R Fagard

University of Leuven, Louvain, Flemish, Belgium

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Publications (439)2076.95 Total impact

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    ABSTRACT: IMPORTANCE Type 2 diabetes mellitus and associated chronic kidney disease (CKD) have become major public health problems. Little is known about the influence of diet on the incidence or progression of CKD among individuals with type 2 diabetes. OBJECTIVE To examine the association between (healthy) diet, alcohol, protein, and sodium intake, and incidence or progression of CKD among individuals with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS All 6213 individuals with type 2 diabetes without macroalbuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) were included in this observational study. Recruitment spanned from January 2002 to July 2003, with prospective follow-up through January 2008. MAIN OUTCOMES AND MEASURES Chronic kidney disease was defined as new microalbuminuria or macroalbuminuria or glomerular filtration rate decline of more than 5% per year at 5.5 years of follow-up. We assessed diet using the modified Alternate Healthy Eating Index (mAHEI). The analyses were adjusted for known risk factors, and competing risk of death was considered. RESULTS After 5.5 years of follow-up, 31.7% of participants had developed CKD and 8.3% had died. Compared with participants in the least healthy tertile of mAHEI score, participants in the healthiest tertile had a lower risk of CKD (adjusted odds ratio [OR], 0.74; 95% CI, 0.64-0.84) and lower risk of mortality (OR, 0.61; 95% CI, 0.48-0.78). Participants consuming more than 3 servings of fruits per week had a lower risk of CKD compared with participants consuming these food items less frequently. Participants in the lowest tertile of total and animal protein intake had an increased risk of CKD compared with participants in the highest tertile (total protein OR, 1.16; 95% CI, 1.05-1.30). Sodium intake was not associated with CKD. Moderate alcohol intake reduced the risk of CKD (OR, 0.75; 95% CI, 0.65-0.87) and mortality (OR, 0.69; 95% CI, 0.53-0.89). CONCLUSIONS AND RELEVANCE A healthy diet and moderate intake of alcohol may decrease the incidence or progression of CKD among individuals with type 2 diabetes. Sodium intake, within a wide range, and normal protein intake are not associated with CKD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00153101.
    JAMA Internal Medicine 08/2013; 173(18). DOI:10.1001/jamainternmed.2013.9051 · 13.25 Impact Factor
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    Europace 06/2013; · 3.05 Impact Factor
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    ABSTRACT: Cited By (since 1996):687, Export Date: 18 October 2014
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    ABSTRACT: To report blood pressure control in the Hypertension in the Very Elderly Trial, a placebo-controlled trial of hypertensive (systolic blood pressure (SBP) 160-199 mm Hg, diastolic blood pressure (DBP) <110 mm Hg) participants over the age of 80 years, given treatment in three steps: indapamide slow release 1.5 mg alone, indapamide plus 2 mg perindopril and indapamide plus 4 mg perindopril. The difference in control between participants with combined systolic and diastolic hypertension (SDH, DBP90 mm Hg) and those with isolated systolic hypertension (ISH, DBP<90 mm Hg) is determined together with the effects of increments in the treatment regimen. At 2 years, the active treatment lowered blood pressure by 16.5/6.9 mm Hg more than that on placebo in participants with SDH and by 19.3/4.8 mm Hg more in those with ISH. The 2-year falls in pressure on placebo alone were 13.2/8.5 mm Hg in SDH and 8.2/1.5 mm Hg in ISH participants. With full titration of active treatment, 62% of SDH participants achieved goal SBP (<150 mm Hg) by 2 years and 71% of those with ISH. The corresponding results for DBP control (<80 mm Hg) were 40 and 78%. The addition of active perindopril 2 mg roughly doubled the percentage controlled, as did increasing to 4 from 2 mg. Blood pressure control was good with ISH and better than with SDH. The fall in SBP accounted for the observed 30% reduction in strokes, but the 21% reduction in total mortality and 64% reduction in heart failure were greater than predicted.
