Papers by Michael Nurmohamed
International Journal of Clinical Practice, Sep 1, 2010
There is abundant evidence that patients with rheumatoid arthritis (RA) are at elevated cardiovas... more There is abundant evidence that patients with rheumatoid arthritis (RA) are at elevated cardiovascular (CV) risk. The contribution of lipids in general is well recognised, but is as yet unclear in inflammatory diseases such as RA in part because inflammation appears inversely associated with lipid levels in RA. The CARRE study is a cohort study of 353 randomly selected RA outpatients followed since their enrollment in 2001-2002. We used data from this cohort to (i) evaluate the relationship at baseline between lipid levels [total cholesterol (TC), high-density lipoprotein (HDL)-cholesterol and the TC:HDLc ratio] and inflammation [by means of C-reactive protein (CRP)]; and (ii) determine the association of baseline TC and TC:HDLc ratio with incident (fatal and non-fatal) CV events. C-reactive protein correlated negatively with TC (r = -0.184, p = 0.002), more so with HDLc (r = -0.327, p = 0.001) and therefore positively with TC:HDLc ratio (r = 0.204, p = 0.001). These associations were most evident when CRP exceeded 10 mg/l. Furthermore, the TC:HDLc ratio, but not TC, was positively related to event risk, again most marked in those with elevated CRP. Our observations support use of TC:HDLc ratio rather than TC alone in assessing cardiovascular risk in RA patients, especially in those with high inflammatory activity.
Annals of the Rheumatic Diseases, Sep 1, 2009
Objectives: Patients with rheumatoid arthritis (RA) have an increased cardiovascular risk, but th... more Objectives: Patients with rheumatoid arthritis (RA) have an increased cardiovascular risk, but the magnitude of this risk is not known precisely. A study was undertaken to investigate the associations between RA and type 2 diabetes (DM2), a well-established cardiovascular risk factor, on the one hand, and cardiovascular disease (CVD) on the other. Methods: The prevalence of CVD (coronary, cerebral and peripheral arterial disease) was determined in 353 randomly selected outpatients with RA (diagnosed between 1989 and 2001, aged 50-75 years; the CARRÉ study) and in participants of a population-based cohort study on diabetes and CVD (the Hoorn study). Patients with RA with normal fasting glucose levels from the CARRÉ study (RA, n = 294) were compared with individuals from the Hoorn study with normal glucose metabolism (non-diabetic, n = 258) and individuals with DM2 (DM2, n = 194). Results: The prevalence of CVD was 5.0% (95% CI 2.3% to 7.7%) in the non-diabetic group, 12.4% (95% CI 7.5% to 17.3%) in the DM2 group and 12.9% (95% CI 8.8% to 17.0%) in those with RA. With non-diabetic individuals as the reference category, the age-and gender-adjusted prevalence odds ratio (OR) for CVD was 2.3 (95% CI 1.1 to 4.7) for individuals with DM2 and 3.1 (95% CI 1.6 to 6.1) for those with RA. There was an attenuation of the prevalences after adjustment for conventional cardiovascular risk factors (OR 2.0 (95% CI 0.9 to 4.5) and 2.7 (95% CI 1.2 to 5.9), respectively). Conclusions: The prevalence of CVD in RA is increased to an extent that is at least comparable to that of DM2. This should have implications for primary cardiovascular prevention strategies in RA.
