Jacques Blacher

Université Paris 13 Nord, Вильтанез, Île-de-France, France

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Publications (338)1023.57 Total impact

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    ABSTRACT: Background: Research concerning the link between individual vascular risk factors and cognition is plentiful but few studies have investigated the role of global vascular risk. We examined the cross-time associations of several vascular risk scores with cognitive performance during aging. Methods: Using data from the French SU.VI.MAX cohort, we studied a sample of 3061 participants. Framingham coronary heart disease, cardiovascular and stroke risk profiles were computed using baseline data (1994-1996). Cognitive performance was assessed after a mean of 13 years via a battery of six validated instruments. Principal component analysis identified scores for verbal memory and working memory. Associations between risk profiles (as continuous variables and in quartiles (Q)) and subsequent poor performance (defined as cognitive score ≤10th percentile) were examined via logistic regression (odds ratios, 95% CI) and analysis of covariance. Results: All continuous-scale Framingham risk scores assessed at midlife were inversely and uniformly associated with subsequent poor global cognitive performance, and especially in terms of verbal memory. Considering risk score Q, higher Q were associated with poorer performance in verbal memory: The fully-adjusted odds ratios (95% CI), comparing Q4 versus Q1, were 2.84 (1.70, 4.75), 2.31 (1.43, 3.73) and 1.77 (1.13, 2.76) for Framingham coronary heart disease, cardiovascular and stroke risk profiles, respectively. Similar findings were observed when modeling cognitive outcomes as continuous variables using covariance analyses. Conclusion: This study supports the existence of an inverse cross-time association between midlife vascular risk profiles and subsequent poor cognitive performance, especially in the verbal memory domain. Beyond their importance as regards vascular risk, such risk scores may help primary prevention efforts in identifying and targeting middle-aged individuals at high risk of cognitive aging.
    Atherosclerosis 09/2015; 243(1):286-292. DOI:10.1016/j.atherosclerosis.2015.09.023 · 3.99 Impact Factor
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    ABSTRACT: Background: Visit-to-visit blood pressure (BP) variability limits the ability to detect therapeutic effects in hypertension trials. Methods: To enable future renal denervation trials to detect smaller effect sizes and reliably identify technical improvements, we examined within-patient visit-to-visit BP variability, quantified as SD of change from baseline to final BP (SDΔ), in renal denervation (RDN) trials, trials of BP-lowering tablets, and the VOLTAGE study including 4151 patients. Results: The control arms of RDN trials had more visit-to-visit BP variability than tablet trials (SDΔ 23.6 versus 13.5 mmHg; P < 0.001). This might be explained by more prescribed antihypertensive patients in the RDN trials (5.19 ± 0.13 versus 0.11 ± 0.11; P < 0.001). In the VOLTAGE study, as the number of medications prescribed rose from 0 to 4, SDΔ rose: 11.9, 11.2, 12.9, 14.4 and 18.0 mmHg (P < 0.001 for trend). Neither baseline BP, nor demographics, nor diabetes independently affected variability. The sample size required for a trial rises proportionally to the square of the number of medications prescribed (rather than just linearly). The relationship between the number of background medications prescribed in a cohort and the excess test-retest variance closely fitted this quadratic formula (R = 0.98, P = 0.001). Conclusion: Visit-to-visit variability in BP is dramatically larger in patients with more background medications prescribed. If this is due to variable adherence, then future RDN trials, needing to detect smaller effect sizes, would benefit from measures to guarantee adherence. Conceivable measures include enrolling patients on no background medication, preceding each BP measurement with a period off medication, or directly supervising medication intake.
    Journal of Hypertension 09/2015; DOI:10.1097/HJH.0000000000000708 · 4.72 Impact Factor

