A V Kharagjitsingh

HagaZiekenhuis van Den Haag, 's-Gravenhage, South Holland, Netherlands

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Publications (14)51.19 Total impact

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    ABSTRACT: The accretion of bone mass is often impaired in preterm infants, which may contribute to postnatal growth failure. We tested the effects of the vitamin D receptor single-nucleotide polymorphisms (SNPs) c1521g, Fok1, Bsm1, and Taq1 on linear growth up until adulthood in 341 subjects born very prematurely (i.e., <32 weeks of gestation) from the Dutch Project On Preterm and Small-for-gestational-age infants cohort. The GG genotype of the c1521g SNP was associated with a 0.36 [95 % confidence interval (CI), 0.02-0.69] SD taller adult stature and the ff genotype of the Fok1 SNP with a 0.38 SD (95 % CI, 0.02-0.75) taller adult stature. Interaction between these genotypes on stature was observed from the age of 1 year onward (albeit nonsignificantly before the age of 5 years), with adult height being 1.54 (95 % CI, 0.44-2.63) SD taller in subjects carrying both genotypes. The Bsm1 and Taq1 variants were both associated with faster catch-up growth until 2 years of age. Statistical correction for potential confounders did not change our results. We conclude that homozygosity for the minor alleles of both c1521g and Fok1 is associated with a taller adult stature in subjects born very prematurely. The minor alleles of Bsm1 and Taq1 are associated with faster catch-up growth in infancy.
    No preview · Article · Jul 2015 · Journal of Bone and Mineral Metabolism
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    ABSTRACT: Diabetic patients with coronary artery disease (CAD) are often free of chest pain syndrome. A useful modality for non-invasive assessment of CAD is coronary computed tomography angiography (CTA). However, the prognostic value of CAD on coronary CTA in diabetic patients without chest pain syndrome is relatively unknown. Therefore, the aim was to investigate the long-term prognostic value of coronary CTA in a large population diabetic patients without chest pain syndrome. Between 2005 and 2013, 525 diabetic patients without chest pain syndrome were prospectively included to undergo coronary artery calcium (CAC)-scoring followed by coronary CTA. During follow-up, the composite endpoint of all-cause mortality, non-fatal myocardial infarction (MI), and late revascularization (>90 days) was registered. In total, CAC-scoring was performed in 410 patients and coronary CTA in 444 patients (431 interpretable). After median follow-up of 5.0 (IQR 2.7-6.5) years, the composite endpoint occurred in 65 (14%) patients. Coronary CTA demonstrated a high prevalence of CAD (85%), mostly non-obstructive CAD (51%). Furthermore, patients with a normal CTA had an excellent prognosis (event-rate 3%). An incremental increase in event-rate was observed with increasing CAC-risk category or coronary stenosis severity. Finally, obstructive (50-70%) or severe CAD (>70%) was independently predictive of events (HR 11.10 [2.52;48.79] (P = .001), HR 15.16 [3.01;76.36] (P = .001)). Obstructive (50-70%) or severe CAD (>70%) provided increased value over baseline risk factors. Coronary CTA provided prognostic value in diabetic patients without chest pain syndrome. Most importantly, the prognosis of patients with a normal CTA was excellent.
    Preview · Article · Jul 2015 · Journal of Nuclear Cardiology
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    ABSTRACT: Background: Impairment of myocardial fatty acid metabolism assessed by nuclear imaging is associated with increased cardiac mortality for patients undergoing hemodialysis. The reanalysis of beta-methyl- p-iodophenyl pentadecanoic acid (BMIPP) SPECT Analysis for Decreasing Cardiac Events in Hemodialysis Patients (B-SAFE) tried to identify determinants of sudden cardiac death (SCD) for future establishment of prophylactic strategy against SCD. Methods and Results: This study analyzed clinical and scintigraphic data from 677 B-SAFE patients, who had undergone cardiac I-123-BMIPP imaging then had been prospectively followed up, to identify determinants of all-cause mortality. During a 3-year interval, 20 SCDs were observed. SCD patients had a greater C-reactive protein level, more frequently abnormal Q-wave and increased BMIPP abnormality compared to non-SCD patients. There, however, was no significant difference in other clinical, laboratory or hemodialysis parameters between them. Univariate Cox regression analysis identified greater C-reactive protein level (>2.38mg/dl), abnormal Q-wave and greater BMIPP abnormality (summed score>16) as significant prognostic factors for SCD with hazards ratios of 6.83 (95% confidence interval (CI): 1.76–26.47, P=0.005), 17.73 (95%CI: 4.91–63.98, P<0.001) and 10.58 (95%CI, 3.84–29.14, P<0.001), respectively. The patients who had two of the three identified conditions had lower SCD-free rates (log-rank test, P<0.001). Similarly, in multivariate Cox analysis, it showed the maximal hazard ratio of 145.22 (95%CI: 30.34–695.10, P<0.0001) and ROC-AUC of 0.677, when patients had two or all of the SCD risks such as a C-reactive protein level more than 2.38mg/dl, abnormal Q-wave and BMIPP score more than 16. Conclusions: In addition to electrocardiographic abnormality, an increased C-reactive protein level and impaired myocardial fatty acid metabolism are closely and incrementally related to SCD risks in patients undergoing hemodialysis, contributing to appropriate selection of high-risk patients for SCD who could benefit most from a prophylactic approach against SCD.
    No preview · Article · May 2015 · European Heart Journal Cardiovascular Imaging