Ann Rheum Dis, 2006
Background: Rheumatoid arthritis is characterised by inflammation and an increased cardiovascular... more Background: Rheumatoid arthritis is characterised by inflammation and an increased cardiovascular risk. It was recently shown that active early rheumatoid arthritis is associated with dyslipidaemia, which may partially explain the enhanced cardiovascular risk. However, it is unknown when this dyslipidaemia starts. Objective: To investigate the progression of the lipid profile over time and the influence of inflammatory parameters on this lipid profile, in people who later developed rheumatoid arthritis. Methods: Levels of total cholesterol, high-density lipoprotein cholesterol (HDLc), triglycerides, apolipoprotein AI (apo AI), apolipoprotein B (apo B) and lipoprotein(a) (Lp(a)) were determined in 1078 stored, deepfrozen, serial blood bank samples, collected between 1984 and 1999, of 79 blood donors who later developed rheumatoid arthritis. These samples were compared with 1071 control samples of unselected blood donors, matched for age, sex and storage time. Results: Samples of patients who later developed rheumatoid arthritis showed, on average, 4% higher total cholesterol, 9% lower HDLc, 17% higher triglyceride and 6% higher apo B levels than matched controls (p(0.05). The magnitude of the differences in lipid levels between groups, explained by C reactive protein (CRP), was limited. For example, only 3.6% of the difference in HDLc levels between the groups was explained by the CRP concentrations. Conclusion: Patients who later develop rheumatoid arthritis have a considerably more atherogenic lipid profile than matched blood donors at least 10 years before onset of symptoms. As inflammation only marginally explains the differences between the two groups, a modulating effect of lipids on inflammatory processes is hypothesised.
Thrombosis and Haemostasis, Oct 1, 1994
Recombinant hirudin (r-hirudin) is a new anticoagulant with specific antithrombin activity indepe... more Recombinant hirudin (r-hirudin) is a new anticoagulant with specific antithrombin activity independently of antithrombin III. Low molecular weight heparins (LMWH) exert predominantly anti-Xa activity. Therefore, we hypothesized that combined administration of r-hirudin and LMWH would induce a stronger antithrombotic effect as compared to r-hirudin administered alone or combined with unfractionated heparin. To assess the effect on thrombus growth, we determined the accretion of 125I-labeled fibrinogen onto autologous non-radioactive thrombi preformed in the jugular veins of rabbits. The rabbits received unfractionated heparin (80 anti-factor Xa U), LMWH (80 anti-factor Xa U) or r-hirudin (0.3, 5.0 and 10.0 mg/kg) either separately or by combined infusion for a 3 h period. R-Hirudin reduced the thrombus growth in a dose dependent fashion. The combined administration of 80 anti-Xa U LMWH and r-hirudin at a dose of 0.3 mg/kg resulted in a stronger antithrombotic effect as compared to the combined infusion of unfractionated heparin and r-Hirudin (thrombus growth: 14.3% +/- 6.0 vs 28.9% +/- 6.5; p = 0.001). This difference in additive antithrombotic effect of 80 anti-Xa U LMWH versus unfractionated heparin on r-hirudin was also observed when LMWH was combined with 5.0 mg/kg and 10.0 mg/kg r-hirudin versus unfractionated heparin combined with r-hirudin (thrombus growth: 16.4% +/- 1.6 vs 29.1% +/- 3.9; p = 0.01 and 10.1% +/- 1.8 vs 20.4% +/- 4.5; p = 0.001, respectively). In conclusion, this study showed an additive antithrombotic effect of LMWH on the thrombus growth reducing effect of r-hirudin.(ABSTRACT TRUNCATED AT 250 WORDS)
Annals of the Rheumatic Diseases, 2016
Ankylosing spondylitis (AS) is a chronic inflammatory disease with involvement of axial and sacro... more Ankylosing spondylitis (AS) is a chronic inflammatory disease with involvement of axial and sacroiliac joints. In addition, patients with AS have increased risk of cardiovascular disease (CVD), which might be attributed to enhanced inflammatory activity of the arterial wall. In the present study, we compared the level of carotid arterial wall inflammation in patients with AS with healthy controls using (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography with CT. As arterial wall inflammation is reduced by statin therapy, we subsequently assessed the effect of 3-month statin therapy on arterial wall inflammation in AS. We included 24 patients with AS (age 44±10, 72% males) without a history of CVD and 20 controls matched for age and gender. Patients with AS had lower high-density lipoprotein cholesterol and increased C reactive protein (CRP) compared with controls. The 10-year CVD risk was 2% in both groups. Notwithstanding, patients with AS had a 20% increase in arterial wall (18)F-FDG uptake compared with controls. Three-month atorvastatin 40 mg daily significantly lowered low-density lipoprotein cholesterol (baseline 3.55±1.15 mmol/L, -53%) and CRP (baseline 5.0 (1.5-9.3) mg/L, -58%) with a concomitant decrease of carotid arterial wall inflammation (maximum target-to-background ratio from 1.90±0.30 to 1.67±0.27; p=0.009). Patients with AS and without other CVD risk factors have increased arterial wall inflammation, which decreases upon statin therapy. These subjects are not identified as being at risk in current cardiovascular prevention guidelines. Our data support the need to revise CV disease management in AS, with perhaps a role for early statin therapy.