  • La Presse Médicale 09/2015; 44(9). DOI:10.1016/j.lpm.2015.05.014 · 1.08 Impact Factor
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    ABSTRACT: Hypertension (HTN) in chronic kidney disease (CKD) is influenced by blood pressure (BP) and the progression of CKD, including hemodialysis and renal transplantation. To date, the efficacy of antihypertensive drug strategies has chiefly been assessed by measuring steady-state systolic, diastolic and mean arterial pressures (MAP). However, recently elucidated features of the BP curve have highlighted other important goals, that is, the specific roles of pulse pressure (PP), arterial stiffness, pulse wave velocity (PWV) and wave reflections as potentially deleterious factors affecting the progression of HTN and CKD. Pharmacological strategies to date have included progressive withdrawal of alpha-blocking agents; efficacy of beta-blockers for coronary prevention; use of angiotensin blockade in HTN with glomerular injury, using angiotensin-converting enzyme inhibition or receptor blockade, as mono but never double-blockade, to avoid major complications; development of combination therapies with diuretics and/or calcium channel blockers. Nowadays, most clinical trials show that SBP, DBP and MAP-lowering is an effective strategy, although results no longer show preference for any specific drug class.Studies of arterial stiffness in CKD have become crucial. In older individuals, PWV is considerably elevated. The 'stiffness gradient' disappears or is inverted (normally, aortic PWV is lower than brachial PWV). Despite BP-lowering, PP is insufficiently dampened, thus promoting microcirculatory damage, progression of arterial calcifications and disturbed wave reflections, which all increase the risk of mortality. In the absence of effective hemodialysis or graft, increased arterial stiffness is therefore a major cardiovascular risk factor in CKD.
    Journal of Hypertension 07/2015; DOI:10.1097/HJH.0000000000000711 · 4.72 Impact Factor
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    ABSTRACT: The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95 % CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0·97 (95 % CI 0·94, 1·00; dose-response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0·86 (95 % CI 0·69, 1·09; dose-response per 1 mmol/l increment, six studies), with high heterogeneity (I 2= 67 and 47 %, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose-response HR 0·94 (95 % CI 0·89, 0·99), seven studies, I 2= 78 %; highest v. lowest HR 0·82 (95 % CI 0·66, 1·02), nine studies, I 2= 81 %) and HDL-C (dose-response HR 0·81 (95 % CI 0·65, 1·02), five studies, I 2= 30 %; highest v. lowest HR 0·82 (95 % CI 0·69, 0·98), five studies, I 2= 0 %). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.
    The British journal of nutrition 07/2015; 114(3):1-11. DOI:10.1017/S000711451500183X · 3.45 Impact Factor
  • C Chi · C Tai · J Wang · A Protogerou · J Blacher · M E Safar · Y Zhang · Y Xu ·
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    ABSTRACT: Current clinical evidence and latest guidelines recommended the combination antihypertensive therapy with angiotensin-converting enzyme (ACE) inhibitor / angiotensin receptor blocker (ARB) and calcium channel blocker (CCB) in patients with grade 2 to 3 hypertension. However, data are scarce in the comparison between the ACE inhibitor / ARB + CCB (A+C) therapy and other combinations. We therefore conducted a meta-analysis to see if ACE inhibitor/ARB combined with CCB is superior to other combinations.(Figure is included in full-text article.) DESIGN AND METHOD:: A meta-analysis was conducted in 20,669 hypertensives from 9 randomized controlled trials and we compared the A+C therapy with other combinations, in terms of blood pressure (BP) reduction, clinical outcomes and adverse effects. BP reduction did not differ significantly between the A+C therapy and other combination therapies, neither in systolic nor in diastolic BP, with P = 0.43 and P = 0.41, respectively. However, A+C strategy, compared with other combination therapies, achieved a significantly lower incidence of cardiovascular composite endpoints, including cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke (Risk ratio [RR] and 95% confidential interval [CI]: 0.80 [0.70, 0.91], P < 0.001, see as Figure), but similar all-cause mortality (0.90 [0.77, 1.04], P = 0.15) and stroke rate (0.90 [0.77, 1.04], P = 0.09). Moreover, A+C combination therapy exhibited a 3.10 ml/min/1.73m2 greater estimated glomerular filtration rate than other combinations (P = 0.01). Lastly, A+C therapy showed a similar incidence of adverse effects as other combinations (P = 0.34), but had a significantly lower incidence of severe adverse effects (0.85 [0.73, 0.98], P = 0.03). In summary, clinical evidences favor A+C therapy, which is superior to other combinations, in current anti-hypertensive strategy, with greater clinical benefit in cardiovascular outcome and reservation of renal function.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e19-e20. DOI:10.1097/01.hjh.0000467402.25796.00 · 4.72 Impact Factor
  • J. Blacher ·