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    ABSTRACT: Patients with end-stage renal failure (ESRF) are high risk patients for cardiovascular events and are usually evaluated in what concerns myocardial left ventricular ejection fraction (LVEF) and myocardial perfusion before renal transplant. Gated-SPECT myocardial perfusion imaging (G-SPECT MPI) could be used for this evaluation. The aim of this study was to find the prevalence and the predictors of left ventricular dysfunction (LVEF under 45%) and / or an abnormal myocardial perfusion in patients referred for G-SPECT MPI with ESRF before renal transplantation. 112 consecutive patients with ESRF and without known CAD were included. Perfusion was abnormal in 22.3%, LVEF was ≤ 45% in 13.4% and one or both features in 27.7%. Using logistic regression analysis it was found that the predictors LV dysfunction and / or abnormal perfusion imaging were the rest heart rate, (OR=1.1; CI 0.0–1.1; p = 0.007), the QRS width (OR=1.0; CI 1.0–1.1; p = 0.003) and an ECG suggestive of ischemia (OR=2.6; CI 1.0–6.4; p = 0.04). Patients age (OR=1.0; CI 0.9–1.0; p = 0.7) and male gender (OR=1.3; CI 0.5–3.6; p = 0.6), presence of risk factors, namely, diabetes (OR=1.5; CI 0.7–3.6; p = 0.3) or hypertension (OR=0.5; CI 0.2–1.2; p = 0.1), or the presence of angina (OR=1.4; CI 0.4–4.9; p = 0.6) were not predictors of an abnormal perfusion and / or left ventricular dysfunction. In this study, an abnormal G-SPECT MPI study was found in 27.7% of ESRF patients and it was mainly related with ECG findings (rest heart rate, QRS width and an ECG suggestive of ischemia). Atherosclerotic risk factors or even the presence of symptoms were not related with abnormal images.
    Full-text · Conference Paper · May 2015
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    ABSTRACT: The study aims (i) to evaluate changes in myocardial ischaemia on single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) after 2 years in a cohort of high-risk patients with diabetes without cardiac symptoms or known coronary artery disease (CAD) and (ii) to assess the value of baseline computed tomography coronary angiography (CTA)-derived coronary atherosclerosis parameters to predict changes in myocardial ischaemia. The population consisted of 100 high-risk patients with diabetes without cardiac symptoms referred for cardiovascular risk stratification. All patients underwent coronary artery calcium (CAC) scoring, CTA, and SPECT MPI. After 2 years of follow-up, SPECT MPI was repeated to evaluate potential progression of ischaemia. In total, 20% of patients presented with ischaemia at baseline. Of these 20 patients, 7 (35%) still had ischaemia at follow-up, whereas 13 (65%) showed resolution and 4 (20%) showed progression of ischaemia at follow-up. Of the 80 patients without ischaemia at baseline, 65 (81%) had a normal MPI at follow-up and 15 patients (19%) presented with new ischaemia. There were no significant differences in the CAC score or the extent, severity, and composition of CAD on CTA between patients with and without ischaemia at baseline. Similarly, no differences could be demonstrated between patients with and without ischaemia at follow-up or between patients with and without progression of ischaemia. The rate of progression of ischaemia in high-risk patients with diabetes without cardiac symptoms is limited. Few patients presented with new ischaemia, whereas some patients showed resolution of ischaemia. Atherosclerosis parameters on CTA were not predictive of new-onset ischaemia or progression of ischaemia. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
    Full-text · Article · Feb 2015 · European Heart Journal – Cardiovascular Imaging
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    Preview · Article · Jan 2014 · Diabetes care
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    ABSTRACT: The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes. Two hundred and twenty-seven patients from the Hvidoere Study Group were classified in four different progression groups as assessed by change in stimulated C-peptide from 1 to 6 months. CA repeat variants of the IL-10 and IFNγ gene were genotyped and serum levels of IL-10 and IFNγ were measured at 1, 6 and 12 months. IL-10 decreased (P < 0.001) by 7.7% (1 month), 10.4% (6 months) and 8.6% (12 months) per year increase in age of child, while a twofold higher C-peptide concentration at 1 month (p = 0.06), 6 months (P = 0.0003) and 12 months (P = 0.02) was associated with 9.7%, 18.6% and 9.7% lower IL-10 levels, independent of each other. IL-10 concentrations did not associate with the disease progression groups. By contrast, IFNγ concentrations differed between the four progression groups at 6 and 12 months (P = 0.02 and P = 0.01, respectively); patients with rapid progressing disease had the highest levels at both time points. Distribution of IL-10 and IFNγ genotypes was equal among patients from the progression groups. IL-10 serum levels associate inversely with age and C-peptide. As age and C-peptide also associate, a triangular association is proposed. Genetic influence on IL-10 production seems to be masked by distinct disease mechanisms. Increased serum IFNγ concentrations associate with rapid disease progression. Functional genetic variants do not associate with a single progression pattern group, implying that disease processes override genetically predisposed cytokine production.
    No preview · Article · Dec 2011 · Diabetic Medicine
