Papers by Melchior Nierman
Huisarts en wetenschap
De inclusie van deelnemers voor wetenschappelijke onderzoeken in de eerstelijnszorg valt bijna al... more De inclusie van deelnemers voor wetenschappelijke onderzoeken in de eerstelijnszorg valt bijna altijd zwaar tegen. Dit artikel beschrijft hoe een onderzoek naar een nieuwe diagnostische strategie daardoor bijna mislukte. Een alternatieve inclusieprocedure bleek echter wonderwel te werken.
International Journal of Cardiology
Abstract—Lipoprotein lipase (LPL) hydrolyzes triglycerides in the circulation and promotes the he... more Abstract—Lipoprotein lipase (LPL) hydrolyzes triglycerides in the circulation and promotes the hepatic uptake of remnant lipoproteins. Since the gene was cloned in 1989, more than 100 LPL gene mutations have been identified, the majority of which cause loss of enzymatic function. In contrast to this, the naturally occurring LPLS447X variant is associated with increased lipolytic function and an anti-atherogenic lipid profile and can therefore be regarded as a gain-of-function mutation. This notion combined with the facts that 20 % of the general population carries this prematurely truncated LPL and that it may protect against cardiovascular disease has led to extensive clinical and basic research into this frequent LPL mutant. It is only until recently that we begin to understand the molecular mechanisms that underlie the beneficial effects associated with LPLS447X. This review summarizes the current literature on this interesting LPL variant. (Arterioscler Thromb Vasc Biol. 2006;26...
at: is onlineArteriosclerosis, Thrombosis, and Vascular Biology Information about subscribing to ... more at: is onlineArteriosclerosis, Thrombosis, and Vascular Biology Information about subscribing to Subscriptions:
Thrombosis and Haemostasis, 2022
Background In January 2021, the Dutch vaccination program against severe acute respiratory syndro... more Background In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications. Aims This article investigates whether the BNT162b2 vaccine affects anticoagulation control in outpatients using vitamin K antagonists (VKAs). Methods A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. International normalized ratio (INR) results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination. Results A total of 3,148 outpatient VKA users were included, with a mean age (standard deviation) of 86.7 (8.7) years, of whom 4...
Atherosclerosis Supplements, 2006
Journal of Inherited Metabolic Disease, 2006
Lipoprotein lipase (LPL, triacylglycerol acylhydrolase; EC 3.1.1.3) deficiency (OMIM 238600) is a... more Lipoprotein lipase (LPL, triacylglycerol acylhydrolase; EC 3.1.1.3) deficiency (OMIM 238600) is an autosomal recessive inherited condition caused by mutations in the LPL gene, either in a homozygous or in a compound heterozygous state, leading to loss of lipolytic activity and resulting in severe hypertriglyceridaemia and subsequent risk for developing pancreatitis. Numerous LPL gene mutations leading to loss of catalytic function have been described. In this present study, we describe full clinical, biochemical and molecular analyses of severe hypertriglyceridaemic individuals in one Turkish and three Chinese families. We established one novel mutation (delCT1312-1313), a new combination of mutations (S193R and I194T) and four previously reported mutations (L252R, L252V, S193R and I194T) of the LPL gene and report phenotypes for these and four previously described mutations. Finally, we show that two patients homozygous for the LPL gene delCT1312-1313 mutations are characterized by absence of LPL activity that coincides with absence of LPL protein.
