Arnaud Chiolero

Electronic compliance monitoring in resistant hypertension: the basis for rational therapeutic decisions.

Objective Incomplete compliance is one of several possible causes of uncontrolled hypertension. Yet, non-compliance remains largely unrecognized and is falsely interpreted as treatment resistance, because it is difficult to confirm or exclude objectively. The goal of this study was to evaluate the potential benefits of electronic monitoring of drug compliance in the management of patients with resistant hypertension. Methods Forty-one hypertensive patients resistant to a three-drug regimen (average blood pressure 156/106 ± 23/11 mmHg, mean ± SD) were studied prospectively. They were informed that for the next 2 months, their presently prescribed drugs would be provided in electronic monitors, without any change in treatment, so as to provide the treating physician with a measure of their compliance. Thereafter, patients were offered the possibility of prolonging the monitoring of compliance for another 2 month period, during which treatment was adapted if necessary. Results Monitoring of compliance alone was associated with a significant improvement of blood pressure at 2 months (145/97 ± 20/15 mmHg, P < 0.01). During monitoring, blood pressure was normalized (systolic < 140 mmHg or diastolic < 90 mmHg) in one-third of the patients and insufficient compliance was unmasked in another 20%. When analysed according to tertiles of compliance, patients with the lowest compliance exhibited significantly higher achieved diastolic blood pressures (P = 0.04). In 30 patients, compliance was monitored up to 4 months and drug therapy was adapted whenever necessary. In these patients, a further significant decrease in blood pressure was obtained (from 150/100 ± 18/15 to 143/94 ± 22/11 mmHg, P = 0.04/0.02). Conclusions These results suggest that objective monitoring of compliance using electronic devices may be a useful step in the management of patients with refractory hypertension, as it enables physicians to take rational decisions based on reliable and objective data of drug compliance and hence to improve blood pressure control.

Random measurement error and regression dilution bias

Random measurement error is a pervasive problem in medical research, which can introduce bias to an estimate of the association between a risk factor and a disease or make a true association statistically non-significant. Hutcheon and colleagues explain when, why, and how random measurement error introduces bias and provides strategies for researchers to minimise the problem

Has Blood Pressure Increased in Children in Response to the Obesity Epidemic

The associations between elevated blood pressure and overweight, on one hand, and the increasing prevalence over time of pediatric overweight, on the other hand, suggest that the prevalence of elevated blood pressure could have increased in children over the last few decades. In this article we review the epidemiologic evidence available on the prevalence of elevated blood pressure in children and trends over time. On the basis of the few large population-based surveys available, the prevalence of elevated blood pressure is fairly high in several populations, whereas there is little direct evidence that blood pressure has increased during the past few decades despite the concomitant epidemic of pediatric overweight. However, a definite conclusion cannot be drawn yet because of the paucity of epidemiologic studies that have assessed blood pressure trends in the same populations and the lack of standardized methods used for the measurement of blood pressure and the definition of elevated blood pressure in children. Additional studies should examine if favorable secular trends in other determinants of blood pressure (eg, dietary factors, birth weight, etc) may have attenuated the apparently limited impact of the epidemic of overweight on blood pressure in children.

Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout.

Objective Losartan has been shown to increase urinary uric acid excretion and hence to lower serum uric acid levels. The purposes of the present study were: (1) to evaluate the effects of losartan on serum uric acid in hypertensive patients with hyperuricemia and gout, (2) to compare the effects of losartan with those of irbesartan, another angiotensin II receptor antagonist and (3) to evaluate whether losartan 50 mg b.i.d. has a greater impact on serum uric acid levels than losartan 50 mg once a day. Methods Thirteen hypertensive patients with hyperuricaemia and gout completed this prospective, randomized, double-blind, cross-over study. Uric acid-lowering drugs were stopped 3 weeks before the beginning of the study. Patients were randomized to receive either losartan 50 mg or irbesartan 150 mg once a day, for 4 weeks. During this phase, a placebo was given in the evening. After 4 weeks, the dose was increased to losartan 50 mg b.i.d., or irbesartan 150 mg b.i.d. for another 4 week period. Subsequently, the patients were switched to the alternative treatment modality. Enalapril (20 mg o.d.) was given during the run-in period and between the two treatment phases. Serum and urinary uric acid were measured at the beginning and at the end of each treatment phase. Results Our results show that losartan 50 mg once daily decreased serum uric acid levels from 538 ± 26 to 491 ± 20 μmol/l (P < 0.01). Irbesartan had no effect on serum uric acid. Increasing the dose of losartan from 50 mg o.d. to 50 mg twice a day, did not further decrease serum uric acid. This may in part be due to a low compliance to the evening dose as measured with an electronic device. Indeed, whatever the prescribed drug, the mean compliance of the evening dose was always significantly lower than that of the morning dose. The uricosuric effect of losartan appears to decrease with time when a new steady state of lower serum uric acid is reached. Conclusions In contrast to irbesartan, losartan was uricosuric and decreased serum uric acid levels. Losartan 50 mg b.i.d. did not produce a greater fall in serum uric acid than losartan once a day. Losartan might be a useful therapeutic tool to control blood pressure and reduce serum uric acid levels in hypertensive patients with hyperuricaemia and gout.

