Bivalirudin for the treatment of ST-segment elevation myocardial infarction: a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer (The Medicines Company) of bivalirudin to submit evidence for its clinical and cost effectiveness within its licensed indication for the treatment of adults with ST-segment elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention (PPCI), as part of NICE's single technology appraisal (STA) process. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG), which produced a review of the evidence within the manufacturer's submission to NICE. This article describes the manufacturer's submission, the ERG review and NICE's subsequent decisions. The main evidence was derived from one randomized controlled trial (RCT) of STEMI patients intended for PPCI, comparing bivalirudin with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors (GPIs). Bivalirudin was associated with a significant reduction in cardiac mortality at 30 days (p = 0.03) and at 1-year follow-up (p = 0.005), and a significant reduction in major bleeding at 30 days (p < 0.001) and 1 year (p < 0.0001), compared with heparin plus GPI. Stent thrombosis up to 24 hours following PPCI was significantly (p < 0.001) more common with bivalirudin. However, there was no significant treatment effect for stent thrombosis from 1 to 30 days (p = 0.28), or at 1-year follow-up (p = 0.53). There were no significant treatment group differences at 30 days and at 1 year in stroke (p = 0.68 and p = 0.99, respectively), in myocardial infarction [MI] (p = 0.90 and p = 0.22, respectively), or in the need for the revascularization of the target vessel for ischaemia (p = 0.18 and p = 0.12, respectively). There were two decision-analytic models: the base-case scenario used 1-year follow-up data from the RCT; and a sensitivity analysis used 3-year follow-up data. Resource use was primarily drawn from this RCT. Health-related quality-of-life (HR-QOL) estimates were drawn from a UK cohort study. Both models evaluated the incremental costs and outcomes of bivalirudin compared with heparin plus GPI for patients with STEMI intended for PPCI. The analysis adopted a UK NHS perspective over a lifetime horizon. Unit costs were based on year 2009-2010 prices. The model adopted a decision-tree structure to reflect initial events for the initial period (stroke, repeat MI, minor/major bleeding events, repeat revascularization and death) and a two-state Markov component to simulate longer-term survival. The economic analysis suggested that bivalirudin is expected to dominate the heparin plus GPI strategy. This finding was consistent across the probabilistic sensitivity analysis and the vast majority of deterministic sensitivity analyses undertaken. Three exceptions to this finding were observed for the following sensitivity analyses: (1) the exclusive use of eptifibatide as the GPI (incremental cost-effectiveness ratio [ICER] = £1,764); (2) the combination of 100 % eptifibatide use, 100 % radial arterial access and no differential length between strategies for initial hospital stay (ICER = £4,106); and (3) a longer length of ward stay (increase of 0.33 days) for the initial hospitalization (ICER = £415). The Appraisal Committee (AC) gave a positive recommendation for bivalirudin for the treatment of adults with STEMI undergoing PPCI.

Long-term cost-effectiveness of weight management in primary care.

BACKGROUND: As obesity prevalence and health-care costs increase, Health Care providers must prevent and manage obesity cost-effectively. METHODS: Using the 2006 NICE obesity health economic model, a primary care weight management programme (Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity-related conditions (type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background (untreated) weight gain. RESULTS: Mean weight changes in Counterweight attenders was -3 kg and -2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was pound59.83 per patient entered. Even assuming drop-outs/non-attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was 'dominant' (cost-saving) under 'base-case scenario', where 12-month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality-adjusted Life-Year cost was pound2017 where background weight gain was limited to 0.5 kg/year, and pound2651 at 0.3 kg/year. Under a 'best-case scenario', where weights of 12-month-attenders were assumed thereafter to rise at the background rate, 4 kg below non-intervention trajectory (very close to the observed weight change), Counterweight remained 'dominant' with background weight gains 1 kg, 0.5 kg or 0.3 kg/year. CONCLUSION: Weight management for obesity in primary care is highly cost-effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits.

Efficacy of ezetimibe/simvastatin 10/40 mg compared to doubling the dose of low-, medium- and high-potency statin monotherapy in patients with a recent coronary event.

