Jean-Marc Boivin

Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints.

Background and Purpose— Arterial stiffening and thickening and endothelial dysfunction may be associated with cognitive decline or white matter hyperintensities (WMH) independently of blood pressure level. We aimed to investigate, using an integrative approach, the relative contributions of structural and functional vascular factors to the degree of cognitive impairment (primary outcome) and the severity of WMH (secondary outcome) in elderly hypertensive patients with subjective memory complaints, a group prone to dementia. Methods— A prospective, dedicated, cross-sectional population of 198 elderly hypertensive patients (mean age 69.3±6.2 years) with subjective memory complaints underwent a full set of cognitive function assessments, brain MRI with semiquantification of WMH, carotid ultrasonography, carotid–femoral pulse wave velocity, brachial endothelial function, and plasma von Willebrand Factor measurements. Results— After adjustment for the usual cardiovascular risk factors, increased arterial stiffness (as assessed by pulse wave velocity) was significantly and independently associated with memory impairment in men. The severity of WMH was independently associated with increased carotid intima media thickness and stiffness (as assessed by augmentation index) as well as with increased age and plasma levels of von Willebrand Factor, a biomarker of endothelial dysfunction. Conclusions— Our data suggest that vascular abnormalities, independently of blood pressure levels, may play a role in the setting of subjective memory complaints as well as of WMH in elderly hypertensive patients. Arterial thickness and stiffness as well as endothelial function should be assessed simultaneously and may represent additional targets for the prevention of subjective memory complaints and WMH.

Association between orthostatic hypotension and cardiovascular risk, cerebrovascular risk, cognitive decline and falls as well as overall mortality: a systematic review and meta-analysis.

Objective: Several studies have suggested that orthostatic hypotension may be an independent predictor of cardiovascular or cerebrovascular risk and all-cause mortality, particularly in a geriatric population. In 1996, a consensus defined orthostatic hypotension as a SBP fall at least 20 mmHg and/or a DBP fall at least 10 mmHg within 3 min of standing. Methods: Pubmed and Cochrane database were searched up to October 2013 in order to identify prospective studies evaluating, in adult populations, the association between orthostatic hypotension as defined by the 1996 consensus and clinical outcome. Meta-regression was performed when sufficient data were available. Results: A total of 28 prospective studies were found eligible for inclusion in this systematic review. Nine prospective studies found an association between orthostatic hypotension and various cardiovascular events such as coronary disease, heart failure, and arrhythmias. No association was found between orthostatic hypotension and the risk for strokes and falls in the majority of the prospective included studies. Insufficient data were available to perform a meta-analysis for strokes and falls. The meta-analysis of seven prospective studies found that orthostatic hypotension is associated with a significant increased risk for overall mortality [pooled hazard ratio in random-effects model = 1.36 (1.13–1.63), P < 0.001)]. Conclusion: This meta-analysis provides evidence that orthostatic hypotension is associated with a 36% increase in the risk of overall mortality. A systematic review of the literature suggests that orthostatic hypotension is also associated with a higher risk for cardiovascular events. Insufficient data are available to enable a precise assessment of the association of orthostatic hypotension with strokes and falls.

A multifactorial strategy of pain management is associated with less pain in scheduled vaccination of children. A study realized by family practitioners in 239 children aged 4-12 years old

BACKGROUND AND AIMS The multiplicity of vaccine injections during childhood leads to iterative painful and stressful experiences which may lead in turn to anticipated pain and then possibly to a true needle phobia. We aimed at evaluating a multifactorial strategy of pain management combining pharmacological and non-pharmacological approaches during vaccination, as compared to usual care, in 4- to 12-year-old children. METHODS In all, 239 children were enrolled by 25 family practitioners in an open-label study. After a pseudo-randomization, usual pain management (n = 132) was compared to a multifactorial strategy (n = 107) associating preliminary application of an anesthesic patch, preferential use of specified vaccines, child education by the parents and the doctor, parental accompaniment and child distraction with soap bubbles during the procedure. The primary outcome (i.e. child pain) was assessed with a self-report scale named visual analog scale (VAS) of pain. RESULTS A significant decrease in pain was obtained using the multifactorial strategy, as assessed by self-reported VAS (P < 0.0001). This was confirmed by another self-report scale (the facial pain scale revised: P = 0.005), as well as with hetero-evaluations by GPs and parents [Childrens Hospital of Eastern Ontario Pain Scale: P = 0.0007; GPs VAS (P < 0.0001), parents VAS (P < 0.0001)], which were secondary outcome criteria. CONCLUSIONS This multifactorial method significantly decreases vaccination pain in 4- to 12-year-old children. This strategy could make vaccines more acceptable to children and may improve child-doctor relationships and contribute to a decrease in child fear about health care.