Association of cigarettes smoked daily with obesity in a general adult population.

Objective: We analyzed the cross‐sectional association between obesity and smoking habits, taking into account diet, physical activity, and educational level.

Improving Blood Pressure Control Through Pharmacist Interventions: A Meta-Analysis of Randomized Controlled Trials

Background Control of blood pressure (BP) remains a major challenge in primary care. Innovative interventions to improve BP control are therefore needed. By updating and combining data from 2 previous systematic reviews, we assess the effect of pharmacist interventions on BP and identify potential determinants of heterogeneity. Methods and Results Randomized controlled trials (RCTs) assessing the effect of pharmacist interventions on BP among outpatients with or without diabetes were identified from MEDLINE, EMBASE, CINAHL, and CENTRAL databases. Weighted mean differences in BP were estimated using random effect models. Prediction intervals (PI) were computed to better express uncertainties in the effect estimates. Thirty‐nine RCTs were included with 14 224 patients. Pharmacist interventions mainly included patient education, feedback to physician, and medication management. Compared with usual care, pharmacist interventions showed greater reduction in systolic BP (−7.6 mm Hg, 95% CI: −9.0 to −6.3; I2=67%) and diastolic BP (−3.9 mm Hg, 95% CI: −5.1 to −2.8; I2=83%). The 95% PI ranged from −13.9 to −1.4 mm Hg for systolic BP and from −9.9 to +2.0 mm Hg for diastolic BP. The effect tended to be larger if the intervention was led by the pharmacist and was done at least monthly. Conclusions Pharmacist interventions – alone or in collaboration with other healthcare professionals – improved BP management. Nevertheless, pharmacist interventions had differential effects on BP, from very large to modest or no effect; and determinants of heterogeneity could not be identified. Determining the most efficient, cost‐effective, and least time‐consuming intervention should be addressed with further research.

Prevalence of elevated blood pressure and association with overweight in children of a rapidly developing country

We assessed the prevalence of elevated blood pressure (BP) and the association with excess body weight among a large sample of children in the Seychelles, a middle-income rapidly developing country in the African region. Weight, height and BP were measured in all children of four school grades in the Seychelles (Indian Ocean). Excess weight categories (‘overweight’ and ‘obesity’) were defined according to the criteria of the International Obesity Task Force. Two BP readings were obtained on one occasion. ‘Elevated BP’ was defined based on US reference tables. Data were available in 15 612 (86%) of 18 119 eligible children aged 5–16 years in 2002–2004. In all, 13.0% of Boys and 18.8% of girls were overweight or obese. The prevalence of elevated BP was 9.1% in boys and 10.1% in girls. Both systolic and diastolic BP were strongly associated with body mass index (BMI) in boys and in girls. In children with ‘normal weight’, ‘overweight (and not obesity)’ and ‘obesity’, respectively, proportions with elevated BP were 7.5, 16.9 and 25.2% in boys, and 7.5, 16.1 and 33.2% in girls. Overweight (including obesity) could account for 18% of cases of elevated BP in boys and 26% in girls. Further studies should examine the impact of the relationship between BMI and elevated BP on the burden of hypertension in the context of the epidemic of paediatric obesity.