International journal of cardiology, Jan 15, 2016
Nederlands Tijdschrift Voor Geneeskunde, 2010
Annals of the Rheumatic Diseases, Mar 1, 2011
The Journal of Rheumatology, Jun 1, 2008
Rheumatoid arthritis (RA) is associated with an unexplained increased cardiovascular risk. Autoan... more Rheumatoid arthritis (RA) is associated with an unexplained increased cardiovascular risk. Autoantibodies recognizing oxidized low-density lipoprotein (oxLDL-ab) are associated with atherosclerosis in the general population and have been reported in several autoimmune diseases. We investigated relations between oxLDL-ab, inflammation, subclinical atherosclerosis, and cardiovascular disease (CVD) in patients with RA. In a nested case-control study, serum concentrations of oxLDL-ab were measured in 140 RA patients. Ultrasound examination of the carotid artery [i.e., carotid intima-media thickness (CIMT)] was performed in a third of these patients. Correlations were calculated for oxLDL-ab, C-reactive protein (CRP), and high-density lipoprotein (HDL) cholesterol. Regression analyses were used to examine associations between oxLDL-ab and prevalent CVD, and oxLDL-ab and CIMT. OxLDL-ab were positively correlated with CRP (r = 0.33, p < 0.001) and negatively correlated with HDL cholesterol (r = -0.28, p = 0.001). An indication for interaction was found (p = 0.09), suggesting that inflammation modifies the relation between HDL cholesterol and oxLDL-ab. OxLDL-ab were independently associated with intimal thickening, but not associated with prevalent CVD. OxLDL-ab were strongly related with the degree of inflammation and may predispose to a higher risk for CVD, as they were independently associated with subclinical atherosclerosis in patients with RA.
Nature reviews. Rheumatology, Jan 18, 2015
Patients with rheumatoid arthritis (RA) and other inflammatory joint diseases (IJDs) have an incr... more Patients with rheumatoid arthritis (RA) and other inflammatory joint diseases (IJDs) have an increased risk of premature death compared with the general population, mainly because of the risk of cardiovascular disease, which is similar in patients with RA and in those with diabetes mellitus. Pathogenic mechanisms and clinical expression of cardiovascular comorbidities vary greatly between different rheumatic diseases, but atherosclerosis seems to be associated with all IJDs. Traditional risk factors such as age, gender, dyslipidaemia, hypertension, smoking, obesity and diabetes mellitus, together with inflammation, are the main contributors to the increased cardiovascular risk in patients with IJDs. Although cardiovascular risk assessment should be part of routine care in such patients, no disease-specific models are currently available for this purpose. The main pillars of cardiovascular risk reduction are pharmacological and nonpharmacological management of cardiovascular risk fac...
The Journal of Rheumatology, 2015
To investigate the effects of changing inflammation on lipid levels in ankylosing spondylitis. In... more To investigate the effects of changing inflammation on lipid levels in ankylosing spondylitis. In a cohort of 230 patients, lipid levels were measured at baseline and after 52 weeks of treatment with tumor necrosis factor-α-blocking agents (anti-TNF). Total cholesterol (TC; +4.6%), low-density lipoprotein cholesterol (+4.3%), and high-density lipoprotein cholesterol (HDL-C; +3.7%) increased upon treatment. Changes were most evident in patients with substantial reduction in inflammatory levels (TC +8.2% vs +1.6% and HDL-C +8.3% vs +2.2% in patients with C-reactive protein ≥ 10 mg/l normalizing upon treatment vs CRP < 10 mg/l throughout treatment period). Anti-TNF therapy results in lipid changes mostly when inflammation is appreciably modified.