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    ABSTRACT: Background: Major defects in the IGF1 gene are associated with severely reduced cranial and linear growth. The association between IGF1 promoter polymorphisms and growth is uncertain. Aims: To test the effect of the IGF1 192-bp allele on cranial and linear growth and body mass index (BMI) from birth until age 5 years, and on IQ and serum IGF-1 at age 19 years. Methods: In a birth cohort, including 285 individuals born at a gestational age <32 weeks from the Project On Preterm and Small-for-gestational age infants (POPS), cohort anthropometric measurements were analyzed. At age 19 years IGF1 genotype, serum IGF-1 level and IQ were determined. Regression analyses were performed with mixed models. Results: Homozygotes for the 192-bp allele had a slower cranial growth from birth until age 5 years, and a tendency towards less brain sparing and a slower linear growth compared to the other 2 genotype groups. IGF1 genotype was not associated with IQ or BMI development. Head circumference SDS at age 5 years was positively associated with IQ at age 19 years. Conclusion: Homozygosity for the IGF1 192-bp allele is associated with a slower cranial growth from birth until age 5 years in individuals born very preterm.
    No preview · Article · Mar 2011 · Hormone Research in Paediatrics
  • A V Kharagjitsingh · M A J de Ridder · B O Roep · B P C Koeleman · G J Bruining · H J Veeze
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    ABSTRACT: Accelerated early growth prior to childhood type 1 diabetes onset is associated with an increased risk for type 1 diabetes (T1D). We aimed to study early growth, correcting for the previously neglected confounder of familial effects. Infant growth was studied in a retrospective family case-control study of diabetic children in which siblings acted as matched familial controls allowing correction for confounders related to family particulars. Weight and height data were collected from 213 juvenile onset type 1 diabetic children and their 255 healthy siblings. Growth in the first 4 years of life was studied using repeated measurement. The degree of early overgrowth was correlated with age of clinical onset. Birth weight and length did not differ between later diabetic children and their siblings. In the first year of life, weight standard deviation score (SDS) differed between patients and sibs (P = 0.0001). After the first year, both diabetic children and sibs showed parallel enhanced weight and height gain SDS until age 4 years. Earlier onset diabetes was associated with a higher weight SDS at 6 months of age. In this family case-control study the association of increased growth with development of T1D is limited to the first year of life implying that increased growth beyond the first year can be attributed to familial growth patterns, rather than predisposition to T1D per se. Age at disease onset correlated with increased weight in the first 6 months of life, indicating importance of features very early in life on later development of T1D.
    No preview · Article · Oct 2009 · Clinical Endocrinology
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    ABSTRACT: The purpose of the study was to evaluate the prevalence of CAD as well as plaque morphology in asymptomatic patients with type 2 diabetes using multi-slice computed tomography (MSCT). In addition, the relation between calcium score and MSCT findings was explored. In 70 patients, coronary calcium scoring and non-invasive coronary angiography were performed. Angiograms showing atherosclerosis were further classified as obstructive (> or =50% luminal narrowing) CAD or not. Plaque type (non-calcified, mixed and calcified) was determined. Finally, the relation between calcium score and MSCT findings was explored. A calcium score <10 was observed in 31 (44%) patients. A calcium score of 10-100 was observed in 14 (20%) patients while a score of 101-400 or >400 was identified in 12 (17%) and 13 (19%) patients respectively. Non-invasive coronary angiography showed CAD in 56 (80%) patients. 322 coronary segments with plaque were identified, of which 132 (41%) contained non-calcified plaques, 65 (20%) mixed plaques and 125 (39%) calcified plaques. The percentage of patients with obstructive CAD paralleled increasing calcium score. The presence of CAD was noted in 17 (55%) patients with no or minimal calcium (score <10). MSCT angiography detected a high prevalence of CAD in asymptomatic patients with type 2 diabetes. A relatively high proportion of plaques were non-calcified (41%). Importantly, a calcium score <10 did not exclude CAD in these patients. MSCT might be a useful technique to identify CAD in asymptomatic patients with type 2 diabetes with incremental value over calcium scoring.
    No preview · Article · Apr 2008 · Heart (British Cardiac Society)
  • A V Kharagjitsingh · K Prinsen · H H P J Lemkes · R R P de Vries · B O Roep · K Buschard
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    ABSTRACT: To examine a disputed association between the Lewis(a(-)b(-)) phenotype and Type 1 diabetes (T1D). Lewis red blood cell phenotyping was performed for 97 T1D White patients and 100 control subjects using monoclonal antibodies. Two historical cohorts were also included as a control population. T1D patients had a lower frequency (4.1%) of Lewis(a(-)b(-)) blood group compared with simultaneously tested healthy control subjects (10.0%) and the historical control group (11.1%, P = 0.02). Male T1D patients showed a Lewis(a(-)b(-)) frequency of 8.0%, which was similar to both matched healthy male donors (9.8%) and historical (9.5%) male control subjects. Unexpectedly, none of the female T1D patients displayed Lewis(a(-)b(-)) phenotype, vs. 10.3% and 10.8% of female control subjects (P = 0.039 and 0.017). The Lewis(a(-)b(-)) phenotype occurs less frequently in T1D compared with healthy control subjects with a strong female gender bias.
    No preview · Article · Mar 2008 · Diabetic Medicine
  • A Scholte · J Schuijf · A Kharagjitsingh · M Stokkel · J Jukema · A Deroos · E Vanderwall · J Bax