Discordant Secular Trends in Elevated Blood Pressure and Obesity in Children and Adolescents in a Rapidly Developing Country

Background— The effect of the increasing prevalence of obesity on blood pressure (BP) secular trends is unclear. We analyzed BP and body mass index secular trends between 1998 and 2006 in children and adolescents of the Seychelles, a rapidly developing island state in the African region. Methods and Results— School-based surveys were conducted annually between 1998 and 2006 among all students in 4 school grades (kindergarten and 4th, 7th, and 10th years of compulsory school). We used the Centers for Disease Control and Prevention criteria to define obesity and elevated BP. The same methods and instruments were used in all surveys. Some 25 586 children and adolescents 4 to 18 years of age contributed 43 867 observations. Although the prevalence of obesity in boys and girls increased from 5.1% and 6.0%, respectively, in 1998 to 2000 to 8.0% and 8.7% in 2004 to 2006, the prevalence of elevated BP decreased from 8.4% and 9.8% to 6.9% and 7.8%. During the interval, mean age-adjusted body mass index increased by 0.57 kg/m2 in boys and 0.58 kg/m2 in girls. Mean age- and height-adjusted systolic BP decreased by −3.0 mm Hg in boys and −2.8 mm Hg in girls, whereas mean diastolic BP did not change substantially in boys (−0.2 mm Hg) and increased slightly in girls (0.4 mm Hg). Conclusion— At a population level, the marked increase in the prevalence of obesity in children and adolescents in the Seychelles was not associated with a commensurate secular rise in mean BP.

Proximal Sodium Reabsorption An Independent Determinant of Blood Pressure Response to Salt

The purpose of this study was to evaluate the contribution of renal sodium handling by the proximal tubule as an independent determinant of blood pressure responsiveness to salt in hypertension. We measured blood pressure (BP), renal hemodynamics, and segmental renal sodium handling (with lithium used as a marker of proximal sodium reabsorption) in 38 hypertensive patients and 27 normotensive subjects (15 young and 12 age-matched) on a high and low sodium diet. In control subjects, changing the diet from a low to a high sodium content resulted in no change in BP and increases in glomerular filtration rate (P <0.05), renal plasma flow (P <0.05), and fractional excretion of lithium (FELi, P <0.01). In hypertensive patients, comparable variations of sodium intake induced an increase in BP with no change in renal hemodynamics and proximal sodium reabsorption. When analyzed by tertiles of their BP response to salt, salt-insensitive hypertensive patients of the first tertile disclosed a pattern of adaptation of proximal sodium reabsorption comparable to that of control subjects, whereas the most salt-sensitive patients of the third tertile had an inverse pattern with a high FELi on low salt and a lower FELi on high salt, suggesting an inappropriate modulation of proximal sodium reabsorption. The BP response to salt correlated positively with age (r =0.34, P =0.036) and negatively with the changes in FELi (r =−0.37, P =0.029). In a multivariate analysis, the changes in FELi were significantly and independently associated with the salt-induced changes in BP. These results suggest that proximal sodium reabsorption is an independent determinant of the BP response to salt in hypertension.

Dose-dependent positive association between cigarette smoking, abdominal obesity and body fat: cross-sectional data from a population-based survey.

BackgroundAlthough smokers tend to have a lower body-mass index than non-smokers, smoking may favour abdominal body fat accumulation. To our knowledge, no population-based studies have assessed the relationship between smoking and body fat composition. We assessed the association between cigarette smoking and waist circumference, body fat, and body-mass index.MethodsHeight, weight, and waist circumference were measured among 6,123 Caucasians (ages 35-75) from a cross-sectional population-based study in Switzerland. Abdominal obesity was defined as waist circumference ≥102 cm for men and ≥88 cm for women. Body fat (percent total body weight) was measured by electrical bioimpedance. Age- and sex-specific body fat cut-offs were used to define excess body fat. Cigarettes smoked per day were assessed by self-administered questionnaire. Age-adjusted means and odds ratios were calculated using linear and logistic regression.ResultsCurrent smokers (29% of men and 24% of women) had lower mean waist circumference, body fat percentage, and body-mass index compared with non-smokers. Age-adjusted mean waist circumference and body fat increased with cigarettes smoked per day among smokers. The association between cigarettes smoked per day and body-mass index was non-significant. Compared with light smokers, the adjusted odds ratio (OR) for abdominal obesity in men was 1.28 (0.78-2.10) for moderate smokers and 1.94 (1.15-3.27) for heavy smokers (P = 0.03 for trend), and 1.07 (0.72-1.58) and 2.15 (1.26-3.64) in female moderate and heavy smokers, respectively (P < 0.01 for trend). Compared with light smokers, the OR for excess body fat in men was 1.05 (95% CI: 0.58-1.92) for moderate smokers and 1.15 (0.60-2.20) for heavy smokers (P = 0.75 for trend) and 1.34 (0.89-2.00) and 2.11 (1.25-3.57), respectively in women (P = 0.07 for trend).ConclusionAmong smokers, cigarettes smoked per day were positively associated with central fat accumulation, particularly in women.