Pim van der Harst

Publications (155) View all

• Article: Recurrent and founder mutations in the Netherlands-Phospholamban p.Arg14del mutation causes arrhythmogenic cardiomyopathy.

  P A van der Zwaag, I A W van Rijsingen, R de Ruiter, E A Nannenberg, J A Groeneweg, J G Post, R N W Hauer, I C van Gelder, M P van den Berg, P van der Harst, A A M Wilde, J P van Tintelen
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  ABSTRACT: BACKGROUND: Recently, we showed that the c.40_42delAGA (p.Arg14del) mutation in the phospholamban (PLN) gene can be identified in 10-15 % of Dutch patients with dilated cardiomyopathy or arrhythmogenic cardiomyopathy. The arrhythmogenic burden of the p.Arg14del mutation was illustrated by the high rate of appropriate ICD discharges and a positive family history for sudden cardiac death. METHODS: Our goal was to evaluate the geographical distribution and the origin of this specific mutation in the Netherlands and to get an estimation of the prevalence in a Dutch population cohort. Therefore, we investigated the postal codes of the places of residence of PLN p.Arg14del mutation carriers and places of birth of their ancestors. In addition, a large population-based cohort (PREVEND) was screened for the presence of this mutation. RESULTS: By April 2012, we had identified 101 probands carrying the PLN p.Arg14del mutation. A total of 358 family members were also found to carry this mutation, resulting in a total of 459 mutation carriers. The majority of mutation carriers live in the northern part of the Netherlands and analysing their grandparents' places of birth indicated that the mutation likely originated in the eastern part of the province of Friesland. In the PREVEND cohort we identified six heterozygous PLN p.Arg14del mutation carriers out of 8,267 subjects (0.07 %). CONCLUSION: The p.Arg14del mutation in the PLN gene is the most frequently identified mutation in Dutch cardiomyopathy patients. The mutation that arose 575-825 years ago is likely to have originated from the eastern part of the province of Friesland and is highly prevalent in the general population in the northern part of the Netherlands.
  Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 04/2013; · 1.44 Impact Factor
• Source

  Available from: Peter de Jonge

  Article: Association between anxiety but not depressive disorders and leukocyte telomere length after 2 years of follow-up in a population-based sample.

  P W Hoen, J G M Rosmalen, R A Schoevers, J Huzen, P van der Harst, P de Jonge
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  ABSTRACT: BACKGROUND: Telomere length is considered an emerging marker of biological aging. Depression and anxiety are associated with excess mortality risk but the mechanisms remain obscure. Telomere length might be involved because it is associated with psychological distress and mortality. The aim of this study was to test whether anxiety and depressive disorders predict telomere length over time in a large population-based sample. Method All analyses were performed in a longitudinal study in a general population cohort of 974 participants. The Composite International Diagnostic Interview (CIDI) was used to measure the presence of anxiety and depressive disorders. Telomere length was measured using monochrome multiplex polymerase chain reaction (PCR) at approximately 2 years of follow-up. We used linear multivariable regression models to evaluate the association between anxiety and depressive disorders and telomere length, adjusting for adverse life events, lifestyle factors, educational level and antidepressant use. RESULTS: The presence of anxiety disorders predicted shorter telomeres at follow-up (β=-0.073, t=-2.302, p=0.022). This association was similar after controlling for adverse life events, lifestyle factors, educational level and antidepressant use (β=-0.077, t=-2.144, p=0.032). No association was found between depressive disorders and shorter telomeres at follow-up (β=0.010, t=0.315, p=0.753). CONCLUSIONS: This study found that anxiety disorders predicted shorter telomere length at follow-up in a general population cohort. The association was not explained by adverse life events, lifestyle factors, educational level and antidepressant use. How anxiety disorders might lead to accelerated telomere shortening and whether this might be a mediator explaining the excess mortality risk associated with anxiety deserve further investigation.
  Psychological Medicine 08/2012; · 6.16 Impact Factor
• Article: The Association between Intelligence and Telomere Length: A Longitudinal Population Based Study

  E.M. Kingma, P. de Jonge, P. van der Harst, J. Ormel, J.G.M. Rosmalen
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  ABSTRACT: Low intelligence has been associated with poor health and mortality, but underlying mechanisms remain obscure. We hypothesized that low intelligence is associated with accelerated biological ageing as reflected by telomere length; we suggested potential mediation of this association by unhealthy behaviors and low socioeconomic position. The study was performed in a longitudinal population-based cohort study of 895 participants (46.8% males). Intelligence was measured with the Generalized Aptitude-Test Battery at mean age 52.8 years (33-79 years, SD = 11.3). Leukocyte telomere length was measured by PCR. Lifestyle and socioeconomic factors were assessed using written self-report measures. Linear regression analyses, adjusted for age, sex, and telomere length measured at the first assessment wave (T1), showed that low intelligence was associated with shorter leukocyte telomere length at approximately 2 years follow-up (beta = .081, t = 2.160, p = .031). Nearly 40% of this association was explained by an unhealthy lifestyle, while low socioeconomic position did not add any significant mediation. Low intelligence may be a risk factor for accelerated biological ageing, thereby providing an explanation for its association with poor health and mortality
  PLoS ONE 01/2012; 7(11):-. · 4.09 Impact Factor
• Article: The fibrosis marker galectin‐3 and outcome in the general population