OBJECTIVE: The aim of the study was to compare the efficacy/safety of doubling the dose of low-, medium- and high-potency statins on lipids/lipoproteins versus ezetimibe/simvastatin (EZE/SIMVA) 10/40 mg in patients with a recent coronary event. METHODS: In this open-label study, patients were stratified by baseline statin therapy (low, medium and high potency) and randomized equally to statin dose doubling or EZE/SIMVA 10/40 mg for 12 weeks. Primary analysis concerned change in low-density lipoprotein cholesterol for the whole population. Treatment-by-stratum interaction evaluated the consistency of treatment effect across statin potency strata. Post hoc analysis of between-group efficacy within strata was performed using ANCOVA. RESULTS: Within each stratum, EZE/SIMVA produced significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B and non-high-density lipoprotein cholesterol (HDL-C) compared to statin doubling. Numerical trends toward smaller between-group reductions were observed with higher-potency statins and reached statistical significance for apolipoprotein B and non-HDL-C. No significant between-group differences in HDL-C and C-reactive protein were observed within each stratum. EZE/SIMVA produced larger reductions in triglycerides versus low-potency statin, whereas it was similarly effective compared with intermediate-/high-potency statins. The safety/tolerability profiles of the treatments were similar across the strata. CONCLUSIONS: EZE/SIMVA 10/40 mg produced greater improvements in lipids with a similar safety profile compared to doubling the dose of low-, medium- and high-potency statins.

Lipid-altering efficacy of ezetimibe/simvastatin 10/40 mg compared with doubling the statin dose in patients admitted to the hospital for a recent coronary event: the INFORCE study.

BACKGROUND: The aim of this study was to investigate the efficacy and safety profile of switching to ezetimibe/simvastatin (Eze/Simva) 10/40 mg compared with doubling the statin dose upon discharge in patients taking a statin and admitted to the hospital for the investigation of a coronary event. DESIGN: This phase IV, multi-centre, randomised, open-label, active-controlled, parallel group study enrolled 424 patients (aged >/= 18 years) hospitalised for an acute coronary event and taking a stable dose of a statin (>/= 6 weeks) that could be doubled per the product label. Upon discharge from the hospital, patients were stratified by their statin dose/potency (high, medium and low) and randomised 1 : 1 to doubling of the statin dose (n = 211) or Eze/Simva 10/40 mg (n = 213) for 12 weeks. The primary efficacy variable was the absolute low-density lipoprotein cholesterol (LDL-C) value (mmol/l) at study end-point. RESULTS: Mean baseline LDL-C for the two treatment groups were 2.48 and 2.31 mmol/l for the Eze/Simva and statin groups respectively. At study end-point, least squares mean LDL-C values were 1.74 mmol/l in the Eze/Simva group and 2.22 mmol/l in the statin group resulting in a significant between-group difference of -0.49 mmol/l (p /= 0.160). Significantly more patients achieved LDL-C levels < 2.5 (< 100 mg/dl; 86% vs. 72%), < 2.0 (< 77 mg/dl; 70% vs. 42%) and < 1.8 mmol/l (< 70 mg/dl; 60% vs. 31%) with Eze/Simva than statin (all p /= 3 x upper limit of normal (ULN) or creatine kinase >/= 10 x ULN between the groups. CONCLUSIONS: In patients taking a statin and admitted to the hospital for investigation of a coronary event, treatment with Eze/Simva 10/40 mg for 12 weeks produced greater improvements in lipids with a similar safety profile compared with doubling of the statin dose.

The Counterweight programme: Prevalence of CVD risk factors by body mass index and the impact of 10% weight change.