Acta Paediatrica, 2006
To assess whether early initiation of statin therapy for heterozygous familial hypercholesterolae... more To assess whether early initiation of statin therapy for heterozygous familial hypercholesterolaemia favourably affects lipid profiles or vascular morphological changes. Children and adolescents aged 10-16 y with heterozygous familial hypercholesterolaemia were administered fluvastatin (80 mg/d) for 2 y in a single-arm two-centre study. Carotid B-mode intima-media thickness (IMT) and M-mode arterial wall stiffness (beta) were recorded. Eighty of the 85 enrolled subjects completed the trial. The median decrease in low-density lipoprotein (LDL) cholesterol from baseline at last study visit was 33.9%; median decreases in total cholesterol, triglycerides and apolipoprotein B were 27.1%, 5.3% and 24.2%, respectively; the median increase in high-density lipoprotein (HDL) cholesterol was 5.3%. Changes in carotid arterial wall thickness and stiffness versus baseline were fractional and statistically non-significant (delta IMT -0.005 mm, 95% CI -0.018 to +0.007 mm, n=83; and delta beta = 0.017, 95% CI -0.219 to +0.253, n=79). Adverse events, all non-serious, were reported by 58 subjects (68.2%); four were suspected to be drug-related. Change in hormone levels and sexual maturation were appropriate for this age group. Fluvastatin lowered LDL cholesterol, total cholesterol and apolipoprotein B levels effectively over a prolonged period in children and adolescents with heterozygous familial hypercholesterolaemia. Carotid IMT and wall stiffness remained largely unchanged.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objective— Lipoprotein lipase (LPL) exerts 2 principal actions, comprising enzymatic hydrolysis o... more Objective— Lipoprotein lipase (LPL) exerts 2 principal actions, comprising enzymatic hydrolysis of triglyceride-rich lipoproteins (TRLs) and nonenzymatic ligand capacity for enhancing lipoprotein removal. The common LPLS447X variant has been associated with cardiovascular protection, for which the mechanism is unknown. We therefore evaluated enzymatic and nonenzymatic consequences of this LPL variant on TRL metabolism. Methods and Results— TRL apolipoprotein B100 (apoB100) metabolism was determined in 5 homozygous LPLS447X carriers and 5 controls. Subjects were continuously fed and received infusion of stable isotope l -[1- 13 C]-valine. Results were analyzed by SAAMII modeling. Also, preheparin and postheparin LPL concentration and activity were measured. Compared with controls, carriers presented increased very low–density lipoprotein 1 (VLDL 1 ) to VLDL 2 apoB100 flux ( P =0.04), increased VLDL 2 to intermediate-density lipoprotein (IDL) apoB100 flux ( P =0.02), increased IDL to ...
BACKGROUND Direct oral anticoagulants (DOACs) are an alternative for vitamin K antagonists (VKA) ... more BACKGROUND Direct oral anticoagulants (DOACs) are an alternative for vitamin K antagonists (VKA) in the treatment and prevention of venous thromboembolism (VTE). Patient preferences for treatment options have not been extensively explored. METHODS A random sample of 200 patients was obtained from those treated with VKA for deep vein thrombosis, pulmonary embolism or both at the Thrombosis Service Amsterdam. Preference for DOACs relative to VKA was assessed using a treatment trade-off technique administered as a questionnaire sent to all patients. The trade-off consisted of four consecutive scenarios: 1 (no need for laboratory control), 2 (decreased bleeding risk), 3 (less interactions with food and other drugs), 4 (higher efficacy). RESULTS The response rate was 68%. In scenario 1, 36% of patients would switch to a DOAC. This proportion rises to 57% (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.6-3.3) for scenario 2. Scenario 3 resulted in 64% of patients preferring a DOAC (O...
Blood, 2021
Background: In January 2021, the Dutch vaccination programme against SARS-CoV-2 was started. Clin... more Background: In January 2021, the Dutch vaccination programme against SARS-CoV-2 was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications. Aims: To investigate whether the BNT162b2 vaccine affects anticoagulation control in outpatients using Vitamin K antagonists (VKAs). Methods: A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. INR results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination. Results: A total of 3148 outpatient VKA users were included, with a mean age (standard deviation (SD)) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol and 33.0% phenprocoumon. We observed a decr...