    Journal of human hypertension 03/2011; 26(3):157-63. DOI:10.1038/jhh.2011.10 · 2.69 Impact Factor
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    Journal of Hypertension 01/2011; 29:e113. DOI:10.1097/00004872-201106001-00279 · 4.22 Impact Factor
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    Journal of Hypertension 01/2011; 29:e137. DOI:10.1097/00004872-201106001-00337 · 4.22 Impact Factor
  • Journal of Hypertension 01/2010; 28. DOI:10.1097/01.hjh.0000379290.51000.cf · 4.22 Impact Factor
  • Journal of Hypertension 01/2010; 28. DOI:10.1097/01.hjh.0000378615.12074.78 · 4.22 Impact Factor
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    ABSTRACT: Self or home blood pressure measurement (HBPM) is increasingly popular. Its prognostic value and clinical interest in the diagnosis and follow-up of hypertension are well established. In addition, experts widely agree on the fact that it improves hypertension management and therapeutic compliance. In particular, HBPM often allows to detect white coat hypertension (to be confirmed by 24-hour ambulatory blood pressure measurement). Unfortunately, a large part of HBPM devices in the European Union have not fulfilled independent validation criteria. Furthermore, many patients buy and use such devices without medical supervision. This consensus document summarizes the advantages and disadvantages of HBPM and the conditions of a proper use, in agreement with the recent European and American guidelines.
    Journal de pharmacie de Belgique 07/2009;
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    ABSTRACT: The maternally imprinted insulin-like growth factor 2 (IGF2) gene is an important fetal growth factor and is also suggested to have postnatal metabolic effects. In this study, we examined whether common polymorphisms in IGF2 (6815_6819delAGGGC, 1156T>C and 820G>A (ApaI)) and a microsatellite marker in the close vicinity of IGF2 were linked to or associated with birth weight and adult metabolic risk factors. Polymorphisms were genotyped in 199 monozygotic complete twin pairs, 109 dizygotic complete twin pairs, 15 single twins, 231 mothers and 228 fathers recruited from the East Flanders Prospective Twin Survey. Conventional and parent-of-origin specific linkage and association analyses were carried out with birth weight, adult body height and parameters quantifying obesity, insulin sensitivity and dyslipidaemia measured at adult age (mean age 25 years). In the parent-of-origin specific association analysis, in which only the paternally inherited allele was incorporated, the 1156T>C SNP (single nucleotide polymorphism) showed significant association with IGF-binding protein 1 (IGFBP1) levels (T and C (mean (95% CI)): 13.2 (12.1-14.3) and 16.2 (14.6-18.0) ng ml(-1), P=0.002). No linkage was observed in either the conventional or in the parent-of-origin specific linkage analysis. This study suggests that paternally inherited alleles of a common polymorphism in the IGF2 gene affect IGFBP1 levels.
    International journal of obesity (2005) 06/2009; 33(9):962-70. DOI:10.1038/ijo.2009.126 · 5.39 Impact Factor
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    ABSTRACT: Children born small for gestational age are at increased risk of developing type 2 diabetes in adulthood. The satiety signal leptin that regulates food intake and energy expenditure might be a possible molecular link, as umbilical cord leptin levels are positively correlated with birth weight. In the present study, we examined whether common single nucleotide polymorphisms (SNPs) in the leptin (LEP; 19G>A) gene and its receptor (LEPR; Q223R and K109R) are associated with birth weight and adult metabolic risk factors for type 2 diabetes in twins.