OBJECTIVES: To examine relationships between body mass index (BMI), prevalence of physician-recorded cardiovascular disease (CVD) risk factors in primary care, and changes in risk with 10% weight change. METHODS: The Counterweight Project conducted a baseline cross-sectional survey of medical records of 6150 obese (BMI ≥ 30 kg/m(2)), 1150 age- and sex-matched overweight (BMI 25 to <30 kg/m(2)), and 1150 age- and sex-matched normal weight (BMI 18.5 to <25 kg/m(2)) controls, in primary care. Data were collected for the previous 18 months to examine BMI and disease prevalence, and then modelled to show the potential effect of 10% weight loss or gain on risk. RESULTS: Obese patients develop more CVD risk factors than normal weight controls. BMI ≥ 40 kg/m(2) exhibits increased prevalence of type 2 diabetes mellitus (DM), odds ratio (OR) men: 6.16 (p < 0.001); women: 7.82 (p < 0.001) and hypertension OR men: 5.51 (p < 0.001); women: 4.16 (p < 0.001). Dyslipidaemia peaked around BMI 35 to <37.5 kg/m(2), OR men: 3.26 (p < 0.001); women 3.76 (p < 0.001) and CVD at BMI 37.5 to <40 kg/m(2) in men, OR 4.48 (p < 0.001) and BMI ≥ 40 kg/m(2) in women, OR 3.98 (p < 0.001). A 10% weight loss from the sample mean of 32.5 kg/m(2) reduced the OR for type 2 DM by 30% and CVD by 20%, while 10% weight gain increased type 2 DM risk by more than 35% and CVD by 20%. CONCLUSION: Obesity plays a fundamental role in CVD risk, which is reduced with weight loss. Weight management intervention strategies should be a public health priority to reduce the burden of disease in the population.

Empowering primary care to tackle the obesity epidemic: the Counterweight Programme.

OBJECTIVE: To improve the management of obese adults (18-75 y) in primary care. DESIGN: Cohort study. SETTINGS: UK primary care. SUBJECTS: Obese patients (body mass index > or =30 kg/m(2)) or BMI> or =28 kg/m(2) with obesity-related comorbidities in 80 general practices. INTERVENTION: The model consists of four phases: (1) audit and project development, (2) practice training and support, (3) nurse-led patient intervention, and (4) evaluation. The intervention programme used evidence-based pathways, which included strategies to empower clinicians and patients. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation. MAIN OUTCOME MEASURES: Proportion of practices trained and recruiting patients, and weight change at 12 months. RESULTS: By March 2004, 58 of the 62 (93.5%) intervention practices had been trained, 47 (75.8%) practices were active in implementing the model and 1549 patients had been recruited. At 12 months, 33% of patients achieved a clinically meaningful weight loss of 5% or more. A total of 49% of patients were classed as 'completers' in that they attended the requisite number of appointments in 3, 6 and 12 months. 'Completers' achieved more successful weight loss with 40% achieving a weight loss of 5% or more at 12 months. CONCLUSION: The Counterweight programme provides a promising model to improve the management of obesity in primary care.

Inherited pericentric inversion (X)(p11.4q11.2) associated with delayed puberty and obesity in two brothers.

We report two brothers with hypogonadotropic hypogonadism (HH), obesity and short stature associated with a maternally inherited pericentric inversion (X)(p11.4q11.2). On the basis that either breakpoint might disrupt a gene whose function is critical to normal sexual development we mapped the chromosomal breakpoints using two-colour fluorescent in situ hybridisation (FISH). The position of both the Xp11.4 and Xq11.2 breakpoints was refined using a panel of ordered BAC clones. No known genes were shown to map to the breakpoint regions. While we cannot entirely exclude the possibility that association between the clinical and cytogenetic phenotypes in the family is coincidental, it is possible that the inversion is responsible for HH through alternative molecular mechanisms such as position effects.

Pitavastatin.

The growing number of trials that have highlighted the benefit of intensive lowering of total- and low density lipoprotein (LDL)-cholesterol levels especially with statins has created a need for more efficacious agents. Pitavastatin is a new synthetic 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor, which was developed, and has been available in Japan since July 2003. Metabolism of pitavastatin by the cytochrome P450 (CYP) system is minimal, principally through CYP 2C9, with little involvement of the CYP 3A4 isoenzyme, potentially reducing the risk of drug-drug interactions between pitavastatin and other drugs known to inhibit CYP enzymes. To date, human and animal studies have shown pitavastatin to be potentially as effective in lowering LDL-cholesterol levels as rosuvastatin; although, head-to-head studies are yet to be conducted.

The effect of high dose atorvastatin therapy on lipids and lipoprotein subfractions in overweight patients with type 2 diabetes.