    Journal des Maladies Vasculaires 03/2015; 40(2). DOI:10.1016/j.jmv.2014.12.013 · 0.24 Impact Factor
  • J. Blacher ·

    Journal des Maladies Vasculaires 03/2015; 40(2). DOI:10.1016/j.jmv.2014.12.078 · 0.24 Impact Factor
  • J. Blacher ·

    Journal des Maladies Vasculaires 03/2015; 40(2). DOI:10.1016/j.jmv.2014.12.149 · 0.24 Impact Factor
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    ABSTRACT: Renal transplantation is the best renal replacement modality for patients with end-stage renal disease in terms of patient survival and quality of life. Despite substantial improvement in recipient outcome, stiffness of the large arterial system and cardiovascular (CV) mortality remain high compared to age- and sex-matched subjects in the general population. In addition to traditional CV risk factors, transplantation-specific parameters emerge and are related to immune interactions, drug specifications, and donor characteristics. Some of these parameters appear to be modulators of risk factors and graft and recipient outcome. Acute rejection, for example, appears as a major and independent determinant of high arterial stiffness in recipients of kidney grafts. Furthermore, past history of CV events, low graft filtration function, and donor age determine long-term patient and graft outcome. Living kidney donors, on the other hand, are normally protected especially that they are carefully selected prior to transplantation. Despite a similar long-term outcome compared to the general population, donors may be at higher risk for stiffening of the large arterial system, especially if they cluster with time, CV comorbidities.
  • Piotr Jankowski · Jacques Blacher · Thomas Weber ·
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    ABSTRACT: Central blood pressure is closer to the heart, coronary and carotid arteries, which are the most important sites of cardiovascular events. The influence of cyclic stretch (owing to cyclic changes in blood pressure) on the arterial wall has been documented at every stage of atherosclerosis development. Apart from mediating atherosclerosis progression and plaque instability, the pulsatile component of blood pressure is the main mechanism leading to plaque rupture and, consequently, to acute coronary syndromes and other vascular complications. A number of studies reported a significant relation between central blood pressure and the extant of coronary atherosclerosis as well as between central blood pressure and cardiovascular risk in patients with coronary heart disease. A lot of attention has been given recently to break the link between pulse pressure and cardiovascular events. Because of the vicious circle consisting of arterial wall stiffness, pulse pressure, and atherosclerosis, the most promising intervention is reduction in arterial stiffness, although increase of the potential benefit requires interventions aiming at all three components of the vicious circle.

