Blood Pressure in Children

Importance of Salt in Determining Blood Pressure in Children
Meta-Analysis of Controlled Trials
Feng J. He; Graham A. MacGregor
From the Blood Pressure Unit, Cardiac and Vascular Sciences, St George’s University of London, London, United Kingdom.

To assess the effect of reducing salt intake on blood pressure in children, we carried out a meta-analysis of controlled trials. Trials were included if participants were children ( 18 years), and duration of salt reduction must have been for 2 weeks. Mean effect size was calculated using a fixed-effect model, because there was no significant heterogeneity. Ten trials of children and adolescents with 966 participants were included (median age: 13 years; range: 8 to 16 years; median duration: 4 weeks; range: 2 weeks to 3 years). Salt intake was reduced by 42% (interquartile range [IQR]: 7% to 58%). There were significant reductions in blood pressure: systolic: –1.17 mm Hg (95% CI: –1.78 to –0.56 mm Hg; P<0.001); diastolic: –1.29 mm Hg (95% CI: –1.94 to –0.65 mm Hg; P<0.0001). Three trials of infants with 551 participants were included (median duration: 20 weeks; range: 8 weeks to 6 months). Salt intake was reduced by 54% (IQR: 51% to 79%). There was a significant reduction in systolic blood pressure: –2.47 mm Hg (95% CI: –4.00 to –0.94 mm Hg; P<0.01). This is the first meta-analysis of salt reduction in children, and it demonstrates that a modest reduction in salt intake causes immediate falls in blood pressure and, if continued, may well lessen the subsequent rise in blood pressure with age. This would result in major reductions in cardiovascular disease. These results in conjunction with other evidence provide strong support for a reduction in salt intake in children.

Hypertension. 2006;48:861.

© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Haemostatic Factors and the Risk of Cardiovascular Death in Patients With Coronary Artery Disease. The AtheroGene Study

P.E. Morange at al.

To get a better insight into the role of hemostasis in coronary artery disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen, thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP) complexes on the risk of cardiovascular event in a prospective cohort of CAD patients.

The prospective Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline. After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death, but not of nonfatal event. Except for vWF, these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF, fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model, fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI) associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to 1.55) and 1.29 (1.09 to 1.53), respectively.

Conclusions. In patients with coronary artery disease, fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.
We examined the association between 5 hemostatic markers and the incidence of fatal cardiovascular events in the prospective Atherogene cohort, including 1057 individuals with coronary artery disease at baseline. Fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2793.

© 2006 American Heart Association, Inc.

Hypertension: Acupuncture Research Program

Stop Hypertension With the Acupuncture Research Program (SHARP)
Results of a Randomized, Controlled Clinical Trial

Eric A. Macklin; Peter M. Wayne; Leslie A. Kalish; Peter Valaskatgis; James Thompson; May C.M. Pian-Smith; Qunhao Zhang; Stephanie Stevens; Christine Goertz; Ronald J. Prineas; Beverly Buczynski; Randall M. Zusman

Case studies and small trials suggest that acupuncture may effectively treat hypertension, but no large randomized trials have been reported. The Stop Hypertension with the Acupuncture Research Program pilot trial enrolled 192 participants with untreated blood pressure (BP) in the range of 140/90 to 179/109 mm Hg. The design of the trial combined rigorous methodology and adherence to principles of traditional Chinese medicine. Participants were weaned off antihypertensives before enrollment and were then randomly assigned to 3 treatments: individualized traditional Chinese acupuncture, standardized acupuncture at preselected points, or invasive sham acupuncture. Participants received 12 acupuncture treatments over 6 to 8 weeks. During the first 10 weeks after random assignment, BP was monitored every 14 days, and antihypertensives were prescribed if BP exceeded 180/110 mm Hg. The mean BP decrease from baseline to 10 weeks, the primary end point, did not differ significantly between participants randomly assigned to active (individualized and standardized) versus sham acupuncture (systolic BP: –3.56 versus –3.84 mm Hg, respectively; 95% CI for the difference: –4.0 to 4.6 mm Hg; P=0.90; diastolic BP: –4.32 versus –2.81 mm Hg, 95% CI for the difference: –3.6 to 0.6 mm Hg; P=0.16). Categorizing participants by age, race, gender, baseline BP, history of antihypertensive use, obesity, or primary traditional Chinese medicine diagnosis did not reveal any subgroups for which the benefits of active acupuncture differed significantly from sham acupuncture. Active acupuncture provided no greater benefit than invasive sham acupuncture in reducing systolic or diastolic BP.