Few data are available on the effects of high dose statin therapy on lipoprotein subfractions in type 2 diabetes. In a double blind randomised placebo-controlled trial we have studied the effects of 80 mg atorvastatin over 8 weeks on LDL, VLDL and HDL subfractions in 40 overweight type 2 diabetes patients. VLDL and LDL subfractions were prepared by density gradient ultracentrifugation. Triglycerides, cholesterol, total protein and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. Atorvastatin 80 mg produced significant falls in LDL subfractions (LDL(1) 66.2 mg/dl:36.6 mg/dl, LDL(2) 118:56.6 mg/dl, LDL(3) 36.9:19.9 mg/dl all P < 0.01 relative to placebo) and VLDL subfractions (VLDL(1) 55:22.1 mg/dl, VLDL(2) 40.1:19.1 mg/dl, VLDL(3) 52.6:30 mg/dl all P < 0.01 relative to placebo). There was no change in the proportion of LDL present as LDL(3). There was a reduction in the proportion of VLDL as VLDL(1) and a reciprocal increase in the proportion as VLDL(3). Changes in VLDL subfractions were associated with changes in lipid composition, particularly a reduction in cholesterol ester and a reduction in the cholesterol ester/triglyceride ratio. Effects on HDL subfractions were largely neutral. High dose atorvastatin produces favourable effects on lipoprotein subfractions in type 2 diabetes which may enhance antiatherogenic potential.

Fluvastatin.

Fluvastatin was the first wholly synthetic statin to the market and is effective in reducing total and low density lipoprotein cholesterol, which translates into reductions in coronary heart disease events. The Lescol Intervention Prevention Study has established the effectiveness of the early use of statins in reducing recurrent events in high-risk patients with coronary heart disease post percutaneous coronary interventions. Fluvastatin is well-tolerated with few side effects. The occurrence of significant abnormalities in liver enzymes is infrequent, and the risk of myositis and rhabdomyolysis seems to be less than with other statins. There have been no reports of fatal rhabdomyolysis to date. The potential for drug interactions with fluvastatin is low. It seems safe in combination with cyclosporin and there have been few reports of rhabdomyolysis when using fluvastatin in combination with other lipid-lowering agents. It is nevertheless important to be vigilant for this potentially important side effect and, as with other statins, inform patients of the potential risk and suggestive symptoms. Fluvastatin provides a useful option in treating hypercholesterolaemia in patients at high risk of coronary heart disease.

Neuroprotection in ischemia-reperfusion injury: an antiinflammatory approach using a novel broad-spectrum chemokine inhibitor.

Cerebral ischemia-reperfusion injury is associated with a developing inflammatory response with pathologic contributions from vascular leukocytes and endogenous microglia. Signaling chemokines orchestrate the communication between the different inflammatory cell types and the damaged tissue leading to cellular chemotaxis and lesion occupation. Several therapies aimed at preventing this inflammatory response have demonstrated neuroprotective efficacy in experimental models of stroke, but to date, few investigators have used the chemokines as potential therapeutic targets. In the current study, the authors investigate the neuroprotective action of NR58-3.14.3, a novel broad-spectrum inhibitor of chemokine function (both CXC and CC types), in a rat model of cerebral ischemia-reperfusion injury. Rats were subjected to 90 minutes of focal ischemia by the filament method followed by 72 hours of reperfusion. Both the lesion volume, measured by serial magnetic resonance imaging, and the neurologic function were assessed daily. Intravenous NR58-3.14.3 was administered, 2 mg/kg bolus followed by 0.5 mg/kg hour constant infusion for the entire 72-hour period. At 72 hours, the cerebral leukocytic infiltrate, tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8)-like cytokines were analyzed by quantitative immunofluorescence. NR58-3.14.3 significantly reduced the lesion volume by up to 50% at 24, 48, and 72 hours post-middle cerebral artery occlusion, which was associated with a marked functional improvement to 48 hours. In NR58-3.14.3-treated rats, the number of infiltrating granulocytes and macrophages within perilesional regions were reduced, but there were no detectable differences in inflammatory cell numbers within core ischemic areas. The authors reported increased expression of the cytokines, TNF-alpha, and IL-8-like cytokines within the ischemic lesion, but no differences between the NR58-3.14.3-treated rats and controls were reported. Although chemokines can have pro- or antiinflammatory action, these data suggest the overall effect of chemokine up-regulation and expression in ischemia-reperfusion injury is detrimental to outcome.