ASAIO transactions / American Society for Artificial Internal Organs
The efficacy and safety of a low molecular weight heparin (LMWH) given as a single predialysis bo... more The efficacy and safety of a low molecular weight heparin (LMWH) given as a single predialysis bolus injection was compared to standard heparin (SH) administered with a continuous infusion in a randomized, 6 month, open follow-up study in 70 patients undergoing hemodialysis. No major bleeding or adverse events were encountered during a total of 4,000 dialysis procedures (2,000 with LMWH). Clot formation in the extracorporeal circuit was minimal and comparable between the groups at 4, 13, and 26 weeks after the start of the study. No accumulation of LMWH anticoagulant activity was noted. It is concluded that the use of LMWH is a safe, effective, and less complex alternative to SH.
BMC musculoskeletal disorders, 2015
Ankylosing spondylitis (AS) is an inflammatory disease with documented elevated cardiovascular (C... more Ankylosing spondylitis (AS) is an inflammatory disease with documented elevated cardiovascular (CV) risk due to systemic inflammation and a higher prevalence of CV risk factors. CV risk management (CV-RM) could be an effective method to reduce CV mortality and morbidity in AS patients. We assessed CV risk and evaluated guideline adherence according to the Dutch CV-RM guideline. This study was conducted with a cohort of consecutive AS patients eligible for treatment with a tumor necrosis factor (TNF) -α inhibitor. Data from the Dutch National Institute for Public Health and Environment was used to compare the prevalence of CV risk factors in AS patients with the Dutch background population. In total, 254 consecutive AS patients were included. The prevalences of hypertension (41% vs 31%) and smoking (43% vs 27%) were substantially higher in AS patients as compared to the general Dutch background population. Of 138 AS patients older than 40 years the 10-years CV risk could be calculate...
Annals of the Rheumatic Diseases, 2015
Arthritis research & therapy, 2006
Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascul... more Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51...
The Journal of rheumatology, 2005
Cardiovascular morbidity and mortality appear to be enhanced in rheumatoid arthritis (RA), which ... more Cardiovascular morbidity and mortality appear to be enhanced in rheumatoid arthritis (RA), which might be due to an increased prevalence of cardiovascular risk factors such as dyslipidemia. It was recently shown that effective disease modifying antirheumatic drug treatment had a favorable influence on the lipid profile in patients with active RA. As infliximab markedly reduces disease activity in RA, we investigated the effects of infliximab on the lipid profile. Infliximab was administered at baseline and at 2 and 6 weeks in patients with active RA. Total cholesterol and HDL-cholesterol concentrations were measured and their ratio, the atherogenic index (an important cardiovascular risk factor indicator), was assessed. Sixty-nine patients were enrolled. The Disease Activity Index score (DAS-28) was 5.9 (SD +/- 1.4) at baseline and decreased to 4.6 (+/- 1.4) after 2 weeks and further to 4.1 (+/- 1.5) after 6 weeks. Total cholesterol level was 5.2 mmol/l at baseline and increased to ...
The Journal of rheumatology, 2015
Patients with inflammatory arthritis (IA) have an increased risk of cardiovascular diseases (CVD)... more Patients with inflammatory arthritis (IA) have an increased risk of cardiovascular diseases (CVD), suggesting a high rate of CVD-related hospitalizations, but data on this topic are limited. Our study addressed hospital admissions for CVD in a primary care-based population of patients with IA and controls. All newly diagnosed patients with IA between 2001 and 2010 were selected from electronic medical records of the Netherlands Institute for Health Services Research Primary Care database, representing a national network of general practices. Two control patients matched for age, sex, and practice were selected for each patient with IA. Hospital admission data for all patients was retrieved from the Dutch Hospital Data. There were 2615 patients with IA and 5555 controls included in our study. CVD-related hospital admissions were observed more frequently among patients with IA as compared with control patients: 48% versus 36% (p < 0.001) in a followup period of 4 years. Patients wi...