    International journal of obesity (2005) 12/2008; 32(11):1745-1746. DOI:10.1038/ijo.2008.92 · 5.39 Impact Factor
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    ABSTRACT: Earlier studies have demonstrated the interaction between ADD1 and ACE in relation to arterial properties. We investigated whether arterial characteristics might also be related to interactions of ADD1 with other renin-angiotensin system genes. Using a family-based sampling frame, we randomly recruited 1064 Flemish subjects (mean age, 43.6 years; 50.4% women). By means of a wall-tracking ultrasound system, we measured the properties of the carotid, femoral and brachial arteries. In multivariate-adjusted analyses, we assessed the multiple gene effects of ADD1 (Gly460Trp), AGT (C-532T and G-6A) and AT1R (A1166C). In ADD1 Trp allele carriers, but not in ADD1 GlyGly homozygotes (P-value for interaction < or =0.014), femoral cross-sectional compliance was significantly higher (0.74 vs 0.65 mm(2) kPa(-1); P=0.020) in carriers of the AT1R C allele than in AT1R AA homozygotes, with a similar trend for femoral distensibility (11.3 vs 10.2 x 10(-3) kPa(-1); P=0.055). These associations were independent of potential confounding factors, including age. Family-based analyses confirmed these results. Brachial diameter (4.35 vs 4.18 mm) and plasma renin activity (PRA) (0.23 vs 0.14 ng ml(-1) h(-1)) were increased (P< or =0.005) in AGT CG haplotype homozygotes compared with non-carriers, whereas the opposite was true for brachial distensibility (12.4 vs 14.4 x 10(-3) kPa(-1); P=0.011). There was no interaction between AGT and any other gene in relation to the measured phenotypes. ADD1 and AT1R interactively determine the elastic properties of the femoral artery. There is a single-gene effect of the AGT promoter haplotypes on brachial properties and PRA.
    Journal of Human Hypertension 10/2008; 23(1):55-64. DOI:10.1038/jhh.2008.113 · 2.69 Impact Factor
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    Journal of Internal Medicine 09/2008; 241(1):89 - 91. DOI:10.1046/j.1365-2796.1997.t01-1-49884000.x · 5.79 Impact Factor
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    ABSTRACT: A total of five studies have been included in this work. The first two studies describe cardiovascular response changes to (simulated) microgravity in healthy subjects. In a third study, the circulatory response to standing is discussed in five cosmonauts before and after short-duration spaceflight. The last two studies deal with failing adaptive mechanisms of orthostatic blood-pressure control in patients who are prone to head-up tilt induced syncope. The team of Professor A. E. Aubert (F. Beckers, K. Couckuyt and J. Liu) from the Laboratory of Experimental Cardiology of the University Hospital in Leuven was involved in the completion of this thesis. Part of the work has been coordinated by Dr. W. Wieling (J. Gisolf and J.M. Karemaker) of the Academic Medical Center in Amsterdam and by Professor H. Ector (T. Reybrouck) of the Division of Clinical Cardiology in Leuven.
    IRBM 09/2008; 29(4):287-288. DOI:10.1016/j.rbmret.2008.03.004 · 0.38 Impact Factor
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    ABSTRACT: To quantify the relative risk reductions achieved with different regimens to lower blood pressure in younger and older adults. Meta-analyses and meta-regression analyses used to compare the effects on the primary outcome between two age groups (<65 v > or =65 years). Evidence for an interaction between age and the effects of treatment sought by fitting age as a continuous variable and estimating overall effects across trials. Primary outcome: total major cardiovascular events. 31 trials, with 190 606 participants, were included. The meta-analyses showed no clear difference between age groups in the effects of lowering blood pressure or any difference between the effects of the drug classes on major cardiovascular events (all P> or =0.24). Neither was there any significant interaction between age and treatment when age was fitted as a continuous variable (all P>0.09). The meta-regressions also showed no difference in effects between the two age groups for the outcome of major cardiovascular events (<65 v > or =65; P=0.38). Reduction of blood pressure produces benefits in younger (<65 years) and older (> or =65 years) adults, with no strong evidence that protection against major vascular events afforded by different drug classes varies substantially with age.
    BMJ (online) 05/2008; 336(7653):1121-3. DOI:10.1136/bmj.39548.738368.BE · 16.38 Impact Factor
  • R. Fagard, F. Dobbels
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    ABSTRACT: Jaren geleden gold voor patiënten met ischemisch hartlijden, en meer in het bijzonder voor hen die een hartinfarct doormaakten, wekenlange bedrust en strenge beperking van de fysieke activiteit. Men was er immers van overtuigd dat die langdurige rust nodig was voor stevige littekenvorming van het infarct en dat fysieke activiteit uitzetting van het litteken, aneurysmavorming en eventuele ruptuur in de hand zou kunnen werken. In de jaren vijftig van de vorige eeuw begon men zich evenwel te realiseren dat het gevaar voor ruptuur en aneurysmavorming van het infarct als gevolg van fysieke activiteit verwaarloosbaar was. Bovendien leidde langdurige bedrust op fysiek vlak tot orthostatische intolerantie en tot een hogere incidentie van veneuze trombose en longembolieën. Op psychosociaal vlak kwam men tot de conclusie dat deze houding het moreel aantastte, aanleiding gaf tot wanhoop, angsten opriep en resulteerde in ernstige ongerustheid over het hervatten van een normaal leefpatroon. Dit alles leidde tot een agressievere aanpak van de patiënt met ischemisch hartlijden, aanvankelijk uitsluitend tijdens het ziekenhuisverblijf, dat tevens progressief werd ingekort, later gevolgd door het trainen van de ambulante patiënt in speciaal daartoe opgestelde revalidatieprogramma’s.
