volunteers, pairing 42 younger volunteers (25 Ϯ 1 years) with 45 older volunteers (71 Ϯ 1 years). This was a double-blind, crossover, designed study. Blood velocity and brachial artery diameter, as measured with ultrasound imaging, were assessed before and after 5 minutes of forearm circulatory arrest. Serum markers of lipid peroxidation, total antioxidant capacity, endogenous antioxidant activity, vitamin C, plasma nitrite, nitrate, and 3-nitrotyrosine were also determined. With placebo, there was an agerelated reduction of brachial artery vasodilatation in young (7.4% Ϯ 0.6%) vs older (5.2% Ϯ 0.4%) patients. Antioxidant consumption improved flowmediated vasodilatation in older participants (placebo, 5.2% Ϯ 0.4%; antioxidant, 8.2% Ϯ 0.6%). Flow-mediated vasodilatation declined after antioxidant therapy in younger participants (placebo, 7.4% Ϯ 0.6%; antioxidant, 5.8% Ϯ 0.6%). Age was associated with a reduction in reactive hyperemia, but antioxidants did not alter the response in the younger or older groups.Comment: The data demonstrate that antioxidant consumption can acutely restore some elements of endothelial function in older patients. Antioxidants, however, apparently disrupt normal endothelial-dependent vasodilatation in younger individuals. The data must be rectified with clinical trials that have failed to demonstrate a beneficial effect of long-term antioxidant administration on cardiovascular health (Kris-Etherton PM et al, Circulation 2004;110:637-41). There are, however, certainly marked differences in study design between short-term interventional studies, such as in this report, and longer-term clinical trials of antioxidant therapy on cardiovascular health. The current study suggests some link between endothelial dysfunction and oxidative stress in older patients. The authors note the assay used in this study reflects peroxynitrite and that peroxynitrite may originate from multiple sources. The data cannot therefore be directly translated to imply potential benefits of long-term antioxidant therapy. Additional background work will be required before consideration of designing clinical trials evaluating the oral antioxidant cocktail used in this report.

Inter-arm blood pressure difference and mortality: a cohort study in an asymptomatic primary care population at elevated cardiovascular risk

“…1 On recent meta-analysis the authors observed a trend towards higher HRs for survival differences when using simultaneous IAD measurement methods compared with sequential methods, thus survival differences reported here may under-estimate the true figures for this cohort. 25 This analysis was undertaken following publication of the AAA trial and was not specifically powered to assess a pre-defined difference in survival by IAD.…”

“…47 Some authors have labelled an IAD ≥15 mmHg 'subclavian stenosis', 7,48 but there is no direct radiological evidence from general populations, such as the cohort studied here, to confirm that this is the anatomical cause of an IAD. 1 Structural changes in large arteries as a result of hypertension begin early in the course of the condition and cardiovascular and peripheral vascular disease are late sequelae of a process of gradual arterial stiffening. 49 Recent cross-sectional studies have associated systolic IADs ≥10 mmHg with elevated ankle-brachial pulse wave velocity, an indicator of increasing vascular stiffness.…”

“…62 The association of an IAD with peripheral arterial disease confirms the authors' previous finding that IADs have a high specificity for prediction of reduced anklebrachial index. 1,27 This is not routinely assessed in primary care and requires time, equipment, and expertise. 63,64 Diagnosis of peripheral arterial disease can however identify people who can benefit from interventions, and is a domain of the current Quality and Outcomes Framework in the UK.…”

“…However, these data add to the body of evidence identifying IADs as cross-sectional and prospective risk markers for cardiovascular and peripheral vascular disease. 1,65 Blood pressure control is worse in people without established cardiovascular disease (those receiving primary prevention), compared with those with established disease (secondary prevention). 66 Therefore, recognition of novel cardiovascular risk markers to refine risk prediction and stratify treatment priorities can be informative, 67 and patients will benefit, because communication of excess cardiovascular risk is associated with improved patient adherence to healthy lifestyle changes.…”

“…1 Previous studies have demonstrated associations between systolic inter-arm differences (IADs) ≥10 mmHg or ≥15 mmHg and reduced survival in cohorts with established vascular disease or high cardiovascular risk. [2][3][4][5][6][7] The need to explore this association in cohorts more representative of a general population has been identified.…”