Thrombosis Research, 1992
In previous studies the new antithrombotic drug DS (MF 701, Mediolanum Farmaceutici, Milan) showe... more In previous studies the new antithrombotic drug DS (MF 701, Mediolanum Farmaceutici, Milan) showed an equivalent efficacy compared 10 standard heparin in preventing thrombosis in (he extracorporeal circuit of chronic hemodialysis patients. In none of these studies a consecutive series of hemodialysis procedures with DS were investigated.
Seminars in Arthritis and Rheumatism, 2011
Objectives: Rheumatoid arthritis (RA) is associated with increased risk of cardiovascular disease... more Objectives: Rheumatoid arthritis (RA) is associated with increased risk of cardiovascular disease. Carotid intima media thickness (cIMT) is frequently used to identify populations at elevated cardiovascular risk. A systematic literature search and meta-analysis were performed to evaluate cIMT difference between RA and controls. Methods: The literature was screened to identify all available studies comparing cIMT in RA patients and controls. Random effects meta-analysis was performed to estimate the overall mean cIMT difference between both groups. Meta-regression was performed to assess the influence of age and the degree of comparability regarding established cardiovascular risk factors on cIMT difference. Potential publication bias was examined by a funnel plot and Egger test. Results: From 22 studies, cIMT data were available from 1384 RA patients and 1147 controls. In 17 of the studies, RA patients had a statistically significantly greater cIMT. The overall mean cIMT difference was 0.09 mm (95%CI: 0.07-0.11 mm). Heterogeneity was observed (I 2 72.5%, P Ͻ 0.001). A likely source of heterogeneity was the difference in cardiovascular risk factors between RA patients and controls at baseline, but not age. The funnel plot did not show a skewed or asymmetrical shape, which was supported by the Egger's test (P ϭ 0.87). Conclusions: Our observations support the current evidence base for an increased cardiovascular burden in RA and support the use of cIMT in observational studies in RA patients. The next step is to determine its utility as a surrogate cardiovascular risk marker in RA in prospective studies.
Seminars in Arthritis and Rheumatism, 2011
Objectives: Changes in the lipid profile have been described in patients with rheumatoid arthriti... more Objectives: Changes in the lipid profile have been described in patients with rheumatoid arthritis (RA) following therapy with tumor necrosis factor (TNF)-alpha blocking agents. However, thus far, results have been inconsistent. Therefore, we investigated changes in lipid levels after TNFalpha blocking therapy using meta-analysis of published data. Methods: The literature was searched to identify studies assessing changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol, triglycerides, atherogenic index (ie, TC/HDLc ratio), and apolipoprotein levels in response to TNF-alpha blocking therapy. Weighted mean levels of lipids at different time points and subsequent changes in these lipid levels between these time points were calculated with multivariate linear mixed models. Results: Data were available on TC in 15 studies encompassing 766 RA patients and on HDLc in 14 studies encompassing 736 RA patients. TC increased significantly (maximum increase of 10%) and HDLc increased significantly in the first 2 to 6 weeks of therapy (maximum increase of 7%), after which it remained more or less stable. The atherogenic index did not significantly change over time. There was too limited information to evaluate changes in other lipids and apolipoproteins. Conclusions: TNF-alpha blocking therapy has a modest effect on TC and HDLc levels in RA patients with no significant overall effect on the atherogenic index. Whether TNF-alpha blocking effects on qualitative lipid changes (structure and function) are more relevant to their presumed vascular benefits requires further study. RA 393 0049-0172/11/$-see front matter
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Papers by Michael Nurmohamed