Key Words: acupuncture • blood pressure • hypertension • randomized clinical trial • traditional Chinese medicine

Hypertension. 2006;48:838.

© 2006 American Heart Association, Inc.

Tetrahydrobiopterin and Cardiovascular Disease

An L. Moens; David A. Kass
From the Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Md.

Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, which are essential in the formation of neurotransmitters, and for nitric oxide synthase. It is presently used clinically to treat some forms of phenylketonuria (PKU) that can be ameliorated by BH4 supplementation. Recent evidence supports potential cardiovascular benefits from BH4 replacement for the treatment of hypertension, ischemia-reperfusion injury, and cardiac hypertrophy with chamber remodeling. Such disorders exhibit BH4 depletion because of its oxidation and/or reduced synthesis, which can result in functional uncoupling of nitric oxide synthase (NOS). Uncoupled NOS generates more oxygen free radicals and less nitric oxide, shifting the nitroso-redox balance and having adverse consequences on the cardiovascular system. While previously difficult to use as a treatment because of chemical instability and cost, newer methods to synthesize stable BH4 suggest its novel potential as a therapeutic agent. This review discusses the biochemistry, physiology, and evolving therapeutic potential of BH4 for cardiovascular disease.
Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, which are essential in the formation of neurotransmitters, and for nitric oxide synthase (NOS). BH4 replacement may help treat hypertension, ischemia-reperfusion injury, and cardiac hypertrophy with chamber remodeling, by restoring functional NOS. This review discusses BH4 biochemistry, physiology, and evolving uses to treat cardiovascular disease.

Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2439.

© 2006 American Heart Association, Inc.

Cardioverter-Defibrillator in Patients With Brugada Syndrome

Outcome After Implantation of a Cardioverter-Defibrillator in Patients With Brugada Syndrome: A Multicenter Study

Frédéric Sacher, MD at al.

Background— Brugada syndrome is an arrhythmogenic disease characterized by an increased risk of sudden cardiac death (SCD) by ventricular fibrillation. At present, an implantable cardioverter-defibrillator (ICD) is the recommended therapy in high-risk patients. This multicenter study reports the outcome of a large series of patients implanted with an ICD for Brugada syndrome.

Methods and Results— All patients (n=220, 46±12 years, 183 male) with a type 1 Brugada ECG pattern implanted with an ICD in 14 centers between 1993 and 2005 were investigated. ICD indication was based on resuscitated SCD (18 patients, 8%), syncope (88 patients, 40%), or positive electrophysiological study in asymptomatic patients (99 patients, 45%). The remaining 15 patients received an ICD because of a family history of SCD or nonsustained ventricular arrhythmia. During a mean follow-up of 38±27 months, no patient died and 18 patients (8%) had appropriate device therapy (10±15 shocks/patient, 26±33 months after implantation). The complication rate was 28%, including inappropriate shocks, which occurred in 45 patients (20%, 4±3 shocks/patient, 21±20 months after implantation). The reasons for inappropriate therapy were lead failure (19 patients), T-wave oversensing (10 patients), sinus tachycardia (10 patients), and supraventricular tachycardia (9 patients). Among implantation parameters, high defibrillation threshold, high pacing threshold, and low R-wave amplitude occurred, respectively, in 12%, 27%, and 15% of cases.

Conclusion— In this large Brugada syndrome population, a low incidence of arrhythmic events was found, with an annual event rate of 2.6% during a follow-up of >3 years, in addition to a significant risk of device-related complications (8.9%/year). Inappropriate shocks were 2.5 times more frequent than appropriate ones.

Circulation. 2006;114:2317-2324.
© 2006 American Heart Association, Inc.