    No preview · Article · Mar 2007 · Journal of Nuclear Cardiology

  • No preview · Article · Dec 2006 · Clinical Immunology
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    ABSTRACT: We studied whether serum interferon (IFN)-gamma or interleukin (IL)-10 levels and their corresponding functional polymorphic genotypes are associated with partial remission of type 1 diabetes (T1D). A multi-centre study was undertaken in patients with newly diagnosed T1D and matched controls. T1D patients were followed for 3 months and characterized for remission status. Partial clinical remission was defined as a daily insulin dose <or= 0.38 units/kg/24 h with an HbA1c <or= 7.5%. Thirty-three patients and 32 controls were phenotyped for serum concentrations of IFN-gamma and IL-10 and genotyped for functional polymorphisms of the IFN-gamma and IL-10 genes. Sixteen of 25 informative patients (63%) remitted. Serum IFN-gamma concentrations were significantly decreased in remitters but increased in non-remitters compared to controls, and did not change over time in any group. IFN-gamma genotypes corresponded with serum levels in controls and non-remitters, but not in remitters who displayed the lowest serum IFN-gamma levels despite more often carrying high-producing IFN-gamma genotypes. Neither the frequency of IL-10 genotypes nor serum IL-10 concentration differed between patients and controls. The combination of high-producing IFN-gamma genotype together with low serum IFN-gamma concentration at the time of diagnosis provided a strong positive predictive value for remission. Serum IFN-gamma concentrations predicted by genotype and observed serum levels were discordant in remitters, suggestive of regulation overruling genetic predisposition. Although high-producing genotypes were less frequent in remitters, they were predictive of remission in combination with low serum IFN-gamma levels. These data imply that remission is partially immune-mediated and involves regulation of IFN-gamma transcription.
    Full-text · Article · Oct 2006 · Clinical & Experimental Immunology

Publication Stats

150 Citations
51.19 Total Impact Points


  • 2015
    • HagaZiekenhuis van Den Haag
      's-Gravenhage, South Holland, Netherlands
  • 2008-2015
    • Medisch Centrum Haaglanden
      's-Gravenhage, South Holland, Netherlands
  • 2008-2014
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2011
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
  • 2006
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
    • Erasmus MC
      Rotterdam, South Holland, Netherlands