Actos (pioglitazone): a new treatment for type 2 diabetes.

Type 2 diabetes is increasingly common and can be difficult to control. By directly targeting insulin resistance, the thiazolidinediones offer a new mode of treatment. Here, the pharmacology, clinical trial evidence, side-effects and current clinical uses of pioglitazone are reviewed.

A common phenotype associated with atherogenesis in diverse mouse models of vascular lipid lesions.

The introduction of a range of different genetic modifications in mice results in altered lipoprotein metabolism and the development of vascular lipid lesions. At present, however, it is unclear to what extent the molecular events underlying lipid lesion formation are similar in these different mouse models of atherosclerosis. The aim of this study was to compare the protein expression pattern of lipid lesions from seven different mouse lines with varying susceptibility to vascular lipid lesion development, to determine to what extent lesions induced by different genetic interventions have a similar composition. The proteins we have measured, using quantitative immunofluorescence, are proteins whose expression is known to be modulated during atherogenesis in humans, including plasminogen activator inhibitor (PAI)-1, transforming growth factor (TGF)-beta 1, osteopontin and the macrophage marker CD11b. In all the mice lines we have investigated, PAI-1 was elevated wherever lesions developed. Active TGF-beta was depressed in the vessel wall of mice which developed lipid lesions, particularly in the intima. In contrast, TGF-beta 1 antigen (active plus latent TGF-beta 1) was increased at lesion sites. Accumulation of osteopontin and, with the marked exception of apolipoprotein(a) transgenic mice, tissue macrophages occurred at sites of lipid deposition in the vessel wall. Each lesion, irrespective of its size and the mouse strain in which it developed, had similar amounts of PAI-1, active TGF-beta and osteopontin per unit area of lesion. These data are consistent with a common phenotype accompanying atherogenesis, irrespective of the genetic basis of susceptibility.

The pan-chemokine inhibitor NR58-3.14.3 abolishes tumour necrosis factor-alpha accumulation and leucocyte recruitment induced by lipopolysaccharide in vivo.

Chemokines participate in the regulation of leucocyte recruitment in a wide variety of inflammatory processes, including host defence and diseases such as asthma, atherosclerosis and autoimmune disorders. We have previously described the properties of Peptide 3, the first broad-specificity chemokine inhibitor in vitro. Here, we report the properties of NR58-3.14.3, a retroinverso analogue of Peptide 3. NR58-3.14.3 inhibited leucocyte migration induced by a range of chemokines, including monocyte chemoattractant protein-1 (MCP-1) (2.5 nM), macrophage inflammatory protein-1alpha (MIP-1alpha) (5 nM), regulated on activation, normal T-cell expressed and presumably secreted (RANTES) (20 nM), stromal cell-derived factor-1alpha (SDF-1alpha) (25 nM) and interleukin-8 (IL-8) (30 nM), but did not affect migration induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or complement C5a (> 100 microM). NR58-3.14.3 is therefore approximately 1000-fold more potent than Peptide 3 but retains the broad-spectrum chemokine inhibitory activity of the parent peptide. In vivo, pretreatment with a systemic dose of 10 mg of NR58-3.14.3, but not the inactive derivative NR58-3.14.4, abolished leucocyte recruitment in response to intradermal injection of 500 ng of MCP-1 into rat skin. This suggests that NR58-3.14.3 is a functional chemokine inhibitor in vivo as well as in vitro. We utilized NR58-3.14.3 as a tool to investigate the role of chemokine activity during leucocyte recruitment in response to lipopolysaccharide (LPS) in vivo. NR58-3.14.3, but not NR58-3.14.4, abolished leucocyte recruitment in response to intradermal injection of 50 ng of LPS into rat skin. Furthermore, NR58-3.14.3 completely inhibited LPS-induced accumulation of tumour necrosis factor-alpha (TNF-alpha). This data is consistent with a model in which multiple chemokines act in parallel upstream of TNF-alpha. NR58-3.14.3 is therefore a powerful anti-inflammatory agent in vivo, suppressing proinflammatory cytokine production and leucocyte recruitment in response to endotoxin stimulus in rat skin.