  R. A. de Boer, D. J. van Veldhuisen, R. T. Gansevoort, A. C. Muller Kobold, W. H. van Gilst, H. L. Hillege, S. J. L. Bakker, P. van der Harst
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  ABSTRACT:   de Boer RA, van Veldhuisen DJ, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, Bakker SJL, van der Harst P (University of Groningen). The fibrosis marker galectin-3 and outcome in the general population. J Intern Med 2012; 272: 55–64.Objective.  Galectin-3 is involved in fibrosis and inflammation and plays a role in heart failure, renal disease, obesity and cancer. We aimed to establish the relationship between galectin-3 and cardiovascular (CV) risk factors and mortality in the general population.Design and subjects.  This study included 7968 subjects from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, with a median follow-up of approximately 10 years. Plasma galectin-3 was measured in baseline samples.Main outcome measures.  We investigated the relationships between galectin-3 levels, demographic characteristics and risk factors of CV disease. We determined the prognostic value for all-cause, CV and cancer mortality.Results.  The mean age of the population was 50 ± 13 years. Mean blood pressure was 129/74 mmHg, mean cholesterol was 5.7 ± 1.1 mmol L−1 and median galectin-3 was 10.9 ng mL−1 [interquartile range (IQR) 9.0–13.1]. Galectin-3 levels correlated with a wide range of risk factors of CV disease, including blood pressure, serum lipids, body mass index, renal function and N-terminal pro-B-type natriuretic peptide (P < 0.0001). We observed a strong association between galectin-3 and age. Furthermore, we found a gender interaction, with female subjects (n = 4001) having higher median galectin-3 levels (11.0 ng mL−1, IQR 9.1–13.4 vs. men (n = 3967) 10.7 ng mL−1, IQR 8.9–12.8; P < 0.0001), and galectin-3 levels in women more strongly correlated with risk factors of CV disease. After correction for the classical CV risk factors (smoking, blood pressure, cholesterol and diabetes), galectin-3 levels independently predicted all-cause mortality (hazard ratio per SD galectin-3 1.09, 95% CI 1.01–1.19; P = 0.036), but not CV and cancer mortality separately.Conclusions.  Galectin-3 is associated with age and risk factors of CV disease, with a strong gender interaction for these correlations. Galectin-3 predicts all-cause mortality in the general population.
  Journal of Internal Medicine 11/2011; 272(1):55 - 64. · 5.48 Impact Factor
• Article: The fibrosis marker galectin-3 and outcome in the general population.

  R A de Boer, D J van Veldhuisen, R T Gansevoort, A C Muller Kobold, W H van Gilst, H L Hillege, S J L Bakker, P van der Harst
  [show abstract] [hide abstract]
  ABSTRACT: Galectin-3 is involved in fibrosis and inflammation and plays a role in heart failure, renal disease, obesity and cancer. We aimed to establish the relationship between galectin-3 and cardiovascular (CV) risk factors and mortality in the general population. This study included 7968 subjects from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, with a median follow-up of approximately 10 years. Plasma galectin-3 was measured in baseline samples. We investigated the relationships between galectin-3 levels, demographic characteristics and risk factors of CV disease. We determined the prognostic value for all-cause, CV and cancer mortality. The mean age of the population was 50 ± 13 years. Mean blood pressure was 129/74 mmHg, mean cholesterol was 5.7 ± 1.1 mmol L(-1) and median galectin-3 was 10.9 ng mL(-1) [interquartile range (IQR) 9.0-13.1]. Galectin-3 levels correlated with a wide range of risk factors of CV disease, including blood pressure, serum lipids, body mass index, renal function and N-terminal pro-B-type natriuretic peptide (P < 0.0001). We observed a strong association between galectin-3 and age. Furthermore, we found a gender interaction, with female subjects (n = 4001) having higher median galectin-3 levels (11.0 ng mL(-1) , IQR 9.1-13.4 vs. men (n = 3967) 10.7 ng mL(-1) , IQR 8.9-12.8; P < 0.0001), and galectin-3 levels in women more strongly correlated with risk factors of CV disease. After correction for the classical CV risk factors (smoking, blood pressure, cholesterol and diabetes), galectin-3 levels independently predicted all-cause mortality (hazard ratio per SD galectin-3 1.09, 95% CI 1.01-1.19; P = 0.036), but not CV and cancer mortality separately. Galectin-3 is associated with age and risk factors of CV disease, with a strong gender interaction for these correlations. Galectin-3 predicts all-cause mortality in the general population.
  Journal of Internal Medicine 10/2011; 272(1):55-64. · 5.48 Impact Factor