    12/2007: pages 467-471;
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    ABSTRACT: We determined the genetic contribution of 18 anthropometric and metabolic risk factors of type 2 diabetes using a young healthy twin population. Traits were measured in 240 monozygotic (MZ) and 138 dizygotic (DZ) twin pairs aged 18 to 34 years. Twins were recruited from the Belgian population-based East Flanders Prospective Twin Survey, which is characterised by its accurate zygosity determination and extensive collection of perinatal and placental data, including information on chorionicity. Heritability was estimated using structural equation modelling implemented in the Mx software package. Intra-pair correlations of the anthropometric and metabolic characteristics did not differ between MZ monochorionic and MZ dichorionic pairs; consequently heritabilities were estimated using the classical twin approach. For body mass, BMI and fat mass, quantitative sex differences were observed; genetic variance explained 84, 85 and 81% of the total variation in men and 74, 75 and 70% in women, respectively. Heritability estimates of the waist-to-hip ratio, sum of four skinfold thicknesses and lean body mass were 70, 74 and 81%, respectively. The heritability estimates of fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance and beta cell function, as well as insulin-like growth factor binding protein-1 levels were 67, 49, 48, 62 and 47%, in that order. Finally, for total cholesterol, LDL-cholesterol, HDL-cholesterol, total cholesterol:HDL-cholesterol ratio, triacylglycerol, NEFA and leptin levels, genetic factors explained 75, 78, 76, 79, 58, 37 and 53% of the total variation, respectively. Genetic factors explain the greater part of the variation in traits related to obesity, glucose intolerance/insulin resistance and dyslipidaemia.
    Diabetologia 11/2007; 50(10):2107-16. DOI:10.1007/s00125-007-0784-z · 6.88 Impact Factor
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    ABSTRACT: To study the genetic and environmental determination of variation in Heath-Carter somatotype (ST) components (endomorphy, mesomorphy and ectomorphy). Multivariate path analysis on twin data. Eight hundred and three members of 424 adult Flemish twin pairs (18-34 years of age). The results indicate the significance of sex differences and the significance of the covariation between the three ST components. After age-regression, variation of the population in ST components and their covariation is explained by additive genetic sources of variance (A), shared (familial) environment (C) and unique environment (E). In men, additive genetic sources of variance explain 28.0% (CI 8.7-50.8%), 86.3% (71.6-90.2%) and 66.5% (37.4-85.1%) for endomorphy, mesomorphy and ectomorphy, respectively. For women, corresponding values are 32.3% (8.9-55.6%), 82.0% (67.7-87.7%) and 70.1% (48.9-81.8%). For all components in men and women, more than 70% of the total variation was explained by sources of variance shared between the three components, emphasising the importance of analysing the ST in a multivariate way. The findings suggest that the high heritabilities for mesomorphy and ectomorphy reported in earlier twin studies in adolescence are maintained in adulthood. For endomorphy, which represents a relative measure of subcutaneous adipose tissue, however, the results suggest heritability may be considerably lower than most values reported in earlier studies on adolescent twins. The heritability is also lower than values reported for, for example, body mass index (BMI), which next to the weight of organs and adipose tissue also includes muscle and bone tissue. Considering the differences in heritability between musculoskeletal robustness (mesomorphy) and subcutaneous adipose tissue (endomorphy) it may be questioned whether studying the genetics of BMI will eventually lead to a better understanding of the genetics of fatness, obesity and overweight.