Efficacy and tolerability of fluvastatin extended-release delivery system: a pooled analysis.

BACKGROUND: At high doses, the pharmacokinetics of fluvastatin immediate-release (IR) are nonlinear, possibly due to saturation of hepatic uptake. Fluvastatin delivery to the liver in a slower but sustained fashion would be expected to avoid hepatic saturation without elevating systemic drug levels. OBJECTIVE: This pooled analysis compared the efficacy and tolerability of extended-release (XL) 80-mg and IR 40-mg formulations of fluvastatin in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and raising high-density lipoprotein cholesterol (HDL-C) levels in patients with hypercholesterolemia. METHODS: Data were pooled from 3 double-blind, randomized, active-controlled, multicenter, parallel-group studies that compared changes in lipid and apolipoprotein levels with fluvastatin XL 80 mg at bedtime (HS) with changes in fluvastatin IR 40 mg HS or BID in patients aged > or =18 years with primary hypercholesterolemia (consistently elevated LDL-C level [> or =160 mg/dL] and plasma TG levels < or =400 mg/dL). The primary efficacy variable was percent change in LDL-C from baseline. RESULTS: The pooled analysis provided an intent-to-treat efficacy study population of 1674 patients. At 4 weeks, fluvastatin XL 80 mg HS reduced LDL-C levels by a mean of 36.3% (median 38%), significantly greater than a mean reduction of 25.9% (median 27%) seen with fluvastatin IR 40 mg HS, and an incremental additional mean reduction in LDL-C of 10.4% (P < 0.001). At 4 and 24 weeks, fluvastatin XL 80 mg HS provided an LDL-C reduction equivalent to fluvastatin IR 40 mg BID (P < 0.001 for noninferiority). Significant, dose-related changes in HDL-C, LDL-C:HDL-C ratio, total cholesterol, TG, and apolipoprotein A-I and apolipoprotein B levels also occurred. Mean HDL-C level increased by 8.7% and median TG level decreased by 19% with fluvastatin XL 80 mg HS (P < 0.001 and P < 0.05 vs fluvastatin IR 40 mg HS, respectively). Maximum mean increases in HDL-C level (21%) and median decreases in TG level (31%) with fluvastatin XL 80 mg HS occurred in patients with type IIb dyslipidemia and the highest baseline TG. Adverse events were mild, with similar frequency in all treatment groups. CONCLUSIONS: Once-daily administration of fluvastatin XL 80 mg provides enhanced efficacy with an additional 10.4% reduction in LDL-C levels compared with fluvastatin IR 40 mg HS, and superior increases in HDL-C levels, particularly in patients with elevated TG levels (P < 0.05 vs fluvastatin IR 40 mg HS). Fluvastatin XL 80 mg HS has a good tolerability profile and is effective as starting and maintenance lipid-lowering treatment in patients with type II hypercholesterolemia.

Lipoproteins and their subfractions in psoriatic arthritis: identification of an atherogenic profile with active joint disease.

OBJECTIVES: (a) To characterise the lipid profile in psoriatic arthritis and investigate whether there are similarities to the dyslipoproteinaemia reported in rheumatoid arthritis and other inflammatory forms of joint disease; (b) to investigate whether there is an atherogenic lipid profile in psoriatic arthritis, which may have a bearing on mortality. METHODS: Fasting lipids, lipoproteins, and their subfractions were measured in 50 patients with psoriatic arthritis and their age and sex matched controls. RESULTS: High density lipoprotein cholesterol (HDL cholesterol) and its third subfraction, HDL(3) cholesterol, were significantly reduced and the most dense subfraction of low density lipoprotein (LDL), LDL(3), was significantly increased in the patients with psoriatic arthritis. Twenty patients with active synovitis had significantly lower total cholesterol, LDL cholesterol, and HDL(3) cholesterol than their controls. 25% of the patients with psoriatic arthritis had raised Lp(a) lipoprotein levels (>300 mg/l) compared with 19% of controls, but this was not statistically significant. CONCLUSION: Raised levels of LDL(3) and low levels of HDL cholesterol are associated with coronary artery disease. Such an atherogenic profile in a chronic inflammatory form of arthritis is reported, which may be associated with accelerated mortality.