Association of menopause and hormone replacement therapy with large artery remodeling

OBJECTIVE To evaluate the remodeling of large arteries according to age at menopause, duration of menopause, and use of hormone therapy (HT). DESIGN A cross-sectional study consisting of baseline measurements of a multicentric randomized trial were used to evaluate arterial parameters. SETTING The study was conducted in France, Belgium, and the Netherlands in academic hospitals and private clinics. PATIENT(S) Postmenopausal women (n = 538) with mild hypercholesterolemia. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Common carotid artery intima-media thickness (CCA-IMT), central pulse pressure, and aortic stiffness (carotid-femoral pulse wave velocity) were measured and centrally controlled for quality. Multivariate regression analysis was used to assess the possible covariates associated with arterial parameters. RESULT(S) Women were 58 ± 6 (mean ± SD) years of age with an age of 50 ± 5 at menopause and a mean duration of menopause of 8 ± 7 years. Lower age at menopause, time since menopause, and absence of HT use were independently associated with worsening of the arterial parameters. After multivariate analysis, HT was associated with a lower CCA-IMT (-40 μm [range -64 to -1]), whereas lower age at menopause and menopause duration were respectively associated with a CCA-IMT increase (25 μm/5 y and 27 μm/5 y). Similarly, values of central pulse pressure and pulse wave velocity were lower in HT users (-3.1 mm Hg [-5.1 to -0.9] and -0.31 m/s [-0.63 to -0.02], respectively) but worsened with age at menopause and menopause duration. CONCLUSION(S) The age at menopause, the time since menopause, and the use of HT are independently associated with the thickening and stiffening of the large arteries. CLINICAL TRIAL REGISTRATION NUMBER NCT00163163.

Influence of the recommendations on the implementation of home blood pressure measurement by French general practitioners: a 2004-2009 longitudinal survey.

Objectives To assess the implementation of home blood pressure measurement (HBPM) by French general practitioners (GPs) in current practice in 2009 and to assess the evolution of practices between 2004 and 2009; the perceived benefits and limitations of the method; and the adherence to methodological European [European Society of Hypertension (ESH) 2007] or French [La Haute Autorité de Santé (HAS) 2005] recommendations. Method Two phone surveys on a representative random sample of French GPs in 2004 and then in 2009. Results Five hundred and forty and 801 GPs were contacted in 2004 and 2009, respectively, in which 511 and 500 participated, including the same 214 in both surveys. The proportion of HBPM users increased between 2004 (70%) and 2009 (92%) (P < 0.0001). The majority still remained occasional users (71%), whereas a minority (21%) used this method nearly systematically in 2009. In 2009, both users and nonusers highlighted the lack of reliability of devices (19 and 47%) and lack of patient reliability (27 and 24%) and patient anxiety (47 and 29%). The expected benefit was primarily the detection of white-coat effect (70%), therapeutic adaptation (36%), diagnostic aid (25%), and better compliance with treatment (14%). Masked hypertension detection (2%) and prognostic interest (0.7%) were marginal. The GPs declared rarely adopting ESH methodology (3% of users), but more often HAS methodology (33%). Adherence to the complete methodology was rare (absolute adherence <1%), but more often ‘minimal’ (three morning and evening measurements, at least 3 days with an upper arm cuff: 17%). Contraindications of HBPM use were not known. Conclusion Despite greater use of HBPM after enactment of the recommendations, the methodology is not strictly implemented, making its diagnostic and prognostic value uncertain.

CALCIUM CHANNEL BLOCKERS USE IS ASSOCIATED WITH A BETTER COGNITIVE PERFORMANCE IN OLDER HYPERTENSIVE PATIENTS WITH SUBJECTIVE MEMORY COMPLAINTS: 9D.07

Background and Purpose: Hypertension is strongly associated with cognitive decline and a promising candidate for dementia prevention. Our aim was to investigate the association between different antihypertensive treatments and cognitive performance in elderly hypertensive patients presenting with subjective memory complaints (SMC). Methods: 378 elderly hypertensive patients > 65 years (mean age 70.4 ± 6.3 years) treated with at least one antihypertensive agent and presenting with SMC but without dementia were prospectively recruited and underwent a combination of neuropsychological tests, a brain MRI with semi-quantification of White Matter Hyperintensities (WMH), carotid echotracking, brachial endothelial function and ambulatory blood pressure (BP) assessments. Results: None of the 3 composite scores (memory score, verbal fluency, visual memory capacity) was found associated with BP levels. Age and gender-adjusted analyses showed a significant and positive association between the memory score and calcium channel blockers (CCBs) use (users: +0.14 ± 0.09 versus non-users: −0.12 ± 0.06, p = 0.016). Multivariate analyses showed that CCBs use was significantly associated with a better memory score, independently from age, male gender, WMH, and carotid wall cross-sectional area, which were associated with worse memory scores. Conclusions: In elderly hypertensive treated patients with SMC, CCBs use was associated with better memory performances independently of BP level and macro and microvascular alterations, suggesting a specific neuroprotective effect of this pharmacological class. Interventional controlled trials are required to confirm the specific protective effect of CCBs on cognitive decline. Figure 1. No caption available.