  • Diabetes & Metabolism 03/2015; 41:A36-A37. DOI:10.1016/S1262-3636(15)30129-4 · 3.27 Impact Factor
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    ABSTRACT: It was reported that, in addition to blood pressure (BP) level, BP variability could also provide prognostic value of target organ damage, cardiovascular and all-cause mortality. Therefore, evaluation of patients' BP variability could potentially offer guiding information on their clinical therapy. BP variability could be assessed by calculating standard deviation, coefficient of variation and other parameters of BP readings from 24-h ambulatory BP monitor, known as short-term BP variability. More recently, an emerging BP variability can be derived from regular home and office BP recordings for 1 week or several months, known as long-term BP variability. Although the cause and meaning of fluctuated BP was not well elucidated, several factors, including age, mean BP, heart rate variability and arterial stiffness, may influence patients' BP variability. Most clinical investigations indicated a significant prognostic value of either short- or long-term BP variability, with regards to target organ damage, cardiovascular events and mortality, but controversy exists in this field, especially its incremental prognostic value in addition to BP level. Till now, there is no solid evidence indicating any effective agent in terms of BP variability reduction, but some clinical studies favor CCB in reducing both short- and long-term BP variability. Further studies are warranted to investigate the standardized evaluation of patients' BP variation, its cause and added prognostic significance, as well as effective treatment.
  • A.D. Protogerou · M.E. Safar · G.E. Plante · J. Blacher ·
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    ABSTRACT: Arterial stiffening, especially of the large elastic arteries, is a fundamental vascular aging trait, which is, however, accelerated in the presence of genetic and environmental factors. It is an early marker of subclinical arterial disease but also a well-established biomarker of clinical cardiovascular disease events and cardiovascular disease mortality. Preventive strategies calcium channel blockade and allopurinol, a careful individualized de-stiffening strategy on the basis of sodium balance, in combination with the renin-angiotensin system blockade, appears to be the currently available optimal strategy.
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    ABSTRACT: In recent clinical investigations, visit-to-visit systolic blood pressure (SBP) variability was proven as a predictor of cardiovascular events and all-cause mortality. However, inconsistent results exist in this association. A meta-analysis of 13 prospective studies was conducted to evaluate the prognostic value of visit-to-visit SBP variability by different parameters in 77,299 patients with a mean follow-up of 6.3 years. The pooled age- and mean SBP-adjusted hazard ratios (HRs) for all-cause mortality were 1.03 (95% confidence interval [CI], 1.02-1.04; P<.001) per 1-mm Hg increase in SBP standard deviation (SD) and 1.04 (1.02-1.06, P<.001) per 1% in SBP coefficient of variation, and the corresponding values of cardiovascular mortality were 1.10 (1.02-1.17, P<.001) and 1.01 (0.99-1.03, P=.32), respectively. Moreover, a 1-mm Hg increase in SD was significantly associated with stroke, with an HR of 1.02 (1.01-1.03, P<.001). Visit-to-visit SBP variability, independent of age and mean SBP, is a predictor of cardiovascular and all-cause mortality and stroke. ©2015 Wiley Periodicals, Inc.
    Journal of Clinical Hypertension 02/2015; 17(2). DOI:10.1111/jch.12484 · 2.85 Impact Factor
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    ABSTRACT: Cardiac involvement in eosinophilia is potentially fatal and requires early diagnosis and prompt treatment. We report here the case of a 71-year-old female patient with eosinophilia > 10,000/mm3 for 2 months due to a myeloproliferative/myelodysplastic syndrome, with a rapidly progressive exertional dyspnea explained by an important circumferential eosinophilic pericarditis. Due to a rapid evolution to a tamponade, an emergent surgical drainage was performed. Subsequent medical treatment combined high-dose corticosteroids (1 mg/kg/day) with hydroxyurea and imatinib. The outcome was favourable with regression of the effusion, of the volume overload symptoms and decrease in eosinophilia.
    Annales de cardiologie et d'angeiologie 01/2015; DOI:10.1016/j.ancard.2014.12.002 · 0.30 Impact Factor
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    ABSTRACT: Background/Aims: Renal function decreases over time as a result of reduction in the number of functioning nephrons with age. In recipients and donors of kidney grafts, renal function decline may be linked differently to various parameters, namely arterial stiffness. Methods: We conducted a prospective cohort study including 101 recipients of kidney grafts and their donors aiming at determining the factors correlating with renal function decline over time. Aortic stiffness was evaluated by the non-invasive measurement of aortic pulse wave velocity. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation and the annualized change was determined. Results: Decline in renal function was estimated at 1-year post-transplantation and annually thereafter (median follow-up 8 years, range 3.6-18.3), as the mean of the annualized decrease in the glomerular filtration rate. In recipients, filtration rate decreased by 4.8 ± 19.7 mL/min/1.73m2 the first post-transplant year, and at a yearly rate of 2.2 ± 3.8 mL/min/1.73m2 thereafter. The first year decline was related to smoking and acute rejection. Later decline was significantly associated with donor age and aortic stiffness. In living donors, renal function decline after the first year corresponded to 0.7 mL/min/1.73m2, was significantly lower than that of recipients (p<0.001), and was determined by donor age at nephrectomy. Conclusion: Recipients of kidney grafts show a glomerular filtration rate decline over time that is significantly associated with donor age and aortic stiffness after the first post-transplant year, while donors demonstrate a lower decline that is mostly determined by age at nephrectomy.
    American Journal of Nephrology 12/2014; 41(1). DOI:10.1159/000371858 · 2.67 Impact Factor
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    ABSTRACT: It has been hypothesized that arterial stiffness leads to generalized microvascular dysfunction and that individuals with type 2 diabetes mellitus (T2DM) are particularly prone to the detrimental effects of arterial stiffness. However, evidence for an association between stiffness and markers of generalized microvascular dysfunction is lacking. We therefore investigated the association between arterial stiffness and skin microvascular function in individuals without and with T2DM. Cross-sectional data were used of The Supplementation en Vitamines et Mineraux Antioxydants 2 (SUVIMAX2) Study (n = 284/62.2 years/48.6% women/0% T2DM (by design)) and The Maastricht Study (n = 737/59.7 years/45.2% women/28.8% T2DM (by design)). Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV). Skin capillaroscopy was used to determine capillary density at baseline, and during reactive hyperemia and venous congestion. Laser Doppler flowmetry was used to assess acetylcholine- and local heating-induced vasoreactivity, and skin flowmotion. In The SUVIMAX2 Study, cfPWV (per +1 SD) was not associated with baseline capillary density (regression coefficient: -0.48 (95% confidence interval: 2.37; 1.41)) or capillary recruitment during venous congestion (0.54% (-0.74; 1.81%)). In addition, cfPWV was not associated with acetylcholine (-0.02% (-0.14; 0.10%)) or local heating-induced vasoreactivity (0.03% (-0.07; 0.12%)). In The Maastricht Study, in individuals without T2DM, cfPWV was not associated with baseline capillary density (-1.20 (-3.17; 0.77)), and capillary recruitment during reactive hyperemia (1.22% (-0.41; 2.84%)) or venous congestion (1.50% (-0.25; 3.25%)). In addition, cfPWV was not associated with flowmotion (-0.01 (-0.07; 0.06)). Results were adjusted for age and sex. Additional adjustments for confounders did not materially change these results. Results were qualitatively similar in individuals with T2DM. Arterial stiffness is not associated with skin microvascular function, irrespective of the presence of T2DM. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    American Journal of Hypertension 12/2014; 28(7). DOI:10.1093/ajh/hpu246 · 2.85 Impact Factor