    International Journal of Obesity 09/2007; 31(8):1295-301. DOI:10.1038/sj.ijo.0803575 · 5.39 Impact Factor
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    Journal of Hypertension 08/2007; 25(7):1521-2. DOI:10.1097/HJH.0b013e3281c4a148 · 4.22 Impact Factor
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    ABSTRACT: Genetic variability in the ADD1 (Gly460Trp) and ADD2 (C1797T) subunits of the cytoskeleton protein adducin plays a role in the pathogenesis of hypertension, possibly via changes in intracellular cation concentrations. ADD2 1797CC homozygous men have decreased erythrocyte count and hematocrit. We investigated possible association between intra-erythrocyte cations and the adducin polymorphisms. In 259 subjects (mean age 47.7 years), we measured intra-erythrocyte Na+ [iNa], K+ [iK] and Mg2+ [iMg], serum cations and adducin genotypes. Genotype frequencies (ADD1: GlyGly 61.5%, Trp 38.5%; ADD2: CC 80.4%, T 19.6%) complied with Hardy–Weinberg proportions. In men, ADD2 CC homozygotes (n=100) compared to T-carriers (n=23) had slightly lower iK (85.8 versus 87.5 mmol/l cells; P=0.107), higher iMg (1.92 versus 1.80 mmol/l cells; P=0.012), but similar iNa (6.86 versus 6.88 mmol/l cells; P=0.93). In men, iK, iMg and iNa did not differ according to ADD1 genotypes. In men, iK (R2=0.128) increased with age and serum Na+, but decreased with serum total calcium and the daily intake of alcohol. iMg (R2=0.087) decreased with age, but increased with serum total calcium. After adjustment for these covariates (P⩽0.04 for all), findings in men for iK (CC versus T: 85.8 versus 87.3 mmol/l; P=0.14) and iMg (1.91 versus 1.82 mmol/l; P=0.03) remained consistent. In 136 women, none of the phenotype–genotype relations reached significance. Changes in intra-erythrocyte cations in ADD2 1797CC homozygous men might lead to osmotic fragility of erythrocytes, but to what extent they reflect systemic changes or are possibly involved in blood pressure regulation remains unknown.
    Journal of Human Hypertension 02/2007; 21(5):387-392. DOI:10.1038/sj.jhh.1002154 · 2.69 Impact Factor

Publication Stats

10k Citations
2,076.95 Total Impact Points


  • 1977–2011
    • University of Leuven
      • • Division of Hypertension and Cardiovascular
      • • Department of Rehabilitation Sciences
      • • Faculty of Medicine
      Louvain, Flemish, Belgium
  • 2006
    • Medical University of Gdansk
      • Department of Rehabilitation
      Danzig, Pomeranian Voivodeship, Poland
  • 2001
    • Peking Union Medical College Hospital
      Peping, Beijing, China
  • 1981–2001
    • Universitair Psychiatrisch Centrum KU Leuven
      Cortenberg, Flemish, Belgium
  • 2000
    • Dublin Dental University Hospital
      Dublin, Leinster, Ireland
  • 1997–1999
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
    • Oulu University Hospital
      Uleoborg, Oulu, Finland
  • 1998
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland
  • 1996
    • University of Helsinki
      • Department of Internal Medicine
      Helsinki, Province of Southern Finland, Finland
    • Queen Astrid Military Hospital
      Bruxelles, Brussels Capital, Belgium
    • Beaumont Hospital
      Dublin, Leinster, Ireland
    • China Academy of Chinese Medical Sciences
      Peping, Beijing, China
  • 1981–1996
    • Catholic University of Louvain
      • Department of Industrial Toxicology and Occupational Medecine
      Лувен-ла-Нев, Walloon, Belgium
  • 1990–1995
    • Universitair Ziekenhuis Leuven
      Louvain, Flanders, Belgium
  • 1993–1994
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
  • 1991
    • Royal Berkshire NHS Foundation Trust
      Reading, England, United Kingdom
  • 1982
    • Hospital of Saint Raphael
      New Haven, Connecticut, United States