Journal of Thrombosis and Haemostasis, 2021
BACKGROUND Direct oral anticoagulants (DOACs) do not require concentration monitoring. However, w... more BACKGROUND Direct oral anticoagulants (DOACs) do not require concentration monitoring. However, whether DOAC concentrations are stable and their variation between and within patients is not well studied. METHODS Patients on vitamin K antagonists (VKA) who switched to rivaroxaban, apixaban, or dabigatran were included between 2018-2020. Blood was drawn at DOAC trough and peak concentrations at week 0, 2 and 8. Plasma drug concentrations were determined by anti-factor Xa concentrations (rivaroxaban, apixaban) or diluted thrombin time (dabigatran). Inter-and intra-individual variability was assessed by calculating the coefficient of variation (CV). Linear regression models were employed to evaluate associations between DOAC trough concentrations and creatinine clearance, previous VKA dosage, and body mass index (BMI). RESULTS 152 patients were included, of whom 96 (63%) male and with a mean age of 73.9±8.4 years. For the inter-individual variability, the CV ranged between 48-81% for trough values and between 25-69% for peak values among patients using the recommended DOAC dose. Intra-individual variability was substantially lower, as here the CV ranged between 18-33% for trough values and between 15-29% for peak values among patients using the recommended DOAC dose. Previous VKA dosage and creatinine clearance were inversely correlated with DOAC trough concentrations. No correlation was found between BMI and DOAC trough concentrations. CONCLUSION Inter-individual variability of DOAC concentration was higher than intra-individual variability. Creatinine clearance and previous VKA dosage were associated with higher DOAC trough concentrations. These findings support further study into an optimal target range, in which the risks of both bleeding and thrombosis are minimal.
Research and Practice in Thrombosis and Haemostasis, 2021
Abstract Background Coagulopathy has been reported in severely ill patients with coronavirus dise... more Abstract Background Coagulopathy has been reported in severely ill patients with coronavirus disease 2019 (COVID‐19). It is unclear whether outpatients with COVID‐19 who are treated with vitamin K antagonists (VKAs) have unstable anticoagulation. Objective To assess the stability of VKA therapy in patients with COVID‐19 through a case‐crossover study. Methods Between February and July 2020, we included patients who tested positive for COVID‐19 from two anticoagulant clinics in the Netherlands. We collected international normalized ratios (INRs) determined between 26 weeks before infection and 12 weeks after. Time in therapeutic range (TTR) and the variance growth rate (VGR) were calculated within patients. Results Fifty‐one patients with COVID‐19 (mean age, 84 years) were included, of whom 15 (29%) were men. Mean TTR in the 26 weeks before COVID‐19 was 80% (95% confidence interval [CI], 75‐85) compared to 59% (95% CI, 51‐68) in the 6 weeks after infection. Mean TTR difference was −23% (95% CI, −32 to −14) with a time above therapeutic range of 38% (95% CI, 30‐47) in the 6 weeks after infection. The TTR rose again to 79% (95% CI, 69‐89) between 6 and 12 weeks after infection. Also, VGR increased, with a mean increase of 4.8 (95% CI, 2.1‐7.5) in the 6 weeks after infection. In the 26 weeks before infection, we registered 19 of 641 (3%) of INR ≥5.0 compared with 35 of 247 (14%) in the 6 weeks after (risk ratio, 4.4; 95% CI, 2.7‐7.3). Conclusions COVID‐19 is associated with a strong decrease in TTR and in therapeutic stability in patients taking VKAs. Additional monitoring in these patients is advised to maximize therapeutic stability.
European Journal of Preventive Cardiology, 2021
Aims To validate the reported increased atherosclerotic cardiovascular disease (ASCVD) risk assoc... more Aims To validate the reported increased atherosclerotic cardiovascular disease (ASCVD) risk associated with very high lipoprotein(a) [Lp(a)] and to investigate the impact of routine Lp(a) assessment on risk reclassification. Methods and results We performed a cross-sectional case-control study in the Amsterdam UMC, a tertiary hospital in The Netherlands. All patients in whom a lipid blood test was ordered between October 2018 and October 2019 were included. Individuals with Lp(a) >99th percentile were age and sex matched to individuals with Lp(a) ≤20th percentile. We computed odds ratios (ORs) for myocardial infarction (MI) and ASCVD using multivariable logistic regression adjusted for age, sex, and systolic blood pressure. Furthermore, we assessed the additive value of Lp(a) to established ASCVD risk algorithms. Lipoprotein(a) levels were determined in 12 437 individuals, out of whom 119 cases [Lp(a) >99th percentile; >387.8 nmol/L] and 119 matched controls [Lp(a) ≤20th pe...
Journal of Thrombosis and Haemostasis, 2020
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial ... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Papers by Melchior Nierman