  • Artery Research 12/2014; 8(4):141. DOI:10.1016/j.artres.2014.09.132

Publication Stats

11k Citations
1,023.57 Total Impact Points


  • 2010-2015
    • Université Paris 13 Nord
      • Unité de recherche en épidémiologie nutritonnelle - UREN (UMR 557) Inserm - INRA - CNAM
      Вильтанез, Île-de-France, France
    • Hôpital "René-Muret - Bigottini" – Hôpitaux Universitaires Paris-Seine-Saint-Denis
      Île-de-France, France
  • 2007-2015
    • Université René Descartes - Paris 5
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
    • Hôpital "Sainte-Périne - Rossini - Chardon-Lagache" – Hôpitaux universitaires Paris Ile-de-France Ouest
      Lutetia Parisorum, Île-de-France, France
  • 2003-2014
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2009-2013
    • Conservatoire National des Arts et Métiers
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • St. James's Hospital
      Dublin, Leinster, Ireland
  • 2002-2011
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2008
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2005
    • Hôpital Paul-Brousse – Hôpitaux universitaires Paris-Sud
      Villejuif, Île-de-France, France
  • 2004
    • Hopital Hôtel-Dieu Grace
      Windsor, Ontario, Canada
  • 1998-2004
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • University of Leuven
      • Division of Hypertension and Cardiovascular
      Louvain, Flemish, Belgium