Association Study of Gene Polymorphisms Involved in Vascular Alterations in Elderly Hypertensives with Subjective Memory Complaints

Background: We have recently shown that vascular abnormalities are associated with cognitive impairment as well as with white matter hyperintensities (WMH) in elderly hypertensive patients presenting with subjective memory complaints (SMC), a population at high risk of developing dementia. The aim of the present study was to identify genetic variants associated with the degree of cognitive impairment and the severity of WMH in the same study population, focusing on genes involved in vascular alterations. Methods: 50 gene polymorphisms known to be associated with vascular alterations (blood pressure regulation, lipid and homocysteine metabolism, thrombosis and inflammation) were genotyped using a multilocus genotyping assay in 369 elderly treated hypertensive patients >60 years of age and presenting with SMC but no dementia. The patients underwent a combination of neuropsychological tests and brain magnetic resonance imaging with semiquantification of WMH. Results: None of the tested polymorphisms were found to be associated with age- and gender-adjusted memory score, visual capacity, body-mass-index-adjusted verbal fluency score or the age-adjusted WMH Fazekas score. Conclusion: Our results suggest that the associations between arterial factors and cognitive decline or WMH are not genetically driven by the genes we investigated, at least at this early stage of cognitive decline.

Can we identify response markers to antihypertensive drugs? First results from the IDEAL Trial

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25–70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was −11.5 mm Hg (indapamide) and −8.3 mm Hg (perindopril). In men, the response was significantly smaller: −4.8 mm Hg (indapamide) and −4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.

Ambulatory 24-h blood pressure assessment of the felodipine-metoprolol combination versus amlodipine in mild to moderate hypertension

OBJECTIVE To measure the time effect profiles of a once daily administered combination tablet felodipine-metoprolol 5/50 mg (Logimax, Astra) and amlodipine 5 mg (Norvasc, Pfizer) on blood pressure and heart rate using 24-h ambulatory blood pressure monitoring. DESIGN Randomized multicentre parallel-group study with a single-blind placebo run-in period of 4 weeks duration and a 6-week double-blind active treatment period. PATIENTS AND METHODS Out of 245 randomized outpatients (90 men, 155 women) with uncomplicated mild-to-moderate primary hypertension and mean sitting diastolic blood pressure (DBP) 95-115 mmHg inclusive, 212 (102 on felodipine-metoprolol, 110 on amlodipine) were eligible for analysis. 24-h ambulatory blood pressure monitoring was performed at the end of the placebo run-in (baseline) and after 6 weeks active treatment (posttreatment). RESULTS Both felodipine-metoprolol and amlodipine induced smooth and consistent reduction in DBP and systolic blood pressure throughout the 24-h period, hence not altering the diurnal rhythm. However, felodipine-metoprolol reduced all average blood pressures (24-h, day- and night-time) more than amlodipine (for 24-h average blood pressure 14.4/9.5 mmHg and 8.9/5.5 mmHg, respectively). Medians of individual diastolic trough-to-peak (T/P) ratios were similar for felodipine-metoprolol and amlodipine (54 and 50%, respectively), while for the systolic T/P ratios, the corresponding values were 74 and 35%, repectively; no significant difference between treatments was seen. As distinguished from amlodipine, both heart rate and rate pressure product were markedly decreased on felodipine-metoprolol throughout the 24-h period and even during the early morning hours. In general, both treatments were well tolerated. CONCLUSIONS Both felodipine-metoprolol and amlodipine achieved optimal control of blood pressure during the inter-dosing interval in line with their pharmokinetic profiles. The vasodilatory adverse events were slightly more reported with felodipine-metoprolol combination, but due to more pronounced lowering of the average blood pressures and the potent additional effect on heart rate and rate pressure product, the efficacy/tolerability balance seems to be equal to or better than that obtained with monotherapy such as amlodipine.

Implementation of Home Blood Pressure Monitoring in Clinical Practice

To investigate the implementation of home blood pressure monitoring (HBPM) guidelines, a phone survey was performed in 366 primary care physicians (PCPs). Of the PCPs, 90% routinely used HBPM for white-coat hypertension, treatment titration, and diagnosis. Thirty percent trusted HBPM more than office measurements. Reported drawbacks were questionable reliability of patients’ reports and devices inaccuracy. Thirty-one percent advised patients on device selection, 38% were aware of validated devices, and 69% reviewed (not averaged) the readings. Seventy-nine percent used higher than recommended threshold for hypertension diagnosis. Although PCPs routinely use HBPM, there are important gaps in their knowledge and educational activities are required.